BCS + PPS Flashcards
ECG interpreta’n ✓
Normal ECG
- Pulse = 300 ÷ # of big boxes btw adjacent R’s
- Sinus rhythm = regular pulse + P waves are round, of same shape + precede EVERY QRS complex
→ If not sure if u see P wave before every QRS, check if RR = consistent !
⚠️ Think ventricular tachycardia if u see absent P wave + tachycardia + high amplitude QRS complex (especially if pt has Hx of MI)
⚠️ Absent P wave + tachycardia + short amplitude = Vfib
- P wave width = 2-3 little squares (represents atrial depolariza’n)
- QRS complex width = < 3 little squares (represents ventricular depolariza’n aka closure of mitral valve)
→ prolonged QRS (i.e >120ms) + dominant S wave in V1 = suggestive of LBBB - ST segment = from point right after S to beginning of T wave, should be a perfectly straight line
-T wave = upright except in leads aVR, aVL, III + V1, represents repolariza’n
- QT interval = count # of small boxes + multiply by 40
→ 350-450 for men + 360-460 for women
→ prolonged QT interval = sign of HYPERCa
→ short QT interval = sign of HYPOCa - PR interval = beginning of P wave to point just before Q, width should be 3-5 little squares (represents time btw atrial + ventricular depolariza’n i.e conduc’n by AV node)
→ prolonged PR interval = > 1 large box
ECG Leads
- V1, V2 = Septal / Posterior = LAD
- V3, V4 = Anterior = LAD (most commonly occluded artery)
- 2 + 3 + aVF (“ferior right”) = Inferior = right coronary in most ppl + left circumflex from left coronary in 10% of ppl
- 1, V5, V6, avL (“15 6 avL” + left lateral”) = Lateral = left circumflex
Axis Devia’n
-30° 0° 30° 60° 90° = Normal
< -30° = Left axis devia’n = +ve QRS complex in Lead 1 + -ve QRS complex in inferior leads
→ ex’s : LBBB, left ventricular hypertrophy, inferior MI
> 90° = Right axis devia’n = -ve QRS complex in Lead 1 and +ve QRS complex in inferior leads
→ ex’s : RBBB, right ventricular hypertrophy, lateral MI, HyperK, P.E, COPD, right sided heart strain, WPW syndrome, ventricular tachycardia
- Know for OSCE *
Coronary anatomy ✓
RCA supplies . . .
- RA
- SA node in 60% of ppl
- AV node in 80% of ppl
LCA supplies . . .
- LA
- most of LV
- SA node in remaining 40% of ppl
Ischemic Heart Disease ✓
Def - IHD = term used to describe the spectrum of heart diseases that results from coronary artery atherosclerosis
→ angina = crushing chest pain radiating to left arm or jaw, characteristic of MI
→ ischemia = ↓ed perfus’n to tissues = when tissue O2 demand > supply = reversible but if persists can cause infarct i.e myocyte death which is irreversible
⟹ Partial occlus’n → ischemia
⟹ Complete occlus’n → ischemia → infarct
Pathophys - gradual but slow enlarg’nt of STABLE plaque (contains mainly smooth muscle cells)
→ GRADUAL occlus’n of coronary vessel(s)
→ GRADUAL ↓ in blood flow → mismatch btw O2 supply + demand to myocardium → ischemia OR . . .
- gradual but slow enlarg’nt of STABLE plaque (contains mainly smooth muscle cells) → COMPLETE occlus’n of coronary vessel(s) → SUDDEN ↓ in blood flow → Infarct
Types
- stable angina / angina pectoris = pain upon exer’n (means there’s at least some blood flow to whatever part of heart) = for STEMI, lasts 1-2 min, pain = relieved by GTN spray
- unstable angina = pain @ rest (means there’s very little blood flow), lasts 3-5 min OR is severe + of new onset OR occurs w/ crescendo pattern
→ could be SSX of N-STEMI or could be diagnosis of its own - Know for OSCE *
Infective Endocarditis ✓
Def - infec’n of endocardial surface of heart including valvular structures + chordae tendineae
RFs
- artificial heart valve
- post heart transplant
- acquired valvular heart disease
- structural congenital heart disease
- previous Hx of infective endocarditis
- hypertrophic obstructive cardiomyopathy
Eti
- Staph. aureus colonizing normal valve OR fungi such as candida albicans / aspergilus fumigatus
- weakly pathogenic bacteria like Strep. viridians colonizing an abnormal valve i.e prosthetic valve / prolapsed mitral valve
SSX = “FROM JANE”
- Fever
- Roth’s spots = white retinal hemorrhage (seen on fundoscopy)
- Osler nodes = on tip of fingers / toes + are painful
- Murmur
- Janeway les’ns = on palm / soles + are NOT painful
- Anemia
- Nail SSX i.e splinter hemorrhage
- Emboli
Ix’s = urgent trans-thoracic echocardiogram (trans-esophageal echo instead if pt has prosthetic valve / intracardiac device OR TTE = -ve but there’s a strong clinical suspic’n of IE) + 3 blood cultures taken 12 hrs apart from each other + from diff sites + a serum sample
Criteria for diagnosis (Duke’s) = 1 major + 3 minor OR 5 minor
→ Major criteria = persistently +ve blood cultures or vegeta’n on echo
→ Minor criteria . . .
⟹ Predisposi’n i.e IV drug use / heart valve pathology
⟹ Fever > 38°C
⟹ Vascular phenomena i.e splenic infarc’n / intracranial hemorrhage / janeway les’ns
⟹ Immunological phenomena i.e Osler nodes / Roth spots / glomerulonephritis
Tx = IV broad-spectrum Abx such as amoxicillin or gentamicin for 4 wks for pts w/ natural heart valve or for 6 wks for pts w/ artificial valve
Complica’ns
- acute heart failure
- disturbance of valve func’n
- stroke b/c part of vegeta’n can detach → get transported via circula’n + cause an embolism
- forma’n of antigen-antibody immune complexes which can impair kidneys + hence cause AKI / glomerulonephritis
- Know for OSCE *
Acute Pericarditis ✓
Def - new onset inflamma’n of pericardium lasting < 4-6 wks
RFs
- male
- 20-50 y/o
- neoplasm
- Cardiac Sx
- transmural MI
- uremia or on dialysis
- viral / bacterial infec’n
- systemic autoimmune disorder
Eti
- TB
- uremia
- post MI
- idiopathic
- viral infec’n such as coxsackie
- systemic autoimmune disorder
SSX = chest pain worse when pt is supine i.e leans back + better when they lean forward + serial electrocardiographic Δs + pericardial fric’n rub i.e sound of walking on snow heard when diaphragm of stethoscope = placed over left sternal border (especially @ end-expira’n w/ pt leaning forward)
Ddx
- MI
- P.E
- pneumonia
- pneumothorax
- costochondritis
Ix’s
- ECG → upwardly concave ST-segment eleva’ns w/ PR-segment depress’ns in most leads
- troponin → if elevated = suggestive of myopericarditis
- CRP → will be elevated
Tx
- NSAID for pain
- PPI for gastric protec’n due to NSAID use
- long term colchicine i.e 3 months to prevent recurrence
→ order FBC before starting colchicine b/c can cause neutropenia + bone marrow suppress’n
→ avoid in pts who are very frail or have impaired mobility due to high likelihood of Tx-related diarrhea
- restrict strenuous physical activities until SSX have resolved + CRP = back to normal
Complica’ns
- chronic constrictive pericarditis (rare + usually occurs 3-12 months later)
- pericardial effus’n due to accumula’n of exudate in pericardial sac → cardiac tamponade (life-threatening)
- Know for OSCE *
Constrictive Pericarditis ✓
Def - chronic condi’n where granula’n tissue forma’n in pericardium results in loss of pericardial elasticity
RFs
- male
- cardiac Sx
Eti
- idiopathic
- after viral infec’n
- TB (in endemic reg’ns)
Pathophys - loss of pericardial elasticity → ventricular filling = restricted → ↓ in end diastolic volume, SV + consequentially CO as well
SSX
- RHF SSX
- fatigue + dyspnea on exer’n due to ↓ in CO
+ve Kussmaul’s sign i.e ↑ of JVP on inspira’n
Ix = 2D echocardiography → may show ↑ed pericardial thickness w/ or w/o calcifica’n
Tx = pericardiectomy i.e removing as much pericardium as possible
Complica’ns
- renal failure
- hepatomegaly
- pulmonary HTN
- metabolic acidosis
- Know for OSCE *
Myocarditis ✓
Def - inflamma’n of myocardium in the absence of ischemia / CAD
RFs
- HIV
- infec’n
- auto immune condi’n
- peri partum / post partum
Eti
- systemic disease
- viral / bacterial / fungal infec’n
- toxins such as snake venom, arsenic, CO, cocaine or heavy metals i.e Cu / Fe / Pb
SSX
- SOB
- fatigue
- palpita’ns
- chest pain
- tachypnea
- orthopnea
- S3 sound (usually when CHF develops as a result)
- rales / crackles “ “
- hepatomegaly “ “
- prominent neck veins “ “
Ddx
- ACS
- pericarditis
- dilated cardiomyopathy
Ix’s
- CXR to check for SSX of CHF
- ECG + CK-MB / troponin to r/o MI
- BNP to confirm whether or not pt has heart failure
→ can be falsely low in obese pts + falsely high in pts w/ CKD
- 8F-FDG PET-CT if it’s chronic
- 2D echo → will show RV dilata’n
Tx
- if hemodynamically stable w/o evidence of LV systolic dysfunc’n → supportive care + treat underlying cause
- if hemodynamically stable w evidence of LV systolic dysfunc’n → treat as u would chronic HF
- if hemodynamically unstable → arterial vasodilator such as Na nitroprusside (may precipitate CN- toxicity especially in pts w/ renal dysfunc’n) + invasive hemodynamic monitoring
Complica’ns
- Afib
- Vtach
- sudden cardiac death
- dilated cardiomyopathy
- Know for OSCE *
Hypertrophic Cardiomyopathy (HCM) ✓
Def - genetic disorder characterized by LVH w/o any identifiable cause i.e ↑ in thickness of wall of LV = most common cardiomyopathy + most frequent cause of sudden cardiac death in young ppl
→ pts = classified as obstructive or non-obstructive based on presence or absence of left ventricular outflow tract obstruc’n @ rest on echocardiography
RF = FHx of HCM or sudden cardiac death
SSX
- SOB
- angina
- palpita’ns
- dizziness / syncope
- systolic ejec’n murmur
- double apical pulse / carotid pulsa’n
- left ventricular lift i.e left parasternal heave
Ddx
- athlete’s heart
- LVH due to HTN
- discrete sub-aortic stenosis
Ix’s
- ECG → will show prominent Q waves, LVH + ST-T wave abnormalities
- CXR → will show cardiomegaly
- echocardiogram → will show LVH
Tx
- asymptomatic but not @ high risk of sudden cardiac death → observe
- asymptomatic but @ high risk of sudden cardiac death → ICD (implantable cardio-defibrilator) + avoiding intense activity
- symptomatic but not @ end-stage heart failure → -ve ionotropic + chronotropic agents i.e β blocker or non-dihydropyridine CCB such as verapamil / diltiazem
- symptomatic + @ end-stage heart failure → β blocker + ACE-I / ARB
Complica’ns
- Afib
- ischemic stroke
- infective endocarditis
- sudden cardiac death
- Know for OSCE *
Dilated Cardiomyopathy ✓
Def - enlargement + dila’n of 1 or both ventricles along w/ impaired contractility i.e left ventricular ejec’n frac’n (LVEF) < 40%
Eti
- 1° = idiopathic → only when all possible causes have been excluded
- 2° = due to HTN / infec’n / ischemic disease / medica’n such as anthracyclines
Pathophys - progressive dilata’n of ventricle(s)
→ mitral + tricuspid insufficiency → ejec’n frac’n further ↓
SSX
- SOB
- PND
- fatigue
- orthopnea
- SSX of CHF
Ddx
- acute pericarditis
- cardiac tamponade
- hypertrophic cardiomyopathy
Ix’s
- echocardiogram for diagnosis
- CXR → cardiomegaly + Ψly signs of CHF
- coronary angiography in pts w/o known Hx of CAD to r/o occult ischemic disease as the cause
Tx = treat like acute HF if it’s acute + like chronic if it’s chronic
Complica’ns
- congestive HF
- sudden cardiac death
- valvular heart disease
- abnormal cardiac rhythms
- thromboembolism b/c when ventricle(s) = dilated blood flow through heart = slower than normal
- Know for OSCE *
Pericardial Effus’n ✓
Def - fluid in pericardial sac beyond its physiological amt i.e ≥ 50 mL
Eti
- trauma
- malignancy
- idiopathic for ex post cardiac Sx
- renal disease i.e uremic pericarditis
- infec’n i.e viral / bacterial pericarditis
SSX
- palpita’ns
- chest pain
- cough / SOB
- syncope / light-headedness
Ddx
- MI
- P.E
- cardiac tamponade
- constrictive pericarditis
Ix’s
- FBC to check for infec’n
- U + E to check for uremia
Tx = pericardiocentesis
Complica’n = cardiac tamponade
- Know for OSCE *
Cardiac Tamponade ✓
Def - when pericardial effus’n gets to the point where it leads to ↑ in intra-pericardial pressure ∴ restricting cardiac filling + leading to ↓ in CO = medical emergency !
RFs
- malignancy
- aortic dissec’n
- purulent pericarditis
Eti = same as pericardial effus’n
Pathophys - ventricular filling = impeded all throughout diastole
SSX
- SOB
- tachycardia
- pulsus paradoxus i.e severe ↓ in BP during inspira’n
- Beck’s triad i.e hypoTN + muffled heart sounds + elevated JVP
Ix’s
- ECG
- TTE for diagnosis → will show pericardial effus’n > 20 mm of echo-free space during diastole btw visceral + parietal pericardium
Tx
- if hemodynamically stable i.e systolic BP > 110 mmHg → NSAID + gastro-protec’n
- if hemodynamically unstable + eti = unknown → pericardiocentesis
- if hemodynamically unstable + eti = known → surgical drainage
Complica’ns
- cardiac arrest
- organ hypoperfus’n
- Know for OSCE *
Inflamma’n + Atherosclerosis ✓
- Inflamma’n = body’s physiological response to any kind of tissue injury i.e infec’n / trauma / hypoxia / radia’n in order to eliminate injurious agents, remove damaged tissue + initiate healing process
→ Acute inflamma’n = vascular Δs + neutrophil accumula’n @ site of injury = controlled by cytokine release which was triggered by injury
a) vasoconstric’n
b) vasodila’n ∴ ↑ in blood flow → ↑ in permeability of capillaries → leakage of plasma proteins through gaps btw endothelial cells so coagula’n cascade can begin
→ ↑in blood viscosity → blood flow slows down i.e STASIS of RBCs → b/c of slow blood flow, neutrophils get pushed to margins i.e NEUTROPHIL MARGINA’N
c) leukocytes loosely attach + detach to endothelial cells @ inflamma’n site via selectins (ROLLING)
→ leukocytes express integrin + bind tightly to integrin ligand (ADHES’N)
→ leukocytes squeeze in btw endothelial cells (DIAPEDESIS / TRANSMIGRA’N)
→ leukocytes move towards injury site or pathogen via chemotaxis
c) macrophages secrete IL-6
→ Liver produces CRP (acts as an opsonin = molecule that makes foreign matter recognizable for immune system by coating it)
→ CRP binds to bacterial cell wall (in the case of bacterial infec’n but could still be produced in other cases of inflamma’n like burns or trauma)
→ macrophages recognize CRP (High CRP = RF for atherosclerosis)
→ PHAGOCYTOSIS
d) REGENERA’N i.e replac’nt of damaged cells w/ the same types of cells but new ones ∴ original structure + func’n = restored (there are scenarios where scar tissue is able to replace damaged cells structurally but not func’nally - see below)
→ for COMPLETE restora’n to happen, there has to be limited tissue destruc’n w/o substantial damage to connective tissue matrix OR damaged cells need to have capacity to regenerate (for ex liver cells)
⟹ when neither condi’n = met, we have scar/fibrous tissue forma’n (= produced by fibroblasts, main component = collagen)
⟹ scar = mechanically strong so structure = preserved, but func’n ≠ preserved b/c scar can’t perform func’n of previous cells
→ sometimes doesn’t end at scarring but instead proceeds to chronic inflamma’n
⟹ in acute inflamma’n exudate i.e what comes out = fluid, fibrin + neutrophils
→ cardinal signs of inflamma’n = heat, redness, pain, swelling + loss of func’n (due to pain)
→ Chronic inflamma’n can either occur as a sudden onset OR as a result of unresolved acute inflamma’n
⟹ usually ends w/ tissue destruc’n + scar forma’n rather than regenera’n
⟹ has high E demand so nutrients get diverted ∴ pt can experience weight loss, anemia of chronic disease + ↓ed host resistance
- Pathophys of atherosclerosis :
- Endothelial damage → LDL accumula’n in tunica intima → recruit’nt of macrophages → LDL = oxidized by ROS → engulf’nt of oxidized LDL produces foam cells → collec’ns of lipid-laden macrophages identified macroscopically as yellow eleva’ns known as fatty streak → death of foamy macrophages
→ release of intra-cytoplasmic lipid
→ forma’n of lipid debris
→ prolifera’n of smooth muscle cells + migra’n from tunica media = last step of atheroma forma’n so what will be seen in arteries
→ secre’n of collagen + other ECM proteins
→ develop’nt of fibrous cap over core
(fibrous cap = thick in stable cap + thin in unstable cap → represents body’s attempt to repair injured vessel wall by scarring)
→ gradual but slow enlarg’nt of STABLE plaque (contains mainly smooth muscle cells)
→ gradual ↓ in blood flow → angina
OR instead of gradual but slow . . .
→ sudden rupture of UNSTABLE/VULNERABLE plaque (contains mainly inflammatory cells)
→ thrombus forma’n
→ MI if it causes partial or complete occlus’n at site of ruptured plaque + ischemic stroke if thrombus dislodges to brain i.e becomes an emboli
OR instead of gradual but slow . . .
→ enlarg’nt of atherosclerotic plaque + weakening of tunica media → aneurysm forma’n → aneurysm rupture
Atherosclerosis = chronic inflamma’n b/c meets the 3 criteria : persistent injury + on-going inflamma’n + repair w/ scaring (that’s what the fibrous cap is)
- Know for OSCE *
Pathophys of Edema + Lymphatic System ✓
Fluid mov’nt across capillary wall = dependent on balance btw hydrostatic + oncotic pressure gradient across capillary
→ hydrostatic pressure draws fluid into tissue from blood
→ oncotic pressure = mainly due to plasma proteins i.e albumin → draws fluid OUT of tissue into blood
→ lymph = fluid that has leaked from blood into tissues → lymphatic vessels return that “leaked” fluid i.e interstitial fluid back to bloodstream to prevent fluid imbalance ∴ causes of edema = anything that . . .
- ↑ hydrostatic pressure i.e in heart failure
- ↑ capillary permeability i.e in inflamma’n
- ↓ oncotic pressure i.e hypoalbuminemia
- obstructs lymph drainage such as a tumor
STEMI + N-STEMI ✓
RFs
> 65 y/o
- HTN
- obesity
- smoking
- diabetes
- dyslipidemia
- physical inactivity
Eti = complete occlus’n of coronary artery due to one of RFs
Pathophys
1. Myocyte necrosis (0-12hrs)
2. Neutrophil accumula’n for acute inflammatory response (12-72 hrs)
3. Organiza’n i.e replac’nt of dead cells by granula’n tissue = 1st step of repair process (3-10 days)
4. Progressive scar tissue deposis’n = 2nd + last step of repair process (wks to months)
SSX
- SOB
- sweat
- nausea
- angina = crushing chest pain due to lactic acid accumula’n that radiates to left arm or jaw (usually happens in an MI)
→ stable = pain upon exer’n = for STEMI
→ unstable = pain @ rest = for N-STEMI
Ix’s
- ECG :
→ STEMI = ST segment eleva’n in ≥ 2 contiguous leads aka raised line (not straight + flat) +/- pathological Q wave +/- T wave invers’n
→ N-STEMI = ST segment depress’n +/- T wave invers’n
- Coronary angiography = inject contrast to visualize blood flow in arteries via x-ray
→ can be used to identify occluded vessels in any part of the body + sites of hemorrhage, aneurysms or stenosis
→ risks = bleeding, aneurysm, stroke, heart attack, death - Cardiac troponin for 1st MI + CK-MB for reinfarc’n → will be high
⟹ Troponin rises after 4-6 hrs, peaks @ 24hrs + returns to normal by 1-2 wks
⟹ CK-MB rises after 4-6 hrs, peaks at 24hrs + returns to normal w/in 48-72hrs - FBC → high WBC + maybe high ESR/CRP
- Lipid profile → high LDL + high ttl cholesterol
- Glucose → could be high
Tx for either = statin b/c prevents already present plaques from dislodging ∴ ↓ morbidity + ↑ survival
Immediate STEMI Tx (“PAIN”)
- Urgent cardio referral for PCI or Fibrinolysis w/in 12hrs if PCI can’t be delivered w/in 2hrs
→ PCI has to be w/in 2 hrs + pt has to have stable angina, STEMI OR N-STEMI + unstable angina - Coronary ANGIOGRAPHY (has to be w/in 12 hrs) + dual anti-platelet therapy i.e aspirin + anti platelet like P2Y12/ADP receptor antagonist
- Aspirin MOA- irreversibly inhibits COX ∴ ↓ produc’n of thromboxane → can’t do platelet aggrega’n → less clotting → risk of arterial occlus’n ↓
- side effects- GI bleeding, ulcers, irrita’n + tinnitus
- C/Is- hypersensitivity, 3rd trimester, < 16 y/o
- ADP receptor antagonist MOA- inhibits ADP from binding to platelets → prevents platelet aggrega’n → ↓ risk of arterial occlus’n
- side effects = bleeding, GI upset + thrombocytopenia
- C/Is = active bleed
- end in “GREL” or “GRELOR”
- IV Morphine
- Nitrate/ GTN
- Nitrates MOA- cause release of NO → guanylate cyclase = activated → GTP = converted to cGMP → ↓ in [intracellular Ca] in vascular smooth muscle cells which causes them to relax → venous vasodila’n + a bit of arterial vasodila’n
- side effects = dizziness, HA + hypoTN
- C/Is = hypoTN, severe bradycardia, inferior MI, aortic stenosis, pt took phosphodiesterase inhibitor in past 24-48 hrs
- ex = GTN spray
N-STEMI Tx i.e Coronary Reperfus’n Therapy (“PATMAN”)
- Possibly PCI + angiography + dual anti-platelet therapy or fibrinolysis
- Asprin 300mg PO
- Ticagrelor 180mg OR clopidogrel if high bleeding risk OR prasugrel if having angiography
- Morphine
- Antithrombin therapy w/ fondaparinux (unless high bleeding risk or immediate angiography)
- Nitrate
After STEMI/N-STEMI Tx
- ACE I
- 80mg atorvastatin
- lansoprazole 30mg od
- β blocker
→ MOA of β blocker - block β adrenergic receptors in heart hence ↓ heart contractility + suppress release of renin
→ side effects = insomnia, cold extremities, HA + GI disturbance, abrupt w/drawal of β blockers can cause rebound tachycardia
→ C/Is = bradycardia, asthma + heart block
→ end in “OLOL”
→ SSX of β blocker overdose = bradycardia, hypoTN, HF, syncope
⟹ Tx = atropine if pt is bradycardic + then glucagon if bradycardia still persists
* atropine = anti muscarinic *
Short term complica’ns
- Vfib (24hrs later) = due to release of K from necrotic myocytes that induced arrhythmia in hyper-excitable tissue around infarct → results in sudden death
- other arrhythmias → usually in inferior infarcts (ex’s- ventricular tachycardia = w/in 4hrs post MI, supraventricular tachycardia + bradycardia)
- acute cardiac failure (can be left or right sided or bi-ventricular) → can lead to cardiogenic shock if very severe + BP maintenance ≠ possible
- cardiogenic shock = when substantial amt of affected myocytes can’t contract anymore
- acute pericarditis (w/in 48hrs post MI)
- mural thrombus
- myocardial rupture (effects depend on site of rupture . . .)
→ Rupture of free wall will lead to cardiac tamponade = fluid w/in pericardial sac (w/in 10 days post MI)
⟹ SSX = raised JVP + muffled heart sounds + pulsus paradoxus (= severe ↓ in BP during inspira’n)
→ Rupture of papillary muscle of mitral valve - acute mitral regurgita’n (24hrs later but in posterior STEMI only) → blood flows back into LA → pressure in LA ↑ → high pressure goes to pulm. circula’n → fluid transuda’n in lung interstitium + alveoli → pulm. edema → acute LV failure
→ Rupture of IV septum will cause acute heart failure
Long term complica’ns
- CHF
- Recurrent MI
- Chronic CHF
- Ventricular aneurysm → can lead to congestive cardiac failure, arrhythmia + dislodging of thrombus
- Dressler’s syndrome = autoimmune pericarditis, occurs 2-10 months after transmural MI
- Know for OSCE *
HTN + Kidney ✓
1- BP regula’n
2- Def, RFs, Eti, Pathophys, SSX, Diagnostic Criteria, Ddx, Ix, 1st line Mx, Complica’ns
1) How does our body detect + respond to BP Δs ? (Baroreceptor reflex through vagus nerve + RAAS)
- High BP baroreceptor reflex :
High BP = detected by baroreceptors in aortic arch + carotid sinus → high BP causes them to fire more ac’n ψs than usual → activates cardiac inhibitory center in medulla + inhibits cardiac acceleratory center → para = stimulated + sympa = inhibited ∴ HR + BP ↓ - a) Low BP baroreceptor reflex :
Low BP = detected by those same baroreceptors
→ low BP causes them to fire less ac’n ψs than usual → activates cardiac acceleratory center in medulla + inhibits cardiac inhibitory center → para = inhibited + sympa = activated ∴ HR + BP ↑
b) Low BP RAAS pathway :
Low BP = detected → juxtaglomerular cells of kidneys secrete renin
→ renin converts angiotensinogen (produced in liver) to angiotensin I
→ ACE converts angiotensin I to ATII (in kidneys)
→ ATII ↑ BP by vasoconstricting = by stimulating release of adrenergens + ↑ing blood volume = by stimulating adrenal glands to release aldosterone which ↑ Na reabsorp’n + since water follows salt, water reabsorp’n ↑ as well but inadvertently causes K to ↓ + stimulating posterior pituitary to release ADH which ↑ water reabsorp’n by causing vasoconstric’n via V1 receptor (will hence ↑ BP) + ↑ing express’n of aquaporin channels on luminal surface
2) Def
- 140-159 + 90-99 = Mild / Stage I
- 160-179 + 100-109 = Moderate / Stage II
≥180 + ≥110 = Severe / Hypertensive crisis
→ SSX of end organ damage = pulm. edema + SOB or dizziness / cardiac ischemia +/- chest pain / renal failure / neurological deficits such as vis’n Δs = Hypertensive Emergency !
⚠️ There must be ≥ 1 SSX of organ damage + severe BP in order to call it a hypertensive emergency otherwise it’s a hypertensive urgency !
RFs
> 60 y/o
- T2D
- obesity
- sleep apnea
- black ancestry
- metabolic syndrome
- aerobic exercise < 3x/wk
- moderate ~ high alcohol intake
- FHx of HTN or coronary artery disease
Eti for 1° / essential = RFs
Pathophys for 1° - high salt intake → ↑ in osmolality → ADH = secreted → we get water reabsorp’n aka water reten’n ↑ → CO ↑ → BP ↑
Eti for 2°
- Chronic renal disease
- chronic disease of the kidney
→ diabetic nephropathy
→ obstructive uropathy
→ chronic glomerulonephritis - reno-vascular disease such as renal artery stenosis → poor perfus’n to kidneys → activa’n of RAAS → TPR + CO ↑ → BP ↑
- acute glomerulonephritis
- acute polycystic kidney disease (APKD)
- autoimmune disease such as polyarteritis nodosa
- Coarcta’n of the aorta
- Endocrine disease
- Pheochromocytoma (↑ed adrenaline produc’n)
→ SSX = HA, sweating + palpita’ns
- Cushing’s syndrome
- Hyperaldosteronism (most common cause of 2° HTN)
⚠️Consider testing for hyperaldosteronism in pts w/ HTN who are younger, hypokalemic or fail to respond to Tx - Drugs
- steroids
- oral contraceptives
- NSAIDs → PGE2 blocked → afferent arteriole vasoconstricts → poor perfus’n → activa’n of RAAS → TPR + CO ↑ → BP ↑ - Pre-eclampsia
Complica’ns = end organ damage due to severe HTN
VASCULOPATHY = due to higher pressure exerted on vessels . . .
- aortic dissec’n
- aortic aneurysm
- endothelial dysfunc’n
- remodeling of arterial walls
- accelera’n of atherosclerosis → structural Δs in arterial wall → ↓ed transport of LDL particles from blood → ↑ed accumula’n of LDL in arterial wall → plaques aka fatty deposits form → stenosis
→ vascular injury → chronic inflamma’n = triggered + vessel compliance ↓
CEREBROVASCULAR DAMAGE
- acute hypertensive encephalopathy (due to cerebral edema)
- stroke (high BP can cause blood clots to form in arteries supplying brain ∴ blocking blood flow to brain + causing stroke)
- intracerebral hemorrhage (high BP can cause thin-walled arteries to rupture ∴ releasing blood into brain tissue)
RETINOPATHY → force of blood against artery walls = too high which causes vessels supplying retina to stretch, narrow + become damaged over time
HEART DISEASE
- aortic dissec’n due to aortic dilata’n
→ Type A involves ascending aorta = more serious than Type B + requires immediate surgical repair
> carotid dissec’n → can cause stroke
> coronary dissec’n → can cause MI
→ Type B ≠ involve ascending aorta
(Tx = medically control BP)
> celiac / mesenteric artery dissec’n
→ can lead to gut ischemia
> renal artery dissec’n → Ψ renal failure
> iliac artery dissec’n → can lead to lower limb ischemia
> external rupture → can lead to exsanginua’n i.e severe blood loss
- MI
- Afib
- CHD
- LVH due to pressure overload → Ψ heart
- accelerates coronary artery atherosclerosis which worsens ischemic heart disease
NEPHROPATHY
- micro-albuminuria
- proteinuria
- renal failure
- chronic renal insufficiency
Tx for T2D OR < 55 + not black
- ACE-I or ARB (Angiotensin II receptor blocker)
- MOA of ACE-I : inhibits ACE ∴ Angiotensin I can’t be converted to ATII ∴ ATII can’t further ↑ BP
- side effects = dry cough, angio-edema + HyperK
- C/Is- African or Caribbean, renal failure, K-sparing diuretics, NSAIDs, pregnant, breastfeeding
→ ibuprofen can make it less effective
→ end in “PRIL”
- MOA of ARB : prevents ATII from binding to its receptor (AT1) ∴ inhibiting it
- side effect = HyperK, ↓ Li excre’n, so watch out for Li toxicity w/ ARBs, ibuprofen can make ARBs less effective
- C/Is : renal failure, K-sparing diuretics, NSAIDs, pregnant, breastfeeding
→ end in “ARTAN”
- Add dihydropiridine CCB or Thiazide-like diuretic
- MOA of dihydropiridine CCB : ↓ entry of Ca into vascular + cardiac cells which ↓ intracellular [Ca] ∴ relaxing arterial smooth muscles aka vasodila’n hence ↓ing BP
- side effects - flushing, ankle edema, HA, palpita’ns
- CI’s = unstable angina + severe aortic stenosis
- end in “PINE”
- MOA of Thiazide-like diuretic = inhibit Na/Cl co-transporter in proximal part of DCT ∴ ↓ing Na reabsor’n + subsequently water reabsorp’n as ∴ blood volume will ↓ + so will BP
- side effects = HypoNa, HypoK + impotence in men
- no C/Is
- end in “THIAZIDE”
- Add other from step 2
- 𝛼1 blocker/antagonist
- MOA : blocks 𝛼-adrenergic receptors found in smooth muscle of blood vessels + urinary tract
→ vasodila’n → ↓ in BP
- side effects = postural hypoTN, syncope + dizziness
- end in “OSIN”
Tx for > 55 and/or Black or Caribbean
- CCB
- Add ARB or Thiazide-like diuretic
- Add the other from step 2
- 𝛼 blocker
Emergency Tx i.e in hypertensive emergency = hydralazine
→ MOA - ↑ levels of cGMP
→ > smooth muscle relax’ in arterioles compared to veins
→ ↓ in BP
- Know for OSCE *
Afib ✓
Def - most common type of arrhythmia
* arrhythmia = irregular pulse *
→ aberrant electrical activity btw pulmonary veins + left atrium ∴ overwhelming regular impulses from SA node
RFs
- HTN
- obesity
- advanced age
- cardiac / thoracic Sx
- obstructive sleep apnea
- congenital heart disease
- myocarditis / pericarditis
- excessive alcohol consump’n
- underlying heart / lung disease
- Hx of atrial arrhythmia, stroke or TIA
- endocrine disorders such as pheochromocytoma, diabetes, hyperthyroidism
Types
- 1st diagnosed = not diagnosed before, irrespective of dura’n or presence / severity of SSX
- Paroxysmal → terminates spontaneously +/- interven’n w/in 7 days of onset but can come back
- Persistent = continues beyond 7 days
- Long-standing persistent = present for > 12 months
- Permanent = Tx has been ended b/c all Tx op’ns failed
Eti = “SMITH”
- Sepsis
- Mitral valve pathology
- Ischemic heart disease
- Thyrotoxicosis
- HTN
Pathophys - RF / underlying heart disease causes dila’n of atria, fibrosis + inflamma’n → aberrant electrical activity from myocytes surrounding pulmonary veins overwhelms SA node, which causes re-entry circuits → propaga’n of irregular electrical activity of atria
SSX - often asymptomatic but can include . . .
- fatigue
- nausea
- palpita’ns
- chest pain
- tachycardia
- SOB / dyspnea
- polyuria (less common)
- dizziness (less common)
- diaphoresis / excessive sweating
Ddx
- atrial flutter
- atrial tachycardia
- hyperthyroidism
- WPW syndrome (ECG will show shortened PR interval)
Ix’s
- ECG → absence of distinct repeating P waves + variable/ irregularly irregular R-R intervals
- “CHA2DS2-VS” to assess pt’s need for anticoagulant
→ Congestive HF - give 1 point if pt has HF SSX
→ HTN - give 1 point if pt has resting BP > 140/90 mmHg on ≥ 2 occas’ns OR = on HTN medica’n
→ Age - give 2 points if pt ≥ 75 y/o
→ Diabetes - give 1 point if pt has fasting glucose > 125 mg/dL OR is on oral hyperglycemic agent
→ Stroke - give 2 points if pt ever had stroke or TIA
→ Vascular - give 1 point if pt ever had MI, aortic plaque or peripheral arterial disease
→ Sex - give 1 point if pt = female
⟹ Ttl of 0 points = no need for anticoagulant
⟹ Ttl of 1 point + female = no need for anticoagulant
⟹ Ttl of 1 point + male = consider anticoagulant
⟹ ≥ 2 points = give anticoagulant
- TSH to r/o hyperthyroidism
- U + E to r/o HypoMg / sepsis / dehydra’n
Emergency Tx i.e if pt is hemodynamically unstable = electrical DC cardiovers’n i.e defibrillator
Regular Tx
- DOAC if anticoagulant = indicated
+ β blocker for rate control
→ can also consider amiodarone
⟹ MOA of amiodarone = class 3 anti-arrhythmics ∴ prolongs plateau phase of myocardial ac’n Ψ / inhibits repolariza’n by slowing influx of Ca + efflux of K
⟹ side effects of chronic use = bradycardia, AV block, hepatitis, photosensitivity, grey discolora’n + pneumonitis, heartburn, dyspepsia
⟹ C/Is = WPW, 2nd or 3rd ° heart bock, prolonged QT interval
- has a long half-life, is highly lipophilic + widely absorbed by tissue, which ↓ its bioavailability in serum ∴ pt must be put on higher dose initially in order to achieve therapeutic level
- Left atrial appendage occlus’n i.e Watchman device if there are absolute C/Is to anticoagulant use OR risk of bleeding outweighs benefits
- Abla’n + pacemaker
Complica’ns
- MI
- heart failure
- stroke b/c due to its rhythm irregularity blood flow through heart becomes turbulent + hence has high chance of forming thrombus (blood clot), which can dislodge to brain + cause stroke
- Know for OSCE *
AV Block ✓
Def - delayed or absent (in Type 3) conduc’n from atria to ventricles
RFs
- LVH
- HTN
- CHF
- sarcoidosis
- ↑ed vagal tone
- cardiomyopathy
- acid base or electrolyte disturbance
- recent cardiac Sx, interven’n or abla’n
- chronic stable coronary artery disease
- AV node blocking agents i.e β blockers, CCBs, digitalis / digoxin, adenosine
Eti
→ 1st ° or Mobitz I = usually due to high vagal tone or medica’n
→ Mobitz II + Type 3 i.e complete heart block = usually due to block in His-Purkinje system but can also be due to digoxin + anti-arrhythmics from all 4 classes
Pathophys - inappropriate conduc’n through AV node → SA node can’t do its job of controlling HR → CO can ↓ + pt can die
SSX = syncope + HR < 40
Ix = ECG
→ Type 1 = CONSISTENT prolonged PR interval i.e > 0.2 secs
→ Type 2 Mobitz I = PROGRESSIVE prolonging PR interval + loss of QRS complex
→ Type 2 Mobitz II = PROGRESSIVE prolonging PR interval W/O loss of QRS complex
→ Type 3 / complete heart block = inconsistent PR intervals
Emergency Tx = temporary pacing
Regular Tx
- 1st ° or Type 2 Mobitz I asymptomatic = monitor only
- 1st ° or Type 2 Mobitz I symptomatic = discontinue all AV node blocking medica’ns
- Type 2 Mobitz II or Type 3 = discontinue all AV node blocking medica’ns + then do cardiac resynchroniza’n therapy or place permanent pacemaker
Ventricular Tachycardia ✓
Types
- sustained → rhythm lasts > 30 secs OR hemodynamic instability occurs in < 30 secs
- non sustained → rhythm lasts < 30 secs + presents w/ tachyarrhythmia w/ > 3 beats of ventricular origin
RFs for both
- CAD
- long QT syndrome
- Brugada’s syndrome
- electrolyte imbalance
- left ventricular systolic dysfunc’n
- idiopathic dilated cardiomyopathy
- cardiomyopathies such as Chagas’ disease
- drugs that prolong QT interval such as macrolide Abx, chlorpromazine, haloperidol, anti-arrhythmic drugs such as digoxin, flecainide, sotalol, + dofetilide
- hypertrophic cardiomyopathy = genetic disorder resulting in myocardial cell disorganiza’n + asymmetrical thickening of ventricle
Eti for both
- ischemic heart disease (most common cause)
- illicit drugs i.e cocaine/meth (for sustained only)
- electrolyte imbalances such as HypoK, HypoCa or HypoMg
- infiltrative cardiomyopathy → can result from SLE, sarcoidosis, amyloidosis, RA + hemochromatosis
SSX for non sustained
- tachycardia
SSX for sustained
- tachycardia
- hypoTN
- weak pulse
- syncope due to cerebral hypoperfus’n from hypoTN
- dyspnea + chest discomfort due to inadequate coronary perfus’n
Ddx for non sustained
- electrical artifact
- supraventricular tachycardia w/ aberrant conduc’n
Ddx for sustained
- Panic
- Sepsis
- Electrical artefact
- Hyperthyroidism
- Acute hemorrhage
- Pheochromocytoma
- Supraventricular tachycardia w/ aberrancy
- Supraventricular tachycardia w/ pre-excita’n
Ix’s for both
- U + E
- cardiac markers to r/o MI
- previous Hx of IHD i.e MI / PCTA / CABG (MUST BE PRESENT TO DIAGNOSE VTach !)
- ECG → tachycardia + wide QRS complex + left axis devia’n (MUST BE PRESENT TO DIAGNOSE VTach !)
Emergency Tx i.e pt is hypotensive / in cardiac failure or has ischemia = cardiovers’n
→ once pt = stable give lidocaine 1.5mg/kg IV
→ if this terminates tachycardia, infuse @ 2mg/min for up to 24 hrs but if tachycardia continues consider addi’nal lidocaine bolus of 0.5-0.75mg/kg, amiodarone (300mg bolus via large bore cannula in large vein or centrally + then 900mg 24 hr infus’n → DC cardiovers’n (150- 200J) under seda’n if drug therapy fails
Tx for non sustained
- if due to electrolyte abnormality correct it
- if NOT due to electrolyte abnormality give β blocker or CCB → catheter abla’n → anti-arrhythmic drug such as flecainide (100-200 mg orally bd) or propafenone (150-300 mg orally td)
Tx for sustained
- hemodynamically unstable ventricular tachycardia w/ pulse = synchronized cardiovers’n + treat cause if present
- torsades de pointes = IV Mg SO4 → remove hurtful drugs + correct electrolyte abnormalities
- catecholaminergic polymorphic ventricular tachycardia = β blocker → implantable cardioverter defibrillator
- hemodynamically stable sustained ventricular tachycardia = IV anti-arrhythmic drug such as adenosine or procainamide + treat cause if present → synchronized cardiovers’n
⟹ MOA of adenosine - activates specific K channels → Ca influx = inhibited → AV node conduc’n = slowed
⟹ side effects- skin flushing, lightheadedness, nausea + sweating
⟹ C/Is = COPD, asthma + heart block
- ongoing = implantable cardioverter defibrillator → anti-arrhythmic monotherapy such as mexiletine (200 mg orally every 8 hrs) /
flecainide (100-150 mg orally bd) / propafenone (150-300 mg orally every 8 hrs) / sotalol (80-160 mg orally bd)
Complica’ns for non sustained
- Vfib
- sudden death
- cardiomyopathy
- ICD related infe’cn
Complica’ns for sustained
- Vfib
- cardiomyopathy
- sudden cardiac death
- amiodarone-induced thyroid dysfunc’n
- implantable cardioverter defibrillator-related infec’n or malfunc’n
Circula’n order ✓
- RA receives deO2ated blood from everything above chest from SVC + from everything below chest from IVC
- RA → RV via tricuspid valve
- RV → 2 pulm. arteries via pulm. valve
- Blood gets O2ated in lungs
- Lungs → LA via the 4 pulm. veins
- LA → LV via mitral valve
- LV → ascending aorta via aortic valve + then to rest of body
- If LV can’t efficiently pump blood we get pulm. fluid overload *
Cardiac conduc’n system ✓
- SA node generates ac’n Ψ
- Ac’n Ψ spreads to atria ∴ causing them to contract
- AV node delays conduc’n to give time for atria to empty before ventricles begin contracting (on ECG the delay is the horizontal line btw the 1st P wave + QRS complex)
- AV node sends signal via Bundle of His
- Bundle of His splits off into left + right bundle branch which send signal to left + right ventricle respectively ∴ causing them to contract
- Purkinje fibers of ventricles receive signal
→ they have the fastest conduc’n velocities in the heart
Ionotropic v.s Chronotropic v.s Dromotropic effect ✓
- Ionotropic = ↑ in contractility of ventricle myocytes which ↑ SV
- Chronotropic = ↑ in frequency of ac’n ψ of pacemaker cells in SA node which ↑ HR
⟹ para releases Ach → Ach binds to M2 receptors on cardiomyocytes + SA node
→ contractility + HR ↓ = -ve ionotropic + chronotropic effect
⟹ sympathetic system releases NA → NA binds to B1 receptors on cardiomyocytes + SA node → contractility + HR ↑ = +ve ionotropic + chronotropic effect
- Dromotropic = ↑ in conduc’n (AV node)
Aortic regurgita’n ✓
Def- diastolic leakage of blood from aorta into LV, acute AR = surgical emergency !
RFs
- aortitis (= inflamma’n of the aorta 2° to systemic diseases such as syphilis, Behcet’s, Takayasu’s, reactive arthritis + ankylosing spondylitis)
- endocarditis
- rheumatic fever
- Marfan’s syndrome
- bicuspid aortic valve
Eti
→ Acute causes . . .
- type A aortic dissec’n extending to aortic valve
- damage to leaflets from infective or non-infective endocarditis
→ Chronic causes . . .
- aortic stenosis
- calcific disease
- Marfan’s syndrome
- congenital bicuspid aortic valve
General Pathophys - retrograde flow of blood from aorta into LV → ↑ in left ventricular volume + dilata’n of the chamber → initially leads to ↑ in CO but that ↑ in CO leads to disten’n + ↑ed pressure in peripheral arteries ∴ causing ↑ in peripheral systolic pressure → eventually, this causes worsening of the regurgita’n, which can cause peripheral systolic pressure to rapidly↓+ in severe disease can cause cardiovascular collapse (this phenomenon causes the wide pulse pressure that’s characteristic in severe aortic regurgita’n)
Pathophys for Acute AR - end-diastolic pressure in LV ↑ sharply → heart tries to compensate by ↑ing HR + contractility to keep up w/ ↑ed preload, but = insufficient to maintain normal SV
Pathophys for Chronic AR - ↑ in left ventricular volume + pressure causes ↑ in wall tens’n → to compensate for ↑ed wall tens’n, heart wall undergoes hypertrophy (both concentric + eccentric hypertrophy can occur but most of the time is eccentric) → in eccentric hypertrophy, sarcomeres are laid down in SERIES + it results from VOLUME overload v.s in concentric hypertrophy, sarcomeres replicate in PARALLEL + it results from PRESSURE overload → systolic HTN occurs 2° to ↑ed SV → the volume overload, which is directly related to the severity of the leak, results in ↑ in left ventricular end-diastolic volume
⟹ In chronic AR, most pts remain asymptomatic for decades b/c LV maintains stroke volume w/ compensatory chamber enlarg’nt + hypertrophy
SSX
- soft S1
- orthopnea
- collapsing pulse
- diastolic murmur
- low diastolic pressure
- narrow pulse pressure
- cyanosis (sign of acute AR)
- Corrigan’s sign = forceful carotid pulse
- pallor (sign of cardiogenic shock)
- raised JVP (sign of cardiogenic shock + CHF)
- basal lung crepita’ns due to pulm. edema
- tachypnea (sign of acute AR w/ pulm. edema)
- dyspnea (caused by pulm. edema in acute AR)
- PND (sign of chronic AR due to progressive left ventricular dysfunc’n)
- fatigue (sign of chronic AR due to progressive left ventricular dysfunc’n)
- weakness (sign of chronic AR due to progressive left ventricular dysfunc’n)
Ddx
- Aortic stenosis
- Mitral stenosis
- Mitral regurgita’n
- Pulmonary regurgita’n
Ix’s
- ECG
- color flow doppler + pulse wave doppler
- CXR → may show cardiac enlarg’nt
Tx for Acute AR
- ionotropes such as dobutamine (0.5 micrograms/kg/min IV, max dose = 20 micrograms/kg/min) + vasodilators + urgent valve replac’nt / repair
Tx for Chronic AR
- aortic valve Sx if ejec’n frac’n > 55% and/or LVESD (LV end-systolic diameter) < 50 mm
Complica’ns
- arrhythmias
- heart failure
- sudden death
- operative mortality
- myocardial ischemia
- infective endocarditis
- Know for OSCE *
Where on kidneys do diuretics act on ? ✓
- Thiazide like diuretics = DCT
- Loop diuretics = Na K Cl co transporter
Heart Failure ✓
1- Define cor pulmonale + recall common causes
2- Def, RFs, Eti, Pathophys, SSX, Diagnostic Criteria, Ddx, Ix, 1st line Mx, Complica’ns
- Cor pulmonale = right heart failure specifically b/c of lung disease such as a massive P.E (massive P.E involves proximal pulm. artery = only one that will cause ACUTE cor pulmonale)
→ Pathophys - lung disease → pulmonary HTN → cor pulmonale
→ CHRONIC causes of cor pulmonale
- pulmonary fibrosis
- COPD (most common chronic cause)
- recurrent small P.Es (will cause pulm.HTN but slowly)
- LHF = more common than RHF
RFs for Acute HF
> 70 y/o
- HTN
- smoking
- arrhythmias
- previous CVD
- previous chemo
- excessive alcohol intake
- previous episode of heart failure
- FHx of ischemic heart disease or cardiomyopathy
⚠️NSAIDs, nondihydropyridine CCBs like diltiazem or verapamil can exacerbate heart failure !
Eti for LHF = CAD (most common cause) + HTN
Patophys for LHF based on Eti
- CAD → direct ischemic damage to myocardium → remodeling + scar forma’n → ↓ in contractility + CO
- chronic / poorly controlled HTN → ↑ed afterload → ↑ed workload on the heart → LVH to compensate
SSX for LHF
- SOB
- tachypnea
- cold + clammy in periphery
- peripheral / central cyanosis
- paroxysmal nocturnal dyspnea
- orthopnea (= SOB when lying down)
ETI for RHF
- most common cause = as a result of LHF + when this happens it’s called Chronic HF but can also happen acutely b/c of . . .
- pulm. HTN
- massive P.E
- circulatory collapse
- MI that involved RV but spared LV
- tricuspid or pulmonic valve insufficiency b/c will cause volume overload
- things that cause impaired filling such as constrictive pericarditis, tricuspid stenosis, systemic vasodilatory shock, cardiac tamponade, hypovolemia, SVC syndrome
- congenital heart disease such as pulmonic stenosis (b/c will cause chronic pressure overload) or ASD (b/c will cause volume overload)
PATHOPHYS for Chronic RHF :
- before it happens, RV will be slowly damaged over a period of time due to lung disease such as COPD / pulm. fibrosis / recurrent small pulmonary emboli
- in early stages, there’s enough time for RV to compensate so we get RVH but eventually RV will decompensate
SSX for Chronic RHF = “HEAP”, PND, cough, orthopnea + dyspnea
- Hepatomegaly
- Elevated JVP b/c jugular veins = congested
- Ascites
- Peripheral edema i.e pitting edema in lower extremities
Ddx for RHF
- MI
- PE
- Cirrhosis
- Emphysema
- Viral pneumonia
- Respiratory failure
- Nephrotic syndrome
- Community acquired pneumonia
Ix’s for both
- BNP if echo not readily available → will be elevated = secreted from ventricular myocardium especially LV myocardium (can also be elevated in LVH, right ventricular overload, P.E, diabetes, cirrhosis, sepsis + GFR < 60)
→ can be falsely low in pt taking ARB + falsely high in pt w/ kidney failure - ECG + Troponin → to r/o MI
- LFTs → to r/o liver disease (in the case of hepatomegaly)
- CXR (“ABCDPE”)
→ Alveolar edema
→ kerley B lines (in stage 2 heart failure)
→ Cardiomegaly (no cardiomegaly in “MCM” i.e MI + constrictive pericarditis + mitral stenosis)
→ Dilated upper lobe vessels
→ Pleural Effus’n (in stage 3 heart failure)
→ Extra- previous CABG / prosthetic valve / pacemaker / defibrillator - perihilar pulmonary edema on CXR i.e bat-wing shape = indicative of CHF ! *
⚠️ Cardiomegaly DOES NOT ALWAYS mean heart failure !
→ could be pericardial effus’n or cardiomyopathy
HF Staging
I = no fatigue / palpita’ns / SOB w/ physical activity
II = slight “ “
III = SSX w/ light physical activity
IV = SSX @ rest or w/ any type of physical activity
Emergency Tx for Acute HF
- IV furosemide bolus if there’s pulm. edema + admit to CCU + stop NSAIDs / diltiazem / verapamil b/c can exacerbate heart failure !
→ MOA of furosemide = loop diuretic ∴ binds + inhibits Na-K-Cl co-transporter on thick ascending limb of loop of Henle ∴ inhibiting Na + Cl reabsorp’n + subsequently water reabsorp’n as well
→ side effects = dehydra’n + hypoTN
→ C/Is = anuria + severe electrolyte deple’n
→ end in “IDE”
⚠️ HF pts w/ renal disease might require higher doses of furosemide !
- ionotrope such as dobutamine if systolic BP < 100
- vasodila’n via nitrate infus’n if systolic BP > 100
Regular Tx for severe HF i.e w/ ↓ed ejec’n frac’n = ACE-I/ARB + β blocker
→ aldosterone antagonist → SGLT-2 inhibitor
⟹ aldosterone antagonists end in “ONE” i.e spironolactone / eplerenone) → act on collecting duct of kidney
⟹ side effects of aldosterone antagonists = HyperK (cause HyperK by interfering w/ K excre’n which is why they’re called “K sparing diuretics”), breast tissue growth
Indica’ns for CRT-D (Coronary Resynchroniza’n Therapy Device)
- EF ≤ 35%
- Stages 3 or 4
- Wide QRS i.e ≥ 150 ms + LBBB
Complica’ns for LHF
- RHF due to fluid overload
- arrhythmias (in acute heart failure)
- cardiogenic shock due to pump failure
- respiratory failure due to fluid overload → give pt CPAP in this case
- P.E, ACS, CVAs + rupture of myocardium = common causes of sudden death in pts w/ heart failure
- Know it for OSCE *
Aortic dissec’n ✓
Def - tear in tunica intima of aorta
RFs
- HTN
- smoking
- FHx of aneurysm or aortic dissec’n
- connective tissue disorders like Marfan’s or Ehlers-Danlos syndrome
Eti = RFs
Types
- Type A = involves ascending aorta
- Type B = ascending aorta ≠ involved
SSX
- sudden tearing/stabbing chest pain that might radiate to back
- blood pressure differential btw both arms or both legs (> 20 mmHg difference in systolic BP)
Ix’s :
- ECG to r/o STEMI
- TTE or CT if TTE isn’t available → CT will show widened mediastinum
- Consider TOE for definitive diagnosis
Tx
1. β blocker or non-dihydropyridine CCB + IV opioid
2. EVAR or open air if pt = hemodynamically unstable OR it’s a confirmed type A OR a complicated type B
Complica’ns
- cardiac tamponade
- aortic incompetence
- Know for OSCE *
Mitral stenosis ✓
Def - narrowing of mitral valve orifice
RFs
- female
- streptococcal infec’n
Eti
- RA
- SLE
- carcinoid syndrome
- amyloid deposi’n in mitral valve
- degenerative calcifica’n (in the elderly)
- infective endocarditis w/ large vegeta’ns
- rheumatic heart disease due to rheumatic fever (= most common cause of mitral stenosis)
- congenital mitral stenosis (2° to parachute mitral valve or Lutembacher’s syndrome)
- inborn errors of metabolism such as Hurler-Scheie syndrome or Anderson-Fabry disease
Pathophys - filling of LV ↓ → pressure in LA ↑ → pulmonary congest’n + CO = limited b/c restricted orifice limits filling of LV
SSX
- dyspnea
- orthopnea
- diastolic murmur
- neck vein distens’n
- opening snap on ausculta’n
Ddx
- unexplained Afib
- left atrial myxoma = LA tumor that can obstruct mitral orifice + hence mimic SSX of mitral stenosis
Ix’s
- ECG → Afib / left atrial enlarg’nt / RVH
- trans-thoracic echocardiogram → hockey stick-shaped mitral deformity
- CXR → double right heart border indicating enlarged LA, prominent pulmonary artery + Kerley B lines
Tx
- diuretic such as furosemide (40 mg orally od initially + then titrate according to response to Tx, max dose = 600 mg/day) or bumetanide (0.5 mg orally od initially + then titrate according to response to Tx, max dose = 10 mg/day)
→ percutaneous balloon valvotomy → ivabradine if pt ≠ pregnant (2.5-5 mg orally bd initially + then titrate according to response to Tx + HR, max dose = 15 mg/day) or β blocker such as atenolol (25-100 mg od)
Complica’ns
- aFib
- stroke
- pulmonary HTN
- infective endocarditis
- warfarin induced hemorrhage
- Know for OSCE *
Mitral regurgita’n ✓
Def - retrograde flow from LV into LA
RFs
- Hx of MI
- Hx of IHD
- Hx of cardiac trauma
- elevated systolic BP
- infective endocarditis
- mitral valve prolapse
- Hx of rheumatic heart disease
- Hx of congenital heart disease
- hypertrophic cardiomyopathy
- left ventricular systolic dysfunc’n
- anorectic, dopaminergic drugs or serotonergic drugs such as ergotamine, pergolide + cabergoline
Eti
> ACUTE causes . . .
- infective endocarditis
- acute rheumatic fever
- ischemic papillary muscle dysfunc’n or rupture
- acute dilata’n of LV due to ischemia or myocarditis
> CHRONIC causes . . .
- infective endocarditis
- mitral valve prolapse
- acute rheumatic fever
- mitral annular enlarg’nt
- myxomatous degenera’n of mitral leaflets or chordae tendineae
- acute dilata’n of LV due to ischemia or myocarditis
- ischemic papillary muscle dysfunc’n or rupture
Pathophys - ↑ in blood volume w/in LA → ↑ed preload delivered to LV during diastole → left ventricular volume overload
> in chronic progressive MR, ventricular remodeling occurs so CO can be maintained
» initial ↑ in ejec’n frac’n is usually observed
SSX
- fatigue
- dyspnea on exer’n
- holosystolic murmur
- ↓ed exercise tolerance
- lower extremity edema
Ddx
- Atrial myxoma
- Aortic stenosis
- Mitral stenosis
- Infective endocarditis
- Acute coronary syndrome
- Aortic or pulmonic valve disease
Ix’s
- ECG → may show underlying arrhythmia or prior infarct
- trans-thoracic echo for presence + severity of MR + to check for structural + flow abnormalities
Tx = Surgical valve replac’nt
Complica’ns
- Afib
- post op stroke
- pulmonary HTN
- prosthesis stenosis
- post op endocarditis
- left ventricular dysfunc’n → CHF
- prosthesis dysfunc’n after valve replac’nt
- recurrent MR or peri-valvular regurgita’n after valve replac’nt
- Know for OSCE *
Congenital heart defects ✓
Left to R. shunt types
- ASD = hole btw L. + R. atria so extra blood flows into R. side of heart causing it to stretch + enlarge
→ SOB, difficulty feeding, poor weight gain, LRTIs
→ can cause stroke in pts w/ DVT
→ refer to pediatric cardiologist → if small + asymptomatic watch + wait → can be corrected surgically using a transvenous catheter closure (via femoral vein) or open heart surgery
→ in adults, anticoagulants (such as aspirin, warfarin) = used to ↓ risk of clots + stroke - VSD = most common one = hole btw L. + R. ventricle so extra blood flows into lungs ∴ causing high pressure in lungs, small VSD = asymptomatic, pansystolic murmur @ left sternal border
→ poor feeding, dyspnea, tachypnea, FTT
→ pts are at ↑ed risk of developing infective endocarditis
→ refer to pediatric cardiologist → if small + asymptomatic watch + wait → can be corrected surgically using a transvenous catheter closure (via femoral vein) or open heart surgery - PDA (prematurity = RF)
→ murmur on newborn exam
→ SOB, difficulty feeding, poor weight gain, LRTIs
→ pts = typically monitored until 1 y/o using echos + then after 1 y/o trans-catheter or surgical closure can be performed - Coarcta’n of the aorta = narrowing of aorta
→ weak femoral pulses, tachypnea, labored breathing, poor feeding, grey + floppy baby
→ Ix for immediate diagnosis = 4 limb BP
→ in cases of critical coarcta’n i.e risk of HF + death shortly, PGE such as alprostadil = given after after birth to keep ductus arteriosus open while waiting for Sx → Sx is then performed to correct coracta’n + ligate ductus arteriosus
Right to L. shunt types
- Tetralogy of Fallot = VSD + pulm. valve stenosis + RVH + overriding aorta (Rubella = RF)
→ cyanosis, clubbing, poor feeding, poor weight gain, ejec’n systolic murmur
→ in neonates, PG infus’n can be used to maintain ductus arteriosus but ttl surgical repair via open heart Sx = definitive Tx - Transposi’n of the great arteries = aorta + pulm. artery aren’t in their normal posi’n due to failure of aorticopulmonary septum to spiral during septa’n
→ often diagnosed during pregnancy on antenatal scans. If not detected during pregnancy will present w/ cyanosis, tachypnea + ‘egg-on-side’ appearance on CXR w/in a few days of birth
→ PG infus’n can be used to maintain ductus arteriosus but surgical repair = definitive Tx - Ebstein’s anomaly = when tricuspid valve doesn’t develop properly
→ gallop rhythm heard on ausculta’n, cyanosis, dyspnea, tachypnea, poor feeding
→ diagnosed w/ echo - Truncus arteriosus = pulm. artery + aorta are a single vessel ∴ there’s way too much blood flow to the lungs = FATAL so must be treated !
Features of innocent murmurs in kids ✓
” 5 S’s “
- soft i.e < grade 2/5 + no thrill
- short
- systolic
- symptomless
- situa’n dependent i.e quieter w/ standing or only appears when child is acutely ill
Aorta + its branches ✓
→ Ascending aorta gives rise to left + right coronary arteries which supply the heart hence they’re called the coronary vessels
→ Ascending aorta turns upwards + backwards to become aortic arch . . .
The 3 branches of the aortic arch =
- Brachiocephalic trunk → 2 branches
→ right subclavian supplies right arm + right common carotid right side of head and neck
→ right common carotid → 2 branches = right internal and right external
- Left common carotid artery → 2 branches = left internal carotid + left external carotid
- Left subclavian artery
Although left + right subclavian have diff origins, they both become axillary artery when they enter axilla
Axillary artery continues into arm as brachial artery which bifurcates @ cubital fossa into ulnar + radial artery
The aortic arch then turns downwards to become the descending / thoracic aorta (@ T4)
The thoracic / descending aorta then becomes the abdominal aorta (below the diaphragm i.e @ T12)
* has less elastin than descending aorta *
The abdominal aorta has 3 anterior branches =
- Celiac trunk → 3 branches = left gastric, splenic + common hepatic
- Superior mesenteric artery
- Inferior mesenteric artery
- abdominal aorta bifurcates @ L4 into its 2 terminal branches = right + left common iliac
→ each bifurcate into internal + external iliac
Each external iliac becomes femoral artery when enters thigh, its branch = deep artery of the thigh
- they become popliteal artery at the knee → 2 branches
→ anterior tibial → terminates into dorsalis pedis artery
→ posterior tibial → supplies posterior compart’nt of leg + plantar reg’n
Branches of descending abdominal aorta from diaphragm to iliacs ✓
” Inferior Prostitutes Cause Sad Swollen Red [Testicles In Men] Living In Sin “
- Inferior Phrenic artery
- Celiac (abdominal aorta)
- SMA (abdominal aorta)
- Suprarenal (middle)
- Renal (branches off abdominal aorta @ L2)
- Testicular
- Lumbars
- IMA (abdominal aorta)
- Sacral
AAA ✓
Def - localized, permanent, abnormal dilata’n of a blood vessel in this case AA by > 1.5x or > 50% its normal diameter, ruptured aneurysm = surgical emergency !
- majority = below renal arteries
⚠️ All 3 blood vessel layers have to be involved for it to be a TRUE aneurysm !
RFs:
> 55 y/o
- FHx
- atherosclerosis
- hypercholesterolemia
- male (for occurrence)
- female (for risk of rupture)
- PMHx of connective tissue disorder
- HTN + current/previous smoking = strongest RFs
- other aneurysms such as iliac / femoral / popliteal so if pt has aneurysm in 1 of those 3 always check for AAA
Intact AAA = asymptomatic
SSX of RUPTURED AAA
- hypoTN
- abdo or back pain
- non-tender pulsatile abdominal mass
- blue toe syndrome bilaterally due to emboli
- flank ecchymosis / grey Turner sign → suggests retroperitoneal bleeding
Classifica’n
- Saccular = spherical shape + develops at 1 side of vessel wall = more likely to rupture b/c wall tens’n ≠ distributed equally
- Fusiform = spindle shape; involves all of vessel’s circumference
- False / Pseudo = expanding pulsatile hematoma that forms as a result of a leaking hole in an artery + stays in continuity w/ arterial lumen = false aneurysm b/c has no endothelial lining i.e doesn’t involve all 3 vessel layers
Ix for diagnosis = aortic U/S if ur not sure if it’s an aneurysm but if ur sure it’s an aneurysm do CT instead
Eti
- infec’n
- atherosclerosis
- inflammatory i.e CA, polyarteritis nodosa
- post dissec’n i.e after an accident
- congenital diseases such as tuberous sclerosis, Marfan’s, Ehlers-Danlos syndrome
Pathophys - enlarg’nt of atherosclerotic plaque → pressure / ischemic atrophy of media + loss of elastic fibers
→ weakening + dilata’n of aortic wall → aneurysm forms @ that weak spot
Ix’s
- U/S for SCREENING → don’t use in emergency setting b/c won’t necessarily catch rupture
- CT angiogram for diagnosing rupture
Treat if aneurysm = ruptured OR pt is symptomatic OR asymptomatic but aneurysm > 5.5 cm OR asymptomatic but aneurysm > 4 cm + growing > 1cm/yr → if these criteria aren’t met just use conservative Mx i.e smoking cessa’n, controlling BP + U/S monitoring every 6 months
Tx = Open repair or EVAR
→ open repair if pt < 70 y/o + EVAR if pt > 70 y/o
⟹ EVAR = through b/l femoral access, requires annual surveillance for endoleak + if there’s an endoleak, that will require Sx
→ open repair = longer recovery time but has longer durability
⟹ can use trans-abdominal approach or retroperitoneal approach which is good for obese pts or pts w/ multiple prior abdominal surgeries
Open repair complica’ns
- incis’nal hernia
- spinal cord ischemia
- lower extremity ischemia
- graft infec’n → has very high mortality
- colon ischemia → pt will have bloody stools the day after
Complica’ns
- ileus
- post op AKI
- ischemic colitis
- intestinal obstruc’n
- abdominal compartment syndrome
- Know for OSCE *
Cardiac Arrest ✓
Def - sudden circulatory failure as a result of a cardiac arrhythmia
RFs
- CAD
- HCM
- long QT syndrome
Eti
- Vifb = shockable
- Vtach = shockable
- pulseless electrical activity = non shockable
- asystole = nonshockable
SSX
- unresponsive
- lack of pulse
- abdonalr breathing
Ix’s :
- continuous cardiac monitoring to see if it’s a shockable rhythm or not
Tx :
- CPR
- Defibrilla’n +/- epinephrine
(if it’s a shockable rhythm) → can consider amiodarone or lidocaine if unresponsive to shock
Complica’ns
- death
- anoxic brain injury
- Know for OSCE *
Respiratory Arrest ✓
Eti
- asthma
- 2° to resp. arrest
- severe pneumonia
- acute on chronic respiratory failure
- plugged tracheostomy
- overdose of drug that causes respiratory depress’n such as morphine/barbiturates
Tx
1. A + B of ABCD
2. Ventila’n w/ 100% O2
3. Treat underlying cause
Cardioresp. arrest ✓
Def - cessa’n of adequate heart func’n + respira’n resulting in death
Eti
- P.E
- CAD (75% of cases = due to this)
- myocarditis
- tetralogy of Fallot
- valvular heart disease
- myocardial hypertrophy
- heart failure (if ejec’n frac’n < 35%)
- inherited disorders like Brugada syndrome / short QT syndrome / long QT syndrome
- bronchospasm due to pneumonia / pulmonary edema / pulmonary hemorrhage
- severe asthma or COPD
- respiratory muscle weakness (for ex due to spinal cord injury)
Ddx
- Acidosis
- Hypoxia
- Hypothermia
- Hypovolemia
- Hypo or HyperK
- Cardiac tamponade
- Thrombus / acute MI
- Tens’n pneumothorax
- PE / Thromboembolism
- Toxic overdose of drugs
Emergency Tx = Basic Life Support → Defibrilla’n → Advanced Life Support → Post-resuscita’n care → Long-term Mx
PAD ✓
Def - narrowing or blockage of arteries that carry blood from heart to limbs = type of PVD
RFs
> 40 y/o
- T2D
- HTN
- HLD
- smoking
- sedentary lifestyle
Eti = atherosclerosis
SSX
- intermittent claudica’n i.e leg pain that starts when pt walks + stops when they rest
- “6 P’s” when it becomes limb ischemia i.e . . .
→ pain
→ pallor
→ paralysis
→ paresthesia
→ perishingly cold
→ pulselessness (late sign)
Ddx
- nerve root compress’n
- Baker’s cyst (pain will be present even at rest + area behind knee will be swollen + tender)
Order of Ix’s
- ABI
> 1.3 = calcified vessels
→ 0.8-1.3 = no PAD
→ 0.5-0.79 = mild~moderate PAD + claudica’n
< 0.5 = severe PAD i.e critical limb ischemia + pain even @ rest - duplex U/S
- CT angiography w/ contrast = gold std for diagnosis
Complica’n’s
- arterial ulcers
- acute limb ischemia = sudden ↓ in limb perfus’n that threatens viability of that limb hence = vascular emergency !
Emergency Tx i.e if there’s acute limb ischemia = surgical embolectomy + unfractionated heparin (if pt has Afib) → amputa’n if leg = non-viable
Regular Tx
- Smoking cessa’n + BP / glucose control
- Exercise training i.e structured + supervised program of regularly walking to point of near-maximal claudica’n pain, resting + repeating again
- Medical Tx i.e 80mg statin + 75mg clopidogrel daily + naftidrofuryl oxalate (5-HT2 receptor antagonist that acts as a peripheral vasodilator)
- Sx . . .
- endovascular angioplasty + stenting
- endarterectomy i.e cutting vessel open + removing atheromatous plaque
- bypass Sx = using graft to bypass blockage
- Know for OSCE *
Carotid artery stenosis ✓
Def - narrowing of carotid artery lumen
RFs
- smoking
- older age
- Hx of CVD
Eti = atherosclerosis plaque
Classifica’n
- Mild stenosis = < 50% diameter reduc’n
- Moderate stenosis = 50 - 70% diameter reduc’n
- High grade stenosis = > 70% diameter reduc’n
- Near-occlus’n
- Occlus’n = completely occluded carotid artery
SSX = transient visual SSX i.e . . .
- homonymous hemianopia
- temporary vis’n loss in ipsilateral eye
Ix’s
1. duplex U/S
2. head/neck/chest CTA
Tx
- asymptomatic + stenosis < 70% = antiplatelet therapy + cardiovascular risk reduc’n i.e managing RFs
- asymptomatic + stenosis ≥ 70% + good surgical candidate = carotid endarterectomy + cardiovascular risk reduc’n i.e managing RFs
- asymptomatic + stenosis ≥ 70% + poor surgical candidate = carotid artery stenting + cardiovascular risk reduc’n i.e managing RFs
- symptomatic + ipsilateral carotid stenosis ≥ 50% = carotid endarterectomy or stenting + managing RFs + lipid-lowering therapy i.e statin
- symptomatic + ipsilateral carotid stenosis < 50% = antiplatelet therapy + managing RFs + lipid-lowering therapy i.e statin
Complica’n = ischemic stroke
Varicose veins ✓
Def - distended superficial veins measuring > 3mm in diameter, usually in legs
RFs
- FHx
- DVT
- female
- obesity
- prolonged standing
- pregnancy b/c uterus causes compress’n of pelvic veins
Eti = venous valve incompetence
Pathophys - valve doesn’t func’n properly → blood pools → ↑ed pressure → veins distend
SSX = asymptomatic or . . .
- heavy / dragging sensa’n in legs
- edema
- itchy legs
- leg cramps
- restless legs
- leg fatigue or aching w/ prolonged standing
Ddx
- reticular veins = dilated blood vessels in the skin measuring 1-3mm in diameter
- telangiectasia/spider veins/thread veins = dilated blood vessels in the skin measuring < 1mm in diameter
Ix = duplex U/S
→ valve closure time > 0.5 second = indicative of reflux in superficial system
→ valve closure time > 1 second = indicative of reflux in deep system
Tx
- if due to pregnancy → usually improves after delivery
- symptomatic w/ no evidence of PVD or tributary insufficiency only = phlebectomy or foam sclerotherapy
- symptomatic superficial vein insufficiency w/ no evidence of PVD or truncal axial insufficiency only
= endovenous thermal abla’n (via radiofrequency or laser) → foam sclerotherapy if that doesn’t work →
open Sx (stripping + liga’n) - symptomatic w/no evidence of PVD w/ both truncal axial + tributary insufficiency = endovenous thermal abla’n + either phlebectomy or foam sclerotherapy → foam sclerotherapy of truncal + tributary veins if that doesn’t work → open Sx + phlebectomy
- symptomatic w/ no evidence of PVD + perforator veins w/ reflux = located near healed or active venous ulcers → either foam sclerotherapy or endovenous thermal abla’n + compress’n therapy (i.e bandage or stockings) → perforator Sx if that doesn’t work + compress’n therapy
- deep vein obstruc’n = stenting or reconstruc’n
Complica’ns
- DVT
- chronic venous insufficiency
- Know for OSCE *
Ulcers ✓
Def - wounds or breaks in skin that heal slowly or not at all due to underlying pathology
Types
- arterial ulcer pathophys - PAD → insufficient blood supply to skin
- venous ulcer pathohys - venous insufficiency → pooling of blood + waste products in skin
Arterial v.s Venous ulcers
- well defined borders v.s irregular borders
- less likely to bleed v.s more likely to bleed
- more painful v.s less painful
- pain = worse w/ eleva’n v.s better w/ eleva’n
- arterial occurs on toes + heels, has deep punched-out appearance + leg might be cold w/ no palpable pulses
Ix’s = ABI to check if pt has PAD
Tx for arterial ulcer = like PAD
Tx for venous ulcer
- constant nurse wound care i.e clean → debride → dress
- analgesia
- Abx if infected
- compress’n stockings
Necrotizing Fasciitis ✓
Def - rare but life-threatening subcutaneous soft-tissue infec’n that progressively extends to deep soft tissues including muscle fascia + overlying fat, but not into underlying muscle = surgical emergency !
→ also known as flesh-eating bacteria due to the release of toxins
→ Fournier’s gangrene = necrotizing fasciitis of perineum + genital reg’n
RFs
- IV drug use
- Varicella zoster infec’n
- non-traumatic skin les’ns
- cutaneous injury / Sx / trauma
- contact w/ pt w/ group A strep infec’n
Types
Type I - polymicrobial infec’n caused by anaerobes such as Bacteroides, Clostridium or Peptostreptococcus + facultative anaerobes such as certain Enterobacterales (E. coli, Enterobacter, Klebsiella, Proteus)
Type II - monomicrobial infec’n caused by Streptococcus pyogenes i.e group A strep + sometimes Staph aureus or MRSA = usually seen in older pts w/ underlying illness
Pathophys - bacteria = introduced into skin + soft tissue due to minor trauma / Sx / puncture wound → infec’n extends through fascia but not into underlying muscle → release of bacterial toxins cause systemic SSX such as fever, tachycardia, hypoTN
SSX
- severe pain
- fever
- N + V
- hypoTN
- tachycardia
- lightheadedness
Ddx
- cellulitis
- impetigo
- erysipelas
Ix’s
- surgical explora’n
- blood + tissue cultures
- FBC, U + E, creatinine kinase, lactate
Tx
1. Emergency surgical debridement + supportive care + high dose broad spectrum ABs
2. Pathogen specific AB
Complica’ns
- death
- skin loss + scarring
- Know for OSCE *
Gangrene ✓
Def - decay of body tissue = complica’n of necrosis
RFs
- diabetes
- malignancy
- renal disease
- drug / alcohol abuse
- atherosclerosis (for ischemic)
- smoking (for ischemic gangrene)
- contaminated wound (for infectious
- trauma or abdominal Sx (for infectious gangrene)
Types
- infectious gangrene
- ischemic gangrene
Eti for infectious gangrene
- necrotizing fasciitis
- gas gangrene (usually caused by Clostridium perfringen or other clostridium species)
Eti for ischemic gangrene
- venous obstruc’n
- Atherosclerosis / PAD
- diabetes-associated microangiopathy
- hypercoagulable states such as IV drub abuse, vasculitis, malignancy, or antiphospholipid syndrome
SSX
- rotting appearance
- crepitus in gas gangrene
Ix’s
- FBC
- CMP
- LDH
- coagula’n panel
- blood culture to check for bacteremia
Tx
- necrotizing fasciitis + still waiting for culture + sensitivity results =
surgical debridement + intensive supportive care + empirical broad-spectrum Abx - gas gangrene = intensive supportive care+ surgical debridement ± amputa’n + IV Abx
- ischemic gangrene w/ viable extremity = IV heparin + thrombolytic therapy
- ischemic gangrene w/ threatened or non-viable extremity (limb expectancy > 2 yrs) = IV heparin +
surgical revasculariza’n ± amputa’n - ischemic gangrene w/ threatened or non-viable extremity (limb expentancy ≤ 2 yrs = IV heparin + percutaneous transluminal angioplasty (PTA) ± amputa’n
Complica’ns
- loss of limb
- sepsis → shock
- acute renal failure
- hemolysis b/c 𝛼 toxin= produced in gas gangrene = metallo-enzyme that causes lysis of erythrocytes, leukocytes, platelets, fibroblasts + muscle cells
Asthma ✓
Def - chronic inflammatory obstructive lung disease b/c “obstructs” air from exiting lungs by ↑ing airway resistance = reversible
⚠️ If FEVC1 measured over FVC measured < 0.7 or 70% = obstructive pb !
Eti
- Atopic / Extrinsic aka due to allergen exposure (pollen, pet, dust, etc)
- Nonatopic / Intrinsic aka due to irritant exposure (cold, smoking, exercise, aspirin induced)
→ less common than atopic
→ mainly neutrophils as opposed to eosinophils like in atopic - Hygiene hypothesis = ppl who are exposed to allergens early in life = less likely to develop asthma later in life as an adult *
Pathophys
1. Allergen/irritant = inhaled + transported by dendritic cell that has MHC-II molecule
2. Dendritic cell presents antigen aka allergen to Th-2 cell
3. On its membrane, Th-2 cell has CD4 molecule + T-cell receptor (specific to particular antigen)
4. CD4 molecule interacts w/ MHC-II molecule of dendritic cell + T-cell receptor interacts w/ allergen via binding
5. Interac’n triggers Th-2 to release IL-4 + IL-5
6. IL-4 activates plasma cells to produce IgE antibodies
7. IgE antibodies bind to mast cells which triggers mast cell to undergo degranula’n
8. When mast cells degranulate they produces histamines + leukotrienes
9. IL-5 activates eosinophils which will release leukotrienes + cytokines + proteases (chronically eventually damage respiratory system)
10. Histamines + Leukotrienes affect bronchioles → inflamma’n, broncho-constric’n + ↑ in mucus produc’n → airways narrow + resistance ↑
11. If this happens chronically, we can get fibrosis, which will cause PERMANENT airway narrowing instead of REVERSIBLE airway narrowing
SSX of poorly controlled asthma
- frequent breathing pbs
- use of reliever medica’n > 3x/wk
- cough + wheeze upon expira’n
- SSX wake pt up at night
Ix’s
- FeNO or spirometry w/ bronchodilator reversibility for diagnosis (FeNo preferably)
→ FeNO > 40 ppb = diagnostic
→ only use spirometry for pts > 5 y/o
⟹ reversibility i.e ↑ in FEV1 ≥12% = diagnostic
Tx for adults i.e > 12 y/o
- SABA (short acting β2 agonist)
= reliever inhaler ∴ should only be used when pt has attack (usually salbutamol aka ventolin)
- MOA = activate β2 receptors in bronchioles which causes relaxa’n of smooth muscles of bronchi i.e bronchodila’n
- side effects = HAs, palpita’ns, tachycardia, anxiety + tremors
- cau’ns = CVD such as angina
- end in “TAMOL” or “TEROL”
- Add Low dose ICS = preventer inhaler so must be taken everyday
- MOA = ↓ mucus secre’n + mucosal inflamma’n + widens airways
- side effects = oral thrush / candidiasis (fungal infec’n) + hoarse / raspy voice
→ if thrush happens change to large volume spacer - cau’ns = children
- end in “ONE”
- Add Leukotriene receptor antagonist (LTRA) to ICS + SABA
- MOA = competitively block leukotriene receptors ∴ ↓ bronchoconstric’n, vascular permeability + mucus secre’n
- side effects = liver toxicity
- CIs = liver impair’nt
- end in “LUKAST”
- Add LABA to low dose ICS + SABA
- end in “EROL”
⚠️ LABAs MUST ALWAYS BE USED W/ ICS !
- LAMA (anti-muscarinic drug / muscarinic receptor antagonist) or methylaxnthine derivative
- MOA of LAMA = competitively binds to M3 receptors in trachea / bronchioles so Ach can’t bind + activate them ∴ inhibiting para. system from broncho-constricting
- side effects = dry mouth
- C/Is = narrow angle glaucoma b/c inhibits para so instead of ciliary muscles constricting they will relax which will worsen humour drainage
- end in “TROPIUM”
- MOA of Meth. derivative = bronchodilates by inhibiting phospho-diesterase ∴ can no longer convert CAMP to 5-AMP which ↑ CAMP levels
- side effects = insomnia, N/V, seizure, arrhythmia, metabolized by cytochrome P-450 + blocks adenosine
- C/Is = arrhythmia or seizure disorder
- end in “PHYLLINE”
Tx for pts btw 5 + 12 y/o = same as adults but no leukotriene receptor antagonist + instead of LAMA = ↑ dose of ICS
1. SABA
2. ICS
3. LABA such as salmeterol
→ only continue LABA if pt has good response to it
4. Up titrate ICS to medium dose
5. ↑ dose of ICS to high dose
6. Specialist referral + asthma review every 3 months to consider ↓ing corticosteroid by 25-50%
Tx for pts < 5 y/o = same as adults but no LABA or LAMA
1. SABA
2. ICS or leukotriene antagonist
3. Add the other one you didn’t give in step 2
4. Specialist referral
Emergency Tx for adults
- O2 mask + nebulized SABA (2.5-5 mg) w/ SAMA + ICS
→ monitor vitals, O2sat, pCO2 + peak flow / PEFR
Emergency Tx for children
1. Salbutamol inhaler via a spacer device → start w/ 10 puffs every 2 hrs
2. Nebulizer w/ salbutamol or ipratropium bromide
3. Oral prednisone
4. IV hydrocortisone
5. IV Mg SO4
6. IV salbutamol
7. IV aminophylline
8. ICU admiss’n for intuba’n + ventilator
Acute Complica’ns
MODERATE
- Peak Expiratory Flow Rate (PEF) 50-70% best or predicted → do measured / normal
- normal speech
- RR < 25/min
- HR < 110 bpm
SEVERE
- PEF 33-50% best or predicted
- can’t finish sentences
- RR ≥ 25/min
- HR ≥ 110 bpm
LIFE THREATENING (just 1 criteria = enough to make it life threatening !)
- PEF < 33% best or predicted
- O2sat < 92%
- Normal pCO2
- bradycardia / hypoTN / dysrhythmia
- exhaus’n / coma / confus’n
Chronic Complican’s
INTERMITTENT
- SSX < 1x/wk
- nocturnal SSX ≤ 2x/month
- PEF/FEV1 variability < 20%
- FEV1/PEF ≥ 80% predicted
MILD persistent
- PEF/FEV1 variability 20-30%
- FEV1/PEF ≥ 80% predicted
MODERATE persistent
- PEF/FEV1 variability ≥ 30%
- FEV1/PEF 60-80% predicted
- nocturnal SSX ≥ 1x/wk
SEVERE persistent
- PEF/FEV1 variability ≥ 30%
- FEV1/PEF ≤ 60% predicted
- frequent exacerba’ns
- frequent nocturnal SSX
- limited physical activity
Prognosis - improves after early childhood but can return in young adulthood
- Know for OSCE *
At which level does trachea bifurcate ? ✓
Trachea bifurcates into left + right main bronchi @ carina (T5)
Why are aspirated foreign bodies far more likely to enter + obstruct RIGHT bronchus ? ✓
B/c right main bronchus = wider, shorter + more vertical than left main bronchus
An object aspirated while standing or sitting upright will usually be found in the … ✓
Inferior por’n of right lower lobe
An object aspirated while supine will most often end up in the … ✓
Superior por’n of right lower lobe
How many lobes do the right + left lungs have ? ✓
Right = 3
→ upper/superior lobe
→ middle lobe
→ lower/inferior lobes
Left = 2
→ upper/superior lobe
→ lower/inferior lobe
How many fissures does each lung have ? ✓
Right lung has 2 fissures
→ Horizontal fissure btw superior + middle lobe
→ Oblique fissure btw middle + inferior lobe
Left lung has 1 fissure = Oblique fissure
Pleural Effus’n ✓
Def - when fluid collects in pleural space (space in btw parietal + visceral pleura)
→ empyema = infected pleural effus’n
⟹ pleural aspira’n will show pus, low pH, low glucose + high LDH = treated w/ chest drain + Abx
Types
- Exudative (has to have ≥ 1 of the following . . .)
→ Pleural protein : serum protein ratio > 0.5
→ Pleural LDH : serum LDH > 0.6
→ Pleural LDH > 2/3 of upper limit of normal serum LDH - Transudative → low protein content i.e < 30g/L
Exudative causes = inflamma’n causes protein to leak out of tissues + into pleural space i.e . . .
- TB
- RA
- pneumonia
- lung cancer
- mesothelioma
Transudative causes (fluid moves across or shifs into pleural space)
- congestive HF
- hypoTSH
- hypoalbuminemia
- Meigs syndrome = pleural effus’n + benign ovarian tumour + ascites
SSX
- cough
- chest pain
- u/l ↓ed breath sounds
- u/l dullness on percuss’n
- u/l ↓ed or absent tactile fremitus
- tracheal devia’n away from effus’n (in very large effus’n)
Ix’s
- CXR
→ blunting of costophrenic angle
→ fluid in lung fissures
- pleural U/S
- LDH + measure protein in serum + pleural fluid
- RBC of pleural fluid b/c >100,000 RBC/mm³ in PE / malignancy / trauma
- WBC of pleural fluid b/c lymphocyte > 90% = suggestive of either TB or lymphoma
- culture + pH of pleural fluid to check if it’s empyema
Tx
- if due to congestive HF = diuretic
- if empyema = empirical IV Abx → therapeutic thoracentesis (i.e drain) if pt gets worse
- if due to malignancy + pt has good performance status (i.e Karnofsky score > 30% or ECOG score of 0 or 1) = pleurodesis or intercostal drainage (pleural catheter drainage)
- if due to malignancy + pt has few yrs left to live or poor performance status (i.e Karnofsky score ≤ 30% or ECOG score ≥ 2) = therapeutic thoracentesis
Complica’ns
- atelectasis/lobar collapse
- pleural fibrosis (if was due to TB or mesothelioma)
Purpose of ciliated cells in trachea + bronchi ✓
To sweep mucus secre’ns + debris out of lungs + towards mouth
What are the func’ns of the 2 types of alveolar cells ? ✓
Type I Pneumocytes = to participate in gas exchange across alveolar-capillary membrane
Type II Pneumocytes
1) Regenerative cells of the lung i.e when lung damage occurs, they proliferate + have the ability to regenerate Type I cells
2) Contain foamy vesicles called lamellar bodies which continuously produce pulmonary surfactant that covers luminal surface of alveoli
Ventila’n v.s Diffus’n v.s Perfus’n ✓
- Ventil’an = process by which air moves in + out of lungs
- Diffus’n = spontaneous mov’nt of gases w/o the use of any E effort by the body btw alveoli + capillaries in lungs
- Perfus’n = process by which cardiovascular system pumps blood throughout lungs
Why does the trachea have rings of cartilage ? ✓
To prevent it from collapsing
Shape of Hgb - O2 dissocia’n curve ✓
Sigmoidal shape b/c of +ve cooperativity → when No O2 = bound, Hgb = in tense state aka hard for O2 to bind → but when 1st O2 binds it causes Hgb affinity for O2 to ↑ hence Hgb switches from tense to relaxed state + this continues until 4 O2 molecules = bound
Right + Left shifts in Hgb - O2 dissocia’n curve ✓
Right shift = RELEASE O2 to tissues
- ↓ pH i.e more acidic
- ↑ temp
- ↑ pCO2
- ↑ 2,3 DPG (crea’n of 2,3 DPG = favored in low pH)
Left shift = hold on to tissues
- ↑ pH
- ↓ temp
- ↓ pCO2
- ↓ 2,3 DPG
- CO b/c CO binding causes conforma’nal change that makes Hgb hold tightly to its O2; CO is also bad b/c it’s occupying binding spots that should have been for O2 so also ↓ O2-carrying capacity of Hgb
What is CarboxyHgb ? ✓
Hgb bound to CO
⚠️ Recall that Hgb binds to CO w/ 250x more affinity than it does O2 !
What is MetHgb ? ✓
Hgb w/ Fe3+ instead of Fe2+ ∴ can’t bind to O2 but has high affinity for CN- so pt can be given nitrates to treat CN- poisoning b/c MetHgb = caused by exposure to nitrates or dapsone
⚠️ Recall that Fe2+ is the only form of Fe that can bind to O2 !
Hypoxemia vs Hypoxia ✓
HYPOXEMIA = low O2 content in blood which can lead to HYPOXIA = when tissues are O2 starved
Shunt v.s dead space ✓
Both = mismatch btw ventila’n + perfus’n (V/Q) + hence gas exchange can’t take place
- Shunt = GOOD PERFUS’N but POOR VENTILA’N i.e lungs are doing their job but not enough air is coming in → paO2 ↓ + we get hypoxemia
⟹ ex’s: pneumonia, foreign body, food obstruc’n - Dead space = GOOD VENTILA’N but POOR PERFUS’N i.e air is coming in but lungs aren’t perfusing i.e P.E
⚠️ Dead spaces = normal in conducting zone but NOT in respiratory zone !
What are the 3 ways that CO2 is transported ? ✓
1- Bound directly to Hgb via N-terminus to form carbaminoHgb (makes up 5% of CO2 content in blood)
2- Dissolved in plasma (5%)
3- BICARBONATE BUFFER SYSTEM (90%)
a) CO2 produced by peripheral tissues enters erythrocytes through diffus’n where it combines w/ H2O to produce H2CO3 in a rxn catalyzed by carbonic anhydrase
b) H2CO3 instantaneously dissociates into H+ and HCO3- → generated H+ = buffered by deoxyHgb aka Hgb binds to free H+ ions
→ this buffering = important in maintaining pH in venous blood + RBCs w/in physiologic range
c) Finally, a large por’n of generated HCO3- moves outward from RBC into plasma in exchange for a chloride ion pumped inward (CHLORIDE SHIFT). Chloride shift happens in reverse when it’s time for CO2 to be expired through lungs
Neuron ac’n Ψ process ✓
- @ Rest = -70mV b/c of higher [Na ions] outside compared to inside (-ve means polarized); there’s more [K ions] inside than outside
- Stimulus causes voltage-gated Na channels in axon membrane to open → Na ions move down their [ ] gradient causing inside to become more +ve = DEPOLARIZA’N
- Depolariza’n travels along length of axon = Propaga’n *
- Na channels close + K channels open causing K ions to move out ∴ inside becomes -ve again
= REPOLARIZA’N - K channels open + close slowly so too many K ions diffuse out ∴ making inside way too -ve (aka more -ve than -70) = HYPERPOLARIZA’N / REFRACTORY PERIOD (no ac’n Ψ can occur during this period)
- K channels finally close → hyperpolariza’ n = corrected + inside goes back to initial resting Ψ
ABG Analysis ✓
- Hypoxemia = pO2 < 80 + O2sat < 95%
- Normal blood pH = 7.35-7.45
- Normal pCO2 = 35-45mmHg or 4.7-6.0 kPa
- Normal bicarb = 22-26mM
- pCO2 low = alkaline + high = acidic
- pH + pCO2 match = resp. acidosis / alkalosis
- pH + HCO3- match = meta. acidosis / alkalosis
- If the other value = normal then it’s UNCOMPENSATED, but if bicarb / pCO2 = abnormal as well, then we have RESP / RENAL COMPENSA’N *
- Know for OSCE *
Causes of metabolic acidosis + how to calculate anion gap ✓
⚠️ Lungs might compensate by HYPERventilating !
1) Keto-acidosis causes
- alcohol
- starva’n
- convuls’n
- high exercise
2) Excessive inges’n of toluene
3) Excessive loss of HCO3-
- diarrhea
- intestinal / biliary intuba’n
- addison’s disease
- fistula
4) Carbonic Anhydrase inhibitors
5) High anion gap causes (“MUDPILES”)
- MetOH
- Uremia i.e buildup of sulfates / nitrates / urates in blood that would normally be excreted in urine but aren’t b/c of renal insufficiency
- DKA
- Propylene glycol
- Isoniazid or Iron
- Lactic acidosis
- Ethylene glycol i.e antifreeze or EtOH
→ can cause uric acid crystals to precipitate in urine
- Salicylates (aspirin for ex)
⚠️ Anion gap = Na - (Chloride + Bicarb) = elevated if > 12
Causes of Metabolic Alkalosis ✓
⚠️ Lungs might compensate by HYPOventilating !
1) HCl loss
- vomiting
- NG suctioning
- intestinal fistulae
- antacid use
2) Excessive admin. of HCO3-
3) Hypovolemia
- thiazide diuretics
- loop diuretics
- dehydra’n
4) ↑ed renal acid secre’n
- K deple’n
- 2° HypoPTH
- diuretic therapy
- hyperaldosteronism
- exogenous mineralocorticoids
Causes of Resp. Acidosis ✓
ANYTHING CAUSING HYPOVENTILA’N !
- There could be renal compensa’n aka it attempts to ↑ bicarb *
1) Airway obstruc’n
- asthma
- COPD
- pneumonia
- bronchospasm
- laryngospasm
2) Resp. center depress’n
- anesthesia
- opioid / sedative / narcotic overdose
- brain tumor
3) Circulatory collapse
- cardiac arrest
- pulm. edema
4) Neurogenic
- MS
- myxedema
- cervical spine injury
- myasthenic crisis
- muscular dystrophy
- phrenic nerve injury
- paralytic agents / PO4’s
- Guillain Barré syndrome
5) Restrictive effects
- ARDS
- ascites
- obesity
- hydrothorax
- pneumothorax
Causes of Resp. Alkalosis ✓
ANYTHING CAUSING HYPERVENTILA’N !
- There could be renal compensa’n aka it attempts to ↓ bicarb *
1) Hypoxia
2) Lung Disease
- pneumonia
- P.E
3) CNS resp. stimula’n
- fever
- liver disease
- cerebral vascular accident or stroke
4) Anxiety / Panic attack / hyperventila’n syndrome
5) Pregnancy
6) Progesterone derivatives or salicylate intoxica’n
7) Hyperthyroidism
8) Delirium tremors
9) CHF
10) Sepsis
11) Peritonitis
12) Hepatic insufficiency
13) Mechanical ventila’n
CO poisoning ✓
- SSX = HA, confus’n, bright red cheeks
- Ix for diagnosis = ABG → will show low O2 satura’n + high carboxyHgb
The 3 fluid compartments ✓
2/3 ICF + 1/3 ECF (75% Interstitial Fluid + 25% Plasma)
The 3 types of dehydra’n ✓
- HYPOosmolal = losing LESS water aka more Na
→ ECF volume will ↓ in all 3 but especially in hypo b/c will get rid of water to make it more [ ]ed ∴ ICF volume will ↑
→ Plasma osmolarity will ↓ - HYPERosmolal = losing MORE water
→ ICF volume will ↓ b/c will try to give water to ECF
→ Plasma osmolarity will ↑ - ISOosmolal = losing both in same amts
→ ICF volume won’t change
Pathophys - ↓ in BP/ volume / hyperosmolarity
➔ ADH = secreted from posterior pituitary (thnx to hypothalamic osmo-receptors) ➔ water reabsorp’n ↑
➔ urine specific gravity + osmolality ↑ (urine will be more [ ]ed)
Tx = IV Hartmann’s solu’n
How does ORT work ? ✓
Uses SGLT-1= type of 1° active transport, specifically symport / co-transport of Na + glucose in jejunum
→ glucose uses E associated w/ Na to be uptaken against its [ ] gradient
Agonist vs Antagonist ✓
- Agonist = drug that binds to receptor to produce cellular response
→ Full Agonist = has full efficacy aka will produce 100% response ∴ = better for short term opioid Tx aka overdose but not for long term
→ Partial Agonist = less efficacy hence will never produce 100% response ∴ = better for long term opioid addic’n Tx
→ Inverse Agonist = binds to same receptor/binding site as endogenous agonist but produces “inverse” aka opposite effect as original - Antagonist = doesn’t directly produce a cellular response but instead BLOCKS effect of endogenous agonist
→ Surmountable Antagonism / Competitive = antagonist + endogenous agonist bind to same binding site so the one w/ the smaller kA will have > affinity + will win
→ will cause curve to shift to the right but W/O ↓ing max response
→ Insurmountable Antagonism = ↓ max response of endogenous agonist, doesn’t matter how much agonist is added, shifts curve to the right
⟹ Non-competitive = antagonist + endogenous agonist bind to diff sites
⟹ Irreversible = antagonist binds so strongly to binding site that it’s irreversible aka covalent binding (H2/ionic = reversible b/c = weak binding)
⚠️ Only agonists have efficacy b/c they produce a cellular response while antagonists don’t !
Sympathetic v.s Para (anatomy + chemical transmiss’n) ✓
→ Pre = CNS to ganglion
→ Post = ganglion to effector organ
- Symp :
→ short pre + long post ganglionic fibers that reside near spinal cord
→ Ach for pre + NE for all post except post that innervate sweat glands
→ dilate pupil, inhibit saliva produc’n, dilate bronchi, ↑ HR, inhibit GI organs (intestines / stomach / pancreas / gallbladder) + relax bladder i.e suppress bladder contrac’n + contract sphincters - Para :
→ long pre + short post that reside in effector organs
→ neurotransmitter = Ach for both pre + post
→ constrict pupil, stimulate saliva produc’n, constrict bronchi, ↓ HR, stimulate GI organs, stimulate lacrima’n + contract bladder via contrac’n of detrusor muscle + relaxa’n of sphincters
What are the 4 receptor types ? ✓
- Inotropic/channel-linked = directly coupled to an ion channel
→ fast (millisecs) - G-protein coupled = single protein w/ 7 transmembrane domains
→ slower than ionotropic
→ most receptors fall w/in this category
a) Adenergic R’s = receptors that bind epinephrine / adrenaline + norepinephrine
- 𝛼1 = cause vascular smooth muscle contrac’n aka vasoconstric’n + pupillary dilator muscle contrac’n + intestinal / bladder sphincter muscle contrac’n (norepinephrine mainly binds to these)
- 𝛼2 = inhibit sympathetic aka inhibits insulin release/lipolysis/humour produc’n
- β1 = ↑ HR (on SA node) + contractility (on ventricular cardiomyocytes) + renin release + lipolysis
- β2 = activate smooth muscle relaxa’n in vessels + bronchi aka vasodila’n + bronchodila’n + lipolysis + cellular uptake of K + humour produc’n
- β3 = breakdown of fat aka lipolysis, thermogenesis in skeletal muscle + bladder relaxa’n
b) Choligernic R’s = receptors that bind Ach
→ Muscarinic (mainly activate para) = G-protein coupled, efflux of K + influx of Na/Ca
⟹ M1 = enteric NS
⟹ M2 = ↓ HR (on SA node) + ↓ contractility (on cardiomyocytes)
⟹ M3 = in bladder + trachea / bronchioles smooth muscle → cause broncho-constric’n
→ Nicotinic (both symp + para) = ligand ionotropic receptor
⟹ Nn (n = for “neuro” aka autonomic ganglia + adrenal medulla)
⟹ Nm (m = for “NMJ” of skeletal muscle)
- Tyrosine-kinase linked receptors, ex = insulin
→ slow response but not as slow as nuclear receptors - Nuclear receptors = intracellular while the others = transmembrane, ex = levothyroxine
→ ligands of these receptors have to be hydrophobic b/c are intracellular
→ regulate gene express’n
→ slowest response of the 4
Microcytic v.s Normocytic v.s Macrocytic Anemia ✓
Anemia = ↓ [ ] Hgb / Hematocrit / RBC count below normal range for age + sex
→ Men = Hgb < 13 g/dL
→ Non-pregnant women
= Hgb < 12 g/dL
→ Pregnant women + Children ≤ 5 y/o
= Hgb < 11 g/dL
Ψ SSX :
- pale conjunctiva + mucous membranes
- brittle nails / koilonychia (spoon nails) / platonychia (flat nails)
- skin dryness
- brittle + dry hair
- weakness / fatigue
- lack of [ ]
- SOB during exercise
- hypoTN / feeling faint
- angular cheilitis, painful glossitis, atrophic gastritis (in Fe def anemia)
- Microcytic = MCV < 80 (causes = “TAIL”)
- Thalassemia = normal ferritin + the microcytic anemia is NOT new
- Anemia of chronic disease = high ferritin + the microcytic anemia is new
→ ex’s- RA, temporal arteritis, chronic infec’n / inflamma’n, rare causes like renal cell carcinoma, Hodgkin lymphoma, Castleman disease + myelofibrosis - Iron deficiency = low ferritin ➔ RBC shape will be normal, color will be pale b/c it’s hypochromic + like all microcytic anemias RBC size will be small
⚠️ Hgb should ↑ by > 20 after taking Fe supplement for > 3-4 wks so if that’s not the case suspect drug interac’n !
→ Causes of Fe deficiency:
⟹ ↓ed intake - poor diet or vegetarian diet
⟹ ↑ed demand - pregnancy / infants / puberty
⟹ Malabsorp’n - gastrectomy / celiac
⟹ Blood loss
a) Genitourinary tract
→ endometrial polyp = most frequent cause of Fe deficiency in pre-menopausal women
→ metrorrhagia = bleeding in btw periods (usually in puberty or close to menopause)
→ hematuria
b) GI tract = most frequent cause of Fe deficiency in adult men + post-menopausal women
→ esophageal varices
→ diaphragmatic hernia
→ gastric ulcer
→ chronic aspirin use
→ neoplasm / cancer
→ UC
→ diverticular disease
- Lead poisoning
- Normocytic = MCV w/in normal range aka 80-100
➔ Hemolytic / Hyperproliferative
= high reticulocyte count, ex: sickle cell, hem. anemia (can be inherited or acquired)
> Hemolysis = pre-mature peripheral RBC destruc’n , typically seen when life span ↓ from 120 days to < 30 days → doesn’t always cause anemia b/c bone marrow can compensate by ↑ing RBC produc’n (= known as compensated hemolytic disease)
→ can be intravascular (= pathological + usually acute + FATAL, happens in snake bites for ex) OR extravascular = excacerba’n of physiological process, usually chronic + NOT FATAL except if excess bilirubin crosses BBB
⟹ intravascular SSX = Schistocytes i.e fragmented RBCs w/ a helmet or triangular shape + Hbemia + Hburia b/c of ↓ed haptoglobin
⟹ causes of intravascular hemolysis . . .
a) Membrane pb i.e cytoskeleton defects = Coombs -ve
⟹ hereditary spherocytosis = ankyrin or spectrin deficiency or band 3 abnormality
⟹ hereditary ellipsocytosis = a + b spectrin defects
b) Hgb pb i.e abnormal structure like in SCD OR imbalance in globin chains synthesis like in thalassemia
c) Enzymopathies
→ pyruvate deficiency
→ glucose-6 PO4 dehydrogenase (G6PD) deficiency = X-linked
⚠️ G6PD = necessary b/c protects RBC from endo + exogenous oxidants ∴ w/o it, oxidizing agents convert Hgb to MetHgb (Fe3+ heme group) ∴ RBC = denatured + precipitates as Heinz bodies
⟹ extravascular hemolysis SSX = jaundice + hyperbilirubinemia + high LDH
⟹ causes of extravascular hemolysis . . .
a) Immune pb i.e antibody attack on RBC
> Autoimmune
→ AIHA = Coombs +ve (direct coombs) → Coombs = a type of direct antiglobulin test
⟹ RBC morphology = polychromasia, macrocytes, nucleated RBCs, spherocytes, agglutina’n + high reticulocyte count
⟹ warm reacts w/ RBC at 37°C + cold at 4°C, usually IgG antibodies for warm
⟹ Tx for warm AIHA = transfus’n
→ Cold AIHA gets worse in low temps ∴ Tx = treat underlying condi’n + avoid cold weather
→ CAD (Cold Agglutin Disease) = self-limiting usually (= IgM antibodies w/ complement activa’n)
→ PCH (Paroxysmal Cold Hburia) = severe + sometimes fatal (= IgG antibodies w/ complement activa’n)
> Alloimmune i.e transfus’n rxn / HDFN / marrow transplant → ex = pt w/ blood group A = transfused w/ incompatible blood of group B
b) Drug associated
c) RBC mechanical trauma (≠ immune i.e no antibody involv’nt) → will appear as fragmented cells or schistocytes on blood film (for MAHA)
d) Micro-angiopathic hemolysis (MAHA) i.e TTP (thrombotic thrombocytopenic purpura) / DIC (Disseminated intravascular coagula’n) / HELLP / HUS (Hemolytic uremic syndrome)
e) Valve hemolysis = usually due to artificial heart valves, grafts or perivalvular leaks
f) March Hburia = RBC damage btw small feet bones due to prolonged marching / running
g) Infec’ns like malaria or clostridia
➔ Non-hemolytic / Hypoproliferative
= low reticulocyte count
= aplastic anemia or anemia of chronic disease
- Macrocytic = MCV > 80
a) Megaloblastic → will show hyper-segmented neutrophils aka > 5 segments
= due B9 OR B12 deficiency OR drug
- Causes of B9 def
→ ↓ed intake i.e poor diet
→ ↑ed demand such as . . .
⟹ neonates
⟹ pregnancy (supplemental folic acid = given ≥ 1 month prior to concep’n + during early pregnancy to ↓ risk of neural tube defects)
→ Anti-folate drugs such as . . .
⟹ hydroxyurea
⟹ methotrexate
⟹ sulfonamides
⟹ anti-convulsants like phenytoin
→ Malabsorp’n such as . . .
⟹ chronic alcohol overuse
⟹ jejunum resec’n
⟹ jejunum pathologies like steatorrhea, celiac disease + tropical sprue
b) Non megaloblastic → will show NORMAL OR HYPO-segmented neutrophils on blood smear
→ NORMAL = due to alcoholism, liver disease, hypoTSH, hemolysis or drugs
→ HYPO = due to myelodysplastic syndromes
- Causes of B12 def
→ ↓ed Intake i.e poor diet
→ Malabsorp’n (achlorhydria i.e stomach can’t produce HCl, alcoholism, etc)
→ Intrinsic factor deficiency → Intrinsic Factor = secreted by parietal cells + forms complex w/ B12 to transport it to ileum for absopr’n + protect it from digest’n by GI enzymes
⟹ pernicious anemia = most common cause of B12 deficiency = autoimmune disease that causes destruc’n of parietal cells or IF via anti-parietal or anti-IF antibodies, only Tx = life long parenteral IM B12 injec’ns (1mg/wk + then monthly)
⟹ gastrectomy / gastric bypass Sx
⟹ congenital IF def
→ small intestine disease
⟹ small intestine resec’n (b/c of absence of terminal ileum)
⟹ Crohn’s (b/c of absence of terminal ileum just like surigcal resec’n)
⟹ tropical sprue
→ Small intestine parasites + bacteria
⟹ diphyllobothrium latum / fish tapeworm
⟹ blind loop syndrome = shorter small intestine due to bacteria overgrowth in intestine
⟹ diverticulosis
→ Drugs . . .
⟹ NO
⟹ PPI
⟹ Metformin
⟹ Colchicine
⟹ Neomycin
⚠️Prolonged B12 deficiency will cause IRREVERSIBLE nerve damage !
Blood smear terminology ✓
- Hypochromia = pale RBCs b/c contain less Hgb
➔ in microcytic anemia - Hyperchromia = presence of hyper-segmented neutrophils, bilirubin + LDH will be ↑ed
➔ in macrocyclic anemia - Anisocytosis = varia’n in RBC sizes, FBC will show ↑ed RDW
➔ in Hbopathies or myelodysplastic syndromes - Poikilocytosis = varia’n in RBC shapes = HAS TO BE THALASSEMIA
Central v.s peripheral type anemia ✓
- Central type = pb = bone marrow itself
→ ex’s = leukemia, aplastic anemia, myelofibrosis, myelodysplastic syndromes - Peripheral type = pb ≠ bone marrow itself but something else such as lack of nutrients in blood, kidney failure, EPO deficiency, ↑ed destruc’n due to hypersplenism / autoimmune / Hbopathy or blood loss i.e menstru’an / pathological bleeding
Structure of Fetal + Adult Hgb ✓
- Fetal Hgb = 2 𝛼 + 2 γ chains, can’t bind as well to 2,3 DPG ∴ has higher O2 affinity b/c 2,3 DPG can’t ↓ Hgb affinity for O2
- Adult Hgb = 2 𝛼 + 2 β chains, each chain = linked to heme group (Fe2+) that an O2 molecule can bind to, so 4 O2 molecules max can bind to 1 Hgb
4 types of hypersensitivity rxns ✓
ANTIBODY MEDIATED
- Type 1 = basically like acute inflamma’n w/ mast cells + IgE + Th2 cells = immediate response (= for allergic rxns i.e asthma / anaphylaxis)
- Type 2 = opsoniza’n + phagocytosis- w/ IgM or IgG
= for cell bound antigens
ex’s: organ rejec’n (via cytotoxic T cells), Grave’s, myasthenia gravis - Type 3 = complex mediated (complexes of IgM/IgG)
ex’s: RA, SLE, reactive arthritis, polyarteritis nodosa
T-CELL MEDIATED
- Type 4
ex: TB, MS, scabies, Guillain-Barre, Mantoux test
Anaphylaxis ✓
Def - most severe form of an immediate hypersensitivity rxn (= Type 1 rxn)
Eti = exposure to allergen i.e food (1/3 of cases), drugs, insect sting, latex
→ most common triggers = nuts, fish + shellfish, eggs + milk
→ kids that have milk + egg allergy usually outgrow them whereas fruit or seafood allergy tend to stay forever
→ bee sting leaves stinger whereas wasp sting DOES NOT leave stinger !
Pathophys - allergen = introduced into body by ingest’n / inhala’n / parenteral or skin contact → on 1st exposure, plasma cells of susceptible person make IgE antibodies specific to that antigen
→ IgE antibodies attach to high-affinity Fc receptors on basophils + mast cells
→ on subsequent exposure, binding of antigen to IgE antibodies leads to bridging + triggers degranula’n of mast cells
SSX
- SOB
- hypoTN
- pruritus
- urticaria
- erythema
- airway swelling
- angioedema i.e swelling of deeper tissues such as as eyelids, lips, mouth
⚠️ ≥ 1 of the ABC’s has to be affected for it to be anaphylaxis !
Ddx
- asthma
- septic shock
- panic disorder
- cardiogenic shock
- hypovolemic shock
- foreign body aspira’n
- acute COPD exacerba’n
Ix’s
- ABG to check for elevated lactate
- mast cell tryptase → will be high, normally = undetectable in healthy person who hasn’t had anaphylaxis in the past hrs
→ should be done NO LATER later than 4 hrs later ! - skin prick test
⚠️ Make sure pt hasn’t put lo’n or cream on inner forearm + that they didn’t take histamines or steroids
- Mark areas w/ pen or marker + include +ve + -ve control
→ +ve control = histamines + -ve control = water - Apply 1 drop of each allergen / control on their marked spot
- Prick each of those spots (use diff needle for each spot)
- Press entire forearm w/ paper towel
- Wait 15 mins + analyze results
→ +ve control should have rxn + -ve control should have NOTHING !
Emergency Tx = IM Adrenaline / Epinephrine (0.5 mg)
→ remove cap → stab needle in lateral thigh → count for 10 secs → Repeat after 5 mins if there’s no improv’nt
→ Epinephrine MOA - vaso-constric’n to maintain BP + divert blood away from skin,↓ throat swelling which opens airways + prevents further release of histamine
Tx after stabiliza’n = oral antihistamines
- Know for OSCE *
COPD ✓
Def - PROGRESSIVE IRREVERSIBLE airway obstruc’n = usually due to cigarette smoking but interestingly, only a minority of smokers will actually develop COPD
RFs
- advanced age
- cigarette smoking → inactivates 𝛼1 antitrypsin in lungs, which leads to ↑ed ac’n of elastases → ↑ed breakdown of elastic tissue
- 𝛼1 antitrypsin deficiency (genetic) → causes lack of antiprotease
→ COPD, chronic bronchitis + emphysema have common clinical features b/c they all share the common trigger of SMOKING !
→ chronic bronchitis = productive cough for 3 consecutive months for 2 consecutive yrs
→ emphysema = permanent dilata’n of airways distal to terminal bronchiole
Pathophys in small airways - chronic inflamma’n → healing by fibrosis → airway stenosis
Pathophys in resp. bronchioles - destruc’n of walls w/ loss of elastic tissue but W/O sig fibrosis → airway dilata’n + emphysema
Pathophys in terminal bronchioles - irritant i.e smoking causes inflammatory response → neutrophils + macrophages = recruited to release inflammatory mediators such as oxidants + proteases → protease-mediated destruc’n of elastin → loss of elastic recoil → airway collapse during exhala’n → incomplete exhala’n → ↑ in CO2 + chest hyperinfla’n due to trapped air
SSX
- barrel chest
- SOB due to airway obstruc’n
- hyper-resonance on percuss’n
- coarse crackles + wheezing on ausculta’n
- sputum produc’n due to hyperplasia of mucus-producing glands in submucosa + of goblet cells on surface epithelium
→ productive cough = earliest SSX of COPD + if pt continues smoking . . .
⟹ sudden SOB upon exer’n
⟹ disease advances
⟹ SOB upon min. exer’n
⟹ disease advances
⟹ SOB at rest
⚠️ cough + sputum present means LARGER airways = involved v.s SOB present means SMALLER airways = involved
Ddx
- TB
- CHF
- Asthma
- Lung cancer
- Bronchiectasis
Ix’s
- FBC → might show polycythemia = ↑ed hematocrit i.e > 55% due to ↑ed EPO produc’n
- O2 sat = 88-92% b/c they require hypoxic drive to breathe
- ABG to check for resp. failure
- 𝛼1 antitrypsin level in pts w/ FHx of COPD or atypical COPD pts i.e young or non-smoker
- Spirometry for diagnosis → should show that there’s airflow obstruc’n
- CXR
→ CXR Findings (“FEBS”) . . .
- Flattened diaphragm i.e loss of sharp borders
- Eight anterior ribs (indicates hyperinfla’n b/c usually only up to 6 = visible)
- Barrel shaped on lateral view due to retrosternal air trapping
- Stretched out heart (heart looks like it was pulled vertically)
Emergency Tx = SABA
Regular Tx
- Smoking cessa’n therapy + both pneumococcal / influenza vaccina’ns + pulmonary rehab if they had an exacerba’n
- inhaled SABA or SAMA
- What to add if pt is still symptomatic . . .
→ if FEV1 >50% = inhaled LAMA or LABA
→ if FEV1 <50% = Inhaled LAMA or LABA+ICS - If still symptomatic add LABA+ICS or if already on LABA+ICS add LAMA
- Theophylline
Short Term Complica’ns
- respiratory failure
- acute exacerba’n = sustained worsening in pt’s SSX beyond normal day to day varia’n such as worsening of SOB or cough or ↑ed sputum produc’n = most commonly caused by infec’n but can also be caused by . . .
→ P.E
→ LVF
→ pneumothorax
→ lung carcinoma
⚠️ In an infective exacerba’n of COPD, focus of infec’n = airways v.s in pneumonia = alveoli
→ CXR in COPD = clear lung fields v.s in pneumonia = consolida’n
Long Term Complica’ns
- lung cancer
- cor pulmonale
→ initially RV will undergo hypertrophy to compensate, but eventually will decompensate - Know for OSCE *
Pneumonia ✓
Def- inflamma’n of lung parenchyma / alveolar space due to an infective agent
→ aspira’n pneumonia = when infec’n develops due to aspira’n of food or fluids = usually in pts w/ impaired swallowing i.e demented or after stroke = associated w/ anerobic bacteria
RFs
> 65 y/o
- COPD
- alcohol abuse
- poor oral hygiene
- contact w/ children
- use of acid-reducing drugs
- resides in healthcare facility
- exposure to cigarette smoke
Eti
- viral
- fungal
- bacterial = most common
→ hospital acquired pneumonia = when pt gets pneumonia ≥ 2 days after they’ve been admitted to hospital, 60% of cases of HAP = due to gram -ve bacteria such as . . .
- E.coli
- S.aureus
- Hemophilus (green sputum)
- Pseudomonas (green sputum)
- S. pneumoniae (rust colored sputum)
- Klebsiella (red currant jelly sputum)
→ causes aspira’n lobar pneumonia in pts w/ alcohol overuse + diabetes mellitus
→ CAP (community acquire pneumonia) = when pt gets pneumonia outside of hospital i.e in everyday life
⟹ most common cause of community acquired pneumonia = streptococcus pneumonias / pneumococcus
⟹ can also be caused by atypical bacteria such as mycoplasma pneumoniae, chlamydophila pneumoniae, chlamydia psittaci + coxiella burnetii
SSX
- SOB
- fever
- chills
- productive cough
- consolida’n on CXR
- coarse crackles + dullness on percuss’n due to lung tissue either collapsed or filled w/ sputum
Subtypes (can only classify on autopsy)
- Lobar pneumonia = characterized by diffuse inflamma’n affecting entire lobe(s)
→ may present w/ pleuritic chest pain that gets worse when pts cough + the regular pneumonia SSX - Bronchopneumonia = characterized by b/l (most of the time) widespread patchy inflamma’n = centered on airways
Ddx
- TB
- P.E
- CHF
- Covid
- Lung cancer
- Emphysema
- Pneumothorax
- Acute bronchitis
- COPD / Asthma / Bronchiectasis exacerba’n
Ix’s
- sputum culture
- CRP → will be high
- FBC → WCC will be high
- CXR → will show consolida’n
- CURB 65 score = used to asses severity of community acquired pneumonia :
→ C = sudden onset of confus’n
→ U = Urea > 7 mmol/L
→ R = RR ≥ 30
→ B = BP < 90 (sys) or ≤ 60 (dia)
→ 65 = ≥ 65 y/o
→ give 1 point if pt has it + add points
⟹ 0-1 point = outpt Tx at home
> 2 points = admit to medical ward
≥ 3 points = admit to ICU b/c risk of death ↑ as score ↑
Tx for community acquired pneumonia :
500 mg amoxicillin td for 5 days if LOW or MODERATE severity → if pt has penicillin allergy or amoxicillin = unsuitable for ex if atypical pathogen = suspected, instead, give 200 mg doxycycline 1st day + then 100 mg od for 4 days OR clarithromycin 500 mg bd for 5 days / erythromycin (in pregnancy) 500 mg qd for 5 days → co amoxiclav + clarithromycin / erythromycin if HIGH severity (same dosage as previous) + NO penicillin allergy but if pt has penicillin allergy levofloxacin 500 mg bd for 5 days
Atypical pneumonia
= pneumonia caused by organisms that can’t be detected via gram stain or cultured in the normal way
→ Eti = “ Legion of psittaci MCQs “
– Legionella pneumophila
– Chlamydia psittaci
– Mycoplasma pneumoniae
– Chlamydophila pneumoniae
– Q fever i.e coxiella burnetii
→ Tx = macrolide such as clarithromycin, fluoroquinolone such as levofloxacin + tetracycline such as doxycycline
Complica’ns
- septic shock
- heart failure
- pleural effus’n
- acute respiratory distress syndrome (ARDS)
⚠️ Recall that consolida’n = when air in lungs = being replaced by something else i.e less black + in pneumonia that “something else” is acute inflammatory EXUDATE + in pulm. edema it’s TRANSUDATE !
⚠️ Be specific when describing consolida’n on CXR i.e right middle lobe consolida’n
What pts are at risk of aspira’n pneumonia ? ✓
- septic pts w/ ↓ed consciousness
- intoxicated pts i.e alcohol overuse
- acute stroke pts w/ impaired swallowing
Inspira’n v.s Expira’n ✓
Inspira’n v.s Expira’n
- Inspira’n = diaphragm contracts / pulls down + external intercostal muscles contract which moves ribs up + out → lung volume ↑ → pressure ↓ → air moves in (from high to low pressure)
- Expira’n = external intercostal muscles relax which moves ribs down + in, diaphragm relaxes/moves upward + internal intercostal muscles contract → lung volume ↓ → pressure ↑ → air moves out (from high to low pressure)
Resp. Failure ✓
Def - impaired gas exchange btw lungs + blood ∴ causing hypoxia (w/ or w/o hypercapnia)
Type 1 = Hypoxemia
Type 2 = Hypoxemia + Hypercapnia
RFs
- cardiac failure
- pneumothorax
- airway obstruc’n
- pulmonary infec’n
- cigarette smoking
- toxic fumes + gases
- chronic lung disease
- alveolar abnormalities
- perfus’n abnormalities
- hypercoagulable states
- opioid / sedative medicines
- traumatic spinal or thoracic injury
Eti
Resp. causes
- P.E
- Pneumonia
- Bronchiectasis
- Pneumothorax
- Acute epiglottitis
- Pulmonary edema
- Acute asthma exacerba’n
- ARDS including from Covid infec’n
- Alveolar abnormalities such as emphysema or Goodpasture’s syndrome
- Chronic lung disease such as COPD, CF, pulmonary fibrosis, chronic interstitial lung disease
Non resp causes
- Severe anemia
- Shock (septic and/or cardiogenic)
- Poisons such as chlorine gas or CO
- Drug overdose (opioids or sedative medicines)
- Hypovolemia (from hemorrhage or dehydra’n)
- Neuromuscular disorders such as Guillain-Barre, myasthenia gravis, muscular dystrophy, poliomyelitis
Traumatic causes
- Blood loss
- Spinal injury
- Direct thoracic injury
Ix’s = O2sat + ABG
Emergency Tx = mechanical ventila’n
- Know for OSCE *
1° Lung Cancers ✓
1) Def, RFs, Eti, Pathophys, SSX, Diagnostic Criteria, Ddx, Ix, 1st line Mx, Complica’ns
2) Lung nodule classifica’n
3) Define paraneoplastic syndrome + explain the pathophys of SIADH in small cell carcinoma
4) Describe the clinical presenta’n of Pancoast + Horner’s syndrome
5) Briefly outline the pathology of malignant mesothelioma, highlighting its associa’n w/ asbestos exposure + its dismal prognosis
- Epi
- lung cancer = 2nd most common cancer in the UK + peak incidence = 50-60 y/o
- 80-90% of cases can be attributed to cigarette smoking b/c contain carcinogenic compounds like benzopyrene
- asbestos alone ↑ risk of lung cancer + has synergistic RF effect when combined w/ smoking
Types of lung cancers
- majority = carcinomas
→ carcinoma of the lungs = most likely to metastasize to adrenal glands - 40% = adenocarcinoma = most common type of lung cancer in NON-SMOKERS !
→ tends to arise in peripheral smaller airways + mainly affects women
→ pre-malignant les’n for this = called atypical adenomatous hyperplasia = asymptomatic - 25% = SCC = strongly associated w/ smoking
→ tends to arise in larger airways near lung hilum
→ pathophys = metaplasia → dysplasia → carcinoma - 15% = small cell lung carcinoma
= highly aggressive tumor b/c of rapid growth rate + early spread
→ there’s no grading for this b/c = automatically high grade
→ unlike adenocarcinoma doesn’t have pre-malignant les’n
→ has the strongest associa’n w/ smoking out of all the types
→ usually arises in a central loca’n - 10% = large cell carcinoma
= undifferentiated carcinomas that can’t otherwise be categorized microscopically i.e lack morphological features of the other forms of lung cancer - the others = carcinoid / large cell neuroendocrine carcinoma
SSX
- cough
- SOB due to airway obstruc’n
- hemoptysis b/c of bleeding from tumor
- chest wall pain due to chest wall invol’vnt
- stridor / wheeze on insipra’n due to upper airway obstruc’n
- hoarse voice due to invas’n of left recurrent laryngeal nerve
- SVC obstruc’n b/c of pressure exerted by tumor → blood flow = obstructed → venous pressure ↑ + we get interstitial edema + retrograde collateral flow → collateral venous systems i.e azygous venous system / internal mammary venous system / long thoracic venous system try to pick up the slack but venous pressure still remains high = oncological emergency ! → give dexamethasone to ↓ tumor swelling
Staging = TNM
→ use CT scan for T + PET / PET-CT for N + M
Tx = small cell lung carcinoma v.s all the others
→ chemo for small cell b/c Sx = ineffective
→ chemo as well for the others but can use Sx if stage = low
- Lung nodules
- lung nodule > 20 mm = 81% chance it’s cancer
- lung nodule 8-20 mm = 15% chance it’s cancer
- lung nodule 4-7 mm = 1% chance it’s cancer
- lung nodule < 4 mm = 0% chance it’s cancer
- Paraneoplastic syndrome
= syndrome (i.e. collec’n of SSX) caused by substances produced by tumor cells that act remotely from the tumor itself
= common in lung cancers especially small cell lung carcinoma
→ ex 1- produc’n of PTH-related peptide by tumor cells → causes Ca to be released from bone into bloodstream hence SSX = HyperCa SSX
→ ex 2 - SIADH = produc’n of ADH by tumor cells
→ ex 3 - ACTH secre’n by tumor cells
→ will cause b/l adrenal cortical hyperplasia → cortisol produc’n will ↑ hence SSX = thirst + polyuria = features of cushing’s syndrome (pt usually dies before those manifesta’ns happen)
→ ex 4 - Lambert Eaton Myasthemic Syndrome (LEMS) = auto-antibodies block voltage gated Ca channels in presynaptic membrane ∴ blocking release of Ach
- Pancoast’s tumor = cancer in apex of lung involving 8th cervical nerve +
1st + 2nd thoracic nerves
→ can manifest as Pancoast’s syndrome = shoulder pain radiating in an ulnar distribu’n down the arm OR as Horner’s . . .
→ Signs of Horner’s = “PAME”
- PTOSIS (drooPY eyelid)
- ANHYDRIOSIS
- MIOSIS (constricted pupil)
- ENOPHTHALMOS (eyeball sinks inwards)
⚠️ Horner’s = ipsilateral
- Mesothelioma = malignant tumor of the pleura associated due to asbestos exposure
- has long latency period btw time of exposure + tumor develop’nt
- usually occurs in 60 y/o men
- SSX = SOB + chest pain +/- pleural effus’n
- diagnosis = made by cytological examina’n of pleural fluid OR histological examina’n of pleural Bx
- tumor spreads extensively w/in chest wall + eventually encases entire lung
- has no grade b/c by defini’n = highly aggressive
- prognosis = 18 months after diagnosis
- Know for OSCE *
Diffuse parenchymal lung diseases ✓
Def - large group of condi’ns characterized by inflamma’n centers on interstitium of alveolar walls
→ ex = asbestosis - diffuse fibrosis of lung parenchyma due to exposure to very high levels of asbestos
→ main SSX = gradually worsening SOB + eventual chronic respiratory failure
Eti
- idiopathic such as idiopathic pulmonary fibrosis
- pneumoconiosis i.e inhaling inorganic/mineral dusts like coal, silica or asbestos
- extrinsic allergic alveolitis or hypersensitivity pneumonitis
- side of effect of drugs like bleomycin or amiodarone or chest radia’n
- multi system diseases like sarcoidosis or SLE that can also involve lung
Pathophys - expans’n of interstitium by an inflammatory cell infiltrate i.e pneumonitis or alveolitis
→ gas exchange = impaired + we get SOB
⟹ episodes of alveolitis or pneumonitis might be followed by complete regenera’n i.e no residual damage to alveoli but in some instances, inflamma’n = followed by repair + scarring . . .
» release of fibrogenic cytokines by macrophages → collagen = secreted
→ scar tissue develops → over time scarring destroys func’nal units of lungs + as a result, lungs = converged into a mass of cystic air spaces separated by dense scarring = HONEYCOMB LUNGS
Ix = spirometry → will show restrictive effect
Complica’ns
- cor pulmonale
- fibrosis of lung tissue → oblitera’n of pulmonary arterioles + capillaries → gradual pulmonary HTN
What is interstitium ? ✓
Tissue that lies btw alveoli + contains pulm. artery capillaries = thin which is good b/c allows alveoli + capillaries to lie very close to one another ∴ ensuring optimal gas exchange
Drugs that need to be dose adjusted when pt quits smoking ✓
X
Pulmonary TB ✓
Def - infectious disease caused by Myobacterium TB = NOTIFIABLE DISEASE !
→ TB = small slow growing acid-fast rod-shaped bacillus w/ thick lipid-rich cell wall
→ = transmitted by air droplets i.e coughing / sneezing / talking + can only infect humans
→ can get reactivated after several months or yrs
→ even if sick person leaves room, room remains infectious for 30 mins
→ usually transmitted indoors + not outdoors b/c Myo TB = killed by UV light
RFs
- elderly
- HIV +ve
- alcohol
- silicosis
- apical fibrosis
- diabetes mellitus
- immunosuppressive medica’n
- born in endemic reg’n i.e Africa / Asia /Latin America
Pathophys - myo TB infects upper por’n of lower lobe of lung i.e apex → it gets engulfed by alveolar macrophages but doesn’t get destroyed thnx to cord factor which is a glycolipid in TB’s cell wall that’s directly cytotoxic to macrophages + prevents intracellular killing by phagocytic cells by preventing fus’n of vesicles containing the bacterium w/ lysosomes
→ over time fibrous scar develops around les’n which can be further calcified
→ les’n called Ghon focus = produced
→ Ghon focus + lymph node les’n form Ghon complex = calcified scar in lung parenchyma + hilar lymph node
→ cell mediated immune response (via Th1 cells) controls infec’n but leads to overproduc’n of TNF γ ∴ causing macrophages to damage healthy tissue
→ like in other chronic inflamma’ns we get forma’n of a granuloma = spherical collec’n of epitheloid macrophages w/ a small area of central necrosis
= formed to contain bacterium in an anoxic + acidic env’nt → that center undergoes liquefica’n + coagulate necrosis which produces caseous necrosis (also destroys healthy tissue)
→ caseous necrosis = unique to TB → if caseous necrotic material reaches lymph or bloodstream can cause miliary TB
→ can get ACTIVE TB if pt = immunosuppressed OR has inadequate T-cell immunity
- Latent TB can progress to active TB *
SSX
- chills
- fever
- anorexia
- no appetite
- hemoptysis
- night sweats
- uveitis sometimes
- weakness or fatigue
- persistent dry cough for ≥ 3wks
- cachexia (i.e weight loss + muscle wasting)
* pt w/ latent TB might be asymptomatic *
Ddx
- Covid
- sarcoidosis
- lung cancer
- fungal infec’n
- non-tuberculous mycobacteria
- community-acquired pneumonia
Ix’s
- Interferon γ blood test
- 3 sputum samples for smear (i.e ZN stain) + culture or 3 gastric aspirates in children
→ smear will detect acid-fast bacillus
→ culture will tell us exactly what acid fast bacillus it is
1-3 wks for visible growth on liquid media
⟹ 3-8 wks for visible growth on lowenstein jensen solid media
⟹ Pts w/ +ve sputum smear = HIGHLY CONTAGIOUS
⟹ -ve sputum smear but +ve culture = CONTAGIOUS but not as much as above
⟹ -ve sputum + -ve culture = NON CONTAGIOUS - CXR Findings (“CREG”)
→ Cavities in lung apices (i.e upper lobe consolida’n)
→ Ranke complex (= calcified Ghon complex + calcified mediastinal lymph nodes = seen in healing TB infec’n)
→ Enlarged lymph nodes in right or left hilum of lung
→ Ghon’s complex (seen in UNTREATED TB infec’n)
Tx = “RIPE” i.e quadruple therapy of rifampicin, isoniazid, pyrazinamide + ethambutol (1st 3 = hepatotoxic)
→ RIPE for 2 months
→ R + I = for 4 addi’nal months
⟹ for 10 addin’al months instead if pt has CNS involv’nt
- rifampicin MOA = inhibits RNA synthesis
→ side effect = red/orange body fluids (not dangerous) - isoniazid side effect = peripheral neuropathy i.e numbness / tingling in hands + feet
⟹ pyridoxine (vit B6) = co-prescribed w/ it to ↓ risk of peripheral neuropathy - pyrazinamide side effects = muscle/bone pain + gout/kidney stones b/c causes hyperuricemia
- ethambutol side effects = color blindness or ↓ in visual acuity
TB notifica’n process (TB = notifiable disease so as soon as pt = diagnosed must do contact tracing w/o delay !)
1. Notify closest + most prolonged contacts (this will usually be household contacts)
2. Widen circle until there’s no evidence of transmiss’n
3. WGS (whole genome sequencing) for relatedness
4. Screening contacts for latent + active TB
5. Vaccinate those contacts if no C/I + treat those who are actively infected
- Know for OSCE *
What is DOT for TB ? ✓
DOT = Direct Observed Therapy = HCP provides undeserved groups like homeless ppl, prisoners, drug users + vulnerable migrants w/ TB Tx by watching them swallow to ensure compliance
Sarcoidosis ✓
Def - chronic non-caseating granulomatous disease that often affects lungs, if untreated can progress to pulm. fibrosis + restrictive lung physiology
→ r/o exposure to beryllium b/c berylliosis has same SSX as sarcoidosis
→ disappears in most pts after 2 yrs
RFs
20-50 y/o
- FHx
- black female
- of Scandinavian descent
SSX
- children will usually be asymptomatic
- in black female will present w/ SOB + dry cough
→ lung SSX (in 90% of cases lungs = affected)
- mediastinal lymphadenopathy
- pulm. fibrosis
- pulm. nodules
→ skin SSX
- erythema nodosum i.e b/l tender, red bruises on shins
- lupus pernio i.e raised purple les’ns on nose/cheeks
→ Lofgren’s syndrome = erythema nodosum + b/l hilar lymphadenopathy + polyarthralgia
→ systemic SSX
- fever
- fatigue
- weight loss
→ liver SSX
- liver nodules
- cirrhosis
- hepatosplenomegaly
→ eye SSX
- uveitis
- conjunctivitis
- optic neuritis
Ddx
- TB
- Berylliosis
- Lymphoma
Ix’s
- CXR findings
→ b/l hilar and/or right paratracheal lymphadenopathy
→ b/l pulm. infiltrates (especially in upper lobes) - FBC → anemia, leukopenia
- HyperCa + low PTH sometimes b/c of ↑ed Vit D produc’n by macrophages in granulomas
- serum ACE → often elevated
- bronchoscopy for diagnosis → histology of mediastinal lymph nodes will show non-caseating granulomas w/ epitheloid cells
- U+E / LFTs / ECG / U/S to check if any other organs = affected
Tx = oral corticosteroids or IV if pt can’t tolerate PO + ventilatory support if pt = in acute resp. failure
→ co prescribe w/ bisphosphonates to protect against osteoporosis
Complica’ns
- pulm. fibrosis
- pulm. HTN
- corticosteroid related infec’n
- corticosteroid related osteoporosis
- corticosteroid related hyperglycemia
- Know for OSCE *
Idiopathic Pulmonary Fibrosis ✓
Def - rare chronic life-threatening fibrotic lung disease that progresses over the course of several yrs, usually presents in pts ≥ 60 y/o
→ characterized by forma’n of scar tissue w/in lungs
RFs
- FHx
- male
- smoking
No known Eti
- medica’ns such as amiodarone, bleomycin, biologics, long term nitrofurantoin use
SSX
- clubbing
- progressive dyspnea on exer’n
- nonproductive cough over several months
- systemic SSX such as fatigue + cachexia
- b/l crackles in lower zone
Ix’s
- CXR → basilar, peripheral, b/l, asymmetrical, reticular opacities
- high resolu’n CT → increased reticul’an + honeycombing
Tx for acute exacerba’n = admit to hosptial + give high dose corticosteroid
Regular Tx = anti fibrotic therapy i.e pirfenidone or nintedanib + smoking cessa’n + pulm. rehab + annual flu vaccine → lung transplant
Complica’n = acute exacerba’n → worsening in exercise tolerance
- Know for OSCE *
Bronchiectasis ✓
Def - abnormal dilata’n of bronchi due to destruc’n of elastic + muscular components of bronchial wall = obstructive pb → causes long term productive cough, more common in women
RFs
- CF
- immunodeficiency
- 1°ciliary dyskinesia
- previous infec’n (especially H. influenza + pseudomonas aeruginosa)
Eti
- Post-infectious (18% of cases)
- COPD (15% of cases)
- Connective tissue disorders such as RA or Sjogren syndrome
- Asthma
- Immunodeficiency
- Allergic bronchopulmonary aspergillosis
- Aspira’n or inhala’n injury
Pathophys - micro-organisms colonize airways → chronic airway inflamma’n → bronchial wall edema + ↑ed mucus produc’n
→ neutrophils, T lymphocytes + other inflammatory cells = recruited to airways + subsequently release inflammatory cytokines, proteases + reactive oxygen mediators
→ progressive airway damage + recurrent infec’ns
SSX
- SOB
- cough
- fatigue
- hemoptysis
- A LOT of sputum produc’n
→ ≥ 3 of above had to have been present for ≥ 48hrs in order to diagnose
- weight loss
- recurrent chest infec’ns
- yellow nail syndrome = bronchiectasis + yellow nails + lymphedema
SSX on exam / ausculta’n
- clubbing
- SSX of cor pulmonale i.e raised JVP / peripheral edema
- crackles scattered throughout that change or clear when pt coughs
Ddx
- TB
- COPD
- Asthma
- Pneumonia
- Lung cancer
- Chronic sinusitis
- Pulmonary fibrosis
Ix’s
- high resolu’n chest CT for diagnosis → will show thickened bronchial dilata’n
- CXR → ring shadows + tram track opacities
- sputum culture
- FBC to r/o differentials
Regular Tx = Healthy diet + exercise + Vit D supplementa’n + airway clearance techniques such as active breathing / directed coughing for 15-30 mins (2-3x / day)
Tx for exacerba’n
1. sputum culture
2. Abx for 7-14 days
→ ciprofloxacin for P. aeruginosa
Complica’ns
- exacerba’ns
- cor pulmonale
- ischemic stroke
- respiratory failure
- severe hemoptysis
Cystic Fibrosis ✓
Def - autosomal recessive disease caused by defect of CFTR gene found on chromosome 7 (usually due to a dele’n of Phe508) = most common LETHAL genetic disease in pts of European descent
RFs
- FHx
- white ethnicity
- both parents being carriers of mutant CFTR alleles
Pathophys - CFTR gene codes for Cl channel that secretes Cl in lungs + GI tract + reabsorbs Cl in sweat glands
→ Phe508 dele’n → misfolded protein → protein absent from cell membrane → Cl + water secre’n ↓
→ intracellular [Cl] ↑
→ compensatory ↑ in Na reabsorp’n via ENac (epithelial Na channels) to ↑ water reabsorp’n
→ ↑ in Na reabsorp’n results in a more -ve transepithelial Ψ difference + secre’n of abnormally thick mucus into lungs, GI tract +
pancreas → in pancreas this leads to blockage of exocrine ducts, early activa’n of pancreatic enzymes + eventual auto-destruc’n of the exocrine pancreas which is why most pts require supplemental pancreatic enzymes
SSX
- failure to thrive
- chronic sinusitis
- child tasting salty
- voracious appetite
- hyperexpans’n on CXR
- thick sputum produc’n
- recurrent resp. infec’ns
- chronic wet-sounding cough
- genital abnormality (in males)
- steatorrhea due to fat malabsorp’n
- failure to pass meconium in neonate i.e meconium ileus
Ddx
- GERD
- Asthma
- Celiac disease
- Failure to thrive
- Chronic aspira’n
- 1° ciliary dyskinesia
- 1° immunodeficiency
- Protein-losing enteropathy
Ix’s
- newborn blood spot testing = performed on all children shortly after birth → will pick up most CF cases
- genetic testing
- pilocarpine-induced sweat test = gold std → will show ↑ed [Cl], > 60 = diagnostic
- newborn screening i.e IRT (immunoreactive trypsinogen) → will be ↑ed in newborn w/ CF due to clogging of pancreatic duct
- Regular sputum samples = sent for bacterial culture to check for infective exacerba’n
→ Pts infected w/ P. aeruginosa have a 2-3 fold ↑ed risk of death over 8 yrs
Tx
- chest physio bd (↑ frequency if they have infective exacerba’n)
- high calorie diet for children
- nebulized / inhaled dornase alfa (= DNase) → cleaves neutrophil-derived DNA in sputum to ↓ viscosity + ∴ help w/ sputum removal
→ mannitol dry powder (inhaled) for adult pts who can’t use DNase / whose lung func’n = rapidly ↓ing (i.e FEV1 ↓ > 2% / yr) or who can’t take any other type of osmotic agent - Prophylactic flucloxacillin tablets to ↓ risk of bacterial infec’ns (especially staph aureus infec’ns)
- nebulized hypertonic saline → facilitates mucus clearance
- Pancreatic enzyme replac’nt therapy i.e CREON tablets to replace missing pancreatic enzymes
- being up to date on vaccina’ns to prevent infec’ns (pneumococcal, influenza, varicella)
Complica’ns
- pancreatic insufficiency → in 90% of pts
- delayed puberty
- being underweight
- ↓ed female fertility
- deficient in fat soluble vitamins
- ↓ed bone mineral density → osteoporosis
- chronic liver disease (30% of adults w/ CF develop liver disease)
- CF related diabetes (uncommon in children < 10 y/o, 50% of adults w/ CF develop CF related diabetes + require Tx w/ insulin)
- upper airway complica’ns such as nasal polyps + sinusitis (prevalence ↑ w/ age)
- male infertility due to absent vas deferens (in 99% of males w/ CF hence most male CF pts = infertile)
- prone to staph. aureus + pseudomonas aeruginosa
→ = very difficult to get rid of b/c can become resistant to multiple Abx
→ ↑ morbidity + mortality in CF pts
→ can be treated w/ long term nebulized Abx such as tobramycin or oral ciprofloxacin
Causes of chest pain ✓
“CP4MT2A”
- Costochondritis
- P.E
- Pleural Effus’n
- Pneumothorax
- Pericarditis
- MI
- Cardiac Tamponade
- Aortic dissec’n
- Abdominal pb like GERD or hernia
Pneumothorax ✓
Def - air in pleural space = life threatening
→ traumatic = due to trauma - lung gets punctured → air leaks into pleural space = open pneumothorax i.e air can move in + out (= most common type of pneumothorax)
→ 1° spontaneous = happened w/o any underlying cause = common in tall, thin young men who smoke
→ 2° spontaneous = happened as a result of underlying lung disease such as CF / COPD / necrotizing lung infec’n / lung malignancy (1° or metastatic)
→ iatrogenic - as a result of thoracentesis, bronchospcy, etc
RFs
< 40 y/o
- TB
- CF
- FHx
- COPD
- chest trauma
- severe asthma
- cigarette smoking
- tall + slender body build
- recent invasive medical procedure
Pathophys - we need the -ve pressure inside lungs so air can move from high to low but due to accumula’n of air in pleural space, we have an ↑ in intrapleural pressure ∴ lung can’t reinflate
Tens’n v.s Closed pneumothorax
- tens’n pneumothorax = air can enter but can’t leave = most dangerous out of the 3 b/c air keeps on entering but has nowhere to leave ∴ amt of air in pleural space keeps ↑ing
- closed pneumothorax = air can leave but addi’nal air can’t enter
SSX of tens’n pneumothorax
- SOB
- hypoxia
- chest pain
- tachypnea
- tachycardia
- hypoTN
- tracheal devia’n away from side of pneumothorax due to ↑ in central venous pressure
- ↓ed breath sounds + hyper resonance on percuss’n + hyperinfla’n of hemithorax (on AFFECTED side for all 3)
Ddx
- MI
- P.E
- Pleural effus’n
- COPD exacerba’n
- Asthma exacerba’n
- Esophageal perfora’n
- Bronchopleural fistula
- Fibrosing lung disease
Ix’s
- erect CXR
- clotting profile b/c if INR ≥ 1.5 or platelets ≤ 50 x 10⁹/L, MUST BE CORRECTED BEFORE INSERTING CHEST DRAIN in pts who are NOT critically unwell !
- CT thorax b/c can detect small pneumothorax that CXR can’t
Emergency Tx (i.e for suspected tens’n pneumothorax)
- Immediate decompress’n by inserting large bore cannula in 4th/5th intercostal space in midclavicular line → hiss of air confirms diagnosis
* open thoracostomy instead if tens’n pneumothorax = 2° to trauma * - High flow O2
- Chest drain + hospital admiss’n
→ insert drain in triangle of safety i.e apex of axilla + 4th intercostal space mid clavicular line + anteriorly in 2nd intercostal space
⟹ after inserting drain do CXR to check posi’n of drain
Tx for large 1° spontaneous i.e > 2cm = aspirate + for any other 1° pneumothorax = discharge w/ written advise to come back to ED if SOB worsens + pulmonology f/u in 1-2 wks
Tx for large 2° spontaneous = chest drain + hospital admiss’n
Tx for moderate 2° spontaneous i.e 1-2 cm = percutaneous aspira’n ± high flow O2
Tx for small 2° spontaneous i.e < 1 cm = high flow O2 + observa’n for 24 hrs + hospital admiss’n
Complica’ns of chest drain
- air leaks around drain site → indicated by persistent bubbling of fluid, particularly on coughing
- surgical / subq emphysema = when air collects in subq tissue
- Know for OSCE *
CXR analysis ✓
- Lungs should be black on CXR so if they’re white i.e instead of being sharp as they should be, lung borders = as if they’re blurry then that could mean …
→ no air getting in due to atelectasis / lung collapse
→ consolida’n i.e air is still getting in but something is replacing that air i.e . . .
⟹ a solid structure such as a tumor
⟹ pus (i.e in infec’n like pneumonia → alveoli will still be white on bronchogram)
⟹ fluid such as . . .
- blood in trauma or vasculitis
- water in pulm. edema
⚠️ If u suspect that “something” is fluid do CT or U/S !
- In right lung collapse, left lung will be really dark = compensatory hyper-infla’n of left lung b/c it has to compensate for the collapsed right lung
AKI ✓
Def - acute but usually reversible ↓ in renal func’n, ≥ 1 of the following criteria has to be met for diagnosis . . .
→ ↑ in serum Cr by ≥ 0.3 mg/dL or 25 micromol/L w/in 48 hrs
→ ↑ in serum Cr to ≥ 1.5 times baseline w/in past 7 days
→ Urine volume < 0.5 mL/kg/hr for past 6 hrs
RFs
- Sx
- sepsis
- trauma
- pancreatitis
- cardiac arrest
- advanced age
- drug overdose
- nephrolithiasis
- malignant HTN
- diabetes mellitus
- iodinated contrast
- underlying kidney disease
- excessive fluid loss such as in hemorrhage
- myeloproliferative disorders such as multiple myeloma
- Na retaining states such as CHF, cirrhosis, nephrotic syndrome
- nephrotoxins like vancomycin, penicillin, cancer Tx, NSAIDs, ACE-I’s, diuretics
Eti
1) Pre-renal = most common of the 3 = due to ↓ed renal perfus’n → ischemia
Causes :
→ pre renal azotemia = most common cause of AKI in hospitalized pts
→ renal artery stenosis
→ low blood volume
⟹ shock
⟹ severe burn
⟹ heart failure
⟹ dehydra’n, vomiting, diarrhea
⟹ major blood loss i.e hemorrhage
→ drugs (“DAAN”)
⟹ Diuretics
⟹ ARBs
⟹ ACE-I’s → cause vasodila’n of efferent arterioles which causes blood flow to be too fast
⟹ NSAIDs → vasoconstrict afferent arteriole
Diagnosis = high Urea : Cr ratio (i.e > 20) + urine output improves w/ fluids
2) Intrinsic / Renal = direct injury to kidney parenchyma i.e pb = nephrons themselves
Causes
- contrast (can prevent this type of AKI by giving NS)
- glomerulonephritis
- acute interstitial nephritis (AIN) → will cause eosinophils in urine
→ pt will also have fever, rash + flank pain
- acute tubular necrosis (ATN) → will cause granular brown casts in urine
→ can be caused by nephrotoxic drugs like vancomycin, amino-glycosides, contrast media, cisplatin, heavy metals like lead, heme pigments in rhabdomyolysis, ethylene glycol
Diagnosis = low Urea : Cr ratio (i.e < 15)
3) Post-renal = ureter or renal vein obstruc’n (ureters usually) → obstruc’n HAS TO BE B/L b/c if it’s u/l the other can do the work of both
Causes
- BPH
- lymphoma
- urinary reten’n
- renal calculi / kidney stones
- stricture of ureter/urethra (= most common at renal calyces + renal pelvis)
⚠️ All 3 types of AKI will cause low GFR (w/in a few days), low urine output + high Cr
⚠️ Obstruc’n of renal tract must always be excluded in anuric pt !
Ddx
- CKD
- iatrogenic
Ix’s
- FENa
→ < 1% = pre-renal
→ > 2 % = ATN
Emergency Tx - rehydrate w/ NS (0.9%) if volume depleted → stop all nephrotoxic drugs after doing the following Ix’s . . .
⟹ urine dipstick + urine microscopy + culture
⟹ U+E, FBC, LFTs, ABG, Ca, MM screen
⟹ U/S of kidneys, ureters + bladder
→ treat HyperK if present
→ dialysis IFF pt has life-threatening or intractable pulmonary edema / uncontrollably rising K / severe (i.e pH < 7.2) or worsening acidosis
Complica’ns
- uremia → pericarditis, encephalopathy
- HyperK
- HyperPhos
- metabolic acidosis
⚠️ Kidneys have 30 mins w/o blood supply before they start to shut down !
- Know for OSCE *
Kidney stones (nephrolithiasis) ✓
= most common at renal calyces + renal pelvis
→ can also occur at trigone b/c that’s where ureters join together before emptying their urine into bladder
→ larger stones tend to remain confined to kidney but smaller stones can pass into ureter + cause ureteric colic (VERY SEVERE PAIN !)
SSX
- vomiting
- hematuria
- renal colic i.e u/l descending groin pain i.e from top to bottom (due to stone moving)
→ DON’T use X-ray b/c might show Ca stones b/c they’re white but won’t show uric acid stones → use U/S instead → only pb w/ U/S = won’t show stones < 5 mm ∴ use CT KUB instead
Ix = CT KUB
Complica’ns
- obstruc’n
- hydronephrosis
- infected stone → sepsis
Complica’ns of obstruc’n
- HTN
- AKI
- Hydroureter + hydronephrosis due to ↑ in pressure proximal to stone
- u/l obstructive uropathy i.e loss of kidney func’n on affected side
- UTI → ascends to kidney + becomes pyelonephritis → rapid destruc’n of kidney → sepsis (immediate complica’n)
Tx for non obstructed stone
- if stone < 7 mm = likely to pass on its own so just hydra’n + analgesia w/ NSAIDs
Emergency Tx for obstructed stone = nephrostomy = inser’n of tube through abdominal wall into renal pelvis through which urine can drain freely
- Know for OSCE *
Nephrotic v.s Nephritic ✓
Nephrotic
- severe PROteinuria (≥ 3.5 g/L/day, urine might have frothy appearance)
- hypoalbuminemia (≤ 30 g/L)
- edema + HLD + hypercoagulability
Nephritic
- hematuria
- oliguria
- minor proteinuria
- red cell casts in urine
- Know for OSCE *
Glomerulonephritis ✓
Def - inflamma’n of glomeruli
→ SSX = nephrotic or nephritic syndrome
Nephrotic Eti
- minimal change disease = most common cause of nephrotic syndrome in children
- membranous nephropathy = most common cause of nephrotic syndrome in adults
→involves deposits of immune complexes in glomerular basement membrane
→ histology will show IgG + complement deposits on basement membrane
→ can occur 2° to malignancy, SLE or drugs such as NSAIDs - HSP
- diabetic nephropathy
- focal segmental glomerulosclerosis
- Goodpasture syndrome → anti GBM antibodies attack glomerulus + pulmonary basement membranes
⟹ pt will present w/ acute kidney failure + hemoptysis
Nephritic Eti
- HSP
- vasculitis
- lupus nephritis
- IgA nephropathy → histology will show IgA deposits + mesangial cell prolifera’n
- post-streptococcal glomerulonephritis → presents 1-3 wks after strep infec’n such as tonsillitis or impetigo ⟹ usually affects pts < 30 y/o + pts usually make full recovery
Ix = renal Bx for diagnosis
Tx = treat underlying cause
Tx for nephrotic syndrome = diuretics, statins + anticoagula’n
Complica’ns of nephrotic syndrome
- HTN
- HLD
- thrombosis
- Know for OSCE *
Polycystic kidney disease ✓
Def - genetic disorder where healthy kidney tissues = replaced by cysts
RFs
- HTN
- male
- proteinuria
Types
- autosomal dominant
- autosomal recessive
Eti based on type
- autosomal dominant
→ muta’n of PKD1 gene on chromosome 16 (most of the time)
→ muta’n on PKD2 gene on chromosome 4 - autosomal recessive = due to mutat’n of PKHD1 gene on chromosome 6 = more rare but more severe
→ often picked up on antenatal scan → scan will show oligohydramnios
SSX
- flank pain
- mitral regurgita’n
- colonic diverticula
- hematuria if cyst ruptures
- underdeveloped ear cartilage, low-set ears + flat nasal bridge for recessive
Ix’s = U/S of renal tract + genetic testing
→ diagnostic criteria . . .
- ≥ 3 renal cysts (u/l or b/l) if ≤ 39 y/o
- ≥ 2 cysts in each kidney if 40-59 y/o
- ≥ 4 cysts in each kidney if ≥ 60 y/o
Tx
- Antihypertensives for HTN
- Analgesia for acute pain
- Abx for infec’ns
- Drainage of symptomatic cysts
- Dialysis / transplant for end-stage renal failure
- Tolvaptan in autosomal dominant to slow progress’n
Complica’ns
- kidney stones
- recurrent UTIs
- cerebral aneurysms
- hepatic, splenic, pancreatic, ovarian, prostatic cysts
- end stage renal failure (usually occurs around 50 y/o for dominant + before adulthood for recessive)
- Know for OSCE *
SIADH ✓
Eti
- post op
- chest infec’n
- drugs i.e TCAs, SSRIs, carbamazepine, sulfonylureas
- CNS disturbance such as traumatic brain injury
- ADH secreting tumor such as in small lung cancer
Pathophys - ↑ in ADH secre’n by posterior pituitary → ↑ in water reabsorp’n → diluted blood + [ ]ed urine
SSX = HypoNa SSX
Ddx = other causes of HypoNa
Ix’s
- U + E → HypoNa
- serum osmolality → will be low
- urine osmolality + urine Na → will both be high
- CT thorax, abdomen + pelvis + head MRI to check for malignancy
Tx
- admit if HypoNa = severe i.e < 125
- treat underlying cause
- fluid restric’n (750-1000 mL/day)
- tolvaptan = vasopressin receptor antagonist so blocks ADH receptors
→ can only be initiated by endocrinologist + requires close Na monitoring i.e every 6 hrs
Complica’ns
- Know for OSCE *
HypoNa ✓
= most common electrolyte abnormality → serum osmolality must be low i.e < 280 mOsm/kg for it to be true HypoNa !
RFs
- old age
- SSRI use
- ecstasy use
- hospitaliza’n
- thiazide diuretic use (especially if pt also takes PPIs)
Eti
- Hypovolemic HypoNa = ↓ in blood volume for whatever reason i.e severe diarrhea or vomiting, pancreatitis, severe hypo-albuminemia, mineralo-corticoid deficiency
→ in this type of HypoNa we expect to see hypovolemia SSX i.e pallor, ↓ed skin turgor, tachycardia, orthostatic hypoTN - Hypervolemic HypoNa = due to fluid overload i.e CHF, pulmonary edema, AKI, CKD, cirrhosis, nephrotic syndrome
→ in this type of HypoNa we expect to see SSX of fluid overload - Euvolemic HypoNa causes . . .
→ high fluid intake
→ medica’ns such as vasopressin, thiazide diuretics, antidepressants + opioids
→ syndrome of inappropriate ADH secre’n
→ psychogenic polydipsia = when pt compulsively drinks >10 L of water/day
SSX of SEVERE HypoNa i.e cerebral edema maybe
- progressive HA
- N/V
- AMS / Δ in level of consciousness
Ix’s
- U + E → Na will be < 135 mmol/L
- Serum glucose (random or fasting) to r/o hyperglycemia-associated HypoNa
- Serum osmolality → must be < 280 mmol/kg or mOsm/kg for it to be true HypoNa
→ if normal check for hyperproteinuria or hyperlipidemia
→ if > 280 check for hyperglycemia/mannitol or sorbitol use/recent contrast - Physical Exam
- If there are fluid overload SSX = Hypervolemic
a) Urinary Na < 20 = due to CHF / cirrhosis / hypoalbuminemia
b) Urinary Na > 20 = due to renal failure
- If there are dehydra’n SSX = Hypovolemic
a) Urinary Na < 20 = due to EXTRArenal loss i.e vomiting, diarrhea, bowel obstruc’n
b) Urinary Na > 20 = RENAL loss i.e diuretic use, mineralocorticoid deficiency
- No SSX of hypo or hypervolemia = Euvolemia
a) Urine osmolality < 100 = 1° polydipsia or beer potomania
b) Urine osmolality > 100 = SIADH, hypoTSH or adrenal insufficiency
Tx
- for hypervolemic HypoNa = fluid + Na restric’n + treat underlying cause
- for hypovolemic HypoNa = 0.9% saline (isotonic saline)
- for euvolemic HypoNa = calculate electrolyte free water clearance = (Urine Na + K) / Serum Na
→ if < 0.5 then Tx = 1L fluid restric’n
→ if btw 0.5-1 then Tx = 0.5L fluid restric’n
→ if > 1 give tolvaptan 15 mg od → monitor Na every 6hrs → aim for Na of 130
Complica’ns
- osteoporosis
- ↑ed risk of falls
- cerebral edema in severe HypoNa (Tx = IV mannitol) → brain hernia’n → death
- osmotic demyelina’n syndrome if u correct HypoNa too quickly
→ Na [ ] should not change > 10 mmol/L in 24 hrs !
→ SSX usually occur after 2 days → dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confus’n, coma - Know for OSCE *
HyperNa ✓
RFs
- Li use
- 1° hypodipsia
- large salt intake
- renal [ ]ing defect
- limited access to water
- ↓ in ability to [ ] urine (in old age for ex)
- GI disorders such as prolonged vomiting or severe watery diarrhea like in viral gastroenteritis
Eti
- free water loss causes (most common)
- Na overload such as in mineralocorticoid excess
- pure free water intake deficit i.e impaired thirst mechanism or not consuming enough water
SSX
- ↓ed JVP
- oliguria
- weight loss
- impaired thirst
- orthostatic hypoTN
- diarrhea or vomiting
Ix’s = urine + plasma osmolality
→ urine osmolality ≤ plasma osmolality suggests diabetes insipidus
→ urine osmolality ≥ plasma osmolality suggests pure volume deple’n NOT due to diabetes insipidus
→ urine osmolality ≈ plasma osmolality suggests renal [ ]ing defect (usually due to renal failure, osmotic diuresis or diuretic use)
Tx - treat underlying cause if possible
→ correct dehydra’n by replacing free water losses → correct hypovolemia if present by giving electrolytes + free water
Complica’ns
- CPM
- cardiac toxicity
- Tx related brain edema
- Tx related hyperglycemia
- rhabdomyolysis (not common)
- Know for OSCE *
HypoK ✓
RF = psychiatric pts due to their medica’ns
Eti
- ↑ed entry of K from blood to tissues / cells
→ chloroquine intoxica’n
→ ↑ed β adrenergic activity such as in Cushing’s syndrome b/c catecholamines (adrenaline, cortisol) promote K ENTRY into cells by ↑ing Na K ATPase activity which is why excess admin of β agonists can cause HypoK
→ alkalosis b/c H+ ions will LEAVE cells to enter blood to correct pH which will cause K to leave blood + ENTER cells
→ ↑ed availability of insulin b/c insulin ↓ serum K by stimulating Na/K ATPase pump
- K loss from upper GI tract i.e prolonged vomiting
- K loss from lower GI tract
→ villous adenoma → will cause diarrhea + rectal secre’ns = rich in K
→ vasoactive intestinal peptide secreting tumor (VIPoma) - K loss from urine
→ loop + thiazide diuretics
→ hypomagnesemia
→ mineralocorticoid excess such as in 1° aldosteronism/Conn’s syndrome
Asymptomatic for mild-moderate
SSX for severe
- constipa’n
- generalized weakness
- muscle pain
Ix = ECG → ≥ 1 of the following signs . . .
- T wave invers’n
- long PR interval
- flat T waves in almost all leads (flat = shaped like P wave)
Tx
1) Oral K + plenty of fluids (w/ or after meals)
2) IV KCl in pts w/ severe N/V or abdominal distress
→ 0.9% NaCl = preferred infus’n fluid as 5% glucose may cause trans-cellular shift
of K into cells + hence worsening the HypoK
Complica’ns
- flaccid paralysis
- rhabdomyolysis
- muscle weakness
- hepatic encephalopathy in pts w/ cirrhosis
- cardiac arrhythmias + sudden cardiac death
→ pts w/ CHF, on digoxin or aggressive therapy for hyperglycemia such as in DKA = most @ risk of this
- Know for OSCE *
HyperK ✓
= MEDICAL EMERGENCY b/c can cause paralysis, arrhythmias + cardiac arrest
Eti
- ↓ed renal excre’n . . .
→ NSAIDs
→ mineralocorticoid deficiency
→ acute or chronic renal insufficiency such as in AKI or CKD (stage 4 or 5)
→ ACE-Is / ARBs b/c cause a state of hypoaldosteronism - ↓ed entry of K into cells i.e metabolic acidosis b/c MORE H+ ions will leave blood to ENTER cells to correct pH ∴ LESS K will ENTER cells
- ↑ed exit of K out of cells
→ TLS
→ rhabdo
→ admin of mannitol b/c will cause ↑ in osmolality i.e plasma becomes more [ ]ed b/c more solutes leave cells to enter blood (K included)
SSX
- diarrhea
- vomiting
Ix = ECG → will show ≥ 1 of the following signs . . .
- long PR interval
- flat or completely absent P waves
- broad/wide QRS complexes aka broad + short instead of tall + pointy (i.e looks more like a T wave)
- tall tented T waves in almost all leads aka tall + pty instead of broad (i.e looks more like QRS complex)
Emergency Tx i.e HyperK ECG signs OR K > 6.5 = IV Ca gluconate b/c stabilizes cardiac muscle cells hence ↓ing risk of arrhythmia (asystole specifically)
→ insulin dextrose b/c insulin drives K from extracellular to intracellular space by stimulating Na K ATPase pump + dextrose = to prevent hypoglycemia
- Know for OSCE *
Should you treat asymptomatic bacteriuria ? ✓
NO unless pt = pregnant !
UTIs (in adults + kids) ✓
Def - infec’n of kidneys, bladder or urethra that are more common in women
→ usually caused by E. coli + 2nd by Klebsiella pneumoniae
→ most common UTI = infectious cystitis (bladder infec’n)
RFs in kids
< 1 y/o
- female
- previous UTI
- sexually active
- urinary obstruc’n
- uncircumcised boys in 1st yr of life
RFs in men
> 50
- BPH
- previous UTI
- catheteriza’n
- urological Sx
- urethral stricture
- ureter or kidney stones
RFs in women
- sexual activity
- spermicide use
- post menopause
- Hx of recurrent UTIs
SSX
- nocturia
- confus’n (in older pts)
- suprapubic pain/tenderness
- cloudy or foul smelling urine
- urinary frequency and/ or urgency
- macroscopic hematuria i.e visible hematuria
- dysuria i.e pain/burning/stinging during urina’n
- CVA tenderness = in btw 12th rib + spine (on their back, on each side for each kidney)
Ddx
- urethritis
- prostatitis
- epididymitis
- renal cancer
- bladder cancer
- prostate cancer
- pyelonephritis
- ureter or kidney stones
- vaginitis, overactive bladder
- urethral syndrome / abacterial cystitis = UTI SSX w/o infec’n
Ix’s
- gram stain
- MSU for urine microscopy + culture
- urine dipstick → only diagnostic if shows +ve nitrites or +ve leukocytes w/ RBCs
Tx in adults = nitrofurantoin (narrow spectrum AB, avoid in 3rd trimester of pregnancy) if GFR ≥ 45 OR trimethoprim/ sulfamethazole if there’s low risk of resistance
→ MOA of trimethoprim / sulfamethazole = inhibits folic acid forma’n by preventing bacterial convers’n of tetrahydrofolate to its active form
→ side effects = rash, photosensitivity + folate deficiency
→ C/Is = 1st trimester, liver or renal failure + hematological disorder
a) if they’re < 65 y/o + NOT pregnant treat if pt has ≥ 2/3 of the following . . .
- cloudy urine
- dysuria
- nocturia
OR has ≥ 1 of those 3 + relevant dipstick
b) if they’re ≥ 65 y/o treat if pt has new onset dysuria OR ≥ 2 of the following . . .
- temp is 1.5ºC above normal in last 12 hrs
- new frequency or urgency
- new incontinence
- new or worsening delirium
- new suprapubic pain
- visible hematuria
c) If they’re pregnant just treat
Preven’n for women
- hydrating + urinating after intercourse
- taking prophylactic Abx if she has Hx of recurrent UTIs
Dura’n of Adult AB Tx
- 3 days for non pregnant woman that is otherwise healthy (regardless of age)
- 5-10 days for immunosuppressed women or pts w/ abnormal anatomy or impaired kidney func’n
- 7 days for men, pregnant women or catheter-related UTIs
Tx in children
a) ≤ 2 months = ampicillin for 7-14 days
b) > 2 months = cefixime for 7-14 days
⚠️ Recurrent UTIs in children requires f/u U/S in 6 wks + DMSA scan in 4-6 months !
Complica’ns
- sepsis b/c stone can get infected
- prostatitis (in men)
- renal func’n impairment
- pyelonephritis (especially in pregnant women)
- PROM / pre term labor (in pregnant women)
- Know for OSCE *
Atypical UTIs in children ✓
SSX
- child = seriously ill
- poor urine flow
- abdominal / bladder mass
- ↑ed Cr
- septicemia
Ix’s for children < 6 months
- urgent USS during infec’n
- MCUG scan once infec’n resolves
- routine DMSA 4 months later
- Know for OSCE *
Mx of fever in pt < 3 months old ✓
- Urgent referral for peds assess’nt in hospital
- Ix’s
- FBC
- CRP
- blood culture
- urinanalysis
- stool culture if baby has diarreha
- CXR if baby has resp SSX
- Know for OSCE *
Acute Pyelonephritis ✓
Def - severe infectious inflammatory disease of renal parenchyma, renal calices + renal pelvis
RFs
- UTI
- diabetes
- pregnancy
- stress incontince
- frequent sexual intercourse
- foreign body in urinary tract i.e calculus / catether
- immunosuppressive state i.e HIV / transplanta’n / chemo/ long term or high dose corticosteroid use
Eti - usually E. coli just like UTIs
SSX = fever + N/V + loin/back pain + UTI SSX (especially CVA tenderness)
Ddx
- UTI
- PID
- urethritis
- acute prostatitis
- lower lobe pneumonia → do CXR to rule it out
Ix’s
- urinanalysis → might show . . .
⟹ +ve nitrites
⟹ +ve leukocytes
⟹ WBC casts → indicate UTI of renal origin - urine culture + sensitivity
Tx = oral Cefalexin for 7-10 days while waiting for culture
→ IV ceftriaxone or co-amoxiclav instead if pt = vomiting
Complica’ns
- renal failure
- sepsis (do Sepsis 6 immediately if pt = septic)
- lack of response to Tx (usually pts w/ kidney stone or renal abscess)
- Know for OSCE *
CKD ✓
Def in adults - abnormalities in kidney structure or func’n for ≥ 3 months
Def in children - GFR < 60 for > 3 months + ≥ 1 of the following . . .
- proteinuria
- albuminuria
- pathologic abnormalities on histology or imaging
RFs
> 50 y/o
- HTN
- diabetes
- kidney disease
- chronic use of nephrotoxic drugs such as NSAIDs
Eti
1. Diabetic nephropathy
2. HTN
3. Other causes i.e . . .
- amyloidosis
- lupus nephritis
- obstructive uropathy
- membranous nephropathy
- rapidly progressive glomerulonephritis
- cystic disorders of the kidney such as PCKD
Pathophys - Eti → renal injury → ↑ in intraglomerular pressure w/ glomerular hypertrophy b/c kidney has to compensate for nephron loss in order to maintain normal GFR
→ ↑ in glomerular permeability + ↑ in ATII produc’n due to renal injury
→ renal scarring w/in glomerulus
SSX
- asymptomatic or . . .
- anemia SSX once GFR ↓ to < 50 due to ↓ in EPO produc’n
- uremia due to kidney failure
- N/V due to uremia
- anorexia due to uremia
- restless legs due to uremia
- pruritus due to uremia + scratch marks due to the pruritus
- edema b/c ↓ in GFR causes ↑ in salt + water reten’n
- foamy urine due to proteinuria b/c kidneys are leaking protein
Ddx
- glomerulonephritis
- nephrotic syndrome
- obstructive uropathy
- diabetic nephropathy
- ischemic nephropathy
- hypertensive nephrosclerosis
Ix’s
- for diagnosis → GFR < 60 mL/min/1.73 m^2 over 3 months OR ≥ 1 indicators of kidney damage i.e proteinuria / microscopic OR Urine albumin : Cr ratio (ACR) consistently > 3 mg/mmol
- urinalysis → Ψ hematuria or proteinuria (quantified by urine albumin : Cr ratio)
- U+E → elevated urea + Cr + electrolyte abnormalities
- renal U/S → kidney atrophy (can diagnose CKD if kidney atrophy = present w/ obstruc’n, hydro-nephrosis or bladder reten’n)
- BP/ lipid profile / A1c to identify RFs
Staging
- G1 = GFR ≥ 90
- G2 = GFR from 60-89
- G3a = GFR from 45-69
- G3b = GFR from 30-44
- G4 = GFR from 15-29
- G5/ESRD = GFR ≤ 15 OR pt is already on dialysis (these pts require long-term dialysis or transplant)
Criteria for nephrology referral (only 1 = needed)
- GFR < 30
- ACR > 70 (ACR = Albumin : Cr Ratio)
- accelerated progress’n i.e ↓ in GFR of 25% in past yr
- 5 yr risk of requiring dialysis > 5%
- uncontrolled HTN despite being on ≥ 4 antihypertensives
Tx
- Statin 20mg to ↓ risk of CVD
- BP + glucose control
→ BP target for ACR > 70 = < 130/80
→ BP target for ACR <70 = < 140/90
a) ACE-I/ARB titrated to highest dose if pt has ACR > 70 OR HTN + ACR > 30 OR diabetes + ACR > 3
* Monitor K wile they’re under Tx ! *
b) Dapagliflozin (SGLT-2 inhibitor) if pt has diabetes + ACR > 30
- G5 stage or pt has uremia = dialysis + then transplant from deceased or living donor if can find available kidney
→ peritoneal dialysis can be done at home
⟹ catheter = inserted into abdomen + dialysis fluid = instilled → fluid + toxic waste products = removed + drained from body on a daily basis
→ hemodialysis = done in hospital ∴ pt has to come in 3x/wk + each sess’n lasts 3-4hrs
⟹ pt’s blood = removed from body through AV fistula / AV graft / dialysis catheter + is then returned after traversing dialysis membrane + dialysis solu’n
- Renal Diet i.e low Na, low protein, low K + low PO4
Complica’ns
- anemia → treat w/ IV iron +/- artificial EPO
- CVD
- pulmonary edema due to fluid overload
- HyperK due to kidney’s inability to excrete K
- metabolic acidosis due to kidney’s inability to excrete acid (happens when GFR is < 50) → treat w/ oral Na bicarb
- renal osteodystrophy / CKD mineral + bone disorder (CKD-MBD) in advanced CKD b/c kidney can’t activate Vit D → HypoCa
→ HyperPTH + HyperPhos to compensate → bone mineral imbalance → bone weakening
→ bone pain + fractures
→ gait + limb weakness
⟹ treat w/ PO4 binders such as Ca acetate + calcitriol b/c it ↓ PTH - Know for OSCE *
Indica’ns for Dialysis ✓
(“AEIOU”)
- Acidosis (pH < 7.1)
- Electrolyte pb i.e K > 6.5
- Ingest’n of SLIME toxins (Salicylates, Li, IsopropanOH, MetOH + Ethylene Glycol)
- Overload of fluid
- Uremia i.e High Urea : Cr ratio
- Know for OSCE *
Indica’ns for dialysis in salicylate overdose ✓
- coma
- seizures
- acute renal failure
- pulmonary edema
- serum [salicylate] > 700mg/L
Tx for salicylate overdose ✓
- Activated charcoal
- IV Na Bicarb to enhance elimina’n of aspirin in urine
Insulin + Glucagon ✓
- Insulin = secreted by β cells of pancreatic islets of Langerhans to ↓ blood glucose
- Glucagon = secreted by 𝛼 cells of pancreatic islets of Langerhans to ↑ blood glucose
Type 1 + 2 Diabetes Mellitus ✓
Def - diabetes mellitus = group of metabolic diseases where pt has high blood glucose either b/c pancreas isn’t PRODUCING insulin at all (i.e Type 1 → usually occurs in young ppl) OR b/c tissues aren’t RESPONDING to insulin (i.e Type 2 / insulin resistance → usually occurs in older ppl)
⟹ Idiopathic Type 1 = no identifiable antibody
⟹ Auto-immune Type 1 = identifiable antibody = attacking β cells + hence preventing them from making insulin
RFs for T2D
> 40 y/o
- FHx
- HTN
- CVD
- PCOS
- stress
- dyslpidemia
- gesta’nal diabetes
- non white ancestry
- overweight or obese
SSX
- unexplained weight loss / ↑ in appetite for T1D
- polydipsia due to loss of water in urine
- polyuria due to glucose in tubules drawing water in
- glucose in urine (= abnormal in non-diabetic pt)
- acanthosis nigricans in T2D (rare tho) = usually in neck, armpits or groin area
⚠️ High glucose can also cause blurry vis’n !
⚠️ Polyuria = greater urine output i.e > 3L / day v.s urinary frequency = peeing more OFTEN than usual !
Ddx
- diabetes insipidus
- psychogenic polydipsia
- T2D for T1D + vice-versa
- gesta’nal diabetes if pt = pregnant
Diagnostic Criteria for T2D
- SSX + Fasting glucose > 7mmol OR any other glucose > 11.1 mmol OR HbA1c > 6.5% (CANNOT R/O diabetes just b/c HbA1c = normal !)
→ DON’T use HbA1c in . . .
⟹ pts who had diabetic SSX for < 2 months
⟹ pancreatic Sx / damage
⟹ pts suspected of having T1D
⟹ pts who require hospital admiss’n
⟹ children b/c they have higher RBC turnover rate
⟹ pts on medica’ns that can quickly ↑ blood glucose such as steroids or anti-psychotics
⟹ presence of genetic / hematologic / illness-related factors that influence HbA1c + its measur’nt such as pregnancy
Tx for T1D
- Detemir basal bolus insulin injec’n bd (= rapid acting insulin) + 75-150 mg oral aspirin od IF pt = pregnant b/c = at risk of developing pre-eclampsia → fixed dose insulin (in NON-PREGNANT adults only !)
⚠️ amitriptyline if pt has burning pain in feet / difficulty sleeping / ↓ed GFR
Tx for T2D
- Lifestyle Δs + after 3-6 months check if pt reached target HbA1c, if not . . .
- Metformin OR DPP-4 inhibitor / pioglitazone / sulfonylurea if metformin = contraindicated OR SGLT-2 inhibitor if the other 3 aren’t appropriate for pt
- Add SGLT-2 inhibitor if pt has chronic heart failure or established atherosclerotic CVD
→ if pt = at high risk of DKA i.e already had DKA / is unwell w/ intercurrent illness or is on very low carb diet such as keto diet, fix modifiable risks before starting them on SGLT-2 inhibitor - ↑ dose of metformin
- Triple therapy i.e metformin + 2 of the other op’ns
→ Metformin
⟹ MOA - oral biguanide that ↓ glycogenolysis + gluconeogenesis
⟹ C/Is - advanced heart pb or renal pb hence must stop it if GFR < 30
⟹ Side effects
- nausea
- diarrhea
- abdominal discomfort
- ↑ed [lactic acid] → lactic acidosis (very rare but can be fatal)
- B12 deficiency due to ↓ed B12 absorp’n (after prolonged metformin use)
⟹ monitoring → U+E before prescribing + then yrly (STOP IT IF GFR < 30 !)
⟹ don’t take before or after contrast
⟹ stop it temporarily if sick + restart it after 24-48 hrs
→ SGLT-2 inhibitors : (end in “GLIFLOZIN”)
⟹ MOA- inhibits SGLT 2’s which are proteins expressed in PCT of kidneys that reabsorb filtered glucose from tubular lumen + also co- transport Na along w/ glucose → glucose + Na reabsorp’n ↓ → urinary excre’n of glucose ↑
⟹ C/I = dialysis
⟹ Side effects
- DKA
- urinary urgency
- genital fungal infec’ns
- hypoTN due to fluid deple’n b/c of the ↓ in Na reabsorp’n
→ DPP-4 inhibitors - (end in “LIPTIN”)
⟹ MOA - DPP-4 enzyme degrades incretin hormones such as GLP-1 + GIP which ↑ insulin secre’n + ↓ glucagon secre’n ∴ by inhibiting DPP-4 we have ↑ed insulin secre’n by GLP-1 + GIP
⟹ C/I = T1D, DKA + Hx of pancreatitis
⟹ Side effects
- HA
- UTI
- URTI
- arthralgia
- nasopharyngitis
→ Sulfonylureas : (begin in “GLI” + end in “IDE”)
⟹ MOA - bind to + inhibit ATP sensitive K channels on pancreatic β cells → ↓ in K efflux
→ β cell membrane depolarizes
→ Ca channels open → influx of Ca
→ ↑ in intracellular [Ca] stimulates pancreatic β cells to release insulin irregardless of blood glucose levels
⟹ C/Is = none
⟹ Side effects
- weight gain hence should be avoided in obese pts
- hypoglycemia (especially after a missed meal, exercise or taking high dose of sulfonylurea),
Acute complica’ns
- DKA (more in Type 1) → urinalysis will show ketones in urine + ABG will show metabolic acidosis
- HHS (more in Type 2)
- Hypoglycemia b/c of . . .
→ sulphonylurea use
→ injecting too much insulin
→ exercising more than usual
→ excessive alcohol consump’n
→ ingesting less glucose i.e not eating enough
RFs for chronic complica’ns
- FHx
- HTN
- smoking
- dyslipidemia
- excess weight
- long disease dura’n b/c the more the disease progresses, the more glucose there is + high glucose = directly toxic to β cells
Chronic complica’ns
- Microvascular
→ UTIs
⟹ urinalysis might show +ve leukocytes or nitrites but only give Abx in pregnant pt
→ Nephropathy (NOT the same as diabetic kidney disease)
⟹ screen via microalbuminuria 1st + then Urea / Cr b/c Urea / Cr happens later + then via GFR
⟹ in end stage kidneys can no longer activate Vit D so we get HypoCa + hence 2° HyperPTH
→ Retinopathy i.e cotton wool spots (due to retinal ischemia or retinal infarct as a result of diabetes) + even blindness
⟹ screen via fundoscopy, retinal photography + fluorescein angiography where indicated
⟹ classifica’n . . .
- maculopathy = more common in T2D
- proliferative retinopathy (PDR) =
more common in T1D
→ 50% of these pts = blind in 5 yrs
- non-proliferative diabetic retinopathy (NPDR)
→ Peripheral Neuropathy → diabetic foot ulcers due to poor wound healing + loss of sens’an so pt doesn’t realize foot is injured + neuropathic pain
⟹ complica’n of diabetic foot ulcer = osteomyelitis
⟹ screen via peripheral vascular exam + motor / sensory neuro exam
⟹ treat neuropathic pain w/ amitriptyline, duloxetine, gabapentin or pregabalin
→ Autonomic Neuropathy → diabetic gastroparesis i.e delayed gastric emptying → SSX = vomiting, early satiety, postprandial fullness + pt feels bloated
→ Ischemic CN 3 palsy
- Macrovascular
→ HTN
→ stroke
→ heart disease
→ recurrent skin infec’ns
→ peripheral vascular disease
⚠️ Exogenous v.s Insulinoma i.e endogenous insulin overproduc’n v.s Sulphonylurea
- Insulin = ↑ in all 3
- C-peptide = undetectable in exo + ↑ in other 2
- Sulphonylurea = only detectable in sulphonylurea
- Know for OSCE *
DKA ✓
Def - acute complica’n of diabetes (Type 1 usually) = fatal if left untreated = leading cause of morbidity + mortality in children w/ T1D
Precipitating factors
- MI
- infec’n
- missed insulin doses
- alcohol excess (acutely)
SSX
- N/V
- dehydra’n
- hyperventila’n
- acetone breath
- abdominal pain
- ↓ed consciousness
- polyuria + polydipsia
Pathophys - dehydra’n → uncontrolled lipolysis → excess of free fatty acids → they get converted into ketone bodies
Ix’s
- dipstick + ABG → will show ketosis + metabolic acidosis
- U + E → might show HypoK
- glucose → mild-moderate hyperglycemia ( > 200 mg/dL or 11 mmol/L)
- FBC → leukocytosis = common in DKA
Diagnostic criteria (all must be met)
- Glucose > 11 mmol/l or known diabetes mellitus
- blood pH < 7.3
- Bicarb < 15 mmol/l
- Ketones > 3 mmol/l or urine ketones ++ on dipstick
Tx in adults
1. 500 ml 0.9% NS for 10-15 mins
2. Fixed-rate infus’n of fast acting insulin until acidosis resolves
3. Correct K w/ 40mmol of KCl
4. Heparin if pt = immobile or unconscious (for DVT ppx)
Tx in children
- Correct dehydra’n evenly over 48 hrs via bolus fluid followed by maintenance fluid in order to dilute ketones + hyperglycemia
⚠️ Don’t correct any faster or else u might cause demyelina’n syndrome ! - Fixed rate insulin infus’n → allows cells to start using glucose again hence switching off ketone produc’n
Complica’ns
- HypoK due to high dose insulin
- cerebral edema in children b/c rapid correc’n of dehydra’n + hyperglycemia causes rapid shift in water from extracellular space to intracellular space in brain cells hence causing brain to swell which can lead to brain cell destruc’n + death
HHS ✓
Eti - life threatening complica’n of T2D
3 Hallmarks = HypoTN + Hyperosmolality + Severe Hyperglycemia (usually due to infec’n or inadequate insulin therapy)
SSX
- N/V
- confus’n
- HypoTN
- tachycardia
- diabetes SSX
- dehydra’n SSX i.e ↓ed skin turgor / dry oral mucosa
Ix’s
- dipstick + ABG to r/o DKA → absent ketosis + minimal acidosis unlike DKA
- glucose → severe hyperglycemia i.e > 600 mg/dL or 33.3 mmol/L
- serum osmolality → will be > 320 mOsm/kg
- FBC → leukocytosis = common in HHS
Tx = same as DKA . . .
- Fluid replac’nt w/ NS
- Insulin infus’n
- Subq Heparin for VTE Ppx
HHS ✓
Eti - life threatening complica’n of T2D
3 Hallmarks = HypoTN + Hyperosmolality + Severe Hyperglycemia (usually due to infec’n or inadequate insulin therapy)
SSX
- N/V
- confus’n
- HypoTN
- tachycardia
- diabetes SSX
- dehydra’n SSX i.e ↓ed skin turgor / dry oral mucosa
Ix’s
- dipstick + ABG to r/o DKA → absent ketosis + minimal acidosis unlike DKA
- glucose → severe hyperglycemia i.e > 600 mg/dL or 33.3 mmol/L
- serum osmolality → will be > 320 mOsm/kg
- FBC → leukocytosis = common in HHS
Tx = same as DKA . . .
- Fluid replac’nt w/ NS
- Insulin infus’n
- Subq Heparin for VTE Ppx
Causes of poor wound healing ✓
“DID NOT HEAL”
Diabetes
Infec’n / Irradia’n
Drugs i.e chemo / steroids
Nutri’nal deficiencies (Zinc / Vit A / Vit C) + Neoplasia
Object i.e foreign material
Tissue necrosis
Hypoxia
Excess tens’n on wound
Another wound
Low temp / Liver pb
Hypoglycemia ✓
Def - blood glucose < 4 mmol/L
RFs for newborns
- preterm
- SGA
- LGA
- infants of mothers w/ gesta’nal diabetes
Eti in adults - uncommon in pts who don’t have diabetes but can be due to . . .
- alcohol ingest’n
- adrenal insufficiency
Eti in newborns
- physiological → newborn blood glucose ↓ in first 1-2 hrs after delivery due to transi’n from continuous supply from placenta to intermittent supply via milk feeds but stabilizes w/in 1st 48 hrs of life
- low glycogen reserves due to prematurity or fetal growth restric’n
- disorders that cause excess insulin secre’n such as meconium aspira’n syndrome or polycythemia
- ↑ed glucose utiliza’n such as in infec’n
SSX for diagnosis in adults = Whipple’s triad . . .
- hypoglycemia SSX i.e . . .
→ confus’n
→ seizures
→loss of consciousness
→ visual Δs
→ hunger
→ tremor
→ weakness
→ sweating
→ palpita’ns
→ tachycardia
→paresthesia - low plasma glucose [ ] when above SSX = present
- SSX disappear after glucose level is returned to normal
SSX in newborns (can be asymptomatic)
- pallor
- seizures
- sweating
- irritability
- tachypnea
- jitteriness/tremors
- poor feeding
- weak or high-pitched cry
- Δ in level of consciousness
Classifica’n for adults
- mild = pt conscious + able to swallow + doesn’t have neuro SSX
- moderate = pt conscious + able to swallow but has neuro SSX i.e difficulty speaking or concentrating / confus’n / HA / weakness / drowsiness
- severe = pt unconscious
Tx for mild = give 15-20g fast-acting glucose such as . . .
- 4 Gluco tabs (1 tab contains 4g of glucose)
- 200ml of fruit juice
- 59ml bottle of GlucoJuice
Tx for moderate + pt = cooperative
- 200ml of fruit juice or 59ml bottle of GlucoJuice
Tx for moderate + pt ≠ cooperative
- 2 tubes of GlucoGel
⚠️ you must check that pt’s gag reflex is present prior to doing this
Tx for severe
1. ABC
2. place pt in recovery posi’n
3. if pt is on insulin infus’n STOP IT !
4. If pt already has an IV give 100mls of 10% Glucose or 1mg of IM Glucagon
- Know for OSCE *
Diabetes Insipidus ✓
Def - metabolic disorder characterized by absolute or relative inability to [ ] urine
RFs
- pituitary Sx
- les’n in pituitary stalk
- traumatic brain injury
- congenital pituitary abnormalities
- craniopharyngioma (= intracranial tumor)
- genetic muta’n such as muta’n in AVPR2 receptor = X linked recessive
Eti
→ Central / Cranial = ↓ in synthesis or release of ADH
- idiopathic
- pituitary Sx
- brain tumor
- brain injury
- genetic muta’n in ADH gene
- brain infec’n such as meningitis or encephalitis
→ Nephrogenic = collecting ducts of kidneys aren’t responding appropriately to ADH
- idiopathic
- HypoK
- HyperCa
- kidney diseases such as PCKD
- long term Li therapy b/c Li ↓ collecting duct response to ADH
SSX
- polyuria
- postural hypoTN
- dehydra’n b/c of polyuria
- hypotonic urine i.e VERY dilute urine
- polydipsia b/c of dehydra’n + polyuria
Ddx
- HyperCa
- diuretic use
- diabetes mellitus
- psychogenic polydipsia
Ix’s
- urine osmolality → will be very low
- serum glucose to r/o diabetes
- serum Ca to r/o HyperCa
- urine dipstick to r/o diabetes or underlying renal disease
- 24 hr urine collec’n for volume → will be > 3L/ 24hr
- water depriva’n / desmopressin stimula’n test (diagnostic Ix)
1. pt avoids all fluids for up to 8 hrs before test
2. after that water depriva’n, urine osmolality measured
3. if urine osmolality = high, DI = ruled out
4. urine osmolality < 300 = enough to diagnose DI b/c means that pt ≠ able to [ ] urine
5. give synthetic desmopressin to figure out if eti = cranial or nephrogenic
6. urine osmolality = measured over the 2-4 hrs following desmopressin admin
7. if after desmospressin is given, urine osmality ↑, that means pb = central but if it remains low that means pb = kidneys
→ should not be performed in pts w/ renal insufficiency / hypovolemia or uncontrolled diabetes mellitus
Tx for Central = desmopressin
→ pt shouldn’t take too much in order to avoid HypoNa
⟹ b/c of that HypoNa risk, serum Na should be checked every 1-3 months
Tx for Nephrogenic
1. Treat underlying cause, stop nephrotoxic drugs + maintain adequate fluid intake
2. Low Na diet + thiazide diuretics or indomethacin to ↓ urine output
Complica’ns
- bladder dysfunc’n due to excess urine produc’n (in nephrogenic)
- iatrogenic HypoNa (in central)
Obesity ✓
Def - chronic adverse condi’n where pt has excessive amt of body fat
RFs
- hypoTSH
- hypercortisolism
- corticosteroid therapy
Eti (mainly in Western world)
- large por’ns
- mental illness
- eating disorders
- sedentary lifestyle
- poor dietary habits
Ddx
- HypoTSH
- Cushing’s syndrome
BMI ≥ 30 = obesity
→ 30-34.9 = Grade I obesity
→ 35-39.9 = Grade II obesity
→ ≥ 40 = Grade III obesity i.e morbidly obese
Obesity + hormones
- ghrelin = high b/c ↑ appetite
- leptin = low b/c ↓ appetite + ↑ satiety so when there isn’t enough of it ur constantly hungry + never feel full ∴ will eat more
Tx
- Dietary Δs + ↑ in physical activity
- Medica’n i.e orlistat IF pt has BMI ≥ 28 + comorbidity OR BMI ≥ 30
→ orlistat = lipase inhibitor ∴ ↓ absorp’n of dietary fat - Bariatric Sx if pt has BMI ≥ 40 OR BMI ≥ 35 + comorbidity such as HTN / diabetes / GERD / sleep apnea
Complica’ns
- T2D
- HTN
- HLD
- metabolic syndrome
- non alcoholic fatty liver disease
- Know for OSCE *
Diagnostic criteria for metabolic syndrome ✓
≥ 3/4 of the following . . .
- HTN
- BMI >30
- Impaired glucose tolerance
- Dyslipidemia w/ raised triglycerides >150 mg/dL or ↓ed LDL
- Know for OSCE *
HypoTSH in adults ✓
Types
- 1° = thyroid gland is the pb
→ TFT will show high TSH + low T3/T4
- 2° = pituitary gland is the pb
→ TFT will show low TSH + low T3/T4
RFs
- female
- Turner’s
- 30-50 y/o
- Down syndrome
- radiotherapy to head + neck
- Li use b/c inhibits T3/T4 synthesis + their release
- iodine deficiency b/c iodine = needed to produce T3/T4
- FHx of autoimmune thyroiditis i.e Hashimoto’s
→ pts w/ Hashimoto’s will have antithyroid peroxidase (TPO) or antithyroglobulin (Tg) antibodies
Eti for 1°
- Hashimoto’s = most common cause in iodine sufficient areas / developed world
- Tx for hyperthyroidism i.e carbimazole / propylthiouracil
radioactive iodine / thyroid Sx
- Li use b/c inhibits produc’n of thyroid hormones in + thyroid gland
- amiodarone b/c interferes w/ thyroid hormone produc’n + metabolism
Eti for 2° (less common)
- Sx to pituitary
- radiotherapy
- pituitary adenomas
- Sheehan’s syndrome = avascular necrosis of pituitary gland due to PPH
Pathophys
- thyroid gland mainly produces T4
→ T4 gets converted to T3 which has metabolic roles (stimula’n of cellular O2 consump’n / E genera’n)
→ for whatever reason thyroid gland isn’t producing enough T4 (in 1°)
→ not enough T3 as well consequentially
→ pituitary ↑ produc’n of TSH to compensate (-ve feedback)
SSX : ↓ in metabolism so . . .
- constipa’n
- weight gain
- hair thinning
- ↓ed appetite
- depressed mood
- ↓ in temp so pt feels colder i.e cold intolerance
- hoarse voice
- in addi’n to having the same metabolic SSX as any other hypoTSH, Hashimoto’s also has ↑ed anti-TPO antibodies, anti-thyroglobulin + non-pitting myxedema
Ddx
- 1° v.s 2°
- anemia
- depress’n
Ix’s
- T4 + serum TSH
- FBC to r/o anemia
- anti TPO + anti-Tg to check for Hashimoto’s if eti = 1°
Tx = oral levothyroxine = synthetic vers’n of T4
→ Check for SSX improv’nt + measure TSH after 2-3 months of Tx
⟹ if TSH is still high that means dose is too low so ↑ it
⟹ if TSH is now low that means dose is too high so ↓ it
⚠️ Advise pts to avoid Ca + Fe supplements b/c they can ↓ levothyroxine absorp’n !
Complica’ns
- Afib
- angina
- osteoporosis
- pregnancy complica’ns
→ miscarriage
→ fetal neurological
maldevelop’nt
⟹ this is why women of childbearing age = encouraged to wait until they’re euthyroid before they try to conceive
- myxoedema coma = hypoTSH + multi organ failure
→ usually in older untreated pts w/ multiple comorbidities = medical emergency !
- Know for OSCE *
HypoTSH in children ✓
Eti
- Congenital = child is BORN w/ an underactive thyroid gland
→ screened for during newborn blood spot screening test
⟹ SSX (assuming it got missed at birth) . . .
- poor feeding
- prolonged neonatal jaundice
- constipa’n / sleeping more than expected / ↓ed activity
- slow growth + develop’nt
- Acquired = child or adolescent suddenly develops an underactive thyroid gland although it was previously working normally . . .
→ most common cause = Hashimoto’s
→ T1D + celiac don’t cause it but are associated w/ it
→ same SSX as adults i.e fatigue, low E, poor growth, weight gain, constipa’n, dry skin, hair loss as well as poor school performance
SSX = ↓ in metabolism so . . .
- constipa’n
- weight gain
- hair thinning
- ↓ed appetite
- depressed mood
- ↓ in temp so pt feels colder i.e cold intolerance
- in addi’n to having the same metabolic SSX as any other hypoTSH, Hashimoto’s also has ↑ed anti-TPO antibodies, anti-thyroglobulin + non-pitting myxedema
Ix’s
- T4 + serum TSH
- thyroid U/S
- anti TPO + anti-Tg to check for Hashimoto’s if eti = acquired
Tx = oral levothyroxine
- Know for OSCE *
Thyrotoxicosis ✓
Def - clinical syndrome of hyper-metabolism due to ↑ed free thyroxine (T4) and / or free triiodothyronine (T3) serum levels regardless of etiology
→ hyperthyroidism = when it’s specifically due to excessive endogenous thyroid hormone produc’n
Types
- 1° = thyroid gland is the pb
→ TFT will show low TSH + high T3/T4 - 2° = pituitary gland is the pb
→ TFT will show high TSH + high T3/T4
RFs :
- female
- tobacco use
- FHx of Grave’s
- high iodine intake
Eti for 1° (“GIST”)
- Grave’s = autoimmune hyperthyroidism = most common cause of thyrotoxicosis
→ Grave specific SSX in addi’n to regular hyperthyroidism SSX =
- exophthalmos
- diffuse goiter W/O nodules
- thyroid acropachy = hand swelling + finger clubbing
- pretibial myxedema = deposits of glycosaminoglycans under the skin on anterior aspect of leg as a rxn to TSH receptor antibodies → that area of skin will have a discolored, waxy, + edematous appearance = SPECIFIC TO GRAVE’S !
→ pathophys of Grave’s - immune system produces TSH receptor antibodies that stimulate TSH receptors on thyroid
- inflamma’n i.e thyroiditis (De Quervain’s thyroiditis, post partum thyroiditis, drug induced thyroiditis)
- solitary toxic thyroid nodule
- toxic multinodular goiter
- Eti for 2° = TSH secreting pituitary adenoma
SSX = ↑ in metabolism so . . .
- diarrhea
- weight loss
- ↑ed appetite
- ↑ed sweating
- anxious mood
- ↑ in temp so pt feels warmer i.e heat intolerance
Ix’s
- serum T4 + TSH
- TSH receptor antibodies (TRAb) for Grave’s
* Subclinical hyperthyroidism = low TSH but NORMAL normal T3/T4 + little to no SSX *
→ for subclinical always repeat TFT !
Tx = thyroid drugs
1. carbimazole for 12-18 months
→ side effect = neutropenia + agranulocytosis ∴ pt should tell u if they notice any infective SSX, especially a sore throat
2. propylthiouracil (PTU) which ↓ convers’n of T4 to T3
3. β blocker (propanolol) for adrenergic SSX i.e tachycardia/sweating + for thyroid storm
4. ttl thyroidectomy if all else fails
→ these pts will require life long levothyroxine
Complica’n = thyroid storm / thyrotoxic crisis = only in thyrotoxicosis due to hyperthyroidism
→ SSX = fever, tachycardia + delirium
- Know for OSCE *
The 5 cancers that metastasize to bone ✓
“BLT KP”
- breast (#2)
- lung (#3)
- thyroid
- kidney
- prostate (#1)
⚠️ All = osteoLYTIC metastasis except prostate = osteoSCLEROTIC metastasis !
- Know for OSCE *
Common malignancies that metastasize to the liver ✓
“CS yr PBL”
- Colon
- Stomach
- Pancreas
- Breast
- Lung
Liver metastases = common b/c of its rich vasculature i.e portal venous system
Thyroid Cancer ✓
RFs
- female
- head + neck irradi’an
- FHx of thyroid cancer
Types
- papillary carcinoma (most common type) = well differentiated
→ spreads through lymph nodes - Hürthle cell carcinoma
- follicular = spreads directly through blood
SSX
- voice hoarseness
- cervical lymphadenopathy
Ddx = benign thyroid nodule
Ix’s
- TSH
- neck U/S to get dimens’ns of nodule + see if it’s solid or cystic
→ micro calcifica’ns, marked hypoechogenicity + irregular margins = U/S features that should make u suspect malignancy - FNA for diagnosis
Tx
- newly diagnosed papillary, follicular, or Hürthle = active surveillance or Sx
- anaplastic = Sx + chemoradia’n
- offer ttl thyroidectomy to pts/ w/ ≥ 1 of the following . . .
→ T3 or higher stage primary tumor
→ reg’nal lymph node involvement i.e N1
→ distant metastatic disease i.e M1
Complica’ns
- airway obstruc’n
- post op HypoPTH
- post op recurrent laryngeal nerve nerve damage
- Know for OSCE *
Thyroid eye disease ✓
Def - autoimmune inflammatory disease of the orbit = most common cause of exophthalmos in adults
RFs
- female
- current smoking
- african american
- autoimmune diseases like pernicious anemia, SLE, Addison’s, vitiligo, celiac, RA
Eti = Grave’s usually
SSX
- lid lag
- eye dryness
- eye redness
- watery eyes
- pain behind eyes
- mild photophobia
- proptosis/exophthalmos i.e eye bulging
- lagophthalmos i.e incomplete eyelid closure
- upper eyelid retrac’n especially in lateral aspect of eyelid = lateral flare
- restrictive myopathy i.e restrictive eye mov’nts due to swollen tissues
- blurry or double vis’n requires PROMPT INTERVEN’N b/c it means sight = threatened !
Ddx = allergic conjunctivitis but if there’s SSX like lid retrac’n or blurry vis’n u can rule it out
Tx
→ moderate to severe = corticosteroid therapy
→ sight threatening = urgent orbital decompress’n Sx + IV corticosteroid
- Know for OSCE *
HLD ✓
Modifiable RFs
- diet
- high BP
- smoking
- diabetes
- low HDL
- high LDL
- high BMI
- lack of exercise
Non-modifiable RFs
- male sex
- advanced age
- African American or South Asian ethnicity
- FHx of premature CVD or sudden death (i.e before 55 in men + 65 in women)
Eti
→ 1° = genetic
→ 2° = hypoTSH, diabetes, renal disease, liver disease, alcohol
SSX = corneal arcus = lipid deposits in cornea
Ix’s
- TFTs
- U + E
- Fasting glucose
- LFTs (ALT, AST, ALP) + GGT (gamma)
- full fasting lipid profile i.e ttl cholesterol, LDL, HDL, triglycerides
Tx = statin, cholestyramine
- statin MOA → ↓ hepatic cholesterol synthesis by targeting rate limiting enzyme in cholesterol synthesis → upregula’n of LDL receptors + ↑ed hepatic uptake of LDL cholesterol from circula’n i.e less LDL in blood
- statin monitoring → LFTs before prescribing, then again @ 3 months, then again @ 12 months
- side effects = muscle pain, abdo pain, nausea + diarrhea
- C/I = pregnancy
- don’t take w/ grapefruit
- cholestyramine MOA → bile acid sequestrant ∴ ↓ bile acid reabsorp’n in small intestine
→ side effects = abdominal cramps + constipa’n, ↓ed absorp’n of fat soluble vitamins, bleeding/bruising due to ↓ed Vit K absorp’n, cholesterol gallstones
→ if rhabdo = suspected (severe muscle ache / prolonged ie / crush Injury), measure CK
⟹ stop statin if CK > 5x upper limit of normal
⟹ ↓ statin lose if CK < 5x upper limit of normal
Complica’n = CVD
- Know for OSCE *
Addison’s disease / Autoimmune 1° adrenal insufficiency ✓
Def - autoimmune disease where adrenal glands don’t produce enough steroid hormones (cortisol + aldosterone in particular) = rare but is life threatening if pt goes in addisionian crisis
→ 2° adrenal insufficiency = pituitary gland is the pb → it’s not adequately releasing ACTH which is necessary to stimulate adrenal glands
⟹ could be due to hypoplasia (congenital underdevelop’nt) of pituitary / pituitary Sx / surgery / radiotherapy
RFs
- female
- adrenal hemorrhage
- adrenocortical auto-antibodies
- auto-immune disease, especially celiac
Pathophys - destruc’n of adrenal cortex → impaired synthesis + secre’n of all steroids from all 3 cortical layers (90% of adrenal cortex has to be destroyed to cause SSX) → pt has deficiency in cortisol + aldosterone → ↑ in ACTH due to inhibited -ve feedback
Pathophys of addisonian crisis due to abruptly stopping long term corticosteroid medica’n (type of 3° adrenal insufficiency) - long term steroid use i.e > 3 wks
→ hypothalamus = suppressed during that time b/c there were steroids from another source
→ exogenous steroid = suddenly w/drwan → hypothalamus doesn’t “wake up” fast enough
→ endogenous steroids don’t get adequately produced
SSX
- anorexia
- depress’n
- weight loss
- muscle cramps
- muscle weakness
- fatigue + ↓ed libido
- bronze hyperpigmenta’n (especially on skin creases)
SSX of Addisonian crisis
- N/V
- dizziness
- hypoglycemia
- confus’n + weakness
- abdominal tenderness
- hypoTN (especially postural hypoTN)
Ddx
- hyperthyroidism
- anorexia nervosa
- hemochromatosis
- occult malignancy
Ix’s
- morning serum cortisol → will be low
⟹ we take it in the morning b/c that’s when cortisol levels = at their peak so if they’re low during that time that’s suspicious - Synacthen / ACTH stimula’n test for diagnosis (ideally performed in the morning)
- Give pt Synacthen (synthetic ACTH)
- Check blood cortisol 30 mins before + 60 mins after dose
→ synthetic ACTH will stimulate adrenal glands to produce cortisol → cortisol level should at least double in healthy adrenal glands
→ if it doesn’t it means there’s adrenal insufficiency - Plasma ACTH to distinguish btw 1° + 2°
→ high = 1° b/c when glucocorticoid levels are normal that causes -ve feedback loop that inhibits ACTH release but since glucoortioid levels = low, that -ve feedback is now inhibited
→ low = 2°
- U + E → might show HypoNa + HyperKa due to low glucocorticoids + mineralocorticoids
Emergency Tx
- IV infus’n of 0.9% saline to reverse fluid + Na deficiency
- Correct hypoglycemia w/ IV dextrose
- 100 mg IV hydrocortisone bolus
→ do all this even if u just SUSPECT Addison’s !
Ongoing Tx = LIFELONG hydrocortisone (a glucocorticoid) to replace cortisol + fludrocortisone (a mineralocorticoid) to replace aldosterone if also deficient
→ pts = given steroid card, ID tag + emergency letter to alert emergency services that they depend on steroids for life
⚠️ Doses should not be missed, as they are essential to life + dose should be doubled during acute illness to match normal steroid response to illness !
→ Pt + their close contacts = taught to give IM hydrocortisone in an emergency
Complica’ns
- Cushing syndrome 2° to over-replac’nt of glucocorticoids
- osteopenia / osteoporosis due to over-replac’nt of glucocorticoids b/c excessive bone exposure to glucocorticoids causes ↓ in osteoblast activity + ↑ in osteoclast activity
- Know for OSCE *
Things to remember about long term corticosteroid use ✓
” C STOP “
- Can worse glycemic control in diabetes, cause immunosupress’n, neutrophilia, high WBC count + ↑ risk of mania
- S = double pt’s dose when they’re Sick to prevent adrenal crisis
- T = pt should carry steroid Tx card to alert others that they’re steroid dependent
- O = Osteoporosis preven’n w/ bisphosphonates / Ca / Vit D
- P = PPIs for gastroprotec’n
→ pts should avoid NSAID use w/ these - Know for OSCE *
Cushing’s syndrome ✓
Def - persistent excess of circulating glucocorticoids (specifically cortisol)
RFs
- adrenal adenoma
- pituitary adenoma
- adrenal carcinoma
- exogenous glucocorticoid use
Eti
> ACTH dependent = excessive cortisol secre’n by adrenal glands due to high ACTH levels
- Pituitary ACTH-secreting adenoma (most common cause)
→ in this case ONLY it’s called Cushing’s disease
→ will cause adrenal cortex hyperplasia - Ectopic ACTH-secreting tumors such ACTH-producing small cell lung cancer cells → results in excess cortisol secre’n by adrenal gland
> ACTH independent = excessive cortisol secre’n by adrenal glands despite suppressed ACTH
- adrenal adenomas
- b/l adrenal hyperplasia
- adrenal carcinomas (very rare)
- exogenous admin of glucocorticoids in the Tx of another disease (most common cause)
SSX
- tan skin
- weight gain
- purple striae
- easy bruising
- muscle weakness
- peripheral vis’n loss
- hirsutism (in women)
- buffalo hump
- moon face i.e face = rounder
- pigmenta’n (in ACTH-dependent causes)
- truncal / abdominal / central obesity
- menstrual irregularities in women + libido loss in men due to gonadal dysfunc’n
Ddx
- obesity
- metabolic syndrome
Ix’s
- pregnancy test in women of childbearing age to r/o pregnancy
- glucose levels → might be high b/c cortisol promotes produc’n of free glucose in the body + ↑ insulin resistance
- Either 1a or 1b for diagnosis . . .
1a) late-night salivary cortisol → will be high
1b) low dose dexamethasone suppress’n test (preferred in pts w/ renal failure) or 24 hr urinary free cortisol in pregnant pt
- Serum ACTH to figure out if it’s ACTH independent or dependent
→ will be high in dependent + low in independent
Tx depends on cause
→ for ex if due to adrenocortical adenoma remove it surgically via adrenalectomy + treat peri-operatively w/ IV hydrocortisone
Complica’ns
- HTN
- osteoporosis
- metabolic syndrome
- T2D due to insulin resistance
- CVD (most common cause of death)
- nephrolithiasis b/c excess cortisol interferes w/ how kidneys handle Ca ∴ can cause Ca kidney stones
- Nelson’s syndrome - b/l adrenal gland removal → no more steroid hormones → no more -ve feedback on pituitary → pituitary tumor can expand + produce excess ACTH
- Know for OSCE *
Hyperaldosteronism ✓
Def - excess aldosterone
→ 1° = adrenal glands are the pb i.e they’re producing too much aldosterone
→ 2° = something is causing too much renin to be released hence too much aldosterone is being secreted
RFs
- HTN
- FHx of hyperaldosteronism
- FHx of early onset of HTN and/or stroke
Eti for 1°
- b/c adrenal hyperplasia (most common cause)
- aldosterone secreting adenoma (usually a u/l adrenal adenoma)
→ in this case it’s called Conn’s syndrome
- familial hyperaldosteronism (very rare)
Eti for 2°
- heart failure
- renal artery stenosis
- liver cirrhosis + ascites
Ix’s
- aldosterone : renin ratio (ARR)
→ will be high in 1°
→ will be low in 2 °
- U + E → will show high Na + low K b/c ↑ in Na reabsorp’n means ↑ in K excre’n in urine
- CT or MRI to check for both adrenal tumor + adrenal hyperplasia
Tx
- dietary Na restrict’n
- surgical adrenalectomy for pts w/ u/l Conn’s syndrome
- lifelong MRA (eplerenone /spironolactone) in pts w/ b/l Conn’s syndrome or u/l who can’t / don’t want to go undergo Sx
Complica’ns
- MI
- HTN
- stroke
- heart failure
- impaired renal func’n
- Know for OSCE *
Pituitary tumors ✓
- Pituitary adenomas = most common disease of the anterior pituitary = BENIGN tumors
Types
- Func’nal
→ Prolactinomas → secrete excess prolactin = most common type of func’nal adenoma = treated w/ dopamine agonist b/c dopamine inhibits prolactin
⟹ SSX :
- osteoporosis + ↓ in libido in both sexes
- amenorrhea / oligomenorrhea i.e 4-9 periods / yr instead of 12 + galactorrhea in women + ED + gynecomastia in men
⟹ Ix = prolactin level + brain MRI to identify pituritary tumor
→ GH secreting adenomas - will cause HAs / visual pbs (usually in men or post-menopausal women) + ACROMEGALY i.e thick hands + feet, protruding lower jaw, coarse facial appearance, larger tongue, excessive sweating, oily skin + ↑ in collar size
⟹ mortality rate = 2x that of normal popula’n b/c of LVH + CVD as a result of insulin resistance
→ TSH secreting adenomas - produce excess TSH ∴ cause hyperthyroidism SSX
⟹ mortality rate = 2x that of normal popula’n b/c of LVH + CVD as a result of insulin resistance
NON-FUNC’NAL = don’t secret any hormones
- Know for OSCE *
Ca distribu’n in our body ✓
- 98.9% = skeleton
- 1% = intracellular
- 0.1% = extracellular (45% bound to albumin, 10% unbound as a free ion)
Vit D + Ca ✓
- Vit D synthesis = cholesterol → 25 hydroxyla’n (in liver) → 1 hydroxyla’n (in kidneys)
- HIGH Ca INHIBITS parathyroid glands from releasing PTH
- LOW Ca STIMULATES parathyroid glands to release PTH + PTH ↑ Ca by . . .
→ stimulating kidneys to convert inert form of Vit D to its active form which helps ↑ Ca b/c active form of Vit D = necessary for Ca absorp’n in small intestine
→ ↑ing osteoClast activity ∴ Ca + PO4 will be released from hydroxyapatite
→ ↓ing serum PO4 by inhibiting tubular reabsorp’n of PO4 i.e promoting urine excre’n of PO4 + since PO4 binds to Ca, if there’s less PO4 to bind to it, there’s more free Ca
- Mg = required for PTH secre’n + sensitivity ∴ low Mg will cause low PTH hence causing HypoCa
- Calcitonin = released by C cells of thyroid gland → ↓ Ca + PO4 by inhibiting osteoclasts
⚠️ blood pH affects Ca level b/c lower pH = more H+ ions to bind to albumin → higher [Ca] b/c less albumin = available to bind to Ca
1° HyperPTH ✓
Def - ↑ in PTH due to pb in parathyroid gland itself such as parathyroid adenoma
Eti - tumor of parathyroid glands
RFs
- FHx
- 50-60 y/o
- female sex
- Past or current Li Tx
SSX
- anxiety
- myalgia
- depress’n
- poor sleep
- memory loss
Ddx
- sarcoidosis
- multiple myeloma
Ix’s = serum Ca + PTH
Tx = remove tumor surgically
Complica’n = calciphylaxis = calcifica’n of tunica media of small vessels
- Know for OSCE *
2° HyperPTH ✓
Def - ↑ in PTH as a response to HypoCa b/c of . . .
- CKD
- aging
- Vit D def (could be due to inadequate sunlight exposure, malbasorp’n, etc)
Ddx = 1°
Ix’s = serum Ca, ALP + PTH
Complica’n = nephrolithiasis b/c excess Ca can precipitate + cause kidney stones
- Know for OSCE *
HypoPTH ✓
Def - low PTH
RFs
- parathyroid Sx
- hypomagnesemia
- thyroid gland Sx b/c parathyroid glands might have been removed accidentally
SSX = complica’ns of HypoCa b/c of consequential ↓ in Ca i.e dry hair + brittle nails
Ddx
- hypomagnesemia
- hypoalbuminemia
- CKD / renal failure
Ix’s = Ca, Albumin, Mg + PTH
Tx
- for symptomatic acute = IV Ca
- for asymptomatic acute = oral Ca
- for chronic = oral Ca + calcitriol
Complica’ns = cataracts = after long term HypoCa !
- Know for OSCE *
HyperCa ✓
Def - high Ca
Eti
- 1° HyperPTH
- Thiazide diuretics
- High bone turnover
- Cancers that produce excess Ca or PTH
- HYPER Vit D (due to excessive intake OR overactiva’n)
→ ex of overactiva’n of Vit D = by epithelioid macrophages in granulomatous diseases such as TB or sarcoidosis
SSX
- nausea
- fatigue
- lethargy
- confus’n
- polyuria
- polydipsia
- constipa’n
Ix’s
- PTH
- Vit D
- CXR
- TFTs
- Albumin
- Ca, PO4, U+E
- Myeloma Screen
- Urinary Ca excre’n
- ECG → short QT interval
Tx = 0.9% NaCI to make pt euvolemic
Complica’ns
- pancreatitis
- renal failure
- kidney stones
- Know for OSCE *
HypoCa ✓
Def - low Ca
Eti
- Cancer
- HypoPTH
- PTH resistance
- Acute pancreatitis
- Toxic shock syndrome
- Acute rhabdomyolysis (crash injuries)
- Ca chelators (ex : citrate in blood transfus’n)
- VitD deficiency (PTH will be high to compensate)
- Bone breaking inhibitors like bisphosphonates or calcitonin
SSX
- seizures
- muscle cramps
- muscle fascicula’ns
- finger or periroral paresthesia
- tetany i.e involuntary muscle contrac’ns
+ve Trousseau sign and/or +ve Chvostek sign = twitching of facial muscles when facial nerve = tapped
Ix’s
- Mg
- PTH
- Vit D
- Ca, PO4, U+E
- corrected Ca if albumin = low
- B12 / Folate / Ferritin / Celiac screen (b/c pb could be malabsorp’n)
Tx = IFF Ca < 1.8 mmol/L OR pt has tetany / seizures / +ve Trousseau or Chovstek sign = oral CaCO3 or IV Ca gluconate
Complica’ns
- dry hair
- brittle nails
- life threatening arrhythmia
- Know for OSCE *
The 3 categories of jaundice ✓
- Pre hepatic - excessive RBC breakdown i.e hemolysis → too much bilirubin for liver to conjugate
→ unconjugated bilirubinemia
→ normal urine color b/c only conjugated bilirubin is water soluble + normal stool color b/c flow of bile to duodenum isn’t impaired
⟹ ex’s = SCD or other hemolytic condi’ns - Intra-hepatic - ↓ed hepatocyte func’n for whatever reason
→ liver = able to conjugate bile but not fully
→ mix of conjugated + unconjugated bilirubin in blood → dark urine b/c of conjugated bilirubin + normal stool color b/c flow of bile to duodenum isn’t impaired
⟹ ex’s = cirrhosis, hepatitis, hepatic tumors b/c directly affect hepatocytes - Post-hepatic - drainage of bile = obstructed but b/c liver doesn’t have a pb it’s able to conjugate bilirubin → conjugated bilirubinemia → dark urine b/c of conjugated bilirubin + pale stool b/c bilirubin gives stool it’s brown color so when there’s something obstructing flow of bile to small intestine, stool ends up pale b/c it doesn’t contain any bilirubin
⟹ ex’s = gallstones, stricture, pancreatitis
LFT analysis ✓
- High ALT + AST = liver pb
- High Gamma + ALP = bile flow pb
Why does zone 1 of liver regenerate 1st + not zone 2 or 3 ? ✓
B/c zone 1 = closer to portal vessels
Liver v.s Vit K v.s Inhibitors pb (in bleeding / coagula’n issue) ✓
- Liver hepatocytes = produce all coagula’n factors except 8 (made by hepatic sinusoidal endothelial cells) + secrete TPO = necessary for platelet produc’n ∴ liver pb can affect both coagula’n time + platelet count
→ can also affect spleen b/c . . .
liver disease → portal HTN → splenomegaly → hyper-splenism → ↑ platelet sequestra’n
→ thrombocytopenia - Vit K = necessary for factor 2, 7, 9, 10 + Protein C + S so can affect COAGULA’N TIME but NOT PLATELET COUNT !
→ Causes of low Vit K . . .
- chronic diarrhea
- anti Vit K medica’n such as warfarin
- fat malabsorp’n b/c Vit K = fat soluble
- biliary duct obstruc’n(b/c Vit K = fat soluble
- parenteral nutri’n i.e receiving nutrients via IV
- new born b/c don’t have gut flora yet to make Vit K
- broad spectrum ABs → might kill gut flora that produce Vit K
⟹ What test can help you differentiate btw liver pb + Vit K deficiency ?
→ Factor 5 + Factor 7 activity assay b/c if only factor 7 = ↓ then it’s a Vit K pb but if both = ↓ then it’s a liver pb b/c liver produces both + 7 whereas Vit K is only needed for 7
- Inhibitors = antibodies circulating in blood that inhibit coagula’n factors
→ most common = inhibitors to factor 8
→ cause acquired Hemophilia A
Scenario 1: pt has ↑ed PT but no liver or Vit K pb
→ do mixing test of their blood w/ normal plasma . . .
a) if PT = corrected = factor 7 deficiency
b) If PT ≠ corrected = inhibitor pb
Scenario 2 : pt has ↑ed aPTT but no liver or Vit K pb
→ do mixing test of their blood w/ normal plasma . . .
a) if aPTT = corrected = factor 8 / 9 / 10 / vWF deficiency
b) If aPTT ≠ corrected = inhibitor pb
→ factor 7 = shortest half life out of all the Vit K dependent clotting factors, hence will be the 1st whose levels start to ↓ if the pt is deficient in Vit K
Acute liver failure ✓
Def - rapid ↓ in hepatic func’n = jaundice + coagulopathy i.e INR > 1.5 + hepatic encephalopathy in pts w/ no prior Hx of liver disease
2 most common causes = paracetamol overdose + viral hepatitis (in that order)
RFs
- female
- pregnancy
- chronic Hep B
- fasting / malnutri’n
- chronic paracetamol use
- chronic alcohol misuse → alcohol = bad for liver b/c alcohol dehydrogenase converts it to acetylaldehyde which generates ROS
SSX
- tenderness on right side
- pruritus due to elevated bilirubin
- fetor hepaticus = rotten egg / garlic breath
- hepatic encephalopathy SSX i.e confus’n, agita’n, irritability
Ix’s
- INR > 1.5
- LFTs → hyperbilirubinemia + elevated ALT + AST
- U + E → elevated urea + creatinine (due to renal failure)
Complica’ns
- GI bleed
- renal failure
- cerebral edema
- hepatic encephalopathy
⚠️ Safe dose of paracetamol in 24hrs = 4g !
→ gets conjugated into NAPQI by glutathione which is safe but when there’s too much paracetamol, glutathione gets depleted + we get oxidized free radicals which damage hepatocytes via the peroxida’n of lipids in cell membranes
→ paracetamol overdose Tx = IV N-acetylcysteine b/c it replenishes glutathione
⟹ 1st infus’n = 150mg / kg in 200mL 5% glucose
infus’n over 60 mins
⟹ 2nd infus’n = 50mg / kg in 500mL 5% glucose infus’n over 4 hrs
⟹ 3rd infus’n = 100mg / in 1L 5% glucose infus’n over 16 hrs
Addi’nal Mx
- check salicylate levels as well
- psych assess’nt
- Know for OSCE *
Drugs that can precipitate hepatic encephalopathy in pts w/ chronic liver disease ✓
- drugs w/ constipating effects i.e opioids
- drugs that ↓ K b/c HypoK ↑ renal ammonium produc’n i.e loop + thiazide diuretics
- drugs w/ sedative effects i.e benzos, antihistamines such as chlorphenamine
Drinking recommenda’ns ✓
Max of 14 units / wk spread evenly over ≥ 3 days + max of 5 units in a single day
Equivalent of 1 unit
- 1/2 a pint of cider or weak beer
- 1/2 a small glass of wine
Larger/stronger vers’ns of the above = 3 units
Binge drinking defini’n ✓
- For men = > 8 units of alcohol in a single sess’n
- For women = > 6 units of alcohol in a single sess’n
Pathophys of alcohol + brain ✓
Alcohol = depressant so stimulates GABA receptors in brain → relaxing effect on rest of brain
→ alcohol also inhibits NMDA / glutamate receptors → further relaxing effect b/c glutamate = excitatory neurotransmitter → so in chronic drinkers, body’s way of compensating is to down regulate GABA system + up regulate glutamate system
NAFLD ✓
Def - excessive fat in liver cells, specifically triglycerides
RFs
- HTN
- obesity
- smoking
- diabetes
- dyslipidemia
- sedentary lifestyle
- metabolic syndrome
Pathophys - fat deposits interfere w/ normal func’ning of liver cells
Progress’n - NAFLD → NASH (Non-alcoholic steatohepatitis) → fibrosis → cirrhosis
SSX = asymptomatic
Ix’s
- LFTs → raised ALT
- Liver Bx = gold std → will tell you if it’s in hepatitis stage or cirrhosis stage
- Liver U/S to see if it has progressed to hepatic steatosis → will see ↑ed echogenicity if that’s the case
- ELF (enhanced liver fibrosis) blood test to see if progressed to fibrosis
→ measures HA, PIIINP + TIMP-1)
⟹ < 10.51 means advanced fibrosis = unlikely (check this every 3 yrs in NAFLD pts)
⟹ > 10.51 means there’s advanced fibrosis - Transient elastography / FibroScan to check if fibrosis has progressed to cirrhosis
Tx
- exercise
- weight loss
- Mediterranean diet
- alcohol + smoking cessa’n
- controlling diabetes, HTN + HLD
- refer to liver specialist if there’s fibrosis → might give vitamin E, pioglitazone
- liver transplanta’n in end stage liver disease
Complica’n = cirrhosis
SSX of alcohol intoxica’n ✓
- tremor
- slurred speech
- bloodshot eyes
- smelling of alcohol
- telangiectasia (dilated capillaries on the face)
Diagnostic criteria for alcohol dependence ✓
≥ 1 of the following SSX . . . (“CT WPOC”)
- Compul’sn to drink
- Tolerance
- W/drawal SSX
- Primacy
- Ongoing use
- Control loss
Alcohol w/drawal ✓
Ix’s
- FBC
- U + E
- LFTs
- B12
- folate
- Mg
- lipase
- glucose
- CRP
- CK
- head CT if head injury = suspected
SSX of alcohol w/drawal i.e 6-12 hrs later . . .
- tremors
- anxiety
- agita’n
- irritability
- loss of appetite
- N/ V
- sweating
→ 12-24 hrs after stopping = above + hallucina’ns
→ 24-48 hrs after stopping = above + seizures
→ 24-72 hrs after stopping = delirium tremens
⟹ SSX of delirium tremens = above + tachycardia, pyrexia + visual hallucina’ns = medical emergency !
Tx for DT = ABCDE if pt has seizure + high flow O2 + IV lorazepam or IM Haloperidol
Tx for regular w/drwal = IV Pabrinex
Mx
- CIWA score = based on w/drawal SSX
- Chlordiazepoxide / Librium to combat effects of w/drawal = benzodiazepine
Wernicke’s Encephalopathy ✓
Def - neurological emergency caused by thiamine deficiency
→ usually due to chronic alcohol overconsump’n b/c alcohol ↓ thiamine absorp’n
RFs
- AIDS
- chemo
- malnutri’n
- previous GI Sx
- alcohol dependence
SSX
- mental slowing
- confus’n
- impaired [ ]
- ataxia i.e difficulty w/ coordinated mov’nts
- ocular motor findings
i.e gaze palsies, CN 6 palsies, impaired vestibulo-ocular reflexes
Ix’s
- therapeutic trial of parenteral thiamine → diagnosis = clinical improv’nt after admin of thiamine
- LFTs to see if due to alcohol related liver disease
- serum ammonia to r/o metabolic encephalopathy 2° to hyperammonemia
Emergency Tx = IV Pabrinex (thiamine) for 5-7 days → oral thiamine → multivitamin to replenish deficient vitamins
Complica’ns
- seizures
- hearing loss
- Korsakoff syndrome / Korsakoff’s psychosis
Alcohol related liver disease ✓
Eti = long term excessive alcohol consump’n
RFs
- hep C
- female
Pathophys - excess drinking causes buildup of fat in liver (this is reversible w/ abstinence from alcohol) → alcohol related hepatitis (usually reversible w/ permanent abstinence from alcohol if it’s mild) → alcohol induced cirrhosis
Ix’s
- AST + ALT = elevated
- AST : ALT ratio > 2
Tx
- alcohol w/drawal Mx via oxazepam PO or IV diazepam → lorazepam PO
- weight loss + smoking cessa’n
- nutri’nal supplementa’n
- influenza + pneumococcal vaccines
- corticosteroids in severe alcoholic hepatitis
Complica’ns
- portal HTN
- coagulopathy
- renal failure
- hepatocellular carcinoma
- Wernicke-Korsakoff Syndrome (WKS) = Wernicke encephalopathy + Korsakoff syndrome
→ Korsakoff syndrome = amnestic disorder caused by chronic alcohol overuse
⟹ SSX = confabula’n, personality Δs + permanent memory loss i.e pt can’t form new memories
How to screen for harmful alcohol use ? ✓
“CAGE”
C = Cut down → ask pt if they ever think they should cut down ?
A = Annoyed → do they get annoyed when others comment on their drinking ?
G = Guilty → do they ever feel guilty about drinking ?
E = Eye opener → do they ever drink in the morning to help hangover or nerves ?
Cirrhosis ✓
Def - end stage of chronic liver disease = characterized by fibrosis + regenerative nodules b/c of liver trying to regenerate itself
→ 5 yr survival = 50% once it has developed
RFs
- obesity
- IV drug use
- alcohol misuse
- unprotected sex
Eti
- Hep B / Hep C
- NAFLD
- autoimmune hepatitis
- alcohol related liver disease
SSX
- melena
- hematemesis
- telangiectasia
- jaundice + pruritus
- spider nevi (> 5 = pathological)
- bruising due to abnormal clotting
- leukonychia due to hypo-albuminemia
- portal HTN b/c cirrhosis ↑ resistance to blood flow livers ∴ causing ↑ed back pressure on portal system
- thrombocytopenia b/c portal HTN → splenomegaly → ↑ed plt destruc’n
- ascites due to portal HTN
- esophageal varices / caput medusa due to portal HTN b/c back pressure in portal system causes swollen + tortuous vessels @ sites where collaterals form btw portal + systemic venous systems
Ix’s
- Liver Bx to confirm it’s cirrhosis
→ Mallory bodies = sign of irreversible liver cell injury - albumin → will be low
- U + E → HypoNa + HyperK
- clotting profile → prolonged prothrombin time
- LFTs → hyperbilirubinemia + elevated ALT + AST
- U/S to screen for hepatocellular carcinoma
Mx
- MELD score every 6 months for estimated 3 month mortality chance → uses Cr, bilirubin, INR + Na
- U/S + AFP every 6 months for hepatocellular carcinoma screening
- Endoscopy every 3 yrs to check for esophageal varices = asymptomatic until they start bleeding
→ due to the high blood flow, bleeding from varices can cause patients bleed out very quickly - Child-Pugh score to assess severity of cirrhosis + prognosis
→ give score of 1-3 for each
→ “ABCDE” mnemonic . . .
A = Albumin
B = Bilirubin
C = Clotting i.e INR
D = Dila’n i.e ascites
E = Encephalopathy
→ score of 5-6 = class A → 1yr survival = 100%
→ score of 7-9 = class B → 1yr survival = 80%
→ score of > 10 = class C →1yr survival = 45%
Tx
- Treat underlying cause i.e . . .
- lifestyle Δs for NAFLD
- antiviral drugs for hep C
- immunosuppressants for autoimmune hepatitis - Liver transplant if there are features of decompensated liver disease i.e “AHOY” . . .
A = Ascites
H = Hepatic encephalopathy
O = Oesophageal varices
Y = Yellow (jaundice)
Complica’ns
- bleeding + thrombosis
- ascites due to portal HTN
- hepatocellular carcinoma
- spontaneous bacterial peritonitis due to ascites
- malnutri’n b/c cirrhosis ↓ amt of protein liver produces + disrupts ability of liver to store glucose as glycogen / release glucose from glycogen
- cachexia b/c less protein = available to maintain muscle tissue + muscle tissue = broken down for fuel since liver isn’t releasing glucose when needed
- hepatorenal syndrome b/c portal HTN causes portal vessels to release vasodilators → vasodila’n leads to ↓ in BP → kidneys respond by activating RAAS → renal vasoconstric’n results in kidneys being starved of blood
- hepatic encephalopathy b/c liver cells can no longer metabolize ammonia + collateral vessels btw portal + systemic circula’n means ammonia can bypass liver + directly enter systemic system
→ main SSX = asterixis
→ Tx = lactulose → PO4 enemas → stop diuretics if Na < 130mmol/L → avoid sedatives → consider IV broad spectrum ABs such as rifaximin (can only be initiated by hepatology consultant !) - Know for OSCE *
⚠️ Liver enzymes = poor indicators of liver func’n b/c are usually low in end-stage cirrhosis
→ albumin + INR/PT = better
⟹ PT = even better than albumin due to shorter half life
Viral Hepatitis ✓
ALL 5 ARE NOTIFIABLE DISEASES !
- Hep A = RNA virus, can get vaccinated for it before travelling to endemic area such as S. Asia
→ incuba’n period = 2-4 wks
→ most common viral hepatitis worldwide is but rare in the UK
→ Tx = supportive b/c resolves on its own - Hep B = reverse transcriptase DNA virus, has vaccine, incuba’n period = around 10 wks
→ Tx = nothing b/c is
self limiting but can often give anti viral therapy to slow progress’n
⟹ 2 consecutive tests conducted ≥ 3 months apart = needed before starting antiviral therapy - Hep C = RNA virus, no vaccine
→ Tx = direct-acting antivirals - HepD = RNA virus, no vaccine
→ Tx = pegylated interferon 𝛼 - HepE = RNA virus, no vaccine, incuba’n period = 1-2 months
→ Tx = supportive
→ A+E = fecal oral route i.e via ingest’n of contaminated food/water or direct contact w/ infected person
→ B+C = blood or other bodily fluids i.e sex (B can also transfer perinatally i.e vertical transmiss’n), RFs = needles + unsafe sex
→ D = have to get B first
Hep B
Def- most common liver infec’n worldwide = caused by HBV i.e Hep B virus
RFs
- IV drug use
- incarcera’n
- sex workers
- unprotected sex
- men who have sex w/ men
- mom w/ Hep B during pregnancy
- endemic reg’n such as Asia or Africa
Eti
- chronic viral hepatitis
- alcohol related liver disease
- non alcoholic fatty liver disease (NAFLD)
- less common causes = hemochromatosis, CF, autoimmune hepatitis
Asymptomatic
Ix’s
- LFTs → elevated ALT + AST + maybe hyperbilirubinemia
- albumin → will be low
- U + E → HypoNa
- Hep B surface antigen (HBsAg)
→ +ve means ACTIVE infec’n (will be detected 4 wks after exposure to virus) - Hep B surface antibody (HbsAb)
→ +ve means past infec’n / current infec’n / vaccinated - IgM/IgG core antibodies
→ useful b/c will appear after window for HBsAg has passed + before HbsAb appears
→ +ve IgM w/ high titre = ACTIVE ACUTE INFEC’N
→ + ve IgM w/ low titre = ACTIVE CHRONIC INFEC’N
→ +ve IgG = PAST INFEC’N - e antigen → +ve means ACTIVE infec’n + that’s it’s very early in infec’n ∴ pt is the MOST CONTAGIOUS they can be
- serum HBV DNA = direct count of viral load (used to monitor response to Tx) ∴ might initially be high but should then be 0 if Tx is working
Who should get nucleoside analogue Tx i.e antiviral therapy ?
a) ≥ 30 y/o + HBV DNA > 2000 + abnormal ALT
b) < 30 y/o + HBV DNA > 2000 + abnormal ALT + evidence of fibrosis
c) HBV DNA > 20,000 + abnormal ALT
d) Detectable HBV DNA + cirrhosis
Complica’ns
- cirrhosis
- Hep B reactiva’n
- fulminant liver failure
- hepatocellular carcinoma
- Hep B associated glomerulonephritis
Hep C (= more chronic)
RFs
- incarcera’n
- sex workers
- unprotected sex
- IV/intranasal drug use
- men who have sex w/ men
- needle injury in healthcare
- HIV (these pts = less likely to clear Hep C)
Eti
- chronic viral hepatitis
- alcohol related liver disease
- non alcoholic fatty liver disease (NAFLD)
- less common causes = hemochromatosis, CF, autoimmune hepatitis
No SSX b/c = asymptomatic
Ix’s
- HCV antibody enzyme immunoassay (EIA) for screening
→ +ve means ACTIVE OR PAST infec’n - HCV RNA PCR for diagnosis
→ +ve means ACTIVE INFEC’N - LFTs → ALT might be high
Tx = Direct-Acting Antivirals (DAAs) i.e sofosbuvir / daclatasvir
Complica’ns
- cirrhosis
- skin complica’ns
- hepatocellular carcinoma
- cryoglobulins in skin / kidneys (@ low temps)
- Know for OSCE *
Autoimmune Hepatitis ✓
Def - chronic inflammatory disease of the liver of unknown etiology
RFs
- immune dysregula’n
- HLA genetic pre disposi’n
- female sex (just like most auto immune condi’ns)
Types
- Type 1 → typically affects women in their late 40s/50s
→ presents around or after menopause
→ SSX = fatigue + features of liver disease = more chronic progress’n than type 2
→ auto antibodies = ANA, anti-actin + anti SLA/LP - Type 2 → usually affects young girls
→ presents w/ acute hepatitis , jaundice + high transaminases (i.e ALT + AST)
→ auto antibodies = anti-LKM1 + anti-LC1
Ix’s
- albumin → will be low
- INR → PT will be prolonged
- γ globulins → will be high
- LFTs → hyperbilirubinemia + elevated ALT + AST
- Liver Bx → will show interface hepatitis + plasma cell infiltra’n
Tx = high dose corticosteroid i.e prednisolone + immuno-suppressants such as azathioprine to control disease
Complica’ns = side effects of long term corticosteroid use
- Know for OSCE *
Liver cancer ✓
→ 1° liver cancer = cancer originates from liver
⟹ main type = hepatocellular carcinoma
→ 2° = cancer metastasized to liver but originates from somewhere else
RF = cirrhosis
SSX = weight loss + liver disease SSX
Ix’s
- liver U/S = 1st line
- 𝛼 fetoprotein (AFP) = tumor marker for hepatocellular carcinoma
- CT + MRI for staging
- Bx for histology
Barcelona Staging
- Stage 0 = single tumor < 2cm + liver is working normally
- Stage A = up to 3 tumors that are all < 3 cm + liver is working well
- Stage B = > 3 tumors in liver but liver is still working well
- Stage C = cancer has spread elsewhere or pt doesn’t feel well / is less active
- Stage D = severe liver damage
Tx
- Stage 0 or A + good surgical candidate = resec’n or thermal abla’n
- Stage 0 or A but NOT good surgical candidate = RFA → TACE (transarterial chemo-emboliza’n) = IR procedure
- Stage B = TACE or TARE
- Stage C = monoclonal antibody → TARE after trying 2 monoclonal antibodies
- Stage D = hospice ± liver transplant
- Know for OSCE *
Upper GI bleed ✓
Def - bleeding from esophagus, stomach or duodenum
→ blood loss originates proximal to ligament of Treitz (= @ duodojejunal junc’n)
→ source of bleeding = gastroduodenal artery usually
Eti
- peptic ulcers = most common cause → should definitely suspect this as cause of upper GI bleed in pt w/ Hx of chronic NSAID use
- esophageal varices → usually 2° to portal HTN in pts w/ Hx of alcohol misuse
- gastric carcinoma → will be accompanied w/ unwanted weight loss + usually seen in “high risk” pts i.e male smokers > 55 y/o who maybe have past Hx of H. pylori infec’n
- Mallory-Weiss tear = tear of esophageal mucosa
SSX (1 is enough)
- melena
- hematemesis
- bright red blood on NG tube
- coffee ground emesis (looks like coffee ground due to exposure to stomach acid)
Ix- Glasgow Blatchford score or Rockall’s score if after an endoscopy
→ w/ Glasgow-Blatchford Bleeding Score, score > 0 means pt = @ high risk for upper GI bleed
U + E → elevated urea
Emergency Tx = “ABATED”
A = ABCDE
B = Bloods i.e . . .
→ FBC for Hgb + platelets
→ U+E for urea
→ INR
→ LFTs to check if due to liver disease
→ crossmatch 2 units of blood
A = Access (ideally 2 large bore cannulas)
T = Transfus’n
→ FPP (contains blood, platelets + clotting factors (fresh frozen plasma) for pts w/ MASSIVE bleed
→ Platelets in pts w/ active bleed + platelet count < 50
→Prothrombin complex concentrate in pts on warfarin
E = Endoscopy (must be done w/in 24 hrs)
D = Drugs → stop anticoagulants + NSAIDs + give terlipressin +
broad spectrum Abx if due to esophageal varices
⚠️ In hypovolemic shock tachycardia comes BEFORE hypoTN, hypoTN comes after loss of > 15% of blood volume !
- Know for OSCE *
Lower GI bleed ✓
Def - GI blood loss originating after duodojejunal junc’n
Eti
- Crohn’s
- anal fissure
- colon polyps
- ischemic colitis
- infectious colitis
- rectal cancer
- diverticular disease
- internal hemorrhoids
- Meckel’s diverticulum (occurs @ around age 2)
→ SSX = abdo pain + tenderness in RIF + bloody stool
→ Littre’s hernia = protrus’n of meckel’s diverticulum through an abdominal weakness
SSX = hematochezia i.e bright red blood per rectum
Emergency Tx i.e if theres’s hypoTN + tachycardia = IV fluids + transfus’n if there’s sig. active blood loss
- Know for OSCE *
Gastric cancer ✓
Def - stomach cancer
→ 2 most common types = intestinal type adenocarcinoma + diffuse type adenocarcinoma
RFs
- smoking
- High Na diet
- gastrectomy
- pernicious anemia
- H. pylori infec’n (strongest RF)
- polyp w/ medium grade dysplasia
- intestinal metaplasia of columnar type @ gastric cardia
- nitrate consump’n b/c bacteria in mouth can convert nitrate to nitrite (is an additive in cured meats)
SSX
- N + V
- dysphagia
- abdominal pain
- unwanted weight loss
- Trosier’s sign (indicates metastasis)
Ddx = peptic ulcer disease
Ix’s
- metabolic panel
- FBC → might show anemia
- upper GI endoscopy + Bx → signet ring cells will show prominent invasive growth w/in all layers of gastric wall
Tx
- localized = Sx or chemoradiotherapy if pt ≠ suitable for Sx
- metastasized = chemo
- Know for OSCE *
Metaplasia v.s Dysplasia ✓
- Metaplasia = cell changes into another cell type but that other cell type is a normal cell type
→ can be pathological like in GERD or physiological like the cervix during puberty
= reversible if agent that caused the change = removed but if progresses into dysplasia = irreversible - Dysplasia or carcinoma in situ = normal cell becomes an abnormal cell = pre-malignant i.e can lead to cancer
→ ≠ cancer b/c base’nt membrane hasn’t been invaded + has no metastatic Ψ due to lack of access to lymph or blood
GERD ✓
In adults
RFs
- FHx
- male
- obesity
- older age
- alcohol + smoking
- hiatus hernia = hernia’n of stomach up through diaphragm
SSX = “DOAC”
- Dysphagia + Dyspepsia
→ dypepsia = pain after eating /
bloating / hoarse voice
- Odynophagia
- Acid regurgita’n i.e heartburn
- Chest pain (epigastric pain) = made worse by lying down or bending forward, @ night or after eating spicy foods
Ddx = peptic ulcer disease
Ix’s
- 1st line = PPI trial i.e put them on PPI + see if SSX improve
- gold std = 24hr ambulatory pH monitoring
→ pH of esophagus will be < 4 which is abnormal (only do if diagnosis = uncertain) - EGD → will show erosive esophagitis or Barrett’s esophagus
Tx
- Lifestyle Δs i.e weight loss, smoking cessa’n + avoiding known precipitants such as alcohol / coffee / fatty foods
- Full dose PPI for 1-2 months (lasoprazole)
⟹ MOA - irreversibly inhibits H+/ K ATPase in parietal cells ∴ can’t export H+ into gastric lumen, so no HCl produc’n
⟹ side effect = ↓ed Fe absorp’n b/c gastric acid ↑ iron absorp’n + these medica’ns ↓ gastric acid
⟹ end in “PRAZOLE”
→ H2 receptor antagonist such as ranitidine if PPI doesn’t work
⟹ MOA - ↓ gastric acid secre’n by reversibly binding to histamine H2 receptors on parietal cells
⟹ side effect = gynecomastia
⟹ end in “DINE”
Complica’ns
- erosive esophagitis (most common complica’n) → can cause ulcers, bleeding + stricture
- Barrett’s esophagus = stratified squamous epithelia of esophagus is becoming like epithelium of stomach i.e non ciliated columnar w/ goblet cells = ex of metaplasia → can lead to esophageal adenocarcinoma
In Children - usually occurs in children < 2 months old
SSX
- NBNB emesis
- chronic cough
- hoarse cry
- poor weight gain
- unexplained reluctance to feed
- distress after feeding
- faltering growth
Ddx of vomiting in children
- overfeeding
- appendicitis
- gastroenteritis
- Intestinal obstruc’n
- pyloric stenosis (NBNB emesis as well)
- infec’ns such as UTI / tonsillitis / meningitis
Ix = clinical but refer them to pediatrician if it persists after pt is 1 y/o or if pt is not responding to Tx
Tx
- Trial alginate therapy if baby = breastfed or thickened formula feeds if baby = bottle fed
- PPI trial if pt has ≥ 1 of the following . . .
- unexplained feeding difficulties
- distressed behavior
- growth faltering
Advice to give to parents
- don’t overfeed baby
- small, frequent meals
- keep baby upright after feeding
- regular burping to help milk settle
- Know for OSCE *
Alarm GERD SSX that require urgent endoscopy referral (i.e < 2 wk wait) to check for Barrett’s ✓
- N + V
- anemia
- GI bleed
- weight loss
- raised platelet count
- dysphagia regardless of age
- new dyspepsia + pt > 55 y/o
- FHx of GI cancer in 1st ° relative
- upper abdominal mass on palpa’n
H. pylori ✓
Def - spiral shaped gram -ve bacteria associated w/ chronic gastritis + peptic ulcers (especially duodenal ulcers) = RF for peptic ulcer disease, gastric adenocarcinoma + MALT lymphoma
→ produces ammonium OH which creates alkaline env’nt that helps it survive in acidic mucosa of stomach antrum but that in turn causes gastric mucosal damage
→ test all pts who present w/ dyspepsia for H. pylori
⟹ pt had to have been 2 wks PPI free for test to be accurate
Ix’s
- stool antigen test
- urea breath test (uses radiolabeled carbon 13)
- H. pylori antibody test (blood)
- rapid urease test during endoscopy (also known as CLO test) → involves taking a small Bx of stomach mucosa → sample = added to liquid medium that contains urea → ↑ in pH means pt = H. pylori +ve
Tx = Triple therapy for 7 days i.e 2 Abx (amoxicillin + clarithromycin) + 1 PPI
→ amoxicillin MOA = penicillin i.e β lactam AB → inhibits bacterial cell wall forma’n by inhibiting cross-linking of peptidoglycan in bacterial cell wall (but some bacterial strains such a E. coli are resistant to β lactam Abx b/c produce β lactamase = enzyme that breaks down β lactam rings)
⚠️ Use metronidazole instead if pt has penicillin allergy = nitroimidazole AB that damages bacterial DNA
→ clarithromycin MOA = macrolide → inhibit 50S subunit of bacterial ribosomes = bacteriostatic AB b/c inhibits bacterial protein synthesis
→ side effects = prolonged QT interval + diarrhea b/c also kills guts flora
→ C/Is = pregnancy, prolonged QT interval
→ end in “OMYCIN” (vancomycin ≠ macrolide)
- Know for OSCE *
Peptic ulcer disease ✓
Def - break in mucosal lining of stomach or duodenum > 5mm in diameter all the way down to submucosa ( < 5mm or w/o depth = EROS’N NOT ULCER !)
RFs
- ↑ing age
- smoking
- FHx of peptic ulcer disease
- Past Hx of peptic ulcer disease
- H. pylori infec’n + chronic NSAID use = strongest RFs
Eti = H. pylori infec’n or NSAID use
Pathophys
→ duodenal ulcers = usually due to hypersecre’n of gastric acid in H. pylori infec’n = more common
→ gastric ulcers = due to longstanding H.pylori infec’n + severe inflamma’n → gastric mucin degrada’n (mucin = viscous gel-like bicarb protective layer secreted by surface mucus cells)
SSX
- N + V
- dyspepsia
- upper GI bleed SSX
- epigastric / abdominal pain (radiating to back for duodenal ulcer)
→ duodenal ulcer pain = worse @ night + w/ stress + = pain goes DOWN w/ eating hence these pts tend to GAIN weight
→ gastric ulcer pain = pain goes UP w/ eating hence these pts tend to LOSE weight
Ix’s
- upper GI endoscopy for diagnosis
- H. pylori C-13 urea breath test or stool antigen test to check for H. pylori
Tx = stop NSAIDs + full dose PPI therapy for 4-8 wks (even if pt = H.pylori -ve)
Complica’ns
- upper GI bleed from ulcer (most common complica’n)
- scarring + stricture
- gastric outlet obstruc’n = narrowing of exit of stomach due to scarring + stricture → SSX = early fullness after eating, upper abdominal discomfort, abdominal disten’n + vomiting (particularly after eating)
→ can be treated w/ balloon dila’n during an endoscopy or in OR - perfora’n (= life threatening so must be urgently treated w/ surgical repair) → can cause peritonitis
⟹ SSX of peritonitis = pyrexia, tachycardia
⟹ SSX on exam . . . - guarding = involuntary tensing of abdominal wall muscles when palpated to protect painful area below
- rigidity = involuntary persistent tightness / tensing of abdominal wall muscles
- rebound tenderness - rapidly releasing pressure on abdomen creates worse pain than pressure itself
- percuss’n tenderness
- Know for OSCE *
NSAIDs various MOAs ✓
- anti inflammatory via ↓ vasodila’n hence ↓ blood flow hence less inflammatory mediators can come
- anti pyretic via inhibi’n of PG synthesis in hypothalamus
- analgesic via ↓ PG synthesis which control nociceptors
→ COX 1 = affects GI ∴ ONLY non selective NSAIDs will cause GI SSX b/c will bind to both COX-1 + COX-2
→ COX 2 selective = NO GI SSX !
⚠️ NSAIDs can ↓ the anti-hypertensive effects of ACE-Is !
Gastritis ✓
Def - inflamma’n of gastric mucosa
RFs
- alcohol
- NSAID use
- H. pylori infec’n
- auto immune disease
Eti
- NSAIDs / alcohol
- chronic H. pylori infec’n → induces inflamma’n w/ gastric mucin degrada’n + ↑ed mucosal permeability
- auto immune atrophic gastritis → anti-parietal cell antibodies stimulate a chronic inflammatory, mononuclear + lymphocytic infiltrate involving oxyntic mucosa ∴ leading to loss of parietal + chief cells in gastric corpus
SSX
- N/V
- anorexia
- dyspepsia
Ddx
- GERD
- peptic ulcer disease
Ix = H. pylori C-13 urea breath test or stool antigen test → might test +ve for H.pylori
Tx = treat cause
Complica’ns
- achlorhydria
- B12 deficiency
- gastric carcinoma
- gastric lymphoma
- Know for OSCE *
Esophageal cancer ✓
Def - cancer of the esophagus
→ 2 main types = SCC + adenocarcinoma
RFs
- FHx (SCC)
- male (both)
- alcohol (SCC)
- smoking (both)
- older age (both)
- GERD (adenocarcinoma)
- hiatal hernia (adenocarcinoma)
- Barrett’s esophagus (adenocarcinoma)
SSX
- dysphagia
- odynophagia
- unwanted weight loss
Ddx = achalasia
Ix’s
- EGD + Bx
- CT thorax + abdomen → for metastasis
- FDG PET scan → for metastasis that CT might not have identified
Tx = Sx → chemoradiotherapy
- Know for OSCE *
Achalasia ✓
Def - esophageal motility disorder due to impaired relaxa’n of lower esophageal sphincter i.e LES fails to open during swallowing
SSX
- dysphagia
- regurgita’n
- weight loss
- substernal chest pain
Ix’s
- EGD → bird beak appearance
- Upper GI swallow
- Manometry
Tx
- CCB or sublingual isosorbide dinitrate while waiting for definitive Tx
- botulinum toxin → gastostomy if needed (for poor surgical candidates)
- Heller’s cardiomyotomy = indicated for. . .
→ pts < 40 y/o who will require lifelong dila’ns or botulinum toxin injec’ns
→ pts w/ recurrent or persistent SSX after multiple medical Tx
→ pts who choose Sx initially
→ pts at high risk for perfora’n w/ pneumatic dila’n i.e pts who had prior Sx in esophagogastric junc’n
Complica’ns
- GERD
- esophagitis
- esophageal perfora’n
- aspira’n pneumonia
- esophageal cancer
Eosinophilic Esophagitis ✓
Def - chronic, immune / allergen mediated condi’n where eosinophils build up in esophagus
RFs
- male
- FHx
- children / young adults
- white
- Hx of atopy
Pathophys - eosinophil build up in esophagus → damage + inflamma’n of esophagus
SSX
- heartburn
- chest pain
- dysphagia
Ix’s
- EGD
→ can be normal or can show . . . - fixed esophageal rings
- focal esophageal strictures
- diffuse esophageal narrowing
- crêpe-paper mucosa
- Bx for diagnosis
→ peak eosinophilic count ≥15 +/- eosinophil micro abscesses, layering, degranula’n + subepithelial sclerosis
Tx
1. Topical corticosteroid (budesonide) or PPI for 8-12 wks
2. Repeat EGD + Bx
3. Maintenance therapy or ↑ dose
Complica’ns
- FTT
- esophageal stricture
- esophageal perfora’n
IBD ✓
Crohn’s
Def - autoimmune condi’n that causes transmural i.e full-thickness inflamma’n of the entire GI tract, extends from mouth to anus, TI = linked to genetic defect in NOD-2 gene
RFs
- FHx
- white ethnicity
- 15-40 y/o or 50-60 y/o
- smoking (= protective factor for UC)
SSX
- RIF pain
- weight loss
- mouth ulcers
- prolonged diarrhea
- perianal les’ns i.e skin tags / fistulae / abscesses / anal fissure
- NO PR BLEEDING
Ddx
- UC
- IBS
- appendicitis
- ectopic pregnancy
Ix’s
- FBC → might show anemia
- B12 → might be low
- Fe study → b/c IBD pts = @ risk of malnutri’n
- ESR / CRP → will be elevated
- OGD + Bx for diagnosis
Tx = oral corticosteroids such as prednisolone → immuno-modulators such as methotrexate / infliximab / dalimumab if SSX = poorly controlled
Complica’ns
- gallstones
- anal fissure
- colorectal cancer
- intestinal obstruc’n
- fistulae / abscesses
- anemia / B12 deficiency
UC
Def - inflamma’n confined to mucosal + submucosal layer of colon, rectum = almost always involved
RFs
- infec’n
- FHx of IBD
- human leukocyte antigen B-27
SSX
- rectal bleeding
- bloody / mucus diarrhea
- SSX of severe UC = > 6 bloody stools / day + ≥ 1 of the following …
→ fever > 37.8°C
→ tachycardia > 90 bpm
→ Hgb < 10.5g/dl
→ ESR > 30mm/hr
Ddx
- IBS
- Crohn’s
- diverticulitis
Ix’s
- stool microscopy + culture to r/o infec’n
- fecal calprotectin → will be elevated
- EGD + Bx for diagnosis
- FBC → might slow high platelet b/c of inflamma’n + in UC might show anemia
- CRP → will be elevated
- albumin b/c in severe disease might be low
Acute Tx for severe = IV hydrocortisone
Acute Tx for mild-moderate = aminosalicylate → corticosteroid
Regular Tx = oral aminosalicylate (end in “SALAZINE”)
Complica’ns
- stricture
- perfora’n
- colorectal cancer
- massive lower GI bleed
- 1° sclerosing cholangitis (PSC)
- toxic megacolon = atonic colon w/ dilata’n = @ risk of perforating ∴ = surgical emergency !
→ presenta’n = rigid abdomen + dilated loops of colon on AXR
→ Emergency Tx = subttl colectomy w/ end ileostomy
- Know for OSCE *
UC v.s Crohn’s ✓
→ Crohn’s . . .
- cobblestone
- patchy (skip les’ns)
- transmural so isn’t just limited to 1 area
- wall thickening
- stricture
- deep knife-like / fissuring ulcers
- epitheloid i.e non-caseating granulomas
- goblet cells
→ UC
- mucosal inflamma’n w/ broad + superficial mucosal ulcers
- pseudopolyps
- diffuse
- extends proximally from rectum continuously
- wall thinning
- crypt abscess
Celiac Disease ✓
Def - autoimmune disease triggered by eating gluten
RFs
- FHx
- T1D
- Down’s
- IgA deficiency
- auto immune thyroid disease
Eti = exposure to gluten (even in trace amts)
→ must carry either HLA-DQ2 (in 95% of pts) or HLA-DQ8 to have Celiac !
SSX
- anemia
- bloating
- weight loss
- steatorrhea
- IgA deficiency
- FTT in children
- chronic diarrhea
- abdominal pain / discomfort
- dermatitis herpetiformis = pruritic les’ns over buttocks + arms / legs / trunk due to IgA deposi’n
Ix’s
- IgA + Anti TTG IgA antibodies = 1st line
→ antibodies will be normal or elevated (normal doesn’t exclude diagnosis !)
OR Anti TTG IgG or anti EMA antibodies if pt = IgA deficient → elevated
- Endoscopy + duodenal Bx = gold std → will show subttl villus atrophy, crypt hypertrophy + intra epithelial lymphocytes
Tx = gluten free diet
Complica’ns
- dermatitis herpetiformis
- osteoporosis / osteopenia
- iron /B9 / B12 deficiencies
- hyposplenism b/c of excessive loss of lymphocytes
- Know for OSCE *
When to test for Celiac ✓
Adult w/ new diagnosis of T1D OR child w/ FHx of celiac, autoimmune thyroiditis, T1D, juvenile chronic arthritis, Down, Turners’ or selective IgA deficiency OR child w/ any of the following SSX . . .
- FTT
- chronic constipa’n
- persistent diarrhea
- dermatitis herpetiformis
- recurrent abdominal pain
⚠️ Don’t start gluten free diet w/o having an official diagnosis of Celiac !
- Know for OSCE *
Cow’s milk protein allergy ✓
Def - condi’n in children < 1 y/o where their body doesn’t react well to cow’s milk (≠ the same as lactose intolerance !)
→ can present in breastfed babies if mom consumes dairy products
→ in IgE mediated rxn occurs w/in 2 hrs of consuming milk v.s in non-IgE mediated can occur over several days
RFs
- formula fed babies
- personal or FHx of other atopic condi’ns
SSX
- vomiting
- weight loss / FTT
- watery stools
- atopic dermatitis
- distended non-tender abdomen
- allergic rxn SSX such as hives, angioedema, watery eyes, sneezing
Tx = mom has to exclude dairy from her diet
→ mom can use hydrolyzed formula instead
- Know for OSCE *
IBS ✓
Def - chronic abdominal pain + bowel dysfunc’n
RFs
> 50 y/o
- FHx
- PTSD
- female
- physical / sexual abuse
- previous enteric infec’n
SSX =”ABC”
→ consider IBS if pt has had the following SSX for ≥ 6 months . . .
- abdominal pain (often relieved w/ defeca’n)
- bloating
- Δ in bowel habit
Ddx
- IBD
- Celiac
- infec’n
Ix = FBC to r/o infec’n
Tx
- exercise
- laxatives for SSX relief
- eliminating precipitating substances such as caffeine, lactose or fructose
Complica’n = diverticulosis
- Know for OSCE *
Anorexia nervosa ✓
Def - eating disorder characterized by low body weight due to restric’n of calorie intake + intense fear of gaining weight + distorted self-percep’n of body image
RFs
- female
- teenage / puberty
Diagnostic criteria
- restric’n of E intake that leads to a low body weight given pt’s age, sex, physical health + develop’ntal trajectory in the case of children
- intense fear of gaining weight / becoming fat or persistent behavior that prevents weight gain despite being underweight
- distorted percep’n of body weight + shape / disproportionate influence of weight + shape on self-worth or denial of seriousness of one’s low body weight
SSX
- bradycardia
- postural ↓ in BP
- cool peripheries
- significantly low body weight
- amenorrhea in women
Ddx
- depress’n
- bulimia nervosa
- hyperthyroidism
- avoidant restrictive food intake disorder = no distorted self image
Tx (goal = for pt to reach a healthy body weight)
1. structured eating plan + psychotherapy
2. inpt admiss’n + pyschotherapy if weight < 75% of where they should be
Bulimia nervosa ✓
Def - eating disorder characterized by recurrent episodes of binge eating followed by purging i.e compensatory behaviors such as self-induced vomiting, fasting, excessive exercise, misuse of laxatives / diuretics /enemas
RFs
- female sex
- personality disorder
- Hx of sexual abuse
- FHx of depress’n
- FHx of eating disorder
- FHx of alcohol use disorder
- childhood overweight or obesity
Diagnostic criteria
- Episodes of binge eating i.e pts feel that they can’t control their eating
- Inappropriate compensatory behavior to prevent weight gain
- Above behaviors must occur ≥ once/wk for a period of 3 months
- disproportionate influence of weight + shape on self-worth
- disturbance doesn’t occur exclusively during episodes of anorexia nervosa
SSX
- normal weight
- dental eros’n
- parotid gland hypertrophy
- Russel’s sign = calluses on knuckles where they have been scraped across teeth → indicative of self-induced vomiting
- alkalosis on ABG
Ddx
- MDD
- anorexia nervosa
- binge eating disorder = NO compensatory behaviors after episodes of binge eating
Tx = CBT for adults + family therapy for children → SSRI or SNRI
Transfus’n rxns ✓
RFs
- IgA deficiency
- prior pregnancy
- Hx of tranfus’n rxn
- Hx of transplanta’n
- previous transfus’n
- immuncompromised
Types
- Allergic / anaphylactic rxn = Type I hypersensitivity rxn against plasma proteins in transfused blood
→ minutes to 2-3 hrs due to release of pre-formed inflammatory mediators in degranulating mast cells
→ SSX = urticaria, pruritus, wheezing (anaphylaxis), hypoTN (anaphylaxis), respiratory arrest (anaphylaxis) + shock (anaphylaxis)
- Acute hemolytic transfus’n rxn = Type II hypersensitivity rxn caused by RBC destruction by IgM-type antibodies
→ during transfus’n or w/in 24 hrs due to pre-formed antibodies
→ SSX = fever, hypoTN, tachypnea, tachycardia, flank pain, hemoglobinuria (in intravascular hemolysis) + jaundice (in extravascular hemolysis)
- Febrile non-hemolytic transfus’n rxn = accumula’n of cytokines created by donor WBCs during storage of blood products, more common in children
→ SSX = fever, HAs, chills + flushing
- Transfus’n-related acute lung injury (TRALI)
→ occurs 6 hrs later
→ SSX = fever, cough, hypoTN, dyspnea/ tachypnea - Delayed hemolytic transfus’n rxn
= anamnestic response to foreign antigen on donor RBC previously encountered by recipient such as Rh D or other minor blood group antigens, typically causes extravascular hemolysis + is usually self-limiting
→ onset = over 24 hrs but usually presents w/in 1-2 wks due to slow destruc’n by reticulo-endothelial system
→ SSX = usually asymptomatic but pt can present w/ mild fever + hyperbilirubinemia
⚠️ Furosemide = safe Tx to give w/o having to worry about tranfus’n rxn
- Know for OSCE *
When should u do blood transfus’n ? ✓
When pt’s Hgb < 7
Anticoagulant vs Antiplatelet v.s Thrombolytic drugs ✓
- Anticoagulant = doesn’t prevent new clots from forming but prevents EXISTING clots from growing by inhibiting coagula’n cascade
- Antiplatelet = INHIBITS CLOT FORM’AN by preventing platelets from sticking together
- Thrombolytic drug = PROMOTES CLOT BREAKDOWN by activating thrombolysis / fibrinolysis
DIC (Disseminated Intravascular Coagula’n) ✓
Def - too much bleeding + clotting @ the same time
RFs
- organ destruc’n
- hematological malignancies
- major trauma such as burn or severe infec’n
Eti
- acute DIC = subacute bleeding + diffuse thrombosis
- chronic DIC = rapid onset bleeding + thrombosis → results in hypoperfus’n + infarc’n + end organ damage
Pathophys - continuous GENERA’N of intravascular fibrin + DEPLE’N of procoagulants + platelets → too much clotting + not enough clotting at the same time
SSX
- oliguria + hypoTN + tachycardia (when progresses to shock)
- SSX of thrombosis i.e purpura fulminant, gangrene, aural cyanosis
- SSX of bleeding i.e petechiae, ecchymosis (bruising), oozing, hematuria
Ix’s
- PT → will be prolonged
- fibrinogen → will be low
- D dimer → might be elevated
- FBC → will show thrombocytopenia
Emergency Tx = platelet transfus’n + coagula’n factors + coagula’n inhibitors
Complica’ns
- hemothorax
- hemorrhage
- acute renal failure
- cardiac tamponade
- intracerebral hematoma
- thrombosis → ischemia → gangrene → loss of digits
- Know for OSCE *
Veins of leg ✓
- main veins of leg = greater + lesser saphenous veins (superficial) + tibial, popliteal, femoral veins (deep)
- common iliac veins fuse w/ IVC at L5
Coagula’n Panel ✓
- INR = ratio of pt PT to mean PT (PT= how much time it takes for blood to clot)
→ ↑ed INR = pt takes too long to clot
→ ↓ed INR = pt clots too quickly i.e likely to have DVT - PTT = used to see if heparin is working
P.E + DVT ✓
Embolism = occlus’n of a vessel by undissolved material that is transported via the circula’n such as a blood clot / air / fat
→ clinical effects of embolism depend on what vessel = occluded + what tissue that vessel supplied
RFs for PE (provoked = caused by identifiable RF)
- obesity
- smoking
- OCP use
- FHx of VTE
- pregnancy
- active malignancy
- recent VTE (vessel wall damage)
- immobility i.e Sx / long travel / bed rest for > 5 days (stasis)
→ can prevent it during Sx w/ intra-operative compress’n socks
- major physical trauma w/in past 2 months (vessel wall damage)
- genetic thrombophilias i.e protein C / protein S deficiency or antiphospholipid syndrome (hypercoagubility)
Eti for P.E = DVT 90% of the time + PVT 10% of the time (pelvis)
→ DVT Eti = Virchow’s triad . . .
a) Vessel wall damage - endothelial cell damage promotes thrombus forma’n, usually at venous valves
b) Venous stasis - poor blood flow aka stasis promotes thrombi forma’n
c) Hypercoagubility aka more prone to clot (usually genetic)
Pathophys of Clotting
- Thromboxane (TXA2) binds to platelets + makes platelets aggregate at site of injury
→ forms loose platelet plug (platelets adhere to plug via vWF) - Coagula’n cascade
→ Extrinsic pathway (= faster than intrinsic) : 12 activates 11 → 11 activates 9 → 9 forms complex w/ 8 → complex activates 10
→ Intrinsic pathway - 3 activates 7 → 7 activates both 9 + 10
⟹ both intrinsic + extrinsic result in activa’n of factor 10
→ Common pathway - 10 forms complex w/ 5 + Ca
→ that complex activates prothrombin activator
→ prothrombin activator activates 2
→ 2 goes from prothrombin to thrombin
→ 2 polymerizes / links w/ 1 (fibrinogen) to now become fibrin + activates 13 via Ca
→ 13 turns fibrin into fibrin mesh + now we have stable plug that shouldn’t easily dislodge
* Vit K = necessary b/c Vit K epoxide reductase needs to make Protein C + S func’nal + carboxylate 2, 7, 9, 10 so they can be active *
- Fibrinolysis aka getting rid of clot - Tissue plasminogen activator (tPA) = secreted by endothelial cells + converts plasminogen to plasmin → plasmin breaks down fibrin mesh → D-dimer = produced
→ Complex of Protein C + S degrade 5 + 8
P.E Pathophys - medium-sized embolus → occlus’n of a segmental pulm. artery b/c clot in vessel creates dead space / shunt where gas exchange can’t occur → mismatch btw perfus’n + ventila’n, (NO perfus’n b/c blood is able to reach lungs but isn’t getting O2ated in those lungs)
→ pulm. infarc’n +/- pleuritis + effus’n
SSX
- SOB
- tachypnea
- pain on 1 side of chest
- hypoxemia (i.e O2 sat < 95%)
- hemoptysis i.e coughing blood
- sinus tachy on ECG
- calf pain + erythema + swelling + warmth + Ψ loss of func’n (for VTE)
Ix’s
- CTPA to diagnose P.E but V/Q scan instead if pt has kidney pb or is allergic to contrast dye
- Wells score to figure out if DVT = cause of P.E (Well’s score > 4 = DVT likely)
- If Wells score = +ve do proximal leg vein U/S + if -ve do D-dimer + follow steps 4 + 5
- If U/S = +ve start Tx + if it’s unprovoked DVT do CT scan of abdomen + pelvis to r/o malignancy + if -ve do D-dimer test
- If D-dimer = +ve repeat U/S + if -ve it’s NOT DVT !
- If repeat U/S = +ve start Tx + if -ve it’s NOT DVT !
Tx = anticoagulants for 3 months if provoked + for 6 months if unprovoked
- DOAC (Direct Oral Anti-Coagulant)
- MOA = Direct Factor 2 or 10 inhibitor
- side effects = hemorrhage, rash, nausea
- C/Is = high risk of bleeding
- Factor 10 inhibitors end in “XABAN” - Warfarin → must monitor via INR (we expect it to ↑ to 2-3 but if it ↑ above 5 STOP it immediately + give IV Vit K + Prothrombin Complex Concentrate to reverse effects of warfarin)
- MOA : inhibits Vit K epoxide reductase ∴ blocks γ-carboxyla’n of the Vit K dependent clotting factors i.e 2, 7, 9, 10, C + S
- side effects = warfarin-induced skin necrosis, bleeding, bruising, diarrhea, jaundice, N/V, teratogenic
- C/Is : pregnancy b/c = teratogenic, liver disease, active bleed
- Cau’ns : drug interac’ns can either ↑ or ↓ anticoagula’n effect
- avoid contact sports due to risk of bleed + don’t take w/ alcohol b/c can ↓ anticoagula’n effect
- don’t stop it w/o consulta’n, do not double missed dose
→ drugs that ↑ it i.e lower INR = PPIs, SSRIs, quinolones, grapefruit, cranberry juice
→ drugs that ↓ it i.e raise INR = alcohol, rifampicin, carbamazepine
- Heparin → MUST monitor PTT !
- MOA : binds + activates antithrombin ∴ inhibiting thrombin
→ LMWH for cancer pts or stable pts w/ normal renal func’n
→ Unfractionated hep for pts who may still require thrombolysis or have renal pb
- side effects = bleeding + HITT (Heparin Induced Thrombo-cytopenia Thrombosis = auto-immune rxn)
- C/Is = active bleed, Hx of HITT, platelet count ≤ 100,000/mm
- Know for OSCE *
PE ECG Findings ✓
- sinus tachy (most common finding)
- T wave invers’n in anterior leads
- S1Q3T3 i.e S wave in lead 1, Q wave in lead 3 + T wave invers’n in lead 3
Post op DVT ppx ✓
- LMWH for ortho Sx (unfractionated heparin instead if pt has renal failure)
- Fondaparinux Na for abdominal / bariatric / cardiothoracic Sx OR for pts w/ with LE immobiliza’n / fragility fractures of pelvis, hip or proximal femur
→ dose = 2.5 mg subq OD - Know for OSCE *
ASA Classifica’n ✓
ASA I = normal healthy pt
ASA II = mild systemic disease (controlled asthma for ex)
ASA III = severe systemic disease (asthma w/ frequent inhaler use for ex)
ASA IV = pt w/ severe systemic disease that’s a constant threat to their life
ASA V = moribund pt that is not expected to survive w/o opera’n
ASA VI = brain dead pt whose organs are being removed for dona’n purposes
Fasting requirements for Sx ✓
- water + other clear liquids = up to 2 hrs before induc’n of anesthesia
- food + milk-containing drinks = up to 6 hrs before induc’n of anesthesia
Suxamethonium / succinylcholine MOA ✓
Short-acting depolarizing muscle relaxant ∴ can cause malignant hyperthermia in pt w/ any RFs
What do we monitor in anesthesia induc’n ? ✓
Vitals + ECG
Causes of post-op confus’n ✓
- PE
- infec’n
- electrolyte abnormality i.e hypoglycemia / HypoNa
Colloids v.s Crystalloids ? ✓
- Colloids = large molecule solu’ns ∴ stay in bloodstream longer
- Crystalloids = solu’ns w/ small molecules, move rapidly throughout body
→ NS, LR i.e Hartmann’s, dextrose
Effects of propofol after injec’n ✓
- ↓ in BP
- resp. depress’n
- painful sensa’n on injec’n
- hypnosis
Ddx of post op fever ✓
” 5 W’s”
Post op day 1-2 = “WIND” i.e lungs . . .
- P.E
- aspira’n
- atelectasis
- pneumonia
Post op day 3-5 = “WATER” i.e UTI / CAUTI
Post op day 5-7 = “WALK” i.e DVT, abscess
Post op day 10 = “WOUND”
→ inspect wound for redness, swelling, drainage of pus or blood
When do cardiac complica’ns in non-cardiac opera’ns most frequently occur ? ✓
W/in the first 72 hrs after Sx
What is parity ? ✓
Amt of times woman has given birth to fetus that was ≥ 20 wks gesta’n
Pregnancy + VTE ✓
Pregnancy RFs
- advanced maternal age
- BMI > 30
- parity > 3
- smoker
- varicose veins
- pre-eclampsia
- immobility
- FHx of unprovoked VTE
- low risk thrombophilia
- multiple pregnancy
- IVF pregnancy
Pregnant woman w/ 3 RFs should be started on LMWH from 28 wks gesta’n – 6 wks postnatal + those w/ > 3 RFs should begin LMWH immediately till 6 wks postnatal !
Thrombotic thrombocytopenic purpura (TTP) ✓
Def - deficiency of ADAMTS 13 either due to gene muta’n on chromosome 9q34 or develop’nt of neutralizing antibodies
= characterized by mechanical RBC destruc’n in microcircula’n + thrombocytopenia due to consump’n + tissue ischemia + infarct b/c of microcircula’n obstruc’n
RFs
- black
- female
- obesity
- cancer therapy
- pregnancy (especially end of term or post partum)
Eti
- pregnancy
- post infec’n
-drugs i.e ciclosporin, OCP, penicillin, clopidogrel, aciclovir
- tumors
- SLE
- HIV
Pathophys - deficiency of ADAMTS-13 → ↑ in vWF → aggrega’n of circulating platelets → thrombi forma’n in microvasculature / microcircula’n
Diagnostic criteria
- fever
- renal insufficiency
- thrombocytopenic purpura
- microangiopathic hemolytic anemia (only visible on blood film)
- neuro SSX i.e HA / confus’n / blurry vis’n / tinnitus / lethargy / seizures
⚠️ Need ≥ 3/5 to diagnose !
Ix’s
- FBC → will show thrombocytopenia + anemia
- haptoglobin (= produced by liver) → will be low b/c so many RBCs are being destroyed so it’s busy binding to released Hgb
- blood smear → will show microangiopathic hemolytic anemia w/ schistocytes
- urinalysis → might show proteinuria due to renal insufficiency
- U + E → urea + creatine might be elevated due to renal insufficiency
- direct coombs test → to r/o AIHA
Tx = plasma exchange w/in 24 hrs + corticosteroids → immuno- suppressants → splenectomy
Complica’ns
- MI
- ischemic stroke
- renal dysfunc’n
- Know for OSCE *
1° v.s 2° hemostasis ✓
1° hemostasis = forma’n of weak platelet plug = mediated by interac’n btw platelets + vessel wall
→ disorders of 1° hemostasis = usually due to platelet or vWF abnormality
⟹ Thrombasthenia Glanzmann
= genetic GPIIb / IIIa deficiency ∴ causes impaired platelet aggrega’n
→ main SSX = gingival bleeding + epistaxis (uncontrolled nose bleed) + heavy periods
⟹ Bernard Soulier
= genetic GPIb deficiency ∴ causes impaired platelet adhes’n
→ main SSX = bleeding + enlarged platelets + mild thrombocytopenia on blood smear
⟹ Von Willebrand’s disease
2° hemostasis = stabliza’n of platelet plug = mediated by coagula’n factors
→ disorders of 2° hemostasis = usually due to inherited or acquired coagula’n factor(s) abnormality such as Hemophilia
Von Willebrand Disease ✓
Def - bleeding disorder where pt = deficient qualitatively or quantitatively in vWF ∴ platelet adhes’n = impaired + we get excessive bleeding
= most common inherited bleeding disorder
→ severity depends on type
→ usually detected accidentally b/c of metrorrhagia, pre-op lab exam (pt has prolonged bleeding time) or after tonsillectomy / abor’n b/c pt had mucocutaneous bleeding
RFs
- FHx
- incest
Eti
- Type 1= quantitative partial deficiency
= autosomal dominant = most common of the 3 but isn’t severe - Type 2 = func’nal abnormality = autosomal dominant + is rare
- Type 3 = complete deficiency = autosomal recessive + rare but is the most severe of the 3
SSX
- post op bleeding
- getting bruised easily
- excessive bleeding from minor wounds
- menorrhagia i.e extremely heavy periods
Ix’s
- PT → will be normal
- vWF antigen (for diagnosis) → will be low
- APTT → will only be prolonged if factor 8 activity < 35% of its normal activity ∴ can’t exclude vWF even if APTT = normal
Emergency Tx i.e in severe blood loss = platelet transfu’n
Regular Tx = vWF containing concentrate
Inherited Hemophilia ✓
Def - X linked recessive disorder where pt = deficient in either factor 8 or 9
RFs
- FHx
- male
Eti
- Hemophilia A = factor 8 deficiency
- Hemophilia B = factor 9 deficiency
SSX
- bleeding into muscles
- hemarthrosis (bleeding into a jt) → causes fixed jts
- mucocutaneous bleeding i.e epistaxis / gum bleeding
Ix’s
- PT → will be normal
- APTT → will be prolonged
- X ray to check for hemarthrosis
- plasma vWF to r/o vW disease
- LFTs to make sure it’s not a liver pb
- plasma factor 8 or 9 assay → will be ↓ed or absent
Tx = factor 8 or 9 replac’nt depending on type of hemophilia pt has
Complica’ns
- hemorrhage
- jt / muscle damage such as synovitis, arthropathy, muscle atrophy
- Know for OSCE *
SCD ✓
Def - AR disorder where pt has sickle-cell shaped RBCs instead of normal RBCs
→ SSX start @ age 1 b/c prior to that pt = protected by fetal Hgb
→ if heterozygous = sickle cell TRAIT NOT SCD !
RFs = African American or Mediterranean
Eti - missense mutat’n in β chain of Hgb gene → causes new codon which codes for valine instead of glutamic acid → valine = hydrophobic → mutated Hgb polymerizes under deO2ated condi’ns → RBCs have sickle cell shape
→ RBCs = reversibly sickled INITIALLY IF reO2ated but after multiple cycles become IRREVERSIBLY SICKLED via Gardos pathway (Ca-activated K channel where Ca enters cell + activates K channel → causes K efflux along w/ water → cell becomes dehydrated → HbS precipitates + polymerizes)
Pathophys
- VASO-OCCLUSIVE CRISIS :
→ sickled RBCs = more adhesive than normal RBCs so stick to one another + to walls of vessel + have shorter lifespan (20 days instead of 120) → poor blood supply to tissue → hypoxia
= most common crisis in sickle cell
= triggered by O2 condi’ns such as stress / infec’n / dehydra’n / cold weather - SEQUESTRA’N CRISIS :
→ pt has overactive spleen (hypersplenia) b/c spleen = “sequestering” more RBCs than normal to destroy sickled RBCs → can cause splenomegaly - APLASTIC CRISIS :
= sudden ↓ in Hgb w/ reticulocytopenia
→ can happen b/c of hydroxyurea use or streptococcal infec’n but most often happens b/c of Parvovirus B19 = virus that replicates in erythroblasts + causes red rash covering cheeks that spares nasolabial folds (“slapped cheek syndrome”) → causes reticulocytopenia + severe ↓ in Hgb b/c suppresses bone marrow’s ability to make RBCs ∴ making the anemia worse - HEMOLYTIC CRISIS = ↑in hemolysis rate to destroy sickled RBCs ∴ causing sudden ↓ in Hgb + reticulocytosis + hyperbilirubinemia
SSX + Complica’ns
- Due to vaso-occlusive crisis :
→ bone pain, dactylitis (swollen digits), silent cerebral infarct, limp in children
→ acute chest syndrome (b/c of lung infarct) = when vessels supplying lungs become clogged w/ RBCs = medical emergency w/ high mortality !
⟹ SSX = fever, SOB, shortness of breath, chest pain, cough + hypoxia → CXR will show pulmonary infiltrates - Due to hypersplenia / asplenia :
→ splenomegaly, ↑ed risk of infec’n from encapsulated bacteria (i.e streptococcus pneumoniae /meningococcus such as neisseria meningitides / Hemophilus influenza Type B which often cause septicemia + salmonella typhi / staph. aureus / E.coli which often cause osteomyelitis) - Due to hemolytic crisis :
→ kidney damage b/c of free floating Hgb after RBC destruc’n
→ vasospasm / abdo pain / pulm.HTN b/c of less NO due to arginase release + NO = required for smooth muscle relaxa’n / vasodila’n
- Due to the anemia itself :
→ pale palmar creases / mucous membranes, fatigue + Fe overload from transfus’n
Ix’s
- Electrophoresis
> 75-95% = SCD, 43-45% = SCT - Peripheral Blood Smear
→ smear will show sickle-shaped cells + nucleated RBCs + purple Howell-Jolly bodies aka remnants of RBC nuclei due to destruc’n by spleen
Emergency Tx for acute painful sickle cell crisis = subq morphine
Regular Tx
- prophylactic vaccina’n against encapsulated bacteria i.e pneumococcus, hemophilus influenza B + meningococcus
- paracetamol / ibuprofen for in vaso-occlusive crisis
⟹ paracetamol MOA - acetaminophen → inhibits COX but doesn’t bind to COX1/COX2 like NSAIDs which is why it’s an anti-pyretic + analgesic but NOT an anti-inflammatory
⟹ side effect = non itchy skin rash
⟹ C/Is = liver disease, < 3 months old (same for ibuprofen) - frequent transfus’ns (when severe i.e pt has sequestra’n crisis / B19 infec’n / hyperhemolytic crisis)
- Ψ bone marrow transplant
- Know for OSCE *
Thalassemia Major ✓
Def - complete absence of both β chains = most severe form of β thalassemia (AR)
→ pts = transfus’n dependent + like SCD, infants = protected by fetal Hgb
→ thalassemia minor = heterozygous muta’n aka muta’n in only 1/2 of genes so instead of LACK of β chain we get UNDERPRODUC’N of β chain *
- β = 2 genes v.s 𝛼 = 4 genes *
- 𝛼 thalassemia = due to gene DELE’N NOT muta’n like in β *
→ 1 gene deleted = asymptomatic
→ 2 genes deleted = 𝛼 thalassemia minor aka trait / carrier = mild hypochromic (pale RBC b/c they have less Hgb than they should) microcytic anemia
→ 3 genes deleted = 𝛼 thalassemia intermediate / HbH disease = severe hypochromic microcytic anemia
⟹ transfus’n only needed in old age or pregnancy
→ 4 genes deleted = hydrops fetalis
= 4 γ chains will form tetramer Hgb called Hgb Bart’s in newborn = fatal
RF = Mediterranean
Pathophys - produc’n of β-globin chains = deficient or absent → imbalance btw 𝛼 + β chains → precipita’n of excess 𝛼 chains in erythroid precursors + maturing RBCs → membrane damage + cell destru’n → cells can’t survive → ineffective erythropoiesis → anemia
SSX + Complica’ns
- fatigue, pale skin, stunted growth / delayed puberty due to anemia
- jaundice (due to hyperbilirubinemia as a result of intravascular hemolysis)
- chronic Fe deposi’n due to multiple transfus’ns
→ can result in bronze skin, arrhythmia, precipita’n, hepatosplenomegaly
Ix’s
- Fe study → will show low ferritin
- Reticulocyte count → will be high
- FBC → will show microcytic anemia
- Hgb electrophoresis → will show larger %age of HbF + HbA2 + absent or very low HbA
Tx = life long transfus’ns + Fe chela’n (drugs that remove excess Fe from body)
- Know for OSCE *
Pancytopenia ✓
Def - ↓ in all 3 blood cells i.e RBCs, WBCs + platelets
Eti- central or peripheral
→ Central = ↓ed PRODUC’N by bone marrow
⟹ ex - aplastic anemia = due to aplasia or hypoplasia of bone marrow
→ Peripheral = ↑ed peripheral DESTRUC’N
SSX
- infec’n
- anemia
- purpura
- petechiae
- easy bruising
- gum bleeding
Splenomegaly + Lymphadenopathy ✓
1) Splenomegaly = palpable spleen i.e speen has enlarged ≥ 2x its normal size
Eti
- portal HTN
- inflammatory diseases like RA or SLE
- chronic bacterial infec’ns such as TB or brucellosis
- chronic parasitic infec’ns such as leishmaniasis or malaria
- hematological condi’ns such as hemolytic anemia or leukemia
- acute infec’ns such as septic shock, typhoid or infective endocarditis
2) Causes of lymphadenopathy (“CHICAGO”) :
- Cancer i.e hematological malignancies like Hodgkin lymphoma, Non-Hodgkin lymphoma, Acute Leukemia, Myelofibrosis, CML in blastic crisis or metastasis
- Hypersensitivity such as after vaccin’an
- Infec’ns
> VIRAL
→ Infectious Mono / Epstein Barr Virus
→ CMV
→ HSV 1/2
→ Rubella
→ Herpes Zoster
→ HIV
→ Human Herpes Virus 6 (HHV-6)
→ Parvovirus Β19
→ Hepatitis Viruses
> BACTERIAL
→ streptococcal infec’ns
→ salmonella
→ brucella
> FUNGAL = in immunosuppressed pts
> PARASITIC
→ toxoplasma
→ leishmania
- Connective tissue disorders like RA, SLE, Sjogren syndrome, dermato-myosiitis
- Atypical lymphoproliferative disorders like Castleman disease or Wegener’s granulomatosis
- Granulomatous disorders like TB or sarcoidosis
- Others like Kikuchi lymphadenitis or immunodeficiency
Leukemia ✓
Def - malignant transforma’n of hematopoietic precursor cells in bone marrow = most common cancer in children
→ ALL = most common form of acute leukemia in children, peak prevalence = 2-5 y/o
→ AML peak prevalence = < 2 y/o
→ CML = caused by Philadelphia chromosome ∴ ALL CML pts will be Philadelphia +ve !
⚠️ Philadelphia chromosome DOESN’T CAUSE ALL but DOES ↑ RISK !
RFs
- Down syndrome
- Kleinfelter syndrome
Types
- Acute Myeloid Leukemia
- Chronic Myeloid Leukemia
- Acute Lymphoid Leukemia
- Chronic Lymphoid Leukemia
→ acute = immature so can’t perform their func’n @ all, blasts rapidly ↑ in # ∴ disease progresses very quickly
→ chronic = mature-ish so can perform some of their func’ns, blasts ↑ in # slowly ∴ disease progresses slowly + gradually
→ myeloid = precursor to all WBCs (except lymphocytes) + RBCs + platelets
⟹ myeloid = larger blasts, more cytoplasm + cytoplasm might contain granules
→ lymphoid = precursor to lymphocytes
⟹ lymphoid = smaller blasts + cytoplasm lacks granules
Myeloid v.s Lymphoid Classficia’n :
- Myeloid = M0-M7
→ M0 = minimally differentiated
→ M1 = no matur’an
→ M2 = w/ matura’n
→ M3 = hyper granular promyelocytic (has favorable prognosis so NO transplant for M3 pt)
→ M4 = myelomonocytic
→ M5a = monoblastic
→ M5b = monocytes
→ M6 = erythroleukemia
→ M7 = megakaryoblastic
- Lymphoid = L1-L3
→ L1 = small + monomorphic
→ L2 = large + heterogeneous
→ L3 = Burkitt cell type
SSX = “ N- BLAST “
- Neutropenia → will make child more prone to infec’ns hence they’ll often be febrile
- Bone pain → child might have difficulty walking
- Lymphadenopathy
- Anemia + weight loss → will cause pallor + lethargy
- Splenomegaly
- Thrombocytopenia → will cause bleeding / petechial rash / purpura
→ petechial rash means pt has SEVERELY LOW PLT COUNT i.e < 20K
⚠️ Suspect leukemia if child has the following SSX (“CHILD CANCER “) . . .
→ Continual unexplained weight loss
→ HAs accompanied by early morning vomiting
→ ↑ed swelling or persistent bone / jt pain
→ Lump or mass (especially in abdomen, neck, chest, pelvis, armpits)
→ Develop’nt of excessive bruising / bleeding or rash
→ Constant or recurrent infec’ns
→ A whitish color behind pupil
→ Nausea that persists or vomiting +/- seizures
→ Constant tiredness or noticeable paleness
→ Eye / vis’n Δs suddenly + persistently
→ Recurrent or persistent fevers of unknown origin
AML ✓
RFs
> 65 y/o
- previous chemo TX
- radian or benzene exposure
- previous hematological disoder
Ix’s
- FBC → anemia, leukocytosis, neutropenia, thrombocytopenia
- Blood smear/ film → will show blast cells → ≥ 20% blast cells confirms AML diagnosis
Tx = chemo
Complica’ns
- DIC
- infec’ns
- pancytopenia
- tumor lysis syndrome = oncological emergency !
CML ✓
RF = > 65 y/o
Ix’s
- blood smear/ film → will show mature myeloid cells
- FBC → anemia, leukocytosis, thrombocytopenia or normal platelet count
- bone marrow bx (required to confirm phase of disease) → will show granulocytic hyperplasia
Tx = tyrosine kinase inhibitor
Complica’n = pancytopenia
ALL ✓
RF = < 5 y/o
Ix’s
- blood smear/ film → will show lymphoblasts
- FBC → anemia, leukocytosis, thrombocytopenia
- bone marrow aspirate + bx →
≥ 20% lymphoid blast cells confirms diagnosis
Tx = chemo + CNS Ppx to prevent CNS disease
Complica’ns
- pancytopenia
- tumor lysis syndrome
CLL ✓
RF = > 60 y/o
Ix’s
- blood smear/ film → will show smudge cells (not diagnostic tho)
- FBC → anemia + leukocytosis (specifically lymphocytosis)
Tx = tyrosine kinase inhibitor IFF pt = symptomatic
Lymphoma ✓
- Hodgkin’s Lymphoma
Def - hematological malignancy arising from mature B cells = characterized by presence of Hodgkin’s cells + Reed-Sternberg cells
RFs
- FHx
- Hx of EBV infec’n
- young adult < 35 y/o or > 55 y/o
SSX
- fever
- weight loss
- night sweats
- cervical +/- supraclavicular lymphadenopathy
Ix’s
- FBC → anemia + thrombocytopenia
- CXR → will show bulky mediastinal lymphadenopathy
- PET / CT for staging
Tx = chemo
- Non-Hodgkin’s Lymphoma = B or T cell lymphoma
Types
- Lymphoblastic
- Anaplastic Large Cell
- Burkitt’s = starry-sky appearance of intermediate-sized lymphoid cells interspersed w/ macrophages surrounded by clear spaces on Trephine Bx = associated w/ c-MYC oncogene
RFs
> 50 y/o
- HIV
- male
- Hep C
- celiac disease
- H.pylori infec’n
- Hx of EBV infec’n
- Sjogren syndrome
- human herpes virus 8
SSX
- fever
- fatigue
- weight loss
- night sweats
- splenomegaly
- lymphadenopathy
Ix’s
- lymph node Bx → will be +ve
- bone marrow Bx → will be +ve
- PET / CT for staging
- LFTs → will be elevated if spread to liver
- blood smear → will show nucleated RBCs
- FBC → will show pancytopenia + lymphocytosis
- LDH → will be elevated (indicates rate @ which lymphoma = spreading)
Tx = chemo → excis’n or radiotherapy
Multiple Myeloma ✓
Def - B cell neoplasia characterized by prolifera’n of abnormal plasma cells in bone marrow that produce excessive light chains (usually kappa) → results in abnormal monoclonal antibody called paraprotein (usually abnormal IgG)
- we also get amyloid deposits *
Pathophys - cytokines such as IL-1 + TNFs → osteoblast progenitor cells = inhibited from becoming osteoblasts → osteoblast activity ↓ + osteoclast activity ↑ so bone breaking ↑ b/c there aren’t osteoblasts to inhibit them
SSX
- HyperCa SSX
- Bence Jones protein
- hepatosplenomegaly occas’nally
- ↑ed risk of infec’n due to ↓ in Ig produc’n
- bone pain + ↑ed risk of fractures due to lytic les’ns
- anemia b/c bone marrow crowding suppresses erythropoiesis
- thrombocytopenia due to bone marrow crowding → ↑ed risk of bruising + bleeding
- Rouleaux forma’n → indicates hyperviscosity (causes blurry vis’n, dizziness + HAs)
- lytic les’ns on X ray due to bone marrow infiltra’n by plasma cells + cytokine-mediated osteoclast overactivity
Ix’s
- peripheral blood film → will show Rouleaux forma’n
- serum electrophoresis → will show elevated M protein in blood/urine
- bone marrow aspira’n + Bx for diagnosis → ≥10% plasma cells in bone marrow = enough to diagnose
- serum free light chain → will show Bence Jones protein = diagnostic
Tx = chemo
Complica’ns
→ leukopenia
→ recurrent infec’ns
→ fracture of vertebral bodies
→ renal failure b/c light chains = directly toxic to kidney + also b/c Bence Jones protein produces casts that obstruct tubular lumen hence causing tubular / renal inflamma’n
SVC obstruc’n (cancer complica’n) ✓
Def - oncological emergency where SVC = obstructed due to tumor compress’n
Eti = lung cancers or lymphomas that grow so big that they start to compress SVC
Pathophys - cancer grows so big that it starts to compress SVC → venous return from head, thorax + upper extremities to RA = interrupted → ↑ in venous pressure
SSX
- SOB
- pulseless JVD
- visual disturbance
- swelling of face, neck + arms
- distended neck + chest veins
Ix’s
- CXR
- chest CT for diagnosis
Emergency Tx if eti = unknown =
secure airway + radiotherapy + corticosteroid
Emergency Tx if malignancy = known = secure airway + percutaneous endovascular stenting
Tumor Lysis Syndrome (cancer complica’n) ✓
Def - oncological emergency where tumor cells release their contents into bloodstream after chemo
→ HyperK
→ HyperPhos
→ Hyperuricemia b/c of released nucleic acids
→ HypoCa b/c Phos binds to Ca so the more Phos = released the less freely floating Ca there is
⚠️ ≥ 2 of the above must be present for diagnosis !
Eti = Cancer Tx
Pathophys - high tumor burden so when chemo / radia’n = initiated there’s a rapid lysis of tumor cells
SSX
- lethargy
- arrhythmia
- N/V due to HyperK
- diarrhea due to HyperK
- seizures / muscle cramps / tetany due to HypoCa
Ix = U + E + serum urate / uric acid
Emergency Tx = Ca gluconate for HyperK → intense IV fluid resucita’n +/- loop diuretic → rasburicase for hyperuricemia
Complica’ns
- uric acid precipita’n + CaPO4 deposi’n in renal tubules can cause renal vasoconstric’n → ↓ in renal blood flow → pre-renal AKI
Myelodysplastic syndrome ✓
Def - ineffective + dysplastic hematopoiesis = step right before AML
RF = > 70 y/o
SSX
- pallor
- fatigue
- exercise intolerance
- petechiae / purpura
Ix’s
- FBC → anemia, leukopenia, thrombocytopenia
- reticulocyte count → inappropriately low or normal i.e not what it should be when u look @ ° of anemia
- bone marrow aspira’n w/ Fe stain → blasts < 20%
- bone marrow core Bx → hypercellular marrow
- bone marrow cytogenetic analysis to check for chromosomal abnormalities that could be causing the MDS
Tx for symptomatic = hematopoietic GFs → DNA methyltransferase inhibitors
Complica’ns
- AML
- infec’ns
- bleeding
Essential thrombocythemia ✓
Def - ↑ in size + # of circulating platelets due to prolifera’n of abnormal megakaryocytes in bone marrow
SSX
- bleeding
- splenomegaly
- livedo reticularis
- erythromelalgia = burning redness + pain in limbs
Ix’s
- FBC → thrombocytosis
- blood smear → thrombocytosis w/ varying °s of platelet anisocytosis (varia’n in SIZE)
Tx = anti platelet therapy such as aspirin or clopidogrel
→ omeprazole ↓ effect of clopidogrel ∴ pts taking both should be switched to diff PPI
Complica’ns
- AML
- bleeding
- arterial / venous thrombosis
- intrauterine death / spontaneous abor’n if occurs during pregnancy
Infec’n ✓
1- Role of white + red pulp of spleen
2- Describe systemic + specific SSX of pt w/ infec’n
1) Func’ns of White pulp
- antigen presenting cells can enter which activates residing T cells who in turn activate B cells so they can become plasma cells
- pathogen enters follicles directly = where B cells are + they present antigen to T cells which activates T cells who then activate B cells = co stimula’n
- B cells fight off encapsulated bacteria
Func’ns of Red pulp
- platelet sequestra’n
- destruc’n of old or damaged RBCs
- phagocytosis of opsonized bacteria by macrophages
- storage of RBCs in case of severe blood loss
2) Systemic SSX of pt w/ infec’n → fever +/- tachycardia / tachypnea, fatigue, chills, HA, anorexia
→ If in Upper Resp. Tract → nasal congest’n + discharge / sore throat /enlarged tonsils / cough
→ If in Lower Resp. Tract → productive or dry cough / pleuritic pain / dyspnea / tachypnea
→ If in Urinary Tract → dysuria (painful urina’n) / urinary urgency / costovertebral angle pain/ hematuria / urethral discharge
→ If in CNS → AMS / disorienta’n / neck stiffness / CN palsies / seizures
→ If in skin or soft tissue → edema, erythema, pain, heat
Anemia of chronic disease ✓
Def - anemia due to underlying disease
Eti
- RA
- SLE
- HIV
- GCA
- malaria
- liver disease
- renal failure
- cancers like lymphoma or myeloma
Cancer ✓
1- Compare + contrast benign + malignant tumors
2- Define tumor grade + stage + explain how they differ from one another
3- Give ex’s of the diff terminology used for pre-malignancy in diff anatomical sites
4- Tumor markers
1) Neoplasm or tumor = abnormal tissue mass w/ uncontrolled growth
→ can be benign or malignant + it’s when it’s malignant that we call a tumor cancer
⟹ Benign =
- slower growing
- well circumscribed
- often encapsulated
- NOT locally invasive
- NO metastatic Ψ
- very well differentiated cells i.e cells closely resemble cells of origin
- cellular uniformity throughout tumor i.e tumor cells look exactly or roughly the same
- few mitoses
- normal nuclear : cytoplasmic ratio
⟹ Malignant =
- faster growing
- poorly circumscribed
- non-encapsulated
- invasive growth
- has metastatic Ψ
- variable differentia’n (can range from well to poorly differentiated)
- cellular pleomorphism (i.e of variable size + shape)
- plenty of mitoses
- high nuclear: cytoplasmic ratio
- nuclear hyperchromatism (chromatin condensa’n)
2) Staging = for malignant tumors + grading = for pre + malignant tumors
→ grading for malignant = how aggressive tumor is
→ grading for pre-malignant = how LIKELY it is to become malignant
→ staging = extent of spread, helps for prognosis
3) Tumor w/ “epithelium” in it’s name means that it’s a tumor that affects lining of a body surface i.e squamous epithelium for skin / esophagus + glandular epithelium for resp / GI tract
→ carcinoma = malignant tumor of an epithelium = most common type of malignant tumor, usually metastasizes via lymph
⟹ SCC = keratin form’an + intercellular bridges btw cells
⟹ adenocarcinoma = glandular / acinus forma’n + mucin produc’n
→ “sarcoma” = malignant, usually metastasizes via bloodstream
⟹ osteosarcoma (bone)
⟹ liposarcoma (adipose)
⟹ chondrosarcoma (cartilage)
⟹ angiosarcoma (blood vessel)
⟹ leiomyosarcoma (smooth muscle)
⟹ rhabdomyosarcoma (striated muscle)
→ melanoma / mesothelioma / lymphoma or leukemia / glioma = malignant as well
→ melanomas can mimic almost all tumors ∴ must perform immuno-histochem
→ “oma” = benign tumor
ex’s- squamous cell papilloma, hemangioma, leiomyoma, osteoma
→ “adenoma” = benign tumor of glandular epithelium except in GI where it refers to pre-malignant
4)
- AFP for liver cancer
- CEA for colon cancer
- Ca 15-3 breast cancer
- Ca 19-9 for pancreatic cancer
- Ca 125 for ovarian cancer
- PSA for prostate cancer
- β hCG for testicular cancer
Hemochromatosis / Fe Overload ✓
Def - autosomal recessive disorder where too much Fe = released from macrophages
RFs
- FHx
- male
- white
- 40-50 y/o
- supplemental Fe
SSX
- fatigue
- weakness
- arthralgia
- bronze skin
- hepatomegaly
Ix’s
- serum transferrin satura’n → will be > 45%
- serum ferritin → will be elevated
Tx = low Fe diet → Fe chela’n therapy
⚠️ These pts should avoid Vit C v/c Vit C ↑ Fe absorp’n
Complica’ns
- T2D
- CHF
- cirrhosis
- bone loss
- hepatocellular carcinoma (HCC)
- hypogonadism → loss of libido + impotence in men
- Know for OSCE *
Till what age is newborn still considered a neonate ✓
Till 28 days of life
Neonatal Jaundice ✓
Def - when neonate has serum bilirubin > 5 mg/dL or > 85.5 micromol/L
→ physiological jaundice = after first 24hrs of life + resolves spontaneously w/in 10 days = b/c of fetal hepatic + immaturity + their RBCs have a higher hemolysis rate than our RBCs
→ pathological jaundice = W/IN first 24hrs of life !
RFs
- breastfeeding
- low birth weight
- maternal diabetes
Eti for pathological jaundice based on timing
→ < 24 hrs = RBC pb i.e . . .
- rhesus hemolytic disease
- ABO hemolytic disease
- G6PD deficiency
- hereditary spherocytosis
→ > 14 days = non-RBC pb i.e. . .
- prematurity
- biliary atresia
- hypoTSH
- UTI / TORCH infec’n
- breast milk jaundice b/c components of breast milk inhibit the liver’s + inadequate breastfeeding may lead to slow passage of stools hence ↑ing absorp’n of bilirubin in intestines
Ix’s
- transcutaneous bilirubin (TcB) = screening that all newborns get 24-48 hrs after birth (for newborns that are visibly jaundiced it has to be w/in 24 hrs of birth !)
- ttl serum bilirubin for diagnosis
- FBC + blood film to r/o polycythemia
- conjugated bilirubin b/c elevated levels indicate hepatobiliary cause
- blood type testing of mother + baby to r/o ABO or rhesus incompatibility
- direct Coombs Test to see if mom has ABO or Rh antibodies
- G6PD levels to r/o G6PD deficiency
- TFTs to rule out hypothyrodisim as cause
- blood + urine cultures if infec’n = suspected
Tx = plot ttl bilirubin levels on Tx threshold charts
→ Tx op’ns = phototherapy or exchange transfus’n which involve removing blood from baby + replacing it w/ donor blood
⟹ phototherapy converts unconjugated bilirubin into soluble isomers that can be excreted in urine w/o requiring liver conjuga’n
1. remove baby’s clothing down to diaper to expose skin + eye patches to protect eyes
2. light-box shines blue light on baby’s skin (little or no UV light = used)
3. once phototherapy = complete, rebound bilirubin = measured 12-18 hrs later
→ side effect = bronze baby syndrome
Complica’n = kernicterus = brain damage due to high bilirubin levels b/c bilirubin can cross BBB → leads to permanent damage i.e cerebral palsy, deafness + learning disability
Gesta’nal Immune Thrombocytopenia ✓
= diagnosis of exclus’n, other competing diagnosis = ITP
→ there’s no Ix to differentiate btw the 2 but if pt had thrombocytopenia prior to being pregnant, then we can r/o gesta’nal ITP whereas Hx of past pregnancies complicated by thrombocytopenia makes it a very likely diagnosis
Pathophys - autoantibodies against platelet glycoproteins i.e GPIIb/IIa + GPIb/IX → circulating platelets = destroyed → thrombocytopenia
SSX = bleeding w/o any identifiable cause
Ix = FBC → will show thrombocytopenia
Only treat if pt = symptomatic
→ Tx = IVIG + corticosteroid
Hemolytic Disease of the Fetus + Newborn (HDFN) ✓
Def - when Rh -ve pregnant woman carries Rh +ve baby for the 2nd time OR she was transfused w/ RhD antigen
Pathophys - memory B lymphocytes await reappearance of RBCs containing RhD antigen i.e subsequent pregnancy of Rh +ve baby
→ when challenged by those RBCs, the B lymphocytes differentiate into plasma cells + produce IgG
→ maternal IgG crosses placenta + attaches to fetal RBCs that have expressed RhD antigen
→ those RBCs are then sequestered by macrophages of the fetus’ spleen
→ extravascular hemolysis occurs → splenomegaly → portal HTN → can lead to hydrops fetalis
⟹ antibodies aginst RhD antigen usually develop after 28th wk of gesta’n or postpartum
Ix’s
- maternal blood type b/c we need to know if she’s Rh -ve
- maternal serum Rh antibody screen (in 2nd pregnancy) → will be elevated (assuming previous pregnancy was Rh + ve baby or she was transfused w/ Rh +ve blood)
Tx = prophylactic 500 IU anti-D @ 28 + 34 wks gesta’n for pregnant Rh -ve women
Hemorrhagic disease of the newborn ✓
Def - bleeding in 1st days of life
Pahtophys - Vit K deficiency b/c their guts don’t have bacteria to make Vit K yet → defective γ-carboxyla’n of glutamate residues of clotting factors 2, 7, 9 + 10 → elevated PT → hemorrhagic disease of the newborn
Neonatal Immune thrombocytopenia ✓
= diagnosis of exclus’n
SSX
- sudden appearance of petechial rash
- sudden appearance of bruising and / or bleeding but child is otherwise healthy
→ 60% of children w/ ITP have previous Hx of viral illness
→ most children w/ ITP recover spontaneously after 3-6 months but 20% will develop chronic ITP
Sjogren syndrome ✓
Def - chronic inflammatory autoimmune disorder characterized by ↓ in lacrimal + salivary gland secre’n
RFs
- RA
- SLE
- middle age women
- scleroderma / systemic sclerosis
Eti
→ 1° = occurs spontaneously
→ 2° = due to RA or SLE
SSX
- dry eyes
- xerostomia i.e dry mouth
- jt pain + stiffness
Ix’s
- Schrimer’s test → insert folded filter paper under lower eyelid w/ end hanging out
⟹ +ve if if < 5 mm of paper is wet after 5 mins
- salivary gland Bx
- anti Ro / SSA + anti La / SSB → will be +ve
- rheumatoid factor might be +ve but obviously it’s not RA
Tx based on SSX
- dry eyes = artificial tears → ciclosporin drops → cholinergic drug such as pilocarpine
- dry mouth = salivary substitute such as fluoride gels, saliva-stimulating lozenges or chewing gums
- MSK SSX = NSAIDs for pain → DMARD → oral corticosteroid
- vasculitis = corticosteroid → Iv Ig → rituximab
Complica’ns
- oral thrush
- dental cavities
- blepharitis
- corneal ulcers
- keratoconjunctivitis sicca
- Know for OSCE *
Polymyositis / Dermatomyositis ✓
Def - idiopathic autoimmune disorder that causes muscle inflamma’n
RFs
- female
- black
- children or > 40 y/o
Eti
- cancer
- viral infec’ns such as Coxsackie or HIV
Diagnostic criteria
- Progressive, symmetrical, proximal muscle weakness
- Muscle Bx shows necrosis / phagocytosis / regenera’n / inflamma’n
- Elevated Creatine Kinase or Aldolase
- Electromyography typical findings
- One of the following skin Δs . . .
- Gottron les’ns / papules = purple papules on knuckls, elbows or knees
- heliotrope rash on face / eyelids
- periorbital edema
- photosensitive erythematous rash on back, shoulders + neck
→ SSX 1-4 present = polymyositis
→ SSX 1-5 present = dermatomyositis
Ddx = other things that cause elevated creatine kinase
- MI
- AKI
- rhabdomyolysis (in rhabdo CK will be ≥ 10,000)
- statin use
- strenuous exercise
Ix’s
- muscle Bx
- creatinine kinase + aldolase → ≥ 1 of the 2 will be elevated b/c = released by inflamed muscle tissue
- ANA → often +ve but not always
- Jo 1 antibody → will be +ve
Tx = corticosteroid + photoprotec’n if there’s skin involv’nt
Antiphospholipid syndrome ✓
Def - when pt persistently has elevated antiphospholid antibodies
→ can be lupus anticoagulant, anti cardiolipin antibody and/or anti β2 glycoprotein 1 so test all 3 antibodies !
RFs
- SLE
- auto immune disease
- auto immune + rheumatological disease
Eti = 1° or 2° to SLE
SSX
- migraine
- livedo reticularis (usually in young white women)
- pregnancy morbidity i.e loss of ≥ 3 embryos before 10th wk of gesta’n
Complica’ns
- stroke
- MI
- P.E / DVT
- pre eclampsia
- pregnancy loss
- placental abrup’n
- TIA / ischemic stroke
Tx = long term warfarin to prevent thrombosis or LMWH + aspirin instead if pt = pregnant
SLE ✓
Def - chronic multisystem autoimmune disorder
RFs
> 30 y/o
- female
- African descent but living in Europe / U.S
Eti
- regular lupus
- neonatal lupus = SLE in pregnant woman + anti SSA / Rho = +ve
→ SSX = cytopenia + transaminitis + heart block + diffuse or peri-orbital rash - drug induced lupus (“SHIPP MT”)
→ Sulfonamides
→ Hydralazine
→ Isoniazid
→ Procainamide
→ Phenytoin
→ Minocycline
→ TNF 𝛼 inhibitors
SSX (need ≥ 4)
- oral ulcers
- leukopenia
- lymphopenia
- renal dysfunc’n
- photosensitive rash
- malar butterfly rash
- non erosive polyarthritis
- discoid rash (on head + neck)
+ve anti dsDNA / anti smith / anti phospholipid antibodies
Ix’s
- ANA (most SENSITIVE but NOT specific for lupus i.e by itself can’t diagnose lupus but should definitely make us suspect lupus especially if pt has SSX b/c it’s the antibody that’s most commonly +ve in lupus)
→ = Ix that we use to r/o lupus since it’s the most sensitive
→ can also be +ve in RA, EBV, TB, Hep C or even in perfectly healthy person - anti dsDNA → if +ve it means there’s renal involv’nt i.e lupus nephritis = most SPECIFIC for lupus hence is used for diagnosis
- C3/C4 → both will be low
- anti-smith → if +ve u can diagnose lupus but very few lupus pts will have a +ve anti-smith
- anti histone → if +ve it means it’s drug induced lupus
- anti cardiolipin antibody or some other anti phospholipid antibody → could be +ve if pt also has antiphospholipid syndrome
- APTT → might be prolonged if pt also has antiphospholipid syndrome
- U + E → elevated urea + Cr due to renal dysfunc’n
Tx = hydroxychloroquine + lifestyle Δs → add corticosteroids if there’s skin manifesta’ns or lupus nephritis → add immunosuppressant if there’s hematological manifesta’ns
Lifestyle Δs
- sunscreen use
- smoking cessa’n
- contraceptive pill use
- cardio-protective diet i.e high fish oil + low saturated fat
Complica’ns
- anemia of chronic disease
- leukopenia
- thrombocytopenia
- lupus nephritis
- anti phospholipid syndrome = ↑ in coagulability → ↑ in risk of DVT, thrombotic events, pregnancy loss, pre-mature birth
- Know for OSCE *
Vasculitis ✓
Def - chronic blood vessel inflamma’n
RFs = white + > 50 y/o
Eti = large, medium or small vessel vasculitis
Systemic SSX
- fever
- malaise
- myalgia
- arthralgia
Small vessel SSX
- hematuria
- palpable purpura
- otorrhea / ear pain / muffled sensa’n in ears
- nasal discharge / epistaxis / nasally ulcers / sinus pain / wheeze
Medium vessel SSX
- abdominal pain
- cutaneous ulcers
- foot and/or wrist drop
Large vessel SSX
- vis’n loss
- carotid bruits
- asymmetric brachical pusles
- upper extremity or jaw claudica’n
Ix’s
- ESR / CRP → will be elevated
- ANCA auto antibody → will be +ve
- urinalysis to check for hematuria
- Bx of affected tissue → will show vessel wall necrosis, fibrinoid necrosis, RBC extravasa’n + karyorrhexis i.e fragmenta’n of nucleus + break up of chromatin into unstructured granules
Tx = corticosteroid
Complica’n = aortic aneurysm
Raynaud’s phenomenon ✓
Def - painful physical response to cold temps
RFs
- female
- FHx
- connective tissue disorder
Eti
1° = not due to underlying disorder
2° = due to underlying disorder such as SLE or scleroderma
Pathophys - cold temp → vasospasm → digits initially turn pale due to vasoconstric’n → then turn blue due to cyanosis → then turn red once reperfused
Tx = keeping hands warm + CCB such as nifedipine
⚠️ These pts should avoid β blockers b/c can make their SSX worse !
Complica’n = ischemic digit
Systemic sclerosis / Scleroderma ✓
Def - autoimmune condi’n involving inflamma’n + fibrosis of connective tissues, skin + internal organs
→ has high morbidity + mortality
SSX = (“CREST”)
- Calcinosis → Ca deposits under skin (usually on fingertips)
- Raynaud’s → MUST BE PRESENT TO DIAGNOSE !
- Esophageal dysmotility
- Sclerodactyly i.e hardening of skin on hand that causes hand to have claw shape
- Telangectiasia i.e broken blood vessels on skin
⚠️ If pt has scleroderma SSX but all antibodies = -ve suspect malignant condi’n called paraneoplastic scleroderma !
Types
- Limited cutaneous systemic sclerosis → SSX = CREST
- Diffuse cutaneous systemic sclerosis = CREST SSX + internal organ involv’nt such as CAD / HTN / pulm. fibrosis / scleroderma renal crisis (= medical emergency that presents w/ severe HTN + renal failure)
Ix’s
- serum auto antibodies → +ve ANA in 90% of pts
- anti-centromere antibodies → most often associated w/ limited cutaneous systemic sclerosis
- anti-Scl-70 antibodies → most often associated w/ diffuse cutaneous systemic sclerosis
Emergency Tx for scleroderma renal crisis = ACE-Is → any addi’nal anti-hypertensive → renal dialysis or transplant
Regular Tx
- DMARDs + rituximab
- avoiding smoking
- gentle skin stretching to maintain ROM
- regular emollients
- avoiding cold triggers (for Raynaud’s)
Complica’ns
- skin ulcers
- hypoTSH
- heart / lung / kidney involv’nt
- Know for OSCE *
Erythema Nodosum ✓
Def - delayed-type hypersensitivity rxn that presents w/ erythematous, tender nodules on shins due to inflamma’n of subq fat
→ overtime nodules settle + become bruises
Triggers
- TB
- gastroenteritis
- streptococcal throat infec’ns
- drugs such as NSAIDS or OCP
- pregnancy
- malignancy
- inflammatory condi’ns such as IBD or sarcoidosis
SSX = red, inflamed, subcutaneous nodules across both shins
Ix’s to see if idiopathic or due to underlying disease
- throat swab for strep
- CXR to r/o TB + sarcoidosis
- stool microscopy + culture to r/o campylobacter + salmonella
- fecal calprotectin for IBD
Tx = supportive b/c usually resolves spontaneously w/in 6 wks
- rest
- leg eleva’n
- NSAIDs → K iodide → intrales’nal cortisteroid injec’n
Erythema Multiforme ✓
Def - mild, self-limiting, Ψly recurring mucocutaneous inflammatory condi’n = hypersensitivity rxn
RFs
- herpes simplex virus
- mycoplasma pneumonia
Eti
- viral infec’n
- drugs
SSX
- widespread itchy les’ns that resemble a bull’s eye
→ erupt over 24 - 48 hrs + last 1-2 wks
Ix = clinical diagnosis
Tx = topical emollient → topical or oral corticosteroid
1° immune deficiency ✓
1- Def, RFs, Eti, Pathophys, SSX, Diagnostic Criteria, Ddx, Ix, 1st line Mx, Complica’ns
2- What features of a clinical Hx might lead you to suspect 1° immune deficiency
1)
Types
- Antibody deficiencies = 50% of cases
→ pts = more susceptible to . . . - C. fetus
- S. aureus
- M. hominis
- H. influenzae
- P. aeruginosa
- enteroviruses
- U. ureolyticum
- N. meningitidis
- S. pneumoniae
- G. lamblia protozoa
a) Selective IgA deficiency (= asymptomatic)
→ lack of serum + mucosal IgA but normal IgG + IgM
→ most pts = asymptomatic but are at ↑ed risk of mucosal infec’ns especially viral ones + at ↑ed risk of having anaphylactic rxn to blood products
b) X linked agammaglobulinemia
→ B cells + ALL Igs = completely absent OR very low
→ age of onset = 6-12 months (affects males mainly)
→ Tx = IVIG therapy to prevent infec’ns + bronchiectasis
c) CVID (common variable immunodeficiency)
→ onset = any age
→ pts might have auto-antibodies + SLE
→ pts will have recurrent sino-pulmonary infec’ns + consequentially bronchiectasis
→ serum IgG + IgA = low in ALL pts + serum IgM = low in 50% of pts
→ Tx = IVIG therapy + prophylactic Abx
- B cell deficiencies
→ cause ↑ed susceptibility to enterovirus + encapsulated bacteria infec’ns - Cellular / T cell deficiencies
→ pts = more susceptible to . . . - S. typhi bacteria
- Non tuberculous mycobacterium including BCG
- C. albicans, H. capsulatum, A. fumigatus + C. immitis fungi
a) DiGeorge syndrome (AD) = contiguous gene dele’n involving 22q11.2 reg’n on 1 copy of chromosome 22
→ causes defects in 3rd + 4th pharyngeal arches
→ pt will have almost completely absent T cells due to thymic hypoplasia
→ SSX (“CATH”):
- Congenital Cardiac defects
- Abnormal / dysmorphic facial features i.e narrow palpebral features, hypertelorism (↑ed distance btw eyes), micrognathia (smaller than normal jaw), cleft palate, low set ears, fish shaped mouth
- Thymic hypoplasia
- HypoCa due to no parathyroid glands → may present as neonatal seizures
> Wiskott Aldrich syndrome (X-linked) → causes “ERT” i.e severe Eczema, Recurrent bacterial infec’ns + Thrombocytopenia (pt will have petechiae)
b) Ataxia-Telangiectasia → SSX . . .
- progressive cerebellar ataxia that starts at early age
- telangiectasia in ear lobes + conjunctivae
(“ spider veins “ i.e broken blood vessels) → develops after 2 y/o
- SCID (Severe Combined Immunodeficiency) = only 20% of immunodeficiency cases but are the most severe
→ disturbs develop’nt + func’n of BOTH T cells + B cells + can lead to early death in the 1st yr of life
→ 50% = X-linked + the ones that are autosomal recessive are due to muta’ns in the genes for T cell receptor signaling such as JAK3 (Janus kinase 3), ADA (Adenosine Deaminase) + ZAP70 kinase (zeta-chain protein kinase 70)
→ pts will have the following SSX :
- weight loss
- chronic diarrhea
- persistent candidiasis
- low ttl lymphocyte count
- recurrent SEVERE infec’ns
- absent thymic shadow on X-ray
- failure to thrive due to hypermetabolism
⚠️ Present thymic shadow doesn’t r/o SCID !
→ pts = more susceptible to . . .
- ALL viruses
- P. carinii + T. gondii protozoa
- L. monocytogenes, S. typhi + enteric flora bacteria
- same bacteria as antibody deficiency + same myobacterium + fungi as cellular deficiency
→ these pts have to be isolated in +ve pressure to eliminate risk of infec’n
→ Tx = early diagnosis obviously + bone marrow transplant before they start school
- Phagocyte deficiencies = 18% of cases
→ pts often present w/ infec’ns of the skin + reticuloendothelial system
→ pts = more susceptible to . . . - P. carinii protozoa
- A. fumigatus + C. albicans fungi
- Non tuberculous mycobacterium including BCG
- S. aureus, P. aeruginosa, S. typhi, N. asteroides + enteric flora bateria
- Complement deficiencies
→ pts often present w/ blood borne infec’ns caused by encapsulated bacteria such as bacteremia + meningitis
→ pts = more susceptible to same bacteria as antibody deficiency ESPECIALLY N. meningitidis
a) C1 esterase inhibitor deficiency → AD disorder that will cause recurrent episodes of well-demarcated angioedema w/o urticaria (most commonly affects skin or mucosal tissues of upper resp. + Gl tracts
→ pathophys → inhibits classical pathway + bradykinin inflammatory pathway ∴ resulting in agnioedema b/c of excess produc’n of bradykinin which is a potent vasodilatory mediator
⟹ can be precipitated by trauma-dental work, opera’ns or infec’ns
b) Hereditary Angioedema (HAE) → AD disorder caused by defective gene on chromosome 11
→ leads to non-painful, non-pruritic + non-pitting edema
⟹ edema in the larynx can lead to asphyxia’n + abdominal anigoedema attacks require Sx
⟹ Tx = purified C1 inhibitor by slow IV infus’n, FFP (fresh frozen plasma) in case of emergency, tracheostomy in sig laryngeal edema + selective bradykinin B2 receptor antagonist for acute HAE in adults
→ Type 1 = low C1 inhibitor + low C4 + C2
→ Type 2 = dysfunc’nal C1 but normal or elevated in level + low C4 + C2
→ Type 3 = mutat’n of clotting factor 12
→ disinhibits bradykinin pathway → C4 + C1 inhibitor levels will be normal
2) SSX that should make u suspect 1° immunodeficiency . . .
- pt needs IV Abx to clear infec’ns
- FHx of 1° immunodeficiency
- recurrent deep skin or organ abscesses
- persistent mouth thrush or fungal skin infec’n
- infant fails to gain weight or grow normally
> 4 new ear infec’ns w/in 1 yr
> 2 pneumonias w/in 1 yr
> 2 months on Abx w/ little effect
> 2 serious sinus infec’ns w/in 1 yr
> 2 deep-seated infec’ns including septicemia
COVID ✓
Def - acute infectious respiratory disease caused by SARS-Cov2
RFs
- T2D
- CVD
- CKD
- HTN
- male
- obesity
- smoking
- older age
- pregnancy
- immunosuppres’n
- respiratory disease
- residing in long term facility
- contact w/ possible or confirmed case
SSX
- fever
- cough
- dyspnea
- altered sense of taste / smell
Ix’s
- RT PCR → will be +ve
- rapid antigen test → will be +ve
Tx = self limiting but treat SSX as needed i.e anti pyretics, analgesics
Complica’ns
- AKI
- DIC
- thrombosis
- resp. failure
- cardiac arrest
- Know for OSCE *
Influenza ✓
Def - self-limiting acute respiratory tract infec’n caused by ssRNA viruses influenza A or B
→ transmitted through respiratory droplets i.e coughing / sneezing / talking
→ goes away in 10 days
RFs
≥ 65 y/o
- T2D
- CKD
- pregnancy
- immunosuppres’n
- healthcare worker
SSX
- fever
- dry cough
- fatigue
- HA
- sore throat
- jt / muscle ache
⚠️ Flu SSX v.s common cold SSX
- abrupt SSX onset v.s gradual onset
- fever v.s no fever
- pt feels wiped out v.s pt feels fine
Ix = rapid throat or nasal swab or PCR (more accurate)
Regular Tx = vaccine for Ppx but is self limiting
Tx for pts at risk of influenza complica’ns = Oral oseltamivir OR inhaled zanamivir (both are bd for 5 days)
→ Tx should be started w/in 48 hrs of onset of SSX
Complica’ns
- otitis media
- sinusitis
- bronchitis
- encephalitis
- viral pneumonia
- febrile convuls’ns (in young children)
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HIV / AIDS ✓
Def - infec’n caused by retrovirus = retrovirus b/c encodes reverse transcriptase enzyme
→ inherently error-prone ∴ has high rate of muta’n which is why there’s often the pb of resistance
→ can be transmitted through bodily fluids i.e blood, sperm + breast milk
→ 10-20% of ppl w/ HIV in the UK = undiagnosed
RFs
- needle stick injury
- high maternal viral load
- IV drug use + needle sharing
- unprotected receptive anal sex
- unprotected receptive vaginal sex
Pathophys - virus gains entry into cells by attaching to CD4 receptor + co-receptor (CCR5 or CXCR4) via its envelope glycoproteins
→ once integrated into host DNA, virus resides in nucleus of infected cells + can remain quiescent for extended periods of time OR can become transcriptionally active + use human host cell machinery to replicate itself
→ viral RNA + proteases take over hence we see ↓ in CD4 T cells
SSX
- fever
- diarrhea
- weight loss
- skin rashes
- night sweats
- uveitis sometimes
- oral ulcers / angular chelitis / oral thrush
Ix’s
- serum HIV ELISA → will be +ve
- serum HIV rapid test → will be +ve
- CD4 count = monitored every 3-6 months in early disease + every 2-3 months in late disease
> 500 = asymptomatic
< 350 = immunosuppressed
< 200 = AIDS - HIV RNA / viral load to monitor if Tx is working
Tx for everyone
- antiretroviral therapy (ART) = triple therapy i.e 2 nucleotide reverse transcriptase inhibitors / NRTIs (tenofovir + emtricitabine) + third agent such as (bictegravir = protease inhibitors that target HIV’s protein processing)
- pre exposure ppx for high risk adults = emtricitabine + tenofovir disoproxil = taken before + after sex in . . .
→ men or transgender individuals who have sex w/ men
→ HIV -ve sexual partners of HIV +ve individuals w/ detectable or unknown viral load unless the partner has been on ART for ≥ 6 months + viral load is < 200
⟹ if taken as prescribed chance of being infected wi/ HIV via sexual intercourse by up to 99%
- post exposure ppx for 28 days
- yrly cervical cancer screening
- avoiding live vaccines but being up to date on all vaccines that they can get
- moms should avoid breastfeeding
Addi’nal Tx / Mx
- pt w/ AIDS = given co-trimoxazole to protect against PCP (pneumocystis jirovecii pneumonia)
Complica’ns :
- Kaposi sarcoma = neoplasm of vascular endothelial cells due to herpes virus 8 (usually occurs in immuno-compromised pts or pts w/ poorly controlled HIV but can also occur spontaneously in men of Eastern European descent + Sub-Saharan Africans)
→ progresses from patch to erythematous (red or purple) cutaneous plaques in lower extremities / face / oral mucosa / genitalia
→ on Bx we’ll see proliferating spindle cells forming slit-like spaces filled w/ blood
→ can affect GI + pulm. systems ∴ should do screening for occult GI bleed via occult blood test + for pulm. les’ns via CXR - AIDS opportunistic infec’ns
→ Cryptosporidium = genus of protozoal pathogens that cause watery diarrhea + abdo. cramps
⟹ other SSX include . . .
- N/V, fever, weight loss, SSX of dehydra’n i.e ↓ed skin turgor + dry mucous membranes, orthostasis
= mild + self-limiting in immuno-competent pts but severe + life-threatening if immunocompromised
⟹ diagnosis = made by stool antigen test or by detec’n of luminal oocysts via acid-fast staining
⟹ Bx of colon + then light microscopy on acid-fast stain will show cryptosporidiosis i.e small, round oocysts on colonic epithelial surface
⟹ Tx = supportive i.e fluids, electrolytes + anti-parasitic therapy
→ Candida albicans
⟹ causes oral thrush + esophagitis
⟹ staining w/ Gomori methenamine Ag or periodic acid-Schiff will show pseudohyphae + budding yeasts
→ Cryptococcus neoformans
⟹ can cause meningitis in AIDS pts
⟹ staining w/ India ink or mucicarmine will show encapsulated yeast w/ narrow-based budding
→ CMV (= herpes virus 5)
⟹ can cause esophagitis, pneumonia + retinitis in AIDS pts
⟹ diagnosis = made w/ ELISA to detect anti-CMV Ig + PCR amplifica’n of viral DNA
⟹ light microscopy might show intracellular inclus’n bodies known as Cowdry bodies
→ MAC (Myobacterium avium complex)
⟹ causes atypical pneumonia + GI infec’ns in AIDS pts
⟹ light microscopy will show acid-fast, periodic acid-Schiff +ve bacilli
⟹ pts w/ AIDS = given azithromycin for MAC Ppx
- Know for OSCE *
General STI Mx ✓
- Tx
- full screening for other STIs
- advice about avoiding sexual activity until STI = treated
- contact tracing
- preven’n of future infec’ns
Chlamydia ✓
Def - most common STI in the UK
RFs
- previous STI
- unprotected sex
< 25 y/o + sexually active
- having sex w/ infected partner
- new sex partner
- multiple sex partners
Eti - Chlamydia trachomatis = gram -ve intracellular bacterium ∴ enters + replicates w/in cells before rupturing cell
→ it’s due to this unique life cycle that it can’t be cultured on artificial media
SSX in women
- asymptomatic
- dysuria
- pelvic pain
- cervical inflamma’n
- abnormal vaginal bleeding
- yellow, cloudy vaginal discharge
SSX in men
- dysuria
- penile discharge
Ix = nucleic acid amplifica’n test (NAAT) for diagnosis → will be +ve
⟹ sample can be collected via . . .
- vulvovaginal swab
- endocervical swab
- 1st catch urine sample
- urethral swab (in men)
- rectal swab (after anal sex)
- pharyngeal swab (after oral sex)
Tx = doxycycline OR erythromycin instead if pt = pregnant or breastfeeding
→ MOA of doxycycline = tetracycline AB - inhibit 30S subunit ∴ inhibit bacterial protein synthesis ∴ is a bacteriostatic AB
⟹ side effects - GI distress, abd. discomfort, photosensitive rash
⟹ C/I = pregnancy b/c of risk of hepatotoxicity to mother, children < 8 y/o due to permanent yellow / brown discolora’n of fetal teeth + impairment of long bone growth
⟹ should not be taken w/ Fe, Ca or Mg b/c they chelate w/ tetracyclines ∴ preventing adequate absorp’n
⟹ end in “CYCLINE”
Complica’ns
- LGV
- cervical cancer
- reactive arthritis
- PID if left untreated + infec’n ascends
- ectopic pregnancy (as a result of the PID)
- infertility in women if infec’n ascends (as a result of the PID)
- epididymitis + prostatitis in men if infec’n ascends
Complica’ns in pregnancy
- infants born to women w/ untreated chlamydia = @ risk of neonatal conjunctivitis + pneumonia
- PROM
- Low birth weight
- Preterm delivery
Who gets chlamydia screening ?
- every sexually active person < 25 y/o annually or when they change sexual partner
→ everyone that tests +ve gets retested 3 months after Tx
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Gonorrhea ✓
Def - STI caused by Neisseria gonorrhea = gram -ve diplococcus bacterium
→ infects mucous membranes w/ columnar epithelium i.e endocervix urethra, rectum, conjunctiva + pharynx
→ spreads via contact w/ mucous secre’ns from infected area
→ due to unique life cycle can’t be cultured on artificial media
RFs
- black
- 20-29 y/o
- unprotected sex
- having another STI
- men who have sex w/ men
- multiple recent sex partners
SSX in men
- dysuria
- epididymo-orchitis
- odorless green / yellow penile discharge
SSX in women = often asymptomatic but can sometimes present w/ . . .
- dysuria
- pelvic pain
- green / yellow vaginal discharge
Ix’s
- NAAT → will be +ve for gonorrhea DNA or RNA
- culture = definitive diagnosis test → will show +ve chocolate agar culture
- charcoal endocervical swab should be taken for microscopy, culture + AB sensitivities before initiating AB Tx = important due to high rates of AB resistance
Tx
1. Single dose of IM ceftriaxone if sensitivities are NOT known OR single dose of oral ciprofloxacin 500mg if sensitivities = known
2. F/u test of cure w/ NAAT testing if pt = asymptomatic + w/ culture instead if pt = symptomatic
→ do culture 72 hrs after Tx
→ do RNA NAAT 7 days after Tx
→ do DNA NAAT 14 days after Tx
Complica’ns
- PID if left untreated + infec’n ascends
- ectopic pregnancy (as a result of the PID)
- chronic pelvic pain (as a result of the PID)
- infertility in women if infec’n ascends (as a result of the PID)
- Disseminated gonococcal infec’n (DGI) → SSX = tenosynovitis, migratory polyarthritis + dermatitis
→ can lead to Fitz Hugh Curtis syndrome
Pregnancy complica’n = gonococcal conjunctivitis in neonate = contracted from mother during birth
→ neonatal conjunctivitis i.e ophthalmia neonatorum
= medical emergency characterized by sepsis, eye perfora’n + blindness !
- Know for OSCE *
Syphilis ✓
Def - STI caused by Treponema pallidu bacterium = spiral shaped bacteria
→ transmitted by contact w/ infected area whether through oral, anal or vaginal sex
→ incuba’n period = 21 days on avg
RFs
- sex worker
- illicit drug use
- HIV or other STI
- unprotected sex
- multiple sex partners
- having syphilis during pregnancy
- sexual contact w/ infected person
Eti
- congenital syphilis = pregnant pt w/ syphilis gives it to baby during pregnancy
- 1° syphilis = single painless chancer @ original site of infec’n + local lymphadenopathy → heals spontaneously
- 2° syphilis = 4-8 wks after 1° syphilis infec’n = when it spreads via blood → leads to wide spread vasculitis → SSX = condylomata lata (grey wart-like les’ns around genitals + anus), low-grade fever + lymphadenopathy → SSX resolve 3-12 wks later but pt can enter latent syphilis stage = when pt becomes asymptomatic despite still being infected
- 3° syphilis = latest stage
→ gummatous les’ns + neuro + cardio SSX → can occur yrs after initial infec’n
Neurosyphilis - can occur @ any stage if infec’n reaches CNS + presents w/ . . .
- HA
- paralysis
- altered behavior
- ocular syphilis (affecting the eyes)
- tabes dorsalis = demyelina’n affecting posterior columns of spinal cord
SSX
- uveitis
- fatigue
- diffuse rash
- lymphadenopathy
- rhinitis + hepatosplenomegaly in congenital syphilis
- painless ulcer (chancer) in anogenital reg’n = hallmark sign of 1° syphilis
Ix’s
- antibody test for screening
- PCR or dark field microscopy of swab from les’n for diagnosis
→ will show coiled spirochaete bacterium w/ a corkscrew appearance + motility - treponemal serology tests = +ve for life ∴ could be past or active infec’n
- non treponemal serology tests → +ve means active infec’n
- rapid plasma reagin (RPR) + VDRL test = SENSITIVE but not specific = used to assess if pt has active syphilis infec’n
→ higher # = > chance that pt has active disease
Tx = single dose of IM benzathine benzylpenicillin
→ MOA - inhibits bacterial cell wall synthesis
Complica’ns
- HIV
- Jarisch Herxheimer rxn = rxn that occurs w/in first 24 hrs of AB therapy due to rapid killing of treponemes
→ SSX = HA, acute fever + myalgia
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HPV / Genital warts ✓
Def - STI caused by HPV 6 + 11
→ peak incidence = 16-25 y/o
RF = intercourse @ an early age
Eti - HPV = non enveloped dsDNA
Ix = clinical diagnosis
Tx = Podophyllotoxin gel to affected areas or cryotherapy / acetic acid / surgical excis’n (in non pregnant + non immunocompromised pt !)
- Know for OSCE *
Trichomoniasis ✓
Def - STI caused by protozoan trichomonas vaginalis, most common nonviral STI worldwide, affects females more than males
→ requires genitourinary medicine referral
SSX (50% of cases = asymptomatic) . . .
- itching
- dysuria
- vaginal discharge
- dyspareunia
Diagnostic Ix = charcoal swab w/ microscopy
→ in women swab should be taken from posterior fornix of vagina i.e behind cervix
→ in men use urethral swab or first catch urine
Tx = metronidazole + contact tracing
Complica’n = can ↑ risk of . . .
- BV
- PID
- cervical cancer
- contracting HIV by damaging vaginal mucosa
- pregnancy-related complica’ns such as preterm delivery
- Know for OSCE *
PID ✓
Def - acute ascending polymicrobial infec’n of female gynecological tract frequently associated w/ Neisseria gonorrheae or Chlamydia trachomatis
→ begins in cervix + if untreated can ascend to upper genital tract
Subtypes
- endometritis = inflamma’n of endometrium
- salpingitis = inflamma’n of fallopian tubes
- oophoritis = inflamma’n of ovaries
- parametritis = inflamma’n of parametrium = connective tissue around uterus
- peritonitis i.e inflamma’n of peritoneal membrane
Eti
- Neisseria gonorrhea → tends to produce more severe PID
- Chlamydia trachomatis
- Mycoplasma genitalium
RFs
- IUD use
- prior history of PID
- onset of intercourse at young age
- prior chlamydia or gonnorhea infec’n
- unprotected intercourse w/ multiple sexual partners
SSX
- Pelvic or lower abdominal pain
- abnormal vaginal discharge
- abnormal bleeding
- dyspareunia
- fever
- dysuria
SSX on exam
- pelvic tenderness
- inflamed cervix
- cervical excita’n / mo’n tenderness
Ix’s
- NAAT swabs for gonorrhea + chlamydia
- NAAT swabs for Mycoplasma genitalium if available
- HIV test
- syphilis test
- high vaginal swab to look for BV, candidiasis + trichomoniasis
- microscopy → absence of pus cells = can r/o PID
- pregnancy test to r/o ectopic pregnancy
- CRP + EST → will be elevated
Tx for mild to moderate = ceftriaxone + doxycycline + metronidazole + treat sexual contacts as well (don’t wait for swab to start Tx)
Tx for severe = admit for IV Abx + then switch to oral Abx once pt can tolerate PO
Complica’ns
- sepsis
- infertility
- tubo ovarian abscess
- chronic pelvic pain
- ectopic pregnancy
- Fitz Hugh Curtis syndrome = adhes’ns btw liver + peritoneum due to infec’n + inflamma’n of Glisson’s capsule (liver capsule)
- Know for OSCE *
Bacterial Vaginosis ✓
Def - overgrowth of anaerobic bacteria in vagina + loss of lactobacilli bacteria
→ NOT sexually transmitted
RFs
- Cu coil
- smoking
- recent Abx use
- multiple sexual partners
- excessive vaginal cleaning such as douching or using vaginal cleaning products
Eti = anaerobic bacteria
→ Gardnerella vaginalis (most common)
→ Mycoplasma hominis
→ Prevotella species
Pathophys - lactobacilli bacteria produce lactic acid in vagina → keeps vaginal pH < 4.5 → BV causes loss of these good bacteria → vaginal pH ↑ → alkaline env’nt enables anaerobic bacteria to multiply
SSX = watery grey / white vaginal discharge w/ fishy smell
→ usually more noticeable after menses or intercourse
Ix = vaginal swab for pH + microscopy
→ normal vaginal pH = 3.5-4.5 so pH > 4.5 = suggestive of BV
→ microscopy will show clue cells
No Tx for asymptomatic BV
Tx for symptomatic = metronidazole orally or by vaginal gel = nitroimidazole AB that damages bacterial DNA
⚠️ pts should not drink alcohol while on Tx b/c can cause disulfiram-like rxn w/ N+V, flushing + sometimes more severe SSX such as shock + angioedema
Complica’n = can ↑ susceptibility to chlamydia, gonorrhea + HIV
Complica’ns during pregnancy
- PROM
- miscarriage
- preterm delivery
- chorioamnionitis
- low birth weight
- postpartum endometritis
- Know for OSCE *
Vaginal thrush (vulvovaginal candidiasis) ✓
Def
RFs
Eti
Pathophys
SSX
- thick, white vaginal discharge
- itchiness around vagina
- soreness / pain during sex or urina’n
Ix
Tx
Complica’ns
- Know for OSCE *
Herpes simplex virus ✓
Def - virus that causes cold sores / oral herpes (herpes labialis) + genital herpes (STI)
→ oral herpes / cold sores = caused by HSV-1
→ genital herpes = caused by HSV-1 or HSV-2
RFs
- HIV infec’n (RF for clinical disease)
- immunosuppressive drugs (RF for clinical disease)
- high risk sexual behavior (RF for seropostitivity)
Eti - virus spreads through direct contact w/ affected mucous membranes or via viral shedding in mucous secre’ns
→ virus can be shed even pt is asymptomatic
Pathophys - after initial infec’n virus becomes latent in associated sensory nerve ganglia → pt can develop SSC months or yrs after initial infec’n when latent virus = reactivated
⟹ trigeminal nerve ganglion in oral herpes
⟹ sacral nerve ganglia in genital herpes
SSX chronology of oral herpes
1. tingling sensa’n
2. vesicular throat + mouth ulcers
3. ulcerative throat + mouth ulcers
SSX genital herpes (appear w/in 2 wks)
- genital ulcerative / blistering les’ns but can also cause mouth les’ns
- neuropathic type pain i.e tingling / burning / shooting pain
- fatigue
- HAs
- dysuria
- inguinal lymphadenopathy
→ if first time SSX can last 3 wks whereas in recurrent episodes, SSX = milder + resolve more quickly
Ix’s
- diagnosis can be made clinically but HSV PCR swab from les’n can confirm diagnosis + causative organism
- viral culture if les’ns = present → virus will be detected
Tx = aciclovir
→ MOA- inhibits DNA synthesis + viral replica’n
SSX Mx
- paracetamol
- topical vaseline or lidocaine 2% gel
- cleaning w/ warm salt water
- wearing loose clothing
- avoiding intercourse w/ SSX
Genital herpes + pregnancy → after an initial infec’n w/ genital herpes mom will develop antibodies to the virus → during pregnancy these antibodies can cross placenta → fetus has passive immunity + is protected during labor + delivery
Complica’n of genital herpes during pregnancy = baby contracting neonatal herpes simplex infec’n during labor + delivery
→ has high morbidity + mortality
⟹ Tx for 1st time genital herpes + pregnant = aciclovir + continue it from 36 wks onwards to ↓ risk of genital les’ns during labor + delivery
→ C-sec’n if pt = symptomatic
→ vaginal delivery if pt = asymptomatic + > 6 wks have passed since initial infec’n
⟹ Tx for recurrent genital herpes = prophylactic aciclovir from 36 wks onwards to ↓ risk of genital les’ns during labor + delivery
- Know for OSCE *
Chicken Pox ✓
→ highly contagious + usually occurs during childhood
→ incuba’n period ≈ 14 days (can range from 9-21 days)
RFs
- exposure to varicella
- 1-9 y/o
- non immunized
- occupa’nal exposure such as military recruits or ppl who work w/ children
Eti = Varicella zoster virus
Pathophys - susceptible person = exposed to virus either by direct contact w/ les’ns or through infected droplets i.e through coughing or sneezing
→ after contact, virus spreads to reg’nal lymph nodes = 1° phase
→ on days 4-6 infec’n spreads to liver, spleen + other cells w/in reticuloendothelial system
→ day 9 = 2° phase where mononuclear cells transport virus to skin + mucous membranes hence causing rash
→ virus = detectable in nasopharynx 1-2 days before onset of rash + pt is infectious @ this time
→ once ALL les’ns have crusted over pt is no longer infectious !
SSX
- fever (usually 1st SSX)
- malaise
- wide spread pruritic, vesicular rash that starts on trunk or face + spreads outwards
Ix = clinical diagnosis
Pts @ risk for moderate complica’ns
≥ 13 y/o
- pts w/ chronic skin disease such as atopic dermatitis
- pts w/ underlying pulmonary disease
- pts on long term salicylate therapy
- pts receiving short course or intermittent oral corticosteroids
Pts @ risk for severe complica’ns
- neonates
- pregnant women
- immunosuppressed pts
Tx for pts w/ moderate risk = oral aciclovir
Tx for pts w/ severe risk = IV aciclovir
Addi’nal Mx
- pts should not go to school for 5 days or until all les’ns are crusted over + should avoid high risk ppl during that time
- pts should trim nails, keep cool + use calamine lotion for itchiness
Complica’ns
- death
- pneumonia
- encephalitis
- hepatitis
- 2° bacterial infec’n
- can lie dormant + reactivate later in life as shingles or Ramsay Hunt syndrome
→ SSX of Ramsay Hunt syndrome = acute ipsilateral facial paralysis, Δ in taste, ear pain + hearing loss
→ Tx = oral aciclovir + corticosteroids
- chickenpox in mother around time of delivery can lead to life threatening neonatal infec’n
→ Tx = varicella zoster Igs + aciclovir
Complica’ns in pregnancy
- varicella pneumonitis
- hepatitis
- encephalitis
- fetal varicella syndrome
- severe neonatal varicella infec’n if mom = infected around delivery
- congenital varicella syndrome if mom = infected in first 28 wks of gesta’n
→ fetal growth restric’n
→ microcephaly
→ cataracts + inflamma’n in eye (chorioretinitis)
→ hydrocephalus
→ learning disability
→ limb hypoplasia / underdeveloped limbs
- Know for OSCE *
Impetigo ✓
Def - contagious bacterial skin infec’n
→ usually occurs in children 2-5 y/o but can also occur in older children + even adults
→ Ix = clinical diagnosis but can do swab + culture if disease = extensive
Eti - usually caused by staph. aureus but can also be caused by strep pyogenes
Classifica’n
- Non Bullous impetigo (more common form) → typically occurs around nose or mouth
→ SSX = vesicles → gold / honey colored crust
→ Tx = hydrogen peroxide 1% cream / fusinic acid if localized + oral flucloxacillin if severe or wide spread
- Bullous impetigo = always caused by staph aureus
→ more common in children < 2 y/o but can also occur in older children + even adults
→ in severe infec’ns when les’ns are widespread = called staphylococcus scalded skin syndrome
→ SSX . . .
- itchy + painful bullae → grow + form golden / honey crust when they burst → eventually heal w/o scarring
- fever + general malaise.
→ Tx = flucloxacillin
Mx
- tell pts to not touch or scratch les’ns - good hand hygiene
- avoiding sharing face towels + cutlery
- pts need to be off school until all les’ns have healed or they have been treated w/ Abx for ≥ 48 hrs
Complica’ns
- cellulitis if infec’n gets deeper in skin
- sepsis
- scarlet fever
- post streptococcal glomerulonephritis
- staphylococcus scalded skin syndrome
- Know for OSCE *
Cellulitis + Erysipelas ✓
→ erysipelas = superficial skin infec’n i.e only involves upper dermis but also has lymphatic involv’nt
→ cellulitis = infec’n of deep dermis + subq tissue
RFs
- diabetes
- venous insufficiency
- eczema
- edema
- lymphedema
- obesity
- previous episodes of cellulitis
Eti
- group A strep (strep pyogenes mainly)
- group C strep (strep dysgalactiae mainly)
SSX
- u/l pain, swelling, redness, warmth
- golden / yellow crust indicates staph. aureus infec’n
- fever + tachycardia → means it’s severe so treat w/ IV flucloxacillin
Ddx
- vasculitis
- insect bite
- gout attack
- lymphedema
- herpes zoster
- septic bursitis
- osteomyelitis
- septic arthritis
- contact dermatitis
- erythema migrans
Eron Classifica’n
- Class 1 = no systemic toxicity or comorbidity
- Class 2 = mild systemic toxicity or comorbidity
- Class 3 = significant systemic toxicity i.e confus’n / tachycardia / tachypne / hypoTN OR a significant comorbidity such as PAD or morbid obesity
- Class 4 = sepsis or life threatening such as necrotizing fasciitis
Ix’s
- clinical diagnosis
- always check blood glucose in pt w/ recurrent skin infec’n to check for diabetes
Tx for Class 1 or 2 = oral flucloxacillin → clarithromycin instead if pt has penicillin allergy + erythromycin instead if pt has penicillin allergy + is also pregnant
Tx for Class 3 / 4 or if pt is frail / immuno-compromised / has significant lymphedema / facial cellulitis / periorbital cellulitis = admit for IV flucloxacillin → IV co-amoxiclav instead it pt has facial or orbital cellulitis
Complica’ns
- sepsis
- endocarditis
- osteomyelitis
- septic arthritis
- bacteremia i.e bacteria in blood stream
- Know for OSCE *
Candidiasis / Thrush ✓
Def - oral yeast infec’n caused mainly by Candida albicans
RFs
- T2D
- HIV
- dry mouth
- malignancy
- chemo / radiotherapy
- malabsorp’n / malnutri’n
- poor oral hygiene (especially in older pts who wear dentures)
SSX
- burning mouth pain
- unpleasant taste in mouth
- spotty red areas on buccal mucosa
- white or yellowish plaques in oral mucosa
- cracks / ulcers / crusted fissures radiating from angles of mouth
Ix = superficial smear of les’n for microscopy → will be +ve for Candida hyphae
⚠️ Test for diabetes if pt has recurrent candidiasis !
Tx = clotrimazole or miconazole dissolved in mouth
→ MOA - antifungal that prevents forma’n of ergosterol (part of fungal cell membrane) by inhibiting cytochrome P450-dependent demethyla’n rxn
→ end in “NAZOLE”
→ order LFTs before prescribing antifungals b/c they’re hepatotoxic
Complica’n = esophageal candidiasis (usually happens in severely immunocompromised pts)
→ SSX = dysphagia + odynophagia
- Know for OSCE *
LGV ✓
Def - LGV (lymphogranuloma venereum) = penile or vulvar inflamma’n + ulcera’n caused by Chlamydia trachomatis = endemic to the tropics i.e Africa / India / Southeast asia
RFs
- 20-40 y/o
- other STIs
- HIV sero +ve
- risky sexual behavior
SSX chronology
- 1 ° stage → single painless ulcer on penis, vaginal wall or on rectum if pt had anal sex
- 2 ° stage → lymphadenitis i.e swelling, inflamma’n + pain in inguinal or femoral lymph nodes
- 3 ° stage → proctitis i.e inflamma’n of rectum + anus (occurswks later)
⟹ will cause anal pain, tenesmus + Δ in bowel habit
Ix’s
- NAAT on genital or lymph node specimen
→ will test +ve for Chlamydia trachomatis - anoscopy swab for gram staining
- RT-PCR = only way to confirm diagnosis → will be +ve for LGV
- test pt for other STIs as well
Tx = doxycycline for 21 days
→ erythromycin instead if pt = pregnant, breastfeeding or = allergic to tetracyclines
Complica’ns
- reactive arthritis
- ↑ed susceptibility to HIV + other STIs
- chronic inflamma’n can lead to scaring, fibrosis + lymphedema of genitals or to stricture + fistulae forma’n if there’s anorectal involv’nt
- Know for OSCE *
Tropical STI - Chancroid ✓
Def - STI that mainly occurs in poor countries
= caused by gram -ve bacteria coccobacillus Hemophilus ducreyi = co factor in HIV transmiss’n so always check these pts’ HIV status
→ sexual partners w/in 10 days prior to onset of SSX must be traced + treated even if asymptomatic !
RFs
- male
- unprotected sex
- substance abuse
- multiple sex partners
- not being circumcised
- sexual contact w/ sex worker
Eti - infec’n occurs through contact w/ mucous membranes such as during sex or via abras’ns in skin of genital reg’n
SSX
- bubo forma’n / lymphadenitis
- painful genital papules → in later stages will pustulate + then ulcerate + we now have painful genital ulcers
Ix’s
- bubo aspirate + gram stain of ulcer swabs → will be +ve for gram -ve cocobacilllus
- culture of the above → will specifically identify Hemophilus ducreyi
- Hemophilus ducreyi PCR → will be +ve
- RPR rest to check for syphilis co-infec’n (usually -ve)
- HSV PCR + viral culture to make sure it’s not herpes
- HIV testing
Tx = azithromycin or cefrtiaxone
Complica’ns
- inguinal abscess
- urethral and/or rectovaginal fistulae
- Know for OSCE *
Pyrexia of unknown origin (PUO) ✓
Eti
INFECTIOUS CAUSES
- TB
- abdo. infec’ns
- Infective endocarditis
- viral infec’ns like HIV, EBV, CMV
→ consider geography . . .
⟹ for ex in Mediterranean pt consider Brucella / Leishmaniasis + in returning traveler consider Dengue fever, malaria, enteric fever from typhoidal salmonella
CONNECTIVE TISSUE DISEASES
- RA
- Still’s disease
- SLE → mainly in young adults
- Temporal arteritis + polymyalgia rheumatica (elderly pts usually)
MALIGNANCY b/c some neoplasms produce pyrogenic cytokines
→ accounts for 18% of FUO + includes lymphomas, hyper-nephromas, colorectal + CNS cancers
Classifica’n
- Classic FUO
- fever > 38.3°C
- dura’n of > 3wks
- no diagnosis after > 2 outpt visits or 3 days of hospital Ix - Nosocomial /Health-care associated) = fever > 38.3°C on several occas’ns
- Neutropenic (immune-deficient)
- fever > 38.3°C
- neutrophil count < 500
- no diagnosis after 3 days of hospital Ix - HIV-related FUO
- fever > 38.3°C
- dura’n of > 3wks for outpts + > 3 days for inpts
- Know for OSCE *
Why might pts taking broad spectrum Abx might get diarrhea ✓
B/c AB killed healthy gut flora as well
→ if diarrhea = smelly ≠ due to Abx → if diarrhea ≠ smelly = due to Abx
⚠️ Another common cause of Abx induced diarrhea = C diff !
→ C diff = hard to get rid of b/c of its spore forma’n
Traveller’s Diarrhea ✓
Def - ≥ 3 unformed stools in past 24 hrs during trip to third world country + ≥ 1 of the following SSX . . .
- fever
- N/V
- bloody stools
- abdominal cramps
- tenesmus → feeling that you still need to empty bowels even after having BM
RFs
< 30 y/o
- immunocompromised
- travelling when it’s hot + wet season in that country
Eti = Campylobacter jejuni usually, spread by . . .
- raw or improperly cooked poultry
- untreated water
- unpasteurized milk
Incuba’n period = 2-5 days + SSX usually resolve after 3-6 days
Ix’s
- stool culture + sensitivity to identify causative bacteria / pathogen
- stool occult blood
- stool ova + parasite in case causative pathogen = parasite + ≠ bacteria
Tx = loperamide + azithromycin
- Know for OSCE *
Malaria ✓
Def - parasitic infec’n caused by protozoa of the genusPlasmodium
= transmitted to humans by being bitten by infected female Anophelesmosquito but can also be transmitted by blood transfus’n or organ transplanta’n
RF = travelling to endemic area i.e India / West or Central Africa
Eti
- Plasmodium malariae
- Plasmodium knowlesi
- Plasmodium vivax (dormant liver stage but can reactivate)
- Plasmodium ovale (dormant liver stage but can reactivate)
- Plasmodium falciparum = most severe
Pathophys - during a blood meal infected femaleAnophelesmosquito injects sporozoites in victim
→ sporozoites rapidly enter hepatocytes + reproduce by asexual fiss’n (tissue schizogony) to form pre-erythrocytic schizont (this part of the life-cycle produces no SSX)
→ after a period of time merozoites = released into bloodstream to penetrate erythrocytes after attaching via receptors
→ most merozoites undergo blood schizogony to form trophozoites which evolve into schizonts which rupture to release new merozoites
→ disrupts RBC membrane integrity + causes RBC lysis
→ rupture of erythrocytes releases toxins that induce release of cytokines from macrophages ∴ resulting in malaria SSX
SSX
- fever that spikes very high every 48 hrs
- chills
- sweats
- myalgia
- diarrhea
- anorexia
- HA
- jaundice
- pallor due to anemia
- hepatosplenomegaly
Ix’s
- Glemsa stained thick + thin blood film → will show plasmodium thropozoites inside RBCs
⟹ 3 -ve samples taken over 3 consecutive days = required to exclude malaria ! - RDT → but can only detect falciparum + vivax
- LFTs → unconjugated hyperbilirubinemia
- FBC → might show anemia
Tx for pts w/ falciparum malaria = admit for IV artesuntate
Tx for all others = riamet
Malaria ppx before travelling to endemic area
- mosquito spray
- using mosquito nets in sleeping areas
- antimalarial medica’n such as . . .
→ malarone
→ doxycycline
→ mefloquine
Complica’ns
- AKI
- cerebral malaria → can lead to seizures, ↓ed consciousness + even coma
- Know for OSCE *
Lyme Disease ✓
Def - infectious disease transmitted to humans through the bite of an Ixodes scapularis tick that was infected w/ Borrelia burgdorferi bacteria
RF = outdoor activities
SSX
- fatigue
- at early stage presents w/ flu-like SSX + erythema migrans i.e spreading target symbol rash @ site of tick bite (rythema migrans develops w/in 1-2 wks)
- late stage manifesta’ns = arthritis, heart block + facial nerve palsy (bilaterally usually)
Ix = enzyme immunoassay or immunofluorescence assay → will be +ve
Tx = doxycycline
- Know for OSCE *
Scabies ✓
Def - highly contagious skin infesta’n caused by mite Sarcoptes scabiei
→ can take up to 8 wks after initial infesta’n for SSX to appear
RFs
< 15 y/o or > 65 y/o
- overcrowded living condi’ns
- immunocompromised
- living in close quarters w/ others who are infected
Eti - transmitted through direct + prolonged skin-to-skin contact
Pathophys - mite burrows into skin + lays its eggs in stratum corneum
→ delayed-type IV hypersensitivity rxn to mites/eggs occurs ≈ 30 days after initial infec’n
SSX
- widespread itching sparing that’s worse @ night
- incredibly itchy small red spots, btw finger webs but can spread to whole body
- track marks where mites burrowed
- other household members w/ similar SSX
- crusted scabies = seen in immunosuppressed pts such as HIV pts → isolate these pts + treat them w/ single dose oral Ivermectin
Ix = clinical diagnosis but can microscopy to detect eggs or scyballa (fecal pellets)
Tx - permethrin 5% cream → malathion 0.5% cream
⟹ permethrin cream should be applied on whole body when skin is cool + should be left on for 8 -12 hrs before you wash it off + repeat whole process a wk later to kill hatched eggs that survived 1st round
- Know for OSCE *
Head lice ✓
Def - scalp infesta’n caused by Pediculus humanus capitis parasite
→ usually occurs in school aged children
→ = transmitted by head to head contact or by sharing equipment that touches head such as combs or towels
SSX = itchy scalp
Tx = Dimeticone 4% lotion on hair
→ should be left on hair for 8 hours i.e overnight + then washed off
⟹ do this for 8 days to kill any head lice that have hatched
- detec’n combing to check success of Tx
- Know for OSCE *
Folliculitis ✓
Def - inflamma’n of hair follicle
→ most common cause of superficial folliculitis = Staph. aureus
RFs
- shaving
- diabetes
- immunosuppress’n
Eti
- gram -ve bacteria (Klebsiella, Enterobacter, Proteus)
- viral
- fungal
- parasitic
- eosinophilic pustular in infants (= on scalp)
- drug induced i.e Li, isoniazid, corticosteroids
SSX = erythematous papules or pustules in areas w/ terminal hair growth such as head, neck, axilla, groin + buttocks
Ix’s
- bacterial skin swab for PCR if there is a definite pustule that can be unroofed w/ a 15 blade
- viral skin swab for PCR if Hx + exam = suggestive of Herpes simplex infec’n
Tx for uncomplicated folliculitis = nothing b/c = self-limiting
Tx for recurrent / deep folliculitis due to methicillin susceptible stap. aureus (MSSA) = cefalexin = cephalosporin
Tx for recurrent / deep folliculitis due to MRSA = clindamyacin
Tx for gram -ve folliculitis = topical benzyl peroxide
- Know for OSCE *
Delirium ✓
Def - acute state of confus’n
Causes (“VVITAMEN Double D’s”) :
- Vitamin deficiencies - thiamine, B12, nicotinic acid
- Vascular disorders - cerebrovascular hemorrhage or infarc’n / vasculitis
- Infec’n - UTI, pneumonia, sepsis, meningitis, encephalitis, malaria
- Toxins - CO, heavy metals, barbiturate/benzo/SSRI w/drawal
- Alcohol intoxica’n or w/drawal (delirium tremens = most severe form of alcohol w/drawal)
- Metabolic - hypoxia, electrolyte abnormalities such as HypoNa or HyperCa, hypo or hyperglycemia, uremia, liver failure, thyrotoxicosis
- Epilepsy
- Neoplasm
- Drugs - benzos, analgesics such as morphine, anti-cholinergics, anti-convulsants, anti-parkinsonism medica’ns, steroids
- Dehydra’n
- Sx
- Sleep depriva’n
Emergency Tx = low dose haloperidol
→ MOA = dopamine D2 receptor antagonist
- Know for OSCE *
Dementia ✓
Def - > 3 months of GRADUAL confus’n
RFs
- FHx
- HTN
- female
- old age
- diabetes
- head trauma
- hypoTSH
Eti
1) Alzheimer (50-60%) (MMSE typically ↓ 3 points / yr)
→ SSX = 8 A’s
- Aphasia
- Altered percep’n
- Apathy i.e lack of drive to do things
- Amnesia → pt will lose their short term memory 1st + then they’ll lose their long term memory
- Amyloid-β plaques extracellularly + hyperphosphorylated Tau intra- cellularly
- Anosognosia = not realizing that something is wrong i.e not realizing that ur forgetting stuff
- Agnosia = loss of ability to recognize things via senses i.e objects, ppl,smells, sounds, tastes although the sense itself isn’t defective
- Apraxia = loss of ability to execute or carry out learned purposeful mov’nts despite having desire + physical ability to perform those mov’nts
- Vascular dementia (15-20%)
→ SSX = stepwise ↓ in cognitive ability w/ late onset memory impair’nt + pt has RFs such as HTN / T2D - Lewy body dementia (10-15%)
→ SSX = Parkinsonism, progressive cognitive decline, visual hallucina’ns, delus’ns, fluctuating levels of alertness + REM sleep disorders
⚠️ Regular Parkinson’s can also have Lewy bodies !
- Fronto temporal dementia / Pick’s disease
→ SSX = early Δs in personality / behavior ± aphasia
Ddx
- depress’n
- normal aging
- temporal lobe seizure
- intracranial space occupying les’n i.e tumor
Ix = 6 part MMSE test → tests orienta’n, ability to repeat, calcula’n, recall, language + copying
→ 27-30 = normal
→ 25-26 = cognitively impaired
→ 21-24 = mild dementia
→ 10-20 = moderate dementia
→ 0-9 = severe dementia
Tx for mild ~ moderate = Achesterase inhibitor
→ MOA - inhibits Achesterase from breaking down Ach
→ side effects = too much para b/c Ach is it’s neurotransmitter
⟹ hypersaliva’n, hyperlacrima’n, urinary reten’n, diaphoresis, GI hypermotility, emesis
→ C/Is = bradycardia, urinary reten’n, gastric ulcers
→ end in “MINE”
- Tx for for moderate ~ severe = add NMDA receptor antagonist such as memantine
→ side effects = constipa’n, HA, drowsiness, HTN, hallucina’ns, balance pbs - Know for OSCE *
Delirium v.s Dementia ✓
- fluctuates v.s progresses
- days ~ wks v.s permanent
- reversible v.s NOT reversible
Pressure sores / Pressure ulcers ✓
Def - localized damage to skin + underlying soft tissue over a bony prominence b/c of prolonged immobiliza’n
RFs
- Sx / immobility
- older age
- ICU stay
- sensory impairment
Ix = clinical diagnosis
Ppx for pressure ulcers = pressure reducing aids + frequent repositioning
Regular Tx = wound dressing, analgesia + diet optimiza’n
Tx for deep ulcers i.e stage 3 or stage 4 = debridement of necrotic tissue + flap reconstruc’n
Complica’ns
- sepsis
- cellulitis
- osteomyelitis
- Know for OSCE *
Eczema / Atopic Dermatitis ✓
Def - chronic inflammatory skin condi’n characterized by dry + itchy skin
→ usually diagnosed before 5 y/o
→ these pts tend to have more food allergies than the avg popula’n
RFs
< 5 y/o
- muta’ns in filaggrin gene
- personal or FHx of eczema or other atopic diseases such as asthma or allergic rhinitis
SSX = dry, red itchy paches of skin on flexor surfaces i.e knee / elbow
Ddx
- irritant contact dermatitis
- allergic contact dermatitis
Ix = clinical diagnosis
Tx = emollients → hydrocortisone → eumovate → betnovate → dermovat
Complica’ns
- flares
- breakdown of skin’s protective barrier gives an easy entry for infective organisms (staph. aureus usually)
- eczema herpeticum = viral skin infec’n in eczema pts → = caused by HSV or VZV
→ SSX = widespread, painful, vesicular rash + systemic SSX such as fever, lethargy, lymphadenopathy, irritability + ↓ed oral intake
→ Tx = aciclovir
- Know for OSCE *
Allergic contact v.s Irritant contact dermatitis ✓
Allergic contact dermatitis = T cell-mediated, delayed-type hypersensitivity response to exogenous agent
Irritant contact dermatitis = localized, inflammatory skin response to a chemical or physical agent
→ not immune mediated unlike allergic contact dermatitis
RFs
- infants for irritant contact
- Hx of atopic dermatitis
- working w/ chemicals i.e hairdresser, HCPs
SSX = erythematous, indurated, scaly plaques localized to areas that came into contact w/ allergen or chemical
Ddx = each other
Tx = identifying + avoiding of offending allergen / chemical
- Know for OSCE *
Diaper rash ✓
Def - contact dermatitis in diaper area due to fric’n btw skin + diaper
RFs
- delayed diaper changing
- irritant soap products
- vigorous cleaning
- poorly absorbent diapers
- diarrhea
SSX = sore, red, inflamed skin in diaper area sparing creases
Tx
- switching to highly absorbent diapers
- prompt diaper changing
- using water or gentle alcohol free products to clean diaper area
- not wearing diaper all the time
- nystatin if it’s fungal infec’n
Complica’ns
- eros’n
- ulcera’n
- candida infec’n
- cellulitis
Erthryoderma ✓
Def - severe + Ψly life-threatening condi’n that presents w/ diffuse erythema + scaling, involves ≥ 90% of skin surface area = dermatological emergency !
Eti = psoriasis
SSX
- warm psoriatic les’ns
- fever
- malaise
- tachycardia
- lymphadenopathy
- peripheral oedema
Ix = clinical diagnosis
Emergency Tx = ciclosporin + infliximab
Mx
- bed rest in a warm room (30-32°C)
- emollients + cool, wet dressings
- treating complica’ns
- nutri’nal support
Complica’ns
- dehydra’n
- hypothermia
- cardiac failure
- sepsis
- protein loss
- death
- Know for OSCE *
How to use the Rule of 9’s to calculate %age of TBSA lost after burn ✓
- head + neck = 9%
- each arm = 9%
- torso = 18%
- back = 18%
- each leg = 18%
- groin area = 1%
- Know for OSCE *
Classifying burns ✓
1st ° / superficial burn
→ depth = epidermis
→ SSX = pain, redness + mild swelling
2nd ° / superficial partial burn
→ depth = papillary reg’n of dermis
→ SSX = pain, blisters, splotchy skin + severe swelling
3rd ° / deep partial burn
→ depth = reticular reg’n of dermis
→ SSX = white, leathery + relatively painless
Full thickness burn
→ depth = hypodermis / subq
→ SSX = charred, no sensa’n, w/ eschar
- Know for OSCE *
Parkland formula for fluid resucita’n in burn pts (for the 1st 24 hrs) ✓
In children
3 ml x % TBSA burned x pt’s weight in kg
In adults
4 ml x % TBSA burned x pt’s weight in kg
Emergency Tx for burn to thorax ✓
Aggressive IV fluid resucita’n using Parkland formula → escharotomy → urgent transfer to burn center
Indica’ns for transfer to burn center ✓
- burns ≥ 2% TBSA in children or ≥ 3% in adults
- full thickness burns
- circumferential burns
- any burn that hasn’t healed after 2 wks
- suspici’n that burn = due to non-accidental injury (must be done w/in 24 hrs)
Inhala’n injury ✓
Def - injury caused by inhaling lots smoke i.e after a house fire
SSX
- harsh cough
- hoarse voice
- burns to face
- singed hair / eyebrows / eyelashes
- soot around face, mouth + nose
Initial Tx = intuba’n
