Pathology: ALL Flashcards
These are using CLIs and Pathology information
What is the pathophysiology of atherosclerosis?
- Chronic stress on the endothelium (e.g., due to arterial hypertension and turbulence)
- Endothelial cell dysfunction, which leads to:
- Invasion of inflammatory cells (mainly monocytes and lymphocytes) through the disrupted endothelial barrier
- Adhesion of platelets to the damaged vessel wall
- PDGF stimulates the migration and proliferation of smooth muscle cells (SMCs) in the tunica intima and mediates the differentiation of fibroblasts into myofibroblasts - Inflammation of the vessel wall
- Macrophages and SMCs ingest cholesterol from oxidized LDL and transform into foam cells (macrophages filled with lipid droplets).
- Foam cells accumulate to form fatty streaks (early atherosclerotic lesions).
- Lipid-laden macrophages and SMCs produce extracellular matrix (e.g., collagen) deposition → development of a fibrous plaque (atheroma)
- Inflammatory cells in the atheroma (e.g., macrophages) cause → weakening of the fibrous cap of the plaque due to the breakdown of extracellular matrix → minor stress ruptures the fibrous cap
- Calcification of the intima
- Plaque rupture → exposure of thrombogenic material (e.g., collagen) → thrombus formation with vascular occlusion or spreading of thrombogenic material
What are the histopathology findings in MI
- Gross and microscopic
What is the difference between a STEMI and a NSTEMI
Coronary artery occlusion
Partial coronary artery occlusion
Decreased myocardial blood flow → supply-demand mismatch → myocardial ischemia
Usually affects the inner layer of the myocardium (subendocardial infarction)
Typically manifests clinically as unstable angina and/or NSTEMI
Complete coronary artery occlusion
Impaired myocardial blood flow → sudden death of myocardial cells (if no reperfusion occurs)
Usually affects the full thickness of the myocardium (transmural infarction)
Typically manifests clinically as STEMI
Etiology of Athlerosclerosis
Traditional ASCVD risk factors
Nonmodifiable risk factors
Advancing age
Male sex
Race and ethnicity
Modifiable risk factors
Smoking
Diabetes mellitus
Hypertension
Dyslipidemia (↑ total cholesterol, ↓ HDL cholesterol)
What is the general pathogenesis of IHD
- increase need for O2 or a decreased supply of O2.
- Pathogenesis
- Lack of blood supply, decreased O2, therefore decreased ATP, Loss of myocyte
- function, cell swelling Ischemia (1-2min) then progress
- to Necrosis (20-40min). Inflam. (Neutrophils, Macrophages, Healing, Scar)
Comlications of MI acute and long term
0-24 hours
Sudden cardiac death
Arrhythmias (e.g., ventricular fibrillation)
Acute heart failure → pulmonary edema
Cardiogenic shock
1-3 days
Fibrinous pericarditis
3-14 days
Papillary muscle ischemia or rupture → mitral regurgitation
Interventricular septal defect → acute VSD (left to right shunt)
Ventricular free wall rupture → cardiac tamponade
Ventricular pseudoaneurysm
2 weeks +
True ventricular aneurysm → mural thrombus
Dressler pericarditis
Arrhythmias (e.g., AV block)
Congestive heart failure
Reinfarction
This is a slide showing cardiac myocytes: what stage of MI is this and what miscroscopic features are seen? What gross morphology would be present?
acute phase. in the first few hours. the dead myocytes still have nucleus but they have pyknosis (darkening) and smaller. there are few fibrosis (normal). there is leakage of blood keeping some tissue alive. increase RBC. Acute MI <24 h shows contraction bands being made.
GROSS: Normal in the first 4 hours, after will show a dark red area where infart occured
This is a slide showing cardiac myocytes: what stage of MI is this and what miscroscopic features are seen? What gross morphology would be present?
After inflammatory period- increased macrophages eating dead cells. no nucleus in myocytes. haemorrhage and inflammation clearing and being replaced by macrophages. Replaced by granulation tissue- then granulation tissue replaced by collagen bundles
GROSS: Dark red area, (at the 2 week mark there will be a yellow centre with red boarders.
This is a slide showing cardiac myocytes: what stage of MI is this and what miscroscopic features are seen? What gross morphology would be present?
Elongated cells (fibroblasts) are starting to replace dead cardiomyocytes. The process of granulation tissue forming also includes sprouting capillaries and inflammatory cells (lymphocytes, macrophages).
Necrosis is occuring and macrophages and lymphocytes are phagocytosing dead cells.
This process is typical of the granulation stage, which begins approximately two weeks after necrosis development.
GROSS: Yellow centre with red boarder.
Total replacement of dead cells by scar tissue. band of scar tissue and rest of myocardial tissue. white tissue is collagen bundles (scar tissue).
This is a slide showing cardiac myocytes: what stage of MI is this and what miscroscopic features are seen? What gross morphology would be present?
Total replacement of dead cells by scar tissue. band of scar tissue and rest of myocardial tissue. white tissue is collagen bundles (scar tissue).
SLIDE SHOWS: Healthy myocardium (left side) and myocardial scarring (most of the right side) are visible. The scar tissue appears white-grey because of fibrosis and loss of cardiomyocytes.
GROSS: Small white scar
What features are seen on a microscopy of a vessel which shows athlerosclerosis?
there is damage in lumen where thickening is occurring and increased macrophages- leakage of fat. as lesion increases in size, it will develop bigger plaques. increased proliferation of cap creating fibrosis cap.
What is the lipid deposition pathway
Chylomicrons: large triglyceride rich particles made by the intestine, which are involved in the transport of dietary triglycerides and cholesterol to peripheral tissues and liver.
LVDLP: produced by the liver and are triglyceride rich.
ILDL: removal of triglycerides from VLDL by muscle and adipose tissue results in the formation of IDL particles which are enriched in cholesterol
LDL: derived from VLDL and IDL particles and they are even further enriched in cholesterol. LDL carries the majority of the cholesterol that is in the circulation. - deposit in tissues
HDL: play an important role in reverse cholesterol transport from peripheral tissues to the liver, which is one potential mechanism by which HDL may be anti-atherogenic
mechanism of action, indications, contraindications, and side effects of lipid lowering medications: statins
MOA 1.Inhibit HMG CoA reductase which is the rate limiting enzyme in cholesterol synthesis in the liver, thereby ↓ the amount of cholesterol produced by the liver
2.Subsequently, liver cells respond to the decreased cholesterol concentration by activating the transcription factor Sterol Regulatory Element Binding Protein (SREBP) to ↑ LDL receptor expression on cells. Thus, ↑ cholesterol is extracted from blood and taken up into cells for storage or excretion. (Main effect)
Indications
Hypercholesterolemia, hyperlipidemia, high risk of CAD
Contraindications Pregnancy or breastfeeding, renal impairment
Side effects Mild: Myalgia, GI disturbance, raised concentration of liver enzymes (transaminase) in plasma, insomnia, rash
Serious, but rare: rhabdomyolysis, angioedema
mechanism of action, indications, contraindications, and side effects of lipid lowering medications: ezetimibe
Ezetimibe
MOA Inhibits the absorption of cholesterol from the duodenum by blocking transport protein NPC1L1 in the brush border of enterocytes, without affecting the absorption of fat-soluble vitamins, triglycerides or bile acids → ↓cholesterol concentration
Indications Hypercholesterolemia - with statin
Contraindications Breastfeeding
Side effects Diarrhoea, abdominal pain, headache, rash and angioedema
mechanism of action, indications, contraindications, and side effects of lipid lowering medications: Fibrates
Fibrates
MOA Fibrates are agonists at the nuclear receptor transcription factor PPARɑ → ↑expression of lipoprotein lipase and inhibits synthesis of apoprotein C-III which normally inhibits lipoprotein lipase. This increases lipolysis and the elimination of triglyceride rich particles from plasma.
This also causes a shift in the size/composition of LDL particles from small/dense to large, buoyant particles, which have greater affinity for the LDL receptor and are therefore catabolised more rapidly.
Indications Dyslipidemia
Contraindications Avoid use with statins
Also contraindicated if creatinine clearance is under 30 mL/min or if the patient has severe renal dysfunction.
Side effects Rhabdomyolysis (occurs in patients with renal impairment), GI symptoms, pruritus and rash, gallstones (only with clofibrate, due to increased bile production)
PCSK9 inhibitors
MOA PCSK9 is an enzyme that normally reduces the number of available LDL receptors on cells, mainly hepatocytes. Inhibitors (which are monoclonal antibodies) of this enzyme thereby ↑ the number of receptors, resulting in more LDL cholesterol being removed from circulation.
Indications In Australia, PCSK9 inhibitors have been approved for those with familial hypercholesterolemia who cannot lower blood cholesterol to certain levels with standard medications, or those who cannot tolerate standard medications
Contraindications Pregnancy
Route and frequency SC injection every 2-4 weeks
Desired effects Reduced LDL in blood flow due to increase in receptor availability
Side effects * Flu-like symptoms such as cold, nausea, back pain and joint pain
* soreness or itchiness at injection site
* muscle pain
mechanism of action, indications, contraindications, and side effects of lipid lowering medications: PCSK9 inhibitors
PCSK9 inhibitors
MOA PCSK9 is an enzyme that normally reduces the number of available LDL receptors on cells, mainly hepatocytes. Inhibitors (which are monoclonal antibodies) of this enzyme thereby ↑ the number of receptors, resulting in more LDL cholesterol being removed from circulation.
Indications In Australia, PCSK9 inhibitors have been approved for those with familial hypercholesterolemia who cannot lower blood cholesterol to certain levels with standard medications, or those who cannot tolerate standard medications
Contraindications Pregnancy
Side effects * Flu-like symptoms such as cold, nausea, back pain and joint pain
* soreness or itchiness at injection site
* muscle pain
Develop a differential diagnosis for acute chest pain and identify key aspects of a patient’s presentation that suggest each diagnosis.
DDX, type of pain, vital signs and one test result to confirm.
ACS (MI, unstable angina): central crushing chest pain, hypertension, raised troponins
Aortic dissection: central ripping pain, leg weakness, radioradial/ femoral delay, xray shows widenned mediastinum.
Pericarditis → cardiac tamponade: worse when lying flat, tachycardia and hypotensive, ECG shows spodics sign, and changing QRS height. follows infection.
PE: unilateral pleuric chest pain, tachypneic, pleural rub, right heart strain, d-dimer.
Pneumothorax: sharp ulilateral chest pain, Auscultation: breath sounds absent
Percussion: hyperresonance.
GORD: worse after eating food, especially spicy foods, relieved with PPI, normal vital signs.
Describe demographics, aetiology/pathophysiology, risk factors, clinical features (+ atypical presentations), investigation findings for an ACS
Demographics: M>F, >55 yr. Old
Aetiology/ pathophysiology
1. Atherosclerosis – most commonly
2. Coronary artery dissection.
3. Vasospasms
4. Myocarditis
5. Vasculitis
6. Global hypertension
7. Severe anaemia
8. Severe aortic stenosis
Risk Factors
Increasing age, Male gender, Pmhx of angina and/or known CAD, Family history of CAD, Diabetes mellitus, Systolic HTN, Smoking, Hyperlipidaemia, Alcohol, Stress, Poor diet/sedentary lifestyle
Clinical Features
- Chest pain – central crushing chest pain with radiation to left arm, shoulder, neck, jaw and/or epigastrum.
- Dyspnoea, pallor, nausea & vomiting, diaphoresis, anxiety, dizziness, light-headedness, syncope
- In diabetics, chest pain may be completely absent due to polyneuropathy
Investigation findings
Unstable Angina
* ECG= no ST elevation
* Troponin negative
NSTEMI
* ECG= ST depression +/- T wave inversion (no ST elevation)
* Troponin positive
STEMI
* ECG= ST elevation
* Anterior STEMI= V1-V4
* Inferior = II,III,aVF
* Lateral = V5-V6, I, aVL
Troponin Positive
Describe the complications (immediate and long term) of acute coronary syndrome.
Acute
cardiac failure and death – mostly to VF/VT
arrhythmias – 90% patients <24 hours
dead tissue stimulates inflammation
CHF – heart unable to support CO
cardiogenic shock (RV involvement)
pericarditis
mural thrombus formation
myocardial wall rupture tamponade
→ occur 3-7 days post MI Papillary muscle rupture → mitral regurgitation
Chronic
chronic IHD/ischaemic cardiomyopathy
result in CHF
arrhythmias
ventricular aneurysm
mural thrombus
papillary muscle contraction mitral reg
dilated cardiomyopathy
Outline the acute management of acute coronary syndrome
STEMI and NSTEMI
STEMI: reperfusion stabilisation
* Aspirin PO 300mg stat
* Clopidogrel
* Opioids (fentanyl)
* PCI if available within 90 minutes with unfractionated heparin
* Thrombolysis if PCI isn’t available
o Fibrinolytic agent with heparin
o Get patient to area with cath lab
* Consider admission to CCU
NSTEMI: plaque
* Aspirin PO 300mg stat
* Beta blockers
* Anti-platelet eg ticagrelor or clopidogrel
* Opioids
* Anticoagulant
* Nitrates
Compare the indications, contraindications and complications of percutaneous intervention and thrombolysis for management of ACS.
Percutaneous Coronary Intervention: utilising stents
contraindications: high risk of bleeding, hypercoaguability state, cannot withstand cardiac surgery.
complications: coronary artery injury/ rupture - renal failure, stroke, MI
Thrombolysis: break up and dissolve clot.
- used if chest pain cannot be PCI in first 90 min, or in rural setting.
- contraindications: prior intercranial hemorhhage, AD, high risk of bleeding.
- Complications: arrthymias, systemic bleeds.
Discuss the limitations of assessing and managing acute coronary syndrome in a rural setting.
Assessing
* Transport to hospital; delayed arrival to the hospital or delay in seeking hospital care
* Triage; may be delayed due to staffing
* Availability of equipment; blood forms, blood collection, ECG machines, drugs
* Availability of staffing; doctors or nurses
* Availability of diagnostic testing is limited
* Cultural and language difference may be a barrier to receiving information in the form of a history; may also impede examination
Managing
* Availability of PCI
* If thrombolysis is contraindicated and PCI is not available, the patient has to be transported to another facility where PCI is available. After 12 hours, the infarct may be complete.
* Availability of certain medications including pain relief
* Follow up of bloods/testing sent away
Explain the components and, indications and benefits of the cardiac rehabilitation program.
what is it, components and benefits.
- Support, exercise & education to help strengthen patient’s hearts after a cardiac event such as ACS
- Timing: early referral, early attendance
Components:
* Thorough assessment of MH, smoking, medications, exercise capacity and QOL
* Health behaviour change, lifestyle risk factor management (physical activity, diet, smoking cessation)
* Intermittent reassessment and adjustment of plans
* Follow up (transfer of care)
Benefits
* Reduced CVD mortality
* Reduced hospital admissions
* Improvement in quality of life
* Improved cardiovascular risk profile
Outline the long-term management of acute coronary syndrome/coronary heart disease, including the management of stable angina.
When pain comes on
1. glyceryl trinitrate spray 400 micrograms sublingually, repeat every 5 minutes if pain persists, up to a total of 3 doses if tolerated
TO decrease risk
2. education of patients
3.
Antiplatelet: aspirin and P2Y12 inhibitor: PCSK9 enzyme that normally reduces the number of available LDL receptors on cells, mainly hepatocytes. Inhibitors of this enzyme thereby ↑ the number of receptors, resulting in more LDL cholesterol being removed from circulation.
Statins: Inhibit HMG CoA reductase - the rate limiting enzyme in cholesterol synthesis in liver, thereby ↓ the amount of cholesterol produced by the liver - liver cells respond to ↓ cholesterol by activating the transcription factor (SREBP) to ↑ LDL receptor expression on cells. Thus, ↑ cholesterol is extracted from blood and taken up into cells for storage or excretion.
Beta blockers: bind to B1 and 2 receptors (B1 are heart ones) and stop nor-adrenalin and adrenalin from increasing cardiac function.
Angiotensin converting enzyme inhibitors: inhibits angiotensin 1 converting to A2 therefore, vasodalation of blood vessels
Calcium channel blockers: preventing calcium from entering myocytes. Calcium causes the heart and arteries to squeeze (contract) more strongly. By blocking calcium, calcium channel blockers allow blood vessels to relax and open.
Compare the mechanism of action, indications, contraindications, route and frequency of administration, desired effects and side effects of lipid lowering medications: statins, ezetimibe, fibrates and PCSK9 inhibitors.
STATIN: Inhibit HMG CoA reductase, ↓ the amount of cholesterol produced by the liver - liver cells respond to ↓ cholesterol by activating the transcription factor (SREBP) to ↑ LDL receptor expression on cells. Thus, ↑ cholesterol is extracted from blood and taken upfor excretion.
* first line
* cannot take while breastfeeding or preg
* SE: myalgia, GI upset
EZETIMIBE:Inhibits absorption of cholesterol from the duodenum by blocking transport protein NPC1L1 in the brush border of enterocytes → ↓cholesterol concentration.
* cannot take while breatfeading
* GI upset, pain, headache.
FIBRATES: stimulate cellular fatty acid uptake, conversion to acyl-CoA derivatives, and catabolism by the beta-oxidation pathways, which, combined with a reduction in fatty acid and triglyceride synthesis, results in a decrease in VLDL production.
* avoid use with statins
* rhabdomyolysis, GI symtoms
PCSK9 inhibitors: PCSK9 is an enzyme that normally reduces the number of available LDL receptors on cells, mainly hepatocytes. Inhibitors of this enzyme thereby ↑ the number of receptors, resulting in more LDL cholesterol being removed from circulation.
* do not use in pregnancy
* flu like symtoms, sores and ithcing.
Describe the demographics, risk factors, clinical features, diagnostic criteria, management and complications of essential hypertension.
Demographics: M>F,
Risk factors: FHx or PMH CKD, hypertension, diabetes, dyslipidaemia, stroke, early onset coronary heart disease and low birth weight
* Modifiable lifestyle factors include: smoking, diet, weight control, obesity, exercise, recreational drug use, alcohol intake
Clinical features:
* Often asymptomatic
* Blood pressure ≥ 140/90 mmHg
* Retinopathy
* Other: headache, visual changes, dyspnoea, chest pain
Investigations:
* Cardiac exam
* Urine dip stick
* Blood tests: fasting metabolic panel with estimated GFR, lipid panel
* 12-lead ECG
* Blood pressure treatment targets: Generally, for patients who require BP-lowering therapy the aim is to reduce BP to below 140/90 mmHg.
* Lifestyle Advice
* Pharmacological Treatments:
* ACE inhibitors, (ARB), calcium channel blockers, Thiazide and thiazide-like diuretics
(Beta Blocker not recommended)
Complications:
Stroke, CAD, Kidney disease, Heart Failure, AF, retinopathy, PVD, Aortic dissection, death
Summarise the Framingham study and analyse its relevance to the Australian population, e.g. known cardiac risk factors not included in cardiovascular risk assessment.
The Framingham Heart Study (launched 1948) was originally designed to identify common risk factors contributing to cardiovascular disease (CVD). The study now spans over 3 generations, studying the family patterns of CVD, and includes diverse populations.
Risk Factors Identified in Framingham Study: high blood pressure, high cholesterol (HDL vs LDL + total triglycerides), unhealthy eating patterns (fat, sugar, alcohol etc.), age (particularly >50yrs), smoking, physical inactivity and unhealthy weight.
Sex and race changes the impact of risk factors and CVD development.
Australian CV risk calculator
Differences:
* Australian calculator measures 5-year risk while Framingham measures 10-year
* Australian calculator doesn’t include information on the presence of hypertension, and whether there is Tx for hypertension being provided
* Australian calculator incorporates ECG LVH while Framingham does not
Outline the criteria required for screening, using cardiovascular risk assessment as an example.
define screening, then for each screening tool, give a CV example
Screening is defined as “the examination of asymptomatic people in order to classify them as likely or unlikely to have a disease”.
Criteria used for screening
* Condition should be an important health problem Coronary heart disease leading cause of death
* Recognisable latent or early symptomatic stage CVD is progressive and has a variety of early symptoms
* Natural history of the condition should be adequately understood pathophysiology of most of CVD are well understood
* Accepted treatment for patients with recognised disease there are several methods of treatments for CVD including medications, surgery and rehabilitation
* Suitable test or examination that has a high level of accuracy sensitivity of 80% and specificity of 69%
* Test should be acceptable to the population this test is simple, fast and non-invasive
* Agreed policy on whom to treat as patients
* Facilities for diagnosis and treatment should be available can be done online or by a healthcare professional
* Cost of screening (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole no cost
* Screening should be a continuing process and not a ‘once and for all’ project screening is recommended every 2 years
Identify the recommendations regarding cardiovascular risk assessment: who should be assessed, the management for low, medium, and high risk.
Who to Assess
* >45 every 2 years for people at medium to high risk
* Blood tests for people of low risk
* >74 documented as 74 years. This may underestimate the five year risk, but it will give an estimate of the minimum risk.
* Patients with a family history of premature CVD (in a first-degree relative – men aged <55 years, women aged <65 years) or obesity may be at greater risk. Similarly, patients with depression and atrial fibrillation (AF) may also be at increased risk.
* Indigenous Australians greater than 35
Management
Low absolute risk: <10% cardiovascular disease (CVD) risk
* Provide lifestyle advice and education
* Offer pharmacotherapy for hypertension
* Review blood pressure of 140-159 mmHg after two months of lifestyle advice
Moderate risk: 10-15% absolute CVD risk
* Provide intensive lifestyle advice
* Consider pharmacotherapy if systolic blood pressure is 140-159 mmHg or diastolic blood pressure is 90-99 mmHg
* If systolic blood pressure is 130–139 mmHg or diastolic blood pressure is 85–89 mmHg, review BP in six months
* Offer pharmacotherapy for HTN and lipid therapy simultaneously with lifestyle intervention if BP persistently over 160/100 mmHg or if family history of premature CVD or patient is of South Asian, Middle Eastern, Maori, Aboriginal, Torres Strait Islander or Pacific Islander descent
High risk: >15% absolute CVD risk
* Provide intensive lifestyle advice
* Commence pharmacotherapy (simultaneously with lipid therapy unless contraindicated)
Recognise the aetiology, clinical features, investigation findings and management of pericarditis.
clinical presentation
* history of precipitating aetiology
* autoimmune/inflammatory - SLE, RA, ARF
* bacterial/viral infection - TB, COVID, coxsackie, etc.
* cancer - malignancy
* uraemia, post MI/Dressler’s syndrome, trauma
* fever
* chest pain
* sharp, retrosternal, radiates to neck/shoulder
* worse on inspiration, coughing, swallowing, lying supine
* relieves leaning forward
* pericardial friction rub
* pericardial effusion with cardiac tamponade
* triad of hypotension, raised JVP, muffled heart sounds
* tachycardia, pulsus paradoxus
investigations
* ECG
* widespread ST elevation (with concavity) & PR depression
* reciprocal ST depression & PR elevation in aVR
* electrical alternans if effusion
* ECHO
* can show pericardial effusion
* CXR
* increased cardiac silhouette if effusion
* FBC
* leukocytosis, elevated CRP & troponin
management
* treat underlying cause (e.g. dialysis for uraemia)
* anti-inflammatories
* high dose NSAID
* colchicine (continued for 3 months)
* pericardiocentesis or pericardial drain if pericardial effusion
* follow-up as outpatient
Summarise the demographics, risk factors, clinical features and investigation findings of an aortic dissection
AORTIC DISSECTION
Demographics
* 60-80 yr olds: 8.6 per 100 000 people
* Over 80 yrs: 32 per 100 000
* 75% occur in patients aged between 40-70 yrs
* 3 times more common in males than females
Risk Factors
* Male sex
* >65 years old
* Hypertension
* Smoking
* Aneurysm
* Congenital disorders: marfan syndrome,
* Inflammatory disease: aortitis, giant cell arteritis, Takayasu arteritis, Systemic lupus erythematous
* Aortic wall stress: previous cardiovascular surgeries, wall thinning, structural abnormalities
Clinical Features
Abrupt onset of severe chest, back or abdomen pain (ripping or tearing). Precordial or interscapular pain.
* Less than half patients will also present with:
* Pulse deficit
* Murmur of aortic regurgitation
* Hypotension
* Syncope
* Symptoms of malperfusion (stroke, MI, intestinal infarction, renal insufficiency, paraparesis or paraplegia)
Investigation Findings
12-lead ECG – presence of nonspecific ST-segment or T-wave changes.
Chest X-ray – widened mediastinum or abnormal aortic contour (50% patients)
(Sensitivity and specificity of X-ray and ECG are too low for rule-out or rule-in of aortic dissection).
Troponin – elevated if dissection causes myocardial ischemia
FBC – leucocytosis, creatinine elevated with renal artery involvement
CT, echocardiogram and MRI (highly accurate in diagnosis)
Summarise the demographics, risk factors, clinical features and investigation findings of an AORTIC ANEURYSM.
AORTIC ANEURYSM
Demographics
* More common over 50 yrs old
* Affects 4-7% men and 1-2% women over the age of 65
Risk Factors
* Smoking (accounts for about 75% of all abdominal aortic aneurysms)
* Male sex
* Advancing age
* Family history
* Hypertension
* Hypercholesterolaemia
* Atherosclerosis
* Congenital disorders: marfan syndrome, Loeys-Dietz syndrome, Vascular Ehlers-
Clinical Features
Can develop and grow before causing any symptoms.
* Pulsatile mass
* Pain and tenderness on palpation
* May present with abdominal, back or flank pain
* Bruit on auscultation
Ruptured aneurysm: shooting abdominal or back pain with a pulsatile abdominal mass + severe hypotension.
Investigation Findings
* Ultrasound
* CT – size, shape, potential for rupture
Describe the pathophysiology of oedema formation
Starling Forces
* Capillary Hydrostatic Pressure:
* Plasma Colloidal Pressure:
o Osmotic pressure caused by blood proteins draws fluid in
* Interstitial Fluid (Hydrostatic) Pressure:
o Hydrostatic pressure in tissues, may draw or oppose flow from capillary
o Varies with capillary bed: positive in glomerulus, negative in loose tissues like the skin
* Interstitial Fluid Colloidal Pressure:
o Proteins in tissues causes osmosis out of capillary
Pitting vs non-pitting
Pitting oedema:
* Indentation in the affected areas
* Excess fluid mainly composed of water
Non-pitting oedema :
* Associated with conditions affecting the thyroid or lymphatic system
* Build up of proteins, salts & water
Develop a different diagnosis for pedal and pulmonary oedema. Identify key aspects of a patient’s presentation (demographics, risk factors, symptoms and signs) that suggest each diagnosis.
Lower leg oedema and pulmonary oedema
↑ Capillary Hydrostatic Pressure → ↑ Venous Pressure: DVT, congestive HF (R), liver cirrhosis.
↓ Plasma Colloidal Pressure: IBD, malnutrition, nephrotic syndrome
Pulmonary Oedema
CARDIOGENIC
· Decrease in left ventricular systolic function & increase in systemic vascular resistance will lead to increased capillary hydrostatic pressure
· Causes exudation of fluid from vessels into lung interstitium & alveoli
NON-CARDIOGENIC
* Increased capillary permeability results in exudation of protein rich fluid into the alveoli
* Common causes include sepsis and pneumonia (usually
infective causes)
Signs & Symptoms
* Reduced pulmonary compliance
* Dyspnoea, cough
* Orthopnoea
* Paroxysmal Nocturnal Dyspnoea (PND)
* Cyanosis due to inefficient gas exchange
* Crackles on auscultation
Mitral stenosis: At the beginning of diastole, the mitral valve opens but is narrowed so there is decreased filling into LV: Opening snap at beginning of S2 followed by a mid-diastolic rumble (EXPIRATION)
Mitral regurgitation: Mitral valve leaks when LV contracts & blood flows backward into LA: Pansystolic murmur high pitched, soft S1 (EXPIRATION)
Aortic stenosis: Blood is unable to flow freely from LV to aorta during systole. Initial ejection click then crescendo-decrescendo pattern as pressure of blood flow ↑ then ↓ Systolic ejection murmur(EXPIRATION)
Aortic regurgitation: Valve does not close completely, leaking blood into LV: Early diastolic decrescendo murmur (EXPIRATION)
Tricuspid regurgitation: Valve does not close completely, leaking blood backward into RA: Pansystolic murmur high pitched (INSPIRATION)
Describe the demographics, aetiology, risk factors, pathophysiology, clinical features, diagnostic criteria, investigation findings and management of acute rheumatic fever (ARF).
Demographics: ATSI, younger, rual
Aetiology: autoimmune reaction to the bacteria group A streptococcus (S. Pyogenes)
Risk factors: Overcrowding, Poor living, reduced immunity, reduced health literacy
Pathophysiology
1. Molecular mimicry
GAS M protein shares proteinswith cardiac myosin, tropomyosin, and laminin–> T, B cells & antibodies target streptococcal M protein and cardiac myosin. CD4 causing realease of TNF a, IL2 and IFg
Clinical features: Fever, Migratory polyarthritis most commonly in the knees, ankles, elbows, and wrists, congestive heart failure, including chest pain, shortness of breath, fast heartbeat, Fatigue, Chorea, Erythema marginatum, Subcutaneous nodules
DIAGNOSTICALLY must have symptoms - and initial gas infection.
Investigation findings: Positive ASO and anti-DNAase-B titre AND Raised CRP ≥30 mg/L and ESR ≥30 mm/hr
Management: Following confirmation of ARF diagnosis, IM benzathine penicillin G injections must be given every 3-4 weeks for a minimum of 10 years as secondary prophylaxis
- Describe the demographics, aetiology, risk factors, pathophysiology, clinical features, investigation findings and management (including dental and fertility considerations), complications and prognosis of rheumatic heart disease (RHD).
Demographics: around 20 ys, more likely female
Aetiology: Repeated bouts of ARF due to GAS result in the development of RHD
Risk factors: GAS infection, Overcrowding, Low SES, Poor hygiene
Pathophysiology: Damage to heart tissue occurring in ARF leads to the formation of lesions in the cardiac tissue –> Aschoff bodies
Aschoff bodies in the endocardium, inflammation occurs in the L sided valves, and results in fibrinoid necrosis within cusps and/or tendinous cords. This inflammation leads to progressive fibrosis consisting of leaflet thickening, commissural fusion and shortening and thickening and fusion of the tendinous cords resulting in valvular dysfunction.
Clinical Features: Chest pain, Fatigue, Breathlessness, Swelling of the legs.
* Others: Arrhythmia, stroke, endocarditis, and complications during pregnancy.
Ix findings: Characteristic features on ECHO are valve dependent: Mitral valve features
o Prolapse of anterior leaflet
o Thickened leaflet tips
o Restricted posterior leaflet
o Chordal thickening
o Leaflet calcification
o Diastolic doming of anterior leaflet (dog leg appearance)
Management:
1. Secondary prophylaxis
2. Valve specific
* MR → mitral valve repair is the operation of choice OR mitral valve replacement with biological or mechanical prosthesis
o Avoid mechanical prosthesis if concerns about warfarin adherence or future pregnancy
* MS → diuretics are indicated for patients with symptomatic pulmonary venous congestion or pulmonary edema
o Surgically: Percutaneous balloon mitral valvuloplasty (PBMV) or mitral valve repair or replacement
* AR, AS, TR, TS→ valve replacement/ repair
Fertility considerations
* RHD is exacerbated by pregnancy due to the increased CO demand therefore use IUDs or implants
* planning pregnancy or are pregnant require coordinated health care to avoid multiple appointments and incurring of high travel costs and increased time away from their community
* Anticoagulants required post surgery pose serious risks in pregnancy to mum and baby including haemorrhage and teratogenicity
Dental considerations
- All those with ARF and RHD need regular dental review to reduce their risk of infective endocarditis
Complications: HF, Arrhythmia, PuL HTN
Prognosis: Severe carditis at first presentation is correlated with poorest prognosis
Assess strategies involved in the prevention of rheumatic heart disease, including primordial, primary, secondary, tertiary and quaternary prevention.
Primordial: improvements in living conditions that aim to decrease poverty and overcrowding.
1. Bathing and washing clothes
2. Safe disposal of waste water
3. Improving nutrition
4. reduce environmental impacts - pests, dust, temperature, hazards causing trauma
Primary: prevents the autoimmune response to the group A streptococcal infection from occurring. If primary prophylaxis is given during the early stage of the infection, antibiotics will interrupt the autoimmune response, and therefore ARF does not occur. Antibiotics given for infection.
Secondary: reduce the spread of new group A streptococcal strains. These strains may induce acute, chronic or repeated ARF attacks. Through the use of penicillin, group A streptococcus can be eradicated, preventing initial ARF attacks, as well as recurrences of ARF.
Tertiary :prevention of morbidity and mortality, which ultimately works by preventing the complications associated with RHD. This is achieved through the medical management of heart failure, operative management of valve lesions and treatment for the consequences of RHD, including stroke, infective endocarditis and arrhythmia.
Quaternary: Medical surveillance to ensure the patient is not over medicalised.
Relate the signs and symptoms of valvular heart disease (stenosis and regurgitation) to the underlying pathophysiology.
- Stenosis = failure of complete valve opening obstructs forward flow of blood from one heart chamber into another
o due to cusp abnormality e.g. calcification or scarring
MS - dyspnea, orthopnea, PND, ascietes, increased JVP
AS - dyspnea, angina, excertional
TS - increased JVP, arrhythmias
PS - cynosis and raised JVP
- Regurgitation = failure of complete valve closure allows back flow of blood from one heart chamber into the previous
o due to diseased cusps or supporting structures e.g. chordae tendineae or papillary muscles
MR - pulmonary oedema, enlarged heart
AR - wide pulse pressure, hyperkinietic heart beat, displaced heart
TR- hepatomegarly, increased JVP, ascites
PR- right ventricular dialation.
Define heart failure in regard to symptoms and ventricular function. Describe the demographics, aetiology, pathophysiology, clinical features, investigation findings and prognosis (including NYHA symptom score) of heart failure.
(right sided heart failure)
RIGHT HEART FAILURE BODY
o Decreased appetite, anorexia, nausea
o Peripheral oedema
o Weight gain
o Hepatomegaly
o Ascites
o Splenomegaly
o Jugular vein distention
SYSTOLIC DYSFUNCTION
* Ventricles are still being filled but contraction force is reduced, reducing SV and CO
DIASTOLIC DYSFUNCTION
* Heart failure of inadequate filling due to the inability of the cardiac muscle to relax
DEMOGRAPHICS: caused by L
Aetiology: HTN, CAD, TM, Arrhythmias, alcohol, drugs,
Pathophysiology: RV failure increased RV preload (from accumulation) increased RA pressure, systemic venous congestion
As the blood builds up in systemic circulation, peripheral oedema occurs (blood cant drain into IVC) – pitting oedema causing weight gain
Investigation finding CXR : 1) pulmonary vessel (venous) dilatation, moderate and marked, 2) pulmonary oedema, patchy and diffuse, 3) Kerley’s (septal) lines, and 4) pleural effusion.
Define heart failure in regard to symptoms and ventricular function. Describe the demographics, aetiology, pathophysiology, clinical features, investigation findings and prognosis (including NYHA symptom score) of heart failure.
( left heart failure)
LEFT HEART FAILURE
* LUNGS
o Dyspnoea on exertion
o Orthopnoea
o Cough
o Paroxysmal nocturnal dyspnoea
o Cyanosis
o Restlessness
o Fatigue
o Basilar crackles
o Elevated pulmonary capillary wedge pressure
o Tachycardia
SYSTOLIC DYSFUNCTION
* Ventricles are still being filled but contraction force is reduced, reducing SV and CO
DIASTOLIC DYSFUNCTION
* Heart failure of inadequate filling due to the inability of the cardiac muscle to relax
DEMOGRAPHICS: more common than right
Aetiology: HTN, CAD, TM, Arrhythmias, alcohol, drugs,
Blood pushed into the aorta is reduced increased blood in the ventricle LV pressure rises preventing the LA from emptying, raising LA pressure backlog of fluid into lungs
Causes pulmonary congestion (increased pulmonary venous pressure) and the increased pulmonary hydrostatic pressure
This backlog increases RV afterload RV hypertrophy and eventual RV failure as well
Investigation finding CXR : 1) pulmonary vessel (venous) dilatation, moderate and marked, 2) pulmonary oedema, patchy and diffuse, 3) Kerley’s (septal) lines, and 4) pleural effusion.
- Outline the acute and long-term management of heart failure, both pharmacological and non- pharmacological.
ACUTE
* Furosemide IV/IM
* GTN sublingual/oral
* Dobutamine 2.5-15 microg/kg/min IV
* Treat underlying arrhythmia/infection
* <94% O2 = non-invasive ventilation via high-flow O2 mask
* CPAP if unresponsive
* Intubate if unresponsive
* IDC to monitor urine output
LONG-TERM
* All patients: ACE-I/ARB + beta-blocker
* If symptomatic despite max. dose, substitute ACE-I/ARB with ARNI
* Loop diuretics to decrease symptoms
General Education:
* Fluid management advice
* Na/K/dietary intake (e.g. via dietician)
* Physical activity support + obesity advice
* Control other modifiable CVD risk factors
* Management of night-time symptoms via pillows/recliner
* Heart transplantation
* Ventricular-assist devices (till transplant/permanent)
- Describe the demographics, microbiological aetiology, pathophysiology, risk factors, clinical features and investigation findings of acute and subacute infective endocarditis.
- Acute infective endocarditis
o Sudden onset
o Rapidly progressive with high fevers, rigors and sepsis - Subacute infective endocarditis
o Slower, insidious onset
Demographics: M>F, over 60y
Aetiology: 60% Strep. Viridans, 20% Staph aureus
Pathophysiology
1. Preparation of the cardiac valve for bacterial adherence
2. Adhesion of circulating bacteria to the prepared valvular surface
3. Survival of the adherent bacteria on the surface with propagation of the infected vegetation
risk factors: IVDU, weakenned immune system, prostetic valve. birth defects
clinical features:
ACUTE
* Sudden high fever
* Tachycardia
* Fatigue
* Rapid and extensive heart valve damage causing symptoms of heart failure
SUBACUTE
* Fatigue
* Mild fever
* Moderately tachycardia
* Weight loss
* Sweating
* Anaemia
investigation findings:
* Blood cultures – primary investigation and yield the causative micro-organism
* Echocardiography – show heart valve vegetations and damage to the heart
- Understand the pathophysiology, common causes, investigation findings, management (including the use of the CHA2DS2-VASc and HAS-BLED scores) and complications of atrial fibrillation.
Pathophysiology: supraventricular arrhythmia There is pre-excitation of the atria due to bursts of electrical activity from other foci or from aberrant pathways
Atrial fibrillation is sustained by re-entry rhythms. –>Due to the abnormal conduction, the atria contract rapidly but ineffectively, and uncoordinatedly. This leads to stasis of blood within the atra and risk of formation of thromboembolism and stroke
causes
P - Pulmonary causes
I - ischemia/infarction/CAD
R - Rheumatic heart disease/mitral valve regurgitation
A - Alcohol, anaemia
T - Thyrotoxicosis/toxins
E - Electrolytes/Endocarditis
S - Sepsis
investigation findings
ECG
* Irregularly ireegular RR intervals
* Tachycardia is common
* P waves are not discernable (fibrillatory waves)
* Typically narrow QRS complex
FBC: check for anaemia
Electrolytes: check for imbalance
Serum glucose
TSH and T4 levels: screen for hyperthyroidism
Renal Function: eGFR and albumin
management:
1. Reduction of thromboembolism and stroke risk -Use NOACs, antiplatelets
- Symptoms relief (rate/rhythm control)
Rate control: atenolol or metoprolol 25mg
Rhythm control - Electrical cardioversion to restore sinus rhythm - Treatment of associated co-morbidities
CHA2DS2-VASc Score helps to determine the 1 year risk of a thromboembolic event
* Congestive heart failure or LV dysfunction
* Hypertension
* Age 75 years or older
* Diabetes mellitus
* Previous stroke, transient ischemic attack or thromboembolism
* Vascular disease (peripheral arterial disease, complex aortic plaque or prior MI)
* Age 65-74 years
* Sex (female)
complications: Ischemic stroke, Heart failure , Cardiac arrest
- Compare the aetiology, pathophysiology, clinical features, investigations and prognosis of the cardiomyopathies: hypertrophic, dilated, restrictive, and alcoholic.
- Compare the clinical features of common congenital heart diseases: ASD, VSD, PDA, FT, and COA.
L-R
- Atrial Septal Defect (ASD)
Small → asymptomatic until adult, CHF, pulmonary HTN (late, rare). RV hypertrophy
- Ventricular Septal Defect (VSD)
Most are small → asymptomatic, RV hypertrophy, pulmonary HTN and CHF - Patent Ductus Arteriosus (PDA)
IE common, Small → asymptomatic, Large → pulmonary HTN → shunt reversal, Eisenmenger syndrome with cyanosis and CHF
R-L (cynotic)
Tetralogy of Fallot (FT): Clubbing, polycythaemia and paradoxical embolism, Enlarged boot shaped heart on CXR. Mild (pulmonary stenosis) → like VSD, no cyanosis
Obstruction
Coarctation of Aorta (COA)
Infantile/pre-ductal (with PDA) → cyanosis of lower half of body → severe, die early, Calf pain from claudication
Discuss the elements of culturally safe history taking with respect to Aboriginal and Torres Strait Islander patients.
Demonstrating Understanding
Personal Communication
· Rapport:
· Language:
· Listening
· Time
· Non-verbal communication
· Personal Space
· Touch
· Silence
· Eye contact
· “Yes”
Develop a different diagnosis for a leg ulcer and identify key aspects of a patient’s presentation that suggest each diagnosis.
Venous ulcer:
Varicose veins and Venous stasis
Location: Gaiter region Lateral and medial malleoli
Pathogenesis: Venous stasis fluid accumulation in tissue + chronic low grade ischaemia → loss of skin integrity → ulceration
Features: Wet + shallow + irregular, Itchy & often painful
Arterial ulcer:
Atherosclerosis, Buerger’s disease
Location: Toes, M/L malleolus
Pathogenesis: Occlusion of arterial lumen → ischaemia → tissue damage/death → ulceration
Features: Dry + dark, Painful, Absent limb pulses, No bleeding, Trophic changes of the skin
Neuropathic ulcer:
Location: Pressure points Foot pads, ankles,
Pathology: Loss of sensation → repeated trauma → hard callus formation and necrosis of tissue → ulcer formation
Features: Deep + clean + punched out, Surrounding callus, Painless, Bleeds on probing
Malignant / benign tumour Ulcer:
Pathology: Sun exposure epithelial cell → mutation → epithelial cell proliferation and neoplasm → ulceration
SCC: ulcerated, nodular mass, hyperkeratotic, commonly seen on the face but limbs are also affected.
BCC: an elevated nodule with a central, ulcerated crater surrounded by telangiectatic vessels.
Melanoma: A mole like growth with ABCDE (asymmetrical, border irregular, colour multiple, diameter >6mm, evolution), ulceration is rare
Infective Ulcer:
Infection with pathogenic organism → Direct virulence effect of the organism / immune response of the host damage –> tissue ulceration
- Random, Often multiple ulcers, Pus + bleeding, Associated dermatitis
Relate the anatomy of the lower limb arteries to examination sites for peripheral pulses and
ARTERIES:
· abdominal aorta
o > common iliac arteries
§ > internal iliac artery
§ > external iliac artery
· becomes FEMORAL artery
o palpate midway between ASIS & pubic symphysis
o becomes POPLITEAL artery
§ palpate midline of popliteal fossa (posterior knee)
§ > anterior tibial artery
· becomes DORSALIS PEDIS artery
o palpate lateral to EHL tendon
§ > POSTERIOR TIBIAL artery
· palpate posterior & inferior to medial malleolus
relate the anatomy of the lower limb veins to the common sites of deep vein thrombosis (DVT) and varicose vein formation.
VEINS:
· varicosities: superficial veins of upper & lower leg > branches of long saphenous vein & short saphenous vein
· DVTs:
o thigh > Superficial femoral veins, popliteal veins
o calf > Posterior tibial veins, peroneal veins
Outline the demographics, aetiology, risk factors, pathophysiology, clinical features, investigation findings, management and complications of DVT
Demographics: Older age. female.
Aetiology: Virchow’s triad
* Stasis of blood, Endothelial injury and Hypercoagulability state
Risk factors
- recent plaster, immobilisation of lower extremities, increasing age, family hx, cancer, surgery, flights, trauma, smoking, pregnancy, obesity, HF
Pathophysiology Excess thrombosis leading to obstruction and stasis (acute)
1. Risk factors of Virchow’s triad
2. Thrombosis in deep vein of leg
3. Leads to clinical presentation
Clinical features
* Unilateral pain and swelling in the affected area – usually calf or thigh
* Red or discoloured skin
* A firmness or thickening of the vein (cord)
If progressed to PE – dyspnoea, tachycardia, pleuritic chest pain, cough, haemoptysis or syncope
Investigation findings
* Bloods – FBC, INR, aPTT
* D-dimer – if negative can rule out DVT, positive does not confirm
* Duplex ultrasonography – detect blockages or blood clots in deep veins
Management Primary approach is anticoagulation
* Direct oral anticoagulants
* Low-molecular-weight heparin
Complications * PE – clot breaks free and travels to lung
* Post-thrombotic syndrome – development of long-term symptoms in the calf. Damage to the veins results in venous hypertension.
* Increased risks of recurrent thrombosis
Describe the demographics, aetiology, risk factors, pathophysiology, clinical features and investigation findings (including the use of the Wells’ criteria and PERC) of a pulmonary embolus (PE)
DEMOGRAPHICS
Mostly occurs in people >60yrs + those with risk factors identified in PERC/Well’s criteria
AETIOLOGY - Clots
RISK FACTORS
Condition of stasis: e.g. surgery, long flights etc.)
Acute and chronic medical illness (particularly MI, HF, COPD, atherosclerosis)
Well’s score > 4 warrants imaging
If the answer to all of PERC is no, PE can be excluded
PATHOPHYSIOLOGY
Virchow’s Triad: hypercoagulable state, venous stasis, vessel injury → blood clot develops → clot dislodges + migrates to inferior vena cava, RA, RV + gets lodges in pulmonary artery → PE
Dec. perfusion to lung parenchyma distal to clot (leading to ischaemia of lung tissue)
Blood pumped from RV to pulmonary arteries cannot pass clot → inc. pulmonary + RV pressure → inc. RV strain → inc. RV workload + dec. RCA perfusion → symptoms of MI/RHF
Inc. dead space ventilation + V/Q mismatching → chemoreceptors detect inc. CO2 + dec. O2 → signal to the brain to inc. breathing rate
CLINICAL FEATURES
Sharp, pleuritic chest pain + dyspnoea: ischemia of lung tissue distal to clot (chest pain can also be from inc. RV + pulmonary pressure)
Tachypnoea: dec. arterial O2
Tachycardia: inc. RV + pulmonary pressure
Hypotensive: inc. RV workload + dec. RCA perfusion
Pleural rub “velcro sound”/”walking on snow” on inspiration + expiration
May also be calf swelling + tenderness on examination
INVESTIGATION FINDINGS
Positive D-Dimer: body attempts to break down clot (fibrinogen breakdown products in blood)
CXR: Hampton’s hump (rare but specific sign of PE), may also get Westermark’s sign (oligaemia) or pleural effusion - ischemia of lung tissue distal to clot
CT-PA: filling defect - blood pumped from RV cannot pass clot | GOLD STANDARD
ECG: S1Q3T3 pattern - inc. RV + pulmonary pressure
Compare the mechanism of action, indications, contraindications, route and frequency of administration, desired effects, side effects and reversibility of anticoagulant medications: warfarin, NOACs, heparin and low-molecular weight heparin.
Warfarin
MOA: Warfarin competes with vitamin K and inhibits epoxide reductase thus inhibiting the synthesis of vitamin K- dependent clotting factors, thereby leading to reduced clotting
Indications: Prevention and treatment of emboli.
Contraindications: Alcoholism, pregnancy, active bleeds,
Route and frequency: Taken orally, usually at night - and must be taken at the same time each day
Side effects: Severe bleeding, rash, bruising, nausea and vomiting,
Reversibility - Vitamin K1
NOACs: non-vitamin-K-antagonist Oral anticoagulants
MOA: Direct thrombin inhibitors - dabigatran
* Reversibly inhibit both free and fibrin-bound thrombin. Prevents conversion of fibrinogen to fibrin
Factor Xa inhibitors - rivaroxaban and apixaban
* Selective for factor Xa rather than thrombin Thus blocks thrombin production, conversion of fibrinogen to fibrin
Indications: Moderate to high risk unstable angina, STEMI undergoing early invasive management including PCI
Contraindications: Renal impairment (CrCl <30 ml/min), Bleeding risks: Active bleeding, bleeding disorders etc, Pregnancy
Route: All NOACs are taken orally
Side effects Typically well tolerated
- SE mainly bleeding ranging from minor
Reversibility Only for dabigatran → Idarucizumab 5g IV, by bolus or infusion
Heparin
MOA
Unfractionated Heparin
* Potentiates the activity of antithrombin III which inhibits factor 2 (thrombin) and factors 9 and 10
Low Molecular Weight
* Has a greater effect on factor Xa than on thrombin (only inhibits factor Xa, not II)
* Advantages over regular heparin include: longer half life, less bleeding risk, less monitoring, and can be administered by the patient subcutaneously
Indications:Prevention and treatment of thrombotic events such as deep vein thrombosis (DVT) and pulmonary embolism (PE) as well as atrial fibrillation (AF).
Contraindications Absolute: Heparin-induced thrombocytopenia Hx, Known hypersensitivity, Active bleeding
Relative: Bleeding disorders e.g. Hemophilia, Conditions w/ catastrophic bleeding e.g. haemorrhagic stroke, CrCl <30 ml/min
Route and frequency of administration UFH
* Typically taken IV
* Route of administration and dosage of LMWH varies according to indication
* Typically parentally once or BD
Side effects: Bleeding from puncture sites, Wounds, Anaemia
Reversibility Stop UFH or LMWH immediately
- Protamine
Relate the aetiology and risk factors of leg ischaemia to the underlying pathophysiology.
Peripheral Artery Disease (Ischemia)
Aetiology
* Insufficient tissue perfusion due to atherosclerosis in the aorta and peripheral arteries (Atherosclerotic plaques reduce the arterial lumen → arterial insufficiency distal to the occlusion.)
* Often coexists with coronary artery disease (CAD), stroke
Risk Factors (same as Atherosclerosis)
* Smoking
* Diabetes mellitus
* Arterial HTN
* Dyslipidaemia
* FHx: cardiovascular events in the first-degree relatives below the age of 55 (male)/65 (female)
* High homocysteine levels (homocystinuria)
* Obesity
* High fibrinogen levels
* Hyperphosphatasemia
* Stress
* Increased alcohol consumption
Describe the spectrum of clinical presentation of peripheral arterial disease, ranging from asymptomatic disease to critical ischaemia.
Intermittent claudication (10-35% of patients)
* Pain, cramps, or paresthesia (burning, prickling, tingling) distal to arterial occlusion
* Worsens upon exertion
* Completely relieved by rest
* Reproducible
Critical Limb Ischemia/Chronic Limb Threatening Ischemia with Rest Pain
* Severe pain or numbness in the legs and feet while not moving. Worsens when in a reclined position and improves when feet hang off the bed or standing
* Shiny, smooth, dry skin in the legs or feet,
* Absent or diminished pulse in the legs
o Rest pain lasting > 2 weeks, Nonhealing ulcers , Tissue loss (gangrene)
Acute Ischemia: Medical emergency, Sudden onset severe ischemia associated with sensory loss, motor loss and intense pain
Outline the management of peripheral arterial disease and compare this to the management of coronary heart disease.
Management of PAD
Conservative: Smoking cessatio, exercise therapy, Foot care
Medical Therapy
o Antiplatelet therapy reduced morbidity and mortality
Aspirin: irreversible COX inhibition → decreased thromboxane A2 synthesis → decreased plt aggregation
o Cholesterol/Lipid-lowering agents (usually statins)
Statin therapy (ezetimibe, PCSK9 inhibitors) lowers lipids. Lowering LDL-C in particular to the lowest possible target greatly improves cardiovascular outcomes.
o Antihypertensive treatment
ACE-I, ARBs, CCBs,
o Hyperglycaemia control
Revascularisation
* Minimally invasive interventional radiology: percutaneous transluminal angioplasty (PTA) with or without stenting
* Surgical procedures
o Operative vascular reconstruction (bypass surgery): used when a long portion of an artery is completely blocked, causing the patient to experience severe symptoms
o Stenting or stent grafts- for occlusive or aneurysmal disease
Amputation
* Last resort
o in the event of gangrene
Describe the demographics, aetiology, pathophysiology, risk factors and clinical features of varicose veins
Demographic: Women with a BMI greater than 30 are three times as likely to develop varicose veins.
Aetiology caused by weak vein walls and dysfunctional valves.
Risk factors: Age. women, pregnancy, standing.
Pathology: Tortuous veins : Stasis and increased pressure of blood causes veins to change shape
Enlarged, visible veins : Defective deep vein valves leads to backflow, which leads to increased pressure in superficial veins, causing enlargement
Only superficial veins affected: Deep veins rely on surrounding musculature to assist with venous return, superficial veins have no assistance from muscle if valves are defective
Stasis dermatitis : Blood is not able to flow out of superficial veins due to deep vein valve defectiveness, causing stasis and venous hypertension. There is subsequent leakage of blood into tissues and cutaneous inflammation. Skin will be erythematous, dry and itchy.
Venous ulcers (gaiter region): Often follows stasis dermatitis. A wound of the skin has inhibited healing- due to venous insufficiency from varicose vein stasis (lack of oxygen and nutrients) and weakened skin (due to swelling). This inhibited healing leads to ulceration.
Describe the demographics and risk factors of skin cancers in Australia: BCC, melanoma, SCC.
Demographics:
- BCC can develop in younger people however common in people over 40
- SCC most commonly occurs in people over 50
Risk factors
- UV radiation - causes damage to DNA
- Immunosuppression- especially SCC
Melanomas
Family history and genetic susceptibility
- Suggested that one or more first degree relatives with melanoma are at a greater risk of being diagnosed with melanoma
- People with fair skin (lack of melanin) are more susceptible to cancer
- There is an association with the number of benign nevi or moles on the person’s body and melanoma diagnosis- large number of benign nevi and moles, the greater the likelihood of melanoma diagnosis
Compare the demographics, pathogenesis, common and differentiating clinical features, investigation findings and complications of the common causes of vasculitis.
Henoch Schonlein Purpura (IgA Vasculitis)
DEMOGRAPHICS: Children 2-8 yrs. urti
PATHOGENESIS: IgA immune complexes within small blood vessels (arterioles & capillaries) necrotising inflammation
CLINICAL FEATURES: Immune mediated haematuria, Proteinuria, Palpable, purpura, Abdominal pain (colicky)
INVESTIGATIONS: Biopsy of affected organ = IgA deposition
COMPLICATIONS: Renal disease; nephritis, chronic kidney disease, Arthritis – large joints
Wegener’s Polyangitis
DEMOGRAPHICS: Middle-aged adults
PATHOGENESIS: Infectious exposure ANCA BV necrosis neutrophil activation endothelial cell injury & inflammation thrombosis
CLINICAL FEATURES: Ear/nose/throat = sinusitis, nasal disease, subglottic stenosis (specific – loss of nasal septum), otitis media, hearing loss, ear pain, oral lesions
INVESTIGATIONS: Positive (ANCA), BIOPSY
COMPLICATIONS: Glomerulonephritis chronic kidney failure, Orbital mass
Polyarteritis Nodosa (PAN)
DEMOGRAPHICS: Middle-aged or older adults
PATHOGENESIS: Necrotising, Immune complex mediated systemic inflammation of arteries
CLINICAL FEATURES: Systemic features – fever, anorexia, weight loss, myalgia, arthralgia
Skin – cutaneous or subcutaneous nodules, palpable purpura, livedo reticularis, skin infarction
INVESTIGATIONS: Biopsy of affected tissue
Angiography
COMPLICATIONS: Acute renal failure, Polyneuropathy
Buerger’s Disease
DEMOGRAPHICS: MALES, JEWISH, smoking
PATHOGENESIS: Inflammation of arteries hypersensitivity reaction thrombosis segmental, transmural inflammation + lumen thrombosis gangrene
CLINICAL FEATURES: General systemic signs, Pain, Raynaud’s phenomenon
COMPLICATIONS: Gangrenous toes amputation
Kawasaki Disease
DEMOGRAPHICS: children; seen before 5 yrs old
PATHOGENESIS: Delayed hypersensitivity reaction in genetically susceptible individuals – triggered by viral infection
CLINICAL FEATURES: Fever, bilateral nonexudative conjunctivitis, cervical lymphadenopathy, polymorphous rash, oral cavity changes (erythema, cracked lips, strawberry tongue)
INVESTIGATIONS: Coronary artery lesions seen on echocardiogram
COMPLICATIONS: Acquired cardiac disease in children
Giant Cell Arteritis
DEMOGRAPHICS: Older age group: >50 yrs old
PATHOGENESIS: Immune dysfunction to unknown antigen; T cell inflammation and formation of granuloma giant cells = damages blood vessels and causes thrombosis
CLINICAL FEATURES: increasing headache
Diplopia, Tender temporal arteries
INVESTIGATIONS: Thickened palpable, nodular tender temporal artery
COMPLICATIONS: vision loss
Understand the pathophysiology of shortness of breath and develop a differential diagnosis for shortness of breath, identifying key aspects of a patient’s presentation that suggest each diagnosis.
Dyspnoea is the subjective sensation of breathlessness that is excessive for any given level of physical activity.
Pathophysiology is complex – involves activation of several pathways that lead to increased work of breathing, stimulation of receptors of upper or lower airway, lung parenchyma or chest wall and excessive stimulation of the respiratory centre by central and peripheral chemoreceptors.
Pulmonary Embolism: Pleuritic chest pain or Previous PE, Immobilization
Pneumothorax: Trauma/ Malignancy/ Tall and thin :Marfans Syndrome, Tracheal deviation, Absent or reduced breath
Asthma: atopy, Cough at night/ morning, accessory muscles , Bilateral
Consolidation Pneumonia: Cough painful & dry at first, Fever and rigor, Increased vocal fremitus, Reduced breath sounds , Bronchial breath sounds crackles
Pleural effusion: Transudate- cardiac failure, Exudate- Pneumonia, Pulmonary infarction, Displaced trachea and apex beat, Stony Dullness over fluid
Interstitial Lung disease: Drug & occupational Hx, Travel Hx , Reduced Expansion, Cough Clubbing Crackles (3 Cs)
Compare the demographics, aetiology, risk factors, clinical features and chest x-ray findings for the
different types of pneumonia: community-acquired, hospital-acquired, atypical, aspiration, viral, lobar, bronchopneumonia.
community-acquired: sick contacts, smoking, Strep pneumoniae (gram +ve diploccoci) Young, healthy, 1-3 days high fever. Pleuritic chest pain, Rusty sputum, purulent cough, fever, cyanosis, enlarged tonsils, cervical lymphadenopathy, confusion, ↑HR, ↑RR, ↓BP, ↓ expansion, ON XRAY:Unilateral consolidation of lobe.
hospital-acquired:seen in unhealthy, hospital stay >2 days,
Gram negative: Klebsiella, haemophillus influenzae, 1-3 days high fever. Pleuritic chest pain, fever, cyanosis, ↑HR, ↑RR, ↓BP, ↓ expansion, dull percussion, increased fremitus (consolidation), CXR: bronchial (patchy consolidation, usually bilateral lower lobes
atypical: Young people, Mycoplasma pneumoniae, HPC: slow onset, sever dyspnoea, wheeze, dry cough, flu-like symptoms, CXR: interstitial consolidation, appears worse than symptoms suggest.
aspiration: People with dysphagia, Parkinson’s, Accidental ingestion of mixed oral flora, bronchospasms, crackles on auscultation, cough with foul-smelling sputum, CXR: superior segment of right lower lobe (most common site of aspiration) – infiltrates on X-ray
Outline the management of community-acquired pneumonia, including the specific antibiotics used and non-pharmacological management. Understand the use of severity scores (e.g. SMARTCOP/CURB-65) to determine the severity of pneumonia and how this impacts management.
assess severity via severity scores:
CURB-65
· 1 point each for: acute confusion, urea >7, resp rate >30, BP <90/<60, age >65
· 0-1 = treat in community, 2 = inpatient, 3-5 = inpatient & consider ICU
· can use abbreviated version CRB-65 if access to bloods unavailable
§ if any red flags present – tachypnoea >22, tachycardia, hypotension SBP <90, hypoxia <92%, lactate >2, multi-lobar, acute confusion
§ also consider social circumstances e.g. support at home, comorbidities, etc.
o to identity requirement of ICU or higher risk of MORTALITY:
§ SMART-COP
· 2 points each for: SBP <90, oxygen low (PaO2 <70 or O2 sat ≤93% or PaO2/FiO2 <333 if age ≤50 ; , arterial pH <7.35
· 1 point each for: multi-lobar, albumin <35, resp rate >25 if age ≤50 or >30 if age >50, tachycardia >125, acute confusion
· low if 0-2, moderate if 3-4, high if 5-6, very high if 7+
empirical antibiotics
o based on severity
§ low:
· usually managed in community with oral therapy
· monotherapy with amoxicillin OR doxycycline or clarithromycin (if clinical suspicion of atypical pathogens or penicillin allergy)
· combination therapy with amoxicillin + doxycycline (if unable to review or no improvement with monotherapy within 48 hours)
§ moderate:
· combination therapy with oral amoxicillin OR IV benzylpenicillin + oral doxycycline OR clarithromycin
§ high:
· combination therapy with IV ceftriaxone or cefotaxime + IV azithromycin
· additional therapy based on pathogen e.g. staph aureus
· switch once stable to oral amoxicillin + doxycycline or clarithromycin
Discuss the limitations of assessing and managing pneumonia in a rural setting, including availability of investigations.
Assessing pneumonia:
shortage of healthcare staff, particularly those trained in the management of severe pneumonia
Stoic attitude resulting in fewer presentations to health clinics for pneumonia.
CXR machines may not be available in some rural settings. This is an essential component in the diagnosis of pneumonia
There is a delay in diagnosis because certain/most investigations are not available, and thus must be outsourced
Management of pneumonia
* Patients who need intensive care support must be transported to a centre with appropriate equipment.
o Some rural and remote areas do not have equipment necessary to treat severe pneumonia – such equipment include ventilators, oxygen machines, specialist medications.
o Lack of specialist access.
o Delay in arriving to a specialist centre/hospital that can manage pneumonia, leading to progression of symptoms.
Describe the definition, demographics, aetiology, pathophysiology, risk factors, clinical features and long-term management (including home oxygen therapy and non-pharmacological) of COPD.
COPD = chronic pulmonary disease that presents with progressive shortness of breath caused by airway inflammation. It is subdivided into chronic bronchitis and emphysema.
Demographic: M, >60, Smoker, occupation.
Aetiology:Tobacco use, Air pollution, Recurrent pulmonary infections and TB, Premature birth, Alpha-1-antitypsin deficiency
Pathophysiology
C Bronchitis:Bronchial Inflammation IL, TNF, IFNγ, Excess mucous & narrowing (fibrosis) of bronchi
Emphyema: 1. Neutrophil Protease - macrophage MMP. -Alveolar wall & elastic fiber loss. -Loss of recoil, air trap, No inflam/fibrosis.
Clinical features
CB: Cough & Wheezing. Bronchial inflam. & recurrent infections
Emph: Dyspnea, Barrel chest, Alveoli & elastic fiber loss.
Management:COPD X
COnfirm diagnosis, optimise function, prevent deteriation, develop support and stop exaccerbations.
Compare the first line management of infectious and non-infectious exacerbations of COPD.
First-line management (all cause):
* Salbutamol 100 micrograms, up to 10 separate actuations by inhalation via pMDI with spacer, repeated as necessary
* OR terbualine 500 micrograms, 1 or 2 actuations inhalation
* OR ipratropium 21 micrograms, up to 6 separate actuations by inhalation via pMDI with spacer
- Systemic corticosteroids shorten duration of hospital admission and hastens return to previous lung function and stable symptom control.
o Should be used routinely for severe exacerbations of COPD
o 5-day course is adequate of Prednisone 30-50mg orally, once daily. - Oxygen therapy if patient is hypoxaemic aiming for saturations of 88-92%
o Caution due to risk of hypercapnic respiratory failure during an exacerbation
Antibiotic regime:
* Do not use antibiotic therapy unless the patient has clinical features suggestive of bacterial infection
* Shared decision making to determine whether antibiotic therapy is useful
* If indicated – use oral antibiotic therapy for all patients, including hospitalised.
o Amoxicillin 500mg orally, 8-hourly for 5 days OR
o Amoxicillin 1g orally, 12-hourly for 5 days
o Doxycycline 100mg orally, daily for 5 days.
Describe the childhood and adult immunisation recommendations for influenza and pneumonia Prevention.
Infleunza
Annual vaccinations is the most important measure to prevent influenza and its complications and is recommended for all individuals aged 6 months and over.
- Recommended to get in April
- Best protection occurs within the first 3-4 months following vaccination. Not immediately effective
Free flu vaccinations from about May-June for certain population groups: 6m-5y, >65, preg, ATSI,
Pneumococcal
* Bacteria Strep pneumoniae - can cause: meningitis, pneumonia and bacteremia etc.
* Vaccine recommended for: infant/ kids, >70, ATSI >50, conditions,
* Vaccines available in Aus: 13vPCV, 15vPCV and 23vPPV
- All children are recommended to receive 13vPCV in a 3-dose schedule at 2, 4 and 12 months of age. Can be received as early as 6 weeks, then next dose would be 4 months.
- Some Infants and children including Aborigional and Torrest Strait Islander children or those with a risk condition(s) for pneumococcal disease need extra doses.
- A single dose of 13vPCV or 15vPCV is recommended for all non-Indigenous adults at 70 years of age.
Outline the contraindications to, effectiveness/benefits of and complications of the influenza Vaccination.
Contraindications Absolute:
* Anaphylaxis
Precautions:
* Egg allergy, Latex allergy, Guillain-Barre syndromimmune-oncology therapy
Effectiveness/ Benefits
* About 70-90% strain-specific effectiveness in healthy adults for 1-3 years
* In healthy adults is associated with reduced absenteeism and reduced demand on healthcare resources
* Effectiveness does not wane however yearly antigenic drift in the circulating strains of influenza virus results in yearly vaccinations
* In elderly people, the protection conferred against influenza is about 30-60%, but efficacy of preventing hosptalisation and pneumonia is around 50-60%.
Complications
* Injection site reactions - induration, swelling, redness pain
* Systemic reactions few hours after administration and lasts for 1-2 days: fever, malaise, myalgia
* Immediate adverse reaction: hives, angioedema, anaphylaxis
* Fever and febrile convulsions in children under 5 years (associated with vaccines not currently available in Aus)
* Guillain-Barre syndrome
Outline the demographics, aetiology, risk factors, clinical features and investigation findings of Bronchiectasis
DEMOGRAPH: rural, ATSI, SDOH, W, kids.
AEITOLOGY: Obstructive lung disease associated with an impaired host defence or result of an infectious insult.
PATHOPHY: Initial infection → inflammation → impaired mucocilliary clearance → airway mucus hypersecretion + obstruction → microbial colonization/infection → bronchial dilation + airway destruction
RISK FACTORS: post-infection, primary/secondary immune deficiency, asthma
CLINICAL FEATURES Chronic cough, sputum +/- recurrent chest infections (exacerbations), haemoptysis, chest pain, SOB, lethargy + exercise initiation, chronic sinus inflammation + GORD
INVESTIGATION FINDINGS Pathology: FBC, immunoglobulin deficiencies, CRP
Sputum MCS: mostly bacteria
Functional assessment: spirometry + DLCO + 6min walk test
Imaging: CXR, CT
Additional: sweat test, genetic testing
Describe the demographics, aetiology, pathophysiology, risk factors, clinical features and investigation findings for tuberculosis.
DEMOG: overseas-born residents
AEITOLOGY Caused by Mycobacterium tuberculosis - spread when a person with active TB in lungs coughs/sneezes
PATHO: Aerosolization → phagocytosis → phagolysozome blockage + replication → T-helper response (TH1) → granuloma formation → clinical manifestations → active disease + transmission
A) Aerosolization occurs when a person with active tuberculosis forcefully expires through actions such as coughing.
B) Inhaled droplets small enough to reach the alveolar sacs, where they will encounter macrophages, dendritic cells + monocytes. The macrophages will phagocytose the bacteria and attempt to destroy the invader. Dendritic cells migrate to lymph nodes to activate T-helper cells.
C) M. tuberculosis prevents the phagolysosome fusion (combination of phagosome and lysozyme that contains acidic products + degradation enzymes), avoids destruction, begins replicating, and releases DNA, RNA, proteases, and lipids. Additionally, the macrophages will release cytokines + VEGF. VEGF triggers angiogenesis and inc. vascularisation to the lesion. The cytokines will initiate the innate response and recruit NK cells, dendritic cells, neutrophils + macrophages.
D) The T-helper cell response will involve the migration of TH1, Tregs + B cells. These cells will combine to form the granuloma.
E) The granuloma is a prison to wall off the bacteria from spreading systemically.
F) Later, or present, immunocompromisation prevents the granuloma from containing the bacteria. The bacteria will spread and multiply in multiple clinical manifestations.
G) During this phase, the bacteria can be aerosolized by the new infected host and begin the cycle anew.
RISK FACTORS: Close contacts , Medical conditions that worsen, IVDU, homeless, HIV infection, young and old
CLINICAL FEATURES: Sickness/weakness, sudden weight loss, fever, night sweats, (chronic) cough, chest pain (sometimes pleuritic), appetite loss and haemoptysis
INVESTIGATION FINDINGS TST/Mantoux: skin raised if infected with TB
IGRA: blood interferon-gamma release assay test immune response to TB
Culture: most sensitive - acid-fast staining bacteria
Sputum: generally 3 samples - preferably in the morning
CXR: air space consolidation, cavitation + fibrous contraction, particularly in upper lobes
Summarise the aetiology and clinical features of acute bronchitis.
Aetiology
* Viral
o Influenza A and B
o Parainfluenza
o Adenovirus
o RSV
o Rhinovirus
o Coronavirus
* Bacterial
* Environmental (allergens, smoking)
Clinical Features
* Cough
o Coughing bouts with/without sputum production
* Coryzal symptoms
o Runny nose and sore throat
o Headache
o Malaise
o Myalgia
o Chest pain
o Mild dyspnoea
o Fever
* Auscultation findings
o Rhonchi (coarse loud sounds due to large airway constriction)
o Wheezing
o Fine crackles (rare)
Summarise the causes and clinical features of acute respiratory failure and atelectasis.
Acute Respiratory Failure
Causes
* Acute respiratory distress syndrome, COPD or Asthma (obstruction), Opioid overdose or alcohol abuse, Stroke
Clinical Features
* Dyspnoea, Extreme fatigue, Peripheral cyanosis
* With high carbon dioxide levels people experience
o Tachypnoea, Confusion, Blurred vision , Headaches
Atelectasis
Causes:
* Airway obstruction -> nonventilated alveoli -> reabsorption of gas -> lung collapse
* Compression atelectasis: external space occupying lesion (e.g. pleural effusion) -> compresses lung -> forcefully pushes air out of the alveoli
* Adhesive atelctasis: surfactant deficiency or dysfunction -> increase in surface tension of alveoli -> instability and collapse
* Contraction atelectasis: parenchymal scarring leads to contraction of the lung
* Relaxation atelctasis: loss of contact between parietal an visceral tissue (pneumothorax)
* Replacement atelectasis: all alveoli in an entire lobe are replaced by tumour -> loss of volume -> lung collapse
* Post operative atelectasis
Clinical Features
* Can be asymptomatic if small number of alveoli are affected, Acute dyspnoea, Chest pain, Tachypnoea, Tachycardia, Cyanosis, Dullness to percussion, Diminished breath sounds, Decrease tactile/vocal fremitus over affected lung, Possible tracheal deviation
List the demographics and health effects of smoking, including the effects of passive smoking and Vaping.
Outline the principles of motivational interviewing regarding smoking cessation. Describe the management options for smoking cessation.
List barriers to clinicians providing smoking cessation advice.
Describe tge microbiology seen in this image for ARF
acute tonsillitis/pharyngitis caused by GAS without antibiotic treatment → development of antibodies against streptococcal M protein → cross-reaction of antibodies with nerve and myocardial proteins (most commonly myosins) due to molecular mimicry → type II hypersensitivity reaction → acute inflammatory sequela
IMAGE SHOWN: A collagenous nodule (green overlay) is seen within the myocardial tissue. The nodule contains a loose lymphoplasmacytic infiltrate and large eosinophilic cells with an ovoid nucleus (Anitschkow cells, arrowheads). Anitschkow cells are thought to be histiocytes.
These nodules, referred to as “Aschoff bodies,” are thought to represent myocardial granulomas, which are typically found in rheumatic heart disease.
Pathogenesis: Inflam. plasma leak into pericardium coagulation fibrin.
Gross: White ‘fibrin’ covering the surface of heart (Bread & Butter)
Micro: Inflamed pericardium, Fibrin deposits on the surface.
Clinical: Friction rub, weak heart sounds, fibrillations, murmur.
What is shown in thos cross section of a heart valve and what is the pathophysiology behind it.
Photograph of a dissected heart specimen opened to show the endocardial aspect of left atrium and ventricle
The mitral valve is thickened (indicated by arrow) and shows numerous yellow vegetations on the atrial (superior) aspect of the valve (examples indicated by arrowheads).
This gross appearance is typical of infective endocarditis of the mitral valve.
Pathogenesis [1]
Damaged valvular endothelium → exposure of the subendothelial layer → adherence of platelets and fibrin → sterile vegetation (microthrombus)
Localized infection or contamination → bacteremia → bacterial colonization of vegetation → formation of fibrin clots encasing the vegetation → valve destruction with loss of function (valve regurgitation) [11]
Valve involvement [10]
Frequency of valve involvement: mitral valve > aortic valve > tricuspid valve > pulmonary valve
The tricuspid valve is the most commonly affected valve in persons who inject drugs (associated with Pseudomonas, S. aureus, and Candida).
Clinical consequences [1][11]
Bacterial vegetation → bacterial thromboemboli → vessel occlusion → infarctions
Emboli can lead to metastatic infections of other organs.
Formation of immune complexes and antibodies against tissue antigens → glomerulonephritis, Osler nodes
What is this CHD, what is the pathophysiology it causes and what signs are present?
A defect in the ventricular septum leads to a left-to-right shunt, the volume of which is dependent on the size of the defect. Blood flows from the left ventricle to the right ventricle (white arrow) along the pressure gradient (1). This leads to increased RV and LV preload (due to increased end-diastolic volume), ventricular hypertrophy and dilation (double-headed white arrows), and pulmonary hypertension resulting from excessive pulmonary blood flow (2). In end-stage disease, the pressure gradient is reversed because of Eisenmenger syndrome (shunt reversal), leading to the flow of mixed blood to the systemic circulation (white arrow) and subsequent cyanosis (3).
Blue: structures that contain deoxygenated blood; Red: structures that contain oxygenated blood; Purple: structures that contain mixed blood
What is this CHD, what is the pathophysiology it causes and what signs are present?
Cardiac hemodynamics in atrial septal defect
An atrial septal defect causes blood to flow from the left to the right atrium (left-to-right shunt; white arrow), resulting in volume overload of the right atrium and ventricle (1). As a result, there is dilation and compensatory hypertrophy (double-headed white arrows) of the right atrium and ventricle (2). In the late stages, Eisenmenger syndrome with shunt reversal (right-to-left shunt; white arrow) and cyanosis can occur (3).
Blue: structures that contain deoxygenated blood; Red: structures that contain oxygenated blood; Purple: structures that contain mixed blood
What is this CHD, what is the pathophysiology it causes and what signs are present?
Cardiac hemodynamics in patent ductus arteriosus
In patent ductus arteriosus, there is a left-to-right shunt, with blood flowing from the aorta to the pulmonary arteries during both systole and diastole (1). This shunt leads to volume overload (recirculation) of the blood within the pulmonary vessels, the left atrium, and left ventricle (2). Eventually, because of the increased blood flow to the pulmonary circulation, pulmonary hypertension may develop as well as Eisenmenger syndrome, which involves a shunt reversal. The left-to-right-shunt without cyanosis becomes a right-to-left shunt with cyanosis (3).
Blue: structures that contain deoxygenated blood; Red: structures that contain oxygenated blood; Pink: structures that contain mixed blood
What is this CHD, what is the pathophysiology it causes and what signs are present?
Coarctation of the aorta
(1) Stenosis distal to the left subclavian artery results in hypertension (↑ BP) in the upper extremities and the head, and hypotension (↓ BP) in the lower extremities and abdomen.
(2) If coarctation involves the origin of the left subclavian artery, BP in the right arm and head will be higher than in the left arm, lower extremities, and abdomen.
Genetic defects and/or intrauterine ischemia → medial thickening and intimal hyperplasia → formation of a ridge encircling the aortic lumen → narrowing of the aorta → ↑ flow proximal to the narrowing and ↓ flow distal to the narrowing
acyanotic
Brachial-femoral delay: weak femoral pulses
↑ Blood pressure (BP) in upper extremities and ↓ BP in lower extremities
What is this CHD, what is the pathophysiology it causes and what signs are present?
Tetralogy of Fallot
Tetralogy of Fallot is the simultaneous occurrence of:
(a) Pulmonary stenosis
(b) Right ventricular hypertrophy
(c) Ventricular septal defect (VSD)
(d) An overriding aorta (above the VSD)
The hemodynamic effects depend on the extent of right ventricular outflow tract obstruction. With mild obstruction (1), a left-to-right shunt is more pronounced and there is mild cyanosis. With severe obstruction (2), a right-to-left shunt is more pronounced, which results in severe cyanosis. Pulmonary circulation may be supplied via a patent ductus arteriosus
Untreated children tend to squat: squatting → ↑ SVR → ↓ right-to-left shunt → ↑ blood flow to pulmonary circulation → ↓ hypoxemia → relief of symptoms
Cardiac examination findings
Harsh systolic ejection murmur at the left upper sternal border
Single S2
Possible RV heave and systolic thrill
What is this type of cardiomyoapthy and what are the general features and the pathophysiology
Hypertrophic cardiomyopathy
Pathophysiology: Concentric hypertrophy of the left ventricle (including the interventricular septum) → ↓ ventricular relaxation → ↓ diastolic filling and systolic output → ↓ myocardial and peripheral perfusion
Obstructive type (HOCM): left ventricular outflow tract (LVOT) obstruction and mitral regurgitation due to systolic anterior movement (SAM) of the mitral valve [1]
Clinical features: Frequently asymptomatic
Signs of left heart failure (dyspnea, syncope, dizziness)
Arrhythmias
S4 gallop
Possible holosystolic murmur from mitral regurgitation
Sudden death
LV cavity size: Decreased
EF: Normal
Wall thickness: increased
What is this type of cardiomyoapthy and what are the general features and the pathophysiology
Dialated cardiomyopathy
Pathophysiology: Eccentric hypertrophy of the left ventricle → ↓ ventricular contractility → ↓ LVEF
CLinical features: Signs of left heart failure and right heart failure
S3 gallop
Systolic murmur
LV cavity size: increased
EF: Decreased
Wall thickness: Decreased
MOST COMMON
What is this type of cardiomyoapthy and what are the general features and the pathophysiology
Restrictive Cardiomyoapthy
Pathology: Proliferation of connective tissue →
↓ Elasticity of cardiac tissue
Atrial enlargement and severe diastolic dysfunction
Clinical features: Signs of left heart failure and right heart failure
LV cavity size: decreased
EF: Normal
Wall Thickness: Increased
What does this cardiac myocyte slide show and what are the features on examination and causing factors
Myocarditis
Viral: Coxsackie, CMV, EBV, HIV
Bacterial : Diphtheria, leptospirosis etc.
Parasitic : Trypanosoma, Toxoplasmosis, Trichinosis.
Clinical: chest pain, fever, arrhythmias, HF / sudden death.
Microscopy: Lymphocytic Inflammation.fibrosis (late).
What does this miscroscopy slide of the heart show?
What does this miscroscopy slide of the heart show
What does this miscroscopy slide of the heart show
What are some of the mian types of vasculitis? Are they large, medium or small vessel and are the ANCA + or -
- ANCA Positive Vasculitis: (AntiNeutrophil Cytoplasmic Ab)
o Microscopic polyangiitis – MPO (P-ANCA) perinuclear.
o Granulomatosis with polyangiitis (Wegener’s) – PR3 (CANCA) cytopl.
o Eosinophilic granulomatosis with polyangiitis - C-ANCA - ANCA negative Vasculitis:
o Adults: Giant cell arteritis, Behcet’s, Takayasu (Aorta)
o Children: Kawasaki (coronary) IgA vasculitis (Buerger’s).
What are the large vessel vasculitis conditions and their pathophysiology
What are themedium vessel vasculitis conditions and what is their pathophysiology
What is this type of ulcer and what are the features of said ulcer
Venous ulcers: wet, oozing, dermatitis.
* Cause: Varicose veins 90% (1in5 men, 1in3 women).
* Location: Gaiter region.
* Pathogenesis: Venous stasis Ischemic Injury ulcer.
* Features:
* large, multiple, irregular, shallow.
* Wet oedematous, oozing.
* Moist granulating base – bleeds on touch.
* Surrounding eczematous stasis dermatitis.
* Hemosiderin deposition dark skin.
* Mild pain, relieved by elevation.
* Compression bandage - relieve congestion.
What is this type of ulcer adn what are the features of it?
Arterial Ulcers: dry, dark, painful
* Cause: Atherosclerosis (Peirpheral Vascular Disease)
* Pathogenesis: Ischemia.
* Location: tips of toes, distal shin, foot,
* Features:
* Feet: Cold, pale, absent or weak pulses.
* Skin: Shiny, loss of hair – atrophy.
* Ulcer: Dry, Irregular clear border, black necrotic.
* Does not bleed on touch.
* Painful Nocturnal, elevation worsens.
* Note: no compression bandage…!
What is this type of ulcer and what are the features of it?
Neuropathic ulcer: Clean, Caving, Callus, painless
* Cause: Neuropathy, Diabetes*
* Location: Distal leg, pressure points*.
* Pathogenesis: neuronal loss loss of
* sensation injury ulcer (painless)
* Features:
* Painless. Punched-out, deep caving.
* Surrounding callus (hyperkeratosis)
* Probing leads to brisk bleeding (intact artery)
* May also have Impaired sensation and diminished
* positional sense or 2-point discrimination
* (neuropathy).
What type of ulcer is this? and what are the features
Malignant ulcers: tumour, irregular.
* Cause: BCC, SCC, Melanoma & others
* Location: Sun exposed*, Old scars (Marjolin’s ulcer)
* Features:
* Refer to individual tumors (MB3-SSS)
* Irregular tumor / raised edges.
* Painless, Lymphadenopathy, metastases, cancer cachexia.
What types of ulcers are these and what are some of their features?
Pressure Ulcers (decubitus ulcers or bedsores)
Deep, excavating, Over a bony prominence, heel & sacrum.
Elderly, immobile, poor nutrition, vascular disease, diabetes etc.
Pathogenesis: Sustained pressure induced, ischemic skin and soft tissue injury & inflammation furthering tissue damage.
Early sign of red/blue skin discoloration to ulcers within hours*
Sustained compression induced ischemia leading to cellular
damage 5 clinical stages:
1. Non-blanching erythema of intact skin.
2. Partial thickness skin loss, exposed dermis.
3. Full thickness skin loss, subcutaneous fat visible.
4. Exposed deep tendons, fascia or bone
5. Un-stageable: Obscured by slough or eschar.
What is Kawasaki Disease?
- Rare, Acute, febrile, usually selflimited illness of children <5y.
- Arteritis of mainly large to medium-sized vessels, Coronary MI*.
- Delayed type hypersensitivity in Genetically susceptible triggered by Viral infection.
- Cross reacting vascular endothelial antigen.
- Transmural coronary arteritis:
- Self limited healing - 80%
- Aneurysm / Intimal thickening & Obstruction MI (20%).
Erythema, blisters & rashes of Hand, Foot & Mouth with cervical lymphadenopathy. Strawberry toungue. Boys 2:1 Rx: Immunoglobulins + Aspirin
CASE: 42y woman. Swollen, painful leg. H/O long flight / surgery / drugs (OCP), familial.
DVT
CASE: 42y woman. Swollen, painful leg. H/O long flight / surgery / drugs (OCP), familial.
Etiopathogenesis: Stasis of blood in deep veins of leg. Virchow’s triad: Blood: Hypercoag, FV leiden, Lupus, etc. Flow: immobility, long flight, preg., Obesity BV injury: Thrombophlebitis.
Gross: swelling / inflam. Thrombosed vein.
Microscopy: Thrombosis.
Complications: Pulmonary embolism.(paradoxical embolism ?). MB2-HRM-Hemostasis
CASE: 62y traffic police man. Heavy legs, prominent veins, non healing ulcers in gaiter region
Varicose Veins
CASE: 62y traffic police man. Heavy legs, prominent veins, non healing ulcers in gaiter region.
Etiopathogenesis: Defective valves (Acquired or congenital) backflow of blood varicosity.
Gross: dilated tortuous superficial veins.
Microscopy: nil significant.
Complications: Venous stasis, non healing ulceration, dermatitis.
CASE: 72 year old male. h/o Polymyalgia rheumatica. increasing headache 3m, scalp tenderness on left.
(worse on wearing hat). Joint pains, back pain, early morning stiffness. Diplopia 1wk.
Giant Cell Arteritis,
Etiopathogenesis: late age >50y, immune dysfunction to an unknown antigen. (like sarcoidosis). Large arteries, temporal & Aorta. Responds to steroids or Anti-TNF therapy.
Gross: Thickened palpable, nodular tender temporal artery.
Micro: Focal Chronic inflam, granuloma giant cells.
Complications: visual loss optic nerve ischemia. Takayasu Arteritis: similar, young age, <50y, Aortic arch mainly. AKA: pulseless disease.
CASE: 40y male, Fever, recurrent chronic sinusitis, pneumonitis, mucosal ulcerations, renal disease & skin bleed. (granulomatosis polyangiitis)
Wegener’s granulomatosis
Etiopathogenesis: Lung & ANCA +ve* Triad: Necrotizing granulomas: URI, nose, Lungs etc.Necrotizing polyangiitis: Small BV, URI, lungs etc, Glomerulonephritis Crescentic:,P3ANCA in 95%,Immunosuppressive / Anti TNF.
Gross: URI, nose, lungs, skin..
Microscopy: segmental transmural, acutenecrotizing inflame. of small & medium arteries.
Complications: debilitating, recurrent, fatal*, Behcet’s disease, Churg-Strauss Syndrome: allergic vasculitis..
CASE: 22 year female. Recent onset episodic hypertension, abdominal pain, bloody stools. Diffuse body pains and aches. Leg ulcers (cutaneous form)
Polyarteritis Nodosa
Etiopathogenesis: unknown / Post viral immune complex. HBV (30%). Renal, heart, liver & GIT. (not pulmonary, No ANCA)
Gross: arterial ulcers. Kidney hematoma.
Microscopy: segmental transmural, acute necrotizing inflam. of small & medium arteries.
Complications: Acute Renal Failure. Responds to immunosuppression.: children < 4y. Post viral, Coronary vasculitis, MI, self limited, aneurysms. Kawasaki Disease
Case: 72y man. Sudden collapse following Left sided hemiplegia (stroke) at morning walk. No pain. (Acute MI, Bowel infarction, etc.)
AS-Aorta
Etiopathogenesis: Life style, HPTN, DM, Obesity. US Plaque embolism Stroke.
Gross: multiple atheromatous plaques of all stages, some with marginal ulceration.
Microscopy: Atheroma, unstable.
Complications: CHF / SCD, PVD, plaque / thromboembolism, Aneurysm, renal artery block. PVD, GI Ischemia,
Case: 77y man. Sudden collapse while walking: he had an MI 8 weeks ago.
Old healed MI +
Gross: Lateral wall infarction – now healed with thin scar replacing myocardium. Area of scar is protruding out – ventricular aneurysm.
Complications: if alive, this patient would have had hypercoagulability due to scar, mural thrombosis and thromboembolism stroke. (anti plt. Drugs - to prevent). If large area of scar – pt. would have had congestive cardiac failure. (low output)
What does this slide show
Case: 48y female, asymptomatic / SOB (or SBE), Stroke / embolism. P/E mid-systolic click /arrhythmia.
Floppy Mitral Valve: Mitral Valve Prolapse (MVP)
Gross: ballooning and prolapse of mitral valve into atrium.
Microscopy: degeneration, myxoid or mucoid material. Reduced normal fibrous tissue.
Etiopathogenesis: reduced fibrous tissue and increased mucoid material in the valve. Some cases of Marfans syndrome have MVP..
Differential: Ischemia, MI.
Complications: Bacterial endocarditis, thromboembolism, stroke, CCF.
Case: 78y female, Progressive SOB and chest pain. Bilateral pedal edema & Congestive Heart Failure. Chest X-ray shows concentric left ventricular hypertrophy. Her BP is normal.
Calcific Aortic Stenosis
Gross: calcified mounds within cusps (Valsalva sinus).
Microscopy: calcification, bone & bone marrow in valvular fibrosa. Varying inflammation.
Etiopathogenesis: Age associated senile change. Aorta common. Wear & tear, damage Dystrophic calcification. Over normal / bicuspid valve.* Deposits prevent opening of valve stenosis.
Differential: Rheumatic AS.
Complications: Bacterial endocarditis, CCF.
Case: 58y IV drug abuser (Diabetic, RHD AS or other valve disorder). Fever, chills, weakness, lassitude, Murmurs, petechial rash, splinter hemorrhages, etc.,
Infective Endocarditis
Gross: Large irregular destructive vegetation’s. Destruction of chordae tendinae, yellow / pus.
Microscopy: Necrosis, bacterial clumps,inflammation
Etiopathogenesis: Acute: normal valve, highly virulent bacteria (Staph aureus). Subacute: abnormal valve/Immunosuppression. Low virulence (Strep viridans),
Differential: Non Bacterial (NBTE) plts, no inflame., along the line of closure (in DVT, PE etc..) RHD: young, linear, along free border, Immune. SLE: Libman-Sacks – plt.
Complications: septicemia, emboli, septic infarcts, mycotic aneurysm, Glomerulonephritis, Janeway lesion
Case: 38y female, Progressive severe SOB.
Hx of an infection when younger and having to get a kneedle that hurt so she stopped
MS-RHD
Gross: excised mitral valve. Fusion of thickened opaque leaflets, fused chordae tendinae, narrow fish mouth mitral opening.
Microscopy: at this time there would be just fibrous scarring (collagen bundles) early stagewould have Aschoff bodies (perivascular T cell mediated granuloma around fibrinoid necrosis with macrophages/Anitschkow, giant cells & T lymphocytes) in
machH/O recurrent URTI as child. Fever, arthritis and heart problems several years ago. Undergoes mitral valve replacement.
Etiopathogenesis: Genetic, Environmental, Autoimmune. GABH streptococcal M Protein. Cardiac Ag.
Case: 12y indigenous girl. Fever, joint pains, SOB, pericardial rub, Chorea, had infection 3 weeks ago
ARF Vegetations
Gross: mitral valve linear, small vegetation’s & inflammation along the occlusal borders. (Area of damage & exposure of Ag.)
Microscopy: inflammation, T lymphocytes, Aschoff bodies, platelet rich thrombus overlying area of ulceration. Normal valve Vegetations
Etiopathogenesis: Genetic, Environmental, Autoimmune. GABH
streptococcal M Protein. Cardiac Ag.
Differential: Bacterial Endocarditis (large irregular, destructive both sides).
Non Bacterial – only platelets, no inflammation, along the line of closure.
Complications: Bacterial endocarditis, thromboembolism, stroke, CCF.
CASE: 70 yo male, smoker, tall, thin, sudden collaspe with ripping pain to back, dead
AAA: Rupture
* Abdominal Aortic Aneurysm
* (A) External view, gross large aortic aneurysm that ruptured (arrow).
* (B) Opened view, rupture tract indicated by a probe.The wall of the aneurysm is exceedingly thin, and the lumen is filled by a large quantity of layered thrombus.
* Note atherosclerotic obstruction of Iliac arteries.
Case: 72y man. Sudden collapse following Left sided hemiplegia (stroke) at morning walk. No pain. (Acute MI, Bowel infarction, etc.)
AS-Aorta
Gross: multiple atheromatous plaques of all stages, some with marginal ulceration.
Microscopy: Atheroma, unstable.
Etiopathogenesis: Life style, HPTN, DM, Obesity. US Plaque embolism Stroke.
Complications: CHF / SCD, PVD, plaque / thromboembolism, Aneurysm, renal artery block. PVD, GI Ischemia,
78y man. Hypertensive, DM, Obese. Died in car crash / stroke / H/O Stable angina. Had MI 4 weeks before
Healed MI (LAD)
Gross: Horizontal section of ventricles. Anterior wall replaced by white scar. Multiple small scars in posterior wall. anterior wall dilatation - aneurysm.
Microscopy: Collagen bundles (fibrosis) inbetween normal myocardium. No inflam.
Etiopathogenesis: Coronary block, atherosclerosis (others rare). Life style, HPTN, DM, Obesity. Chronic, multiple Healed / Scar (collagen / fibrosis).
Complications: CHF, Aneurysm thromboembolism, stroke, Arrhythmia..
Case: 72y man. Sudden severe chest pain, collapse while watching TV. (unstable)
Gross: Horizontal section of ventricles. Dark brown mid zone (Infarction & Acute inflam) in the posterior wall of LV & posterior 1/3 of septum. Dilated RV, Mural thrombus in LV.
Microscopy: Hemorrhage / dead myocardium (no nucleus). LDH & glycogen loss*. (Special stain).
Etiopathogenesis: Coronary atheroembolism (others rare). Risk Fac: Life style, HPTN, DM, Obesity. US Plaque inflam.
Complications: HF/SCD, Mural thrombus, embolism, Arrhythmia, progressive block.
What is the pathogenesis of a CAP
CASE: * 58y smoker. High fever, chills & rusty sputum 4 days. Past H/ Chronic cough, SOB, similar past multiple episodes.
COPD + Pneum
- Gross: Lung section, distended, Upper zone black spots. Lower solid grey white.
- Microscopy: Lower Zone: alveoli show different stages of acute inflammation (Bronchopneumonia) Upper zone: carbon pigment in centrilobular area with loss of alveolar wall (Centrilobular emphysema).
- Etiopathogenesis: Smoking loss of cilia, occumulation of sputum secondary infection Broncho pneumonia.
- Complications: COPD, emphysema, bronchiectasis, Endstage LD, Carcinoma.
CASE: * 48y male. Non smoker, presents with high fever, chills & rusty sputum 4 days. Past H nil significant.
Lobar Pneumonia
- Gross: Lung section, grey white solid upper lob. Normal lower lobe*
- Microscopy: upper lobe: alveoli are full of WBC neutrophils & macrophages. (one stage only) lower lobe: relatively normal.
- Etiopathogenesis: Community acquired pneumonia in healthy adult. infection by pneumococci (Strep pneumoniae). Gram +ve diplococci. Intact architecture, no destruction of alveoli. Spread through pores
- Complications: rare now. Septicemia, fatal, pleural adhesions.
CASE: * 58y smoker. Severe SOB, barrel chest, Past H/ Chronic, progressive SOB. He is lean, tripod position, on ambulatory O2 *
COPD Emphysema
- Gross: Lung section, distended, black spots all over, more in upper zone.
- Microscopy: Loss of alveolar wall (bullae) carbon pigment in centrilobular area (emphysema)
- Etiopathogenesis: Smoking neutrophil elastase breakdown & loss of alveolar wall – emphysema more in upper zone (CO2).
- Complications: End stage Lung dis, Ca.
- COPD / Chronic Bronchitis / Emphysema…?
CASE: * 62y smoker. Chronic cough, SOB, productive foul smelling abundant sputum. C/S showed mixed normal commensals.
- Gross: Focal, dilated irregular bronchi filled with pus. (visible till pleural margin)
- Microscopy: Destruction of bronchial epithelium replaced by acute/chronic inflammation, necrosis, (pus).
- Etiopathogenesis: Smoking loss of cilia / sputum accumulation / obstruction (tumour / foreign body) infection wall destruction Bronchiectasis. (normal commensal over growth)
- Complications: Septicemia
CASE: 38y Indian. wt loss, cough, blood tinged sputum, Mild/evening fever, since 6 months. Not responding to antibiotics. P/h of chest tap for pleural effusion. (h/o DM, HIV, steroid etc)
Tuberculosis*
Etiopathogenesis: mycobacterium tuberculosis, infection. (HIV, DM, steroid therapy, travel, nutrition, country).
Gross: Lung, apical cavity (opening to bronchus), pleural adhesion / fibrosis.
Microscopy: Caseating granuloma. Epitheloid macrophages, giant cells, lymphocytes, central caseation.
Complications: Milliary, extrapulm spread, lung fibrosis, amyloidosis. (immunosupp*)
CASE: 38y Indian. weight loss, cough, bloody streak sputum, Mild fever, since 6 months.
Miliary TB
Etiopathogenesis: when bacteria spread through lymphatics / veins to RV Lungs only (pulmonary) or into arteries to whole
body (systemic).
Gross: Lung section, multiple grey white small foci / nodules).
Microscopy: Caseating granuloma. Epitheloid macrophages, giant cells, lymphocytes, central caseation.
Complications: systemic can be fatal.
What does this lung miscroscopy show
Relatively normal lung tissue (green overlay) can be seen next to pathologic lung tissue (white overlay) with alveolar infiltrates of mainly neutrophils as well as exudation of erythrocytes. A cross-section of an airway (white outline) also shows purulent infiltrates (examples indicated by black arrows) consisting predominantly of neutrophils.
What does this lung miscroscopy hsow?
Neutrophilic pleuritis is seen at the bottom left of the sample (red overlay). There is also neutrophil invasion with fibrinopurulent exudate seen in the alveoli (green overlay in black circles).
These are typical findings in lobar pneumonia.
What does atypical pneumonia look like on miscroscopy?
What is the difference between chronic bronchitis and emphysemia on miscroscopy
What does this lung miscroscopy slide show?
Describe the demographics, pathophysiology and risk factors for asthma, including triggers for asthma
DEMOGRAPHICS: M>F (child) F>M adults, inner regional
PATHOPHYSIOLOGY:
* bronchoconstriction/bronchial hyperresponsiveness, airway inflammation and mucous impaction
Ag binding leads to T cell differentiation (Th1 + Th2 components):
–>Th2 response: mast cells/ basophils/ eosinophils (IgE release) → mediators of inflammation released (histamine, PGs, LK, enzymes etc.) → bronchial hyperresponsiveness + airway obstruction → asthma symptoms | more important response
–>Th1 response: cell mediated immunity + neutrophilic inflammation
RISK FACTORS + TRIGGERS:
* Risk factors: family hx, allergies, viral respiratory infection, occupational exposures, smoking, air pollution, obesity etc.
* Triggers: tobacco smoke, dust mites, outdoor air pollution, pests, pollen, pets, mold, cleaning + disinfection, sinus infection, allergy, physical exercise, breathing cold + dry air/bad weather (esp. cold), foods, fragrances, (respiratory) infection etc.
. Describe the clinical features and diagnostic criteria of chronic asthma and determine the severity of chronic asthma based on symptoms.
Asthma diagnostic criteria
· No single test to diagnose asthma, thus based off clinical suspicion supported by spirometry
· Recurrent episodes of wheeze, dyspnoea, cough & chest tightness
o Typically occur nocturnally & early morning
o Specific triggers e.g. exercise, aeroallergens
o Personal or history of atopy (allergic rhinitis, dermatitis)
· Widespread wheeze on chest auscultation, signs of atopy
·Spirometry shows airflow limitation/obstruction which is variable & reversible
o Reduced FEV1/FVC ratio <0.7
o Increase in FEV1 or FVC by at least 200mL AND at least 12% 10-15mins post-bronchodilator (SABA)
Outline the long-term management of asthma, including non-pharmacological aspects of management and asthma action plans.
General principles
* Self monitoring via peak flow meter
* Influenza and pneumococcal vaccination
* Avoid triggers eg. take puffer before exercise
* Avoid smoking
Pharmacotherapy
* Preventer - inhaled corticosteroid +/- LABA
* Reliever - inhaled bronchodilator SABA
Compare the mechanism of action, indications, contraindications, method and frequency of administration, desired effects and side effects of inhaled medications used to treat asthma and COPD: SABA, LABA, LAMA and ICS.
Describe the management of an acute exacerbation of asthma and asthma first aid
Summarise the treatment options for lung cancer.
Relate the common sites of metastatic lung cancer to the blood supply and lymphatic drainage of the lung and pleura.
Lung Metastases
-Lymph to thoracic duct to SVC vs straight into pulmonary circulation.
Sites of Metastasis
- Common sites of lymphatic spread:
o Supraclavicular lymph nodes
o Mediastinal lymph nodes
o Subcarinal lymph nodes
o Hilar lymph nodes
- Lower lobe tumours usually drain to subcarinal lymph nodes
- Upper lobe tumours usually drain to upper mediastinal & supraclavicular lymph nodes
- Spread to the pleura either directly or via lymphatic drainage especially by peripheral tumours
- Haematogenous route lung cancers often spread to → brain, bone, liver, adrenal glands, kidney
Describe the clinical features, investigation findings and first line management of paraneoplastic syndrome associated with lung cancer.
Paraneoplastic syndromes : are rare disorders triggered by antibodies against a neoplasm which cross react with normal tissue or by the production of a physiologically active substance by the neoplasm. Commonly present with lung, breast, ovarian and lymphatic cancers.
What does this slide of the lung show and what would be the gross morphological finding sin this condition?
Asthma : Gross & Microscopy
* Gross:
o Inflamed thick bronchi + mucous plugs.
o Excess mucous & mucous plugs (sputum)
- Microscopy:
o Mucous gland & smooth muscle Hyperplasia
o Eosinophilic inflammation.
o Curschmann (epithelial) spirals & Charcot Leyden Crystals (Eos. Protein) in sputum.
Here are images of obstrictive vs restrictive lung disease. Descrive the differences seen in pulmonary function testing.
What does this lung miscroscopy show
Microscopy: Eosinophilic inflammation, hypertrophy & hyperplasia of mucous glands. Mucous in the lumen, Curschman spirals & Charcot Leyden crystals (eosinophil granules
What does this lung miscroscopy show
Asthma presentation : Eosinophilic inflammation, hypertrophy & hyperplasia of mucous glands. Mucous in the lumen, Curschman spirals & Charcot Leyden crystals (eosinophil granules)
What does this lung miscroscopy show
Slinicosis:
consentric layers of fiorous tissue as nodule with black carbon pigment inbetween. there are also fibrotic nodules with carbon pigment
What does this lung miscroscopy show
What does this lung miscroscopy show
Case: 35y man, smoker (14-pack year), 12m history of progressive dyspnoea. P/E finger clubbing and bilateral upper lobe fine inspiratory crackles.
This is the miscroscopy of the lung . What is the diagnosis and what would be seen on chest xray
Silicosis: CXRay: extensive upper lobe fibrocystic change. Micronodular opacities in the mid zones, superior displacement of the hila (fibrosis), small left pneumothorax.
Case: A 28y JCU Int. student presents with cough, low grade fever, night sweats.
He has lost 6kg over 4 months. Had several courses of antibiotics from his
GP but keeps recurring. Clinical examination revealed cervical and axillary
lymphadenopathy.
This is the miscroscopy: what is the diagnosis
TB
What does this lung miscroscpy show
Case: A 41y man @ ED high fever, shaking chills days, coughing up rusty sputum 1 day. Felt alternately cold then hot and sweaty. His chest hurt on breathing. O/E thin white male who was anxious and mildly cyanotic, tachypnea, fine Crackles (rales) and decreased breath sounds over the right lower chest. Temp100.2°F, pulse normal. WBC high, with 70% polys, 18% bands, and 12% lymph. ABG: hypoxia & respiratory alkalosis. Sputum gram-positive diplococci. (Microbiology…?)
What is the diagnosis and what is seen on miscroscopoy
Pneumonia,
CASE: An 18y, presented with recurrent attacks of wheezing since childhood worse during winter. An x-ray of the chest was normal, but PFT during attack demonstrated a markedly decreased FEV1, which improved significantly after he inhaled bronchodilator. The patient was prescribed bronchodilator & steroid inhalers which some relief, but the patient continued to experience episodes of breathlessness in the coming years.
What is the diagnosis, how do you classify severity, how to manage and what is seen on miscroscopy?
Life-threatening (PEFR <33%): 33, 92 CHASE
33: PEFR <33% predicted
92: Sats <92%
Cyanosis
Hypotension
Arrhythmia
Silent chest
Exhaustion
Severe (PEFR <50%): cannot complete sentences, respiratory rate > 25, heart rate >110
Moderate (PEFR <75%)
Mild (PEFR >75%)
Mneumonic O-SHIT-MI for the management of Severe/Life-threatening asthma: Oxygen, Salbutamol, Hydrocortisone (Prednisolone), Ippatropium bromide, Theophylline, Magnesium sulphate, Intubation and ventilation
CASE: 31 year old black man, shortness of breath, chest pain and dry cough since 6 weeks.
Exertional dyspnea, fever & night sweats. He has lost 3 kg weight since his problem
began 3months ago. He is developing reddish bumps over skin on chest, limbs and
groin. His eyes are reddish with tears (congested). Now in resp. distress
What is the likely diagnosis
CASE: 51y male diagnosed with influenza 3 days ago. Presents to ED with worsening SOB, fever cough, green sputum, altered mental status. O2 Saturation 61% (room air), laboured breathing, continued to deteriorate. despite BiPap, Became hypotensive. Slow recovery after difficult
intubation & mechanical ventilation
What is shown on the miscroscopy of the lungs and what is the diagnosis?
What would be different if this was a child and how would that present?
ARDS/ ALI (DAD)
: Epithelial & endothelial injury, inflammation Neutrophils. Exudation Hyaline membrane ( surfactant): Diffuse Alv.Damage (DAD).
* Severe hypoxia, atelectasis, wet heavy lungs filled with exudate.
ARDS (child)
Pathogenesis: Immature lung, surfactant Atelectasis inflammation & exudation.
Gross: Purple congested, wet, airless lungs.
Microscopy: collapsed, inflammed alveoli, Hyaline membrane of plasma proteins with
necrotic cells.
What are some gross and miscroscopic features of the slide
What are some gross and miscroscopic finding sof the below
What are some gross and miscroscopic finding sof the below
Case-1: 72y man, thirsty & confused…!
Recently he noticed that he takes more water butdoes not urinate more. He is confused, Ataxic with tremors. He has lost 4kg. & worsening SOB since 3months, which he attributes to his smoking (40pky) hilar mass, nodular well demarcated. Small blue cells, scanty cytoplasm
Chest x-ray:
Biopsy:
Diagnosis?
Why confused?
Diagnosis? SCLC+SIADH (ADH like protein by Ca cells)
Why confused? Excess ADH like protein (AVP – Argenine Vasopressin) Anti-diuretic causes excess reabsorption of water from urine resulting in hyperosmolar urine & hyponatremia causing
neurologic dysfunction – confusion, delirium, muscle weakness, tremors/ataxia.
severe cases cause cerebral edema & coma.
Case-2: 61y man, droopy left eyelid..!
History: SOB since 2 months, which he attributes to his smoking (50pky). P/E ptosis and left eye miosis & dry skin of the left face. Left, apex, tumor, flush with chest wall Irregular cells forming irregular glands.
Chest x-ray:
Biopsy:
Diag?
Diag? Ad. Ca + Horner Sy (Sympathetic trunk damage.)
Pancoast Tumor:
extreme apex part of lung, left/right, in the superior sulcus (a shallow furrow on the surface of the lung). Invade chest wall > than lungs!. pleura, rib, muscle etc.
Shoulder pain radiating to medial scapula, arm. Compress spinal cord – paraplegia, horner sy – sympathetic stellate ganglion compression.
High grade NSCLC (50% Sq, 30% Ad.Ca, rare SCLC.)
72y male. Chronic smoker, COPD. Worsening cough, wt loss, hemoptysis 6m.
what is shown in the image below
SCC
Etiopathogenesis: smoking (3P deletion), carcinogenesis.
Gross: grey white, well demarcated, round tumour growing out of bronchus in the hilum. Note hilar lymphnode with metastases. (cavitation common)
Microscopy: pleomorphic hyperchromatic squamous cells with dyskeratosis (keratin pearls). Infiltration, inflammation & necrosis.
Clinical: spread late, less hormones (PTH like)
82y female. Non smoker, Worsening cough, wt loss, hemoptysis 3m. (P/H pneumonia, COPD, smoking.)
What is shown in the image below
Adenocarcinoma
Etiopathogenesis: Scar cancer, non smoker. KRAS / EGFR mutations common.
Gross: Large grey white, well demarcated expansile tumour in upper lobe. Separate from major bronchi*. (Peripheral)
Microscopy: pleomorphic hyperchromatic cells forming irregular glands. Infiltration, inflammation, necrosis.
Clinical: Commonest. Non smoker, female, previous injury / scar lungs.
62y smoker with COPD. Recent wt. gain, hypertension, obesity. P/H of COPD (cough, wt loss, hemoptysis.)
What is shown in the image below
Small Cell Ca
Etiopathogenesis: smoking (3p deletion), carcinogenesis. Rb, P53 mutations.
Lack of KRAS / EGFR mutations (NSCC).
Gross: grey white tumour in the hilum, growing along bronchi. Not well demarcated. Hilar lymph node with black pigment.
Microscopy: small, dark cells. Scanty cytoplasm, necrosis common.
Clinical: Poor prognosis, early spread, paraneoplastic sy. (responds to treat). Neuroendocrinehormones.. ACTH
72y male. Non smoker. Mild cough, wt loss, hemoptysis 1m. H/o skin lesions excissed.
What is shown in the image below
Metastases
Etiopathogenesis: hematogenous spread (veins) predominantly by carcinomas. In this case melanoma.
BN10: Arterial spread of bronchogenic carcinoma lung. (local spread)
Gross: Multiple rounded tumours (coin shadows) with patchy black pigmentation.
Microscopy: Melanoma (pleomorphic cells with melanin pigmentation) could be any type of cancer….
Clinical: lungs common site of spread – tumors invade veins right heart lungs more easily (thinner than artery).
What is shown in this lung miscroscopy
What is shown in this lung miscroscopy
What is shown in this lung miscroscopy
What are the main differentiating factors on these lung cancer histories
What are the mian differenciating factors of these lung cancer miscroscopies
Where are the main types of lung cancer located
