Boards Part 2 Flashcards
Pacemaker for
• Third degree AV block or equivalent
(e.g., first degree AV block with LBBB and RBBB)
• Heart rate 3 seconds
• Sick sinus syndrome with symptoms (e.g., syncope)
Most common cause of tachycardia
re-entry
types of supraventricular tachycardia
- Sinus tachycardia
- Paroxysmal supraventricular tachycardia (PSVT)
- Sick sinus syndrome (SSS)
- Wolff-Parkinson-White/Lown-Ganong-Levine (WWW/LGL)
- Atrial flutter
- Atrial fibrillation
sinus tachycardia cause and tx
irritable SA node or atrial focus
Treat primary disorder (rehydrate, o2)
PSVT tx
Vagal manuevers (80%) IV Adenosine or overdrive pacing
BB, CCB, Dig are preventitive
Short PR interval (<.12 sec)
Congenital accessory AV pathway
Tx for it
Wolff-Parkinson Whjite
Radiofrequency ablation is TOC
Sawtooth pattern seen in mitral stenosis, pericarditis and ARF
Atrial flutter
Irregularly irregluar rhythm
tx
Atrial fib
Rate control with BB or CCB
CVA proph with warfarin if chronic
> 3 cons PVCs
Vent Tachycardia
can be paired, multifocal or frequent
can lead to v fib
v tach etiology
- Usually due to ischemic heart disease and/or an acute myocardial infarction
- Prolonged QT syndrome
- Familial
* Typically presternal chest pressure radiating to the jaw and down the ulnar aspect of the forearm * Typically EXERTIONAL * Stress related * Cold temperatures * Following a heavy meal
Tx too
Stable Angina
- Relieved with rest, O2, nitroglycerin
medical tx for CAD
- Treat risk factors
- (e.g., treat HBP, elevated LDL, DM, stop smoking)
- ASA 81 mg daily
- Sublingual nitroglycerin
- Beta blockers
- Calcium channel blockers - verapamil
- Long-acting nitrates transdermal nitroglycerin patches
interventional tx for CAD
- PTCA/stent
- Atherectomy
- CABG
- Progressively diminished exercise tolerance
- Increasing frequency and severity
- Relatively recent onset
(unstable angina with elevated biomarkers)
tx
Unstable Crescendo
Non-ST elevation MI
Immediate Hospitalization
O2, nitrates, BB, Anti-thrombotic tx
- Usually abrupt, severe and persistent
- EKG
- Biomarkers (CPK-MB; troponin-I; SGOT; LDH)
Tx
MI
- 9-1-1
- O2, nitroglycerin, and ASA to limit infarct size
- Early intervention/reperfusion
- tPA (tissue plasminogen activator)
- PTCA/stent, etc.
- Beta blockers: Acute and chronic benefit
- ACE inhibitors/statins: Chronic benefit/plaque stabilization
- Usually younger patient; at rest
- Usually few risk factors
- Occasional history of additional vasospastic disorders (e.g., migraine; Raynaud’s phenomenon)
- Focal spasm of an epicardial artery with ST elevation or spasm on coronary angiography
tx
Prinzmetal’s Angina
- Nitroglycerin
- Calcium channel blockers
- Asymptomatic MI
- May present with post MI complications (e.g., CHF)
- Frequent in diabetics
- “Autonomic dysfunction” prevents chest pain sensation during M
Silent MI
- Similar to angina, but not EXERTIONAL (It’s POSITIONAL)
- Often at night (supine position)
– Heartburn
– Pyrosis
– Dysphagia - Often relieved with nitroglycerin and antacids
- Often midepigastric tenderness on Px
GERD
Causes of Chest Wall Pain
- Usually some form of trauma/strain
– ? Severe coughing paroxysm
– ? Heavy lifting, etc. - Often pleuritic
- Pain may radiate to left shoulder
- Often relieved with sitting up and leaning forward
- Physical exam:
– ? Pericardial friction rub
– ? Pulses paradoxus (decrease in BP with inspiration)
Pericarditis
- Severe, abrupt, radiating to the back
- Physical exam:
– ? Loss of lower extremity pulses
– Possible murmur of AI
Chest Pain Secondary to Aortic Dissection
Chest Pain
- Variable and usually atypical pattern
- Often associated with a history of anxiety and depression
- Often precipitated by situational factors
- Diagnosis by exclusion
Psychophysiological Chest Pain
HTN goals for blacks w/ and w/out organ damage
135/85 if none
130/80 is evidence
HTN definitions
- Normal BP 120.
* Isolated systolic hypertension: Systolic BP >139, normal diastolic BP
aldoseterone does what
Causes Renal Na retention to increase blood volume
Hypertension with not direct cause
Risk factors – Genetics – Sodium consumption – Obesity – Alcohol abuse – Type 2 diabetes – Type “A” personality
Essential HTN
HTN worsened with sodium consumption
types and treatment
Salt Sensitive
– Low renin essential hypertension
• ? Excess production of unknown mineralocorticoid which does not waste potassium
• Dietary sodium restriction helpful
• Diuretics helpful
– Normal / high renin (nonmodulating) essential hypertension
• Possible renal defect (inadequate sodium excretion)
• 25-30% of essential hypertension
• ACE inhibitors helpful
– High renin essential hypertension
• Probably due to increased catecholamine activity
• Beta blockers helpful
• Renin blockers helpful
2ndry HTN causes
• Renal hypertension – Renovascular hypertension – Primary renal disease • Endocrine hypertension – Aldosteronism (usually primary aldosteronism) – Cushing’s disease – Pheochromocytoma – Contraceptive-induced (estrogen stimulates hepatic angiotensinogen production) – Hyper- or hypothyroidism – Hyperparathyroidism • Aortic coarctation • Obstructive sleep apnea
HTN with hypokalemia tx
Spironolactone
– Rapidly escalating hypertension
– Borderline elevated / rising creatinine
– Abrupt creatinine rise following ACE inhibitors
– History of diabetes, dyslipidemia, smoking, ASCVD
dx and tx
Renovascular HTN
• Diagnosis
– Renal artery ultrasonography; MRA; spiral CT scan
– Renal artery angiography +/- renal vein renins
• Treatment
– Ideally, stenting
– Hypokalemia
• ACTH; renal artery ultrasonography
– Plasma aldosterone concentration and plasma renin activity levels
• PAC > 20 and PAC/PRA > 30 highly suggestive
– Imaging: CT/MRI
Hyperaldosteronism
– Symptoms usually include a severe headache, vomiting, visual disturbances, CNS findings (paresis, convulsions, lethargy, coma) cardiac decompensation and oliguria
– Diastolic BP generally >130 mm of mercury, papilledema, retinal hemorrhages
Malignant HTN
furosemide IV 40mg
and either nitroprusside 0.25mcg/kg/mm or nitroglycerin 5mcg/min
Caustion do not lower diastolic BP to
– No evidence of end organ damage (e.g., normal CMP or chronic abnormalities, normal UA,
troponin I, no acute EKG changes, symmetrical pulses, no papilledema or retinal hemorrhages:
Severe HTN
Clonidine 0.1 every 2-3h
– Pregnancy with hypertension, proteinuria and hyperreflexia; may present with convulsions
tx
Eclampsia
mg sulfate 4gIV for convulsions
Hydralazine 5-10 mg IV for HTN (to d < 95)
Consider urgent delivery
HR that compromise perfusion
Generally HR 140 compromises perfusion due to inadequate time for sufficient preload
Physiologic / Cardiac Compensation for CHF
Renal:
– Increased sodium and water retention with renin angiotensin system activation to increase
blood pressure for perfusion and to augment preload
Autonomic nervous system:
– Increased heart rate to increase cardiac output
Cardiac:
– Muscular hypertrophy
– Maladaptive cellular remodeling / fibrosis
systolic CHF and Diastolic CHF
Systolic CHF
– Primarily contractility and/or afterload problem (e.g., acute hypoxemia)
Diastolic CHF
– Primarily preload problem (e.g., “stiff” fibrotic ventricle)
NOT to be confused with right heart failure and left heart failure
CHF symptoms
– Primarily dyspnea on exertion
– Orthopnea / paroxysmal nocturnal dyspnea
Increased pulmonary capillary pressure due to fluid shift from the extremities when supine;
possible impaired apical pulmonary arteriolar oxygenation due to pulmonary effusion
– Dependent edema
– Cheyne-Stokes’ respirations
Primarily CNS symptom likely
CHF physical findings
– Bibasilar inspiratory rales
– Cardiomegaly / laterally displaced PMI; S3gallop
– Dependent edema / pleural effusions / ascites
– Hepatomegaly / positive HJR / JVP >8 cm (major criteria: >16 cm) / jaundice
Lab for CHF
Blood work: CBC, CMP, TSH, UA, NT pro-BNP (byproduct of stretching myocytes)
tx for CHF
Diuretics Sodium restriction BB ACEi Digoxin Vasodilators
RV failure usually due to increased
RV afterload / pulmonary vascular resistance
– Usually due to COPD and increased pulmonary capillary pressure from hyperinflation
– Interstitial pulmonary disease / fibrosis
– Pulmonary vasoconstriction
(e.g., hypoxemia; altitude sickness)
SOB, light head, palpitations, Chest pain, blue skin
Cor Pulmonale
50% mortality in 60 minutes from acute pulmonary embolism
Usually due to acute pulmonary embolism
– Possible high altitude pulmonary edema
(HAPE); acute pulmonary inhalation injury, etc.
Physical findings:
– Right heart failure signs; S4 gallop
tx
Acute cor pulmonale
O2 diuretics, treat underlying cause
Pulmonary Hypertension Treatment
Treat underlying cause
Oxygen
Vasodilators
– Calcium channel blockers; ? sildenafil (Viagra)
Classifications of cardiomyopathies
- Dilated
- Hypertrophic
- Restrictive
- Signs and symptoms of CHF
- Usually die within three years from onset of symptoms
- Rule out ischemic heart disease; work-up like CHF
Dilated Cardiomyopathy
- Second most common cause of CHF after ischemic heart disease
- Reversible if alcohol consumption is discontinued before advanced disease
- “Holiday heart syndrome”
- Arrhythmias (usually AF) after a binge
Alcoholic Cardiomyopathy
- First symptom may be sudden death with strenuous activity (esp in kids and young adults)
- May be slowly progressive and present as atrial fibrillation or CHF in older patients
- Physical findings
Include late systolic ejection murmur along the LLSB radiating to the apex - EKG findings
LVH and often diffuse broad Q waves from increased muscle mass opposite the
electrode; possible LAE; possible atrial fibrillation - Echocardiogram: Diagnostic
Septal hypertrophy, left ventricular hypertrophy and systolic prolapse of the anterior
mitral valve leaflet
and Tx
Hypertrophic Cardiomyopathy
BB or diltiazim (opposite of CHF)
- Diastolic CHF due to infiltrative disorders such as amyloidosis and hemachromatosis;
idiopathic; familial endomyocardial fibrosis - Signs and symptoms of CHF
- Treatment
- Treat diastolic CHF; arrhythmias
Restrictive CM
- Cardiac muscle inflammation
- Usually infection (e.g. viral, bacterial, lyme carditis; Chagas’ disease
- Rarely autoimmune (giant cell myocarditis)
- Symptoms and signs of CHF
- Treatment
- Treat systolic CHF, arrhythmias, underlying disorder
Myocarditis
from multiple etiologies (e.g., infection, acute MI, uremia, trauma /
Dressler’s syndrome, metastatic disease, drugs like INH)
* Symptoms
* Usually chest pain referred to the back with dyspnea
* Usually relieved with sitting and leaning forward
* Physical findings
* Pericardial friction rub; pulses paradoxus
* EKG findings: Often diminished QRS amplitude
and Tx
Pericarditis
Treat underlying cause
Pericardiocentesis: pericardial window
Opening snap rumpble augmented with exercise right CHF findings EKG: LAE Can have A fib
Mitral stenosis
• Increased left atrial pressure with symptoms of pulmonary hypertension and cor
pulmonale
• Regurgitated LV preload and symptoms of reduced cardiac output (e.g., dyspnea on exertion)
– Physical findings
• S3and occasional S4gallop
• Holosystolic murmur at the apex radiating to the left axilla
– EKG findings: LAE; +/- RAE; +/- LVH
– Echocardiogram: Diagnostic
Mitral regurgitation
– Symptoms: • Usually none • Occasional PSVT due to LA “stretch” – Physical findings: • Midsystolic “click–murmur” augmented with isometrics and valsalva (reduced LV preload and leaflet angle with increased papillary muscle “slack”) – EKG: Usually normal – Echocardiogram: Diagnostic
Mitral valve prolapse
- SBE prophylaxis if MR present
- Beta blockers for PSVT
Angina
Exertional Syncope (hypotension from vasodilation and exercising muscles with compromised cardiac output)
Pulses parvus et tardus
Reduced S1-S2 interval and possible paradoxical splitting of S2
S4
Systolic ejection murmur
Aortic stenosis
often asymptomatic
• “Water hammer” pulse with widened pulse pressure (e.g., 140/60); “Quinke’s pulse” with
gentle pressure on nail bed; markedly augmented PMI with lateral displacement
(e.g., head bobbing/”bed spring” pulse)
• Diastolic decrescendo murmur
EKG: LVH
Aortic Regurgitation
SBE prophylaxis indications
– Previous history of SBE; prosthetic heart valves; prosthetic material used for cardiac valve
repair; unrepaired cyanotic congenital heart disease; repaired congenital heart disease with
residual defects at the site of a prosthetic device; cardiac valvular disease in a transplanted heart
• Treatment prior to dental procedures:
– Amoxicillin 2 gm orally one hour before procedure
– Clarithromycin 500 mg one hour before procedure if penicillin allergic
• Treatment prior to procedures on infected skin or musculoskeletal tissue
– Infections often polymicrobial but only staph and beta hemolytic strep bacteremia are likely to
cause endocarditis
– Treat as above pending culture results and consider the addition of TMP SMX DS if suspicious
of MRSA
Categories of hyperlipoproteinemia
• Type II-a hyperlipoproteinemia
– Elevated cholesterol; normal triglycerides
• Type II-b hyperlipoproteinemia
– Elevated cholesterol; elevated triglycerides
• Usually seen with type 2 diabetes
Acquired dyslipidemia
obesity Type 2 DM Hypothyroidism Liver Disease Renal Disease
Treatment goals for risk factors
0 – 2 <70
Risk factors for LDL elevation
– Cigarette smoking – Hypertension (BP 140/90 mmHg or on antihypertensive medication) – Low HDL cholesterol [<65 years – Age (men 45 years; women 55 years) – Lifestyle risk factors • Obesity (BMI 30 kg/m2) • Physical inactivity • Atherogenic diet – Emerging risk factors • Lipoprotein(a) • Homocysteine • Prothrombotic factors • Proinflammatory factors • Impaired fasting glucose • Subclinical atherogenesis
tx for elevated cholesterol
• Nonpharmacologic treatment – Smoking cessation – increases HDL – Weight control – decreases LDL – Exercise – increases HDL – Treatment of underlying problems such as diabetes and hypothyroidism – Dietary treatment • Low saturated fat • No dietary sweets
combo therapy for elevated cholesterol beware of what combo and why
Beware of statin/fibrate combination (myositis; rhabdomyolysis; elevated CPK)
meds for cholesterol and what they target
LDL only - Statin
LDL, HDL, TG - Niacin
TG only - Fibric acid derivatives
LDL - Ezetimibe
Big QRS
Compensatory pause
PVC
PVC falls on what wave cause vent tachycardia
T wave
torsade de pointes (Vent fib with twisting axis) cause
Congential QT syndrome
Long PR consistently prolonged
1 deg AV block
PR interval consistently increases in successive cycles
lack of QRS
Wenkenbach 2 AV block
2:1 P to QRS
Mobitz 2 AV block
3:1 P to QRS
Mobitz 3 AV block
PR interval not the same
Normal QRS
3 AV block
bunny ears
Bundle branch block
Diphasic P wave
RAH or LAH
Large R wave in V1
RVH
Large S wave in V1
Large R wave in V5
LVH
t wave inversion
ischemia
ST elevation
Injury
ST depression
subendocardial infarction
positive stress test
digitalis
significant q waves
infarctions
infarct leads
sig q waves
I and AVL = Lateral
V1, V2, V3, V4 = Anterior
II, III, AVF = inferior
U waves
hypokalemia
A-a gradient
• Difference between alveolar O2and arterial O2
• For arterial PaO2of 80
97-80 = 17 A-a gradient of 17
• Normal A-a gradient is 7-14 on room air
Arterial Blood Gas Analysis PaO2: Measure of Oxygenation
Arterial Blood Gas Analysis PaCO2: Measure of
Ventilation
Pulmonary Function Testing
Major Types of Tests
- Spirometry (pre and post dilator)
- Forced inspiratory maneuvers
- Lung volumes
- Diffusing capacity
- Maximal respiratory pressures
- Pulse oximetry – rest and exercise
Major Types of Pulmonary Disease Identified by PFTs
• Obstructive lung diseases - Asthma, COPD, CF • Restrictive lung disease - Pulmonary fibrosis, sarcoidosis, neuromuscular disease, pulmonary edema • Mixed pattern
PFTs in Obstructive Lung Disease
• Spirometry
- Low FEV1/FVC (12%) in asthma
PFTs in Restrictive Lung Disease
• Spirometry: Reduced FVC but normal or even increased FEV1/FVC ratio (>70%) • Lung volumes: Decreased total lung capacity (<80% predicted) • Diffusing capacity: Usually decreased Use of Pulse Oximetry in Clinic Setting • Measure oxygen saturation at rest • Monitor oxygen saturation . . . - With exercise - With sleep - During procedures
Hyper-responsiveness – response to triggers->Obstruction – usually fully reversible->
Symptoms – cough, wheeze, dyspnea, dec breath sounds
- Airway bronchspasm
- Airway inflammation and mucus
• Bronchospasm
- Airway narrowing
- Usually worse at night
- Triggers: Pollen, drugs, dust, exercise, smoke exercise, cold, stress, colds/flu
Asthma
Assessment of bronchospasm of Asthma
• Spirometry: FEV1 • Peak flow meter • Use of bronchodilators • Symptoms - Particularly nighttime awakenings
FEV1/FVC improves with dilator
Asthma
Signs of poor control of asthma
(rule of 2s)
- Use “rescue” meds >2 times/week
- Nighttime awakening due to breathing >2 times/month
• Defines a severe asthmatic episode that is not responsive to repeated treatments with usual
inhaled medications
Status Asthmaticus
Treatment of Asthma
• Mild disease - Avoid triggers - Use of short-acting inhaler as needed • Moderate-severe disease - Inhaled corticosteroids - Inhaled long-acting bronchodilator - Leukotriene receptor antagonist Especially for aspirin sensitive asthma - Oral steroids - Anti-IgE therapy (Xolair - IgE antagonist injection every 2 weeks)
best way to improve COPD
smoking cessation
Low flattented diaphragm
increased AP diameter
Air trapping
COPD
Therapy in COPD
• Smoking Cessation • Drug Therapy --B2 agonists, anticholinergics • Oxygen Therapy • Exercise/Nutrition • Lung Volume Reduction • Lung Transplantation
• Respiratory manifestations - Persistent, productive cough - Airflow obstruction - Bronchiectasis-dilated airways • Physical findings - Wheezing - Clubbing of digits • Sweat chloride: Sweat chloride level of >60 meq/L - Pancreatic insufficiency with malabsorption • Infertility
Cystic Fibrosis
Restrictive lung diseases
- Interstitial Lung Disease
- Neuromuscular Disease
- Severe Obesity
- Chest Wall/Spine Deformity
- Pleural Disease
interstitial lung dieseases causes
• Drugs - Chemotherapy, amiodaronenitrofurantoin • Toxic Dusts - Asbestos, silica • Hypersensitivity Pneumonitis - Organic dusts Interstitial Lung Disease:Associated with Systemic Disease • Rheumatoid Arthritis • Scleroderma • Systemic Lupus Erythematosis Interstitial Lung Disease:Idiopathic • Sarcoidosis • Idiopathic Pulmonary Fibrosis
• Shortness of breath - Particularly with exercise • Cough - Usually non-productive • Radiographic - Diffuse linear (reticular) or nodular markings in lung parenchyma • PFTs - Reduced lung volumes - Reduced diffusing capacity (usually)
Features of ILD
- Military Exposure (ships/tanks)
- Ship-Building
- Boiler worker
- Electrician
- Brake Repair
- Construction
- Building Remodeling
ILD: Asbestos
- Mining
- Sand-blasting
- Metal working
- Glass workers
ILD:Silica
Drug induced ILD
• Cancer patients
- Many chemotherapeutic agents cause ILD, some not until years later
• Cardiac patients
- Amiodarone: Used for arrhythmias
• Arthritis patients: Methotrexate
• Urinary tract infections: Nitrofurantoin
Hypersensitivity Pneumonitis ILD
exposure to organic dusts
agriculture, moldy hay
most common cause of reduction in lung volumes, particularly total lung capacity
• Diffusing Capacity (DLco) is generally not affected
Obesity and restrictive Changes in PFTs
Idiopathic Interstitial Lung Disease - Increased frequency in African-American • Clinical Presentation - Cough, Short of Breath (Lung involvement in 95% of Sarcoid pts) - Skin Rash Erythema Nodosum - Eye symptoms (iritis) - Neurologic symptoms - Joint pains -“Potato” hilar adenopathy -Facial sarcoid granulomatous nodules - “Lupus pernio” - facial sarcoid granulomatous plaque
Sarcoidosis
Sarcoid Dx
• Radiographic - Hilar/Mediastinal Adenopathy - Pulmonary Infiltrates • Pathologic - Granulomas: Non-caseating
• Increased prevalence in older ages
• Progressive fibrosis of the lungs
• Mean survival is only 3-4 years
• Clinical Features
- Crackles in Chest
- Clubbing of Digits is Common
• Exclude Other Causes of Pulmonary Fibrosis
• Characteristic Features on CT: may make diagnosis
Interstitial fibrosis with adjacent normal lung tissue, extensive honeycombing
Idiopathic pulmonary fibrosis
Treatment of ILD
• Known Causes - Avoid/eliminate exposure - Corticosteroids • Sarcoidosis - Corticosteroids - Methotrexate • Idiopathic Pulmonary Fibrosis - No proven therapy, ? Pirfenidone - Transplant
ARF types
• Hypoxemic Respiratory Failure
- Low Oxygen Level
• Hypercapnic Respiratory Failure
- High Carbon Dioxide Level
• Acute Lung Injury: Milder injury to lung
• Acute Respiratory Distress Syndrome (ARDS):
Severe disorder where oxygenation is markedly abnormal (A-a gradient >200)
- Approx 150,000 cases/year mortality 35-50%
• Can be caused by direct injury to lung
- Aspiration gastric contents
- Toxic inhalation – smoke
- Severe pneumonia
- Exposure to drugs toxic to lungs
• Systemic Injury
- Shock/trauma, sepsis, drug overdose, pancreatitis, burn injury
Hypoxemic Respiratory Failure
Pathophysiology of Hypoxemic Respiratory Failure (ARDS)
• Alveoli fill with fluid, become unstable and collapse
• Collapsed alveoli results in V = 0 which is definition of shunt
• Characteristic feature of ARDS is low oxygen that does not respond to supplemental oxygen
(A-a gradient >200)
Treatment of ARDS
• Ventilation: usually an endotracheal tube, occasionally by mask
• Positive pressure throughout ventilation
• Positive end-expiratory pressure (PEEP)
- Supplemental oxygen
- IV fluids and nutrition
- Antibiotics if needed
Cause of death in Hypoxemic Resp failure
infectious complications
- May present as drop in SaO2 since increase in PaCO2 will cause decrease in PaO2
- Diagnosed by arterial blood gas demonstrating increased PaCO2
- If acute, patient will have respiratory acidosis (pH 7.2
Hypercapnic Respiratory Failure
some causes of hypercapnic resp failure
• Advanced COPD - Severe COPD Exacerbation • Severe Asthma - Status Asthmaticus • Neuromuscular Disease • Hypoventilation - Trauma, stroke, drug effect, over-sedation
most common presenting symptom of lung cancer
cough
syptoms of lung cancer
- cough
- Hemoptysis
- Wheeze, shortness of breath
- Dysphagia
- Weight loss
- Chest discomfort
- Signs of metastatic disease
types of lung cancer
• Adenocarcinoma • Squamous Cell Carcinoma • Small Cell Carcinoma (“oat cell”) • Large Cell Carcinoma • Bronchoalveolar Cell Carcinoma (BAC) type of adeno-ca that occurs as often in nonsmokers as in smokers
Staging of Lung Cancer
• Stage 1
- Small (, 3 cm) disease without involvement of any lymph nodes (N0)
• Stage 2
- Larger disease, possible hilar node involvement (N1)
• Stage 3
- Mediastinal lymph node involvement (N2)
• Stage 4
- Metastatic disease (M)
Therapy of lung cancer
• For Non-small Cell Lung Cancer, surgery is the only therapy that offers a significant chance at
long-term survival (>5 years)
• Surgery is possible in Stage 1 disease and in selected patients with Stage 2 disease
• Surgery is generally not recommended except in experimental trials in Stage 3 disease
Methods to stage lung cancer
CT scan
PET scan
ddx of lung nodule
• Granuloma - Usually due to fungal infection - Most often Coccidoidomycosis in Az • Lung Neoplasm - Primary or metastatic • Other unusual causes - Benign tumors including hamartoma, fibroma, etc.
what if you see a neoplasm in the airways
neoplasm (not cocci)
early diagnosis of lung cancer
Routine CT scans
lung cancer metastases sites
bone
brain
liver
adrenal glands
cancer of surface of lung (pleura) often related to asbestos exposure
Mesothelioma
metastatic disease to lungs
Breast
Colon
Kidney
Melanoma
common cold causes and tx
rhinovirus
no antibiotics
treat with tylenol, etcc
• Constitutional symptoms are more prominent than in cold
- Fever, malaise, myalgias
- Often seasonal
• Treatable within first 2 days
- Oseltamvir (Tamiflu): 75 mg bid for 5 days
• Influenza prophylaxis
- Oseltamvir (Tamiflu): 75 mg once daily for 6 days
- Flu shots
Influenza
• Usually viral
• 15% Strep
- Exudate with fever and lymphadenopathy
tx
Acute pharyngitis
Penicillin or erythromycin
- Usually posterior cervical adenopathy, a dull white exudate and possible hepatomegaly or
splenomegaly - Rash if given amoxicillin
Mononucelosis
Penicillin or erythromycin
Acute sinusitis
Narrow spectrum antibiotics
Amoxicillin or Bactrim
sinus obstruction > 12 weeks cause
bacterial or fungal
get sinus CT
Achy ear
- Often due to pseudomonas aeruginosa and occasionally staph aureus
- Generally treated with ciprofloxacin– HC drops topically and debridement; occasionally with
systemic antibiotics
- Avoid Q-tips
Otitis externa (Swimmer’s ear)
usually bacterial following a viral URI
- S. pneumoniae; H. influenza; M. catarrhalis
- RX: amoxicillin although 1/3 resistant; treatment debatable
otitis media
tx for serous otitis media
- Consider antibiotics and/or myringotomy tubes if significant hearing loss and effusion > 3 mo
- Potentially fatal
- Dx: Lateral neck films ; cherry red epiglottis with fiberoptic rhino-laryngoscopy
acute epiglottiis
ampicillin/sulbactam or 2/3 cephalosporin
maybe hospitalization
usually viral
• Characterized by cough, usually with sputum production
• The absence of abnormalities on chest radiography distinguishes from pneumonia
acute bronchitis
severe bronchitis symptoms
- Increased amount of sputum
- Change in color of sputum
- Increased shortness of breath
• Treat severe bronchitis with antibiotics for 7-10 days - azithromycin or levofloxacin
• May need to treat associated bronchospasm (e.g., albuterol; steroids)
• Primary symptom is chest pain, worse with inspiration
• Usually viral
• Treat symptomatically
- Non-steroidal anti-inflammatory drugs
Pleurisy
URI and LRI
What are LRIs
pneumonias
• Infection that extends beyond airways into pulmonary parenchyma (lobe, lobules)
• Characterized by more change in gas exchange (shortness of breath), and presence of abnormal
findings on chest radiograph or CT scan
• Associated morbidity/mortality is much higher than bronchitis
pneumonia
symptoms of pnuemonia
- Cough, usually productive
- Fever, chills
- Dyspnea
- Malaise
- ? Confusion
- Symptoms may vary from severe to absent
Physical Findings in Pneumonia
• Fever and tachycardia
• Tachypnea (RR > 20)
• Auscultation of chest
- Common: Crackles (“rales”)
Types of pneumonia
• Bacteria (most often)
- Gram positive: Strep pneumonia,
- Gram negative: Klebsiella, pseudomonas,
• Fungal
- Coccidioidomycosis (Valley Fever), histoplasmosis, blastomycosis, aspergillis
• Mycobacteria
- Mycobacterium tuberculosis, mycobacterium avium-intracellulare
• Viral
- Respiratory syncytial virus, adenovirus, influenza
Clinical Signs of Severe Pneumonia
• Hypoxemia - SaO2 < 92% • Tachycardia • Hypotension • Altered mental status - Obtundation - Confusion
diagnosis of pnuemonia
• Primarily from history and physical exam
• Chest x-ray / chest CT scan
• Sputum Gram stain and culture
- ? Acid fast bacilli stain, KOH, fungal cultures, mycobacterial cultures, etc.
• Blood cultures
• Serologic testing
- e.g., coccidiomycosis antibody titers
walkling pneumonia
- Some organisms (mycoplasma or chlamydia) may cause mild symptoms
tx for pneumonia
• More severely ill pt, initial empiric coverage w/multiple antibiotics for a variety of pathogens
- e.g., ceftriaxone 2 g IV daily with levofloxacin 750 mg orally daily
• In immuno-suppressed patients, consider bronchoscopy with lavage (bronchoalveolar lavage)
to evaluate for atypical pathogens
• Usual outpatient treatment: Empiric macrolide (e.g., azithromycin) for mild sy mptoms or
quinolone (e.g. levofloxacin) if moderate symptoms
• May present as community-acquired pneumonia; possible history of soil dust exposure (e.g.,
lives in a developing suburban subdivision)
• Often causes a cavity to form within the lung
• Can be associated with severe constitutional symptoms
• Diagnosis: Serologic test or culturebof organisms
Miliary pattern on CXR
eosinophilia
tx
coccidiomycosis
- Most cases will resolve without any treatment
- Can use Diflucan (fluconazole) 200 mg twice daily for therapy
- In severe cases, may use Amphotericin B by IV administration
- Evidence of tuberculosis organisms multiplying in pulmonary or extra-pulmonary site
- Often infectious to others
active TB
- Cough and minor symptoms for 2-4 weeks and central infiltrates on chest x-ray
- Usually not infectious
Primary TB
- “reactivated” tuberculosis; symptoms may be similar to pneumonia with peripheral and apical
chest x-ray infiltrates - Infectious
2ry TB
- Cough
- Weight loss
- Fatigue
- Fever and night sweats
- Sputum production
- Hemoptysis (usually late in disease)
- Dyspnea
TB symptoms
reactivation TB usually involves what
upper lobes
cavity will form
• Patients with a positive Tb skin test, but no evidence of active tuberculosis have what is
termed
latent tb
Approach to Patient with Suspected Latent or Active Disease
• Latent disease: Tb skin testing (PPD-“purified protein derivative” or “Mantoux” testing)
- mandatory in certain occupations
• Suspect active disease
- Isolate the patient
- Sputum AFB smear and AFB culture x 3
- Occasionally will need bronchoscopy
• If find active disease: Skin test all contacts
TB test interpretation
• Positive
- ≥ 10 mm induration
- ≥ 5 mm if:
- HIV
- Immunosuppressed
- Recent close contact
- Radiographic evidence of old TB
Latent TB tx
isoniazid 9 months with B-6
Active TB tx
isoniazid plus B6
Ethambutol
Rifampin
Pyrazinamide
DVT study
Duplex ultrasound
- Pleuritic pain or hemoptysis 65%
- Isolated dyspnea 22%
- Circulatory collapse 8%
No dyspnea is present 27%
Tachypnea (>20) 70%
Tachycardia (>100) 43%
Crackles (rales) 53%
PE
Interventions to Reduce Risk of DVT/PE
• Early ambulation after surgery
• Avoid prolonged immobilization
• Compressive stocking or mechanical compressing devices
• Prophylactic treatment with low-dose heparin in high-risk patients
- e.g., low-dose heparin or Lovenox postoperatively then 4-6 weeks of Coumadin following a
total knee arthroplasty or total hip arthroplasty
Diagnosis of PE
Spiral CT! (contrast enhanced)
VQ scan
D-dimer (sensitive to rule out)
Treatment of Pulmonary Embolism
• Initial therapy: Heparin • In unstable patient – may consider thrombolytic therapy or surgical embolectomy • Long-term therapy: Warfarin (Coumadin) - 1stepisode: 6 months of therapy - 2ndepisode: Lifelong - Predisposing factor: Lifelong
MICROCYTIC ANEMIAS
- IDA
- ACD
- Hemoglobinopathy (eg THAL)
- Sideroblastic anemias (lead poisoning)
• Most common anemia • Most common cause: blood loss • Occasionally malabsorption from: – Gastric surgery – Malabsorptive disorders High Transferring Low serum Iron Low Ferritin
Iron Def Anemia
dietary iron - meat
oral iron
• Characterized by: – ↓Fe – ↑↑Ferritin – ↓ EPO • Develops in: – Chronic infections – Chronic inflammatory disease – Neoplastic disease
anemia of chronic disease
Macrocytic = megalo & non-megalo
Name causes of megaloblastic (oval) anemias
• B12/Folate def • Drugs: – dilantin/OC – hydrea/methotrexate • Some marrow disorders
– ↑ RBC Mass – Normal O2 – Splenomegaly – Increased: WBC / PLTS / B12 / LAP score – JAK-2 Mutation – Bone Marrow Hypercellularity
Primary Polycythemia vera
polycthemia vera tx
– Phlebotomy (do it until hct under 45)
• H/H < 15/45 – decreases thrombotic risk
– Hydroxyurea
Anemia from reduced RBC survival (<100 days) Bone marrow unable to replace RBCs Etiologies Immune - Coomb’s Positive Non-immune - Coomb’s Negative
Hemolytic anemia
– Rapid pallor / anemia – Jaundice – Splenomegaly – Increase: MCV - macrocytosis • Reticulocytes – IMMUNE: (+) Direct anti-globulin test(Coomb’s) – History of pigmented(Bilirubin) gallstones
hemolytic anemia
HEMOLYTIC ANEMIA – ACQUIRED ETIOLOGIES
IMMUNE (Coomb’s +)
Autoimmune Hemolytic anemia(AIHA) Warm: Idiopathic & CLL Cold: Idiopathic & Mycoplasma Alloimmune: Transfusion Drug-induced
– Antibody or complement on RBC (looking for abs on RBC)
– Diagnosis of:
• AIHA
• Hemolytic transfusion reaction
direct coombs
– ATB in SERUM NOT bound to RBC – Patient serum & Donor RBC – The screen in: “type & screen” – In autoimmune hemolysis • both DAT & IAT may be (+) • ATB may be in SERUM & ON RBC
indirect coombs
– Auto-ATB against RBCs
– Warm & Cold Auto-ATB
AIHA
Any Age Usually IgG Variable anemia Etiologies: 65% - Idiopathic 25% - CLL 20% - NHL Other – Meds Clinical Anemia Jaundice Splenomegaly
warm auto ATB
– IgM – Etiologies: • Idiopathic • Mycoplasma • Lymphoma • Mononucleosis – Clinical • Acrocyanosis at cold temperatures • Jaundice • Splenomegaly
cold auto atb
acquired clonal stem cell disease
– Cell membrane anchor defect
– Hemolytic anemia
– Screen using: CD55 and CD59
and treatment
Paroxysmal Nocturnal Hemoglobinuria
Elulizumab
-binds complement C5
Inherited hemolytic blood disease resulting from a mutation in the alpha globin gene
• Normal HGB = “A1”
• Hemoglobin “S”
Sickle Cell Disease
Sickle Cell Types
– “Trait” = Heterozygous = A>S • 8% of Aas • Malaria protection – “Anemia” = Homozygous = SS • sickle cells in PS – Sickle cell – Hemoglobin C = “SC” • fewer sickle cells - more Target / Spherocytes – Sickle-Thal
Vaso-occlusive disease of sickle cell
– SC accumulate in any vascular bed
– Infarction of Marrow/Spleen/Kidney
– Painful crises in long bones
• MOST COMMON PRESENTATION
sickle cell skeletal presentation
- Marrow hyperplasia=osteopenia=fractures
- “Hair-on-end” on skull
- Marrow infarction = osteonecrosis
- Dactylitis
- Osteonecrosis
- Bossing
– 8% of African Americans – A always > S – Under physiologic conditions no vaso-occlusion – Carriers have normal life expectancy – Compared to the general population: • Same risk for: – Heart disease – Stroke – Anesthetic agents
sickle cell trait
– Imbalanced globin chain synthesis: • Ineffective hematopoiesis • Defective Hgb production • Hemolysis • Variable anemia
types and explian
• Beta Thalassemia – Beta reduce or absent – Alpha excess • Alpha Thalassemia – Alpha reduced or absent – Beta excess • Quantitative NOT Qualitative disorder
heinz bodies
excess alpha chains
– Heterozygous carrier – Usually no clinical symptoms – Asymptomatic Splenomegaly 20% – CBC/peripheral smear • Mild anemia(Hct>30) • MCV
B-Thal Minor
• Anemia later and milder than major • Requires less transfusion • Retarded growth/development • Skeletal deformity – EPO increases marrow expansion – Deformities of skull / long bones – Pathologic fractures • Splenomegaly • Milder forms: – Asymptomatic & xfusion independent – Hgb 10-12
B thal Intermedia
• Homozygous “Cooley’s Anemia” • Symptoms begin at 4-6 months • Clinical: – Gallstones – Leg ulcers – Skeletal disease – Anemia Laboratory features • Microcytic anemia • Target cells / Tear drop cells / Basophilic stippling / NRBCs
B thal Major
Pathophysiology Alpha Thalassemia
– 4 copies of α globin gene • 2 copies each Chr. 16 – 1 Deletion = AT Minima – 2 Deletions = AT minor • TRANS: A/- A/-• CIS: AA / --– 3 Deletions = Hgb H Disease – 4 Deletions = Hgb Bart’s
– Silent carrier = (α - / α α) – Trait • Similar to β Thal trait • Mild heme changes • No clinical abnormality
a Thal (silent carrier)
- Mod-severe hemolytic anemia – hypo/micro –retic counts to 15%
- HSM / Gallstones / Leg ulcers
- RBCs contain Hgb H precipitates
– Hgb H Disease (α - / - -)
– Hgb Bart’s (- - / - -) (γ4) =
incompatible with life
other names for myelodysplastic syndromes
– Refractory anemia
• No improvement with Fe / B12 / Folate
– Pre-Leukemia
– Senile anemia
Ringed sideroblasts
myelodysplasia
• Heritable mutation = RUNX-1 • Tobacco • Ionizing Radiation – Highest rate of progression to AL – 75% – Low response to treatment – Median survival ~ 9 MOS. – Chromosome abnormalities: • -5 / -7 = Alkylating Agents • 11 = Topo-II inhibitors Clinical: – Signs / symptoms usually from cytopenias • Anemia • Infection • Bleeding – Usually absent: • Lymphadenopathy • Hepatosplenomegaly Peripheral smear: • Macrocytosis • Hypolobar neutrophils – (Pseudo Pelger-Huet) • Circulating micromegakaryocytes
Myelodysplasia
myelodysplasia therapies
Bone Marrow Transplant is only curative
– van den Berghe Nature 1974 – severe anemia – mild leukopenia – normal or increased platelets – atypical megakaryocytes – indolent – <5% blasts
5q treatment
5q syndrome
Lenalidomide
Myeloproliferative Disorders
• BCR/ABL(+): Chronic Myelocytic Leukemia
• BCR/ABL(-) & JAK2(+):
– Essential Thrombocythemia
– Myelofibrosis with Myeloid Metaplasia
– Polycythemia rubra vera
• JAK2(+/-): Chronic Myelomonocytic Leukemia
• 10% of all leukemias • Adults>>>children • Median age = 50 • M>F • IR only known causative factor (Ionizing Radiation) MPD - CML • BCR/ABL • “Philadelphia Chromosome” Basophilia – Fatigue / weight loss / night sweats – Splenomegaly – Leukostasis from Hyperleukosis 3 phases (Chronic, accelerated, blastic - acute leukemic transformation)
CML
CML treatment
Imatinib (Gleevec)
•Most common MPD •Age at diagnosis: 50-60 JAK + Bone Marrow = increased MEGS •Near-normal life expectancy – PLTS > 600K – Microvascular Thrombi – Bleeding – Splenomegaly – Recurrent first trimester abortions – Leukemic transformation very low
Essential Thrombocytopenia
• 33% asymptomatic at diagnosis
• Fatigue / Weight loss / Fever / Night sweats
• Anemia
• Splenomegaly
– Leukoerythroblastosis
– Single or multiple cytopenias
• Bone marrow - fibrosis - “Dry tap” – Fibrous tissue takes place of normal BM tissue
• Leukemic transformation in 20% during first decade
MYELOFIBROSIS WITH MYELOID METAPLASIA
• Affects all 3 cell lines - RBCs the most • Proliferate without EPO • Serum EPO levels are low • Median age = 60 • Increased HGB/HCT/RBC mass • Bone marrow: Hypercellular • B12 increased from increased WBCs producing B12-binding protein • Symptoms related to increased viscosity – Plethora – Erythromelalgia – Pruritus • Arterial/Venous Thrombosis • Thromboses: » Renal/portal veins » Budd-Chiari » Mesentery
Polycthemia Rubra Vera
– Most common neoplasm in
ALL
ALL sites
Marrow usually
ALL presentation
– Bulky adenopathy
– Mediastinal mass
– Pleural effusions
– +/- hyperleukocytosis
ALL Lab
– ↑ WBC or Pancytopenia +/- Blasts
– LDH (= tumor burden)
– Hypercalcemia
– ↑ Uric acid / LFTs / BUN
ALL treatment phases
– Induction
– CNS
– Consolidation
– Maintenance
• Uncontrolled prolifeation of myeloid progenitors • Replaced hematopoietic elements • Ineffective hematopoiesis • Majority de novo • Treatment related – Chemotherapy: CHR: -5 / -7 / 11 – RT Auer Rods
– Bone marrow failure – Abnormal hemostasis • Thrombocytopenia • Coagulopathy • DIC most common with APL
• Lymphoid Neoplasm • Binucleate giant Reed-Sternberg cell • 75% of pts can be cured • Origin – Germinal B Center lineage • Other adenopathies – Mononucleosis -EBV
Hodgkin’s Lymphoma
Hodgkin’s Lymphoma clinical features
– Adenopathy • 80% Cervical • 50% mediastinal • Nontender / firm-pliable – B symptoms • Fever • Night sweats • Weight loss – Other symptoms • Fatigue • Weakness • Anorexia • Etoh induced node pain • Pruritus
review difference between B cells and T cells
• B cell – Produced and mature in marrow – B cell receptor – Antibody production – Plasma cells • T cell – Produced in marrow – Mature in Thymus – T cell receptor – CD4: Helper T cells – CD8: Cytotoxic T cells
t(2;5)
t(8;14)
t(14;18)
t(11;14)
ALCL
Burkitts
Follicular
Mantle
– Family History – Previous neoplasm – Immune suppression – Infection – “B” symptoms – Weight loss: >10% weight in 6 months – Fever – Night sweats • Physical examination – All node bearing regions including Waldeyer’s – Organomegaly – Skin involvement
NonHodgkins Lymphoma
Non Hodgkins types
- INDOLENT
- Chronic Lymphocytic Leukemia
- Follicular Grade 1/2
- MALT
- Lymphoplasmacytic Lymphoma
- AGGRESSIVE
- Follicular Grade 3
- Diffuse Large Cell
- Anaplastic Lymphoma
- Mantle Cell Lymphoma
- Primary CNS Lymphoma
- Acute Lymphoblastic Lymphoma
• Median seventh decade • BM-PB-LN/L/S • SLL = tissue equivalent of CLL • Incurable/median survival ~ 10 YRS • Can transform to: – Prolymphocytic leukemia – Large B Cell lymphoma (Richter’s) • Treatment • Oral agents - Chlorambucil • IV/Biologics - Rituximab
CLL
• Also called Waldenstrom’s macroglobulinemia • median seventh decade • BM/LN/S • Rarely – PB / extranodal • IgM elevated Very high = hyperviscosity • Generally incurable • MS ~ 9 YRS
Lymphoplasmacytoid Lymphoma
• Median sixth decade • 35% of NHL • BM/LN/S/Extranodal • May transform to aggressive • Early stage - therapy • Advanced stage not curable – Initial treatment may be surveillance t14:18
Follicular Grade 1 or 2
- Median seventh decade
- Three subtypes: MALT/Nodal/Splenic
- Can be nodal or extranodal
- Extranodal often with Autoimmune disease
- Sjogren’s
- Hashimoto’s
- H.pylori gastritis
- Incurable – MS ~ 10 YRS.
- Early MALT treat with antibiotics
Marginal Zone
- Median seventh decade
- M»F
- t(11;14)
- Increased Cyclin D1
- BM/LN/Extranodal sites
- Lymphomatous polyposis
- Incurable
- Shorter MS – 3-5 YRS
Mantle Cell
• 30% of lymphomas • Median age sixth decade • Extranodal in 40% • Curable with chemotherapy – Most with early stage – 50% with advanced • CNS prophylaxis occasional
Diffuse Large B cell lymphoma
• Most common Pediatric NHL • African = “Endemic” Form = EBV + • Western – Adults – Sporadic – EBV -– Mesenteric LN – Ileum – Cecum – Liver - Spleen • Curable with aggressive therapy • CNS prophylaxis required t8:14
Burkitts
– Cutaneous & systemic – Systemic form • children & adults • Expresses t(2;5) • Mainly T cell – Cutaneous • Mostly adults • Isolated skin nodules • Is more indolent and incurable
Anaplastic Large Cell
- Cutaneous T Cell lymphoma
- Multiple cutaneous plaques – nodules
- Generalized erythroderma
- Treatment often topical
Mycosis Fungoides
• In HTLV-1 areas: – Japan – Carribean • Presentation: – High WBC – HSM – Hypercalcemia – Lytic bone lesions • CD-30+ = Ki-1 • t(2;5) • Four clinical presentations: – Smoldering – Chronic – Lymphomatous – Acute
Adult T cell Leukemia/Lymphoma
- Incidence 60x greater than general population
- Median age fourth decade
- Usually ST III/IV
- Often extranodal: GI/BM/CNS
- Primary CNS lymphoma common in this group
- 70% = large B Cell / other = Burkitt-like
Lymphoma HIV associated`
Typles of plasma cell neoplasms
• Clinically Benign: – MGUS • Indolent: – Waldenstrom’s – Indolent Myeloma • Malignant: Plasma Cell Myeloma • Malignant Aggressive: Plasma Cell Leukemia
• Definition: – M Protein(G,A,M)Value < 3.0 g/dl – No Urinary Light Chains – Normal • CBC • Renal function • Calcium • Bone – Bone marrow plasmacytosis < 10%
MGUS
- Monoclonal protein serum a/o urine
2a. Plasmacytoma OR
2b. Marrow plasmacytosis > 10% - CRAB:
• Calcium
• Renal - light chain tub interst nephritis
• Anemia
• Bone - osteoporosis
Rouleax formation
Multiple Myeloma
Myleoma symptoms
back pain headache blurry vision CHF Sausage retinal veins
Collection of plasma cells usually in vertebral body
Solitary Plasmacytoma (treat with bisphosphonates)
virchows triad
– Venous stasis
– Blood vessel damage
– Hypercoagulability
Disorders of Thrombosis -Prophylaxis in Podiatric Surgery
3 significant risk factors
– Prior VTE
– Hormone replacement/Oral Contraception
– Obesity
– Most common heritable risk factor – Factor V resists lysis by Prot C – Caucasians: 5% incidence • Majority = no thrombosis – 20% with VTE + – VTE risk increased by other risk factors
Activate Protein C Resistance
- Increase O2 carrying capacity
- Not for volume replacement
- Symptomatic anemia / acute hemorrhage
- Increase HGB in adult ~ 1 GM / DL
Packed RBCs
- Replaces volume and O2 carrying capacity
- <1% of all xfusions
- Large amount of plasma
Whole Blood
- Wash with saline to remove plasma
* Indication – repeated hypersensitivity reactions
Washed RBCs
- Remove WBCs by filtration
* Indication – multiple non-Hemolytic transfusion reactions
Leukoreduced RBCs
– From whole blood – Preserves labile proteins except Factors V & VIII – Efficacy limited by: • Shortest ½ life of factor being replaced(Often Factor VII) • Degree of factor deficiency – ABO compatible – Indications: • Replace coagulation factors • Factor deficiencies – With bleeding – Scheduled for surgery • DIC • Liver disease • Rapid reversal of warfarin
Fresh Frozen Plasm
– Cold soluble proteins left when FFP is thawed. • FVIII / FXIII / Fibrinogen • vonWillebrand’s Factor – Replacement of Fibrinogen – ABO not needed – Indications: • Deficiencies: – Fibrinogen – F XIII • DIC • Hemophilia A or vWD (when no FVIII concentrate)
Cryoprecipitate
• Diagnosis of exclusion • Common: – 1% of RBC – Up to 30 % of PLT xfusions • inc temp. ≥ 1 deg F near end or following • Recipient ATB vs. Donor leukocyte ATG • Symptoms: – Hallmark is fever – Chills / Hypertension / Tachycardia • Usually transient
Febrile Nonhemolytic Transfusion Reaction
– Most=ABO incompatible • Often mislabeling or wrong ID – 1:25,000 – Mortality 17-60% – Fever/chills/dyspnea/chest pain – Shock-death – Hallmark = Intravascular hemolysis: • Complement fixation by IgM • Hemoglobinemia - Hemoglobinuria – Direct Coomb’s = + – Indirect Bili – Jaundice – ATN
Acute hemolytic transfusion reaction(immune
• Rapid extravascular clearance of xfused RBCs – Immunized prior xfusion(“primary”) – Days or weeks • May be mild and unnoticed • More common than acute: 1:7000 • Hallmark = unexplained decrease in Hgb • Fever / chills • Lab: – Increase Bili / LDH / reticulocyte count – Jaundice – DAT usually + – Decrease in Haptoglobin
Delayed Hemolytic Transfusion Reaction
• Small amount • Sudden onset & rapid progression – Respiratory distress – Vascular collapse – Afebrile • IgE response to transfused proteins • Particularly susceptible IgA deficients
Anaphylactic Reaction
- Noncardiogenic pulmonary edema
- Usually ~ 2 hours after xfusion
- Acute respiratory insufficiency & hypotension
- CXR = bilateral white out
- Fatality 7%
TRALI
Platelets are involved in _________ hemostasis
primary
How does thrombocytopenia present
– SPONTANEOUS BLEEDING
– PERSISTENT BLEEDING
– EASY BRUISABILITY(WITH OR WITHOUT TRAUMA)
– OOZING OF BLOOD - OFTEN FROM MUCOUS MEMBRANES
– UNEXPLAINED GI OR GU TRACT BLEEDING
– UNEXPLAINED RED FLAT PINPOINT RASH - OFTEN LOWER EXTREMITIES
- Intravascular purpura
- Platelet disorders
- <3mm
- Non-palpable
Petachia
thrombocytopenia bone marrow smear
increased cellularity
megakaryocytes
- Most common cause of easy bruising in a healthy adult
- Females > Males
- Decades 2 & 3
- Easy Bruising
- Diagnosis of exclusion
- Bone Marrow = Megakaryocytes OK
- No Splenomegaly
- Rx:Prednisone/Splenectomy/IVIG/Neumega/Romiplostim/Eltrombopag
Immune Thrombocytic Purpura
– dec Platelets and fibrinogen – inc FDP - PT - PTT - Thrombin Time – inc D-Dimer: • degradation of stabilized fibrin • confirms thrombin generation & FXIII cross-linking Non-immune get Schistocytes – thrombosis - smaller vessels – bleeding = Factor Consumption & Plasminolysis – treat etiology
DIC
Diffuse Intravascular Coagulopathy
• Large vWF multimers – Lack protease • Thrombi: CNS - Kidneys - Myocardium • Peak = 20s F = 65% • Clinical: – Fever – MAHA - Thrombocytopenia – Neurologic - Renal – Hematuria – Proteinuria – Schistocytes - NRBCs – Normal: PT/PTT/fibrinogen
TTP
- Children>Adults
- Prior Infection
- vWF protease normal
- MAHA / Thrombocytopenia (< TTP)
- ARF (renal > TTP)
- No Neurologic or Fever
HUS
Platelet Transfusion - Parameters
– 60,000
Definitions of Hemostasis
- Primary: Platelet Plug:
- Platelets + vascular injury = platelet plug
- Requires VWF + FVIII
- Activates secondary
- Secondary: Fibrin Plug:
- Activation of the coagulation cascade = fibrin plug
Disorders of Hemostasis - Coagulation Cascade
• Extrinsic (Checked with PT/INR) – Tissue Factor + FVIIa – Converts X -> Xa – PT/INR • Intrinsic • Initial sequence – Vascular injury – Kallikrein activates F XII – Cascade follows • aPTT
– Prolongation: dec in Fs II/V/VII/X/Fibrinogen
– Extrinsic system abnormalities
– INR(Int. Normalized Ratio) for Warfarin patients
Prothrombin Time(PT
Prolongation is dec for factors II/V/VIII/IX/X/XI/XII
– Intrinsic system
– Rarely affected by fibrinogen
aPTT
Disorders of Hemostasis - Mixing Studies
– Prolonged PT / aPTT from deficiency?
– Mix patient and control plasma
– Correction
• qualitative or quantitave factor abnormal
– Noncorrection = factor inhibitor
• Lupus anticoagulant
(Mix w/normal control. If PTT is corrected it means there is a deficiency (Present with bleed,
bruise) If it doesn’t correct then SLE (these will present with thrombosis)
Abnormal PT
– Vitamin K deficiency • Vitamin K dependent factors measured by PT = II/VII/X – Coagulopathy of liver disease • Initial = Decreased F II/VII/X • Factor V – NOT Vitamin K dependent. – Hepatic disease vs. other prolonged PT
abnormal aPTT
– Hemophilia • A = congenital def of F VIII • B = congenital def of F IX – von Willebrand’s disease • dec vWBF = dec FVIII = inc aPTT • Corrects on mixing – F XII Deficiency – LA • no correction with mixing
Abnormal PT + aPTT
– Coagulopathy of liver disease – Deficiencies of individual factors • Factor II (Prothrombin) • Factor X (Stuart-Prower) • Factor V (Proaccelerin) – DIC – LA
cuases of ataxic gait
posterior column disease
cerebellar degeneration
peripheral neruopathy
