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386 Cards in this Set
- Front
- Back
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Carotid sheath
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Contains 3 structures (follows VAN rule)
Internal jugular vein Common carotid artery VAGUS nerve |
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Left coronary artery
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1. Left anterior descending (LAD)
*MOST LIKELY TO OCCLUDE *Apex *Anterior interventricular septum 2. Circumflex artery *Supplies posterior LV 3. 20%: CFX gives off PD artery *Supplies posterior septum *Supplies inferior LV *In 80%, PD artery comes from RCA |
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When do coronary arteries fill?
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Diastole
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Right coronary artery
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1. Supplies SA and AV nodes
2. Acute marginal artery *Supplies right ventricle 3. 80%: Posterior descending/IV artery *Supplies posterior septum *Supplies inferior LV "That's a RAP": RCA, Acute marginal, PD/interventricular |
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Where are septal defects heard?
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Right heart
Atrial septal defect = Pulmonic Ventricular septal defect = Tricuspid |
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Cardiac output
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Usual equation:
CO = HR x SV Fick equation: CO = Rate of O2 consumption -------------------------- Arterial O2 - Venous O2 |
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Mean arterial pressure
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MAP =
Systolic P x 1/3 + Diastolic P x 2/3 2nd equation: MAP= Cardiac output x PVR |
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Stroke volume
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SV = EDV - ESV
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Cardiac output during exercise: what increases first?
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STROKE VOLUME
HR increases after prolonged exercise |
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Factors influencing myocardial O2 demand
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~CO
HR SV: *Contractility *Afterload *Preload VIA hypertrophic wall tension |
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Factors influencing stroke volume
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SV CAP
*Contractility and preload increase SV *Afterload decreases SV 1. Contractility + = High Ca2+ (i), low Na+ (o) - = B1 block, low O2, high Co2, acidosis 2. Afterload ~ MAP *VaZodilators decrease afterload (HydralaZine) 3. Preload ~ ventricular EDV *Venodilators decrease preload (VeNo-Nitroglycerin) |
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How does Alpha 1 adrenergic stimulation affect vessels?
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Total vessel constriction
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Factors influencing contractility
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CANa Increase contractility:
High intracellular Ca2+ *Catecholamines (stimulate Ca2+ pump in sarcoplasmic reticulum) Low extracellular Na+ *Digitalis/digoxin blocks Na+ pump, causing higher intracellular Ca2+ Decrease: GAB *Gases (low O2, high CO2) *Acidosis *B1 and Ca2+ channel blockers |
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Starling curve
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Force of contration is proportional to INITIAL LENGTH of cardiac muscle fiber
CO vs. Preload/Ventricular EDV |
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Ejection fraction
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How much of the blood sitting in the LV got ejected?
EF = SV / EDV = EDV-ESV/EDV ***Normally >55%*** |
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Nitroglycerin reduces...
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Preload
VeNodilator: VeNo-Nitro |
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Hydralazine reduces...
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Afterload
HydralaZine = VaZodilator |
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Resistance
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ARTERIOLES are the greatest contributor to PVR
R = P/Q (If you don't want R, mind your P's and Q's) R = 8nl/(Pi)(r^4) *n = viscosity (usually ~Hct) |
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Factors influencing viscosity
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Viscosity usually depends on hematocrit
Increased viscosity states: *Lots of RBCs: Polycythemia *Fat RBCs: Hereditary spherocytosis *Lots of protein: Multiple myeloma, etc |
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Cardiac and vascular function curves
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Venous return:
*High at 0 P (Y axis) *Drops with increasing P Cardiac output: *Increases w/increasing P (EDV) to a point *Plateaus at high P |
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S1
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Mitral and tricuspid valve closure
Loudest at mitral valve (higher P) |
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S2
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Aortic and pulmonary valve closure
Loudest at L STERNAL BORDER |
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S3
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Ken-tuck-y (S1-S2-S3)
Occurs in early diastole *RAPID ventricular filling phase Associated w/increased filling pressures *Dilated ventricle NORMAL FINDING in children |
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S4
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Tenn-ess-ee (S4-S1-S2)
Occurs in late diastole *SLOW ventricular filling phase Sound is from atrial kick (high atrial P) *Hypertrophied/stiff ventricle |
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Jugular venous pulse--A wave
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Atrial contraction
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Jugular venous pulse--C wave
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RV contraction
Even though flow from RV to jugular vein is blocked, the tricuspid valve BULGES into atrium |
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Jugular venous pulse--V wave
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Increased atrial P as it fills w/blood
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S2 splitting
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2nd heart sound is actually A2 P2
A2 P2 divide increases w/inspiration *Increased venous return to right heart--> more volume = long time to close |
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Wide S2 splitting: cause
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Splitting w/o inspiration is wide
Splitting w/inspiration is even wider Still A2 P2 PULMONIC STENOSIS |
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Fixed S2 splitting: cause
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Splitting is constant
Still A2 P2 ATRIAL SEPTAL DEFECT (extra volume of inspiration gets evenly dispersed between L and R heart) |
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Paradoxical S2 splitting: cause
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Splitting is P2 A2
Split SHRINKS w/inspiration AORTIC STENOSIS |
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Mitral/Tricuspid regurgitation
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Occurs during systole
Immediate, holosystolic High pitched blowing murmur Mitral regurg *Loudest at apex *Radiates to axilla Tricuspid regurg *Loudest at tricuspid area *Radiates to right sternal border |
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Ventricular septal defect
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Occurs during systole
Immediate, holosystolic Harsh sounding murmur Heard best in R heart (tricuspid area) |
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Aortic stenosis
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Occurs during systole
Ejection click + Crescendo-decrescendo sound PULSUS PARVUS ET TARDUS--> Pulses weak and late compared to heart sounds |
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Mitral valve prolapse
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Occurs during LATE systole
Mid-systolic click + Crescendo sound that stops @S2 Most common valvular lesion |
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Aortic regurgitation
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Occurs during diastole
Immediate High pitched blowing murmur Presents w/wide pulse pressure when chronic |
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Mitral/Tricuspid stenosis
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Occurs during diastole
Opening snap + murmur Tricuspid stenosis gets LOUDER w/inspiration |
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PDA heart sounds
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Continuous, machine-like murmur
Loudest at S2 |
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Navigating heart sounds
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Systole (4), diastole (2) or continuous (1)?
Continuous = PDA *Machine-like murmur Diastole: *Immediate, HP blowing --> Aortic regurg *Opening snap --> Mitral/TC stenosis *Louder during inspriation --> TC stenosis Systole: *Immediate, HP blowing --> Mitral/TC regurg *Immediate, harsh, louder at TC --> VSD *Ejection click, cres/decres --> Aortic stenosis *Mid-systolic click --> MVP |
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Ventricular action potential
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Phase 0 = Rapid upstroke
*Voltage-gated Na+ channels open Phase 1=Initial repolarization *Inactivation of voltage-gated Na+ channels *Voltage-gated K+ channels open Phase 2: Plateau *Voltage-gated Ca2+ channels *Balance w/K+ efflux *Ca2+ gated Ca2+ release (SR) Phase 3: Rapid depolarization *Slow voltage-gated K+ channels *Voltage-gated Ca2+ channels close Phase 4: Resting potential *High K+ permeability |
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Ventricular action potential: Order of ion channels
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Voltage gated Na+
Fast voltage gated K+ Voltage gated Ca2+ Ca2+ gated Ca2+ Slow voltage gated K+ Resting potential w/high K+ permeability |
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Pacemaker action potential
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Occurs in SA and AV nodes
Phase 0: Upstroke *Voltage gated Ca2+ channels Phase 3: *Inactivation of Ca2+ channels *Voltage-gated K+ channels Phase 4: Slow diastolic depolarization *I-f channel (Na+) *Slope determines heart rate |
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Electrocardiogram
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P wave = Atrial depolarization
*Repolarization masked by QRS PR interval = Conduction delay through AV *Includes P wave, ends at QRS *< 200 msec QRS complex: Ventricular depolarization *< 120 msec QT interval: Ventricular contraction *Includes QRS and T wave ST segment: Ventricles depolarized *Isoelectric *From end of QRS to beginning of T wave *Elevation: Pericarditis or transmural MI *Depression: Subendocardial MI T wave: Ventricular repolarization Isoelectric line: After T wave U wave: Hypokalemia, bradycardia, transmural MI |
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P wave
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P wave = Atrial depolarization
*Repolarization masked by QRS |
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PR interval
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PR interval = Conduction delay through AV
Includes P wave, ends at QRS < 200 msec |
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QRS complex
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QRS complex: Ventricular depolarization
< 120 msec |
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QT interval
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QT interval: Ventricular contraction
Includes QRS and T wave |
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ST segment
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"ST is small (non-inclusive)"
ST segment: Ventricles depolarized *Isoelectric From end of QRS to beginning of T wave Elevation: Pericarditis or transmural MI Depression: Subendocardial MI |
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T wave
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T wave: Ventricular repolarization
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Isoelectric line
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After T wave
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U wave
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Inverted wave seen after T wave
Hypokalemia Bradycardia Transmural MI |
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Torsades de pointes
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A type of ventricular tachycardia
Shifting SINUSOIDAL waveforms Can progress to ventricular fibrillation Treat w/Mg2+ Risk factors: Long QT |
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Wolff-Parkinson-White syndrome
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Wolff, Parkinson and White from Kent (snobby county) to try to BYPASS the rules
Caused by a BUNDLE OF KENT *Accessory conduction pathway *Bypasses AV node Ventricles partially depolarize earlier --> DELTA WAVE on ECG May lead to RE-ENTRY current --> SUPRAVENTRICULAR tachycardia Treatment: Amiodarone |
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Atrial fibrillation
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No P waves
Irregularly irregular QRS complexes |
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Atrial flutter
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Regular atrial depolarization >300/minute
Regular ventricular depolarization ~75/minute |
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1st degree AV block
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Asymptomatic
PR interval is prolonged *Normally < 200 msec Repolarization of P wave visible NO DROPPED QRS COMPLEXES |
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2nd degree AV block: Wenckebach
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A.k.a. Mobitz type 1
Usually asymptomatic Progressive lengthening of PR interval until a beat is DROPPED |
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2nd degree AV block: Mobitz Type 2
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Pathologic/Symptomatic
No change in the PR interval (<200 ms) QRS complexes abruptly dropped Often 2 P waves to 1 QRS |
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3rd degree AV block
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Atria and ventricles beat independently of one another
Atrial rate > Ventricular rate Treat w/pacemaker |
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Ventricular fibrillation
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COMPLETELY ERRATIC RHYTHM
No identifiable waves FATAL arrhythmia w/o CPR, defibrillation |
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B1 effect on heart
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Increase heart rate
Increase contractility |
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What do both Alpha-1 and Beta-1 adrenergic stimulation achieve?
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Increased MAP (= CO x PVR)
Beta works on the BEATER: *Increased HR, contractility --> CO Alpha works on the ALTERNATE: *Vasoconstriction --> PVR *Venoconstriction --> Preload --> CO |
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Baroreceptors
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Aortic arch --> INCREASED BP
*BP will never really be low here *CN X --> Near the heart anyway Carotid sinus --> High or Low BP *CN IX --> In the neck anyway *NINE IN THE NECK |
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Chemoreceptors
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Aortic arch and carotid BODY
*High CO2 *Low O2 (< 60 mm Hg) *Low pH Brain chemoreceptors: *CO2 *pH *NOT O2 (can be naturally low in brain) *Responsible for CUSHING RXN |
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Cushing reaction
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Inciting event: Increased ICP
Constriction of arterioles --> Ischemia Brain reaction = Sympathetic activation *Vasoconstriction --> Systemic HTN Peripheral baroreceptors detect HTN and induce bradycardia Result = CUSHING'S TRIAD *HTN (from brain ischemia) *Bradycardia (from periphery) *Resp depression (brainstem hypoperfusion) |
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Largest share of systemic cardiac output
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Liver
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Highest blood flow per gram of tissue
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Kidney
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Large arteriovenous O2 difference
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Heart
Demand met by coronary blood flow |
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Pulmonary capillary wedge pressure is a good approximation of...
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LA pressure
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Wedge pressure is measured with a...
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Swan-Ganz catheter
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Normal right atrial pressure
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< 5 mm Hg
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Normal right ventricular pressures: Systolic and diastolic
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Systolic: < 25 mm Hg
Diastolic: < 5 mm Hg |
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Normal pulmonary artery pressures
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Systolic: < 25 mm Hg
Diastolic: < 10 mm Hg |
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Normal left atrial/pulmonary wedge pressure
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< 12 mm Hg
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Normal left ventricular pressures: Systolic and diastolic
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Systolic: 130 mm Hg
Diastolic: 10 mm Hg |
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Hypoxia causes vasoconstriction
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LUNGS ONLY
In all other organs, hypoxia causes vasodilation |
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Skin autoregulation
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Deals w/temperature control
Sympathetic stimulation most important |
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Edema: Causes
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Capillary pressure (CHF)
Capillary permeability *Toxins *Infection *Burns Decreased plasma proteins *Nephrotic syndrome *Liver failure Increased interstitial osmotic P *Lymphatic blockage |
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Congenital heart disease: Right to left shunts
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Causes early cyanosis (blue babies)
Children may squat --> increase PVR (compress femoral arteries), which allows L heart P to approach R heart P --> directs more blood to lungs The 5 T's: 1. Tetralogy of Fallot *Most common *22Q 2. Transposition of great vessels *Maternal diabetes 3. Truncus arteriosus *22Q 4. Tricuspid atresia 5. Total anomalous pulmonary venous return (TAPVR) |
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Congenital heart disease: Left to right shunts
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Late cyanosis (blue kids) w/clubbing and polycythemia
*Cyanosis only after R--> L transition (Eisenmenger's) Pumping extra fluid into RV --> Increased pulmonary resistance --> ARTERIOLAR THICKENING --> R to L shunt In order of frequency: VSD --> Down ASD --> Down *Fixed split S2 PDA --> Rubella *Close w/indomethacin |
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Tetralogy of Fallot
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Anterosuperior displacement of the infundibular septum
Cyanotic spells PROVe: Pulmonary artery stenosis *MOST important determinant for prognosis RVH (boot heart) Overriding aorta VSD |
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Squatting w/R-->L shunt
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Squatting increases PVR --> compresses femoral arteries
L heart P approaches R heart P --> directs more blood to lungs |
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Transposition of the great vessels
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Failure of aorticopulmonary septum to spiral
Aorta leaves RV while Pulmonary trunk leaves LV Not compatible w/life unless there is a 2nd deformity *VSD, PDA, patent foramen ovale |
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Coarctation of the aorta: Infantile
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INfantile = IN close to the heart
Aortic stenosis is proximal to insertion of ductus arteriosus |
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Coarctation of aorta: Adult type
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ADult = Distal to Ductus
Associated w/Turner's syndrome Associations: *Notching of the ribs (overuse of collateral circulation) *HTN in upper extremities *Weak pulse in lower extremities (check femoral pulse) |
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Patent ductus arteriosus
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Direction of flow in fetal period: R --> L
Direction of flow post-natally: L --> R *Extra blood in pulmonary outflow means increased RV pressure --> RVH Continuous machine-like murmur *Loudest at S2 (highest P time) Close w/indomethacin Keep open w/PGE *May be necessary w/transposition of GV |
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22Q11 syndromes
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Tetralogy of fallot
Truncus arteriosus (aorta and pulmonary trunk fail to separate) |
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Diabetic mothers
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Transposition of great vessels
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Down syndrome
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VSD
ASD Other endocardial cushion defects (AV septal defect) |
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Congenital rubella
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PDA
PAS (pulmonary artery stenosis) |
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Turner's syndrome
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Coarctation of the aorta
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Marfan's syndrome
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Aortic insufficiency
Late complication--think Lincoln |
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Hypertension
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BP > 140/90
Controllable factors: *Smoking *Obesity, DM Uncontrollable factors: *Age *Race/Genetics: Black > White > Asian 90% of HTN is primary (CO, PVR) 10% is secondary to renal disease Complications: *Atherosclerosis *Stroke *CHF *Renal failure *Retinopathy *Aortic dissection |
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Xanthomas
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Plaques or nodules of cholesterol-laden histiocytes in the skin
Especially the eyelids Tendinous xanthomas are also observed (familial hyperlipidemia) |
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Atheroma
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Plaque in blood vessel wall
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Monckeberg arteriosclerosis
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"PIPESTEM ARTERIES"
CALCIFICATION in the media of the arteries Usually benign |
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Arteriolosclerosis
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Complication of primary HTN
Hyaline thickening of the small arteries Malignant HTN --> hyperplastic onion skinning |
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Atherosclerosis
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Fibrous plaques and atheromas form in the intima of arteries (large and medium vessels)
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Arteriolosclerosis vs. Atherosclerosis
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Arteriolo:
*Small vessels *THICKENING of vessel walls Atherosclerosis: *Medium and large arteries *PLAQUES |
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Aortic dissection
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Longitudinal intraluminal tear
*Forms a false lumen *TEARING chest pain radiating to BACK CXR shows mediastinal WIDENING Associations: *HTN *Cystic medial necrosis (Marfan's) |
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Atherosclerosis
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Disease of elastic arteries + large and medium muscular arteries
Possible symptoms: *Angina *Claudication (cramping pain in legs) Risk factors: *HTN (Obesity, DM, Smoking, Genetics) *Hyperlipidemia Process: *Endothelial dysfunction *Macrophage and LDL accumulation *Foam cell formation *Fatty streaks *Smooth muscle migration *Fibrous plaques *Complex atheroma |
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Complications of atherosclerosis
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ANEURYSMS
Ischemia Infarcts Peripheral vascular disease Thrombus Emboli |
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Most likely sites for atherosclerosis
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N < A > C > K (N is actually last)
Abdomen --> Abdominal aorta Coronary arteries Knee --> Popliteal arteries Neck --> Carotid arteries |
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Angina
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CAD narrowing >75%
Stable: ATHEROSCLEROSIS *Retrosternal chest pain w/exertion Prinzmetal's variant: SPASM *Occurs at rest Unstable/Crescendo: THROMBOSIS *No necrosis *Worsening chest pain |
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Myocardial infarction
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Usually caused by ATHEROSCLEROSIS --> Thrombosis
Causes myocyte necrosis (angina doesn't) |
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Sudden cardiac death
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Death from cardiac causes within 1 hour of symptoms
Most commonly due to arrhythmia |
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Chonic ischemic heart disease
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Progresive onset of CHF over many years
Due to chronic ISCHEMIC myocardial damage |
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Red (hemorrhagic) infarcts
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Loose tissues w/collaterals
"a LIL red" --> *Liver *Intestine *Lung |
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Pale infarcts
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Tissues w/single blood supply
"SHeiK" --> Spleen Heart Kidney |
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Coronary artery occlusions: Frequency
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"The LAD wanted an RCA CFX radio"
LAD > RCA >CFX |
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Coronary artery occlusions: Symptoms
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Pain:
*Retrosternal *L arm *L jaw Adrenergic symptoms: *Diaphoresis *N/V Hypoxic symptoms: *SOB *Fatigue |
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MI: First day
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2-4 hours: NO visible change on LM
4+ hours: *Coagulative necrosis *CONTRACTION BANDS Gross appearance: *Dark mottling *Tetrazolium stain: Light |
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MI: 2-4 days
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ARRHYTHMIA RISK
Acute inflammation *Dilated vessels *Neutrophil emigration Extensive coagulative necrosis Gross appearance: Hyperemia *Due to inflammation |
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MI: 5-10 days
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FREE WALL RUPTURE RISK
Macrophages surround neutrophils Gross appearance: *Red border *Yellow-brown center |
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MI: 7 weeks
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VENTRICULAR ANEURYSM RISK
Contracted scar complete Gross appearance: Gray-white |
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MI resolution: Summary
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Mottle:
2-4 hours: Nothing on LM 4+ hours: Contraction bands Red: 2-4 days: Arrhythmia, inflammation Giant pimple: 5-10 days: Macros, Rupture Scar: 7 weeks: Ventricular aneurysm |
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MI diagnosis
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0-6 hours: ECG
*Transmural: ST elevation, Q waves *Subendocardial: ST depression Troponin I: *1st to rise (4 hours) *1 origin (heart) CK-MB: *2nd to rise *2 origins: Heart, skeletal muscle AST: *3rd to rise *3 origins: Heart, skeletal muscle, liver |
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MI complications
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DR. SALAD
D = Dressler's syndrome: *Autoimmune fibrinous pericarditis *Several weeks post-MI *Fibrinous pericardis can also occur 3-5 d post-MI (friction rub) R = Rupture (5-10 days) *Ventricular free wall --> Tamponade *Interventricular septum --> VSD *Papillary muscle --> Mitral regurg S = Shock (cardiogenic) A = Arrhythmia (2-4 days) L = LV failure and pulmonary edema A = Aneurysm (7 wks) *Decreased CO *Risk of arrythmia *Mural thrombi D = Death |
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Dilated (congestive) cardiomyopathy
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#1 cardiomyopathy (90%)
SYSTOLIC DYSFUNCTION Heart looks like a balloon on CXR Causes: ABCCCD Alcohol abuse Beri-Beri (B1) Coxsackie B virus Cocaine Chagas Doxorubicin toxicity Peripartum cardiomyopathy |
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#1 cardiomyopathy
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Dilated/congestive
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Dilated/congestive cardiomyopathy features systolic or diastolic dysfunction?
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Systolic
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Hypertrophic cardiomyopathy
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50% genetic (autosomal dominant)
Cause of sudden death in young athletes Diastolic dysfunction Normal heart size, but inside: *Hypertrophy *Often involves IV septum Findings: *Loud S4 *Apical impulses Treatment: REDUCE CONTRACTILITY *Beta blocker *Ca2+ blocker (Verapamil) |
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Restrictive/Obliterative cardiomyopathy
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Restrictive ~ Fibrosis
Obliterative ~ Deposits Causes: Deposits: *Sarcoidosis *Amyloidosis *Hemochromatosis Fibrosis: *Post-radiation *Endocardial fibroelastosis (kids) *Loffler's (prominent eosinophil infiltrate) |
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Hypertrophic cardiomyopathy involves systolic or diastolic dysfunction?
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Diastolic
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Treatment for hypertrophic cardiomyopathy
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Contractility reducers
Beta blockers Ca2+ channel blockers |
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Restrictive/obliterative cardiomyopathy involves systolic or diastolic dysfunction?
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Diastolic
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CHF features
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Dyspnea on exertion
*Failure of LV output to increase Pulmonary edema *LV failure --> Increased pulmonary venous pressure --> Transudation of fluid HEMOSIDERIN-LADEN MACROPHAGES IN LUNG *"Heart failure cells" Orthopnea *Increased venous return in supine position worsens pulmonary vascular congestion Hepatomegaly/Nutmeg liver *Increased central venous pressure --> Increased resistance to portal flow Edema and JVD: *RV failure increases peripheral venous pressure *Edema = transudation |
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Most common cause of right heart failure
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Left heart failure
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Embolus types
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An embolus moves like a FAT BAT
Fat --> Long bone fracture, liposuction Air Thrombus Bacteria Amniotic fluid --> DIC risk Tumor 95% of PEs arise from deep leg veins Symptoms: *Chest pain *Tachypnea *Dyspnea |
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Complications of endocarditis
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New murmur
Chordae rupture GLOMERULONEPHRITIS Suppurative pericarditis Emboli |
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Bacterial endocarditis: Valves
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Most common = Mitral
IV drug users = Tricuspid |
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Bacterial endocarditis: Symptoms and causes
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Acute = S. Aureus
*Large vegetations on previously normal valves *Rapid onset Subacute = Strep viridans *Smaller vegetations on abnormal/diseased valves *Insidious onset *Associated w/DENTAL procedures Bacteria FROM JANE: Fever Roth spots (white spots on retina) Osler's nodes (finger/toe pad bumps) Murmur Janeway lesions (red lesions on palm/sole) Anemia Nail-bed/splinter hemorrhage Emboli |
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Libman-Sacks endocarditis
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a.k.a. LSE
Seen in SLE (LSE w/SLE) Verrucous (wart-like) lesions on both sides of mitral valve |
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Rheumatic heart disease
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Consequence of pharyngeal S. Pyogenes (Group A Beta-hemolytic) infection
Type 2 hypersensitivity reaction FEVERSS: F = Fever E = Erythema marginatum V = Valvular damage *Mitral > aortic >> tricuspid E = ESR R = Red hot joints (polyarthritis) S = Subcutaneous nodules (Aschoff bodies) + Anitchkow's cells S = St. Vitus' dance (chorea) ASCHOFF BODY = granuloma w/giant cells ANITSCHKOW'S cells = activated histiocytes |
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Cardiac tamponade
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Compression of heart by fluid in pericardium
EQUILIBRATION of diastolic pressures in all 4 chambers Findings: *PULSUS PARADOXUS: Decreased strength of pulse during inspiration *Hypotension *JVD *Soft heart sounds *ELECTRICAL ALTERNANS (height of QRS complex varies) |
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Pulsus Paradoxus
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Decreased strength of pulse during inspiration
Seen with: *Pericardial issues --> Tamponade, pericarditis *Esophageal inflammation --> Asthma, croup |
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Pericarditis
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3 types:
*Serous --> Uremia, RA, SLE, Virus *Fibrinous --> Uremia, RF, Dressler *Hemorrhagic --> TB, neoplasm Findings: *PULSUS PARADOXUS *ST segment ELEVATION *FRICTION RUB *Pericardial pain *Soft heart sounds +/- Chronic adhesive/constrictive pericarditis |
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Syphilus and heart disease
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Tertiary syphilis disrupts the vasa vasorum of the aorta
Dilation of the aorta and valve +/- Calcification ("tree bark") Possible complications: Aneurysm of the ascending aorta Aortic valve incompetence |
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#1 primary cardiac tumor in adults
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Myxoma
90% in atria (usually LA) Ball and valve structure --> Blocking and syncopal episodes |
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Cancers most likely to metastasize to heart
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Melanoma
Lymphoma Make up >50% of heart tumors |
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#1 primary cardiac tumor in kids
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Rhabdomyoma
Biggest association: Tuberous sclerosis (Ash, Green, CardiacRhab, Astrocytoma, Renal Angiomyolipoma) |
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Kussmaul's sign
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Increase in JVP w/inspiration
Cardiac tumor |
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Kussmaul's pulse
|
Pulsus paradoxus
Decrease in pulse strength w/inspiration |
|
|
Telangiectasia
|
SMALL VESSELS
Arteriovenous malformations that look like dilated capillaries May present as part of Osler-Weber-Rendu syndrome: *AD *Nosebleeds *Skin discolerations |
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|
Raynaud's disease
|
SMALL VESSELS
Arteriolar vasospasm in response to cold temperature or emotional stress Raynaud's PHENOMENON if secondary to CT disease: *SLE *CREST |
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|
Wegener's granulomatosis
|
SMALL VESSELS
c-ANCA (+) *CANCA sores will put a WEGE in your relationship Focal necrotizing: 1. Vasculitis 2. Granulomas in lung, upper airway *Perforation of nasal septum *Otitis media (up Eustachian?) *Chronic sinusitis *Cough, dyspnea *Hemoptysis *CXR: Possibly NODULAR DENSITIES 3. Glomerulonephritis *Hematuria *Red cell casts Treatment: *Cyclophosphamide *Corticosteroids |
|
|
The only c-ANCA vessel disease
|
Wegener's granulomatosis (small vessel)
|
|
|
Sturge-Weber disease
|
SMALL VESSELS (Capillary size)
Congenital vascular disorder Sturge --> Sturgeon --> Port *PORT WINE STAIN on face Web --> in brain *INTRACEREBRAL AVM (leptomeningeal angiomatosis) |
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|
Henoch Schonlein Purpura
|
SMALL VESSELS
#1 childhood systemic vasculitis Common triad of symptoms AFTER URI: 1. Skin (purpura--appear + age together) 2. Joints (arthritis) 3. GI (Intestinal hemorrhage) *Abdominal pain and melena Henoch = NOCH knees (joints) Schonlein = Stomach Purpura = Purpura |
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|
#1 childhood systemic vasculitis
|
Henoch Schonlein Purpura (small vessels)
|
|
|
Microscopic polyangitis
|
SMALL VESSELS
Like Wegeners, but LACKS granulomas P-ANCA (+) Lung and UR symptoms Glomerular disease |
|
|
Primary pauci-immune crescentic glomerulonephritis
|
SMALL VESSELS
Vasculitis LIMITED to kidney Pauci immune = Paucity of Abs ANCA (+) |
|
|
Churg-Strauss Syndrome
|
SMALL VESELS
p-ANCA (+) GRANULOMATOUS vasculitis w/EOSINOPHILIA **Churg ~ Urg to scratch** (Seen in atopic patients) Affects lungs, heart, skin, kidneys, nerves |
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|
Small vessel diseases w/granulomas
|
Wegener's --> c-ANCA
Churg-Strauss --> p-ANCA *Strauss ~ "Spouse" of Wegeners |
|
|
Small vessel diseases w/ANCA associations
|
Wegener's --> c-ANCA
Pauci-immune crescentic glomerulonephritis Microscopic polyangitis --> p-ANCA Churg-Strauss --> p-ANCA |
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|
Buerger's disease
|
SMALL AND MEDIUM VESSELS
a.k.a. Thromboangitis obliterans Causes vascular thromboses: *Claudication and severe pain *Superficial nodular phlebitis *Raynaud's *GANGRENE Seen in HEAVY SMOKERS *Tx = Stop smoking |
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|
Kawasaki disease
|
SMALL AND MEDIUM VESSELS
ACUTE necrotizing vasculitis Affects infants and kids *More dangerous than Henoch-Shonlein Purpura CORONARY ANEURYSMS + Very inflammatory: *Strawberry tongue *Fever, lymphadenitis *Congested conjunctiva |
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|
Polyarteritis Nodosa
|
MEDIUM VESSELS
*Only disease to affect strictly mediums IMMUNE COMPLEXES 30% have HBV seroposivity Necrotizing, often involves renal and visceral vessels *Aneurysms and constrictions Symptoms: Flu-like symptoms Melena Neurologic dysfunction CUTANEOUS ERUPTIONS (age differently) *This is the reason for NODOSA Treatment: Same as Wegeners *Corticosteroids *Cyclophosphamide |
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|
Takayasu's arteritis
|
MEDIUM AND LARGE ARTERIES
a.k.a. Pulseless disease Primarily Asian females <40 Granulomatous thickening of the aortic arch and/or proximal vessels *Increased ESR (lg artery involvement) FAN MY SKIN on Wednesday: Fever Arthritis Night sweats MYalgia SKIN nodules Ocular disturbances Weak pulses in extremities |
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|
Temporal arteritis
|
MEDIUM AND LARGE ARTERIES
Primarily affects elderly females Granulomatous inflammation of (usually) carotids *Increased ESR (lg artery involvement) *50% of patients have systemic involvement, polymyalgia rheumatica Unilateral headache Jaw claudication Opthalmic artery occlusion Treat w/high dose steroids |
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|
Vascular diseases: distinguishing features of M+ L Vessel disease
|
Large vessel (2): L is for Ladies
**Both T** **Both ESR (Unique)** **Granulomas** 1. Takayasu *FAN MY SKIN On Wed *Asian females < 40 *Aortic arch Temporal arteritis *Older ladies *Jaw claudication, vision loss *Carotid +/- systemic |
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|
Vascular diseases: distinguishing features of M vessel disease
|
Med vessel only: ONLY 1!!!
Polyarteritis Nodosa **Unique** Immune complexes 30% HBV seroposiitive Kind of an adult version of Henoch-Schonlein purpura *Myalgia (vs. arthritis) *GI damage, melena *Skin eruptions (BUT age differently) Tx: Same as that of Wegeners Cyclophosphamide Corticosteroids |
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|
Vascular diseases: Distinguishing features of S + M vessel disease
|
S + M vessels: Named after objects
*Buerger --> Like a bad habit (SMOKING) *Kawasaki --> Like a KID'S toy Buergers is thrombosing *Claudication w/nodules (phlebitis) *Raynaud's *Gangrene Kawasaki is necrotizing *Super inflammatory (strawberry tongue) *CORONARY ANEURYSMS |
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|
Vascular diseases: Distinguishing features of S vessel disease
|
Vasospasm only (1): Raynaud's
Malformation only (2): *Telangiectasia (nosebleeds, discoloration) *Sturge-Weber (port-wine face, AVM) Inflammatory (5) --> Granulomatous (3) 1. Wegeners (c-ANCA) *Lung/UR/ear effects *Kidney (hematuria, RBC casts) 2. Churg-Strauss (p-ANCA) *Urge to scratch/atopy *Eosinophilia 3. Microscopic polyangitis (Wegeners but p-ANCA) Kidney only: Pauci-immune crescentic Kids only: Henoch-Shonlein Purpura |
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|
Vascular diseases: Unique features
|
1 c-ANCA: Wegeners
1 eosinophilic: Churg-Strauss 2 kids vasculitis: *Henoch-Shonlein Purpura (S) *Kawasaki's disease (S+M) 1 thrombotic --> Buerger's 1 grangrene --> Buergers 1 coronary aneurysm --> Kawasaki 1 strawberry tongue --> Kawasaki 1 immune complex: Polyarteritis nodosa 1 HBV link: Polyarteritis nodosa 1 Asian female < 40 pop --> Takayasu 1 older female pop --> Temporal arteritis 2 ESR: Takayasu, Temporal arteritis 5 granulomas: *Wegeners *Microscopic polyangitis *Churg-Strauss *Takayasu *Temporal arteritis |
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|
Hydralazine
|
Vasodilates arterioles > veins
*Increases cGMP (sm relaxation) Uses: *Severe HTN (1st line in pregnancy) *CHF SE: *LUPUS LIKE SYNDROME *Compensatory tachycardia (bad w/angina) *Fluid retention |
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|
Minoxidil
|
Vasodilates
*Opens K+ channels (sm relaxation) Uses: *Severe HTN *Baldness SE: *Hair overgrowth (hypertrichosis) *PERICARDIAL EFFUSION *Compensatory tachycardia (bad w/angina) *Fluid retention |
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|
Ca2+ channel blockers
|
We FED at the FRAPPE MILL until DIL was TIAd of ZEM
Nifedipine Verapimil Diltiazem Block L-type (voltage-gated) channels in: *Smooth muscle (vessels) *Cardiac muscle *Cardiac AV nodal cells Vessel effect: N > D >V *Nice if you are doing something to vessels Heart effect: V > D > N Uses: 1. Vascular relaxation: HTN + Raynaud's 2. Heart: Decrease rate and contractility *Angina (even Prinzmetals) *SVT (not N--too weak) SE: *Heart: CARDIAC DEPRESSION (AV block, bradycardia, CHF) *CUTANEOUS FLUSHING *Vascular: Fluid retention, dizziness |
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|
Nitroglycerin, Isosorbide dinitrate
|
Releases nitric oxide
*Venodilation > Arteriolar dilation Uses: APE Vasodilation: Angina, Erections Preload reduction: Pulmonary edema SE: *Reflex tachycardia, flushing, headache *Industrial tolerance: MONDAY DISEASE |
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|
Nitroprusside
|
Directly releases NO
*Increases cGMP --> sm relaxation Use: MALIGNANT HTN SE: CYANIDE TOXICITY |
|
|
Fenoldopam
|
Dopamine D1 receptor agonist
Relaxes renal vascular smooth muscle Uses: MALIGNANT HTN |
|
|
Diaxozide
|
Like minoxidil
*K+ channel opener Use: MALIGNANT HTN |
|
|
Malignant HTN treatments
|
FieND
Fenoldopam: D1 agonist *Increases renal flow Nitroprossude: Direct NO release *Relaxes smooth muscle Diazoxide *K+ channel opener--hyperpolarization *Relaxes smooth muscle |
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|
Special side effects of verapimil
|
Ca2+ channel blocker
Most like a B1 blocker AV block Constipation |
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|
Overall effects of nitrates, B blockers
|
EDV
BP Contractility HR Ejection time MVO2 Nitrates lower everything except HR and contractility (increased as a reflex response) Beta blockers lower everything except EDV and ejection time When taken together, the following are lowered: **Heart rate** **Blood pressure** **MVO2** |
|
|
Partial agonist B blockers
|
Contraindicated w/angina
Labetalol Pindolol Acebutolol |
|
|
BP lowering agents: Unique features
|
Hydralazine --> HTN (arterioles)
*cGMP increaser *Pregnant ladies *SLE syndrome Minoxidil --> HTN, Hair loss *K+ opener *Hypertrichosis *Pericardial effusion Nitrates: *APE: Angina, Pulmonary edema, erections *Monday disease Malignant HTN: *Fenoldepam (DA1)--kidney *Nitroprusside (NO) *Diazoxide (K+ opener) Ca2+ blockers: *HARA: HTN, Angina, Reynaud, Arrhythmia *Cardiac depression *Verapamil: AV block, constipation |
|
|
Effect of Nitrate + Beta blockers
|
Lower BP
Lower HR Lower MVO2 |
|
|
Statins
|
HMG-CoA reductase inhibitors
*Prevent synthesis of MEVALONATE (cholesterol precursor) Affects all 3 lipids in a good way, but major effect is LDL Side effects: Elevated LFTs (reversible) Myositis |
|
|
Niacin
|
Inhibits lipolysis in adipose tissue
Reduces hepatic VLDL secretion into circulation Affects all 3 lipids in a good way, but major effect is HDL Side effects: Flushed face |
|
|
Cholestryramine, Cholestipol
|
a.k.a. Bile acid resins
Prevents intestinal reabsorption of bile acids ONLY CONTRAVERSIAL EFFECT *Slight increase in TGs LDL significantly lowered HDL rises slightly SE: Patients hate it *Tastes bad *GI discomfort *Possible ADEK deficiency |
|
|
Ezetimibe
|
Prevents reabsorption of cholesterol @brush border
1 effect: Decreases LDL 1 SE: Rare LFTs |
|
|
Gemfibrozil, Clofibrate, Bezafibrate, Fenofibrate
|
Upregulates LPL to increase TG clearance
Good effects on all 3 lipids, but main effect is TGs SE: Like statins *Myositis *LFTs |
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|
Digoxin/Digitalis
|
75% bioavailability
*t 1/2 = 40 hours *20-40% protein bound Inhibits Na/K ATPase --> Indirectly stops the Na/Ca exchanger 1. Increased intracellular Ca2+ --> CONTRACTILITY 2. AV slowing/SA depression --> SLOWER HR Uses: *CHF *Atrial fibrillation (slows conduction at AV node) SE: 1. Parasympathetic activation *N/V/D *Blurry YELLOW vision 2. ECG changes: *AV slowing (long PR) *More contraction (short QRS, ST scoop, T inversion) |
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|
Digoxin/Digitalis: Interactions
|
Hypokalemia: Makes the Na/K pump work even less effeciently
*Exacerbates dixogin's effects Renal failure (reduced excretion) Quinidine *Competes w/digoxin for tissue binding sites --> Slows clearance |
|
|
Digoxin toxicity: Treatment
|
Mg2+
Normalize K+ (slowly) Lidocaine Cardiac pacer Anti-digoxin Fab fragments (Ab) |
|
|
Class 1 Antiarrhythmics: Info
|
Acts on MUSCLE AND PACEMAKER to slow the HR
Blocks Na+ channels *Selectively depress tissue that is frequently depolarized 1. Muscle: Slows down the rapid UPSTROKE (depolarization) 2. Pacemakers less likely to fire: *Decreases slope of phase 4 depolarization *Increases THRESHOLD for firing in normal pacemaker cells Hyperkalemia increases toxicity for all class I drugs *Na+ blockage promotes K+ buildup outside |
|
|
Class 1A Antiarrhythmics
|
QUeen AMy PROClaims DISO's PYRAMID
Quinidine Amiodarone--class 1-4, actually Procainamide Disopyramide Increase AP duration --> long QT *Increased effective refractory period *Caused by prolonged phase 0 AND prolonged phase 3 via a small interaction with K+ channels Use: Atrial arrhythmias Ventricular arrhythmias SE: Quinidine = Cinched belt, pale *Cinchonism (headache, tinnitus) *Thrombocytopenia *Torsades de pointes (from long QT) Procainamide = SLE-like syndrome |
|
|
Class 1B Antiarrhythmics
|
I'd Buy LIDdy's MEXican Tacos
I'd buy = IB L = Lidocaine M = Mexiletine T = Tocainide Binds both activated and inactivated Na+ channels --> K+ can flow in unchallenged, and AP is SHORTENED *Decreased AP (and QT, ERP) *Acts on Purkinje fibers in ventricle Uses: Ventricular arrhythmia (esp w/MI) Digitalis arrhythmia SE: U feel numb when UR depressed *Local anaesthetic *Cardiac depression |
|
|
Class IC Antiarrhythmics
|
PROP, FLECK and ENter the goal
Propafenone Flecainide Encainide As with all Class I drugs, slow rate of CONDUCTION of the action potential, but no effect on AP duration Really good at prolonging refractory period in the AV node Last resort: Ventricular arrythmias SE: C is for contradiction *Actually pro-arrhythmic (esp post-MI) |
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|
Mnemonic for anti-arrhythmics
|
SoBe PoCa
Sodium Beta blocker Potassium Calcium |
|
|
B blockers
|
Decreases HR, contractility
A-M are selective (no asthma problems) except LABETOLOL and CARVEDILOL Propanolol Esmolol--short acting Metoprolol--dyslipidemia Atenolol Timolol Mechanisms: *Muscle: Decreases cAMP and Ca2+ currents *Pacemaker: Decreases slope of phase 4 (increased PR) Use: *Atrial arrythmias *Ventricular arrythmias *Angina (w/nitrates to decrease HR, BP) SE: CCAMI *Cardiovascular effects (AV block, bradycardia, CHF) *CNS effects (sedation, sleep alt) *Asthma exacerbation (non-selective) *Mask hypoglycemia *Impotence |
|
|
Class III Antiarrhythmics
|
Decreases myocyte activity
K+ channel blockers BIAS: *Bretylium *Ibutilide *Sotalol *Amiodarone --> WPW Block K+ channel, but act like 1A antiarrhythmics *Increased AP duration *Long QT, ERP Uses: Atrial and ventricular arrhythmias (backup) SE: *Bretylium = Arrhythmia, hypotension *Ibutilide = TDP *Sotalol = TDP, excessive B block *Amiodarone--> Photsensitivity, pulmonary fibrosis, PFTs, LFT,s TFTs |
|
|
Amiodarone
|
Class I-IV Antiarrhythmic (Na+, K+, Ca2+)
Used for Wolf-Parkinson-White syndrome SE: PULMONARY FIBROSIS PHOTOSENSITIVITY **MAKE SURE TO CHECK:*** PFTs (risk of fibrosis) LFTs (risk of hepatotoxicity) TFTs (risk of hypo/hyperthyroid) |
|
|
Anti-arrhythmics: Mechanisms
|
1 --> Na+
*Slower upstroke --> Slower HR *Slower phase 4 --> Slower HR *Higher node threshold --> Slower HR 1A: Long QT --> Slower HR 1B: Short QT 1C: Unchanged QT 2 --> Beta blocker *Decreased cAMP, Ca2+ --> contractility *Slower phase 4 --> Slower HR 3 --> K+ *Longer AP --> Slower HR 4 --> Ca2+ *Slower AV node upstroke --> Slower HR *Low Ca2+ influx--> Decreased contractility |
|
|
Adenosine
|
Causes K+ to leave cells --> hyperpolarization
*AV node cells *Vascular smooth muscle cells Use: 1st line for AV nodal arrhythmias Very short-acting (15 seconds) SE: Flushing, hypotension, chest pain |
|
|
K+
|
Depresses ectopic pacemakers in hypokalemia (digoxin)
|
|
|
Mg2+
|
Torsades de pointes
Digoxin antidote |
|
|
Lymph node structure
|
Secondary lymphoid organ
*Many afferents (enter cortex) *1+ efferent (exits by artery, vein) **BTMP** (Cortex to medulla) Cortex: B cells *Primary follicles are dense, dormant *Secondary follicles (active) have pale germinal centers Paracortex: T-cells and HEVs *HEV: Where B and T cells enter from blood *Not well-developed w/DiGeorge Medulla: Medullary cords and sinuses *Cords = Plasmas, lymphocytes *Sinuses = Macrophages, reticular cells Macrophages ~ Mobile (sinuses) |
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|
Upper limb and lateral breast drainage site
|
Axillary nodes
|
|
|
Stomach lymphatic drainage site
|
Celiac nodes
Cecelia, you're breakin my STOMACH |
|
|
Duodenum, jejunum lymphatic drainage site
|
Superior mesenteric nodes
DJ = Tallest (superior) sister |
|
|
Sigmoid colon lymphatic drainage site
|
Colic nodes --> Inferior mesenteric nodes
Sigmoid says there's an INFERIORITY complex behind the COLIC |
|
|
Rectum, anal canal lymphatic drainage (above pectinate line)
|
Internal iliac nodes
|
|
|
Anal canal below pectinate line
|
Superficial inguinal nodes
|
|
|
Testicular lymphatic drainage site
|
Superficial and deep lymphatic plexuses --> Para-aortic nodes
|
|
|
Scrotum lymphatic drainage site
|
Superficial inguinal nodes
|
|
|
Superficial thigh lymphatic drainage site
|
Superficial inguinal nodes
|
|
|
Lateral dorsum of foot lymphatic drainage site
|
Popliteal nodes
|
|
|
Right lymphatic duct drainage
|
Right arm
Right half of head |
|
|
Thoracic duct drainage
|
Everything except what right lymphatic duct drains (right arm, right half of head)
|
|
|
Superficial inguinal node drainage
|
Skin structures below the pectinate line (or pecker)
Anal canal below pectinate line Scrotum Superficial thigh |
|
|
Primary lymphoid organs
|
Lymphoid organs that develop early immune cells
Bone marrow Thymus |
|
|
Secondary lymphoid organs
|
Lymphoid organs that house mature immune cells
Lymph nodes --> Encapsulated Spleen --> Encapsulated MALT, GALT --> Unencapsulated |
|
|
Spleen
|
MBTA (Outside to inside)
MACROS, APCs, T cells--red pulp B cells (Follicles)--white pulp T cells (PALS) Central arteriole Red pulp: *Vascular channels w/fenestrated BM ("BARREL HOOP") *Macrophages (remove encapsulated bacteria) PALS = Periarterial lymphatic sheath Arises from dorsal mesentary but fed by branches of the celiac artery (splenic a) |
|
|
"Barrel hoop" basement membrane
|
Red pulp of the spleen
|
|
|
Where are T cells found in the spleen?
|
PALS
Some in the red pulp |
|
|
Thymus
|
3rd branchial pouch origin
Encapsulated Cortex = Immature T cells Corticomedullary junction *Positive selection (MHC restriction) *Negative selection (nonreactive to self) Medulla = Mature T cells (pale) *Epithelial reticular cells *HASSALL'S CORPUSCLES (granular cell center, concentric epithelial layers) |
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|
Innate immunity
|
Neutrophils
Macrophages Dendritic cells Complement |
|
|
Adaptive immunity
|
B cells (and Ab), T cells
Undergo VDJ recombination |
|
|
Differentiation of T cells
|
After creation in marrow DIRECTLY to thymus
*No receptors or other defining features Thymus: 1. CD4+ CD8+ 2. CD4+ OR CD8+ (cytotoxic) 3. CD4+ T cells further differentiate: *IL-12 --> TH1 *IL-4 --> TH2 |
|
|
IL-12 promotes what type of differentiation?
|
TH1
|
|
|
IL-4 promotes what type of differentiation?
|
TH2
|
|
|
TH1 cells
|
Differentiation induced by IL-12
*Origin: B cells and macrophages Secretes: IL-2 *Stimulates CD8 cells *Autostimulation IFN-gamma *Stimulates MACROS Inhibits TH2 cells via: IFN-gamma |
|
|
TH2 cells
|
Differentiation induced by IL-4
*Origin: Other TH2 cells Secretes: IL-4 *Activates B cells *Induces class switching to IgE > IgG IL-5 *Promotes differentiation of B cells *Induces class switching to IgA *Stimulates eosinophils (production, activation) Inhibited by: IFN-gamma EOSINOPHIL STIMULATION AND IGE CLASS SWITCHING ARE NOT PART OF THE SAME IL FUNCTION |
|
|
TH1 cell secretions
|
IL-2
*Stimulates CD8 cells *Autostimulation IFN-gamma *Stimulates MACROS *Inhibits TH2 cells |
|
|
TH2 cell secretions
|
IL-4
*Activates B cells *Induces class switching to IgE > IgG *Inhibits TH1 cells IL-5 *Promotes differentiation of B cells *Induces class switching to IgA *Stimulates eosinophils (production, activation) |
|
|
What inhibits a TH2 cell?
|
IFN-gamma
|
|
|
What cells control TH1 differentiation?
|
B cells and macrophages (secrete IL-12)
|
|
|
What cells control TH2 differentiation?
|
TH2 cells
|
|
|
MHC I
|
Encoded by 3 genes:
HLA-A HLA-B HLA-C Expressed on almost all nucleated cells Reflects material from RER *Mostly intracellular MEDIATES VIRAL IMMUNITY Pairs w/B2 MICROGLOBULIN to form complete receptor |
|
|
MHC II
|
Encoded by 3 genes:
HLA-DP HLA-DQ HLA-DR Expressed only on APCs *B cells *Macrophages *Dendritic cells Reflects material from acidified endosome *Extracellular material Receptor has alpha and beta subunits *Roughly equal in size |
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|
Immune cells and hypersensitivity
|
Type 1 = IgE (B cells)
Type 2 = IgG (B cells) Type 3 = IgG (B cells) Type 4 = CD8 T cells |
|
|
CD3 complex
|
Cluster of polypeptides associated w/the T cell receptor
Important in signal transduction |
|
|
APCs
|
My BaD (MBD)
Macrophages B cells Dendritic cells Have MHC II complexes Bind to CD4 T cells |
|
|
CD4 T cells: Costimulatory signal
|
After binding to MHC II...
CD28 on CD4 cell + B7 on B cell (or other APC) (7 x 4 = 28) |
|
|
CD8 T cells: Costimulatory signal
|
After binding to MHC 1...
Cytotoxic T cell needs IL-2 from a TH1 helper cell |
|
|
Antibody structure
|
2 light chains + 2 heavy chains
*Each have variable (antigen-recognizing) and constant regions *Each have inter-chain and intra-chain disulfide bonds Fab = Upper half *Binds antigen *Amino end Fc = Lower half *Completely constant (vs. partially) *Carboxy terminal *COMPLEMENT binding (IgG + IgM only) *Carbohydrate chains |
|
|
Antibody diversity
|
Recombination of VJ (light chain) or VDJ (heavy chains) genes
*Addition of nucleotides occurs via terminal DEOXYNUCLEOTIDYL TRANSFERASE Random combination of established heavy and light chains Somatic hypermutation (post-antigen recognition) |
|
|
Isotype switching is mediated by...
|
Cytokines
CD40 ligand *Midlife crisis? |
|
|
Complement binding Abs
|
IgG
IgM Driving a GM gets you COMPLEMENTS? |
|
|
Mature B cells originally express what Abs?
|
IgM
IgD |
|
|
IgG
|
Crosses the placenta (UNIQUE)
Fixes complement (IgG + IgM only) Promotes opsonization Neutralizes bacterial toxins and viruses |
|
|
IgA
|
Monomer or dimer found in secretions
Prevents attachment of bacteria/viruses to mucous membranes Picks up SECRETORY COMPONENT from epithelial cells before secretion |
|
|
IgM
|
Monomer on B cell
Pentamer in serum Produced in the PRIMARY response to an antigen (IgG later) Fixes complement (IgG + IgM only) |
|
|
IgD
|
Unclear function
Found on surface of many B cells and in serum |
|
|
IgE
|
Lowest concentration in serum
1. Activates mast cells and basophils (induces mediator release) *Type 1 hypersensitivity reactions 2. Activates eosinophils during parasitic infection |
|
|
Ig allotype
|
POLYMORPHISM
Immunoglobin epitope that differs among members of the same species Constant regions of light chains or heavy chains |
|
|
Ig isotype
|
Immunoglobin epitope that is common to a class
IgA, IgM, IgG, etc. Determined by heavy chain |
|
|
Ig idiotype
|
Determined by VARIABLE REGION
Immunoglobin epitope determined by antigen binding site |
|
|
Cytokines secreted by macrophages
|
IL-1
IL-6 (also TH cells) IL-8 IL-12 (also B cells) TNF |
|
|
Cytokines secreted by B cells
|
IL-12 (also macrophages)
|
|
|
Cytokines secreted by regulatory T cells
|
IL-10
|
|
|
Cytokine released by both cytotoxic and helper T cells
|
IL-3
|
|
|
Cytokine released by all helper T cells
|
IL-6 (also macrophages)
|
|
|
IL-1
|
Secreted by macrophages
ACUTE INFLAMMATION *Induces chemokines --> WBC taxis *Induces endothelium to express adhesion molecules |
|
|
IL-2
|
Secreted by TH1 cells
Stimulates growth of CD8 and TH1 cells |
|
|
IL-3
|
Secreted by activated T cells
Supports growth and differentiation of BONE MARROW |
|
|
IL-4
|
Secreted by TH2 cells
Promotes B cells Class switching to IgE, IgG *IgE > IgG |
|
|
IL-5
|
Secreted by TH2 cells
Promotes B cells Class switching to IgA Promotes Eosinophils |
|
|
IL-6
|
Secreted by TH cells and macrophages
Stimulates acute-phase reactants and immunoglobins Anemia of chronic disease: IL-6 increases liver production of Hepcidin *Hepcidin stops ferroportin from releasing iron stores |
|
|
IL-8
|
Secreted by macrophages
Neutrophil recruitment "Clean-up on aisle 8" *Neutrophils recruited by IL-8 to clear infections |
|
|
IL-10
|
Secreted by regulatory T cells
Inhibits all other T cells |
|
|
IL-12
|
Secreted by B cells and macrophages
Activates TH1 cells Activates NK cells |
|
|
IFN-gamma
|
Secreted by TH1 cells
Activates macrophages |
|
|
TNF
|
Secreted by macrophages
Mediates SEPTIC SHOCK *WBC recruitment *Vascular leak |
|
|
Helper T cell
Surface proteins |
TCR/CD3 --> T cell
CD4 --> HELPER T cell *Binds to MHC II CD28 --> HELPER T cell *Costimulatory signal CD40L --> HELPER T cell *General APC activation *B cell class switching |
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Cytotoxic T cell
Surface proteins |
TCR/CD3 --> T cell
CD8 --> Cytotoxic T cell |
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B cell
Surface proteins |
Unique:
IgM CD 19-21 Others are in common w/macrophage: MHC II *APC B7: Costimulatory signal CD40 *Class switching |
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Macrophage
Surface proteins |
Unique:
CD14 Receptors for Fc and 3b Others are in common w/B cell: MHC II *APC B7: Costimulatory signal CD40 *Activation by TH cell |
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NK cells
Surface proteins |
Unique:
CD16 CD56 MHC I |
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What activates the CLASSIC complement pathway?
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Ag-Ab complexes: IgG or IgM
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What activates the LECTIN/MANNOSE complement pathway?
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Microbial surface (mannose)
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What activates the ALTERNATIVE complement pathway?
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Microbial surface
Nonspecific activators ESPECIALLY ENDOTOXIN |
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Opsonins in bacterial defense
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IgG
C3b THAT'S IT |
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Decay accelerating factor
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Deficiency leads to complement-mediated lysis of RBCs
Paroxysmal nocturnal hemoglobinuria (PNH) Paroxysmal ~ I don't get it *Are you DAFt? |
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C1 esterase
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Inhibitor of complement activation
Protects self cells along w/DAF Deficiency causees HEREDITARY ANGIOEDEMA *Aunt ESTER and ANGIE in the HEREDITARY tree |
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C3a, C5a
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Anaphylaxins
C5a also participates in neutrophil chemotaxis |
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Anaphylaxins
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C3a, C5a
C5a also participates in neutrophil chemotaxis |
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Neutrophil chemotaxis
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IL-8 (macrophages)
C5a (complement) |
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Deficiency of C3
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Severe, recurrent pyogenic sinus and respiratory tract infections
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Deficiency of C6-8
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Neisseria bacteremia
6-8 is never a NICE time to call |
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C5b-9
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MAC
Responsible for complement-induced lysis |
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C1-4
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Responsible for viral neutralzation
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Classic complement pathway
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C1 binds to Ag-Ab complex (IgG or IgM)
C1-C4b-C2a-3b-5b-6789 The only #out of place is 4 The only "a" is w/complement #2 *"B usually STAYS; A usually floats AWAY" The point where 3b attaches is where opsonization (viral neutralization) can occur |
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Lectin complement pathway
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Lectin binds to mannose on pathogen
Lectin-4b-2a-3b-5b-6789 |
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Alternative complement pathway
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C3 w/B and D bind to endotoxin or other part of microbial surface
C3b-Bb-C3b-5b-6789 DOUBLE C3b |
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Interferons
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Put uninfected cells in an antiviral state
Induce ribonuclease that degrades viral mRNA Increase activity of NK cells Gamma interferon: Increase all MHC I, II expression and antigen presentation Alpha: Alpha BC, KLM *Hep B/C *Kaposi's *Leukemia *Malignant melanoma Beta: Multiple sclerosis Gamma: NADPH oxidase deficiency (Chronic Granulomatous Disease) Inferferon SE = NEUTROPENIA |
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Passive immunity
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Preformed Abs given after exposure to:
Tetanus toxin Botulinum HBV Rabies "TO BE HEALED RAPIDLY" |
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Anergy
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Nonreactivity w/o a costimulatory signal
Self-reactive T cells B cells also become anergic, but less so than T cells |
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Type 1 Hypersensitivity
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"First and fast"
"Anaphylactic and Atopic" IgE has been cross-linked on pre-sensitized mast cells and basophils Antigen exposure = Release of vasoactive amines (histamine) AAA: Anaphylaxis Atopy Allergic rhinitis |
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Type 1 Hypersensitivity: Examples
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AAA:
Anaphylaxis Atopy Allergic rhinitis |
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Atopy: Hypersensitivity type __
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1
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Anaphylaxis: Hypersensitivity type __
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1
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Allergic Rhinitis: Hypersensitivity type __
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1
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Type 2 Hypersensitivity
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Cy-2-toxic
IgM, IgG bind to fixed antigen on "enemy" cell --> Complement-mediated lysis or phagocytosis Examples: Hemolytic anemia Idiopathic thrombocytopenic purpura Erythroblastosis fetalis Rheumatic fever Goodpasture's syndrome Bullous Pemphigoid Grave's disease Myasthenia gravis |
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Type 2 Hypersensitivity: Examples
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Vascular:
*Hemolytic anemia *Idiopathic thrombocytopenic purpura *Erythroblastosis fetalis Heart: Rheumatic fever Kidney, Lung: Goodpasture's Skin: Bullous Pemphigoid (BM) Thyroid: Grave's disease NMJ: Myasthenia gravis |
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Type 2 Hypersensitivity: Vascular examples
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Hemolytic anemia
Idiopathic thrombocytopenic purpura Erythroblastosis fetalis |
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Type 2 Hypersensitivity: Heart
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Rheumatic fever
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Type 2 Hypersensitivity: Kidney, lung
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Goodpasture
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Type 2 Hypersensitivity: Skin
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Bullous pemphigoid
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Type 2 Hypersensitivity: Thyroid
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Grave's disease
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Type 2 Hypersensitivity: NMJ
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Myasthenia Gravis
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Type 3 Hypersensitivity
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Immune complex mediated
*Immediately attracts COMPLEMENT, which attracts NEUTROPHILS SHARPPS SLE Hypersensitivity pneumonitis Arthus reaction: Local, subacute *Intradermal injection of Ag Rheumatoid arthritis Post-streptococcal glomerulonephritis Polyarteritis nodosa Serum sickness: Abs form in 5 days *Usually caused by drugs *IC's deposited systemically |
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Type 3 Hypersensitivity: Examples
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SHARPPS
SLE Hypersensitivity pneumonitis Arthus reaction: Local, subacute *Intradermal injection of Ag Rheumatoid arthritis Post-streptococcal glomerulonephritis Polyarteritis nodosa Serum sickness: Abs form in 5 days *Usually caused by drugs *IC's deposited systemically |
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Type 4 Hypersensitivity
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Sensitized T cells encounter antigen, activate macrophages
Examples: 5 T's TB (PPD test) Thyroid (Hashimoto) Touching (Contact dermatitis) Transplants (Graft vs. host) Type 1 diabetes + MSG: MS + Guillain Barre |
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Type 4 Hypersensitivity: Examples
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The 5 Ts + MSG
TB (PPD test) Thyroid (Hashimoto) Touching (Contact dermatitis) Transplants (Graft vs. host) Type 1 diabetes + MSG: MS + Guillain Barre |
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SLE: Hypersensitivity type ___
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3
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Hypersensitivity pneumonitis: : Hypersensitivity type ___
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3
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Arthus reaction: Hypersensitivity type ___
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3
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Rheumatoid arthritis: Hypersensitivity type ___
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3
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Post-streptococcal glomerulonephritis: Hypersensitivity type ___
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3
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Post-streptococcal glomerulonephritis: Hypersensitivity type ___
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3
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Polyarteritis nodosa: Hypersensitivity type ___
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3
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Serum sickness: Hypersensitivity type ___
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3
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PPD reaction: Hypersensitivity type ___
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4
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Hashimoto's thyroiditis: Hypersensitivity type ___
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4
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Contact dermatitis: Hypersensitivity type ___
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4
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Graft vs. Host disease: Hypersensitivity type ___
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4
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Type 1 Diabetes: Hypersensitivity type ___
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4
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Multiple sclerosis: Hypersensitivity type ___
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4
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Guillain Barre: Hypersensitivity type ___
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4
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Bruton's agammaglobulinemia
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X-linked recessive
Defect in a tyrosine kinase gene **Low B cells** **Low levels of all Abs** Infections after 6 months of age (maternal IgG declines) |
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Thymic aplasia
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Feature of DiGeorge syndrome (22q11)
THC: T = Thymus --3rd pharyngeal pouch *Viral and fungal infections H = Hypocalcemia *Parathyroids --3rd (inf) and 4th (sup) pouch C = Cardiac defects *Tetralogy *Truncus arteriosus |
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Severe combined immunodeficiency (SCID)
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Low B cells and T cells
Defect in stem-cell differentiation due to one of several causes *MHC II presentation defect *Defective IL-2 receptors *Adenosine deaminase deficiency (toxic accumulations kill lymphocytes) Recurrent infection of all kinds (bacterial, viral, fungal, protozoal, etc) |
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IL-12 receptor deficiency
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Diminished TH1
DISSEMINATED MYCOBACTERIAL INFECTION |
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Hyper IgM syndrome
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Defect in CD40 ligand (CD4 T helper cells)
*No CD40-CD40L binding =inability to class switch *B cells make only IgM Severe PYOGENIC infections early in life |
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Wiskott-Aldrich syndrome
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X-linked recessive
Inability to mount an IgM response to capsular polysaccharides *Low IgM *High IgA Wiscott = WIPE *W= Wiscott *I = Infections (pyogenic) *P =Purpura (thrombocytopenic) *E = Eczema Aldrich = IgA (very high) |
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Job's syndrome
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Failure if IFN-gamma production by TH1 cells
*Responsible for stimulating macrophages Poor macrophage function --> Low IL-8 --> Poor neutrophil response FATED: F = Facies (coarse) A = Abscesses (cold, noninflamed) T = Teeth (retained primary) E = IgE (high) D = Dermatologic prob (eczema) |
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Leukocyte adhesion deficiency
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LFA-1 integrin defect
Recurrent bacterial infections NO PUS DELAYED SEPARATION OF UMBILICUS LAD: Lots of infections Absent pus Delayed separation of umbilicus |
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Delayed separation of umbilicus
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Leukocyte adhesion deficiency
LFA-1 |
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Chediak Higashi diease
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Autosomal recessive
Defect in microtubular function Poor lysosomal emptying of phagocytic cells Recurrent pyogenic infections *Staph, strep Partial albinism (pigment release) Peripheral neuropathy (axonal transport) |
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Chronic granulomatous disease
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Lack of NADPH oxidase (or similar enzymes) --> Defect in phagocytosis
Marked susceptibility to opportunistic infection *S. aureus *E. coli *Aspergillus Diagnosis = Negative TETRAZOLIUM dye reduction test Treatment: Gamma interferon |
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Chronic mucocutaneous candidiasis
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T cell dysfunction against CANDIDA
Skin and mucous membrane candida infections |
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Selective Immunoglobin Deficiency
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Deficiency in a specific Ig class
IgA most common *Sinus and lung infections *Milk allergies *Diarrhea |
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Ataxia-telangiectasia
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DNA repair enzymes defect
**Associated w/IgA deficiency** Ataxia (cerebellar) Telangiectasia (spider angiomas) |
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Common variable immunodeficiency
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B cells don't MATURE into plasma cells
*Normal B cell #s *Low plasma cells and Igs Can be acquired in 20s-30s |
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HLA-B27
|
PAIR
Psoriasis Ankylosing spondylosis Inflammatory bowel disease Reiter's syndrome (Urethritis, Uveitis, Arthritis) |
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HLA-B8
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Skinny people...I wish they 8 more
Graves disease Celiac sprue |
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HLA-DR2
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Too (inclusive)
1 rep from each hypersensitivity: Hay fever Goodpastures SLE MS |
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HLA-DR3
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DM Type 1
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HLA-DR4
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DM Type 1
Rheumatoid arthritis *4 walls in a RHEUM |
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HLA-DR5
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5= Tired
Hashimoto's thyroiditis Pernicious anemia/B12 |
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HLA-DR 7
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7 year olds
Steroid responsive nephrotic syndrome |
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Xenograft
|
Transplant from a different species
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Syngeneic graft
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Identical twin or clone
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Allograft
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Nonidentical individual of same species
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ANA
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SLE
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Anti-ds DNA
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SLE
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Anti-Smith
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SLE
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Anti-histone
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Drug-induced SLE
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Anti-IgG
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Rheumatoid arthritis
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Anti-centromere
|
CREST
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Anti-Scl-70
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a.k.a. Anti-topoisomerase
Diffuse scleroderma |
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Anti-topoisomerase
|
a.k.a. Anti-Scl-70
Diffuse scleroderma |
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Anti-mitochondrial
|
Primary biliary cirrhosis
Women |
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Anti-gliadin
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Celiac disease
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Anti-BM
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Goodpasture's
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Anti-epithelial cell
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Pemphigus vulgaris
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Anti-microsomal
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Hashimoto's
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Anti-thyroglobulin
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Hashimoto's
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Anti-Jo-1
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Polymyositis
Dermatomyositis |
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Anti-SSA (anti-Ro)
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Raynaud's
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Anti-SSB (anti-La)
|
Raynaud's
More specific than SSA |
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Which is more specific for Raynaud's, SSA or SSB?
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SSB
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Anti-UI RNP
|
Mixed CT disease
SLE, Scleroderma, etc |
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Anti-smooth muscle
|
Autoimmune hepatitis
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Anti-glutamate decarboxylase
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Type 1 DM
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c-ANCA
|
Wegener's granulomatosis
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p-ANCA
|
Microscopic polyangitis
Pauci-immune crescentic glomerulonephritis Churg-Strauss syndrome |
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|
Cyclosporine
|
Binds to cyclophilins --> Inhibits CALCINEURIN --> IL-2 inhibition
Use: TRANSPLANTS Viral infection Lymphoma Nephrotoxicity --> Prevent w/mannitol |
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Tacrolimus
|
Similar to cyclosporine (IL-2 inhibition)
*Binds to FK-BINDING PROTEIN rather than calcineurin Use: TRANSPLANTS SE: Significant Nephrotoxicity Peripheral neuropathy HTN, pleural effusion Hyperglycemia No lymphoma risk like cyclosoprine, but the nephrotox isn't preventable w/mannitol |
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Azathioprine
|
Anti-metabolite precursor of 6 mercaptopurine
*Interferes w/purine metabolism *Toxic to lymphocytes *ALLOPURINOL PROLONGS Uses: Kidney transplantation Glomerulonephritis Hemolytic anemia SE: Marrow suppression |
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Muromonab-CD3
|
OKT3
CD3 antibody Blocks T cell signal transduction Uses: Kidney transplantation SE: Cytokine release syndrome Hypersensitivity |
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Sirolimus
|
a.k.a. Rapamycin
Binds to mTOR Inhibits T cell proliferation in RESPONSE to IL-2 Use: Kidney transplantation SE: *"Rolls" --> Hyperlipidemia *Thrombocytopenia, leukopenia |
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|
Mycophenolate mofetil
|
GUANa tell the story of Ms. Mofet?
Inhibits guanine synthesis Block lymphocyte production |
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|
Daclizumab
|
IL-2 receptor antibody
|
|
|
Filgrastim
|
G-CSF
Used for BM recovery |
|
|
Sargramostim
|
GM-CSF
Used for BM recovery |
|
|
Thrombopoietin
|
Used for thrombocytopenia
|
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|
Oprelvekin
|
a.k.a. IL-11
Thrombocytopenia |
|
|
Aldesleukin
|
IL-2 activator
Metastatic renal cell carcinoma Metastatic melanoma |
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|
Hyperacute rejection
|
Pre-formed ANTIBODIES in the transplant recipient
Occurs within minutes |
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|
Acute rejection
|
Occurs weeks after transplantation
Cytotoxic T CELLS react against foreign MHCs REVERSIBLE w/cyclosporine, OKT3, etc. |
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|
Chronic rejection
|
Occurs within months to years
ANTIBODY mediated vascular damage --> Fibrinoid necrosis IRREVERSIBLE |
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|
Graft vs. host disease
|
Transplanted T cells attack the host
Maculopapular rash Jaundice, hepatomegaly Diarrhea |
