Cardio Flashcards
[Cardiovascular Embryology] 1. Describe vitelline system for blood cell development 2. What happens to: A. R vitelline vein B. L vitelline vein C. R umbilical vein D. L umbilical vein E. Anterior cardinal vein F. Posterior cardinal veins
- Chorion (membrane that is part of the amniotic sac) establishes connections with umbilical vessels, which establishes connections with vitelline vessels, which establishes connections with umbilical vesicle
- vitelline vessels are yolk sac equivalent - source of blood cells
- All venous drainage (cardinal, vitelline, umbilical veins) into primordial heart is through sinus venosus
- paired dorsal aorta supply the body (later fuse and become descending aorta)
- umbilical arteries return deoxygenated blood to the placenta
2.
A. R vitelline vein –> hepatic vein
B. L vitelline vein –> degrades
C. R umbilical vein –> degrades
D. L umbilical vein –> remains
E. Anterior cardinal vein –> SVC, jugular, subclavian
F. Posterior cardinal veins –> IVC and azygos
[Cardiovascular Embryology]
- Different body parts that are responsible for fetal erythropoiesis
- Different variants of hemoglobin during development
1. Young Liver Synthesizes Blood Yolk sac (3-8 weeks) Liver (6 weeks - birth) Spleen (10-18 weeks) Bone marrow (18 weeks - adult)
- Alpha Always; Gamma goes; Becomes Beta
Fetal hemoglobin = HbF –> alpha2gamma2
Adult hemoglobin = HbA –> alpha2beta2
HbF oxygen dissociation curve shifted left for HbF –> higher affinity for 02 bc of weaker binding to 2,3-BPG –> can extract 02 across placenta from maternal HbA
[Cardiovascular Embryology] Embryologic Derivatives 1. Aortic sac 2. Truncus arteriosus 3. Bulbus cordis 4. Primitive ventricles 5. Primitive atria 6. Sinus venosus (L and R horns) 7. Primitive pulmonary veins 8. Cardinal vein (R)
- Aortic sac –> pharyngeal arches
- Truncus arteriosus –> ascending aorta and pulmonary trunk
- Bulbus cordis –> outflow tract (smooth part) of LV and RV
- Primitive ventricles –> trabeculated part of L and R ventricles
- Primitive atria –> trabeculated part of L and R atria
- Sinus venosus
A. L horn –> coronary sinus
B. R horn –> smooth part of RA - Primitive pulmonary veins –> smooth part of LA
- Cardinal vein (R) –> SVC
[Cardiovascular Embryology]
Describe heart morphogenesis
1. Formation of tubular heart
2. Formation of septated heart
Heart = 1st functional organ in vertebrates, beats spontaneously by 4th week
- Formation of tubular heart: Heart tubes begin in a horseshoe shape - superior to mouth and ventral to the intraembyronic coelom (future pericardial, pleural, peritoneal cavities)
- as head grows, the heart tubes fold ventrally and trap the foregut via the two dorsal aorta –> now head and mouth are superior, pericardial cavity is anterior
- Heart tubes approach each other in midline –> venous drainage develops
- septum transversum (future diaphragm) separates pleural space from peritoneal space - Formation of septated heart: loops to establish left-right polarity (3.5 weeks), needs cilia to rotate properly
- AV endocardial cushions invaded by neural crest cells which organize tissue movement –> endocardial cushions fuse together in dorsal-ventral direction –> create separated left and right canals (circulations)
[Cardiovascular Embryology]
List neural crest cell derivatives (from neuroectoderm)
PNS (dorsal root ganglia, cranial nerves, autonomic ganglia, Schwann cells) Melanocytes Chromaffin cells of adrenal medulla Parafollicular (C) cells of thyroid pia and archnoid mater bones of skull odontoblasts aorticopulmonary septum endocardial cushions
[Cardiovascular Embryology]
Kartagener’s syndrome
Kartagener’s syndrome - rare, autosomal recessive disorder; primary ciliary dyskinesia due to defects in dynein
Triad:
1. situs inversus; dextrocardia - heart points R instead of L
2. chronic sinusitis
3. bronchiectasis (bronchial tubes damaged/enlarged)
CV system functions normally
- also infertility
[Cardiovascular Embryology]
Describe atrial septum development
- Septum primum grows towards endocardial cushions –> narrows foramen primum
- Foramen secudum first forms in septum primum as small hole
- Septum secundum develops as foramen secundum maintains R–>L shunt
- Septum secundum expands and covers most of foramen secundum (residual = foramen ovale)
- Remaining portion of septum primum forms valve of the foramen ovale
- Septum secundum and septum primum fuse to form atrial septum
- Foramen ovale closes and fuses after birth bc of increased LA pressure (blood begins to flow from lungs to the left atrium)
[Cardiovascular Embryology] Describe atrial septal defects (ASD): 1. Patent foramen ovale 2. Ostium secundum type 3. Ostium primum type
- Pathology
ASD: LA–> RA shunt (non-cyanotic babies)
- Patent foramen ovale -NOT a true ASD- failure of septum primum and septum secundum to fuse after birth; in 25% of people and usually left untreated
- no true hole because primum can cover hole of the secundum - Ostium secundum type (90% of ASDs) - inadequate growth of septum primum or secundum
- Ostium primum type (5% of ASDs) - septum primum does not fuse with endocardial cushion; seen in Down syndrome, associated with AV valve defects
- Pathology - can lead to paradoxical emboli (venous thromboemboli that enter systemic arterial circulation)
Embolus (from leg, pelvis) passes through ASD –> LA –> LV –> CNS –> stroke
*embolic stroke + blood clots –> think hole in the heart (bc normally embolus causes PE, for a stroke the clot has to be able to move to the brain)
- with age (lungs getting too much blood for too long) –> pulmonary hypertension and reversal of shunt (like fetal circulation, from R–>L
- Right heart enlargement (hypertrophy) –> RV heave
- fixed S2 splitting
[Cardiovascular Embryology]
- Describe ventricular septum development
- Describe ventricular septal defect
- Muscular interventricular septum forms = opening called interventricular foramen
- Aorticopulmonary septum (neural crest cell derivatives) rotates and fuses with muscular part –> forms membranous interventricular septum and closes the foramen
- Growth of endocardial cushions separates atria from ventricles and contributes to both atrial septation and membranous portion of the interventricular septum
* aorta starts in back, ends up in front, pulmonary starts in front and ends up in back - VSD: LV –> RV shunt (non-cyanotic babies)
- most common congenital heart defect, most commonly occurs in membranous septum
- increased pulmonary blood flow –> LV volume overload –> LV eccentric hypertrophy
- harsh holosystolic murmur with high -moderate pitch; loudest at tricuspid with L to R shunt;
- over time can lead to pulmonary HTN and Eisenmenger’s syndrome
[Cardiovascular Embryology]
Describe the 5 Terrible T’s aka the etiologies behind “blue babies”
Blue babies due to R–>L shunt (Deoxygenated blood mixing with oxygenated blood) *most common cyanotic congenital condition is Tetralogy of Fallot
5 T’s of cyanotic CHD:
- Persistent Truncus arteriosus - 1 joint vessel instead of normal pulmonary artery and aorta
- due to abnormal neural crest cell migration, associated with 22q11 syndromes - Transposition of great vessels - aorta rises from RV, pulmonary artery from LV (switched) –> circulations in parallel (not series)
- need to maintain PDA through PGE
- associated with diabetic mother - Tricuspid atresia - complete absence of tricuspid valve –> undersized or absent right ventricle
- Total anomalous pulmonary venous return (TAPVR) - oxygenated blood returns back to the RA instead of the LA –> closed loop
- Tetralogy of Fallot: A) VSD B) overriding aorta (shifted over RV and the VSD as well as LV) C) RV hypertrophy D) pulmonary outflow tract stenosis most important
- due to abnormal neural crest cell migration –> displacement of interventricular septum anteriorly –> A-D result in R to L shunt
- kids squat to increase SVR (i.e. TPR) –> increased afterload –> increase pressure in LV –> reverse R to L shunt
- findings: clubbing of fingers/toes, “boot shaped” heart on CXR
[Cardiovascular Embryology]
1. Difference between blue babies and blue kids and the conditions that cause each
1A. Blue babies (Cyanotic at birth): R–> L shunts so deoxygenated blood reaches systemic circulation –> cyanosis
-due to: Tetralogy of Fallot (most common), Truncus arteriosus, Tranposition of great vessels, Tricuspid atresia, Total anomalous pulmonary venous return (TAPVR)
B. Blue kids (Acyanotic at birth): L–> R shunt so oxygenated blood is still being circulated, but the lungs are overloaded –> increases pulmonary venous return –> pulmonary HTN (bc right side cannot deal with high volume/pressure situations) –> when R side pressure is high enough, reverses shunt to R –> L (Eisenmenger’s syndrome)
- due to:
i. Volume overload - ASD, VSD, and PDA
ii. Pressure overload - aortic stenosis, pulmonic stenosis, aortic coarctation - treatment contraindicated once Eisenmenger’s develops
[Cardiovascular Embryology]
I. Describe valve development and the associated anomalies
I. Aortic/pulmonary valves - derived from endocardial cushions of outflow tract
Mitral/ tricuspid valves - derived from fused endocardial cushions of AV canal
Valvular anomalies:
A. atretic/stenotic/regurgitant e.g. tricuspid atresia
B. displaced e.g. Ebstein’s anomaly (valve is displaced downwards –> right ventricle is small); associated with lithium treatment for bipolar disorder in pregnant women
[Cardiovascular Embryology]
List aortic arch derivatives
1st arch –> part of maxillary artery (1st is maximal)
2nd arch –> stapedial artery, hyoid artery (S for Second)
3rd arch –> common carotid artery, proximal part of internal carotid artery (C is 3rd letter of alphabet)
4th arch –> (L) aortic arch ( R) proximal part of right subclavian artery
5th arch –> N/A (vestigial)
6th arch –> proximal part of pulmonary artery, (L) ductus arteriosus (degrades on R, becomes ligamentum arteriosum)
- L recurrent laryngeal nerve loops around L ductus arteriosus, R nerve loops around R subclavian artery
[Cardiovascular Embryology]
I. Describe fetal circulation
II. Describe the 3 important fetal shunts
III. What happens at birth and patent ductus arteriosus
A. How to close PDA
B. PDA murmur
I. Highly oxygenated blood from umbilical vein –> IVC (via ductus venosus) –> RA –> LA (via foramen ovale) –> LV –> ascending aorta –> pumped to body –> deoxygenated blood goes back into heart through SVC –> RA –> RV -> pulmonary artery –> descending aorta (via ductus arteriosus) –> iliac arteries –> umbilical arteries –> to placenta for oxygenation
II. Shunts
- Ductus venosus - 02 blood entering fetus from umbilical vein –> IVC (bypass hepatic circulation)
- Foramen ovale - oxygenated blood from IVC shunted from RA –> LA (bypass the lungs)
- Ductus arteriosus - deoxygenated blood from pulmonary artery –> descending aorta –> back to placenta for oxygenation (higher oxygenated blood can go to brain)
III. At birth, infant takes a breath –> decreased resistance in pulmonary vessels -> increased left atrial pressure –> foramen ovale closes
increase in 02 (From respiration) and decrease in prostaglandins –> closure of patent ductus arteriosus PDA
A. indomethacin blocks PG synthesis –> closes PDA (close even small PDAs to prevent infective endocarditis)
- PGE1 and E2 keep PDA open
B. PDA: continuous machine like murmur loudest at S2; due to congenital rubella or prematurity –> L side volume overload and dilatation, best heard at left infraclavicular area
[Cardiovascular Embryology] List fetal-postnatal derivatives 1. Umbilical vein 2. Umbilical arteries 3. Ductus arteriosus 4. Ductus venosus 5. Foramen ovale 6. Allantois
Embryological remannts of fetal circulation
- Umbilical vein –> ligamentum teres hepatis
- Umbilical arteries –> medial umbilical ligaments
- Ductus arteriosus –> ligamentum arteriosum
- Ductus venosus –> ligamentum venosum
- Foramen ovale –> fossa ovalis
- Allantois –> urachus - median umbilical ligament
[Cardiovascular Embryology]
- Differentiate RCA vs LCA anatomy supplied and relate to the EKG leads
- Differentiate Right vs Left dominant circulation
- Differentiate pericardial vs cardiac pain
- RCA = posterior heart –> RA, RV, SA/AV nodes (inferior leads II, III, aVF and posterior leads V1-V3 reciprocal changes bc technically there are no posterior leads)
LCA = anterior heart –> LA, LV, His-Purkinje system, anterior 2/3 interventricular septum (anterior leads V1-V4; left circumflex correlates to left lateral leads I, aVL, V5, V6)
- Right dominant circulation (85% pop) - RCA supplies posterior descending branch of coronary artery i.e. posterior interventricular artery –> which supplies posterior 1/3 interventricular septum, AV node, and posterior wall ventricles
- Pericardial pain referred to C3-C5 dermatomes (shoulder, neck area)
Cardiac pain referred to chest through visceral pericardial afferents that return to T1-T5 via SNS
[Cardiovascular Physiology]
- Describe properties of cardiomyocytes
- Describe the steps of the myocardial action potential
- What is the main difference between excitation-contraction coupling in myocytes
- Cardiac muscle - automatic, involuntary, striated tissue containing uninuclear cells connected by intercalated discs (gap junctions, desmosomes, and tight junctions) –> depolarizing one cell leads to all cells being depolarized
- Myocardial action potential
Phase 0: Rapid upstroke –> rapid Na+ influx through fast channels –> depolarization
Phase 1: Na+ channels inactivated, fast K+ channels open –> K+ efflux –> initial repolarization returns transmembrane potential to 0mV
Phase 2: Plateau because K+ Efflux balanced by Ca2+ influx through slow L channels–> Ca2+ influx triggers Ca2+ release from sarcoplasmic reticulum + myocyte contraction
Phase 3: Rapid repolarization –> Ca2+ channels close and rapid K+ efflux through slow channels
Phase 4: resting potential at -90 mV–> high K+ permeability - Calcium-mediated calcium release
additional Ca2+ that comes into cell during plateau phase prolongs cross-bridge cycling time –> stimulates release of more Ca2+ from sarcoplasmic reticulum
[Cardiovascular Physiology] Define and describe relationships between: 1) stroke volume 2) end diastolic volume 3) end systolic volume 4) cardiac output
Describe Frank Starling Curve
1) stroke volume SV- how much blood is pumped out by LV in one contraction; marker of cardiac function
SV = EDV - ESV
2) end diastolic volume EDV - preload (volume of blood filling the heart); dictates extent of overlap between actin and myosin cardiac muscle fibers
3) end systolic volume ESV- volume of blood left in heart after contraction
4) cardiac output CO- amount of blood the heart pumps out each minute
CO = SV x HR
Relationship between SV and EDV is Frank-Starling ventricular function curve: Stroke volume of the heart increases in response to an increase in the volume of blood filling the heart (EDV) when all other factors remain constant
What happens to SV under the following conditions:
1) increased preload
2) increased afterload
3) increased inotropy (contractility) of the heart
What factors increase or decrease 1, 2, 3 incl the effect of digoxin
1) increased preload –> Increased EDV and SV
A. Preload ~ ventricular EDV = diastolic pressure that distends the ventricle–> increased by valve defects e.g. aortic stenosis/regurgitation
B. decreased by venodilators e.g. nitroglycerin
2) increased afterload –> increased ESV –> decreased SV
A. afterload ~ mean arterial pressure = impedance against which ventricle must eject –> increased by HTN (due to increased peripheral vascular resistance, due to increased arteriolar tone)
B. decrease by vasodilators e.g. hydralazine
`ACEIs and ARBs decrease both preload and afterload
3) increased inotropy (contractility) of the heart –> decreased ESV –> increased SV
A. contractility increased with: increased intracellular Ca2+, decreased extracellular Na+ (impacts Na+/Ca2+ antiporter), catecholamines (SNS tone), and digoxin/digitalis, from foxglove plant (competes for binding with K+ to Na+/K+ ATPase –> therefore Ca2+ cannot leave myocyte via Na/Ca exchanger; use leads to xanthopsia or yellow color vision)
- hypokalemia leads to increased chance of digoxin toxicity
B. contractility decreased with: beta blockage, heart failure, acidosis, hypoxia, and Ca2+ channel blocker e.g. verapimil, amlodipine
[Cardiovascular Physiology]
Describe autonomic control of cardiac output
Describe steps in the Beta1 receptor stimulation of inotropy
- PSNS - reduces HR via vagus nerve (cholinergic M2 receptors on SA and AV nodes)
* M2 = muscarinic –> slow, uses receptor binding - SNS - increases HR and contractility via adrenergic Beta1 receptors on SA, AV nodes and cardiomyocytes
Catecholamine stimulation of contractility via Beta1 receptors:
- Phosphorylation of L-type Ca2+ channels –> remain open longer
- Phosphorylation of proteins in sarcoplasmic reticulum –> increased release of Ca2+
- Phosphorylation of myosin –> increases myosin ATPase –> increases crossbridge cycling
- Phosphorylation of Ca2+ pumps in SR –> increase speed of calcium re-uptake and relaxation
[Cardiovascular Physiology] 1. What is Laplace's Law and connection to MV02 2. Describe types of cardiac hypertrophy A. Concentric vs Eccentric B. Physiologic vs Pathologic
- Laplace’s Law: Wall tension = (PxR)/2 x Thickness
MyoCARDial oxygen consumption (MVO2) is directly related to wall tension and increased by:
Contractility
Afterload
Rate of heart
Diameter of ventricule - Cardiac hypertrophy
A. Concentric vs Eccentric
i. Concentric - due to pressure overload (sarcomeres added in parallel) –> increased wall stress –> LV wall thickens and radius decreases in attempt to reduce stress
ii. Eccentric - due to volume overload (sarcomeres added in series) –> increase in blood volume –> increase in chamber radius
B. Physiologic vs Pathologic
i. Physiologic - reversible
Concentric due to weight-lifting
Eccentric due to pregnancy, endurance training
ii. Pathologic - irreversible
Concentric due to chronic HTN, aortic stenosis
Eccentric due to valvular regurgitation
[Cardiovascular Physiology]
- Relate CO and MAP
- What happens to CO during exercise?
- Fick Principle of calculating CO
- MAP = Mean arterial pressure (average arterial pressure during cardiac cycle), TPR = total peripheral resistance (aka systemic vascular resistance SVR)
MAP = CO x TTR –> perfusion pressure seen by organs
MAP = 2/3 (diastolic P) + 1/3 (systolic P) - When you exercise, SNS vasodilates muscle vascular beds / arteries (via Beta2 adrenergic receptors) to increase blood flow –> blood pressure decreases
to compensate, need to increase CO (=SVxHR)
- early stages of exercise –> both SV and HR increase
- late stages/maximal exercise –> SV plateaus, CO maintained by increased HR only - Fick principle:
CO = rate of 02 consumption / (arterial 02 content - venous 02 content) [L/min]
*02 content = (1.34 x Hb x Sa02) + (0.003 x Pa02) *mostly dependent on [Hb]
[Cardiovascular Physiology] 1. Define resistance using Poiseuille's Equation 2. Difference in resistance bw types of blood vessels and organs 3. Autoregulation of following organs: A. heart B. brain C. kidneys D. lungs E. skeletal muscle F. skin
- Poiseuille equation: Resistance = 8n(viscosity) x length / pir^4
- resistance mostly determined by arteriolar tone (blood volume determined by venous tone)
- viscosity depends on hematocrit (RBCs:total blood volume) - Blood vessels arranged in series (resistances additive); greatest drop in pressure across bv with greatest resistance –> arterioles
Circulations in body organs arranged in parallel –> organ with lowest resistance gets most flow; can dilate/constrict to control flow - Autoregulation
A. heart - local vasodilators (C02, adenosine, NO)
B. brain - local vasodilators (C02, H+)
C. kidneys - myogenic, tubuloglomerular feedback
D. lungs - hypoxia causes vasoconstriction *OPPOSITE in all other organs
E. skeletal muscle - local vasodilators (lactate, adenosine, K+)
F. skin - sympathetic stimulation to maintain temperature control
[Cardiovascular Physiology]
- Equation for net filtration pressure
- Causes of edema
- Net filtration pressure = Pnet = (P cap + Pi if) - (P if + Pi cap)
Pnet = Jv (net fluid flow) / Kf (filtration constant for capillary permeability) - Edema - excess fluid outflow into interstitium (more than can be captured by the lymph)
Pitting edema caused by:
A. increased capillary pressure P cap e.g. heart failure
B. Decreased plasma proteins Pi cap e.g. nephrotic syndrome, liver failure
C. Increased capillary permeability Kf e.g. toxins, infections, burns
D. Increased interstitial fluid colloid osmotic pressure Pi if e.g. lymphatic blockage
[Cardiovascular Physiology] 1. Describe the cardiac output curves 2. Describe the effects on curves + examples of: A. inotropy B. venous return C. total peripheral resistance
- Cardiac output (y axis) increases with right atrial pressure (x axis) until a maximum
- Venous return decreases with increased RAP until it hits 0 –> mean systemic pressure (mean pressure in circulatory system when blood can redistribute equally)
- CO = venous return at operating point (equilibrium) - In general, v hard to isolate these factors bc autonomic nervous system affects them all
A. inotropy - shifts cardiac output curve only
More inotropy –> shifts upwards e.g. digoxin
Less inotropy –> shifts downwards e.g. uncompnesated heart failure, narcotic OD
B. venous return - shifts venous return curve only
More volume, venous tone –> shift upwards e.g. blood infusion
Less volume, venous tone –> shift downwards e.g. hemorrhage, venodilators
C. total peripheral resistance - redistribution of blood to venous side when decreased, vice versa
Increased TPR –> decreased slope of venous return and CO curves e.g. isolated arteriolar venoconstriction
Decreased TPR –> increased slope of venous return and CO curves e.g. exercise, AV shunt
[Cardiovascular Physiology] 1. Describe cardiac cycle illustrated on pressure-volume loop 2. Describe isolated effects of: A. increased preload B. increased afterload C. increased contractility
- LV pressure on Y axis, LV volume on X axis
cardiac cycle needs to lie between end systolic PV relationship ESPVR (contractility) and end diastolic PV relationship EDPVR (compliance)
[SEE PICTURE OF CARDIAC CYCLE CURVE]
2A. increased preload - EDV increases, but ESV stays the same –> SV increases
B. increased afterload - ESV increases –> SV decreases
C. increased contractility - ESV decreases –> SV increases
[Cardiovascular Physiology]
- How does systolic heart failure affect Frank-Starling curve?
- Describe the 3 main types of systolic heart failure
- Differentiate with diastolic heart failure
- systolic heart failure - due to decreased inotropy/contractility or pressure overload –> reduced ejection fraction
- decreased slope (SV is y axis and EDVP/preload is x axis) –> decrease in SV for same level of preload - 3 main types of systolic heart failure:
A. myocardial infarction - loss of myocardium (irreversible membrane disruption)
B. alcoholism - ventricular dilatation due to cardiomyopathy
C. pressure overload - Diastolic heart failure - stiff ventricle inhibits ventricular filling –> EF normal or elevated
[Cardiovascular Physiology] 1. Describe the heart sounds S1 S2 S3 S4
2. Describe splitting A. physiologic B. Wide C. Fixed D. Paradoxical
- Heart sounds
S1 - mitral and tricuspid valve closure; heard loudest at mitral area
S2 - aortic and pulmonary valve closure; heard loudest at left sternal border
S3 gallop “Kentucky”- (abnormal) occurs after S2 early diastole during rapid ventricular filling; associated with increased filling pressures and volume overload (eg heart failure) but can be normal in children and pregnant women
S4 gallop “Tennessee”- (abnormal) “atrial kick” in late diastole right before S1 due to high atrial pressure; associated with ventricular hypertrophy when LA pushes against stiff LV - Splitting
A. Physiologic - (expiration) A2 closes before P2 - but close enough that its 1 sound
(inspiration) chest expands –> intrathoracic pressure becomes more negative –> ↑ venous return –> ↑ RV filling + increased capacitance –> takes longer to empty –> delayed pulmonic valve closure = delayed P2
B. Wide - A2/P2 splitting during expiration and inspiration (worse on inspiration) due to delayed pulmonic valve closure due to pulmonic stenosis, right BBB
C. Fixed - A2/P2 splitting that is constantly wide during expiration and inspiration due to ASD
D. Paradoxical - (expiration) P2 occurs before delayed A2
(Inspiration) single sound due to delayed aortic valve closure due to aortic stenosis, left BBB
[Cardiovascular Physiology]
Cushing reflex in brain injury
Cushing reflex - terminal stages of acute head injury:
triad of HTN, bradycardia, and respiratory depression
cerebral injury –> increased intracranial pressure –> constricts arterioles in brain –> cerebral ischemia –> Activates SNS –> increased HR and contractility –> increases BP (to ensure blood and 02 delivery to the brain) –> but increased BP activates baroreceptors –> Activates PSNS –> bradycardia
- only get part of baroreceptor reflex bc SNS is dominant in vasculature, while PSNS is dominant in heart and overrides SNS tachycardia drive
[Atherosclerosis]
1. Where does atherosclerosis most commonly occur (types of vessels, vessel sites)?
2. Functions of endothelial cells
3. First step in devlpt of atherosclerosis
A. Mechanical injury
B. Chemical injury
4. Effect of injury
- Most common vessels - large and medium-sized muscular arteries
Most common sites - bifurcations, branch points, regions of high curvature - Endothelial cells (ECs) line up in direction of blood flow; modulate immune response, have anticoagulant functions, release vasodilators (e.g. NO, prostacyclin), anti-hypertrophic properties
- First step - endothelial dysfunction / injury
A. mechanical endothelial injury: at branch points, laminar flow disturbed –> flow becomes turbulent, with low flow areas –> disturbed shear leads to high EC turnover, poor alignment, inflammatory genes/altered gene expression, high permeability, oxidative stress
*problem is exacerbated by high pressure (eg HTN)
B. Chemical injury e.g. dyslipidemia (direct correlation bw plasma cholesterol and heart disease), cigarette smoking, diabetes - Both mechanical + chemical injury –> alter endothelial behavior so they are no longer anti-inflammatory, but become pro
- alter substances to be vasoconstrictive
- recruit leukocytes
- release inflammatory cytokines
- produce ROS, become prothombotic
[Atherosclerosis]
- What happens after endothelial dysfunction?
- Exogenous pathway of lipid absorption
- Endogenous pathway
- Endothelial dysfunction allows lipoprotein entry and modification in subendothelial space; principal culprits are LDLs bc of their overflow pathway (high proportion of cholesterol, contain ApoB100)
- Exogenous (small intestine) - lipids (cholesterol, fat, monoglycerides, etc) in food packaged into bile salt micelles –> taken up by intestinal epithelial cell –> broken down into cholesterol esters, phospholipids, and triglycerides –> packaged into chylomicrons which are TG-rich and have ApoB-48 –> released into lymph –> acquire ApoA, ApoE, ApoC from HDLs in the bloodstream –> binds to lipoprotein lipase and offloads TGs to muscle and fat in the form of FFAs –> chylomicron remnants go back to liver and taken up
- Endogenous pathway (liver) - VLDLs composed of TGs and cholesterol, packaged with ApoB-100 –> circulate in blood and interact with HDLs –> acquire ApoE, ApoC, and cholesterol esters –> binds to lipoprotein lipase and offload TGs to muscle and fat in the form of FFAs –> VLDL remnants return to liver –> 50% cleared via ApoE receptor and 50% processed by hepatic triglyceride lipase and LPL to form LDL
* HDL involved in reverse cholesterol transport - transfer of cholesterol from VLDL, IDL, LDL in periphery to liver
[Atherosclerosis] - Inherited disorders 1. Familial hypercholesterolemia A. Inheritance B. Defect C. Plasma lipid pattern
1A. Familial hypercholesterolemia - autosomal dominant (incompletely dominant)
B. Defects: most commonly LDL receptor mutation (300+ mutations IDed)
- also Apo-B100, PCSK9 mutations
C. Homozygous FH - severely elevated cholesterol levels >600 mg/dL
- Heterozygous FH - elevated cholesterol > 250mg/dL
- normal total cholesterol level (incl LDL and HDL): <200 mg/dL
Other genetic dyslipidemias (FOR STEP REVIEW): familial combined hyperlipidemia, Type III hyperlipidemia, ApoC-II deficiency –> atherosclerosis leads to high CRP levels (marker of inflammation)
longer and lower the reduction in circulating LDL-cholesterol –> lower incidence of coronary heart disease e.g. MI
[Atherosclerosis]
What are the consequences of lipoprotein entry into the endothelial cells? How does it contribute to atherosclerotic process
Endothelial dysfunction –> Lipoprotein entry –> Inflammation –> leukocyte recruitment –> SCM and ECM proliferation
After lipoproteins (LDL particles) enter cell, they become oxidized or glycated by the inflammatory processes going on in EC –> recognized by scavenger receptors on macrophages also drawn to the area by the injury –> inflammasome activation of inflammatory process –> forms foam cells (fat-laden macrophages)
Smooth muscle cells SMC in the media become activated as a result of the inflammation –> migrate into the intima
- injury response – body is recognizing atherogenesis as damage/injury and tries to contain it via a fibrous cover –> process makes vessel more and more narrow (“Fatty streak”) but does stabilize atherogenesis and prevents thrombus –> becomes calcified (do not know etiology)
Fatty streak –> plaque progression –> plaque obstructive plaque (Stable angina) –> disruption (unstable angina)–> thrombus (MI/heart attack)
[Atherosclerosis] 1. List non-modifiable risk factors 2. List modifiable risk factors 3. Differentiate primary vs secondary prevention 4. Novel biomarkers that can predict risk A. C-reactive protein B. Lipoprotein a C. homocysteine
Risk factors for atherosclerosis are multiplicative
- List non-modifiable risk factors
- advanced age
- M»F
- heredity - List modifiable risk factors
- dyslipidemia (elevated LDL)
- smoking
- HTN
- diabetes, metabolic syndrome
- lack of physical activity - Primary - delaying/preventing onset of the disease
Secondary - patient already has the problem - goal is to prevent progression of disease - Biomarkers
A. C-reactive protein (CRP) - marker of inflammation associated with CAD –> released from liver in response to inflammatory cytokines
B. Lipoprotein a - linked to ApoB-100, structurally related to prothrombotic plasminogen; size and concentration is genetically determined
C. homocysteine - independent risk factor for cardiovascular disease
[Acute Aortic Syndromes]
- Describe microscopic anatomy of aorta
- Role of fibrillin-1 and deficiency
- Properties of the aorta
- Microscopic anatomy:
A. Intima - endothelial cells overlying internal elastic lamina
B. Media - smooth muscle cells and extracellular matrix of collagen (Strength) and elastic fibers (distension)
- lamellar unit - can withstand high pressure and distend in response –> allows pressure to evenly flow to extremities
C. Adventitia - vaso vasorum (blood vessels) - Fibrillin-1 - glycoprotein that helps maintain structural integrity of aortic wall and valve leaflets by tethering smooth muscle cells to elastin/collagen matrix
- deficiency –> VSMC detachment from matrix –> loss of ECM structural integrity –> Marfan syndrome - Properties - how distensible aorta is (based on shape and mechanical properties) determines:
- how hard LV has to work
diastolic pressure in aorta determines:
- coronary blood flow
- efficiency/dist of blood flow
*elastic component degenerates with age –> aorta stiffens –> systolic bp rises
[Acute Aortic Syndromes] - Aortic Coarctation
- Describe aortic coarctation and etiology/other associated conditions
- When does it cause problems?
- Pathophysiology
- Coarctation - constriction of aorta, esp isthmus
- occurs right as the ductus arteriosus joins the aorta (juxtaductal)
- congenital do not know etiology
- associated with other congenital heart defects –> bicuspid aortic valve, Turner syndrome (XO) - Does not cause problems in utero bc blood shunts from ductus arteriosus and down descending aorta, bypassing the constriction
- problem when baby is born and ductus closes - Pathophysiology - increased load caused by obstruction of the aorta leads to:
- increases afterload (increased pressure the heart has to work against) –> increased LV wall stress –> compensatory LV hypertrophy
- HTN (due to obstruction itself and also bc renal arteries are underperfused –> make renin to boost pressure)
- aortic collaterals –> rib notching classic finding seen later, in kids (not babies)
[Acute Aortic Syndromes] - Aortic Coarctation
1. Clinical presentation of aortic coarctation?
A. Infants
B. Older children and adults
2. Symptoms and signs
- Classic finding - notching on inferior surface of posterior ribs (chest X-ray)
A. Infants - differential cyanosis (bottom half of body), congestive heart failure (tachycardia, poor feeding)
B. Older children/adults –> systolic HTN in upper extremities, reduced lower extremity systolic BP (>20 mmHg)
- radial to femoral pulse delay - Symptoms and signs:
- majority of adults detected via incidental HTN
- one of the few murmurs that is heard on the back –> under left scapula
- bicuspid aortic valve in 30% adults (systolic murmur following ejection click)
[Acute Aortic Syndromes] - BAV
- Describe bicuspid aortic valve BAV and etiology/other associated conditions
- BAV clinical presentation
- Bicuspid aortic valve - 2 leaflets fuse during development –> bicuspid aortic stenosis
- M»F
- unknown developmental etiology: common, can be sporadic or familial (AD)
- 1/2 have dilated aortic root (need to be screened for this)–> can lead to aortic dissection, rupture
- structural alteration similar to that in CT disorders (Marfan, Ehlers-Danlos) *could be tied into etiology
- BAV associated with Turner syndrome, aortic coarctation - Clinical presentation: congenital
- aortic stenosis is most common, presentation at young age
- systolic ejection murmur/click that decreases with valsalva (↑ in intraabdominal pressure –> ↓ venous return to the heart –> ↓ blood flow through stenotic aorta)
Which 2 murmurs increase with valsalva maneuvers?
Valsalva –> ↑ in intraabdominal pressure –> ↓ venous return of the heart –> ↓ volume of heart
- Rapid standing –> also ↓ venous return (orthostatic hypotension)
- can reduce murmur by increasing preload (squatting) or afterload (handgrip)
- Mitral valve prolapse –> billowing of mitral leaflets happens sooner after S1 with lower blood flow –> mid-systolic click happens sooner
- Hypertrophic cardiomyopathy HCM –> exacerbates LV outflow tract obstruction bc ventricles come closer together with lower blood flow
[Acute Aortic Syndromes] - Aortic Dissection
- Describe aortic dissection pathophysiology
- Classification
- Etiology
- Aortic dissection:
- damage to aortic wall - combo of mechanical (HTN) and atherosclerosis –> degeneration of the media (necrosis and fibrosis)
- intimal layer tears (close to Aortic valve) –> high pressure allows blood to gain access to the underlying damaged media –>
- creates “false lumen” in which blood travels within media –>
- blood can propagate proximally (Towards heart) or distally (along aorta) and even encircle the aorta - Classification (Stanford)
- A - involves arch - treated surgically
- B - does NOT involve arch - treated medically - Etiology
- chronic arterial HTN most important risk factor
- smoking, cocaine use, eclampsia pregnancy, trauma
- genetic (Turner, CT disorders e.g Marfan)
- M»F
- 2x more common to begin in ascending (Vs descending) aorta
[Acute Aortic Syndromes] - Aortic Dissection
- Clinical presentation
- Compare/contrast presentation of chest pain in aortic dissection vs MI
- What are 3 things that can happen during catastrophic dissection?
- Clinical presentation - sudden, severe “tearing/ripping” chest pain - starts at maximal intensity (10/10) –> pain radiates to back/scapula –> Death
- HTN on presentation
- 1/2 have aortic regurgitation (blowing, decrescendo murmur heard best at 3rd L intercostal space)
- 1/3 have pulse deficits (can occlude branches of aorta) - MI - pain starts at lower level and gradually increases as myocardium becomes ischemic –> pain radiates to arm, shoulder, neck bilaterally
- Catastrophic dissection
A. False lumen ruptures –> patient dies (nothing you can do)
B. Occlusion of coronary ostia/opening –> MI
C. Proximal rupture into pericardium –> pericardial tamponade –> death
[Acute Aortic Syndromes] - Aortic Dissection
List high risk conditions, pain features, and physical findings indicative of aortic dissection
- High risk conditions - Marfan’s, family h/x of aortic disease, known aortic valve disease, recent aortic manipulation
- High risk pain features most important - chest, back, abdominal pain described as abrupt onset, severe (10/10) intensity, and “ripping or tearing”
- High risk physical findings - perfusion deficit (pulse deficit, systolic BP difference, focal neurological)
- new aortic regurgitation murmur (early diastolic decrescendo murmur, wide pulse pressure)
- hypotension
[Acute Aortic Syndromes] - Aortic aneurysmal disease
1. Define
2. Pathophysiology
A. Compare to pseudo-aneurysms
3. Etiology
A. compare to thoracic aneurysms
4. Clinical presentation incl symptoms of rupture
- Aortic aneurysm - localized/diffuse dilation of artery with diameter greater than 50% normal size (>3cm in abdominal aorta)
- most aortic aneurysms occur below renal arteries (infrarenal aorta), but can occur anywhere - Pathophys - ischemic injury of media (due to atherosclerosis), degradation of aortic medial connective tissue –> media broken down by proteases, poor quality vascular connective tissue –> expansion of aorta and thinning of wall
A. Pseudo-aneurysm - iatrogenic (post-surgical) resulting in hematoma (collection of blood in surrounding tissue) that remains in continuity with arterial lumen - Etiology - most abdominal aortic aneurysms AAA are acquired due to degenerative disease (HTN, smoking, atherosclerosis), acquired infection (Syphilis), inflammatory condition; M 65+ should be screened
A. Thoracic aortic aneurysm associated with family history / underlying genetic disorders e.g. Turner, CT disorders (Marfan, Ehlers-Danlos), Bicuspid aortic valve - Clinical presentation: usually asymptomatic before rupture
- typical finding is pulsatile abdominal mass
A. Symptoms of rupture - sudden onset abdominal OR back pain + hypotension = ruptured AAA
[Hyperlipidemia drugs] 1. HMG CoA reductase inhibitors (statins) A. MOA B. Effects on serum lipid concentration C. Adverse effects
- HMG CoA reductase inhibitors e.g. lovastatin (Mevacor), simvastatin (Zocor), atorvastatin (Lipitor) *first-line –> treatment and prevention of cardiovascular disease, decreased incidence of coronary events/death
A. MOA: Statins are competitive inhibitors of HMG CoA reductase (RLS in de novo cholesterol synthase from HMG CoA –> mevalonate)
- when cholesterol is down in the cell, SREBP (sterol regulatory element binding protein) is activated –> increases de novo biosynthesis (moot point bc of competitive inhibitor)
AND upregulates LDL receptors –> clears atherogenic lipoproteins from circulation via receptor mediated endocytosis
B. Serum lipid concentration
- decreases levels of TG, LDL
- little effect on HDL
C. Adverse effects
- side effects: myopathy (muscle aches, rhabdomyolysis), increased liver enzymes
- contraindicated for active/chronic liver disease, for pregnant women
- interactions: drugs that inhibit organic anion transporter e.g. cyclosporin –> higher plasma levels of statins
- red yeast rice is form of statin - natural but unregulated
[Hyperlipidemia drugs] 2. PCSK9 inhibitors (monoclonal antibodies) A. MOA B. Effects on serum lipid concentration C. Adverse effects
- PCSK9 Inhibitors e.g. evolocumab, alirocumab
A. MOA: inhibit PCSK9 - protein that binds to LDL receptors and delivers to lysosome for disposal –> higher levels of LDL receptors
B. Serum lipid concentration
- decreases levels of LDL
- little effect on TG (decrease), HDL (increase)
C. Adverse effects
- side effects - hypersensitivity rxns
- effective in reducing cardiovascular events, well tolerated but v expensive
[Hyperlipidemia drugs] 3. Cholesterol absorption inhibitors A. MOA B. Effects on serum lipid concentration C. Adverse effects
- Cholesterol absorption inhibitors e.g. ezetimibe (Zetia)
A. MOA: inhibits enterocyte brush border protein NPC1L1 - which inhibits uptake of dietary sterols –> leads to cholesterol uptake in small intestine –> decreased intestinal delivery of cholesterol to liver, increased LDL-R expression
B. Effects on serum lipid concentration
- decreased LDL
- no change in TGs
- slight increase in HDL
C. Adverse effects
- impaired hepatic function
- used with statins
[Hyperlipidemia drugs] 4. Bile acid sequestrants A. MOA B. Effects on serum lipid concentration C. Adverse effects
- Bile acid sequestrants (resins) e.g. cholestyramine, colestipol, colesevelam
A. MOA: positively charged plastics that bind negatively charged bile acids –> prevent their reabsorption –> bile acids secreted in stool –> increased hepatic bile acid synthesis from cholesterol –> liver [cholesterol] decreases
- LDL receptors increased
- but de novo cholesterol production also increased –> this homeostasis offsets LDL reduction
B. Effects on serum lipid concentration
- decrease in LDL
- slight increase in TGs
- slight increase in HDL
C. Adverse effects
- increase in hepatic TG synthesis –> contraindicated in patients with high TGs (>400 mg/dL)
- side effects from the plastics –> GI distress
- prevent interactions with other drugs by taking them at different times
[Hyperlipidemia drugs] 5. Niacin 6. Fibrates A. MOA B. Effects on serum lipid concentration C. Adverse effects
- Niacin
A. MOA: water soluble B3 vitamin that is incorporated into NAD
B. Effects: not been shown to have significant effects even in combo with statins but can decrease LDL, TG, and increase HDL
C. Adverse effects: causes niacin flush; hyperuricemia (gout), hyperglycemia, hepatotoxicity - Fibrates
A. MOA: Activate transcription factor PPARalpha - controls lipid metabolism
B. Effects: Reduces plasma TGs, little effect on LDL (may even increase)
C. Adverse effects: increase risk of myopathy in patients on statins
[Adrenergic agonists/antagonists]
- Where are the sympathetic neurons located?
- ID pre and post-synaptic SNS neurotransmitters
- Describe synthesis of the catecholamines
- Reuptake of NE
- Sympathetic neuron cell bodies in T1-L2 intermediolateral horns of spinal cord, leave through ventral horn –> why pain from viscera is so vague compared to pain from somatic nervous system
- Presynaptic - ACh
Postsynaptic - adrenergic (NE/E but mostly norepi) except ACh in sweat glands and D1 in renal vessels/ smooth muscle
3A. Cytoplasm: Tyrosine + (tyrosine hydroxylase RLS) –> Dopa –> Dopamine
B. Synaptic vesicles: Dopamine –> Norepinephrine
C. Adrenal medulla: Norepinephrine (acts as neurotransmitter) –> epinephrine (acts as hormone)
- NE/E are stored in chromaffin granules of adrenal
*When NE is released into synaptic space –> ATP is released as well
4A. reuptake into synaptic terminal (blocked by cocaine, TCAs)
B. Metabolism of NE to inactive metabolite (MAO in mitochondria, COMT in post-synaptic nerve)
C. diffusion away from nerve terminal
[Adrenergic agonists/antagonists] 1. Alpha1 adrenergic receptors A. MOA B. location C. physiologic effect
- Alpha1 adrenergic receptors
A. MOA: receptor coupled to Gq protein–> activates phospholipase C —> activates inositol triphosphate IP3-DAG cascade –> increased intracellular Ca2+
B. Located on postsynaptic membrane –> post junctional
C. Effects:
i. alpha1B (in vasculature) –> peripheral vasoconstriction and venoconstriction–> increases systolic and diastolic blood pressure
- increased SVR, MAP, and BP –> decreased HR / reflex bradycardia due to baroreceptor reflex
* minimal effects on heart
ii. alpha1A (in bladder sphincter) –> urethral sphincter and prostatic SMC contraction –> urinary retention
iii. mydriasis –> increased intraocular pressure when iris pulls back and obstructs canal of schlemm –> glaucoma
[Adrenergic agonists/antagonists] 2. Alpha2 adrenergic receptors A. MOA B. location C. physiologic effect
- Alpha2 adrenergic receptors
A. MOA: receptor coupled to Gi –> IP3-DAG cascade –> decrease cAMP levels –> inhibits release of neurotransmitters (NE and ACh)
B. Located on presynaptic membrane - nerve terminals of adrenergic and cholinergic neurons
C. Effects:
- autonomic modulation - inhibit NE and ACh release
- inhibit insulin release
- inhibit lipolysis
- decrease aqueous humor production –> decrease intraocular pressure
[Adrenergic agonists/antagonists] 3. Beta adrenergic receptors A. MOA B. location C. physiologic effect
- Beta adrenergic receptors - three types (1,2,3)
A. MOA: increase cAMP levels –> activates protein kinase A –> increase Ca2+ levels
- can be turned off by phophorylation
B. Location:
i. Beta1 - postsynaptic; heart, juxtaglomerular apparatus cells in nephron
ii. Beta2 - pre and postsynaptic; smooth muscle in periphery
iii. Beta3 - adipocytes
C. Effects:
i. Beta1
- increased Ca2+ –> increased inotropy (contractility)
- increased rate of conduction
- increased chronotropy (heart rate) by affecting funny current If; RMP more positive (cells more depolarized), fire more quickly bc close to threshold and reach threshold faster (slope to depolarization steeper)
- increased renin release in kidney nephrons
ii. Beta2
- increased bronchodilation, vasodilation, uterine relaxation
- increased insulin –> moves glucose and K+ into liver and skeletal muscle, respectively –> gluconeogenesis and hypokalemia
- decreased peripheral vascular resistance (opposite of alpha1)
- increased neurotransmitter release (if presynaptic)
- increased aqueous humor production
iii. Beta3
- lipolysis
[Adrenergic agonists/antagonists] Endogenous catecholamines: Epinephrine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Epinephrine
1. Key features: lower doses acts on beta, higher doses has alpha effects; B1=B2, alpha1=2 affinity
- Cardiovascular effects
- Beta1 - increased contractility, HR –> increased CO and systolic BP *increased myocardial 02 demand
- initially, B2 vasodilation in splanchnic beds –> decreased diastolic BP
- then, alpha1 contraction –>increased systolic and decreased diastolic BP –> mean arterial pressure MAP remains the same but pulse pressure increases - Clinical uses: #1 drug of choice for anaphylaxis (IV)
- cardiac arrest
- asthma (bronchospasm)
- local anesthetic
- open angle glaucoma - Toxicities - palpitations, HTN, tremor, anxiety
- contraindicated in hyperthyroidism and those on non-selective beta blockers
[Adrenergic agonists/antagonists] Endogenous catecholamines: Norepinephrine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Norepinephrine
- Key features: alpha1=2; Beta1»2
- at lower concentrations has high affinity for alpha
- at high concentrations, acts on Beta1 (heart) - Cardiovascular effects
- increased SVR (systemic vascular resistance)
- increased systolic and diastolic BP –> increased mean arterial pressure
- reflex drop in heart rate through baroreceptor response - Clinical uses: #1 drug of choice for hypotension in sepsis (IV) –> septic shock (type of distributive shock)
- Toxicities:
[Adrenergic agonists/antagonists] Endogenous catecholamines: Dopamine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Dopamine
1. Key features: effects are dose dependent
- Cardiovascular effects:
- (low dose) DA1 receptors in kidney –> increased renal perfusion –> diuresis
- (medium dose) Beta1 receptor in heart –> increase in contractility
- (high dose) Beta + alpha1 receptor –> increase in peripheral resistance –> increase contractility, HR, BP - Clinical uses: hypotension, low CO
- Toxicities: arrhythmia (Ventricular and supraventricular, widened QRS, angina)
[Adrenergic agonists/antagonists] Receptor-specific agonist: Phenylephrine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Phenylephrine
1. Key features: most specific for alpha1 agonist
- Cardiovascular effects: increased arterial vasoconstriction (skin, splanchnic vessels, skeletal muscles) –> increase BP
- decreased HR due to baroreceptor reflex (reflex bradycardia) - Clinical uses: #2 drug for hypotension (IV) if you cannot use NE
- rhinitis (vasoconstricts to treat nasal congestion)
- mydriasis - Toxicities: black box warning bc it is has active metabolite in liver/tissues –> can cause HTN when supine
[Adrenergic agonists/antagonists] Receptor-specific agonist: Clonidine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Clonidine
1. Key features: alpha2 agonist at presynaptic receptors in medullary brainstem; imadazoline compound; oral and transdermal
- Cardiovascular effects: decrease central SNS outflow –> decrease HR, decrease SVR, increase capacitance
- Clinical uses:
- resistant and urgent forms of HTN
- mgmt of Tourette’s, ADHD
- also used for hot flashes, addiction withdrawal - Toxicities: dry mouth, sedation, depression, rebound HTN
* other drugs in same class: guanabenz, guanfacine (not used)
[Adrenergic agonists/antagonists] Receptor-specific agonist: Isoproterenol 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Isoproterenol
1. Key features: IV only; acts non-selectively at beta receptors; beta1=2 agonist
- Cardiovascular effects:
- Beta1 - increase HR (chronotropy), contractility (intotropy), conduction velocity
- Beta2 - decrease peripheral vascular resistance (decreased afterload on the heart) –> decreased diastolic BP - Clinical uses: stokes-adams attack (syncope due to absent pulse), cardiac arrest, heart block
- Toxicities: tachycardia, HTN, dysrhythmia
* not really used clinically
[Adrenergic agonists/antagonists] Receptor-specific agonist: Dobutamine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Dobutamine
1. Key features: beta1 selective but (-) isomer has some alpha1 effects
- Cardiovascular effects: increased contractility»_space; chronotropic effect
- alpha1 action maintains peripheral resistance (makes it a better drug than isoproterenol) - Clinical uses: #1 drug for cardiogenic shock with maintained BP
- add to NE in septic shock with low CO
- stress test - Toxicities: tachyarrhythmia, PVCs, HTN
[Adrenergic agonists/antagonists] Phenoxybenzamine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Phenoxybenzamine
1. Key features: non-selective alpha antagonist –> blocks both alpha1 and 2 but 1»2; irreversible (blockade lasts 2 days), oral administration only
- Cardiovascular effects: blocks reuptake at presynaptic terminals –> blocks catecholamine-mediated vasoconstriction –> decrease TPR
- metabolically neutral - no effects on glucose, lipids, GFR, ions, etc - Clinical uses: oral
- pheochromocytoma (adrenal medulla tumor with excessive production of catecholamines NE/E) –> causes paroxysmal hypertension
* only used to premedicate patients with this condition before surgery; start with alpha blocker, then beta - or they could suffer a stroke in the OR - Toxicities: orthostatic hypotension, reflex tachycardia, nasal stuffiness, fatigue, nausea
[Adrenergic agonists/antagonists] Phentolamine 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Phentolamine
1. Key features: non-selective alpha antagonist; alpha1=2; reversible (lasts 4 hours); IV or IM only
- Cardiovascular effects: blocks peripheral resistance, causes cardiac stimulation
- Clinical uses: NE extravasation (when IV with NE leaks into the tissue and causes vasoconstriction and necrosis); pheochromocytoma, treating patients on MAO inhibitors who eat tyramine-containing foods (wine, cheese)
- Toxicities: severe tachycardia, arrhythmias, myocardial ischemia
[Adrenergic agonists/antagonists] Prazosin 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Prazosin
- Key features: highly alpha1 selective (1000x»_space; than alpha2) antagonist
- other drugs are terazosin, doxazosin, tamulosin - Cardiovascular effects: post-junctional antagonist
- relaxes arterial and venous smooth muscle –> increases venous capacitance –> vasoilation, decreased TPR
- relaxes smooth muscle in prostate
- metabolically neutral - no effect on glucose, GFR, etc - Clinical uses: benign prostatic hyperplasia BPH
- also HTN, but not first line therapy (which is diuretics)
- used in older men with HTN and BPH - Toxicities: postural hypotension, dizziness, headache, drowsiness, ejaculation problems
[Adrenergic agonists/antagonists] Beta blockers 1. Key features 2. Cardiovascular effects 3. Clinical uses 4. Toxicities
Beta blockers
- Key features: metabolized extensively –> limited bioavailability with oral administration
- Beta1 - in SA node (increase HR), cardiac muscle (contractility, SV), and renal juxtaglomerular cells (renin release)
- Beta2 - on VSM cells (vasodilitation) - Effects: immediate CO ↓ and TPR ↑
- only has BP lowering effect when BP is high
- negative chronotrope (slows HR)
- negative inotrope (decreases contractility)–> lowers CO, workload, V02
- can increase PVR initially, but normalizes long-term
- bronchoconstriction, even if B1 selective
- metabolic/endocrine: block lipolysis –> increased VLDL, decreased HDL; blocks glucose mobilization
- eye: decreases aqueous humor production –> reduce intraocular pressure in the eye - Clinical uses
- propranolol - acute STEMI (decreases myocardial 02 consumption)
- metoprolol in symptomatic heart failure
- hyperthyroidism, glaucoma, migraine
- no longer first line for HTN - - Toxicities
- drug rebound - can precipitate acute MI on sudden withdrawal
- CHF exacerbation - in patients with acute decompensated heart failure
- bradyarrhythmia - in patients with AV conduction defect
- bronchoconstriction - contraindicated with severe obstructive disease
- weight gain, lipid metabolism, worsened glycemic control in DM II
[Adrenergic agonists/antagonists] Beta blockers 1. List non-selective antagonists 2. Beta1 selective antagonists 3. Non-selective beta blockers + alpha blocking activity
- List non-selective antagonists:
- propranolol - prototypical
- pindolol - partial agonist
- nadolol - LONG duration of action
- timolol - ophthalmic, topical tx for glaucoma - Beta1 selective antagonists - used in patients with asthma, COPD, DM
ABEAM
Acebutolol - partial agonist
Betaxolol
Esmolol - parenteral, SHORT duration (10 min 1/2 life)
Atenelol - prototypicals
Metoprolol - prototypicals
- nebivolol - most highly selective beta1; vasodilation via NO release; does not affect lipid/glycemic control - Non-selective beta blockers + alpha blocking activity
- carvedilol - used in CHF and HTN; best choice with nebivolol in diabetic patients
- labetolol - treats HTN in pregnancy
[Ischemic Heart Disease]
- Define ischemia; most common cause?
- Determinants of 02 supply
- Determinants of 02 demand
- Ischemia - myocardial 02 demand»_space; supply; most common cause is atherosclerosis; causes chest pain, decreased contractility, congestive heart failure, necrosis
- Supply = 02 content (coronary blood flow, determined by perfusion pressure and resistance)
- resistance determined by
A. external compression (more blood flow during diastole when less resistance)
B. arterial tone
C. metabolic factors (adenosine vasodilator released with lack of ATP)
D. endothelial factors (endothelial cells release NO –> activates cGMP –> relaxes smooth muscle cells and prevents platelet aggregation )
E. neural factors (SNS - alpha and beta2) - Demand = 02 consumption
A. Ventricular wall stress S = P * r/2h [Laplace Law]
- wall stress is difficult to calculate so we use blood pressure instead
B. Heart rate
C. Ventricular contractility
[Ischemic Heart Disease] Describe ischemic syndromes: 1. Stable angina 2. Unstable angina 3. Variant angina 4. Silent ischemia 5. Syndrome X
Differentiate unstable angina, NSTEMI, and STEMI
- Stable angina - chest pain that occurs with activity/emotions/stress; constant pattern that can be predicted; due to atherosclerotic narrowing of coronary artery
- Unstable angina - chest pain with changes in pattern , gets worse over time; due to platelet aggregation secondary to plaque rupture
- Variant angina i.e. atypical, Prinzmetal’s - occurs with decrease in coronary flow due to transient coronary vasospasms
- Silent ischemia - patients who do not have any warning systems of pain
- Syndrome X - EKG shows ischemia and patient complains of chest pain, but you cannot find any obstruction (believed to be at capillary level)
A. Unstable angina - partially occlusive thrombus; serum biomarkers / enzymes negative, ST depression and/or T wave inversion
B. NSTEMI - enzymes positive, ST depression and/or T wave inversion
C. STEMI - enzymes positive, ST elevation bc transmural infarction (all walls of heart), Q waves later
[Ischemic Heart Disease]
- Descriptors of ischemic chest pain
- Effect on EKG
- Lab diagnosis
- Gold standard for diagnosis
- Descriptors: elephant sitting on chest, burning sensation, choking feeling in throat, toothache, bra too tight
- EKG: ST segment no longer isoelectric - goes up (transmural ischemia) or down (subendocardial ischemia) from baseline
- T wave become inverted
- gold standard diagnosis in first 6 hours post MI - Lab: creatinine kinase isoenzymes; MB fraction is in cardiac muscle (and a little in skeletal muscle); peaks 24 hrs and normalizes after 2 days
- troponin - I and T; peaks 18 hrs post MI and stay elevated longer, for 7-10 days
- LDH - comes from all muscle, but from the myocardium it stays for a long time
- myoglobin - specific for myocardium but v expensive - Gold standard for diagnosis - coronary angiography –> injecting dye in coronary arteries
- radioisotope scan - fibrous tissue forms after MI and does not take up radioisotopes
[Ischemic Heart Disease] 1. Treatment of ischemic heart disease A. treatment of acute angina B. treatment of variant angina C. prevention of recurrent angina D. prevention of acute events
- Myocardial revascularization
- Treatment
A. treating acute angina - nitroglycerine and other organic nitrates
B. treating variant angina - organic nitrates, Ca2+ channel blockers, but NOT beta blockers
C. prevention of recurrent angina - beta blockers (most effective for reducing cardiac ischemia), organic nitrates, Ca2+ channel blockers
D. prevention of acute events - ASA (aspirin), clopidogrel or prasugrel (antiplatelet agent - prevents adhesion step), ACE inhibitors, statin (to lower cholesterol)
*Ca2+ channel blockers used when nitrates or Beta blockers are poorly tolerated (eg bronchospastic disorders, peripheral vascular disease, DMII, dyslipidemia)
- Myocardial revascularization - need to open up artery w/in 90 min
A. percutaneous coronary intervention
B. coronary artery bypass graft (CABG)
[Angina drugs] Organic nitrates 1. MOA 2. Cardiovascular effects 3. Pharmacokinetics 4. Adverse effects
Organic nitrates - nitroglycerin, amyl nitrite, isosorbide dinitrate
- MOA: release NO into smooth muscle cells –> NO activates guanylate cyclase –> increased cGMP –> Activates phosphorylation cascade –> dephosphorylation of myosin light chain –> muscle relaxation
- Cardiovascular effects - no increase in coronary blood flow
A. Low doses (usually dose administered) - affects capacitance vessels (veins) –> venous pooling, venodilation, ↓ diastolic filling pressure –> ↓ venous return (ie preload)
B. High doses - affects resistance vessels (arteries) –> ↓ systemic peripheral resistance, reflex cardiac stimulation of rate and contractility
C. Overall - ↓ heart size and wall tension during systole –> ↓ work of heart; ↓ myocardial 02 demand - Pharmacokinetics: first pass inactivation by nitrate reductase in liver; resistant to denitration in tissues –> release N02 slowly and can be used in larger doses
- tolerance, physical dependence
- oral forms are longer-acting than sublingual forms
- amyl nitrate is only inhalant, shortest half-life - Adverse effects: flushing, headache, orthostatic hypotension, GI distress
[Angina drugs] Describe MOA of additional drugs used to treat angina: 1. sildenafil (Viagra) 2. Pentoxifylline, cilostazol 3. Ranolazine
- NO mediates erectile function by promoting cGMP and relaxing smooth muscle in the corpora cavernosa
- PDE5 - phosphodiesterase mediating cGMP breakdown
- Sildenafil (Viagra) - PDE inhibitor –> ↑ cGMP –> ↑ blood flow –> ↑ erections in males with intact innervation/NO synthesis
- potentiates actions of nitrates used for angina –> could lead to severe hypotension and MI
- other drugs like viagra include vardenafil HCl (Levitra), and tadalafil (Cialis) - Pentoxifylline, cilostazol - inhibit phosphodiesterase which breaks down cAMP –> ↑ cAMP –> promotes relaxation
- Ranolazine (Ranexa) - inhibits inward Na+ current –> reduces intracellular Ca2+ concentration –> reduces tension in heart wall
- for chronic angina, also lowers incidence of atrial flutter
[Angina drugs]
- Sources of Ca2+ in smooth muscle cells
- Types of Calcium channels - T, N, P, L
- Sources of Ca2+ in smooth muscle cells:
A. release from sarcoplasmic reticulum when stimulated by IP3 following alpha receptor stimulation
B. entry through Ca2+ selective channels
C. exit through Ca2+/Na+ exchanger NCX (Na+ enters cell through concentration gradient and Ca2+ leaves)
*intracellular free Ca2+ maintains arterial smooth muscle tone - Types of Calcium channels
T (fast) - pacemaker
N and P - neurotransmitters
L (slow) - important in resistance vessel SMCs, myocardial cells –> contraction
- ↑ in membrane potential, activation of alpha1A receptors –> ↑ probability of L channel opening
[Angina drugs] Calcium Channel blockers - Nifedipine and dihydropyridines DHPs 1. MOA 2 Effects 3. Pharmacokinetics 4. Adverse effects
Nifedipine, Amlodipine and dihydropyridines DHPs
- MOA: inhibit Ca2+ selective L channels carrying slow inward current during depolarization
- nifedipine and DHPs bind to closed L channels –> decrease frequency of opening
- decreased total peripheral resistance TPR - Effects:
- increase coronary blood flow due to vasodilation with modest cardiac stimulation
* stronger vasodilation with nifedipine than verapamil due to action on smooth muscle
- nifedipine used to treat pregnancy-induced HTN
- dihydropyridines treat HTN
- also Raynaud’s, prevent vasospasms in subarachnoid hemorrhages - Pharmacokinetics
- nifedipine: prototype DHP Ca2+ entry blocker; orally effective but large first-pass transformation
- no tolerance and metabolically neutral (Does not aggravate diabetes, glucose, etc) - Adverse effects
- flushing, headaches, hypotension, peripheral edema
- reflex tachycardia (can exacerbate ischemia - avoid in pts with MI)
[Angina drugs] Calcium Channel blockers - Verapamil and diltiazem 1. MOA 2. Cardiovascular effects 3. Pharmacokinetics 4. Adverse effects
Verapamil and diltiazem - nondihydropyridines, greatest effect on cardiac muscle
- MOA: inhibit Ca2+ selective L channels carrying slow inward current during depolarization
- verapamil and diltiazem bind to open L channels - Cardiovascular effects:
- increase coronary blood flow due to vasodilation with moderate cardiac suppression
* stronger vasodilation with nifedipine; of resistance but not capacitance vessels
- anti-arrhythmic properties-
- decrease cardiac contractility and output
- bradycardia (act on SA node_ - Pharmacokinetics
- orally effective, but large first-pass transformation
- no tolerance (unlike organic nitrates), and no aggravation of diabetes, peripheral vascular disease, bronchospasm, glucose, potassium - Adverse effects
- flushing, GI distress, left ventricular dysfunction
- constipation (verapimil)
- excess AV block when in combo with BBs
- skin rash (Steven Johnson syndrome)
- inhibit CYP450
[Antiplatelet, anticoagulant drugs]
Indirect thrombin inhibitors: heparin, LMWH, fondaparinaux
- MOA
- Pharmacokinetics/indications
- Adverse effects
Indirect thrombin inhibitors - heparin, enoxaparin (Lovenox, LMWH), fondaparinux (synthetic pentasaccharide)
- MOA: contains pentasaccharide that binds and activates antithrombin –> Acts as suicide substrate that traps protease (thrombin IIa or Xa)
- highly sulfated mucopolysaccharide –> (-) charge
A. unfractionated heparin (UFH) - inactivates II and X
B. low molecular weight (LMWH) - inactivates X
C. fondaparinaux - inactivates X - Pharmacokinetics: not absorbed from GI tract - give parenterally; does not cross placenta or breast milk
- continuous IV for: DVT treatment/prophylaxis, PE prophylaxis, acute MI treatment
- reverse action by discontinuing (1/2 life ~1 hr) OR giving (+) protamine sulfate antidote for heparin
A. heparin - monitor apTT
B. enoxaparin LMWH has longer 1/2 life and less thrombin inhibition –> used to prevent DVT post-op, treat acute thromboembolic disease
C. fondaparinaux - longest 1/2 life, does not cause HIT but contraindicated in patients with renal failure
- Adverse effects: major bleeding (2% with UFH, 1% with LMWH); contraindicated for any bleeding risk/condition
- osteoporosis
- hypoaldosteronism –> hypokalemia
- heparin induced thrombocytopenia HIT (immune response with Ab against heparin –> activate platelets –> paradoxical thrombosis)
[Antiplatelet, anticoagulant drugs] Direct thrombin inhibitors - desirudin, bivalirudin, argatroban 1. MOA 2. Pharmacokinetics/indications 3. Adverse effects
Direct thrombin inhibitors - desirudin, bivalirudin, argatroban
- MOA: derived from hirudin protein found in leech
- desirudin (recombinant hirudin) and bivalirudin ( bind to catalytic site and exosite 1 of thrombin (II)
- argatroban binds to catalytic site of thrombin - Pharmacokinetics: can reach and inactivate fibrin-bound thrombin
A. Desirudin: most potent thrombin inhibitor, approved for prevention of DVT post-op; t1/2 of ~2 hrs post subcutaneous admin; renal clearance
B. Bivalirudin: used in coronary angioplasty, HIT; t1/2 of ~30 min
C. Argatroban: IV, t1/2 of ~1 hr, monitored by aPTT, used for patients with HIT - Adverse effects: hemorrhage, allergic reactions
[Antiplatelet, anticoagulant drugs]
Oral anticoagulants - warfarin, novel oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban)
- MOA
- Pharmacokinetics/indications
- Adverse effects
Oral anticoagulants - warfarin, dabigatran, rivaroxaban, apixaban, edoxaban
- MOA
A. warfarin: competitive inhibitor of VKORC1 enzyme required to recycle vitamin K to reduced form –> inhibits carboxylation of Vit K dependent clotting factors into functional forms –> inhibits biosynthesis of factors X, IX, VII, II as well as Proteins C and S
B. Novel oral anticoagulants NOACs:
i. dabigatran - direct thrombin inhibitor
ii. rivaroxaban, apixaban, edoxaban - direct factor Xa inhibitors - Pharmacokinetics
A. Warfarin: delayed onset of action bc acts at synthesis of factors (not on the factors directly), narrow TI
- ↓ stroke, complications/recurrence of DVT/PE, risk of valve thrombosis/embolism with mechanical heart valves
- coadminister with heparin to prevent skin necrosis during early hypercoagulable state (Factor VII, Protein C down but factors II, IX, X still up)
B. NOACs - are non-inferior to warfarin; have similar overall bleeding but no ability to monitor - Adverse effects
A. Warfarin: bleeding (4%) –> give fresh frozen plasma to reverse, teratogenic - birth defects/abortion, skin necrosis during early hyper-coagulable state
- conditions that alter response to warfarin: Vit K in diet, pregnancy, liver disease, other drugs (lots of interactions)
[Antiplatelet, anticoagulant drugs]
Fibrinolytic drugs - Alteplase
- MOA
- Pharmacokinetics/indications
- Adverse effects
Fibrinolysis - breaking down fibrin when clot has already formed a thrombus or become an emboli
alteplase (Activase) - recombinant tissue plasminogen administered as a bolus
- MOA: activates plasminogen that is bound to fibrin of thrombus –> activated plasmin dissolves the clot
- non-specific plasmin activation - Pharmacokinetics: t1/2 ~5 min – IV bolus then infusion
- used in acute ischemic stroke, acute MI, PE, DVT, central venous catheter occlusion - Adverse effects: bleeding
- contraindicated in hemorrhage (eg prior, internal, hemorrhagic stroke), head trauma, or surgery
- cerebral vascular lesion, pregnancy, peptic ulcer, severe HTN
[Antiplatelet, anticoagulant drugs]
Antiplatelet agents - aspirin
- MOA
- Pharmacokinetics/indications
- Adverse effects
Antiplatelet drugs - aspirin
- MOA: irreversible acetylates and inhibits cycloxygenase COX1 and COX2 (activated in inflammation) –> platelets can no longer produce thromboxane TXA2 –> inhibits ability to activate other platelets
- also inhibits production of antiplatelet prostacyclin PGI2 in endothelial cells
* low dose aspirin inhibits TXA2 and spares PGI2 - Pharmacokinetics: oral; primary prophylaxis of MI
- Adverse effects: bleeding (hemorrhagic stroke, GI bleeding), ↑ risk of peptic ulcer disease
- pseudo-allergy due to excess leukotriene synthesis
[Antiplatelet, anticoagulant drugs]
Antiplatelet agents - Clopidogrel, prasugrel, ticarelor
- MOA
- Pharmacokinetics/indications
- Adverse effects
Antiplatelet agents - clopidogrel (Plavix), prasugrel (Eficient), ticarelor (Brilinta)
- MOA: more effective than aspirin bc ADP is stronger stimulus of platelet aggregation
- clopidogrel and prasugrel irreversibly inhibit ADP receptor binding
- ticarelor reversible inhibits binding - Pharmacokinetics: oral
- dual antiplatelet therapy - ADP inhibitor + aspirin –> prevent coronary stent thrombosis
- triple therapy - add oral anticoagulant on top
- indications: reduce long-term risk of cardiovascular events in patients with CAD, peripheral artery disease - Adverse effects: bleeding
- ticlodipine ADP receptor inhibitors causes granulocytopenia
[Antiplatelet, anticoagulant drugs]
Antiplatelet agents - Abciximab, tirofiban, epitifibatide
- MOA
- Pharmacokinetics/indications
- Adverse effects
Antiplatelet agents - Abciximab, tirofiban, epitifibatide
- MOA: block GP IIb/IIIa - platelet membrane receptor that binds to fibrinogen/vWF –> inhibits formation of platelet plug
* most effective antiplatelets - block aggregation and adherence regardless of activating stimulus (TXA2 or ADP) - Pharmacokinetics: IV, used during PCI (percutaenous coronary intervention) procedures
A. abciximab - monoclonal antibody against GPIIb/IIIa complex; coronary angioplasty, acute coronary syndrome
B. tirofiban - occupies receptor and inhibits binding
C. eptifibatide - occupies receptor and inhibits binding - Adverse effects: bleeding, thrombocytopenia
[Cardiac arrhythmias]
- Review currents underlying action potentials in different parts of the heart
- What is Bazett’s formula?
- Sinus node and AV node pacemaker cells have slower upstrokes –> slow L-type CA2+ depolarizing current –> takes longer to go from one cell to the other
* beta blockers have most effect
* affected by ANS
All else (Atrial muscle, ventricular muscle, Purkinje fibers) have fast upstroke –> due to fast Na+ depolarizing current (these channels are inactivated in pacemakers)
aforementioned Na+ and Ca2+ are depolarizing currents - inwards flow
K+ channels are repolarizing currents - outwards flow
- Bazett’s formula - normalizes QT for rate bc when rate is fast, QT will be short and vice versa
QTc = QT / sqrt(RR)
- when you need faster conduction in ventricles, action potential shortens to accommodate
[Cardiac arrhythmias]
1. Describe normal mechanism of automaticity
2. Describe how ANS modulates sinus node automaticity
A. PSNS
B. SNS
- Sinus node automaticity due to spontaneous phase 4 depolarization
- maximum diastolic potential (MDP) is -60mV, as opposed to RMP = -90mV in atrial and ventricular myocardium
- Phase 4 depolarization - due to inward “If” funny current that goes through HCN (hyperpolarization-activated cyclic nucleotide-gated) channels
- If current causes depolarization from -60mV to threshold, which is -40mV –> Ca2+ influx depolarization –> action potential –> K+ efflux repolarizes cell –> determines sinus rate - HCN channels mediated by ANS, through M2 and beta1 receptors (either decrease or increase cAMP)
A. PSNS muscarinic stimulation via ACh decreases HCN channel activity –> fewer HCN channels open –> longer to reach threshold –> increase cycle length –> decrease sinus rate
- also more rectifier channels open –> K+ efflux –> MDP is more negative
- fewer open Ca2+ channels –> shifts action potential threshold to be less negative –> takes longer to reach
B. SNS adrenergic stimulation via epi –> more channels available to conduct If current –> faster phase 4 depolarization –> decrease cycle length –> increase sinus rate / automaticity
- increases open Ca2+ channels –> shifts action potential threshold to be more negative –> reach threshold faster
[Cardiac arrhythmias]
- Understand how overdrive suppression and electrotonic interactions modulate latent pacemaker activity
- Hierarchy of pacemakers in heart
- Latent pacemaker activity
A. Overdrive suppression - dominant SA node removes the pacemaker activity of other latent centers –> rapid depolarization of SA node causes buildup of intracellular Na+ –> activates Na+/K+ ATPase which pumps out 3 Na+ for every 2K+ in the cell –> hyperpolarizes cell so it takes longer to reach threshold potential AND antagonizes the depolarizing If current–> suppresses If automaticity
- can try to induce this (make heart work faster) to make arrhythmias go away
B. Electrotonic interactions - if there are gap junctions that connect myocardial and pacemaker cells –> intercellular current will cause relative myocardial depolarization and pacemaker cell hyperpolarization –> slow rate of the pacemaker
- myocardial resting potential RP = -90 mV
- pacemaker max diastolic potential MDP = -60mV
- SA node cells less tightly coupled to myocytes compared to AV node and Purkinje fibers
- Pacemaker hierarchy
Sinus (60-100 depol/min)»_space; AV (40-60 depol/min)»_space; Purkinje (30-40)»_space; ventricular (20-40)
[Cardiac arrhythmias]
Abnormal impulse generation - list types of arrhythmias due to:
1. alterations in normal SA automaticity
2. enhanced automaticity of latent pacemakers
3. abnormal automaticity
- alterations in normal SA automaticity - sinus tachycardia, bradycardia
- escape rhythms - junctional (AV) or ventricular control –> escape beat
- SA»_space; AV node»_space; atrial tissue - sensitive to PSNS vagal stimulation - enhanced automaticity of latent pacemakers - normally latent pacemakers take control if SA node slows below their intrinsic rate; decreased coupling bw latent pacemakers and adjacent myocardial cells –> latent pacemakers fire faster than sinus node –> ectopic beat
- junctional premature complexes
- junctional tachycardia (due to catecholamines, MI, digitalis, aortic/mitral valve surgery) - abnormal automaticity - cells that normally do not have activity develop pacemaking potential under disease states (eg MI, ischemia) –> spontaneous phase IV depolarization even without If current
- ventricular premature complexes (VPCs) or tachycardia
- atrial premature complexes (PACs) or tachycardia
[Cardiac arrhythmias]
Triggered activity - Describe difference between early and delayed afterpolarizations
Triggered activity - not de novo depolarizations, occur after cell has been activated and triggered by that action potential
Early afterdepolarization - another depolarization occurs before/during repolarization (phases II or III)
- occurs when action potential duration is long (long QT), caused by influx of Ca2+ in the slow phase
- series of early afterdepolarizations leads to tachyarrhythmia –> torsades de pointes ventricular tachycardia (iatrogenic - caused by drugs that prolong action potentials)
Delayed afterdepolarization - another depolarization occurs after the cell has repolarized, due to Ca2+ overload of cells
- when they get faster and larger can cause arrhythmia
- due to digitalis, catecholaminergic polymorphic ventricular tachycardia (congenital), right ventricular outflow tachycardia, repetitive monomorphic VT
[Cardiac arrhythmias]
Abnormal impulse conduction - describe decremental conduction and block incl
1. Causes
2. Electrophysiologic mechanisms
3. Explain connection with Nernst equation incl impact of hyperkalemia on EKG
Decremental conduction and block - impaired conduction that can lead to bradycardia or reentry; occurs in nerve fibers with reduced membrane potential
- Causes: due to fibrosis (Lev-Lenegre syndrome which affects SA and AV nodes), MI (abnormal scar tissue), or hyperkalemia
- Electrophysiologic mechanisms:
- Na+ channel inactivation –> widened QRS
- gap junction abnormalities
- prolonged refraction due to disease processes - Nernst equation: K+ eq potential is dependent on K+ outside the cell and inside the cell – usually around -89 mV
- main determinant of RMP is K+ eq potential
- there are other ions that also have permeability (Na+ and Cl-); but at rest, main permeability is K+ –> so in reality actual RMP is a little more positive than K+ eq potential (around -82 mV)
Hyperkalemia: depolarized resting potential BUT decreased excitability
- ↑ extracellular K+ –> ↓ driving force for K+ to leave cell via rectifier channels –> RMP depolarized compared to normal –> more Na+ channels open but are then inactivated –> fewer Na+ channels available for Phase 0 depolarization –> ↓ conduction velocity –> ↑ QRS
[Cardiac arrhythmias]
- Define Reentry
- Causes
- List arrhythmias due to reentry
- Explain connection to wavelength
3 mechanisms of causing tachyarrhythmias: enhanced automaticity, triggered activity, reentry
- Reentry - impulse does not die out after normal activation and re-excites heart after normal refractory period has ended (once pathway is repolarized)
- Caused by unidirectional block and slow conduction velocity (due to fibrotic/scarred myocardium, sequelae to MI)
- Arrhythmias due to reentry:
A. Anatomical reentry (fixed pathway) –> atrial flutter, AVNRT, AVRT (Eg WPW syndrome), ventricular tachycardia due to scar tissue
B. Functional reentry (multiple locations): atrial fibrillation, ventricular fibrillation, polymorphic VT - Wavelength = conduction velocity + refractory period –> path length or circumference needs to be greater than wavelength to support reentry
[Cardiac arrhythmias]
- Describe reentry arrhythmias in ventricular pre-excitation
- EKG signs
- Ventricular pre-excitation –> atrial electrical impulses reach ventricles earlier than expected due to conduction down abnormal accessory pathway (Bundle of Kent) –> bypasses the AV node and connects SA node to ventricular myocardium
used interchangeably with Wolff-Parkinson-White (wpw) syndrome –> ventricular pre-excitation leading to atrioventricular reentrant tachycardias (AVRTs), type of supraventricular tachyarrhythmias (SVTs)
*afib in pt with wpw v dangerous –> can have sudden cardiac death –> need to ablate; treat with procainamide but NOT CCBs or BBs
- EKG signs (anterograde down both AV node and accessory pathway):
- short PR interval –> shortened AV nodal delay
- delta wave (blurred upstroke of QRS) –> impulse making it to ventricles prematurely
- widened QRS –> fusion bw normal conduction and bypass track
[Hypertension]
- Determinants of HTN
- age
- time of day - Classification:
A. Essential HTN
B. Secondary HTN
- High BP determined by Cardiac Output (CO) and Peripheral Resistance (TPR)
A. for younger people, high CO influences HTN –> isolated diastolic HTN
- for older people, high TPR influences HTN –> isolated systolic HTN due to lower arterial compliance (stiffer due to atherosclerosis)
B. BP goes down at night and if it doesn’t –> increased CVD risk
2A. Essential (Primary) HTN - 90%+
- unknown etiology but related to changes in SNS and renin/angiotension/aldosterone system RAAS, renal dysfunction, genetics, environment
B. Secondary HTN - 5-10%
- acute/ chronic kidney disease
- renal artery stenosis –> renal HTN
- endocrine: aldosteronism, hyperthyroid, Cushing
- aortic coarctation (upper extremity HTN)
- obstructive sleep apnea
- drug-induced
[Hypertension] Pathogenesis of major consequences of HTN: 1. Ischemic heart disease 2. Heart failure 3. Stroke 4. Aortic aneurysm 5. Nephrosclerosis 6. Retinopathy
HTN causes ↑ afterload, arterial damage; pressure overload causes concentric hypertrophy (increased risk of ischemic injury bc farther away from bv)
- Ischemic heart disease / MI
A. ↑ myocardial 02 demand bc of ↑ afterload
B. ↓ myocardial 02 supply bc of atherosclerosis due to arterial damage - Heart failure
A. systolic dysfunction bc of ↑ afterload
B. diastolic dysfunction bc of LVH due to ↑ afterload - Stroke
A. Thrombosis / emboli (cerebral/carotid) due to accelerated atherosclerosis bc of arterial damage
B. Cerebral hemorrhage due to weakened vessel wall bc of arterial damage - Aortic aneurysm/dissection due to atherosclerosis and weakened vessel walls bc of arterial damage
- hyaline arteriosclerosis with benign HT
- hyperplastic arteriosclerosis with malignant HT - Nephrosclerosis and renal failure due to weakened vessels walls in kidney
- Retinopathy due to weakened vessel walls in the eye
[Hypertension] 1. BP limits for: A. Normal B. PreHTN C. Stage 1 HTN D. Stage 2 HTN
- JNC-7 Treatment guidelines
1. BP limits for: A. Normal: <120 and <80 B. PreHTN: 120-39 or 80-89 C. Stage 1 HTN: 140-159 or 90-99 D. Stage 2 HTN: >160 or >100
- JNC-7 Treatment guidelines
A. lifestyle modifications (rarely work)
B. drugs for pts 140/90+ (or diabetes/renal pts 130/80+)
- Stage 1: thiazide diuretics HCTZ
- Stage 2: two drug combo (HCTZ + ACEI/ARB)
*not much difference between the different HTN drugs
[Diuretics] Acetazolamide (Diamox) 1. MOA incl site of action 2. Clinical uses 3. Adverse effects incl adverse effects, contraindications
Acetazolamide (Diamox)
- MOA: Acts in proximal tubule
- inhibits carbonic anhydrase–> blocks interconversion of H20 + C02 into H2C03 –> blocks reabsorption of HC03- and also Na+ –> ions + water excreted - Clinical uses:
- mainly to alkalinize urine or counteract metabolic alkalosis
- glaucoma (topical)
- acute mountain sickness - raises C02 content of tissue –> stabilizes deoxyHb
- anticonvulsant - Adverse effects
- alkalinization of urine (pH in urine increases)
- blood pH decreases –> hyperchloremic metabolic acidosis –> compensatory Kussmaul breathing (hyperventilation with deep respiration)
- efficacy in sustaining diuresis is not great / reduces bc Na+ can be reabsorbed at other points in the tubule
- side effects: somnolence, renal K+ wasting
- contraindications: pts with hepatic cirrhosis, allergies to sulfonamides
[Diuretics] Osmotic diuretics eg mannitol, glycerin 1. MOA incl site of action 2. Clinical uses 3. Adverse effects incl adverse effects, contraindications
Osmotic diuretics - mannitol, glycerin parenteral administration
- MOA: act in proximal tubule and descending limb of Henle
- increase osmolarity inside the tubule itself –> oncotically traps water inside the tubular fluid –> expand extracellular fluid volume, decrease blood viscosity, inhibit renin release –> diuresis - Clinical uses:
- increase water excretion preferentially over Na+ excretion
- eliminate toxic substances from GI tract (along with activated charcoal), or renal toxins
- reduce intracranial and intraocular pressure (before optho procedures) - Adverse effects
- side effects: headache, nausea, vomiting
- before diuresis: extracellular volume expansion –> hyponatremia, exacerbation of HF
- after diuresis: dehydration and hypernatremia (from excessive use w/out monitoring)
[Diuretics] Loop diuretics 1. MOA incl site of action 2. Clinical uses 3. Adverse effects incl adverse effects, contraindications
Loop diuretics - furosemide (Lasix), ethacrynic acid most effective diuretics available
- MOA: act at thick ascending limb TAL of loop of Henle
- normally NKCC2 creates positive electrical potential –> drives reabsorption of Mg2+ and Ca2+ ; Loop diuretics inhibit NKCC2 –> increase in Mg2+ and Ca2+ excretion, NaCl and K+ excretion
- block tubuloglomerular feedback by inhibiting salt transport into macula densa
- increase expression of COX2 –> induce PGE2 synthesis –> increase renal blood flow + inhibit salt transport NSAIDs interfere with loop diuretics - Clinical uses:
- first-line for HF - esp tx of acute decompensated HF with fluid overload
- symptomatic tx of pulmonary edema in exacerbation of acute HF (crackles, pitting edema, JVD)
- treats ascites in liver failure
- HTN in patients with comorbid conditions (HF)
- acute hypercalcemia, hyperkalemia - Adverse effects:
- hypokalemic metabolic alkalosis
- hypomagnesiumia, hypocalcemia (rarer)
- ototoxicity (reversible)
- hyperuricemia –> precipitates gout
- contraindications: allergies to sulfonamides (except ethacrynic acid, which does not have sulfonamide)
[Diuretics] Thiazide 1. MOA incl site of action 2. Clinical uses 3. Adverse effects incl adverse effects, contraindications
Thiazides - HCTZ most common drug prescribed for HTN, chlorthiazide (IV), chlorthalidone (longer half life)
- MOA: act at distal convoluted tubule
- inhibits Na+/Cl- NCC symporter on the apical membrane–> less Na+ inside the cell –> increases basolateral Na+/Ca2+ exchanger to concentrate (brings Na+ inside cell and excretes Ca2+ into the interstitium/blood) –> increased Ca2+ reabsorption from lumen/urine (PTH-regulated), increased Na+ and Cl- excretion - Clinical uses:
- first-line for mild-moderate hypertension
- adjunctive with loop diuretics for heart failure
- nephroliathiasis i.e. kidney stones (excess Ca2+ in tubular fluid)
- nephrogenic diabetes insipidus (ADH insensitivity) - Adverse effects
- hypokalemic metabolic alkalosis
- hyperuricemia –> precipitate gout
- hyponatremia, hypocalcemia
- hyperglycemia, hyperlipidemia
- inhibited by NSAIDs
- contraindications: allergies to sulfonamides
[Diuretics]
K+ sparing diuretics - Spironolactone and eplerenone
1. MOA incl site of action
2. Clinical uses
3. Adverse effects incl adverse effects, contraindications
K+ sparing diuretics - spironolactone, eplerenone (more selective, fewer side-effects)
- MOA: acts on collecting tubule
- competitive antagonists of aldosterone receptor –> decrease in Na+ reabsorption, K+ and H+ secretion - Clinical uses: mainly used as aldosterone antagonists
- cirrhosis v responsive to spironolactone
- heart failure (decreased mortality in HF)
- renalvascular HTN
- adrenal tumors
- cardiac or nephrotic edema
- prevents cardiac remodeling - Adverse effects:
- spironolactone may be inhibited by NSAIDs, can cause gynecomastia, impotence, decreased libido
- hyperkalemia
- hyperchloremic metabolic acidosis
- contraindication: chronic renal insufficiency
[Diuretics]
K+ sparing diuretics - triamterine, amiloride
1. MOA incl site of action
2. Clinical uses
3. Adverse effects incl adverse effects, contraindications
K+ sparing diuretics - triamterine, amiloride
- MOA: acts on collecting tubule
- inhibit ENaC Na2+ reabsorption channels in apical cells of collecting tubule –> decrease in Na+ reabsorption, K+ and H+ secretion - Clinical uses:
- hypokalemia from other diuretics
mineralocorticoid excess due to
- primary hypersecretion (Conn’a syndrome, ecoptic ACTH production)
- secondary aldosteronism (heart failure, cirrhosis, nephrotic syndrome)
- Liddle’s syndrome (gain of function ENaC mutation) - Adverse effects:
- triamterene may be inhibited by NSAIDs
- hyperkalemic metabolic acidosis
[Diuretics] ADH antagonists 1. MOA incl site of action 2. Clinical uses 3. Adverse effects incl adverse effects, contraindications
ADH antagonist (vaptans/aquaretics) - conivaptan (V1 and V2), lixivaptan (V2), tolvaptan (V2)
- MOA: act at the principal cells of the collecting tubule
- Non-selective antagonists of V1 and/or V2 ADH receptors –> decrease number of AQP2 channels on apical surface –> decreased water reabsorption
- Lithium and demeclocyline - reduce cAMP in principal cell via unknown etiology - Clinical uses:
- SIADH
- other causes of elevated ADH - Adverse effects:
- nephrogenic diabetes insipidus (treat Li-induced NDI with amiloride)
- renal failure (Lithium and demeclocyline)
- lot of side effects for lithium (thyroid, cardiotoxicity)
[Antihypertensive agents] Direct vasodilators e.g. hydralazine 1. MOA incl site of action 2. Clinical uses 3. Adverse effects incl adverse effects, contraindications
Direct vasodilators - [oral] hydralazine and minoxidil (Rogaine), [parenteral] nitroprusside and diazoxide
- MOA: ↑ cGMP –> smooth relaxation –> lowers total peripheral resistance –> ↓ afterload
- vasodilates arterioles»_space; veins (unlike nitrates)
- minoxidil - opens K+ channels, most potent - Clinical uses:
- severe or refractory HTN
- nitroprusside used for HTN emergencies
- use with nitrates to treat HF
- pseudotolerance - effect wears off quickly unless you use diuretic + beta blocker (to slow HR) - Adverse effects:
- reduced perfusion pressure to kidney –> increased renin and volume retention –> edema
- reflex SNS stimulation –> tachycardia
- hydralazine - lupus syndrome w/ pericarditis
- minoxidil - hypertrichosis (hair growth)
- Differences between ACEI, ARBs, and direct renin inhibitors on RAAS
- Adverse effects
- BP drug selection
1A. ACEI - inhibits conversion of Angiotensin I –> II
- ↓ Ang II and aldosterone levels
- ↑ vasodilatory peptides eg bradykinin
- ↑ plasma renin level, plasma renin activity PRA
B. ARBs - block AT1 (Ang II) receptors
- ↑ plasma renin level, PRA
- ↑ Ang II levels
- ↓ aldosterone levels
C. DRI - inhibition of renin on its substrate
- ↓ PRA, Ang I, Ang II, aldosterone levels
- Adverse effects
- hyperkalemia (aldosterone inhibition)
- hypotension
- worsen renal insufficiency
- fetal injury (teratogenic) do not give in pregnancy
* ACEI - cough - Overall: Start thiazide, CCB, ACEI, or ARB
- blacks: start thiazide or CCB (blacks have lower renin output)
- chronic kidney disease: include renin antagonist
- diabetes: RAAS drug (ACEI or ARB), NO diuretics
[Cardiac arrhythmias]
Sinus bradycardia
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Sinus bradycardia
- Mechanism - decreased automaticity of SA node
- EKG: lower than 60 bpm
- Etiology - ↑ PSNS tone, medication (beta blockers, Ca2+ channel blockers)
- age, atrial fibrosis, SCN5A mutations
- sick sinus syndrome (syndrome incl brady-tachy) - Clinical presentation: fatigue, dizziness, asymptomatic
- Treatment: None, underlying cause if symptomatic, pacemaker (esp with brady-tachy syndrome which can cause afib)
[Cardiac arrhythmias]
1st Degree AV block
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
First Degree AV block
1. Mechanism - slowed conduction in AV node (not really a block)
2. EKG - prolonged PR interval due to ↑ AV delay (0.20+ sec i.e. 5+ small boxes)
3. Etiology
A. Reversible: ↑ PSNS tone, medications, Lyme disease
B. Structural: MI, degenerative disease
4. 4. Clinical presentation - older patients, on beta blockers/Ca2+ channel blockers, digitalis; usually asymptomatic
5. Treatment - adjust meds or nothing
[Cardiac arrhythmias]
2st Degree AV block - Mobitz Types I and 2
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
2st Degree AV block
1. Mechanism - intermittent failure of AV conduction (no QRS after P wave)
A. Mobitz Type I - impaired conduction in AV node
B. Mobitz Type II - conduction block distal to AV node (Bundle of His or Purkinje) –> no possibility for escape rhythm
- EKG
A. Mobitz Type I - degree of AV delay increases (PR interval gets longer) until complete block (no QRS after P wave)
- Wenckebach - PR interval ↑ and RR interval ↓
B. Mobitz Type II - sudden block in AV conduction without gradual lengthening of PR - Etiology
A. Mobitz Type I: ↑ PSNS tone, medications (BB, CCB, digitalis), inferior MI, congenital AV block, myocarditis
B. Mobitz Type II: structural damage/degeneration in His-Purkinje, anterior MI - Clinical presentation
A. Mobitz Type I: asymptomatic, benign, transient - seen in children, athletes, people with high vagal tone
B. Mobitz Type II: dizziness, Stokes-Adam syncope (treat with isoproterenol) - Treatment
A. Mobitz Type I: reversible with removing meds
B. Mobitz Type II: pacemaker even if asymptomatic
[Cardiac arrhythmias]
3rd degree heart block
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
3rd degree heart block - complete heart block
- Mechanism - complete failure of conduction between atria and ventricles –> AV dissociation
- EKG - P waves and QRS complexes have separate rates
- P waves –> still depolarize to SA node
- QRS normal width, 40-60 bpm –> AV escape rhythm
- QRS widened, slower rate –> His-Purkinje escape - Etiology - block below level of AV node (His-Purkinje), anterior MI, degeneration of His-Purkinje
- Clinical presentation - syncope, light-headedness
- many patients also have BBB - Treatment - pacemaker
[Cardiac arrhythmias]
Sinus tachycardia
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Sinus tachycardia
- Mechanism - increased automaticity of SA node
- EKG - rate greater than 100 bpm
- normal P waves and QRS complexes - Etiology - increased SNS (or decreased PSNS)
- Clinical presentation - exercise or excitement
- pathological: fever, pain, low CO, CHF, anemia, hyperthyroidism - Treatment: underlying cause, not the rhythm
[Cardiac arrhythmias]
Atrial premature complexes
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Atrial premature complexes (PAC) = atrial premature beats (APB)
- Mechanism - abnormal automaticity, reentry in atria, delayed afterdepolarizations (triggered activity)
- EKG - earlier than expected P wave with abnormal shape (bc impulse does not originate from SA node), followed by normal QRS (ventricular conduction not impaired)
- Etiology - ↑ SNS tone, stretch, fibrosis
- healthy or diseased hearts
- can lead to atrial tachycardia (ectopic pacemaker is atrial myocyte and not SA node) –> p waves inverted in inferior leads; starts and ends suddenly - Clinical presentation - caffeine, alcohol
- palpitations or asymptomatic - Treatment - remove precipitating factors, or beta blockers
- treat focal atrial tachycardia with cardiac ablation
[Cardiac arrhythmias]
fle
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Atrial flutter - prototypic reentry arrhythmia
- Mechanism - reentrant circuit in RA along tricuspid valve annulus
- EKG - saw-tooth, rapid, regular P waves
- most commonly 300 bpm with 2:1 block –> ventricular rate SVT = 150 bpm - Etiology - areas of scarring, prior surgery, but most often with no heart disease
- related to afib - Clinical presentation - palpitations, dyspnea, chest discomfort
- Treatment
- diagnose via adenosine/vagal maneuver (Carotid sinus massage)–> increases ACh –> AV node conduction block increases –> slow ventricular rate but flutter continues unabated
A. Acute - BBs, CCBs to slow conduction and decrease ventricular rate; cardioversion to restore sinus rhythm
B. Chronic - Ablation
[Cardiac arrhythmias]
Atrial fibrillation
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Atrial fibrillation
- Mechanism - multiple wandering reentrant circuits within the atria –> continual AV node stimulation
- paroxysmal afib (less than 7 days, stop on their own) –> pulmonary vein triggers - EKG - no distinct P waves
- irregularly irregular ventricular rate - Etiology - left atrial enlargement or scarring
- Clinical presentation - palpitations, dyspnea, chest pain –> can lead to heart failure, CVA (stroke) afib one of leading causes of stroke
- mostly pts with enlarged LA (due to HTN, mitral stenosis, CHF, etc) - Treatment -
A. Acute - BBs, CCBs to reduce ventricular rate; cardioversion (shock on QRS) to restore sinus rhythm
B. Chronic - heparin for stroke
i. Rate control - BBs, CCBs
ii. Rhythm control - Class 1C (flecainide), Class 3 (amiodarone, sotalol, ibultilide) to maintain sinus
[Cardiac arrhythmias]
1. Define Paroxysmal supraventricular tachycardia (PSVT)
Mechanisms of PSVT:
2. AV Nodal Reentrant Tachycardia (AVNRT)
3. Atrioventricular Reentrant Tachycardia (AVRT)
4. Atrial tachycardia
- PSVT:
A. Sudden onset and termination
B. atrial rates 140-250 bpm
C. narrow/normal QRS complexes (due to AV conduction)
- due to reentry, initiated by premature atrial beat (PAC)
- treat with IV adenosine, vagal maneuver, ablation - AVNRT - most common form of PSVT
- 2 pathways in/near the AV node (antereograde through slow and retrograde through fast pathways)
- EKG: hidden p waves, normal QRS complexes
- usually teenagers with palpitations, dizziness
- rates usually 190/min - AVRT - one limb of reentry loop is myocardial bypass tract (e.g. Wolff-Parkinson-White syndrome)
- orthodromic AVRT: anterograde through AV node and retrograde through accessory pathway (inverted P wave after QRS)
- rates usually 220 bpm - Atrial tachycardia - ectopic pacemaker is atrial myocyte –> p wave morphology different bc depolarization is from abnormal location (not SA node)
- focal or reentrant
- AV node block (BB, CCBs) until ablation
[Cardiac arrhythmias]
Ventricular arrhythmias - Ventricular Premature Complexes (VPCs)
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Premature ventricular complexes (PVCs) = ventricular premature beats (VPB)
- Mechanism - ectopic ventricular focus fires action potential due to abnormal automaticity, delayed afterdepolarization, reentry
- EKG - widened QRS complex (ectopic beat travels slowly through cell to cells and not fast His-Purkinje)
- Etiology - can occur in healthy and diseased hearts
- ↑ SNS, cardiomyopathy, structural disease
- caffeine, hypoxia - Clinical presentation - often asymptomatic and benign
- palpitations - Treatment - beta blockers if symptomatic
[Cardiac arrhythmias]
Ventricular arrhythmias - Ventricular Tachycardia incl monomorphic, polymorphic, and torsades
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Ventricular Tachycardia incl monomorphic, polymorphic, and torsades
- Mechanism - delayed afterpolarizations (pts w/out structural heart disease), reentry (pts post MI)
- EKG - 3+ consecutive premature ventricular complexes (wide QRS) at 100+ bpm
- monomorphic - due to reentry –> QRS same and regular rate
- polymorphic - multiple ectopic focuses or changing reentry circuits–> QRS complexes and rate change
- torsades de pointes - type of polymorphic VT –> due to early afterdepolarizations in patients with prolonged QT (longer action potential) - Etiology - scar from MI, cardiomyopathy, electrolyte abnormality (hyperkalemia), idiopathic
- Clinical presentation - palpitations, dizziness, syncope
- sustained (30+ sec) - Treatment:
A. Pts post MI - lidocaine, procainamide, cardioversion –> then ICD, amiodarone, K+ channel block
B. Pts w/out structural disease - defibrillation –> then verapamil, BBs, ablation
[Cardiac arrhythmias]
Ventricular arrhythmias - Ventricular Fibrillation
- Mechanism
- EKG
- Etiology
- Clinical presentation
- Treatment
Ventricular Fibrillation
- Mechanism - multiple reentry circuits –> no coordinated contractions –> no cardiac output
- EKG - chaotic irregular appearance, no QRS complexes
- Etiology - initiated by Vtach; due to Long QT, Brugada, prior MI, idiopathic
- Clinical presentation - cardiac arrest
- Treatment - defibrillation –> then ICD (defibrillator) if pt survives and amiodarone to block recurrence
[Cardiac arrhythmias]
Describe genetic mutations that can lead to ventricular arrhythmias
1. Long QT syndrome
2. Brugada
3. Familial catecholaminergic polymorphic VT
4. Arrhythmogenic Right Ventricular Cardiomyopathy
- Long QT syndrome - most common ion channel mutation (K+ or Na+) –> long action potential duration
- precipitated by hypokalemia, swimming, auditory –> syncope, sudden cardiac death
- due to LQT1, 2, 3 genes - Brugada - loss of function of Na+ channel –> peculiar ECG pattern –> predisposes to vfib and sudden cardiac death; M»F
- Familial catecholaminergic polymorphic VT - Ca2+ handling mutation eg Ryanidine receptor RyR2 –> delayed afterdepolarizations –> stress-induced SCD in patients with normal ECGs, no structural heart disease
- Arrhythmogenic Right Ventricular Cardiomyopathy - mutations in desmosomes –> gap junctions affected – > replacement of RV with fibrous tissue
[Antiarrhythmic drugs] Class 1A Drugs e.g. procainamide 1. MOA 2. Clinical uses 3. Adverse effects
Class 1A Drugs e.g. procainamide, quinidine, disopyramide
- MOA - moderate blockade of Na+ channel –> intermediate use dependence and slowing of Phase 0 upstroke
- also block K+ channels –> prolong action potential duration –> prolong refractory period (QT prolongation) - Clinical uses - both atrial fibrillation and ventricular arrhythmias, esp post MI
- procainamide treats wolff-parkinson-white syndrome - Adverse effects -
- QT prolongation –> can precipitate early afterdepolarizations –> ↑ risk of torsades, syncope
- quinidine- cinchonism (tinnitus, headache, dizziness), thrombocytopenia
- procainamide - lupus-like syndrome
- disopyramide - exacerbates HF; contraindicated in urinary retention
[Antiarrhythmic drugs] Class 1B Drugs e.g. lidocaine 1. MOA 2. Clinical uses 3. Adverse effects
Class 1B Drugs e.g. lidocaine, tocainide, mexiletine
- MOA: low binding affinity for open or inactivated Na+ channels with fast kinetics–> low use-dependence
- shorten phases 2 and 3 –> shorten action potential duration and refractory period - Clinical uses - treat ischemia-induced ventricular arrhythmias
- termination of vtach, prevention of vfib
- digitalis-induced arrhythmias
- 1b best post-MI (also amiodarone) - Adverse effects - one of least cardiotoxic –> neurologic incl paresthesia, tremor, convulsions
- extensive first pass metabolism (IV admin)
[Antiarrhythmic drugs] Class 1C Drugs e.g. flecainide 1. MOA 2. Clinical uses 3. Adverse effects
Class 1C Drugs e.g. flecainide, morizine, propafenone
- MOA - strong inhibition of Na+ channels in Phase 0 bc of slow kinetics –> strong use-dependene and marked decrease in upstroke of Phase 0
- minimal effect on action potential duration - Clinical uses - treat both atrial and ventricular arrhthmias
- SVTs including afib + aflutter - can restore/maintain sinus rhythms - Adverse effects - exacerbation of arrhythmias eg atrial flutter, vtach; can cause heart failure
- 1C contraindicated in structural or ischemic heart disease
[Antiarrhythmic drugs] Class 2 Drugs e.g. propranolol, esmolol 1. MOA 2. Clinical uses 3. Adverse effects
Class 2 Drugs are Beta blockers e.g. propranolol, esmolol
- MOA - affects SA and AV nodes (pacemaker potential)
- block SNS –> lower cAMP –> reduction of Na+ and Ca2+ currents –> suppresses abnormal pacemakers
- AV node particularly sensitive –> ↓ phase 4 slope –> ↓ rate of firing –> ↓ automaticity and increased PR interval
- prolonged repolarization –> ↓ reentry - Clinical uses - suppress PVCs, terminate paroxysmal SVTs (eg AVNRT, AVRT)
- esmolol - Beta1 selective with short t1/2 (9 min), used after cardiac surgery for rate control –> controls ventricular response in afib or atrial flutter
- propranolol - post MI as death prophylaxis, vfib - Adverse effects
- contraindicated in Wolff-Parkinson-White (wpw)
- SNS suppression –> hypotension, bradycardia, AV block
- exacerbation of COPD and asthma due to bronchoconstriction
* ivabradine also decreases pacemaker activity –> blocks If in SA node –> reduces HR
[Antiarrhythmic drugs] Class 3 Drugs e.g. sotalol, ibutilide, amiodarone 1. MOA 2. Clinical uses 3. Adverse effects
Class 3 Drugs e.g. sotalol, ibutilide, finde, amiodarone
- MOA - affects myocytes –> block K+ potassium channels –> prolong action potential duration –> ↑ effective refractory period –> ↑ QT interval
- little effect on phase 0 or conduction velocity
- in addition amiodarone decreases phase 4 slope of pacemaker potential –> decreased automaticity of pacemakers - Clinical uses:
A. Sotalol - beta blocker and K+ channel blocker –> treats ventricular arrhythmias incl vtach
B. Ibutilide - conversion of acute atrial flutter and fib to normal sinus rhythm
C. Amiodarone most effective of all can block Na, Ca, K, and beta receptors (Class 1-4 activity) –> treats afib, atach, vtach, vflutter - Adverse effects - QT prolongation
- reverse use dependent (all except amiodarone)- action potential prolonged least at fast HRs and most at slow rates (precipitation of EADs –> torsades risk)
- amiodarone: neurologic effects, gray corneal microdeposits, pulmonary fibrosis and restrictive lung disease, hyper/hypothyroidism, gray-blue skin discoloration and photodermatitis, heart failure, hypersensitivity hepatitis (check LFTs)
[Antiarrhythmic drugs] Class 4 Drugs e.g. verapimil, diltiazem 1. MOA 2. Clinical uses 3. Adverse effects
Class 4 Drugs - Calcium Channel blockers e.g. verapamil, diltiazem
- MOA - affects SA and AV nodes, esp AV node
- block activated and inactivated (but not resting) L-type Ca2+ channels –> prolonged phase 4 –> ↓ automaticity –> ↓ sinus rate
- decrease slope of phase 0 –> ↓ conduction velocity and ↑ refractory periods –> ↓ reentry and ↑ PR interval - Clinical uses:
- prevent paroxysmal supraventricular arrhythmias - (AVNRT, AVRT)
- rate control of rapid ventricular response in afib and atrial flutter - Adverse effects - peripheral vasodilation; AV block, hypotension, constipation
- contraindicated in Wolff-Parkinson-White (wpw) bc conduction in accessory pathway is NOT slowed –> worsens reentry, beta blockers
[Antiarrhythmic drugs] Describe MOA and clinical uses of additional antiarrhythmics: 1. Adenosine 2. Potassium 3. Magnesium 4. Digoxin A. Digoxin Immune Fab
- Adenosine- purine nucleoside that binds to A1 receptor –> activates rectifier K+ current and inhibits L-type CA2+ current –> K+ leaves and Ca2+ cannot enter –> cell is hyperpolarized
- inhibits AV nodal conduction –> ↑ AV nodal refractory period –> conversion of SVTs to sinus rhythm
- t1/2 = 15 sec
- adenosine receptor antagonists - theophylline and caffeine
- side effects: headache, hypotension, flushing, sense of impending doom - Potassium - both hypo and hyperkalemia can cause arrhythmias
- hypo - U wave after T wave
- hyper - peaked T wave with shortened QT interval - Magnesium - ER pts given IV Mg, even if serum levels normal; used to treat torsades
- Digoxin (Digitalis)- positive inotrope with direct vagus PSNS stimulation –> rate control in afib or atrial flutter in patients having heart failure
A. Digoxin Immune Fab - adjunctive to temporary cardiac pacemaker; treatment of digoxin toxicity
[Congenital Heart Disease]
1. Define congenital heart disease
Describe the following congenital heart defects:
- Congenital aortic stenosis
- Pulmonic stenosis
- Congenital heart disease - anatomic (not genetic) abnormality in cardiocirculatory structure/function present at birth
- most common type of congenital effect - Congenital aortic stenosis - tight aortic valve –> LV concentric hypertrophy (muscle becomes thicker) + dilated ascending aorta
- M»F, symptoms incl poor feeding, tachycardia, tachypnea
- harsh crescendo-decrescendo murmur loudest at base - Pulmonic stenosis - causes increased RV pressure and hypertrophy
- symptoms incl dyspnea, exercise intolerance, right sided heart failure (Edema)
- harsh crescendo-decrescendo murmur at L upper sternal border
- can hear a pulmonic valve click - ONLY R sided sound that decreases with inspiration (more blood coming in on inspiration stretches the valve and makes click less pronounced)
[Congenital Heart Disease]
- Anomalous coronaries
- Atrioventricular septal defect
- Anomalous coronaries - coronary artery comes from somewhere else (should be Left main from Left cusp and Right from Right cusp)
- Left main coronary artery from right cusp AND courses between great vessels (pulmonary artery and aorta) –> can cause sudden death (vessels get bigger during exercise and can constrict LCA) –> need bypass surgery
- everything else does not require treatment - Atrioventricular septal defect - inadequate fusion of the superior and inferior endocardial cushions –> large hole between the atria and ventricles
- presentation is before age 1 w frequent respiratory infections, poor weight gain, heart failure
[Valvular disease] Mitral stenosis 1. Etiology incl presentation and complications of acute RF 2. Pathophysiology 3. Presentation 4. Examination
Mitral stenosis - diastolic murmur
- Most common cause is chronic rheumatic fever (fishmouth mitral stenosis) –> occurs after untreated Group A strep infection
- Pathophys: inflammation –> leaflet thickening and calcification –> chordal fusion
- LA»LV pressure gradient –> backs up into pulmonary venous system –> pulmonary edema –> backs up into pulmonary arterial system –> pulmonary HTN
- LA enlargement –> LA dilatation –> stretches atrial conduction fibers –> afib –> thrombus –> stroke - Presentation: dyspnea with exercise at first, at rest when MS is more severe
- increasing HR (Exercise, stress, pregnancy, infection) –> reduces filling time –> worsens MS –> reduces CO - Examination: low-pitched middiastolic rumble (decrescendo) murmur
- opening snap post S2 (tensing of stenotic leaflets)
- shorter interval bw S2 and OS –> more severe
- EKG: LA enlargement (p wave abnormality on V1) + RVH
[Valvular disease]
Mitral regurgitation - Acute and Chronic MR
- Etiology
- Pathophysiology
- Presentation
- Examination
Mitral regurgitation - systolic murmur
- Etiology:
A. Acute - damage - e.g. papillary rupture post-MI, chordae rupture with infective endocarditis
Bi. Primary chronic - mitral valve prolapse
Bii. Secondary chronic / Functional - LV dilatation - Pathophys: portion of LV stroke volume ejected back into LA –> ↑ LA volume and pressure + ↓ CO + ↑ LV volume
A. Acute: ↓ SV (no time to compensate)
B. Chronic: compensation through ↑ LA dilatation, LV eccentric hypertrophy, ↑ LV stroke volume –> EF maintained
- decompensated phase: volume overload –> ↓ SV –> ↓ CO –> heart failure - Presentation
A. Acute: pulmonary edema and congestion
B. Chronic: dyspnea, orthopnea, fatigue, right HF - Examination
A. Acute: decrescendo, not holosystolic bc LV and LA equilibriate
B. Chronic: holosystolic “blowing” murmur, heard best at apex and radiates to axilla; can develop S3 (LV volume overload)
- intensifies with ↑SVR (eg clenching fists)
- EKG: LA enlargement (p wave abnormality on V1) + LVH
[Valvular disease]
Mitral valve prolapse
- Etiology
- Pathophysiology
- Presentation
- Examination
Mitral valve prolapse - systolic murmur
- Etiology: familial (AD) or non (connective tissue disease)
- Pathophysiology: billowing of mitral leaflets into LA during ventricular systole
- leaflets enlarged and myxomatous CT (instead of elastin/collagen)
- can be w/out mitral regurg (but common cause of MR) - Presentation: asymptomatic or chest pain
- Examination: mid-systolic click (tensing of chordae) and then late crescendo systolic murmur heard best at apex
- ↑ Venous return (Eg squatting from standing position) –> decreases murmur –> click and murmur occur later after S1
- vice versa (murmur increases upon valsalva/standing)
[Valvular disease]
Aortic stenosis
- Etiology
- Pathophysiology
- Presentation
- Examination
Aortic stenosis
- Etiology - calcification of aortic valve (adults - normal aging; young adults - bicuspid valve)
- Pathophysiology - blood flow impeded –> ↑ LV pressure needed –> LV concentric hypertrophy –> ↓ LV compliance –> LA hypertrophy to facilitate filling
- Presentation: triad = SAD (syncope, angina, dyspnea)
- Angina - 02 demand (↑ muscle mass and wall stress)»_space; 02 supply
- Syncope during exertion - vasodilation + ventricle cannot ↑ CO due to fixed stenotic valve –> decreased cerebral perfusion pressure
- Congestive heart failure - high afterload –> LV dysfunction –> ↑ pressure of LV, then LA, then pulmonary venous system –> HF, pulmonary congestion - Examination
- crescendo-decrescendo systolic ejection murmur with ejection click that radiates to carotids
- weakened and delayed carotid pulse “pulsus parvus et tardus”
- can develop S4 (stiff LV), or paradoxical splitting (late A2 component of S2 in expiration)
[Valvular disease]
Aortic regurgitation - Acute and Chronic
- Etiology
- Pathophysiology
- Presentation
- Examination
Aortic regurgitation = Aortic insufficiency - diastolic murmur
- Etiology
- aortic root dilatation - 1/2 of all cases
- bicuspid aortic valve
- postinflammatory (endocarditis, RF) - Pathophysiology - blood regurgitates from aorta into LV –> compensate with ↑ SV –> ↑ systemic systolic pressure
Acute AR: ↑ pressure of LV, then LA, then pulmonary venous system –> dyspnea and pulmonary edema
Chronic AR: volume overload –> LV compensates with eccentric hypertrophy –> reduces aortic (therefore systemic) diastolic pressure –> widened pulse pressure - Presentation - strong bounding pulses, head bobbing
- chronic AR: water-hammer pulses, capillary pulsations on nail beds - Examination - blowing decrescendo murmur at left sternal border
- (severe AR) Austin Flint murmur - mid-diastolic rumbling heard at cardiac apex (due to mitral flow)
[Valvular disease] Describe the following: 1. Tricuspid stenosis 2. Tricuspid regurgitation 3. Pulmonic stenosis 4. Pulmonic regurgitation
R side heart murmurs increase with inspiration and decrease with expiration (except for pulmonic valve click seen in pulmonic stenosis)
- Tricuspid stenosis - v rare, sequelae of rheumatic fever
- opening snap and diastolic rumbling murmur; intensifies on inspiration
- increased a wave on JVP - Tricuspid regurgitation - functional (due to RV enlargement); sequelae of rheumatic valvulitis (due to RF)
- holosystolic murmur that increases with inspiration, heard best at lower left sternal border
- pulsatile liver
- increased v wave on JVP - Pulmonic stenosis - congenital, systolic crescendo-decrescendo murmur heard best at 2nd L intercostal space with pulmonic valve click
- Pulmonic regurgitation - due to severe pulmonary HTN, high-pitched decrescendo murmur - sounds the same as aortic regurgitation
[Shock]
- Define shock
- Describe types of low cardiac output shock
- Describe types of distributive shock
- Shock - physiological state with insufficient 02 delivery to the tissues (hypoperfusion) –> cellular energy deficit (low ATP)
- people can be hypoperfused but maintain normal BP through compensatory mechanisms
BP = CO x SVR
- CO = SV * HR
Low CO shock due to problems with SV –> determined by myocardial contractility, preload, and afterload
A. Myocardial contractility –> cardiogenic shock
B. Preload
i. decrease in volume –> hypovolemic shock
ii. obstruction in filling –> Obstructive shock
C. Afterload –> PE
*Compensatory mechanism for low CO shock = tachycardia - Distributive shock due to problems with systemic vascular resistance
A. septic shock
B. neurogenic shock
C. anaphylactic shock
[Shock]
- ID 2 systemic compensatory responses to shock
- Explain how compensatory response correlates with clinical findings of shock
Shock –> hypotension –> compensation
1. Compensatory responses irreversible shock if they fail
A. Baroreceptor response - ↓ arterial pressure –> ↓ baroreceptor firing (aortic arch via CN X; carotid sinus via CN IX) –> synapse on nucleus solitarius (medulla) –> removes tonic inhibition of SNS –> activates SNS, inhibits PSNS –> ↑ vasoconstriction + ↑ HR and BP
B. RAAS (Renin-Angiotensin System) - renin release –> angiotensin II activation –> vasoconstriction and Na+ reabsorption (aldosterone)–> net water retention –> ↑ volume
- Compensatory response: Low CO –> divert blood flow from nonessential vascular beds e.g. skin, muscle, GI tract to heart and brain –> patient appears pale/gray, skin is cool/clammy; mental status changes (agitation, confusion)
- long capillary refill time + cold skin temperature + Livedo reticularis (mottled skin pattern) –> strong likelihood ratio of low CO/shock
- metabolic acidosis –> Tachypnea (compensatory respiratory alkalosis)
[Shock] Describe the types of low Cardiac Output shock: 1. Cardiogenic shock A. Etiology B. Pathophysiology C. Clinical findings
- Cardiogenic shock
A. Etiology - most common cause of pump failure is MI, but also myocarditis, arrhythmia, and valvular heart disease
- leading cause of death for patients with MI, esp STEMI
B. Pathophys: ischemia –> ↓ myocardial contractility –> ↓ CO –> ↓ BP –> ↓ coronary perfusion –> exacerbates ischemia –> worsens myocardial dysfunction –> death
C. Clinical findings
i. High filling pressures –> congestion –> elevation of JVP, pulmonary rales, wheezing, S3
ii. High PVR –> hypoperfusion –> mental status changes, cool/clammy skin, pale/gray, oliguria (low urine output)
iii. Low CO –> low mean arterial pressure (BP) –> tachycardia, faint pulses, PMI displaced laterally
[Shock] Describe the types of low Cardiac Output shock: 2. Hypovolemic shock A. Etiology B. Pathophysiology C. Clinical findings
- Hypovolemic shock
A. Etiology -
i. blood cell loss - hemorrhage due to trauma, post-op
ii. plasma volume loss - GI (cholera), burn
B. Pathophys: intravascular volume depletion –> ↓ preload –> ↓ CO –> ↓ BP
C. Clinical finding
- first sign is narrow pulse pressure due to ↑ peripheral vasoconstriction –> ↑ diastolic BP
- once 2+ L (40% circulating vol) is lost –> ↑ HR and ↓ systolic and diastolic BPs *however, cold + clammy skin is seen at 1L volume lost when HR and BP are still normal
i. Low filling pressure (bc of volume loss) –> clear lungs, normal heart sounds
ii. High PVR –> hypoperfusion –> mental status changes, cool/clammy skin, pale/gray,
iii. Low CO –> low mean arterial pressure (BP) –> tachycardia, faint pulses, PMI displaced laterally
[Shock] Describe the types of low Cardiac Output shock: 3. Obstructive shock I. Pericardial tamponade II. Tension pneumothorax
A. Etiology
B. Pathophysiology
C. Clinical findings
- Obstructive shock
A. Etiology
i. Pericardial tamponade - fluid accumulates within pericardium (which normally has a little fluid to accommodate heart beating)
ii. Tension pneumothorax - injury to lung –> air enters chest bw visceral and parietal pleura –> mediastinum shifts and lung collapses
B. Pathophys: impaired venous return (volume is normal but cannot get into heart) –> ↓ preload –> ↓ CO –> ↓ BP
C. Clinical findings
i. Pericardial tamponade: Beck’s triad of hypotension, muffled heart sounds, and JV distension
- also pulsus paradoxus –> big inspiratory drop in BP; normally small drop in bp but with ↑ pressure –> ↓ compliance in wall of heart –> interventricular septum shifts L –> impedes filling of the LV –> ↓ CO –> big BP drop
- also electrical alternans - morphology of QRS changes beat to beat on same lead –> heart is moving in the chest
- high filling pressure (like cardiogenic shock) but lungs clear
ii. Tension pneumothorax - absent breath sounds, JVD, tracheal/mediastinum deviation to contralateral side
[Shock] Describe types of distributive shock 1. Septic shock A. Etiology B. Pathophysiology C. Clinical findings
- Neurogenic shock
- Anaphylactic shock
Distributive shock - due to decreased systemic vascular resistance SVR; compensatory response is ↑ CO
- Septic shock - ↓ in peripheral vascular resistance
A. Etiology: caused by Gram (+) organisms –> endotoxins trigger release of inflammatory mediators –> problems
B. Pathophys: endothelial cell injury –> ↑ permeability of cell wall –> fluid can escape into the vasculature
- peripheral vasodilatation (NO) –> ↑ CO –> but impaired oxygen utilization
C. Clinical findings: fever, tachypnea
i. low filling pressure –> flat neck veins, tachycardia
ii. low PVR –> warm, dry skin; pink
iii. high CO –> but decreased mean arterial pressure bc of relative volume depletion
- Neurogenic shock - loss of SNS tone due to spinal cord injury
- Anaphylactic shock - due to release of vasodilators incl histamine, leukotriene C4, prostaglandin D2
- treat with epinephrine
[Heart Failure]
1. Describe Stages A-D and drugs prescribed at each stage
- Stage A: high risk for HF without structural disease or symptoms
- HTN, diabetes, obesity, metabolic syndrome, family history
Stage B: structural heart disease w/out devlpt of HF
- prior MI
- depressed LV EF, or LVH
- valvular heart disease
Stage C: structural heart disease with current or prior heart failure symptoms
- diuretics, then ACEI or ARB or BB
- digoxin if systolic dysfunction with afib or S3
Stage D: End-stage HF with refractory symptoms
- treatments are beyond BBs, CCBs –> transplant, hospice
- positive inotropes for palliation
[Heart Failure] Describe compensatory mechanisms in HF: 1. Frank-Starling mechanism 2. Neuro-hormonal activation 3. Natriuretic peptides 4. Ventricular hypertrophy and remodeling
- Frank-Starling mechanism - ↓ contractility –> ↓ SV –> ↑ LV EDV –> ↑ contractility
- Neuro-hormonal activation - body activates systems to maintain perfusion to vital organs (brain, heart, lungs); acutely beneficial but chronic bad (congestion, cardiac fibrosis)
- SNS - ↑ HR, contractility, peripheral vasoconstriction
- RAAS - ↓ CO –> ↓ renal perfusion –> ↑ renin –> Ang I (via angiotensinogen) –> Ang II (via ACE) –> ↑ SVR, ↑ intravascular volume
- ADH (posterior pituitary) - mediated by arterial baroreceptor and Ang II –> ↑ water retention in nephron - Natriuretic peptides - ANP and BNP
- produced in response to stretch –> ↑ Na+ and H20 excretion, promotes vasodilation, and inhibits renin
- counteracts RAAS
- ↑ BNP levels indicate HF - Ventricular hypertrophy and remodeling - ↑ wall thickness –> ↓ wall stress as per Laplace’s law where stress = P x R / 2h(thickness)
[Heart Failure]
Differentiate between R and L HF:
1. Symptoms
2. Physical findings
- Symptoms
A. LHF: from ischemic HD, HTN, myocardial diseases
i. Pulmonary congestion (due to ↑ LV EDV) –> SOB, orthopnea, leg edema, ↑ JVD, nocturnal cough
ii. Low CO –> fatigue, confusion, low urine output –> activates RAAS to increase volume
B. RHF: most commonly due to LHF; abdominal discomfort/distension, early satiety, weight gain
- can get isolated RHF from primary pulmonary HTN –> R sided hypertrophy and dilation (cor pulmonale)
- Physical findings - can present the same way!
A. LHF: rales, wheezing, tachypnea, tachycardia
- S3/S4, MR murmur
- weak pulse, diffuse apical impulse
- cachexia (wasting)
- pulmonary edema
R. RHF: RV heave
- R sided S3/S4
- ascites
- hepatic enlargement, portal hypertension, splenomegaly
- peripheral pitting edema
[Heart failure drugs] Diuretics 1. Loop diuretics 2. Thiazides 3. K+ sparing diuretics
Diuretics
- Loop diuretics (furosemide) - block NKCC2 in thick ascending limb; reduce ECF fluid volume and LV filling pressure (preload) –> reduce congestive symptoms
- hypokalemia - monitor K+ levels!
- hypomagnesia - Thiazides - block NCC in distal convoluted tubule; reduce BP –> reduce afterload and increase Na+ urinary excretion –> Reduce extracellular fluid volume
- hypokalemia, hypomagnesia, and hyponatremia - K+ sparing diuretics - ENaC blockers (amiloride) and aldosterone antagonists (spironolactone)
- spironolactone and eplerenone prevents cardiac fibrosis/remodeling induced by aldosterone + reduces mortality in heart failure
[Heart failure drugs] Vasodilators 1. ACE inhibitors 2. ARBs 3. BiDil 4. Aliskeren 5. Enestro 6. Nitrodilators
Vasodilators
- ACE inhibitors (enalopril, lisonopril)- block conversion of Ang I to Ang II –> ↓ vasoconstriction/ peripheral resistance –> ↓ afterload
- ↓ aldosterone secretion –> ↓ ECF –> ↓ preload
- action enhanced by diuretics / Na+ restriction
- adverse effects: cough, angioneurotic edema (due to decrease in degradation of bradykinin) - ARBs (sartans) - block Angiotensin II receptors
- same effects as ACEIs but do not cause cough or angioedema AND do not affect bradykinin
- not as effective in reducing mortality, so not first line - BiDil (hydralazine + isosorbide dinitrate) - for black patients
- Aliskeren - renin inhibitor; same side effects as ACEIs
- Enestro - inhibits neprilysin (breaks down natruiretics) and contains valsartan; in clinical trials, could replace ACEIs
- Nitroprusside - given IV for acte HF (dilates to ↑ CO)
[Heart failure drugs]
Beta blockers
Beta blockers
- v low dose BB to blunt the high levels of compensatory SNS effects (decrease arrhythmias, reduce remodeling)
- one of the earliest drugs you begin to introduce, sometimes before ACEI
- all drugs have similar efficacies - bisoprolol, carvedilol, metoprolol succinate
- adverse effects: bradycardia, hypotension, fatigue, can exacerbate acute decompensated heart failure
[Heart failure drugs] Inotropes 1. Cardiac glycosides 2. Beta1 agonists 3. Ca2+ sensitizers 4. Bypyridines
Inotropes
- Cardiac glycosides (digoxin, ouabain) - block Na/K pump –> ↑ [Ca+] in heart –> ↑ CO
- digitalis works well –> ↑ renal function (↓ preload), ↑ CO, ↓ heart size, ↓ EDV, ↓ venous pressure, ↓ SNS (↓ HR)
- digoxin used, ouabin is not (low lipid solubility)
- adverse effects: digitalis antagonized by K+ (has low TI) –> Arrhythmias; AV block, visual disturbances
- enhances vagal tone –> slows conduction velocity and increases refraction period - Beta1 agonists (dobutamine)- stimulates Beta1, beta2, and alpha receptors –> ↑ contractility but does not increase peripheral resistance (beta2 balances alpha) –> BP not affected
- norepi for warm septic shock
- epi for cardiac arrest - Ca2+ sensitizers - enhance ability of myosin to contract
- Bypyridines (milrinone, inamrinone) - PDE3 inhibitors –> prevent breakdown of cAMP to AMP –> increase contractility, HR, and also peripheral venous dilator
- safe for short-term, but can cause arrhythmias long-term
[Heart Failure] Acute Decompensated Heart Failure - describe the 4 types and their management: 1. Warm and dry 2. Warm and wet 3. Cold and wet 4. Cold and dry
2x2: Congestion at rest (orthopnea i.e. SOB on lying down, JVD, edema, ascites) x Low perfusion at rest (sleepy, hypotension with ACEI, narrow pulse pressure, low Na+)
- Warm and dry - No congestion x Normal perfusion
- stable chronic HF - what we want patients to be
- symptoms are from something else - Warm and wet - Congestion x Normal perfusion majority of patients
- diurese (furosemide, then thiazide)
- then add vasodilators to ↓ afterload and ↑ perfusion (esp with pulmonary edema or severe HTN) - Cold and wet - Congestion x Low perfusion
- warm up first (↑ perfusion) with inotropes (dobutomine, milrinone)
- then diuretics - Cold and dry - No congestion x Low perfusion (End stage)
- vasodilators if BP is okay; inotropes if BP is low
[Cardiomyopathy] I. Dilated cardiomyopathy 1. Etiology 2. Pathophysiology 3. Clinical findings
I. Dilated cardiomyopathy - dilated heart
- Etiology - many cases idiopathic or familial (AD), others include:
A. viral myocarditis eg coxsackie group B, parvovirus B19, adenovirus - young, previously healthy
- immune-mediated myocyte loss and fibrosis
- self-limited, supportive tx but 1/3 progress to HF
B. Toxins
- chronic alcohol use (5+ years) reversible - oxidative stress and apoptosis
- chemo agents - due to free radicals and apoptosis
C. Peripartum - multifactorial incl prolactin and oxidative stress, 50% recovery rate - Pathophysiology - ventricular dilatation with decreased contractile function and minimal hypertrophy
- myocyte degeneration and volume overload override compensation (↑ SV and SNS) –> ↓ contractility –> ↓ CO and ↑ ventricular filling pressures - Clinical findings - CHF symptoms eg systemic congestion (JVD, edema) and pulmonary congestion (dyspnea, rales)
- S3 (poor systolic function)
- leftward apical impulse displacement
- mitral regurgitation
[Cardiomyopathy] II. Hypertrophic cardiomyopathy 1. Etiology 2. Pathophysiology 3. Clinical findings
II. Hypertrophic cardiomyopathy
- Etiology - familial - AD with variable penetration; mutations in sarcomere genes
- Pathophysiology - LVH not caused by chronic pressure overload (eg HTN, aortic stenosis)
- most common is asymmetric septal hypertrophy
- normal LV systolic function but muscle is stiff (myocyte disarray and fibrosis)–> impaired ventricular compliance + high diastolic pressures –> impaired filling - Clinical findings - usually asymptomatic; most common etiology behind sudden death of young athletes –> prone to arrhythmias (Vfib/VT) due to myocyte disarray
- SOB from increased diastolic LV pressure
- S4 gallop due to contraction into stiff LV
[Cardiomyopathy] II. Hypertrophic cardiomyopathy 4. Describe LVOT obstruction in HCM 5. Differentiate from aortic stenosis 6. Treatment
II. Hypertrophic cardiomyopathy
- 1/4 patients have LV outflow tract obstruction by mitral leaflet –> ↑ LV pressure –> ↑ wall stress + ↑ 02 consumption –> angina
- worsened with ↓ preload (ventricles come together), ↓ afterload and ↑ contractility (heart contracts more vigorously with less resistance –> closer the walls come together)
- myocytes in disarray - Distinguishing HCM (systolic diamond-shape) murmur from aortic stenosis:
- does not radiate to carotids
- accompanied by mitral regurgitation MR (blowing holosystolic murmur)
- valsalva - ↑ HCM (↓ LV size) but ↓ aortic stenosis (↓ blood flow across aorta)
- squatting - ↓ HCM (↑ preload ↑ LV size) but ↑ aortic stenosis (↑ stroke volume)
- can differentiate by administering amyl nitrate (↓ preload and afterload –> makes HCM louder but AS softer) - Treatment:
- beta blockers “-olols” (negative inotrope) –> need to decrease HR so heart can fill
- avoid diuretics (causes dehydration –> ↓ preload), vasodilators (↓ afterload, also with alcohol and hot tub)
[Cardiomyopathy] III. Restrictive cardiomyopathy 1. Etiology 2. Pathophysiology 3. Clinical findings
III. Restrictive cardiomyopathy - abnormally rigid (but not thickened) ventricles –> diastolic dysfunction
- Etiology
- fibrosis/scarring of endomyocardium
- infiltration of myocardium eg amyloidosis (deposition of misfolded insoluble protein)
- primary (multiple myeloma), secondary (inflammatory condition eg RA), familial, or senile; stain with congo red - Pathophysiology - fibrosis/infiltration –> ↓ ventricle compliance –> ↑ diastolic pressure –>
A. ↑ atrial filling pressure –> ↑ systemic and pulmonary venous pressure
B. ↓ ventricle cavity size –> ↓ filling –> ↓ SV –> ↓ CO
- diastolic HF with preserved EF - Clinical findings - biatrial enlargement
- R HF»_space; L HF –> JVD (↑ with inspiration = Kussmaul sign), ascites, peripheral edema, hepatic congestion
- ↓ CO –> weakness, fatigue
- low voltage EKG
[Cardiomyopathy] IV. Arrhythmogenic cardiomyopathy V. Unclassified A. LV Non-compaction B. Stress-induced
- Etiology
- Pathophysiology
- Clinical findings
IV. Arrhythmogenic cardiomyopathy - affects RV as opposed to I-III (LV)
- Etiology - genetic - mutations in desmosomes; progressive
- Pathophysiology - replacement of RV myocardium with fatty and fibrotic tissue –> contractile dysfunction + ventricular arrhythmias
- Clinical findings - another cause of SCD among young athletes
- use cardiac MRI
V. Unclassified cardiomyopathy
A. LV non-compaction - genetic; arrested devlpt of myocardial compaction during fetal growth –> thick myocardium with trabeculae and recesses –> contractile dysfunction + HF + thromboemboli + Ventricular arrhythmias
B. Stress-induced cardiomyopathy - “broken heart syndrome” precipitated by emotional/physical stress
- transient apical ballooning –> chest pain, T wave inversion, troponin
- aka takotsubo (pot japanese catch octupus in)
[Vasculature Diseases]
- Define vasculitis
- Describe 2 main components of clinical presentation
- Vasculitis - immune-mediated, inflammatory destruction of blood vessels; v rare
- etiology unknown; classified by the pathological findings and types of arteries affected
- can present with:
A. T cell response with granuloma formation
B. Immune complex deposition
C. Anti-Neutrophil Cytoplasmic Antibodies (ANCAs) esp diseases that affect capillaries marker, not part of pathology
2A. Constitutional symptoms - fever, rash, myalgia, arthralgia, malaise, weight loss
B. Vascular injury symptoms - depend on vascular bed involved
- ischemia/infarction of affected organs –> thrombosis, fibrosis
[Vasculature Diseases] Giant cell arteritis 1. Pathology 2. Histology 3. Clinical
Giant cell arteritis - large vessel disorder; most common vasculitis in pts 50+, esp Europeans
- Pathology - affects L and M size extracranial branches of external carotid carotid artery e.g. vertebral, ophthalmic, temporal
- all layers of artery
- etiology unknown (infectious?) –> initiates CD4+ T-cell immune response –> monocytes coalesce into giant cells –> cytokine response - Histology - granuloma formation in the media (collection of multinucleated giant cells ie macrophages) –> internal elastic lamina fragmentation –> intimal thickening/fibrosis
- mononuclear cell infiltrates (T cells, that then draw in monocytes)
- skip lesions (not continuous) - need to take large piece when biopsying - Clinical - age 50+ with headache, jaw claudication (pain bc of decreased blood flow), visual symptoms
- scalp tenderness, temporal artery tenderness
- Lab: elevated erythrocyte sedimentation rate (indicates inflammatory process)
- optic nerve ischemia –> BLINDNESS (but v responsive to steroids ie prednisone)
[Vasculature Diseases] Takayasu's Arteritis 1. Pathology 2. Histology 3. Clinical
Takayasu’s Arteritis - large vessel disorder; affects young women 25-35 yo, esp Asian
- Pathology - granulomatous vasculitis of aortic arch; pathologically indistinguishable from Giant cell arteritis –> differs in arteries and people affected
- transmural (across entire wall) fibrous thickening of aortic arch –> narrowing of the major branches ESP subclavian - Histology same as giant cell arteritis
- granuloma formation in the media (collection of multinucleated giant cells ie macrophages) –> internal elastic lamina fragmentation –> intimal thickening/fibrosis
- -> thickening of vessel wall –> occlusion - Clinical
- systemic - fatigue, malaise, weight loss
- pulseless disease - asymmetric BP (upper vs lower extremities, R vs L, carotid vs brachial), bruits over and diminished pulses below subclavian
- pain with use of upper extremities
- renal HTN common
[Vasculature Diseases] Polyarteritis Nodosa 1. Pathology 2. Histology 3. Clinical
Polyarteritis Nodosa - medium artery disorder; affects adults 45-65
- does NOT affect arterioles, capillaries, veins –> NO pulmonary involvement, NO glomerulonephritis (RBC or casts)
- Pathology - necrotizing arteritis of medium/muscular arteries esp at branch points of vessels
- disruption of internal and external elastic lamina –> weakened arterial wall
- large arteries feeding into kidney most commonly affected
* linked to Hepatitis B Virus - Histology - lesions at different stages
- acute - transmural inflammation of arterial wall with fibrinoid necrosis
- healing stage - fibrosis/thickening –> nodule forms –> narrowing of vasculature –> impaired perfusion and ischemic atrophy
- neutrophils are big component (not T cells) - Clinical
- systemic inflammation - fever, myalgias, weight loss
- mononeuritis multiplex - asymmetric neurologic deficit (vasa nervosum - small nerve motor root ischemia)
- renal - HTN due to renal artery stenosis
- skin lesions - palpable purpura (damage to small arteries in dermis –> neutrophilic infiltration of small vessels –> extravasation of RBCs)
- treat with corticosteroid + cyclophosphamide
[Vasculature Diseases] Kwasaki disease 1. Pathology 2. Histology 3. Clinical
Kwasaki disease - medium artery disorder; patients under the age of 4 –> #1 cause of acquired heart disease in children
- Pathology - unknown
- neutrophil influx –> inflammatory response –> transmural intimal destruction –> aneurysms in coronary arteries
- or can remodel –> thrombotic occlusion –> myocardial ischemia - Histology - affects all arterial layers
- Clinical - CRASH and burn
Conjunctival erythema (red, irritated eyes)
Rash on trunk and genitals
Adenopathy - swollen neck lymph nodes
Strawberry tongue + cracked lips
Hand-food changes - Desequamation (peeling) of palms/soles of feet
+ burn - unremitting fever 5+ days in ALL patients, unresponsive to tylenol or NSAIDs
treat with immune globulin (IVIG) + aspirin
[Vasculature Diseases] Buerger disease 1. Pathology 2. Histology 3. Clinical
Buerger disease - aka thromboanginitis obliterans; heavy smokers, males under 40 yo
- Pathology - intermittent claudication associated with smoking
- Histology - segmental necrotizing vasculitis
- Clinical - gangrene –> autoamputation of digits
[Vasculature Diseases]
1. Peripheral arterial occlusive disease
A. Pathogenesis
B. Risk factors
2. Clinical presentation including intermittent claudication
A. Differentiate from pain due to spinal stenosis
3. Clinical findings
- Peripheral arterial occlusive disease (PAD) - flow-limiting stenotic lesion in artery that provides blood supply to limbs
A. commonly caused by atherosclerosis
- during exercise, blood flow increases 10x due to CO increase and compensatory vasodilation –> distal pressure even more reduced –> reduced perfusion to muscle groups distal to atherosclerotic lesion
B. pathology identical to coronary artery disease (risk factors: hyperlipidemia, HTN, smoking, DMII, FH)
- 1/2 patients with PAD have CAD - Clinical presentation
- most common manifestation is intermittent claudication (esp in lower extremities - angina in legs) –> pain with exertion due to reduced blood flow, ceases with standing in place and reproducible within same muscle groups (calf, thigh, etc)
- quantify in terms of street blocks walked
- location of pain determined by anatomical location of lesion e.g. in superficial femoral artery –> calf pain; aortoiliac area –> thigh and buttock pain, male ED
A. similar to neurogenic claudication caused by spinal stenosis –> except latter has discomfort on standing and pain is relieved by sitting down and flexing back - Clinical findings
- absent/diminished pulses eg no dorsalis pedis
- bilateral calf atrophy, shiny skin, hair loss below knees, thickened toe nails
- dependent rubor (peripheral arteries don’t constrict as they should bc ischemic –> hyperemia)
- ankle brachial index ABI- measure systolic bp in arms vs ankles –> normally, ankle pressure should be higher (bc of gravity) –> normally ABI 1+, decreases with arterial disease
- intervene on rest pain or non-healing wounds
[Vasculature Diseases]
Acute limb ischemia
1. pathogenesis
2. 5 P’ s of clinical findings
Acute limb ischemia - limb-threatening event
- Pathogenesis: most commonly due to emboli of cardiac origin –> lodge at artery bifurcations eg femoral artery, iliac, aorta, popliteal
2. 5 P's Pain - severe, acute onset Pulseless Paresthesias - nerves most quickly affected by ischemia Poikylothermia - cold extremities Paralysis - irrecoverable injury
Surgical emergency!
[Heart inflammation/Infection]
Infective endocarditis
1. Pathology
2. Risk factors
Infective endocarditis
- Pathology - microbial infection of heart endocardium (innermost surface + underlying structures) incl heart valves, mural endocardium (walls of the heart chambers)
- damaged endothelium –> platelet adhesion –> formation of vegetation (cluster of platelets, fibrin, cellular debris) –> bacteremia (infection eg dental procedure, contaminated needle) –> allows bacterial attachment and proliferation - Risk factors:
- age 60+, M
- poor dentition or dental infections –> organism is Strep viridans
- IV drug use (tricuspid) –> organism is Staph aureus
- structural heart disease (valvular, congenital)
- prosthetic valve or intravascular devices (catheters, pacemakers) –> organisms are Staph or HACEK
- colon cancer –> S. bovis
- used to be associated with rheumatic fever (post strep pharyngitis infection) in developing countries
[Heart inflammation/Infection] Infective endocarditis 3. Clinical presentation - acute vs subacute 4. Clinical diagnosis 5. Physical findings
- Clinical presentation
A. acute - systemic toxicity due to virulent (Staph aureus, strep pyogenes) attacking normal heart –> destruction of native valve + fatal
- acute onset fever, chills, CHF; hx eg prosthetic, IV drug use
B. subacute - indolent due to common (Strep viridans, enterococci) affecting abnormal heart e.g. structural or congenital heart disease
- fatigue, weight loss, low-grade fever - Clinical diagnosis -
new regurgitant murmur + recurrent/unremitting fever = endocarditis
5. Physical findings - FROM JANE Fever Roth spots Osler nodes (painful, on fingertips) Murmur Janeway lesions (painless, on palm/sole) Anemia Nailbed "splinter" hemorrhage Emboli (common with IV drug use) - can also have neurologic complications --> ischemic and hemorrhage stroke
[Heart inflammation/Infection] Myocarditis 1. Pathology 2. Clinical presentation 3. Etiology - infectious and non-infectious
Myocarditis
- Pathology - viral infection of myocardial cells –> inflammatory infiltrate (of lymphocytes) –> cytokine release –> necrosis and degeneration to adjacent myocytes –> dilated cardiomyopathy
- Clinical presentation - varied presentation but seen in otherwise healthy, young patients –> heart failure and ventricular arrhythmias –> cardiogenic shock
- need to exclude CAD, non-inflammatory diseases - Etiology
A. Noninfectious - cardiotoxic chemo agents
B. Infectious - most common = cardiotropic viruses (parvovirus, HHV6, Coxsackie A and B virus)
- also Borrelia, Trypanosoma cruzi (chagas)
[Heart inflammation/Infection] Lyme carditis Chagas 1. Pathology 2. Clinical presentation
Lyme carditis
- Pathology - caused by Borrelia burgdorferi –> lyme spirochetes directly invade tissues of the heart
- Clinical presentation - erythema migrans, rheumotologic (large joints), neurologic (facial nerve palsy) + palpitations, syncope, chest pain
- AV block (2nd or 3rd/complete)
Chagas disease
1. Pathology - Trypanasoma cruzi (protozoan) infection –> go into quiescent phase and cause chronic-immune mediated myocarditis –> cardiac insufficiency (cardiomyopathy) develops over time
[Heart inflammation/Infection] Acute rheumatic fever 1. Pathology 2. Clinical presentation 3. Differentiate between acute and chronic pathogenesis
Acute rheumatic fever -
- Pathology - autoimmune disease that is sequelae of Group A beta-hemolytic strep infection (eg strep pharyngitis “strep throat”)
- immune-mediated molecular mimicry (M protein is structurally similar to collagen –> Ab against collagen) –> NOT direct infection as with lyme carditis or chagas - Clinical presentation - most commonly children (5-15yo); JONES Criteria:
J-Joints –> polyarthritis (affects large joints) - presents first and disappears within 2-4 wks w no sequelae
O-heart problems –> carditis (SOB, DOE, chest pain), murmur
N-subcutaneous Nodules
E-Erythema marginatum (serpiginous, nonpruritic)
S-Sydenham chorea
In order of how common: carditis»_space; migratory polyarthritis –> chorea»_space; erythema and nodules
3A. Acute RF - Pan-carditis = inflammation of the entire heart (affects all the layers) –> can cause long-term disability (Systolic dysfunction) + death
i. endocarditis - causes mitral regurg
ii. myocarditis - pathognomonic is Aschoff bodies (due to lymphocytes)
iii. pericarditis - friction rub
B. Chronic RF - valvular changes 20+ years post ARF
- immune-mediated inflammatory process continues –> mitral “fishmouth” stenosis
[Pericardial disease]
- What is the pericardium
- Function of pericardium
- Pericarditis + etiology
- Clinical features of acute pericarditis
- Pericardium - membrane enclosing the heart, composed of visceral layer on top of epicardial muscle and parietal layer fused to fibrous pericardium (composed of collagen and elastin)
- Functions:
- limits motion of heart via attachments to diaphragm and mediastinum
- barrier - limits spread of infection from lungs
- fluid provides lubrication between visceral and parietal layers - Pericarditis - inflammatory disease of pericardium - acute or chronic
etiology - majority are idiopathic (probs viral)
- also infectious (viral, bacterial, fungal), non-infectious (post MI, uremia, lupus, trauma) - Clinical features:
- fever
- chest pain - pleuritic (aggravated by inspiration and coughing), and positional (relieved by sitting forward, worsened by lying down); radiates to trapezius ridge
- pericardial friction rub - extra heart sound with 3 components - ventricular systole, early diastolic filling, and atrial contraction
- EKG - diffuse ST segment elevation in ALL leads EXCEPT aVR and V1; PR segment depression
[Pericardial disease]
- Pericardial effusion + Clinical features
- Constrictive pericarditis + Clinical features
- Differences between pericardial tamponade and constrictive pericarditis
- Pericardial effusion - accumulation of fluid within the pericardial sac; increase in volume –> marked increase in pressure –> can compress heart chambers (pericardial tamponade) –> compromises CO
Clinical features:
- soft heart sounds
- reduced intensity of pericardial friction rub
- Ewart sign (dullness over posterior left lung bc of large heart)
- Constrictive pericarditis - post acute pericarditis –> fusion of pericardial layers –> fibrosis and calcification –> impaired diastolic filling
- commonly post radiation or surgery, or idiopathic
Clinical features:
i. reduced CO –> hypotension, fatigue, tachycardia
ii. elevated systemic venous pressures (backward RHF) –> JVD, hepatomegaly, ascites, peripheral edema
- pericardial knock - high - frequency S3 gallop –> increased y descent of pressure tracing (atrial pressure drop during diastole)
- kussmaul sign - JVD increases/worsens with inspiration
- R and L end diastolic pressures are the same (normally R is lower)
- Pulsus paradoxus in cardiac tamponade
- kussmaul sign on constrictive pericarditis
- equal L and R filling pressures in both
- JVP recording: absent y descent in tamponade (ventricular filling impaired), prominent y descent in constriction (y = Atrial pressure decrease during diastole)
