1
Q
Heart embryology
A
Embryonic structure—-> Gives rise to
- truncus arteriosus (TA)–> ascending aorta & pulmonary trunk
- bulbus cordis–> smooth parts (outflow tract) of left & right ventricles
- primitive ventricle–> trabeculated left & right ventricles
- primitive atria–> trabeculated left & right atria
- left horn of sinus venosus (SV)–> coronary sinus
- right horn of SV–> smooth part of right atrum
- right common cardinal vein & right anterior cardinal vein–> SVC
2
Q
Truncus arteriosus
A
- neural crest migration–> truncal & bulbar ridges that spiral & fuse to form the aorticopulmonary (AP) septum–>ascending aorta & pulmonary trunk
- Pathology: transposition of great vessels (failure to spiral), tetralogy of Fallot (skewed AP spetum development), perisistent TA (partial AP septum development)
3
Q
Interventricular septum development
A
- muscular ventricular septum forms. opening is called interventricular foramen
- AP septum rotates & fuses with muscular ventricular septum to form membranosus interventricular septum, closing interventricular foramen
- growth of endocardial cushions separates atria from ventricles and contributes to both atrial separation and membranous portion of the interventricular septum
Pathology: improper neural crest migration into the TA can result in transposition of the great arteries or a persistent TA.
-membranous septal defect causes an initial L-toR shunt shich later reverses to R-to-L shunt due to onset of pulmonary hypertension (Eisenmenger’s syndrome)
4
Q
Interarterial septum development
A
- foramen primum narrows as septum primum grows toward endocardial cushion
- perforations in septum primum form foramen secundum (foramen primum disappears)
- foramen secundum maintains R-to-L shunt as septum secundum begins to grow
- septum secundum contains a permanent opening (foramen ovale)
- foramen secundum enlarges and upper part of septum primum degenerates
- remaining portion of septum primum forms valve of foramen ovale
- Septum secundum and septum primum fuse to form the atrial septum
- foramen ovale usually closes soon after birth because of the increase LA pressure
Pathology: patent foramen ovale, caused by failure of the septum primum and septum secundum to fuse after birth
5
Q
fetal erythropoiesis
A
-fetal erythropoiesis occurs in: Yolk sac (3-10wks) Liver (6wks-birth) Spleen (15-30 wks) Bone marrow (22 wks to adult) ** Young Liver Synthesizes Blood Fetal hemoglobin= alpha2gamma2 Adult hemoglobin= alpha2beta2
6
Q
Fetal circulation
A
- Blood in umbilical vein has a PO2 of 30mmHg and is 80% saturated with O2
- umbilical arteries have low O2 saturation
- 3 important shunts
1. blood entering the fetus through the umbilical vein is conducted via the ductus venous into the IVC to bypass the hepatic circulation
2. most oxygenated blood reaching the heart via the IVC is diverted through the foramen ovale and pumped out the aorta to the head and body
3. deoxygenated blood entering the RA from the SVC enters the RV is expelled into the pulmonary artery, then passes through the ductus arterious into the descending aorta - at birth infant takes a breath; decrease resistance in pulmonary vasculature causes increase left atrial pressures vs. right atrial pressure; foramen ovale closes (now called fossa ovalis); increase O2 leads to decrease prostaglandins, causing closure of ducts arteriosus
- indomethacin helps close PDA
- prostaglandins E1 E2 keep PDA open
7
Q
Fetal-postnatal derivatives
- umbilical vein
- umbilical arteries
- ductus arterious
- ductus venous
- foramen ovale
- allantois
- notochord
A
- umbilical vein–>ligamentum teres hepatis; contained in falciform ligament
- umbilical arteries–> medial umbilical ligaments
- ductus arterious–>ligamentum arteriosum
- ductus venous–> ligamentum venosum
- foramen ovale–> fossa ovalis
- allantois–> urachus-median umbilical ligament; urachus is the part of the allantoic duct btw bladder & umbilicus. Urachal cyst or sinus is a remnant
- notochord–> nucleus pulposus of intervertebral disc
8
Q
Coronary artery anatomy
A
- SA & AV nodes are usually supplied by RCA
- Right dominant circulation= 85%=PD arises from RCA
- Left dominant circulation=8%=PD arises from LCX
- Codominant circulation=7%=PD arises from both LCX & RCA
- Coronary artery occlusion most commonly occurs in the LAD
- coronary arteries fill during diastole
- The most posterior part of the heart is the left atrium; enlargement can cause dysphagia (due to compression of the esophagus) or hoarseness (due to compression of the left recurrent laryngeal nerve, a branch of the vagus).
- Transesophageal echocardiography is useful for diagnosing left atrial enlargement, aortic dissection, thoracic aortic aneurysm.
9
Q
Cardiac output
A
-CO= stroke vol (SV) x HR
-Fickle principle:
CO= rate of O2 consumption/arterial O2 content- venous O2 content
-mean arterial pressure (MAP)= CO x total peripheral resistance
-MAP= 2/3 diastolic pressure + 1/3 systolic pressure
-pulse pressure= systolic pressure-diastolic pressure
-pulse pressure similar to stroke volumber (?)
-SV=CO/HR=EDV-ESV
-during the early stages of exercise, CO is maintained by increase HR and increase SV
-during the late stages of exercise, CO maintained by increase HR only (SV plateau)
-If HR is too high, diastolic filling is incomplete and CO decrease (ventricular tachy)
10
Q
cardiac output variables
A
- stroke vol affected by contractility, afterload, preload. Increase SV when increase preload, decrease afterload, increase contractility
- ***SV CAP
- contractility (and SV) increase with:
- catecholamines (increase activity of Ca2+ pump in sacroplasmic reticulum)
- increase intracellular Ca2+
- decrease extracellular NA+ (decrease activity of Na+/Ca2+ exchanger)
- digitalis (blocks NA+/K+ pump)–> increase intracellular Na+–> decrease Na+/Ca2+ exchanger activity–> increase intracellular Ca2+ - contractility (and SV) decrease with:
- beta 1 blockade (decrease cAMP)
- heart failure (systolic dysfunction)
- acidosis
- hypoxia/hypercapnea (decrease PO2/increase PCO2)
- non-dihydropyridine Ca2+ channel blockers
- SV increase in anxiety, exercise, pregnancy
- failing heart had decrease SV
- myocardial O2 demand is increase by:
1. increase (inc) afterload (arterial pressure)
2. inc contractility
3. inc HR
4. inc heart size (increase wall tension)
11
Q
preload & afterload
A
- preload=ventricular EDV
- afterload=mean arterial pressure (proportional to peripheral resistance)
- vEnodilators (nitroglycerin) decr preEload
- vAsodilators (hydrAlazine) decr Afterload (arterial)
- preload incr with:
1. exercise (slightly)
2. incr blood vol (overtransfusion)
3. excitement (incr sympathetic activity)
12
Q
Starling curve
A
- force of contraction is proportional to end diastolic length of cardiac muscle fiber (preload)
- increase contractility with sympathetic stimulation, catecholamines, digoxin
- decr contractility with loss of myocardium (MI), beta-blocker, calcium channel blockers
13
Q
Ejection fraction (EF)
A
EF= SV/EDV=EDV-ESV/EDV
- EF is an index of ventricular contractility
- EF is normally > or = 55%
- EF decr in systolic heart failure
14
Q
Resistance, pressure, flow
A
change of P= Q x R
- similar to Ohm’s law: change of V=IR
- resistance= driving pressure (delta P)/ flow (Q)= 8n (viscosity) x length/pi x r^4
- total resistance of vessel in series= R1 + R2 + etc
- 1/total resistance in parallel
- viscosity depends mostly on hematocrit
- viscosity increase in:
1. polycythemia
2. hyperproteinemic states (multiple myeloma)
3. hereditary spherocytosis - viscosity decrease in anemia
- pressure gradient drives flow from high pressure to low pressure
- resistance is directly proportional to viscosity and vessel length and inversly proportional to radius to 4th power
- arterioles account for most total peripheral resistance–> regulate capillary flow
15
Q
Cardiac cycle
A
Phases left ventricle:
- isovolumetric contraction-period btw mitral valve closure and aortic valve opening; period of highest O2 consumption
- systolic ejection-period btw aortic valve opening and closing
- isovolumetric relaxation-period btw aortic valve closing and mitral valve opening
- rapid filling- period just after mitral valve opening
- reduced filling-period just before mitral valve closure
Sounds:
- S1- mitral & tricuspid valve closure. Loudest at mitral area
- S2- aortic & pulmonary valve closure. Loudest at left sternal border
- S3- in early diastole during rapid ventricular filling phase. Associated with increase filling pressures (mitral regurgitation, CHF) and more common in dilated ventricles (but normal in children and pregnant women)
- S4- :atrial kick” in late diastole. HIgh atrial pressure. Associated with ventricular hypertrophy. L atrium must push against stiff LV wall.
16
Q
Splitting
- normal splitting
- wide splitting
- foxed splitting
- paradoxical splitting
A
- normal splitting
- inspiration–>drop in intrathoracic pressure–> increase venous return to the RV–> increased RV stroke vol–> increase RV ejection time–> delayed closure of pulmonic valve
- decrease pulmonary impedance (increase capacity of the pulmonary circulation) also occurs during inspiration, which contributes to delayed closure of pulmonic valve - wide splitting
- seen in condition that delay RV emptying (pulmonic stenosis, right bundle branch block)
- delay in RV empyting causes delayed pulmonic sound (regardless of breath)
- an exaggeration of normal splitting - foxed splitting
- seen in ASD–>L to R shunt–> incr RA & RV vol–> incr flow through pulmonic valve such that, regardless of breath, pulmonic closure is greatly delayed - paradoxical splitting
- seen in conditions that delay LV empyting (aortic stenosis, left bundle branch block)
- normal order of valve closure is reversed so that P2 sound occurs before delayed A2 sound
- on inspiration, P2 closes later and moves closer to A2, thereby paradoxically eliminating the split
17
Q
auscultation of the hear
“where to listen: APT M”
A
1.Aortic area: systolic murmur -aortic stenosis -flow murmur -aortic valve sclerosis 2. Left sternal border Diastolic murmur -aortic regurgitation -pulmonic regurgitation systolic murmur -hypertrophic cardiomyopathy 3. Pulmonic area: systolic ejection murmur -pulmonic stenosis -flow murmur (atrial septal defect, patent ductus arteriosus) 4. Tricuspid area Pansystolic murmur -tricuspid regurgitation -ventricular septal defect Diastolic murmur -tricuspid stenosis -atrial septal defect 5. Mitral area systolic murmur -mitral regurgitation Diastolic murmur -mitral stenosis
18
Q
Bedside maneuver—> effects
- inspiration
- expiration
- hand grip (increase systemic vascular resistance)
- valsalva (decr venous return)
- rapid squatting (incr venous return, incr preload, incr afterload with prolonged squatting)
A
- inspiration= incr intensity of R heart sounds
- expiration= incr intensity of L heart sounds
- hand grip (increase systemic vascular resistance)= incr intensity of MR, AR, VSD, MVP murmurs
- valsalva (decr venous return)= decr intensity of most murmurs
- rapid squatting (incr venous return, incr preload, incr afterload with prolonged squatting)= decr intensity of MVP, hypertrophic cardiomyopathy murmurs
- systolic heart sounds include aortic/pulmonic stenosis, mitral/tricuspid regurgitation, ventricular septal defect
- diastolic heart sounds include aortic/pulmonic regurgitation, mitral/tricuspid stenosis
19
Q
Heart murmurs: systolic
1. mitral/tricuspid regurgitation (MR/TR)
A
- mitral/tricuspid regurgitation (MR/TR)
- holosystolic, high-pitched blowing murmur
- mitral-loudest at apex and radiates toward axilla
- enhanced by maneuvers that incr TPR (squatting, hand grip) or LA return (expiration)
- MR often due to ishcemic heart disease, mitral valve prolapse, LV dilation
- tricupsid-loudest at tricuspid area and radiates to R sternal border
- enhanced by maneuvers that incr RA return (inspiration)
- TR can be caused by RV dilation
- Rheumatic fever and infective endocarditis can cause either MR or TR
20
Q
Heart murmurs: systolic
2. aortic stenosis (AS)
A
- aortic stenosis (AS)
- crescendo-decrescendo systolic ejection murmur following ejection click (EC; due to abrupt halting of valve leaflets)
- LV» aortic pressure during systole
- radiates to carotids/heart base
- pulsus parvus et tardus - pulses are weak with a delayed peak.
- can lead to syncope, angina, dyspnea on exertion (SAD)
- often due to age-related calcific aortic stenosis or bicuspid aortic valve
21
Q
Heart murmurs: systolic
3. VSD
A
- VSD
- holosystolic, harsh sounding murmur
- loudest at tricuspid area, accentuated with hand grip maneuver due to increased afterload
22
Q
Heart murmurs: systolic
4. mitral valve prolapse (MVP)
A
- mitral valve prolapse (MVP)
- late systolic crescendo murmur with midsystolic click (MC; due to sudden tensing of chordae tendinaea)
- most frequent valvular lesion
- best heard over apex
- loudest at S2
- usually benign
- can predispose to infective endocarditis
- can be caused by myxomatous degeneration, rhematic fever, chordae rupture
- enhanced by maneuvers that decr venous return (standing or Valsalva)
23
Q
Heart murmurs: diastolic
1. aortic regurgitation (AR)
A
- immediate high pitched “blowing” diastolic decrescendo murmur
- wide pulse pressure when chronic; can present with bounding pulses and head bobbing
- often due to aortic root dilation, bicuspid aortic valve, endocarditis, rheumatic fever
- incr murmur during hand grip
- vasodilators decr intensity of murmur
24
Q
Heart murmurs: diastolic
2. mitral stenosis (MS)
A
-follows opening snap (OS; due to abrupt halt in leaflet tips)
-delayed rumbling late diastolic murmur
LA» LV pressure during diastole
-often occurs secondary to rheumatic fever
-chronic MS can result in LA dilation
-enhanced by maneuvers that incr LA return (expiration)
25
Heart murmurs: continuous
| PDA
- continuous machine-like murmur
- loudest at S2
- often due to congenital rubella or prematurity
- best heard at left infraclavicular area
26
ventricular action potential
| -4 phases
-also occurs in bundle of His & Purkinjie fibers
Phase 0-= rapid upstroke-voltage gated Na+ channels open
Phase 1= initial repolarization-inactivation of voltage-gated Ca2+ channels balances K+ efflux
-Ca2+ influx triggers Ca2+ release from sarcoplasmic reticulum and myocyte contraction
Phase 3= rapid repolarization- massive K+ efflux due to opening of voltage-gated slow K+ channels and closure of voltage-gated Ca2+ channels
Phase 4= resting potential- high K+ permeability through K+ channels
- in contrast to skeletal muscle:
1. cardiac muscle AP has a plateau, which is due to Ca2+ influx & K+ efflux, myocyte contraction occurs due to Ca2+ induced Ca2+ release from the sacroplasmic reticulum
2. cardiac nodal cells spontaneously depolarize during diastole resulting in automaticity due to I (f) channels ("funny current" channels responsible for a slow mixed Na+/K+ inward current)
3. Cardiac myocytes are electrically coupled to each other by gap junctions
27
Pacemaker action potential
Occurs in SA & AV nodes. Key differences from the ventricular action potential include:
1. Phase 0= upstroke-opening voltage-gated Ca2+ channels are permanently inactivated because of the less negative resting voltage of these cells. Results in a slow conduction velocity that is used by AV node to prolong transmission from the atria to ventricles
2. Phase 2= plateau is absent
3. Phase 3= inactivation of Ca2+ channels and incr activation of K+ channels--> incr K+ efflux
4. Phase 4= slow diastolic depolarization- membrane potential spontaneously depolarizes as Na+ conductance incr (I f different from N Na in phase 0 of ventricualr AP)
- accounts for automaticity of SA and AV node
- the slope of phase 4 in SA node determines HR ACh/adenosine decr rate of diastolic depolarization and decr HR, while catecholamines incr depolarization and incr HR
- sympathetic stimulation incr chance that I f channels are open and thus incr HR
28
torsades de pointes
- ventricular tachy, characherize by shifting sinusoidal waveforms on ECG, can progress to ventricular fibrillation
- anything that prolongs OT interval can predispose to torsades de pointes
- treatment includes magnesium sulfate
- congenital long QT syndromes are most often due to defects in cardiac sodium or potassium channels
- can present with severe congenital sensorineural deafness= Jervell & Lange-Nielson Syndrome
29
Atrial fibrillation
chaotic & erratic basline (irregularly irregular) with no descrete P waves in btw irregularly spaced ORS complexes
- can result in atiral stasis and lead to stroke
- treatment includes rate control, anticoagulation, possible cardioversion
30
atrial flutter
- rapid succession of identical, back-to-back depolarization waves
- identical appearance accounts for the "sawtooth appearance of flutter waves
- pharmacologic conversion to sinus rhythm: class IA, IC, III antiarrhythmics
- rate control: beta blocker or calcium channel blocker
31
ventricular fibrillation
completely erratic rhythm with no identifibale waves
| -fatal arrhythmia w/o immediate CPR & defibrillation
32
AV block:
- 1 st degree
- 2nd degree (Mobitz type I or Wenckebach
- Mobitz II
- 3rd degree
1st degree
- PR interval is prolonged (>200 msec)
- asymptomatic
2nd degree
- progressive lengthening of PR interval until a beat is dropped (P wave not followed by a ORS complex)
- usually asymptomatic
Mobitz type II
- dropped beats that are not preceded by a change in the length of PR interval (as in type I)
- abrupt, nonconducted P waves result in a pathologic condition
- often found as 2:1 block, where there are 2 or more P waves to 1 QRS response
- may progress to 3rd degree block
- often treated with pacemaker
3rd degree
- atria & ventricles beat independently of each other
- both P waves & QRS complexes are present, although P waves bear no relation to QRS cmplexes
- atrial rate is faster than ventricular rate
- usually treated with pacemaker
- lyme disease can result in 3rd degree heart block
33
atrial natriuretic peptide
- ANP is released from atrial myocytes in respponse to increase blood volume and atrial pressure
- causes generalized vascular relaxation and decrease Na+ reabsorption at the medullary collecting tubule
- constricts efferent renal arterioles and dilates afferent arterioles (cGMP mediated), promoting diuresis and contributing to the escape from aldosterone mechanism
34
Baroreceptors & chemoreceptors
Receptors:
- aortic arch transmits via vagus nerve to solitary nucleus of medulla (responds only to inc BP)
- carotid sinus transmits via glossopharyngeal nerve to solitary nucleus of medulla (responds to decr & incr in BP)
Baroreceptors
1. hypotension
- decr arterial pressure--> decr stretch--> decr afferent baroreceptor firing--> incr efferent sympathetic firing and decr efferent parasympathetic stimulation--> vasoconstriction, inc HR, incr contractility, incr BP
- important in the response to severe hemorrhage
2. carotid massage
- incr pressure on carotid artery--> incr stretch--> incr afferent baroreceptor firing--> decr HR
3. contributes to Cuhsing reaction (triad of hypertension, bradycardia, respiratory depression)
- incr intracranial pressure constricts arterioles --> cerebral ischemia & reflex sympathetic increase in perfusion pressure (hypertension)--> incr stretch--> reflex baroreceptor induced-bradycardia
Chemoreceptors
1. peripheral
- carotid & aortic bodies are stimulated by decr PO2 (<60mmHg), incr PCO2, decr pH of blood
2. Central
- stimulated by changes in pH and PCO2 of brain interstitial fluid which in turn are influenced by arterial CO2
- do not directly respond to PO2
35
circulation through organs
1. lung
2. liver
3. kidney
4. heart
1. lung-organ with largest blood flow (100% of Cardiac output)
2. liver- largest share of systemic cardiac output
3. kidney- highest blood flow per gram of tissue
4. heart- largest arteriovenous O2 difference because O2 extraction is 80%
- therefore incr O2 demand is met by incr coronary blood flow, not by incr extraction of O2
36
normal pressure
PCWP
- pulmonary capillary wedge pressure (in mmHg) is good approximation of left atrial pressure
- in mitral stenosis, PCWP > LV diastolic pressure
- measured with pulmonary artery catheter (Swan-Ganz catheter)
37
Autoregulation:
1. heart
2. brain
3. kidneys
4. lungs
5. skeletal muscle
6. skin
Autoregulation: how blood flow to an organ remains constant over a wide range of perfusion pressures
factors determing autoregulation
1. heart- local metabolites (vasodilatory) CO2, adenosine, NO
2. brain- local metabolites (vasodilatory) CO2 (pH)
3. kidneys- myogenic and tubuloglomerular feedback
4. lungs- hypoxnia causes vasocontriction
5. skeletal muscle- local metabolites- lactate, adenosine, K+
6. skin- sympathetic stimulation most important mechanism- temperature control
Note: the pulmonary vasculature is unique in that hypoxia causes vasoconstriction so that only causes vasodilationwell-ventilated areas are perfused. In other organs, hypoxia
38
Capillary fluid exchange
Starling forces determine fluid movement through capillary membranes:
1. Pc= capillary pressure- pushes fluid out of capillary
2. Pi= interstitial fluid pressure- pushes fluid into capillary
3. (symbol pi c)= plasma colloid osmotic pressure- pulls fluid into capillary, thus net filtration pressure= Pnet= [(Pc-Pi)]- (PIc-PIi)
```
Kf= filtration constant (capillary permeability)
Jv= net fluid flow= (Kf)(Pnet)
```
Edema-excess fluid outflow into interstitium commonly caused by:
1. incr capillary pressure (incr Pc; heart failure)
2. decr plasma proteins (decr pi c; nephrotic syndrome, liver failure)
3. incr capillary permeability (incr Kf; toxins, infections, burns)
4. incr interstitial fluid colloid osmotic pressure (incr pi i; lympathatic blockage)
39
Congenital heart disease:
Right-to-left shunts (early cyanosis)- "blue babies"
The 5 T's:
1. Tetralogy
2. Transposition
3. Truncus
4. Tricuspid
5. TAPVR
1. Tetralogy of Fallot (most common cause of early cyanosis)
2. Transposition of great vessels
3. Persistent Truncus arteriosus- failure of truncus arteriosus to divide into pulmonary trunk & aorta; most pts have accompanying VSD
4. Tricuspid atresia- characterized by absence of tricuspid valve and hypoplastic RV; requires both ASD & VSD for viability
5. Total anomalous pulomary venous return (TAPVR)- pulomonary veins drain into right heart circulation (SVC, coronary sinus, etc); associated with ASD and sometimes PDA to allow for R-to-L shunting to maintain CO
40
Congenital heart disease:
Left-to_right shunts (late cyanosis)- "blue kids"
- VSD (most common congenital cardiac anomaly)
- ASD (loud S1; wide, fixed split S2)
- PDA (close with indomethacin)
Frequency: VSD> ASD> PDA
41
Eisenmenger's syndrome
- uncorrected VSD, ASD, PDA causes compensatory pulmonary vascular hypertrophy, which results in progressive pulmonary hypertension
- as pulmonary resistance incr, shunt reverses from L-to-R to R-to-L, which causes late cyanosis, clubbing, polycythenia
42
tetralogy of fallot
- tetralogy of fallot is caused by anterosuperior displacement of the infundibular septum
1. Pulmonary infundibular stenosis (most important determinant for prognosis)
2. RVH
3. Overriding aorta (overrides the VSD)
4. VSD
**PROVe
- early cyanosis (tet spells) caused by a R-to-L shunt across the VSD
- isolated VSDs usually flow L-to-R (acyanotic)
- in tetralogy, pulomary stenosis forces r-to-L (cyanotic) flow and causes RVH (on x-ray, boot-shaped heart)
Older patients historically learned to squat to relieve cyanotic symptoms. Squatting reduced blood flow to the legs, incr peripheral vascular resistance (PVR), and thus decr cyanotic R-to-L shunt across the VSD. Preferred treatment is early, primary surgical correction
43
D-transposition of great vessels
- Aorta leaves RV (anterior) and pulmonary trunk leaves LV (posterior)--> separation of systemic & pulmonary circulations.
- not compatible with life unless a shunt is present to allow adequate mixing of blood (eg. VSD, PDA, patent foramen ovale)
- due to failure of the aorticopulmonary septum to spiral
- without surgical correction, most infants die within the first few months of life
44
Coarctation of the aorta
1. infantile type
2. adult type
can result in aortic regurgitation
1. infantile type
- aortic stenosis proximal to insertion of ductus arteriosus (preductal)
- associated with Turner syndrome
- infantile: in close to the heart
- check femoral pulses on physical exam
2. adult type
- stenosis is distal to ligamentum arteriosum (postductal)
- associated wtih notching of the ribs (due to collateral circulation), hypertension in upper extremities, weak pulses in lower extremities
- adult: distal to ductus
- most commonly associated with bicuspid aortic valve
45
Patent ductus arteriosus
- in fetal period , shunt is R-to-L (normal)
- in neonatal period, lung resistance decr and shunt becomes L-to-R with subsequent RVH and/or LVH and failure (abnormal)
- associated with a continous, "machine-like" murmur
- patency is maintained by PGE synthesis and low O2 tension
- uncorrected PDA can eventually result in late cyanosis in the lower extremities (differential cyanosis)
- endomethacin (indomethacin) ends patency of PDA; PGE kEEps it open (may be necessary to sustain life in conditions such as transposition of great vessels)
- PDA is normal in utero and normally closes only after birth
46
Congenital cardiac defect associations
| Disorder & Defect
1. 22q11 syndrome- truncus arteriosus, tetralogy of Fallot
2. Down syndrome- ASD, VSD, AV septal defect (endocardial cushion defect)
3. congenital rubella- septal defects, PDA, pulomary artery stenosis
4. turner syndrome- coarctation of aorta (preductal)
5. Marfan's syndrome- aortic insufficiency and dissection (late complication)
6. infant of diabetic mother- transposition of great vessels
47
Hypertension
- defined as BP> or equal 140/90 mmHg
- risk factors: incr age, obesity, diabetes, smoking, genetics, black>white>asian
- features: 90% of hypertension is primary (essential) and related to incr CO or incr TPR; remaining 10% mostly secondary to renal disease.
- Malignant hypertension is severe (>180/120mmHg) and rapidly progressing
- predisposes to- atherosclerosis, left ventricular hypertrophy, stroke, CHF, renal failure, retinopathy, aortic dissection
48
Hyperlipidemia signs
1. Atheromas-plagues in blood vessel walls
2. xanthomas- plagues or nodules composed of lipid-laden histiocytes in the skin, especially the eyelids (xanthelasma)
3. tendinous xanthoma- lipid deposit in tendon, especially Achilles
4. corneal arcus- lipid deposit in cornea, nonspecific (arcus senilis)
49
arteriosclerosis
1. Monckeberg
2. Arteriolosclerosis
3. Atherosclerosis
1. Monckeberg-
2. Arteriolosclerosis
3. Atherosclerosis
50
Coarctation of the aorta
1. infantile type
2. adult type
can result in aortic regurgitation
1. infantile type
- aortic stenosis proximal to insertion of ductus arteriosus (preductal)
- associated with Turner syndrome
- infantile: in close to the heart
- check femoral pulses on physical exam
2. adult type
- stenosis is distal to ligamentum arteriosum (postductal)
- associated wtih notching of the ribs (due to collateral circulation), hypertension in upper extremities, weak pulses in lower extremities
- adult: distal to ductus
- most commonly associated with bicuspid aortic valve
51
Patent ductus arteriosus
- in fetal period , shunt is R-to-L (normal)
- in neonatal period, lung resistance decr and shunt becomes L-to-R with subsequent RVH and/or LVH and failure (abnormal)
- associated with a continous, "machine-like" murmur
- patency is maintained by PGE synthesis and low O2 tension
- uncorrected PDA can eventually result in late cyanosis in the lower extremities (differential cyanosis)
- endomethacin (indomethacin) ends patency of PDA; PGE kEEps it open (may be necessary to sustain life in conditions such as transposition of great vessels)
- PDA is normal in utero and normally closes only after birth
51
Patent ductus arteriosus
- in fetal period , shunt is R-to-L (normal)
- in neonatal period, lung resistance decr and shunt becomes L-to-R with subsequent RVH and/or LVH and failure (abnormal)
- associated with a continous, "machine-like" murmur
- patency is maintained by PGE synthesis and low O2 tension
- uncorrected PDA can eventually result in late cyanosis in the lower extremities (differential cyanosis)
- endomethacin (indomethacin) ends patency of PDA; PGE kEEps it open (may be necessary to sustain life in conditions such as transposition of great vessels)
- PDA is normal in utero and normally closes only after birth
52
Congenital cardiac defect associations
| Disorder & Defect
1. 22q11 syndrome- truncus arteriosus, tetralogy of Fallot
2. Down syndrome- ASD, VSD, AV septal defect (endocardial cushion defect)
3. congenital rubella- septal defects, PDA, pulomary artery stenosis
4. turner syndrome- coarctation of aorta (preductal)
5. Marfan's syndrome- aortic insufficiency and dissection (late complication)
6. infant of diabetic mother- transposition of great vessels
52
Congenital cardiac defect associations
| Disorder & Defect
1. 22q11 syndrome- truncus arteriosus, tetralogy of Fallot
2. Down syndrome- ASD, VSD, AV septal defect (endocardial cushion defect)
3. congenital rubella- septal defects, PDA, pulomary artery stenosis
4. turner syndrome- coarctation of aorta (preductal)
5. Marfan's syndrome- aortic insufficiency and dissection (late complication)
6. infant of diabetic mother- transposition of great vessels
53
Hypertension
- defined as BP> or equal 140/90 mmHg
- risk factors: incr age, obesity, diabetes, smoking, genetics, black>white>asian
- features: 90% of hypertension is primary (essential) and related to incr CO or incr TPR; remaining 10% mostly secondary to renal disease.
- Malignant hypertension is severe (>180/120mmHg) and rapidly progressing
- predisposes to- atherosclerosis, left ventricular hypertrophy, stroke, CHF, renal failure, retinopathy, aortic dissection
53
Hypertension
- defined as BP> or equal 140/90 mmHg
- risk factors: incr age, obesity, diabetes, smoking, genetics, black>white>asian
- features: 90% of hypertension is primary (essential) and related to incr CO or incr TPR; remaining 10% mostly secondary to renal disease.
- Malignant hypertension is severe (>180/120mmHg) and rapidly progressing
- predisposes to- atherosclerosis, left ventricular hypertrophy, stroke, CHF, renal failure, retinopathy, aortic dissection
54
Hyperlipidemia signs
1. Atheromas-plagues in blood vessel walls
2. xanthomas- plagues or nodules composed of lipid-laden histiocytes in the skin, especially the eyelids (xanthelasma)
3. tendinous xanthoma- lipid deposit in tendon, especially Achilles
4. corneal arcus- lipid deposit in cornea, nonspecific (arcus senilis)
54
Hyperlipidemia signs
1. Atheromas-plagues in blood vessel walls
2. xanthomas- plagues or nodules composed of lipid-laden histiocytes in the skin, especially the eyelids (xanthelasma)
3. tendinous xanthoma- lipid deposit in tendon, especially Achilles
4. corneal arcus- lipid deposit in cornea, nonspecific (arcus senilis)
59
arteriosclerosis
| 1. Monckeberg
- calcification in the media of arteries, especially radial or ulnar.
- usually benign "pipestem" arteries
- does not obstruct blood flow; intima not involved
60
arteriosclerosis
| 2. Arteriolosclerosis
two types:
1. hyaline- thickening of small arteries in essential hypertension or DM
2. hyperplastic- onion skinning in malignant hypertension
61
arteriosclerosis
| 3. Atherosclerosis
firbous plagues and atheromas form in intima of arteries
62
what is atherosclerosis & risk factors
-disease of elastic arteries and large and medium sized muscular arteries
-risk modifiable:
1. diabetes
2. smoking
3. HTN
4. hyperlipidemia
-nonmodifiable
1. age & gender
increase in men and postmenopausal xx
2. positive family hx
63
atherosclerosis: progression
- inflammation important in pathogenesis
1. endothelial cell dysfunction-
2. macrophage & LDL accumulation
3. foam cell formation
4. fatty streaks
5. smooth muscle cell migration (PDGF &FGF)
6. proliferation & extracellular matrix deposition
7. fibrous plague
8. complex atheromas
64
atherosclerosis: complications
1. aneurysms
2. ischemia
3. infarcts
4. peripheral vascular dz
5. thrombus
6. emboli
65
atherosclerosis: location
order by likelyhood
1. abdominal aorta
2. coronary artery
3. popliteal artery
4. carotid artery
66
atherosclerosis: symptoms
1. angina
2. claudication
3. can be asymptomatic
67
what is aortic aneurysms and 2 types
- localized pathologic dilation of blood vessel
1. abdominal aortic aneurysm
2. thoracic aortic aneurysm
68
aortic aneurysms: abdominal
- associated with atherosclerosis
| - occurs more frequently in hypertensive male smokers >50 yo
69
aortic aneurysms: thoracic
-associated with HTN, cystic medial necrosis (Marfan's syndrome) and historically tertiary syphilis
70
aortic dissection
- longitudinal intraluminal tear forming a false lumen
- associated with HTN, bicuspid aortic vale, cystic medial necrosis, inherited connective tissue disorders (Marfan's syndrome e.g.)
- present with tearing chest pain radiating to the back,
- CXC shows mediastinal widening
- the false lumen can be limited to the ascending aorta, or propagate from the descending aorta
- can result in pericardial tamponade, aortic rupture, death
71
ischemic heart dz manifestations: angina
- CAD narrowing > 75%; no myocyte necrosis
1. stable- mostly 2' to atherosclerosis; ST depression on ECF (retrosternal chest pain with exertion)
2. Prinzmetal's variant- occurs at rest 2' to coronary artery spasm; ST elevation on ECG
3. Unstable/crescendo- thrombosis with incomplete coronary artery occlusion; ST depression on ECG (worsening chest pain at rest or with minimal exertion)
72
ischemic heart dz manifestations: coronary steal syndrome
-vasodilator may aggravate ischemia by shunting blood from area of critical stenosis to an area of higher perfusion
73
ischemic heart dz manifestations: myocardial infarction
- most often acute thrombosis due to coronary artery atherosclerosis with complete occlusion of coronary artery & myocyte necrosis
- ECG initially shows ST depression progressing to ST elevation with continued ischemia & transmural necrosis
74
ischemic heart dz manifestations: sudden cardiac death
- death from cardiac causes within 1 hr of onset of symptoms, most commonly due to a lethal arrhythmia (ventricular fib eg)
- associated with CAD (up to 70% of cases)
75
ischemic heart dz manifestations: chronic ischemic heart dz
-progressive onset of CHF over many yrs due to chronic ischemic myocardial damage
76
what are the 5 manifestation of ischemic heart dz
1. angina
2. coronary steal syndrome
3. myocardial infarction
4. sudden cardiac death
5. chronic ischemic heart dz
77
evolution of MI:
1. occlusion
2. symptoms
```
-coronary artery occlusion: LAD>RCA>circumflex
symptoms:
1. diaphoresis
2. nausea
3. vomiting
4. severe retrosternal pain
5. pain in left arm and/or jaw
6. SOB
7. fatigue
```
78
evolution of MI: at specific time: 0-4 hr
1. gross
2. light microscope
3. risk
1. none
2. none
3. arrhythmia, CHF exacerbation, cardiogenic shock
79
evolution of MI: at specific time: 4-12 hr
1. gross
2. light microscope
3. risk
1. occluded artery, infarct, dark mottling; pale with tetrazolium stain
2. early coagulative necrosis, edema, hemorrhage, wavy fibers
3. arrhythmia
80
evolution of MI: at specific time: 12-24hr
1. gross
2. light microscope
3. risk
1. occluded artery, infarct, dark mottling; pale with tetrazolium stain
2. contraction bands from reperfusion injury. Release of necrotic cell content into blood. Beginning of neutrophil migration
3. arrhythmia
81
evolution of MI: at specific time: 1-3days
1. gross
2. light microscope
3. risk
1. hyperemia, occluded artery, infarct, dark mottling, pale with tetrazolium stain
2. Extensive coagulative necrosis. Tissue surrounding infarct shows acute inflammation. Neutrophil migration
3. fibrinous pericarditis
82
evolution of MI: at specific time: 3-14 days
1. gross
2. light microscope
3. risk
1. hyperemic border; central yellow-brown softening-maximally yellow and soft by 10
2. macrophage infiltration followed by granulation tissue at the margins
3. free wall rupture leading to tamponade, papillary muscle rupture, ventricular aneurysm, interventricular septal rupture due to macrophages that have degraded important structural components
83
evolution of MI: at specific time: 2 wks-several mos
1. gross
2. light microscope
3. risk
1. recanalized artery, gray-white
2. contracted scar complete
3. Dressler's syndrome
84
Diagnose of MI
- in 1st 6 hrs, ECG is gold standard
- cardiac troponin I rises after 4 hrs and is elevated for 7-10 days; more specific than other protein markers
- CK-MB is predominantly found in myocardium but can also be released from skeletal muscle. Useful in dx reinfarction following acute MI bcuz levels return to normal after 48 hrs
- ECG changes can include ST elevation (transmural infarct), ST depression (subendocardial infarct), and pathologic Q waves (transmural infarct)
85
Types of infarcts
1. transmural infarcts
- inc necrosis
- affects entire wall
- ST elevation on ECG, Q waves
2. Subendocardial infarcts
- due to ischemic necrosis of <50% of ventricle wall
- subendocardium especially vulnerable to ischemia
- ST depression on ECG
86
ECG dx of MI: infarct location & leads c Q waves
1. anterior wall (LAD); V1-V4
2. anteroseptal (LAD); V1-V2
3. anterolateral (LCX); V4-V6
4. lateral wall (LCX); I, aVL
5. inferior wall (RCA); II, III, aVF
87
MI complications
- cardiac arrhythmia-important cause of death before reaching hospital; common in first few days LV failure and pulmonary edema
- cardiogenic shock (large infarct-high risk of mortality)
- ventricular free wall rupture--> cardiac tamponade; papillary muscle rupture-->severe mitral regurgitation; and interventricular septum rupture-->VSD
- ventricular aneurysm formation- dec CO, risk of arrhythmia, embolus from mural thrombus; greatest risk approximately 1 wk post-MI
- postinfarction fibrinous pericarditis- friction rub (1-3 days post MI)
- Dressler's syndrome- autoimmune phenomenon resulting in fibrinous pericarditis (several wks post-MI)
88
Cardiomyopathies: dilated (congestive) cardiomyopathy
- most common cardiomyopathy (90% cases), -systolic dysfunction ensues
- often idiopathic(up 50% cases familial)
- eccentric hypertrophy (sarcomeres added in series
- other etiologies include chronic Alcohol abuse, wet Beriberi, Coxsackie B virus myocarditis, chronic Cocaine use, Chagas' dz, Doxorubicin toxicity, hemochromatosis, peripartum cardiomyopathy
* **ABCCCD
- findings:
1. S3
2. dilated heart on ultrasound
3. balloon appearance on chest x-ray
- treatment:
1. Na+ restriction
2. ACE inhibitors
3. diuretics
4. digoxin
5. heart transplant
89
Cardiomyopathies: hypertrophic cardiomyopathy
- hypertrophied interventricular septum is too close to mitral valve leaflet, leading to outflow tract obstruction.
- diastolic dysfunction ensues
- 60-70% of cases are familial, autosimal dominant (commonly a beta-myosin heavy chain mutation)
- asymmetric concentric hypertrophy (sacromeres added in parallel)
- associated with Friedreich's ataxia. Disoriented, tangled, hypertrophied myocardial fibers. Cause of sudden death in young athletes
- proximity of hypertrophied interventricular septum to mitral leaflet obstructs outflow tract, resulting in systolic murmur and syncopal episodes.
```
Findings:
1. normal sized heart
2. S4
3. apical impulses
4. systolic murmur
Tx:
1. beta blocker or non-dihydropyridine calcium channel blocker (eg. verapamil)
```
90
Cardiomyopathies: restrictive/obliterative cardiomyopathy
- major causes:
1. sarcoidosis,
2. amyloidosis,
3. postradiation fibrosis,
4. endocardial fibroelastosis (thick fibroelastic tissue in endocardium of young children)
5. Loffler's syndrome- endomyocardial fibrosis with a prominent eosinophilic infiltrate
6. hemochromatosis- dilated cardiomyopathy can also occur
- diastolic dysfunction ensues
91
CHF
- clinical syndrome that occurs in pts c inherited or acquired abnormality of cardiac structure/function, which is characterized by a constellation of clinical symptoms & signs:
1. dyspnea
2. fatigue
3. edema
4. rales
- right HF most often results from LHF. isolated RHF is usually due to cor pulmonale
- ACE inhibitors, beta-blockers (except acute decompensated HF), angiotensin receptor antagonists, spironalactone reduce mortality
- thiazide or loop diuretics are used mainly for symptomatic relief.
- hydralazine with nitrate therapy improves both symptoms and mortality in select patients
92
Abnormality & cause: cardiac dilation
-greater ventricular end diastolic volume
93
Abnormality & cause: dyspnea on exertion
-failure of cardiac output to inc during exercise
94
Abnormality & cause of LHF:
| pulmonary edema, paroxysmal noctural dyspnea
- inc pulmonary venous pressure--> pulomary venous distention & transudation of fluid.
- presence of hemosiderin-laden macrophages "heart failure cells" in the lungs
95
Abnormality & cause of LHF:
| orthopnea (SOB when supine)
-inc venous return in supine position exacerbates pulmonary vascular congestion
96
Abnormality & cause of RHF
| Hepatomegaly (nutmeg liver)
- inc central venous pressure--> inc resistance to portal flow.
- rarely, leads to cardiac cirrhosis
97
Abnormality & cause of RHF:
| peripheral edema
-inc venous pressure--> fluid transudation
98
Abnormality & cause of RHF:
| jugular venous distention
-inc venous pressure
99
Bacterial endocarditis:
1. symtoms
2. acute vs. subacute
3. nonbacterial
4. complications
Symptoms:
1.fever- most common symptoms
2.Roths spots- round white spots on retina surrounded by hemorrhage)
3.Osler's nodes- tender raised lesions on finger or toe pads
4.new murmur. Mitral valve is most frequently involved. Tricuspid valve endocarditis is associated with IV drug abuse (don't tri drugs)
5.Janeway lesions- small, painless, erythematous lesions on palm or sole
6.anemia
7.splinter hemorrhages on nail bed
8.multiple blood cultures necessary for dx. Associated with S. aureus, Pseudomonas, Candida
*Bacteria FROM JANE
Fever, Roth's spot, Osler's nodes, Murmur, Janeway lesions, Anemia, Nail-bed hemorrhage, Emboli
Acute- S. aureus (high virulence). Large vegetations on previously normal valves. Rapid onset
Subacute- viridans streptococci (low virulence). Smaller vegetations on congenitally abnormal or diseased valves. Sequela of dental procedures. More insidious onset.
Endocarditis may be nonbacterial 2' to malignancy, hypercoagulable state, or lupus (marantic/thrombotic endocarditis).
S. bovis is present in colon CA, S. epidermidis on prosthetic valves
100
Rheumatic fever
-consequence of pharyngeal infection with group A beta-hemolytic streptococci
-early death due to myocarditis
-late sequelae include rheumatic heart dz, which affects heart valves:
mitral>aortic>tricuspid (high pressure valves affected most)
-early lesion is mitral valve regurgitation; late lesions is mitral stenosis
-associated with:
1. Aschoff bodies (granuloma with giant cells)
2. Anitschokow's cells- activated histiocytes
3. elevated ASO titers
-immune mediated (Type II hypersensitivity); not direct effect of bacteria. Antibodies to M protein
*FEVERSS:
Fever, Erythema marginatum, Valvular damage (vegetation & fibrosis), ESR inc, Red-hot joints (migratory polyarthritis), Subcutaneous nodules, St. Vitus' dance (Sydenham's chorea)
101
Acute pericarditis
- commonly presents with sharp pain, aggravated by inspiration, relieved by sitting up & leaning forward.
- presents with friction rub
- ECG changes include widespread ST segment elevation and/or PR depression
1. fibrinous-caused by Dressler's syndrome, uremia, radiation. present with loud friction rub
2. serous- viral pericarditis (often resolves spontaneously); noninfectious inflammatory dz (eg. rheumatoid arthritis, SLE)
3. suppurative/purulent- usually caused by bacterial infections (eg. Pneumococcus, Streptococcus). Rare now with abx
102
cardiac tamponade
- compression of heart by fluid (eg. blood, effusions) in pericardium, leading to dec CO
- equilibration of diastolic pressures in all 4 chambers
- findings: hypotension, inc venous pressure (JVD, distant heart sounds, inc HR, pulsus paradoxus
Pulsus paradoxus- dec in amplitude of systolic blood pressure by >= 10 mm Hg during inspiration. Seen in severe cardiac tamponade, asthma, obstructive sleep apnea, pericarditis, croup.
103
syphilitic heart dz
- 3' syphilis disrupts the vasa vasorum of the aorta with consequent atrophy of the vessel wall and dilation of the aorta and valve ring
- may see calcification of the aortic root and ascending aortic arch
- leads to tree bark appearance of the aorta
- can result in aneurysm of the ascending aorta or aortic arch and aortic insufficiency.
104
Cardiac tumors
1. Myxomas-most common 1' cardiac tumor in adults
- 90% occur in atria (left atrium)
- myxomas are usually described as ball valve obstruction in L atrium associated with multiple syncopal episodes
2. Rhabdomyomas-most frequent 1' cardiac tumor in children associated with tuberous sclerosis
- most common heart tumor is a metastasis from melanoma, lymphoma
105
Kussmaul's sign
- inc in JVP on inspiration instead of a normal dec
- inspiration--> negative intrathoracic pressure not transmitted to heart--> impaired filing of right ventricle-->blood backs up into venae cavae-->JVD.
- may be seen with constrictive pericarditis, restrictive cardiomyopathies, right atrial or ventricular tumors, cardiac tamponade
106
Raynaud's phenomenon
- dec blood flow to the skin due to arteriolar vasospasm in response to cold temperature or emotional stress
- most often in fingers and toes
- called Raynaud's dz when primary (idiopathic)
- Raynaud's syndrome when 2' to a dz process such as mixed connective tissue dz, SLE, or CREST (limited form of systemic sclerosis syndrome)
107
Large-vessel Vasculitis:
epidemiology/presentation & pathology/labs
Temporal (giant cell) arteritis
- generally elderly XX
- unilateral HA (temporal artery), jaw claudication
- may lead to irreversible blindness due to ophthalmic artery occlusion
- associated with polymyalgia rheumatica
- most commonly affects branches of carotid artery
- focal granulomatous inflammation
- inc ESR
- treat with high dose corticosteroids
108
Large-vessel Vasculitis:
epidemiology/presentation & pathology/labs
Takayasu's arteritis,
-asian female weak upper extremity pulses), fever, night sweats, arthritis, myalgias, skin nodules, ocular disturbances
- granulomatous thickening of aortic arch, proximal great vessels
- inc ESR
- treat with corticosteroids
109
Medium-vessel Vasculitis:
Polyarteritis nodosa
- Young adults
- hepatitis B seropositivity in 30% pts.
- fever, wt loss, malaise, HA
- GI: abd pain, melena
- HTN, neurologic dysfunction, cutaneous eruptions, renal damage
- typically involves renal & visceral vessels, not pulmonary arteries
- immune-complex mediated
- transmural inflammation of the arterial wall with fibrinoid necrosis
- lesions are of different ages
- many aneurysms and constrictions on arteriogram
- treat with corticosteroids, cyclophosphamide
110
Medium-vessel Vasculitis:
Kawasaki dz
- asian children MI, rupture
| - treat with IV immunoglobulin & aspirin
111
Medium-vessel Vasculitis:
Buerger's dz (thromboangiitis obliterans)
-heavy smokers, males s phenomenon is often present
- segmental thrombosing vasculitis
- treat with smoking cessation
112
Small-vessel vasculitis:
microscopic polyangiitis
-necrotizing vasculitis commonly involving lung, kidneys, skin with pauci-immune glomerulonephritis and palpable purpura
- no granulomas
- p-ANCA
- treat with cyclophosphamide and corticosteroids
113
Small-vessel vasculitis:
Wegener's granulomatosis (granulomatosis with polyangiitis)
- upper respiratory tract: perforation of nasal septum, chronic sinusitis, otitis media, mastoiditis
- lower resp tract: hemoptysis, cough, dyspnea
- renal: hematuria, red cell casts
Triad:
1. focal necrotizing vasculitis
2. necrotizing granulomas in the lung & upper airway
3. necrotizing glomerulonephritis
- c-ANCA
- chest x-ray: large nodular densities
- treat with cyclophosphamide, corticosteroids
114
Small-vessel vasculitis:
Churg-strauss syndrome
- asthma, sinusitis, palpable purpura, peripheral neuropathy (eg. wrist/foot drop)
- can also involve heart, GI, kidneys (pauci-immune glomerulonephritis)
- granulomatous, necrotizing vasculitis with eosinophilia
- p-ANCA, elevated IgE level
115
Small-vessel vasculitis:
Henoch-Schonlein purpura
- most common childhood systemic vasculitis
- often follows URI
- Classic triad:
1. skin-palpable purpura on buttocks/legs
2. arthralgia
3. GI-abdominal pain, melena, multiple lesions of same age
- vasculitis 2' to IgA complex deposition
- associated with IgA nephropathy
116
Vascular tumors:
| strawberry hemangioma
- benign capillary hemangioma of infancy
- appears in first few weeks of life (1/200 births)
- grows rapidly and regresses spontaneously at 5-8 yo
117
Vascular tumors:
| cherry hemangioma
- benign capillary hemangioma of the elderly
- does not regress
- frequency inc with age
118
Vascular tumors:
| pyogenic granuloma
- polypoid capillary hemangioma that can ulcerate and bleed
| - associated with trauma and pregnancy
119
Vascular tumors:
| cystic hygroma
- cavernous lymphangioma of the neck
| - associated with Turner syndrome
120
Vascular tumors:
| glomus tumor
- benign, painful, red-blue tumor under fingernails
| - arises from modified smooth muscle cells of glomus body
121
Vascular tumors:
| bacillary angiomatosis
- benign capillary skin papules found in AIDS pts
- caused by Bartonella henselae infections
- frequently mistaken for Kaposi's sarcoma
122
Vascular tumors:
| angiosarcoma
- rare blood vessel malignancy typically occurring in the head, neck, breast areas
- associated with pts receiving radiation therapy, especially for breast CA and Hodgkin's lymphoma
- very aggressive and difficult to resect due to delay in dx
123
Vascular tumors:
| lymphangiosarcoma
-lymphatic malignancy associated with persistent lymphedema (eg. post-radical mastectomy)
124
Vascular tumors:
| Kaposi's sarcoma
- endothelial malignancy most commonly of the skin, but also mouth, GI tract, resp tract
- associated with HHV-8 & HIV
- frequently mistaken for bacillary angiomatosis
125
Vascular tumors:
| Sturge-Weber dz
- congenital vascular disorder that affects capillary-sized blood vessels
- manifests with port-wine stain (nevus flammeus) on face, ipsilateral leptomeningeal angiomatosis (intracerebral AVM), seizures, early onset glaucoma
-affects small vessels
126
Antihypertensive therapy:
essential HTN
1. diuretics
2. ACE inhibitors
3. angiotensin II receptor blockers (ARBs)
4. calcium channel blockers
127
Antihypertensive therapy:
CHF
- diuretics, ACE inhibitors/ARBs, beta blockers (compensated CHF), K+ sparing diuretics
- beta blockers must be used cautiously in decompensated CHF, and are contraindicated in cardiogenic shock
128
Antihypertensive therapy:
DM
- ACE inhibitors/ARBs, calcium channel blockers, diuretics, beta blockers, alpha blockers
- ACE inhibitors are protective against diabetic nephropathy
129
Calcium channel blockers:
1. names
2. mechanism
3. clinical use
4. toxicity
1. names
- Nifedipine
- Verapamil
- Diltiazem
- Amlodipine
2. mechanism- block voltage-dependent L-type calcium channels of cardiac & smooth muscle and thereby reduce muscle contractility
- vascular smooth muscle-amlopidine=nifedipine>diltiazem>verapamil
- heart-verapamil>diltiazem>amlopipine=nifedipine (verapamil=ventricle)
3. clinical use
- HTN, angina, arrhythmias (not nifedipine), Prinzmetal's angina, Raynaud's
4. toxicity
- cardiac depression, AV block, peripheral edema, flushing, dizziness, constipation
130
Hydralazine:
1. mechanism
2. clinical use
3. toxicity
1. mechanism
- inc cGMP--> smooth muscle relaxation
- vasodilation arterioles>veins; afterload reduction
2. clinical use
- severe HTN, CHF
- first-line therapy for HTN in pregnancy, with methyldopa
- frequently coadministered with a beta-blocker to prevent reflex tachycardia
3. toxicity
- compensatory tachycardia (contraindicated in angina/CAD), fluid retention, nausea, HA, angina, Lupus-like syndrome
131
Malignant HTN Tx
1. nitroprusside
2. fenoldopam
- commonly used drugs include nitroprusside, nicardipine, clevidipine, labetalol, fenoldopam
1. nitroprusside
- short acting
- inc cGMP via direct release of NO
- can cause cyanide toxicity (releases cyanide)
2. fenoldopam
- dopamine D1 receptor agonist
- coronary, peripheral, renal, splanchnic vasodilation
- dec BP and inc natriuresis
132
Nitroglycerin, isosorbide dinitrate
1. mechanism
2. clinical use
3. toxicity
1. mechanism
- vasodilate by releasing nitric oxide in smooth muscle, causing inc in cGMP & smooth muscle relaxation
- dilate veins>>arteries
- dec preload
2. clinical use
- angina, pulmonary edema
3. toxicity
- reflex tachycardia, hypotension, flushing, HA, "monday disease" in industrial exposure:development of tolerance for the vasodilating action during the work week and loss of tolerance over the weekend results in tachycardiac, dizziness, HA upon re-exposure
133
Antianginal therapy goal
Goal-reduction of myocardial O2 consumption (MVO2) by decreasing 1 or more of the determinants of MVO2: end-diastolic volume, blood pressure, Heart rate, contractility, ejection time.
134
cardiac glycosides
1. mechanism
2. clinical use
3. toxicity
4. antidote
- difoxin-75% bioavailability, 20-40% protein bound, t1/2=40 hrs, urinary excretion
1. mechanism
- direct inhibition of Na+/K+ ATPase leads to indirect inhibition of Na+/Ca2+ exchanger/antiport
- inc Ca2+i-->positive inotropy.
- stimulates vagus nerve--> dec HR
2. clinical use
- CHF (inc contractility); atrial fibrillation (dec conduction at AV node and depression of SA node)
3. toxicity
- cholinergic- n/v, diarrhea, blurry yellow vision (think Van Gosh)
- ECG- inc PR, dec QT, ST scooping, T-wave inversion, arrhythmia, AV block
- can lead to hyperkalemia, a poor prognostic indicator
- factors predisposing to toxicity-
1. renal failure- dec excretion
2. hypokalemia- permissive for digoxin binding at K+ binding site on Na+/K+ ATPase 3.quinidine- dec digoxin clearance; displaces digoxin from tissue-binding sites
4. antidote
- slowly normalize K+, lidocain, cardiac pacer, anti-digoxin Fab fragments, Mg2+
135
Antiarrhythmics- Na+ channel blockers (class I)
- local anesthetics
- slow or block (dec) conduction (especially in depolarized cells)
- dec slope of phase 0 depolarization and inc threshold for firing in abnormal pacemaker cells.
- are state dependent (selectively depress tissue that is frequently depolarized (eg. tachycardia))
- hyperkalemia causes inc toxicity for all class I drugs
136
Antiarrhythmics- Na+ channel blockers:
Class IA
"The Queen Proclaims Diso's pyramid."
Quinidine, Procainamide, Disopyramide
-inc AP duration, inc effective refractory period (ERP), inc QT interval
-affect both atrial & ventricular arrhythmias, especially reentrant & ectopic supraventricular & ventricular tachycardia
-toxicity:
1.quinidine- cinchonism: HA & tinnitus
2.procainamide- reversible SLE-like syndrome
3.disopyramide- heart failure
4.thrombocytopenia
5.torsades de pointes due to inc QT interval
137
Antiarrhythmics- Na+ channel blockers:
Class IB
Lidocaine, Mexiletine, Tocainide
**I'd Buy LIDy's MEXIcan Tacos."
-Phenytoin can also fall into the IB category
IB is Best post-MI
-dec AP duration
-preferentially affect ischemic or depolarized Purkinjie and ventricular tissue
-useful in acute ventricular arrhythmias (especially post-MI) and in digitalis-induced arrhythmias
-toxicity: local anesthetic, CNS stimulation/depression, cardiovascular depression
138
Antiarrhythmics- Na+ channel blockers:
Class IC
Flecainide, propafenone
* *IC is Contraindicated in structural heart disease & post-MI
- no effect on AP duration
- useful in ventricular tachycardias that progress to VF and in intractable SVT
- usually used only as last resort in refactory tachyarrhythmias
- for pts without structural abnormalities
- toxicity: proarrhythmic especially post-MI (contraindicated). Significantly prolongs refactory period in AV node
139
Antiarrhythmics-beta blockers (class II)
1. names of medicine
2. mechanism
3. clinical use
4. toxicity
1. names of medicine: metoprolol, propranolol, esmolol, atenolol, timolol
2. mechanism
- dec SA & AV nodal activity by dec cAMP, dec Ca2+ currents
- suppress abnormal pacemakers by dec slope of phase 4
- AV node particularly sensitive--inc PR interval
- esmolol very short acting
3. clinical use
- ventricular tachycardia
- SVT
- slow ventricular rate during atrial fibrillation and atrial flutter
4. toxicity
- impotence, exacerbation of asthma, cardiovascular effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alterations).
- may mask the signs of hypoglycemia
- metoprolol can cause dyslipidemia
- treat overdose with glucagon
- propranolol can exacerbate vasospasm in Prinzmetal's angina
140
Antiarrhythmics-K+ channel blockers (class III)
1. names
2. mechanism
3. toxicity
1. Amiodarone, Ibutilide, Dofetilide, Sotalol
**AIDS**
2. mechanism
-inc AP duration, inc ERP
-used when other antiarrhythmics fail
-inc QT interval
3. toxicity
-Sotalol: torsades de pointes, excessive beta block
-Ibutilide: torsades
-Amiodarone: pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism (amiodarone is 40% iodine by wt), corneal deposits, skin deposits (blue/gray) resulting in photodermatitis, neurologic effects, constipation, cardiovascular effects (bradycardia, heart block, CHF)
-Amiodarone has class I, II, III, IV effects because it alters the lipid membrane
-
-remember to check PFTs, LFTs, TFTs, when using amiodarone
141
Antiarrhythmics-Ca2+ channel blockers (class IV)
1. name
2. mechanism
3. toxicity
1. name
- verapamil, diltiazem
2. mechanism
- dec conduction velocity, inc ERP, inc PR interval
- used in prevention of nodal arrhythmias
3. toxicity
- constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression)
142
Other antiarrhythmics
1. adenosine
2. Mg2+
1. adenosine
- inc K+ out of cells-->hyperpolarizing the cell & dec ICa.
- drug of choice in dx/abolishing supraventricular tachycardia
- very short acting (~15 sec)
- toxicity includes flushing, hypotension, chest pain
- effects blocked by theophylline and caffeine
2. Mg2+
- effective in torsades de pointes and digoxin toxicity.
USMLE First AID
flashcards
Decks in class (9)
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