Cardiovascular System

BSFCR

Case #1:

58-yo male teacher notices the sudden onset of “chest tightness” when he walks across the parking lot to and from school. The pain, which is localized over the sternum goes away when he sits down. He does not experience any pain or discomfort at other times. He has mild hypertension, for which he is on therapy. His cholesterol level is elevated. He does not smoke.

1) What is the most likely diagnosis.

ANGINA PECTORIS: all 3 diagnostic criteria are met:

Substernal chest pain/discomfort

Aggravated by exertion (or emotional stress)

Relieved by rest (or nitroglycerine)

2) Describe fat absorption process starting at the intestine through the formation of chylomicrons.

I) Chylomicrons transport dietary lipids (LCFA) from intestine to peripheral tissues

Step 1: Nascent chylomicrons formed in intestinal mucosa are secreted into lymph and eventually into subclavian vein via thoracic duct.

Nascent chylo’s are rich in dietary TAGs (85%) and contain apoB-48, necessary for chylo assembly

Contain only minimal amount (<3%) dietary cholesterol

Step 2: Addition of apoC-ll & apoE from HDL leads to formation of mature chylos

Step 3: Capillary lipoprotein lipase is activated by apoC-ll and hydrolyzes TAGs in chylos glycerol and FFA in blood

Glycerol is phosphorylated in liver by glycerol kinase into glycerol-3-P used to synthesize more VLDL

FFA enter adipose tissue to produce TAGs for storage

In muscle, FAs oxidized to provide energy

Step 4: apoC-ll returns to HDL

Step 5: Chylo remnants that remain after removal of FFA attach to apoE R’s in liver and are endocytosed

Dietary cholesterol delivered to liver via chylo remnants used for bile acid synthesis and also depresses de novo cholesterol synth

XS cholest excreted in bile

II) VLDL carries TAGs synthesized in liver to peripheral tissues

Step 1: in addition to TAGs, nascent VLDL particles formed in liver also contain some cholesterol (~17%) and apoB-100; these VLDL particles contain apoC-ll and apoE from HDL

Step 2 & 3: conversion of circulating nascent VLDL particles into LDL particles proceeds via IDL

Degradation of TAGs by apoC-ll activated by capillary lipase converts nascent VLDL particles into IDL remnants which then converted to LDL particles

FAs & glycerol released into blood stream

III) Step 4 & 5: LDL particles remaining after metabolism of VLDL & IDL are enriched in cholesterol (~45%), which they deliver to peripheral tissues or to the liver

apoB-100, major lipoprotein on LDL, binds to LDL R’s on cell membranes of target cells in the liver and other tissues

o following R-mediated endocytosis, LDL is degraded in lysosomes, releasing free cholest for use

in membrane synth, bile salt synth (liver), or steroid hormone synth (endocrine tissues, ovaries, testes)

o XS cholest not needed by cells is esterified by acyl CoA:cholesterol acyltransferase (ACAT) &

stored as cholest esters

Free cholesterol in the cytosol has the following regulatory functions:

o Activates ACAT

o Suppresses HMG CoA reductase; ↓ de novo synth of cholest

o Suppresses further LDL-R synth; ↓ further uptake of LDL

IV) Step 6: HDL, “good cholesterol” is synth in the liver and small intestine and carries out reverse transport of cholest from extrahepatic tissues to the liver

HDL also acts as repository of apolipoproteins (i.e. apoC-ll, apoE), which are required in the metab of VLDL and chylos.

Step 7: LCAT mediates esterification of free cholest removed from peripheral tissues by HDL

o HDL is converted from a discoid shape to spherical shape when esterified cholest is xfr’d into

center of molecule

HDL xfr’s cholest esters to VLDL in exchange for TAGs

o Xfr is mediated by cholesteryl ester transfer protein

o Xfr explains why and ↑in VLDL leads to ↓in HDL cholest levels

Step 8: cholesteryl esters are returned to liver via R-mediated endocytosis of HDL

HDL is ↑ by estrogen (women have ↑ HDL levels), exercise, & red wine

3) Describe cholesterol biosynthesis; include its regulatory step and the use of statin group of drugs

Almost all tissues synthesize cholest; liver, intestinal mucosa, adrenal cortex, testes, and ovaries are major contributors to body’s cholest pool

Cholesterol synth & regulation:

Enzymes in both cytosol and SER participate

I) Step 1: HMG CoA is formed by condensation of three molecules of acetyl CoA

-- in liver, HMG CoA is also produced in the mitochondrial matrix serves as intermediate in synth of ketone bodies

II) Step 2: HMG CoA reductase conversion of HMG CoA to mevalonate is the rate-limiting step

Cholesterol, an allosteric inhibitor of gene expression of HMG CoA reductase, provides rapid feedback control of cholest synth w/in cells

STATIN drugs, such as Atorvastatin, Simvastatin, & Pravastatin, act as competitive inhibitors w/ mevalonate for binding to HMG CoA reductase

Hormones control cycling b/w active/inactive forms of HMG CoA reductase via phosphorylation and dephosph, respectively

Sterol-mediated decrease in expression of HMG CoA reductase provides long-term regulation

o Delivery of cholest to liver and other tissues via plasma lipoproteins, such as LDLs and HDLs

leads to ↓ in de novo cholest synth and ↓ in synth of LDL R’s

III) Step 3: Isopentenyl (farnesyl) pyrophosphate is formed in several rxns from mevalonate and is the key 5-Carbon isoprenoid intermed in cholest synth

Isopentenyl pyrophosphate is also a precursor in the synth of Coenzyme Q (ubiquinone) and dolichol, which functions in the synth of CHO side chains in glycoproteins

IV) Step 4: Squalene, 30-C molecule, is formed by several condensation rxns involving isopentenyl pyrophosphate

V) Step 5: Conversion of squalene to cholesterol requires several rxns and involves NADPH reduction

VI) Step 6: Choles is excreted in bile or used to synth bile acids and salts

XS cholest in bile &/or deficiency of bile salts may lead to gall stones

***Synthesis occurs in the liver

**HMG-CoA reductase is the rate limiting step

4) Describe coronary circulation anatomy

is controlled almost entirely by local metabolic factors

exhibits autoregulation

exhibits active and reactive hyperemia

the most important local metabolic factors are hypoxia and adenosine

for ex, increases in myocardial contractility are accompanied by ↑ demand for O2. To meet this demand, compensatory vasodilation of coronary vessels occurs and both blood flow and O2 delivery to contracting heart muscle increase (active hyperemia)

during systole, mechanical compression of the coronary vessels reduces blood flow. After the period of occlusion, blood flow increases to repay the O2 debt (reactive hyperemia)

sympathetic nerves play a minor role

ARTERY SUPPLYLeft Circumflex (CFX) Lateral free wall of left ventricle (LV)

**IN LEFT DOMINANCE -Posterior Descending will branch off CRX & supply posterior wall of LV & Apex

Left Anterior Descending (LAD) Apex, Anterior LV, Anterior septumRight Coronary (RCA) SA & AV nodes, posterior LV, posterior septum, Right Ventricle, inferior

wall (** IN RIGHT DOMINANCE)Acute Marginal (AMA) Right VentriclePosterior Descending/ interventricular (PD)

Posterior septum and inferior wall

RCA & LCA arise in root or aorta; just above aortic valve orifice Coronary arteries run along the epicardial surface & send arterioles into the myocardium LCA quickly divides into LAD & LCX RCA divides into AMA and PD Coronary blood flow is maximally during ventricular diastole and least during isovolumetric contraction Blood flow mainly controlled by local metabolic autoregulation Sympathetic stimulation does not cause significant vasoconstriction

5) Apply your knowledge about neurotransmitters, local metabolites and hormones to the activity of coronary blood vessels in the heart.

The coronary circulation possesses unique pharmacologic characteristics. Prominent among these is its reactivity to adrenergic stimulation. The majority of vasculature in the body constricts to norepinephrine, a sympathetic neurotransmitter the body uses to increase blood pressure. In the coronary circulation, norepinephrine elicits vasodilation, due to the predominance of beta-adrenergic receptors in the coronary

circulation. Agonists of alpha-receptors, such as phenylephrine, elicit very little constriction in the coronary circulation.

↑ O2 (high ATP) is to ↑ perfusion coronary vasodilation b/c demand may ↑ up to 20x’s in situations such as exercise. Local factors that play an important role to this end are: Adenosine, lactic acid, K+, these are the best vasodilators if the coronary circulation.

Molecular Mechansims Underlying the Contracton and Relaxation of Vascular Smooth Muscle

VasoConstriction Molecular Mechanisms1. Adenosine- an agonist for Receptor Operated Calcium Channels (ROC), increase Calcium entry2. NE, and other agonists at the Alpha 1 Receptors3. Endothelin4. ANGII5. ATP, activates a Purinergic ReceptorVasorelaxation 1. NO2. Beta II Agonists, Epinephrine3. Vasoactive Peptive4. Prostacyclin (PGI2)5. Histamine6. Adenosine- Activates a Purinergic Receptor leading to release of NO

Metabolic Changgs that Cause Vasodilation in the systemic Circulation. (dominate pathway)

Decreased P02, Increased PCO2, Decreased pH, increased Lactic Acid levels, increased ATP in intestitium, and increased Adenosine in the interstium.

Vasoactive Agents produced by the Endothellial Cells

VasoDilates- NO, Endothelium Derived Hyperpolarizing Factor (EDHF), and ProstacylinVasoConstricts- Endothelin, Endothelin-Derived Constricting Factor 1 and II

6) Describe the ionic basis of different phases of the ventricular action potential.

Ventricles, atria, and the Purkinje system have stable resting membrane potentials (~ -90 mV). This value approaches the K+ equilibrium potential

Action potentials are of long duration, esp in Purkinje fibers 300 msec

a. Phase 0

Is the upstroke of the AP

Is caused by a transient increase in Na+ conductance. This ↑ results in an inward Na+ current that depolarizes the membrane

At the peak of the AP, the mem potential Na+ equilibrium pot’l

b. Phase 1

Is brief period of initial repolarization caused by outward current, in part b/c of K+ ion movement (favored by both chemical and electrical gradients) out of the cell and in part b/c of ↓ in Na+ conductance

c. Phase 2

Is the plateau of the AP

Is caused by a transient ↑ in Ca2+ conductance inward Ca2+ current, and by ↑ in K+ conductance

Outward/inward movements are ~ equal so memb pot’l is stable

d. Phase 3

Is repolarization

Ca2+ conductance ↓, and K+ conductance ↑ and therefore predominates

High K+ conductance results in large outward K+ current (IK) which hyperpolarizes the membrane back toward the K+ equilib pot’l

e. Phase 4

Resting membrane potential

Period during which inward/outward currents (Ik1) are equal and membrane potent’l approaches the K+ equilibrium potential.

Case 2

A 59-year old man complains of tight chest pressure and shortness of breath after lifting several boxes in his garage approximately 2 hours ago. He says he is having feeling of doom. His medical history is significant to hypertension, hypercholesterolemia and cigarette smoking. On examination, heart rate is 102 beats/min and regular, and his lungs are clear to auscultation. An electrocardiogram shows tachycardia with ST-segment elevation and T inversion in multiple leads including the anterior leads, V1 and V2.

Questions:

1. What is the diagnosis?

ST Elevation Myocardial Infarction of Right ventricle

DIFF: Acute MI, Unstable angina (ST Depression), muscle-skeletal, PE,

2. Describe the biomarkers profile of this patient.

As it is only 2 hours after the acute MI, only the Myoglobin will be elevated.

Biomarker Time to Initial Elevation

Time to Peak Elevation

Time to Return to Normal

Myoglobin 1-2 hrs 8-10 hrs 24 hrsCK-MB isoforms 4-6 hrs 18 hrs <24 hrscTnI ** specific ** 4-6 hrs 12 hrs 3-10 dayscTnT 4-6 hrs 12-48 hrs 7-10 daysLD-I 10-12 hrs 48-72 hrs 7-10 days

3. Which coronary arteries are most likely affected in this case?

ST-segment elevation and T inversion in multiple leads including the anterior leads, V1 and V2 indicates a Right Ventricular infarction. Since the RV is supplied by the RCA, it is the most likely artery to be affected.

4. Though this patient will benefit from taking metoprolol for a long time, he will notreceive this medication immediately. Why?

Metoprolol is a B1 selective blocker. This medication should not be given immediately because it causes a drop in cardiac output. After an MI, peripheral perfusion is already compromised, therefore, it is not advisable to give a B1 blocker right after an MI. However, in the long term management to reduce the pressure on the heart and to prevent remodeling of heart it is beneficial to give a B1 blocker to reduce the cardiac output of the patient so the workload of the heart is reduced thus reducing oxygen demand and preventing another MI.

5. What is the rationale for prescribing aspirin and what is the relevant mechanism of action?

Post MI, patients are at an increased risk of subsequent thromboembolitic events. Aspirin irreversibly inhibits cyclooxygenase (COX 1 & 2) by acetylating serine in the active site thereby inhibiting the formation of prostaglandin and thromboxane. This blocks formation of Thromboxane A2 in platelets, inhibiting platelet aggregation. This anticoagulant effect is beneficial to patients post MI.

6. Describe the normal EKG waves, segments and intervals and their associations with heart function.

Lead I – Right arm negative, left arm positive

Lead II – Right arm negative, left leg positive

Lead III – Left arm negative, left leg positive

Lead aVR – right arm positive, left arm + left leg negative

Lead aVL – left arm positive, right arm + left leg negative

Lead aVF – left leg positive, right arm + left arm negative

Lead V1-V6 – Horizontal plane 4-5th intercostal, right of sternum to mid axillary.

**Interval = beginning to end ; segment = end to beginning***

P wave – Atrial depolarization (SA to AV, Right atrium to Left Atrium)

T wave – Ventricular repolarization

QRS complex – Ventricular depolarization (60-100 ms)

PR interval – Atrial depolarization plus normal delay at the AV node

Start of P wave to start of QRS complex (120-200 ms = less than 5 small boxes)

QT interval – Total time needed for ventricles to depolarize and repolarize.

Start of QRS complex to end of T wave (300-440 ms)

PR segment – End of the P wave to start of the QRS complex

Isovolumetric ventricular contraction

ST segment – Ventricular cells in Phase 2

End of ventricular contraction

End of QRS complex to start of the T wave (80-120 ms = 2-3 small boxes)

7. Explain with the help of the Starling curves positive and negative inotropic effects.

Inotropic effects are those that change myocardial contractility either weaker (negative) or stronger (positive). The Starling curves show the relationship between cardiac output and left ventricular end diastolic volume (preload). Increased preload, mainly due to venous return, leads to increased myocardial stretching (increased tension) and increased cardiac output. Changes in either variable result in movement along the Starling curve (control) while addition of either a positive or negative inotropic agent shifts the curve up or down.

8. What is myocardial oxygen consumption and its importance to ischemia.

Myocytes require oxygen to use ATP to function. Myocardial contraction is the primary factor determining myocardial oxygen consumption (MVO2). The contraction process accounts for 75% of MVO2 with the other 25% being consumed by other cellular mechanisms. Ischemia is an imbalance between the supply of oxygen by the coronary arteries and the demand by the myocytes. Oxygen uptake here is near maximal and the only way to increase supply is to increase blood flow. Angina and ischemia result when this compensation fails to deliver adequate oxygen supply.

A-V difference Oxygen conductance = Aterial O2 – venous O2

Case 3

A 65-year-old white female complains of requiring three pillows in bed in order to breathe comfortably and having to open window to gasp for air at night. She has also has noted increasing shortness of breath while walking as well as swelling of his ankles and legs. She had a myocardial infraction 2 years ago and has a history of chronic hypertension. Physical exam shows distention of neck veins; third heart sound; grade III/VI crescendo aortic systolic murmur; crepitant rales over both lower lobes; lower lung fields are dull on percussion bilaterally; tender hepatomegaly; pitting edema in both lower extremities; cold extremities.

Questions:

1. Describe normal capillary wedge pressure and the genesis of lung edema. Be sure to use the Starling capillary pressures in your description.

Capillary wedge pressure is the pressure in a pulmonary artery after occlusion of that artery as measured by a pulmonary artery catheter. This is an indirect measurement of left atrial pressure and is the gold standard for determining the cause of acute pulmonary edema. Normal physiological values range from 6-12mmHg.

Lung edema is swelling and/or fluid accumulation in the lungs. This is due to either failure of the heart/circulatory system to remove fluid from lung circulation, or to direct injury to lung parenchyma. In the case of heart failure, there is a backup and congestion of pulmonary vasculature leading to increased blood volume and increased hydrostatic pressure. This change in Starlings forces pushes fluids out of the vasculature and into the lungs, where it accumulates as edema.

2) Compare and contrast normal contractility with this disease.

Chronic hypertension leads to a chronic pressure overload on the heart. There is an increase in afterload on the LV. This results in a decrease in stroke volume and an increase in end systolic volume. This patient also had a MI, resulting in a loss of myocardium , which would decrease the ventricular pressure during systole, increase the diastolic pressure and end systolic volume, and further decrease the stroke volume. To maintain the cardiac output, the heart responds by compensatory mechanisms which include: increased preload (Frank Starling relationship), increased release of catecholamines and hypertrophy of cardiac muscle w/ dilation of the chambers and a more globular geometry. Initially, stretching of the heart muscle leads to a stronger contraction of the heart. However, excessive elongation of the heart results in weaker contractions and the geometry

diminishes the ability to eject blood. This results in a ventricle being unable to pump effectively. The compensatory mechanisms increase the work of the heart and contribute to further decline in cardiac performance.

**contraction is inotropic…so starling law doesn’t play a role, myocardial contractility is lost. The only compensation is via starling

3) List the characterstics of this patient that are related to right HF. List two additional characteristics of RHF.

a) shortness of breath- could be due to: LVF causing pulmonary edema; existing pulmonary diseases, congestion of the hepatic veins w/ formation of ascites which produces restricted diaphragmatic movements and dyspnea; or reduced right sided Cardiac output leading to acidosis, hypoxia, and air hunger b) pitting pedal edema – due to elevated right sided pressure which causes accumulation of fluid in the systemic veins and venous congestion dependent edema

c) Distension of Neck Veins – due to elevated atrial pressures caused by decreased ventricular function . Additional characteristics of RVF: d) Abdominal pain- due to expansion of the liver from fluid accumulation which can cause distention of the liver capsule with accompanying right upper quadrant abdominal pain.

e) Sustained systolic heave of the sternum- due to right ventricular hypertrophy.

Sustained hepatojugluar reflex and asicetes, venous congestion

4) Describe the mechanism of action of Digitalis. Describe the therapeutic index of digitalis.

Digitalis inhibits the Na+/K+ ATPase in the myocardial cell membrane increase in intracellular [Na+] diminished Na+ gradient across the cell membrane decreased Na+/Ca2+ exchange (a mechanism that extrudes Ca2+ from the cell) increase in intracellular [Ca2+] increased force of contraction increased cardiac output improved circulation leads to reduced sympathetic activity which then reduces peripheral resistance. Together, these effects cause a reduction in heart rate. Vagal tone is also enhanced, so that the heart rate decreases and myocardial oxygen demand diminishes. Digitalis has a very low therapeutic index. There is only a small difference between a therapeutically effective dose and doses that are toxic or even fatal.

*Inhibits Na/K atpase pump ca2+ active pump affected

5) Explain excitation contraction coupling in ventricle myocardium.

1. The action potential spreads from the cell membrane into the T tubules.

2. During the plateau of the action potential, Ca2+ conductance is increased and Ca2+ enters the cell from the extracellular fluid (inward Ca2+ current)

3. This Ca2+ triggers the release of even more Ca 2+ from the sarcoplasmic reticulum (Ca-induced Ca release) increase in intracellular [Ca2+] 4. Ca2+ binds to troponin C, and tropomyosin is moved out of the way, removing the inhibition of actin and myosin binding.

5. Actin and myosin bind, the thick and thin filaments slide past each other and the myocardial cell contracts. The magnitude of the tension htat develops is proportional to the intracellular [Ca2+].

6. Relaxation occurs when Ca2+ is reaccumulated by the SR by an active Ca2 ATPase pump and Ca2+ is also extruded out of the cell by a Na+/Ca2+ exchange reaction across the cell membrane

6. Describe how an S3 sound is produced?

S3 is an extra heart sound heard in early diastole. It is pathognomic in patients over 40 for ventricular failure. S3 is thought to be due to the rapid deceleration of blood in a failing ventricle that is already full, or S3 may be due to the wall of the dilated ventricle hitting the chest wall on filling in diastole. S3 is best heard in the lateral decubitus position and when the patient is exhaling (exhalation brings the venticle close to the chest wall)

7. Describe how Enalapril would contribute to improve her condition, based on the drug’s mechanisms of action?

Enalapril is an ACE inhibitor which will inhibit the formation of Angiotensin II (AGTII) from Angiotensin I so that there is AGTII. AGTII is a vasoconstrictor and since it is not present there in no vasoconstriction from this chemical. The lack of vasoconstriction will BP and afterload on the heart, as well as allowing for greater capacitance of the veins and VR thus preload. of afterload and preload are desirable consequences for a patient in hear failure. AGTII will also lead to bradykinin because AGTII normally inactivates bradykinin. Bradykinin is a vasodilator so an in bradykinin due to a in its degradation will result in vasodialation which will further preload and afterload. Finally, AGTII promotes the secretion of aldosterone from the adrenal cortex which will result in of water and Na retention which Blood volume and will preload and afterlaod

Case 4

A 59-year-old man complained of pain in the calf muscles during exercise along with coldness and numbness in both legs; his symptoms have been occurring for a year and are relieved by rest. A history reveals that the patient has also been impotent for two years. He has a history of smoking two packs of cigarettes aday for 25 years. His blood pressure is150/100 with diminished peripheral pulses bilaterally; loss of hair over dorsum of feet and hands; decreased temperature in hands and feet; carotid and femoral arterial bruits; atrophy of calf muscles. His labs show elevated LDL and decreased HDL and elevated total serum cholesterol.

Questions:

1. What is the diagnosis?

Arterial insufficiency 2 to atherosclerosis

2. Describe familial hypercholesterolemia.

A type of dyslipidemia in which there is a co-dominant genetic mutation resulting in non-functional LDL-receptors. LDL plasma concentration is increased due to the inability for the tissue to clear it form the plasma. LDL>190 mg/dL is considered very high, LDL<100 mg/dL is considered optimal. Combination of diet and lipid lowering drugs is used to treat patients. Complications include MI, CVA or blood clot in any other part of the arterial system. This is the result of an increased predisposition of these patients to develop arethomas because of the high LDL content in their blood.

3. Describe the significance of omega-3 acids in the diet.

Omega-3 fatty acids lower LDLs, so an increase in omega-3 fatty acids will result in decreased LDLs. If the LDLs are decreased than there is less to incite the formation of atherosclerotic plaques. This will result in a decreased risk of MI and CVA. Omega-s also will lead to a decrease in inflammatory response which will decrease plaque formation.

4. What is the anatomical basis of the symptoms presented in this case?

Atherosclerosis: if it is atherosclerosis, it is occluding the vessels and decreasing blood supply to the extremities. Smoking increases risk for atherosclerosis. If there is occlusion of the vessels the blood would not adequate travel to the extremities. Patient may experience problems such as atrophy, numbness. The carotid and femoral bruits show problems with blood flow.

Berger’s disease: Patient would be at risk because he is a male smoker, and been smoking heavily for many years. Pathology based on the body reaction to nicotine. In addition, towards the lower extremities would be the usual place that would be affected. Sometimes even the nerves could also be affected.

5. Describe the different types of angina.

Stable (Typical) Angina: associated with increased demand, physical activity, and emotional excitement due to critical stenosis. Seen as crushing or squeezing substernal pain radiating down left arm relieved by rest

Prinzmetal variant angina: associated with st elevation, transmural ischemia. Vasospastic. Occurs at rest, awakens the patient from sleep

Unstable (crescendo) angina, reorganization, disruption of plaque, superimposed thrombosis. Pain that occurs with progressively increasing frequency and precipitated by progressively less effort

6. Describe the relationship between vascular resistance and blood flow.

Directly proportional to viscosity and inversely proportional to the radius to the 4th power

7. What are the likely changes seen in Pressure-Volume loop in patients with systemic hypertension?

A person who has systemic hypertension would have increased after load. During the cycle, isovolumetric contraction would increase so the height would be higher. Next phase systolic ejection would not have too much ejected. So there would be more blood left over. Volume loop would be more to the right. After isovolumetric relaxation, there would be more blood left over.

Case 5A 42-year-old woman develops fatigue and dyspnea that have been worsening over approximately 6 months. She complains of occasional palpitations. She describes a serious illness she had as a child, with fever, rash, joint pains. She recovered after approximately a month. Cardiac examination reveals a loud S1, an opening snap, and a diastolic rumble. A chest radiograph shows an enlarged left atrium.

Questions:1. What is the most likely diagnosis?

- Mitral stenosis

2. What are the complications of this disorder?- Pulmonary hypertension, hemoptysis, orthopnea, atrial arrhythmia leading to embolus formation, left

atrial enlargement may impinge on recurrent laryngeal n. causing hoarseness.

3. Define preload and explain how it affects stroke volume and cardiac output.- Preload is the pressure from blood that is stretching the ventricle. The stretching of the myocytes

before contraction.

4. Explain the hemodynamic changes in mitral stenosis.- In MS, the left atrium is having to work harder to force blood past the mitral valve. This causes a build

up of blood in the LA and the build up of back pressure. This back pressure enlarges the LA causing atrial arrhythmias, typically Atrial fibrillation, as well as back pressure into the pulmonary vein and lungs, causing pulmonary hypertension. The pulmonary hypertension manifests itself in dyspnea, hemoptysis, and orthopnea. The atrial fibrillation also increases the risk of embolism which can enter the systematic circulation, and causing a cerebral vascular accident.

5. Describe the pressure profile of the left ventricle and left atrial pressure in normal and a patient with mitral stenosis.

- In a normal person: The left atrium contracts towards the end of diastole in an atrial ‘kick’. This forces the last volumes of blood into the ventricle. The ventricle begins to contract and when the pressure increases, the mitral valve closes. As the pressure increases, isovolumetric contraction takes place until the pressure in the ventricle exceeds the pressure in the aorta and the aortic valve opens. Blood is then forced into the aorta. As blood is expelled from the ventricle, the atria is slowly filled shown by the v wave. As the pressure in the ventricle decreases below the pressure in the aorta, the aortic valve closes and volumetric relaxation begins. When the pressure in the ventricle decreases below the pressure in the aorta, the mitral valve opens. This is the peak of pressure in the atria. When the valve opens, there is initial rapid filling which then slows and ends with the atrial ‘kick’, and the cycle begins again.

- In mitral stenosis: The left atrium never relaxes fully. This causes an increased pressure in all phases of the cycle in the atrium. The stroke volume is decreased as well as cardiac output. This decreased the overall work of the ventricle as blood is not filling it up completely. The atrium is working harder to expel the extra blood past the constriction. 6. How do you determine cardiac output by using oxygen consumption as amarker?

(Fick principle) Cardiac output = O2 consumption [O2]pulmonary vein - [O2]pulmonary artery

O2 consumption for the body is measuredPulmonary vein is measured in a peripheral arteryPulmonary artery is measured in systemic mixed venous blood

Case 6

1. What is the diagnosis?Aortic stenosis – This patient most likely has aortic stenosis based on the symptoms and findings

presented in the case history. The fatigability is probably due to a lack of adequate amounts of blood reaching the peripheral tissues. The dyspnea may be from the increased pressure load on the left ventricle and subsequent blood back up to the left atrium and pulmonary veins and capillaries that lead to pulmonary edema. The soft, crescendo-decrescendo murmur, and the paradoxical splitting of the S2 heart sound are all indicative of an aortic valve problem and decreased blood flow into the aorta itself.

2. Compare and contrast normal left ventricle and aortic pressure with this disease.In the normal cardiac cycle, a pressure versus time graph would show that the left ventricular pressure

and the aortic pressure coincide as soon as the aortic valve opens during systole and continues in this manner until the aortic valve closes in the early stages of diastole. However, in aortic stenosis, the normal pressure versus time graph shows a big difference between the ventricular pressure and the aortic pressure. These two pressures do not coincide between the opening and the closure of the aortic valve because there is not enough blood being pushed into the aorta to create a pressure that matches the ventricular pressure once the aortic valve opens. As a result, the pressure versus time graph shows a higher ventricular pressure and a lower aortic pressure during systole.

3. Compare and contrast normal arterial pulse wave with this disease process.A normal arterial pulse wave shows an initial rapid rise in the arterial pulse followed by a relatively slow

decline. In aortic stenosis, the arterial pulse wave is described as anacrotic. In other words, the initial rise of the pulse is much slower than normal and the fall of the pulse is much faster than normal. This feature of the arterial pulse wave is also called “parvus et tardus”, or “decreased and late”.

4. Compare normal after load with the after load associated with this disease.Afterload in left ventricle with AS is increased due to the increase force of contraction needed to push blood through the stenosed aortic valve

5. Describe the consequences on heart performance.Heart performance will decrease, due to the increase in ESP from the stenosis , increase in ventricular pressure leading to ventricular hypertrophy to compensate and increase in EDP , these all contribute to decrease SV and CO

6. Describe how an S2 sound is produced.S2 sound is generated by aortic and pulmonary valve closure, when the pressure in the aorta/pulmonary artery is higher than in the ventricles. It is loudest at the left sternal border

Case 7

During a routine athletic physical, a 15-year-old boy is found to have a systolic thrill that is palpable at the lower left sternal border accompanied by a harsh, systolic murmur that is best heard at the site of the thrill but it does not radiate to carotids. He is asymptomatic and has no evidence of hypertension, cyanosis, or edema. An electrocardiogram and a chest radiograph are normal.

1. What is the most likely diagnosis? VSD = age, most common congenital cause of pansystolic murmur. Other answer: Hypertrophic cardiomyopathy , heart size is normal , hypertrophy of the septum , thrills and systolic mumor, AD trait , disoriented, tangled and hypertrophied myocardial fibers. May result in left ventricular outflow obstruction , leading to syncope and sudden death in young athletes

2. What are potential sequelae if this condition remains untreated? Possible shunt reversal [R->L] -> cyanosis. Also could cause CHF -> pulmonary HTN

3. What is hyperdynamic circulation and what are the causes? Increase in pulse pressure and blood pressure caused by certain physiological and psychiatric illnesses. The patient often presents with a collapsing pulse and sinus tachycardia. Possible causes are renal disease volume expansion, hepatic failure, AV fistula, anemia, etc

4. What is left to right shunt and what are the consequences? Abnormal flow of blood from the left heart to the right heart. Consequences include compensatory vascular hypertrophy which results in progressive pulmonary hypertension and as pulmonary resistance increases, the shunt reverses from L-> R to R->L which causes late cyanosis.

5. What is the embryologic explanation of a ASD? Failure of the two ends of the interatrial septum to fuse. The three types include: ostium secundum, ostium primum and sinus venosus.

6. What is the genetic basis of hypertrophic cardiomyopathy?Hypertrophic cardiomyopathy is an autosomal dominant disease. 50% Familial AD. Mutation identified in at least 1 of 9 sarcomeric genes. Approx. 45% of these mutations occur in the â myosin heavy chain gene on chrom 14 q11.2-3, while approx. 35% involve the cardiac myosin binding protein C gene. Hypertrophic cardiomyopathy is attributed to mutations in one of a number of genes that encode for one of the sarcomere proteins including:

7. Describe the changes in the HOCM murmur with different maneuvers'?HOCM is normally manifested by a systolic murmur noted on physical examination. Greater obstruction occurs when preload is decreased during standing and valsalva’s maneuver (both decrease venous return) and the murmur becomes intense.

Gene   Locus   Type  MYH7 14q12 CMH1TNNT2 1q32 CMH2TPM1 15q22.1 CMH3 MYBPC3 11p11.2 CMH4  ?  ? CMH5PRKAG2 7q36 CMH6 TNNI3 19q13.4 CMH7MYL3 3p CMH8 TTN 2q24.3 CMH9MYL2 12q23-q24 CMH10ACTC1 15q14 CMH11 CSRP3 11p15.1 CMH12

Case 8

A 60-year-old man complains of sudden loss of consciousness for few seconds. He regains consciousness without any treatment. This episode was associated with racing of heart and lightheadedness. There is no history of any abnormal movements. He had similar episodes few times before. His past history is significant for hypertension and diabetes. His current medications include lisinopril, glyburide, and hydrochlorothiazide. Physical exams reveals the following: blood pressure 90/60 mm Hg, heart rate 46 beats/minute, respiratory rate 14 breaths/minute, temperature 37°C, jugular venous pressure 6 cm. Chest is clear to auscultation and no murmurs are detected. EKG shows P waves unrelated to QRS complex. The patient has normal electrolytes and complete blood count.

Questions:

1. What is the diagnosis?3rd degree block: Complete AV block. Signs pointing to this diagnosis:•loss of consciousness •slow heart rate•EKG showing P waves unrelated to QRS complex

2. Describe the conduction system of the heart.•Action potential originates at the SA node•Action potential conducts to the AV node rapidly •AV delay occurs and at the same time spreads over the atria slowly•Spreads rapidly to the apex through bundle of His and bundle branches •Spreads rapidly over both the ventricles from apex to base through the Purkinje fibers

3. What is Torsades de pointes? Name any drug which can cause this complication?Torsades de pointes is a ventricular tachycardia with a twist of the QRS complex which usually degrades

into ventricular fibrillation. Quinidine can cause this complication.

4. What is the basis of narrow and wide QRS complex?A wide QRS denotes ventricular origin whereas a narrow QRS denotes atrial origin.

5. What is the most likely cause of sudden death in myocardial infarction?Arrhythmia

6. Myocardial infarction of which part of the heart leads to bradycardia and hypotension and why?Infarction of the AV node causes bradycardia and hypotension because it causes an AV block which

leads to the Bundle of His taking over as the intrinsic pacemaker.