Clinical Pathophysiology I · Exam 2 — Study Guide

6 · Cardiac Pathophysiology

Lecture 6 · 14 September 2026 · deck title slide: “Lecture Prepared by: Matthew Ward, DMSc, MBA, PA-C”. The calendar lists Dr. Rappa for this session; who delivered it is not confirmed.

6.1 · Objectives a & b — Anatomy of the heart and function of cardiac structures

The anatomy in this deck is the coronary circulation, because every disease that follows is a problem of supply through it. Three slides (5–7) are pictures only:

Function: what sets the heart’s oxygen demand

Slide 31 names the four determinants of workload: heart rate, preload, afterload and contractility. An increase in any one of them increases the demand for oxygen. That list is the demand half of every ischemia question (section 6.6).

The Frank–Starling law (slide 62)

The more the ventricle fills during diastole, the greater the volume it ejects in the systole that follows; in a healthy heart the end-diastolic volume will equal the stroke volume. The force any single muscle fiber generates is proportional to its initial sarcomere length (preload), and that stretch is set by the end-diastolic volume. Maximal force comes at an initial sarcomere length of 2.6 micrometers, a length rarely exceeded in the normal heart.

6.2 · Objective c — The different lipoproteins

Plaques are made of lipid, and lipid travels in the blood bound to specific proteins. Which lipoprotein carries it changes the risk (slide 12):

Familial hypercholesterolemia (slide 13) is the most common form of genetic hyperlipidemia. The defect is in the low-density lipoprotein receptor on liver cells, so the liver cannot remove cholesterol from the bloodstream. High-fat diets are the acquired counterpart listed on the same slide.

Lecture 7 adds a fourth name: lipoprotein(a), an altered form of low-density lipoprotein linked to coronary and cerebrovascular disease, whose risk is independent of total cholesterol (section 7.7).

6.3 · Objective d — Molecular mechanisms of common cardiopathies

The deck has no single slide for this objective; it is answered across the lecture. Every disease here reduces to one of four mechanisms:

Homocysteine (slide 11)

An intermediary amino acid formed in the conversion of methionine to cysteine, with primarily atherogenic and prothrombotic properties. The vascular injury it causes: intimal thickening, elastic lamina disruption, smooth muscle hypertrophy, marked platelet accumulation, and formation of a platelet-enriched occlusive thrombus.

The molecular picture of a plaque (slide 19)

6.4 · Objective e — Etiologies and risk factors for coronary heart disease

Definition (slide 4). Coronary heart disease, also called ischemic heart disease or coronary artery disease, is the insufficient delivery of oxygenated blood to the myocardium because of atherosclerotic coronary arteries. About 50% of those who die of cardiovascular disease die of it. When the heart’s metabolic demand for oxygen exceeds the supply, the myocardium becomes ischemic; ischemia causes abnormal heart function and abnormal cardiac rhythms, and if prolonged, irreversible damage.

6.5 · Objective f — Formation of coronary atherosclerosis and plaques

The sequence on slides 14–16, in order:

1. Injury to the endothelial cells starts it — from chronic hemodynamic wall stress, toxins, inflammation or hyperlipidemia.
2. The injured endothelium becomes more permeable, and leukocytes are recruited.
3. Low-density lipoprotein leaks through the endothelial wall, where cells and macrophages oxidize it.
4. Oxidized lipid damages both the wall and the smooth muscle cells; more macrophages arrive and keep engulfing lipid.
5. Lipid-filled macrophages become foam cells. Both kinds of macrophage release inflammatory mediators and growth factor, attracting more leukocytes and stimulating smooth muscle proliferation.
6. Excess lipid and debris pool inside the wall to form the lipid core.
7. Plaques with large lipid cores are fragile and rupture, exposing subendothelial proteins, which starts platelet aggregation and thrombus formation; thrombotic material can be incorporated, enlarging the plaque.
8. Over time collagen and fibrin form a cap, which makes the plaque more stable.
9. Plaques grow over years until they begin to occlude the lumen. At 75% occlusion, blood flow is compromised.

What makes a plaque rupture

Slide 16 lists what makes a plaque vulnerable to erosion or rupture: intra-plaque inflammation, a large core with a thin cap, superficial platelet aggregation, a ruptured cap, and severe stenosis. Slides 26–28 give the reasons:

• Risk depends on the composition of the plaque and the mechanical stresses on it. A vulnerable plaque has a large necrotic core under a thin fibrous cap.
• A triggering event of enough magnitude and duration compromises it — for example the shear force of blood flowing at high velocity through a severe stenosis.
• The diseased wall may be rich in vasa vasorum capillaries. Their thin walls hemorrhage, depositing blood products and building pressure inside the plaque.

The consequence (slide 29): thrombosis, and emboli carried downstream to block smaller vessels.

6.6 · Objective g — The pathophysiology of cardiac ischemia

Ischemia starts when oxygen supply is insufficient for the demand of the cardiac cells. With less oxygen, less ATP (adenosine triphosphate) is formed (slide 30). Every cause falls on one side of the balance:

• When plaque builds over years, the heart develops collateral circulation to keep the muscle perfused (slide 31) — one reason a slow occlusion can be tolerated and a sudden one cannot.
• Myocardial oxygen consumption and myocardial blood flow correspond nearly linearly; metabolic signals are the principal determinants of oxygen delivery to the myocardium.

6.7 · Objective h — Coronary syndromes

Coronary syndromes are classified by the severity and onset of cardiac symptoms (slide 33):

The dividing line is mechanism: the chronic syndromes come from a fixed narrowing that fails only when demand rises; the acute ones come from plaque rupture with acute thrombosis (section 6.9).

6.8 · Objective i — Angina pectoris

Angina is intermittent cardiac ischemia that is insufficient to kill cardiac cells. It occurs under conditions that increase the heart’s oxygen demand, and may cause insufficient pumping, leading to pulmonary congestion (slide 34).

6.9 · Objective j — Acute coronary syndrome

Acute coronary syndrome includes both unstable angina and myocardial infarction, because they are hard to distinguish clinically. In both, pain lasts longer than typical angina, and plaque rupture with acute thrombosis is thought to occur (slide 37).

Myocardial infarction results from prolonged or total disruption of blood flow, causing cell death by necrosis or apoptosis. The initiating feature (slide 38):

1. Thrombosis on top of an ulcerated or cracked atherosclerotic plaque
2. Platelets adhere to the ruptured plaque, forming a platelet plug
3. The clotting cascade is activated
4. A growing thrombus occludes the vessel

What the occlusion does depends on collateral circulation, workload, and length of time. A typical infarct has several zones of cells in various stages of necrosis. Complete occlusion follows a pattern (slide 39):

Where infarcts happen (slide 40). Nearly all are in the left ventricular walls:

How the infarcted area changes (slide 40):

6.10 · Objective k — Valvular stenosis, regurgitation and prolapse

Valves are damaged by inflammation with scarring (mitral or aortic), calcification (mitral or aortic), or congenital defects (any valve). The altered hemodynamics raise cardiac workload, and heart failure may result (slide 42).

6.11 · Objective l — Infective cardiopathies

6.12 · Objective m — Blood pressure regulation

No slide in the Cardiac deck teaches this objective. Lecture 7 does, on slides 19–21: blood pressure is set by cardiac output and vascular resistance, resistance is regulated at the arterioles, and a fall in pressure triggers the renin–angiotensin–aldosterone response. The full treatment is in section 7.5.

Where pressure appears in this deck, it is as load on the heart: afterload is one of the four determinants of oxygen demand (slide 31); a high afterload increases mitral regurgitation (slide 48); in aortic regurgitation diastolic pressures fall (slide 53); and poor perfusion pressure is one cause of ischemia (slide 30).

6.13 · Objective n — The cardiac conduction system

No slide in the deck covers the conduction system. The deck mentions rhythm in only two places:

• Ischemia can lead to abnormal cardiac rhythms as well as abnormal heart function (slide 4).
• Mitral stenosis leads, with progression, to atrial fibrillation due to the increased atrial volume (slide 46).

Nothing further is added here, so that nothing on this page goes beyond the deck. If the objective was covered aloud, those notes are the source.

6.14 · Objective o — Structural cardiac pathologies

Myocarditis (slides 59–60)

Characterized by inflammation, leukocyte infiltration and necrosis of the myocardium. The picture: left ventricular dysfunction, general dilation of all four chambers, patchy or diffuse necrotic lesions, inflamed and edematous muscle with leukocyte infiltrates, and endocardial structures that are usually normal.

Cardiomyopathy (slides 61–65)

Some have known causes. Those of unknown cause are grouped by their major pathophysiological feature:

Pericardial disease (slides 66–72)

Rarely primary; usually secondary to another cause. Whatever the cause, fluid accumulates in the pericardial sac and the pericardial structures become painfully inflamed.

An effusion is by definition non-inflammatory fluid. Cardiac tamponade occurs when a large amount of pericardial fluid compresses the heart chambers from outside so that filling is impaired; it is life-threatening (slide 69).

7 · Vascular Pathophysiology

Lecture 7 · 15 September 2026 · deck title slide: “Presented by Stacie Gopal, DMS, PA-C”, “Adapted from Lauren Reynolds, PA-C”. The calendar row names Professor Reynolds; the deck’s own wording is used here.

7.0 · What the recording adds

The 51-minute recording was read in two independent transcriptions and cross-examined. Both agree on everything below. Timestamps are minutes into the recording.

7.1 · Objective a — Anatomy of the vascular system

The vascular system is a closed network of blood and lymph vessels. On the slide 3 overview, the numbered structures are 1 aorta, 2 pulmonary artery, 3 right heart, 4 left heart, 6 abdominal aorta (there is no 5). Slides 4 and 7 show the named arteries and veins, superficial and deep veins, and the hepatic portal system, where veins from the stomach and intestines enter the liver so that nutrients are processed and drugs metabolized on first pass.

From heart and back: the five components (slides 8–9)

The three layers (slide 10)

All three layers are present in arteries and veins, though more clearly demarcated in the thicker arterial wall. The amount of smooth muscle and matrix in the media varies with the hemodynamic demand of the vessel’s location. Capillaries are the exception: they have no media.

Capillaries (slide 11)

A capillary is equal to or slightly smaller than the diameter of a red blood cell — in the lecture, roughly 5–10 micrometers against a red cell of 7–8. The lumen is lined with endothelium and has no media. Capillaries have a large cross-sectional area and a low flow rate; thin walls plus slow flow make exchange easy. Tissues with high metabolic rates, myocardium and brain, have the highest capillary density.

7.2 · Objective b — Functions of the components of the vascular system

Two circulatory loops (slide 6). Pulmonary: deoxygenated blood from the right heart to the lungs. Systemic: oxygenated blood from the left heart to the tissues, returning deoxygenated blood to the right heart. The naming rule she stopped on: an artery carries blood away from the heart and a vein toward it, which is why the pulmonary artery carries deoxygenated blood and the pulmonary vein oxygenated.

Veins hold about 66% of the total blood volume (slide 35), so maintaining that volume is a large part of maintaining blood pressure.

7.3 · Objective c — The healthy wall and its response to injury

Intimal thickening (slides 13–15)

Vascular injury with endothelial dysfunction or loss stimulates smooth muscle cell recruitment and proliferation into the intima:

• Endothelial cells migrate in from uninjured areas or come from precursor cells in the blood — and nitric oxide production falls.
• Smooth muscle cells (or circulating precursors) migrate into the intima, proliferate and synthesize extracellular matrix — the primary pathology of neointimal hyperplasia.
• Platelets activate (a thrombus forms) and leukocytes are recruited (the inflammatory cascade begins).

The result is a thickened intima that narrows the lumen and compromises flow. This neointimal response happens with any form of vascular damage, regardless of cause, and involves wall remodeling and loss of lumen patency.

Key Concepts, response of vascular wall cells to injury (slide 15, an image of the textbook’s box; transcribed here because the deck has no text copy):

• All vessels are lined by endothelium; endothelial cells in specific vascular beds have special features for tissue-specific functions (for example, fenestrated endothelium in renal glomeruli).
• Endothelial function is tightly regulated. Stimuli can shift the phenotype: procoagulant versus anticoagulant, proinflammatory versus anti-inflammatory, adhesive versus nonadhesive.
• Injury of almost any type to the wall produces a stereotyped healing response: smooth muscle proliferation, matrix deposition, and intimal expansion.
• Smooth muscle recruitment is signaled by endothelial cells, platelets and macrophages, and by mediators from the coagulation and complement cascades.
• Excessive intimal thickening can cause luminal stenosis and vascular obstruction.

7.4 · Objective c — Two mechanisms, three sizes of artery

The principal mechanisms of vascular disease (slide 16): narrowing — stenosis or obstruction of the lumen, either progressive (atherosclerosis) or precipitous (thrombosis, embolism) — and weakening, which leads to dilation or rupture. Each vessel type has its own structure for its own physiologic needs, so disease has distinct anatomic distributions (slide 17):

7.5 · Objective c — Blood pressure regulation and hypertension

Blood pressure is determined by vascular resistance and cardiac output (slide 19):

• Vascular resistance is regulated at the arterioles, by neural and hormonal input, as a balance of vasoconstrictors (such as angiotensin) and vasodilators (such as nitric oxide).
• Cardiac output is heart rate times stroke volume, and stroke volume depends on blood volume, which is regulated by sodium excretion or resorption. Water follows sodium: more sodium in the blood pulls in water, raising volume and so pressure — why chronic high sodium intake leads to hypertension.

When pressure falls: the renin–angiotensin–aldosterone response

1. The kidneys secrete renin in response to decreased pressure in the afferent arterioles.
2. Renin cleaves angiotensinogen to angiotensin I.
3. Endothelial catabolism produces angiotensin II, a vasoconstrictor.
4. Angiotensin II raises pressure by increasing smooth muscle tone and adrenal aldosterone secretion, which increases renal sodium resorption.

When pressure is high: hypertension (slide 20)

A common disorder and a risk factor for atherosclerosis, congestive heart failure, renal failure, cerebral hemorrhage and aortic dissection.

7.6 · Objective c — Arteriosclerosis

Literally “hardening of the arteries”: the generic term for arterial wall thickening and loss of elasticity. Four patterns (slide 22):

7.7 · Objective c — Atherosclerosis, from the vessel wall

The major pathogenesis of coronary, cerebral and peripheral vascular disease, and the cause of more morbidity and mortality in the Western world than any other disorder — about half of all deaths (slide 24). Risk comes from acquired, inherited, sex- and age-related factors:

The sequence (slide 25). A chronic inflammatory and healing response of the arterial wall to endothelial injury:

1. Healthy vessel is injured (think risk factors)
2. Low-density lipoprotein accumulates in the wall
3. Monocytes adhere to the endothelium
4. Platelets adhere
5. Smooth muscle cells are recruited, by factors released from activated platelets and macrophages
6. Smooth muscle proliferates, extracellular matrix is produced, T cells are recruited
7. Lipid accumulates
8. Matrix and necrotic debris calcify

7.8 · Objective c — Aneurysms and dissection

An aneurysm is a localized abnormal dilation of a vessel, congenital or acquired, classified by shape. A dissection is blood entering a defect in the arterial wall and tunneling through the medial or medial-adventitial planes (slide 27).

Pathogenesis (slide 28). Arterial walls constantly remodel; anything that compromises the connective tissue of the wall can produce aneurysm or dissection:

Predisposing conditions for aortic aneurysm: atherosclerosis, hypertension, smoking.

7.9 · Objective c — Fibromuscular dysplasia, vasculitis, Raynaud phenomenon, arteriovenous fistula

Fibromuscular dysplasia (slide 31)

A focal irregular thickening of medium and large muscular arteries, exact cause unknown. Segments of wall are thickened by hyperplasia and fibrosis of the media and intima, causing luminal stenosis. Example: the renal arteries (in the lecture also carotid and vertebral; in the renal arteries it can cause renovascular hypertension). The angiographic sign is a “string of beads”, and it may lead to aneurysmal dilation that can rupture.

Vasculitis (slide 32)

Vessel wall inflammation, with manifestations set by the vessel affected; any organ or vessel, but mostly small vessels. About 20 primary forms. Two main pathogenic mechanisms: immune-mediated inflammation, and direct invasion of the wall by infectious pathogens.

Raynaud phenomenon (slide 33)

An exaggerated vasoconstrictive response to cold and emotional stress, mostly in the arteries and arterioles of the extremities. Vasoconstriction → tissue anoxia → return of oxygenated blood produces the color sequence white → blue → red. In the lecture: white from constriction, blue from lack of oxygen, red when flow returns, which is painful because of rapid vessel dilation and a rush of inflammatory signals.

Arteriovenous fistula (slide 34)

An irregular direct connection between an artery and a vein, bypassing the capillaries. Causes: developmental defects; rupture of an arterial aneurysm into an adjacent vein; penetrating injury that pierces artery and vein; inflammatory necrosis of adjacent vessels; or surgical creation for hemodialysis access, to carry high flow at a rapid rate. In the lecture: the vein then remodels until its wall can withstand arterial pressure.

7.10 · Objective c — Veins: varicosities and deep vein thrombosis

Veins have larger diameters and lumens than arteries and hold about 66% of total blood volume. Their thinner media allows greater capacitance, and venous valves prevent gravitational reverse flow. As with arteries, location and structure predict the disease (slide 35):

Varicosities (slide 36). Varicose veins are dilated, tortuous veins caused by chronic high intraluminal pressure and weakened wall support. Esophageal varices are dilated submucosal distal esophageal veins from cirrhosis and portal venous hypertension. Hemorrhoids are varicose dilations of the venous plexus at the anorectal junction. In the lecture, varicose veins and hemorrhoids were both linked to pregnancy.

Deep vein thrombosis (slides 37–38)

A clot in a deep vein, typically of the legs; the third most common cause of death from cardiovascular disease.

Virchow triad (slide 38): (1) damage to the vessel wall, (2) blood flow turbulence, (3) hypercoagulability. Triggers are multifactorial, with the three involved in varying degrees.

What happens to the clot. Over weeks, neutrophils and macrophages infiltrate the fibrin clot, and collagen gradually replaces the fibrin; that remodeling and fibrosis decrease blood flow. If the thrombus dislodges it becomes an embolus that travels through the venous system to the pulmonary artery, occluding it: a pulmonary embolus.