Chapter 4: Cardiovascular Pathology

In order to develop a broader understanding of the cardiovascular system, it is important to develop an understanding of cardiovascular complications and some of the risk features that lead to heart disease.

4.1 Atherosclerosis:

Atherosclerosis is a process of progressive lipid accumulation (atheromatosis) and calcification of the inner arterial walls in the abdominal aorta, lower extremities and the arteries of the heart, brain and kidneys.

Atherosclerotic plaques contain cholesterol, and the most important single factor for their development is a high plasma concentration of total cholesterol, in particular a high concentration of LDL.

Atheromas are yellow streaks or lesions found in arteries at autopsy. They are formed in the intima (lamina intima) by lipid accumulation in macrophages and monocyte adhesion. As more and more cholesterol crystals are deposited, the atheromas grow and the surrounding fibrous and smooth muscle tissue is involved. Finally – as the subendothelial distortion leads to platelet aggregation - large arteriosclerotic plaques are formed. They consist of cholesterol and other lipids, dead cells, collagenous fibres, and there is excessive proliferation of the smooth muscle cells. The fibrosis or sclerosis makes the arterial wall stiff, which lead to systolic hypertension. Later Ca²⁺salts precipitate and a factual calcification of the arterial wall may occur.

Typical for atherosclerosis patients are a high total cholesterol concentration in the blood plasma (total cholesterol above 6.2 mM), a dangerously high LDL and a low HDL fraction in fasting plasma (below 20% of the total). Often the atherosclerotic patient also has a high total triglyceride concentration (above 2 mM). In a fasted patient the triglyceride concentration depicts the precursor concentration of dangerous cholesterol: Very Low Density Lipoprotein (VLDL).

Large atherosclerotic plaques narrow the arterial lumen and produce arterial stenosis with reduced bloodflow. Insufficient oxygen delivery to the tissue is called ischaemic hypoxia, and hypoxic pains develop as in angina pectoris and intermittent claudication. Total occlusion of the arterial lumen is caused by a thrombus or an embolus in the lumen, or by wall bleeding. Disruption of the endothelium results in accumulation of thrombocytes and fibrin with thrombus formation and a complex atheromatous lesion is produced.

Arteriosclerosis (atherosclerosis) manifests itself in the coronary arteries as ischemic heart disease and in peripheral arteries as peripheral arteriosclerosis.

4.2 Ischemic Heart Disease

Atherosclerotic coronary artery disease remains a leading cause of death, and is manifested as focal narrowing in the epicardial coronary arteries. The gradually narrowed vessel segment can be abruptly occluded by clot formation (thrombus) or by vasoconstriction at the atherosclerotic lesion. When a thrombus flows along the arterial tree with the blood and occludes the vessel, it is called an embolus.

Ischemic heart disease is caused by reduced blood flow to a region of the myocardium. Myocardial ischemia diminishes delivery of oxygen and nutrients, and potentially toxic substances such as lactic acid and K⁺ accumulate around the cardiac cells, whereby necrosis may result. The causes are atherosclerosis with atheromas, thrombosis, emboli, or spasms in the coronary arteries.

Coronary blood flow is restricted in the systole by strong myocardial contractions and in diastole by the high heart rate of exercise. Normally, the coronary blood flow in healthy persons is small during systole and increases during diastole (Fig. 4.1A). The high heart rate at exercise implies a short diastolic duration, but the rise in pressure secures a great diastolic blood flow (Fig. 4.1B).

Figure 4.1

Two clinical manifestations of IHD are treated below:

1) Angina pectoris (chest pains) is pain felt beneath the sternum or in the precordial area—often referred to the left arm-shoulder-neck-jaw etc. Exercise and cold bring on hypoxia pains in the substernal or precordial area. Subendocardially situated nerve fibres transmit hypoxic pains. The coronary resistance vessels contain a-adrenergic constrictor receptors and badrenergic dilatator receptors. The vasodilatatory capacity of the coronary resistance vessels can be maximally mobilised already at rest (Fig. 4.1C). Exercise shortens the diastolic duration and restricts the rise in diastolic blood flow further (Fig. 4.1D). The aggravated myocardial ischemia results in a lactate acidosis.

Following sublingual administration of nitro-glycerine, peak concentrations are achieved in the plasma within 1 min. Organic nitrates dilatate constricted coronary vessels, improve the blood flow to the subendocardial (pain sensitive) part of the myocardium, and dilatate resistance and capacitance vessels. This dilatation reduces the venous return to the heart and the arterial pressure (reduced preload and afterload).

The beneficial effect of drugs such as glycerol-trinitrate in angina has been known for more than a century. Recently it was realised that the drugs act by releasing nitric oxide (NO) in the vascular wall.

Ca²⁺-channel blockers block the Ca²⁺ flux into the smooth muscle cells of the coronary arteries, so they relax. The Ca²⁺-channel blockers also reduce the force of contraction and thus the oxygen demand of the myocardium.

Coronary angioplasty is a method by which atheromatous obstructions are dilatated by an inflated balloon.

The arterial oxygen concentration is also reduced in anaemia, CO poisoning and in shock. Patients with hyperthyroidism or hypertension may have increased coronary oxygen demand and all these patients may experience chest pains caused by myocardial hypoxia.

Another manifestation of ischemic heart disease is myocardial infarction.

2) Acute myocardial infarction (AMI) is due to a sudden coronary thrombosis from an atheromatous plaque causing cellular death (infarct) of a myocardial area. Distal to the coronary occlusion the blood pressure is low. The thin-walled subendocardial vessels are squeezed most and receive the smallest blood flow, often leading to subendocardial infarcts. The myocardial infarcts are sometimes silent (which means without pains; the pain relief is due to destruction of subendocardial nerve fibres). The typical infarct causes severe and long lasting pain.

Acute myocardial infarction renders the heart incapable of pumping the minimal blood volume required to transfer sufficient oxygen to the mitochondria.

The patient experiences a sudden chest pain and the pain is lasting for hours in contrast to angina. The patient may develop signs of shock. Necrotic myocardial cells liberate cellular enzymes such as creatine kinase, which peaks in the blood plasma within 24 hours. The total enzyme release depicts the size of the infarction. Lactic dehydrogenase (LDH) isoenzymes peaks a few days later, and LDH 1 is rather specific for myocardial necrosis.

4.3 Heart failure:

Cardiac failure or cardiac insufficiency is a disorder where the heart cannot pump enough blood to satisfy the nutritive needs of the body. Cardiac insufficiency is manifest by a consequential decrease in cardiac output (lower output failure) or by an increase in cardiac output (higher output failure). The cardiac failure can be acute or chronic.

Damming of blood in the vessels behind the insufficient heart pump is typical.

Acute cardiac failure is caused by AMI, acute intoxications, anaesthesia etc. Occlusion of the coronary artery to the left ventricle impairs contractility, and left ventricular failure develops due to the diminished cardiac output from the left ventricle. Initially, the right ventricular output is maintained, whereby the left atrial pressure (and pulmonary venous pressure) is increased beat-by-beat. As a consequence, the left ventricular output will increase until the cardiac outputs of the two ventricles are equal. The increased pulmonary venous pressure leads to reduced lung compliance (dV/dP) and increased respiratory elastic resistance with increased respiratory work and distress. Eventually, plasma fluid flows into the alveoli and pulmonary edema is developed (Fig. 4.2).

Figure 4.2: Formation of pulmonary edema in left ventricular failure (mitral stenosis) and in congestive cardiac failure with ankle edema.

Chronic or congestive cardiac failure occurs in conditions such as IHD and following severe hypertension. In chronic cardiac failure blood is accumulated and expands the venous system and the left ventricle.

Cardiac edema develops during congestive cardiac failure, because the kidneys retain NaCl and water. The accumulated fluid increases venous return, which in turn elevates the right atrial pressure. The rising atrial pressure elevates the venous and the capillary pressure. This causes loss of fluid into the interstitial fluid volume. Accumulation of abnormal volumes of interstitial fluid is the definition of edema.

The low cardiac output and blood pressure causes an increased sympathetic tone with constriction of the afferent renal arterioles to the glomeruli. As a consequence, the renal bloodflow (RBF), and the glomerular filtration rate (GFR) decrease (Fig. 4.2). Also the NaCl concentration decreases in the renal macula densa (Fig. 25-17). The renin-angiotensin-aldosterone cascade is activated, which enhances salt-and water-retention. Angiotensin II is a strong vasoconstrictor, which further decreases the renal blood flow, and aldosterone promotes the reabsorption of NaCl and water from the distal renal system. A certain salt-water retention is beneficial in the early stages of cardiac failure, because of improved venous return and thus improved cardiac output according to Starlings law of the heart. However, prolonged activation of the renin-angiotensin-aldosterone cascade and the sympathetic nervous system, damage the heart muscle further and reduce its contractility. This is because circulating vasoconstrictors, such as catecholamines, vasopressin and angiotensin II, imply an extra workload on the damaged myocardium.

When the salt and water retention results in even a small rise in the osmolarity of plasma, there is a stimulus of osmoreceptors, located close to the neurosecretory cells in the hypothalamus. The osmoreceptors stimulate both production and secretion of vasopressin (antidiuretic hormone, ADH) in the neurosecretory cells. ADH eases the renal reabsorption of water in the outer cortical collecting ducts leading to a low urine flow (antidiuresis).

Vasopressin is also a universal vasoconstrictor.

Increased venous pressure with stasis of blood dilates the central vessels and the heart chambers. The distended atrial wall liberates atrial natriuretic peptide (ANP), which increases Na⁺-excretion and dilates peripheral vessels. This is a partial compensation of the increased preload (the water loss by high urine flow reduces venous return) and afterload (the vasodilatation reduces outflow resistance).

Venoconstriction shifts significant quantities of blood from the peripheral to the central circulation. Since central venous pressure (CVP) varies inversely with TPVR, it is possible to maintain cardiac output in resting patients with congestive heart failure (insufficient contractile force) at the expense of increased CVP, by reduction of TPVR.

When cardiac output decreases more and more during development of congestive heart failure, the compensation fails, and both CVP and end-diastolic ventricular pressure (preload) and volume rises further. The superficial neck veins are expanded, when CVP is abnormally elevated. Eventually, large volumes of plasma water flow from the liver into the peritoneal cavity due to the elevated CVP. Fluid accumulation in the abdomen is called ascites.

Patients with a cardiac output much higher than normal can also develop cardiac failure. The venous return is much too high, and after some time with an over expansion of the heart, the cardiac pump fails to eject the same blood volume as it receives, and an increasing blood volume is accumulated behind the insufficient ventricle. The rise in left atrial pressure leads to pulmonary oedema and eventually the right ventricle fails so peripheral oedema develops.

In hyperthyroidism, all the vessels in the systemic circulation dilate, and the venous return overloads the heart. On the other hand, short-term administration of L-thyroxin to patients with chronic heart failure improves cardiac and exercise performance.

Any major arteriovenous shunt leads a large fraction of the arterial blood directly into the veins. This greatly increases venous return and overloads the heart (Fig. 4.3).

Figure 4.3: Left ventricular pressure-volume loops from a healthy person, and from a person with high metabolic rate (hyperthyroidism) - or a person with arteriovenous shunts.