Pathophysiology and Complications

Pathophysiology & Complications by Tim, Tin Yee & Me
Hypertension and Atherosclerosis

• The normal endothelium appears to exhibit an inhibitory influence on vascular smooth muscle cell growth
• Dysfunctional endothelium in hypertension contributes to or permits vascular smooth cell growth, which contributes to narrowing of the lumen
• increase the distance required for diffusion of oxygen from the lumen à would result in incomplete oxidation and lead to increased concentrations of free radicalsThis oxygen radical formation would contribute to tissue damage and lipid oxidation

Hypercholesterolemia And Atherosclerosis

• Hypercholesterolemia : an excess of cholesterol in the blood
  ¢causes increased formation of superoxide anion which causes impairment of endothelial function
• These alterations were observed in morphologically intact arteries, suggesting that impaired NO-mediated endothelium-dependent relaxation is a precursor of intimal thickening and development of atherosclerotic lesions
• Oxygen free radicals such as O2- can cause a wide spectrum of cell damage, including lipid peroxidation, inactivation of enzymes, alteration of intracellular redox state, and damage to DNA. They participate in the pathogenesis of atherosclerosis

Atherosclerosis

• As a result of endothelial injury, there is a proliferation of cells within the inner layer of the arterial(intima) and accumulation of cholesterol and other lipid within their cytoplasm
• Cholesterol seeps across the damaged endothelium and accumulates in the arterial wall, where it is ingested by macrophages and monocytes à a foamy appearance (foam cells)
• Inflammatory cells, smooth muscle cells, and macrophages migrate into the area, where cholesterol accumulates, and assemble as a soft tissue mass. Some of these cells accumulate so much cholesterol that precipitates as crystals within the cytoplasm disrupting the cells and causing cell necrosis
• Cholesterol crystals debris and enzymes escape from the disrupted cells inducing secondary fibrosis, calcification and other degenerative changes in the arterial wall.
• The end result is an irregular mass of yellow, mushy debris that encroaches on the lumen of the artery and extends more deeply into the muscular and elastic tissue of the arterial wall. The plaque like deposit of material is called and atheromatous plaque or atheroma
• This early soft atheromas obstruct flow. Often the smooth internal lining of the vessel becomes ulcerated over the surface of the fatty deposits, leaving a roughened surface that predisposes thrombus formation
  - They are unstable and especially dangerous because they may break open or haemorrhage stimulating thrombosis, acute occlusion and downstream tissue infarction
• By contrast all atherosclerosis regions tend to be scarred, hard and calcified. They may impede blood flow gradually producing downstream ischemia but they are stable and not commonly the cause of acute thrombosis and infarction because they are not as likely to occlude suddenly
• The initial stage in the development of atherosclerosis is reversible and the newly formed plaques are called unstable plaques. The latter stages, characterized by crystallization of cholesterol and secondary degenerative diseases changes, are irreversible
• The plaques, which become surrounded by fibrous tissue, are called stable plaques, and the vessel become permanently narrowed

Manifestations and complications

• atherosclerotic plaques narrow the arteries by 50 percent or more - the arteries may still be able to supply enough blood to the heart muscle if the individual is not very active and no excessive demands are placed on the heart
  -The blood supply may become inadequate if the subject exerts himself and heart requires more blood to satisfy the increased demands
• Myocardial ischemia is the term commonly used to describe a reduced blood supply to the heart muscle caused by narrowing or obstruction of the coronary arteries
• The clinical manifestations of coronary heart disease are quite variable. Although many individuals are free of symptoms, some experience bouts of oppressive chest pain that may radiate into the neck or arms. The pain, which is caused by myocardial ischemia, is called angina pectoris(“pain of the chest”)
• The usual type of angina is a midsternal pressure discomfort that occurs on exertion and subsides when the person rests. This is known as stable angina
• Unstable angina is characterized by episodes of pain that occur more frequently; last longer, and less completely relieved by nitroglycerine.
• Prinzmetal’s angina is a type of angina that characteristically occurs at rest rather than on exertion and is caused by coronary artery spasm

Arterial Thrombosis

• Blood flow in arteries is rapid. Therefore stasis is not involved in thrombosis of the artery.
• Main cause – injury to the wall of the vessel, secondary to arteriosclerosis
• Arteriosclerotic deposits cause ulceration and roughening of the lining of the artery, thrombi forms on the roughened area.
• Effects of the arterial thrombus formation depend on the location and size of the artery that has become obstructed.
• Blockage of :
  —Coronary artery – Leads to MI
  —Major artery in the leg – Gangrene occurs due to necrosis
  —Artery to the brain – Infarction of portion of brain, stroke

More severe and prolonged mycardial ischemia may percipitate an acute episode called a heart attack
- This event may be manifested as either cesation of normal cardiac contractions, called a cardiac arrest, or an actual necrosis of heart muscle, which is termed a myocardial infarction
Any one of the four basic mechanisms may trigger a heart attack in a patient with a coronary artery disease.
1.Sudden blockage of a coronary artery
2.Hemorrhage into an atheromatous plaque
3.Arterial spasm
4.Sudden greatly increased myocardial oxygen requirements

Myocardial Infarction

• Is a necrosis of heart muscle resulting from severe ischemia
• occurs when blood flow through one of the coronary arteries is insufficient to sustain the heart muscle and when collateral blood flow into the ischemic muscle from other coronary arteries is inadequate
• associated with severe chest pain and often with shock and collapse
• may involve the full thickness of the muscular wall (extending from endocardium to epicardium is called a transmural infarct and is usually the result of thrombosis of a major coronary artery) or only part of the muscular wall(subendocardial infarct)

Cardiac Arrest

• Myocardial ischemia increases myocardial irritability, lead to disturbances of cardiac rhythm(cardiac arrhythmias)
• Arrest occurs when an arrhythmia induced by prolonged or severe myocardial ischemia disrupts the pumping of the ventricles
• Most devastating: uncoordinated quivering of the ventricles that is called ventricular fibrillation(rapidly fatal because the normal pumping action of the ventricles ceases)
  -possible to stop the fibrillation by delivering an electric shock to the heart by means of electrodes applied to the chest
• A less common cause of cardiac arrest is complete cessation of cardiac contractions, which is called an asystole

COMPLICATIONS OF MYOCARDIAL INFARCTS

Patients who sustain a myocardial
infarction are subject to complications that fall into 7 categories:
-Disturbances of cardiac rhythm (arrhythmias)
-Heart Failure
-Intracardial Thrombi
-Pericarditis
-Cardiac rupture
-Papillary muscle dysfunction
-Ventricular aneurysm

ARRHYTHMIAS

• Disturbances of cardiac rhythm – common after Myocardial Infarct
• result from the extreme irritability of the ischemic heart muscle adjacent to the infarct and can frequently be controlled by drugs that reduce myocardial irritability
• most serious arrhythmia - ventricular fibrillation, which leads to cessation of the circulation
• Another type of disturbance of cardiac rhythm occurs if the conduction system of the heart is damaged by the infarct
• Conduction of impulses from the atria to the ventricles may be disturbed(heart block)
• The conduction disturbance may subside spontaneously as the infarct heals, but sometimes it is necessary to insert various types of electrodes directly into the heart in order to stimulate the ventricles to contract properly
• A device of this type is called a cardiac pacemaker
  - electrode is passed into a large vein in the upper arm, near the shoulder, and threaded downward into the heart until it makes contact with the wall of the right ventricle
  - then the electrode is connected to a small battery
  - the electrode stimulates the ventricles at a predetermined rate and causes them to contract at a faster, more normal rate

HEART FAILURE

• Ventricle may be so badly damaged that it is unable to maintain normal cardiac function, and the heart fails
• Heart failure may develop abruptly(acute heart failure) or a more slowly (chronic heart failure), as described in a subsequent section, and may be difficult to treat

INTRACARDIAL THROMBI

• The infarct extends to involve the endocardium, thrombi may form on the interior of the ventricular wall and cover the damaged endocardial surface(mural thrombus)
• Bits of the thrombus may break loose and be carried as emboli into the systemic circulation, causing infarctions in other organs(e.g. brain, spleen, kidneys)
• Some physicians attempt to forestall this complication by administering anticoagulants when a patient has sustained a severe infarction

PERICARDITIS

• an infarct extends to involve the epicardial surface, the inflammatory process resulting from myocardial necrosis may spread to include the overlying epicardium
• lead to accumulation of fluid and inflammatory cells in pericardial sac(pericarditis)
• may cause chest pains

CARDIAC RUPTURE

• patient sustains a transmural infarct, a perforation may occur through the necrotic muscle
• permits blood to leak through the rupture into the pericardial sac
• as the blood accumulates, it compresses the heart so the ventricles cannot fill in diastole(event is called a cardiac tamponade)
• eventually the circulation ceases because the heart is no longer able to pump blood
• Less commonly, rupture occurs through the ventricular septum or papillary muscle
• Full thickness infarction of the ventricular septum may lead to septal perforation (which allows blood to leak from the left ventricle into the right ventricle during ventricular contractions instead of being ejected normally) à the output of blood from the left ventricle is reduced greatly, which often leads to severe heart failure
• An infarcted papillary muscle may tear loose from its attachment to the ventricular wall à a loss of “guy wire” support for the mitral valve leaflet to which it is attached and permits the leaflet to prolapse into the left atrium during systole. This complication results in severe mitral insufficiency, which often leads to heart failure

PAPILLARY MUSCLE DYSFUNCTION

• Normally, the papillary muscle contracts during ventricular systole along with the rest of the ventricle, exerting tension on the chordae to prevent prolapse of the mitral valve leaflets into the left atrium during systole
• If a papillary muscle becomes infarcted, it is unable to contract normally and is less able to control the movement of the attached mitral valve leaflet
• So, even if the papillary muscle does not rupture, its malfunction often allows the mitral valve to prolapse slightly into the left atrium, and a mild degree of mitral insufficiency develops

VENTRICULAR ANEURYSM

• Usually a late complication of myocardial infarction
• It is an outward bulging of the healing infarct during ventricular systole
• There are two adverse effects on ventricular function. The damaged area is unable to contract; so the overall efficiency of the left ventricular function is reduced. Moreover, as the ventricle contracts and the intraventricular pressure rises during systole, the aneurysm fills with blood and balloons out
• Consequently, part of the volume of blood within the ventricle is wasted because it fills the aneurysm rather than being ejected into the aorta, and the cardiac output is reduced correspondingly

References

1. http://hyper.ahajournals.org/cgi/content/full/25/2/155
2. http://hyper.ahajournals.org/cgi/content/full/25/2/155#SEC5
3. http://circres.ahajournals.org/cgi/content/abstract/86/1/101
4. The Nature of Disease, Pathology for the Health Professional, Thomas H Mc Connell, Lipincott.
5. An Introduction to Human Diseases, Pathology and Physiology Correlations,7th edition, Leonard V Crowley.