Untitled Quiz

Integrated Microbiology And Pathology (YIHS300)

• Course offered by the Nelson Mandela University Faculty of Health Sciences Medical School in 2024
• Focuses on Cardiovascular diseases and Systemic pathology

Topic Overview

• Cardiac pathology is a leading cause of morbidity and mortality.
• The lecture series delves into diseases of the heart, categorized by the heart layer (endocardium, myocardium, or pericardium).
• The disease progression often leads to cardiac failure.
• Congenital heart disorders and cardiac neoplasms are also briefly reviewed.

Learning Outcomes (Heart Failure)

• Understand right heart failure regarding pathogenesis, clinical features, pathologic features, and short/long-term consequences.
• Discuss left heart failure in the same manner as right heart failure.
• Compare and contrast left and right heart failure in terms of pathogenesis, clinical features, pathologic features, and short/long-term consequences.

Learning Outcomes (Ischemic Heart Disease)

• Explain the progression of ischemic heart disease without symptoms for years.
• Compare and contrast stable and unstable angina in clinical, physiologic, and morphologic terms.
• Compare and contrast the features and pathophysiology of acute myocardial infarction.
• Describe the spectrum of myocardial infarction changes over time.
• Identify short-term and long-term complications of myocardial infarction.

Learning Outcomes (Congenital Heart Disease)

• Identify and describe common forms of congenital heart disease, including clinical presentation, natural history, and long/short-term complications.
• Describe genetic disorders associated with congenital heart disease.
• Define left-to-right shunts, right-to-left shunts, shunt reversal, and their correlation with clinical presentation.

Learning Outcomes (Cardiac Inflammatory Conditions)

• Describe major cardiac and extracardiac manifestations of rheumatic fever, encompassing its effects on the endocardium, myocardium, and pericardium.
• Compare and contrast rheumatic fever and bacterial endocarditis' effects on the heart.
• Describe the two major patterns of infective endocarditis and the pathologic changes seen in cardiac valves.
• Discuss noninfective endocarditis's pathologic features on cardiac valves.
• Describe myocarditis's clinicopathologic features and common causes along with their consequences.
• Summarize pericarditis's common causes and resultant clinicopathologic features.

Learning Outcomes (Valvular Dysfunction)

• Discuss the causes, clinicopathologic features, and complications associated with cardiac valvular stenosis.
• Describe the etiologies, clinicopathologic features, and complications of cardiac valvular insufficiency.
• Compare and contrast valvular stenosis and insufficiency.
• Outline cardiac disorders that lead to valvular stenosis and insufficiency.

Learning Outcomes (Hypertension)

• Describe the pathogenesis and the gross and microscopic adaptive changes in the myocardium resulting from pulmonary hypertension
• Discuss the pathogenesis and the gross and microscopic adaptive changes in the myocardium resulting from systemic hypertension.
• Describe mechanisms + epidemiology of primary hypertension, and discuss causes of secondary hypertension.
• Compare and contrasting the pathogenesis and clinicopathologic features of primary and secondary cardiac tumors.

Learning Outcomes (Pericardial Disease)

• Classify pericarditis: acute, chronic, and constrictive
• Compare and contrast the clinical features of haemopericardium(acute effusion) and constrictive pericarditis.
• Discuss the pathology of chronic pericarditis associated with infections like rheumatic fever and TB.
• Discuss aetiopathogenesis and clinical presentations of haemopericardium (cardiac tamponade).
• Describe clinicopathological features and common causes of myocarditis, and their consequences.
• Compare and contrast the clinicopathologic features of dilated, restrictive, and hypertrophic cardiomyopathies.

Cardiac Failure

• Heart failure arises when adaptive mechanisms fail to meet peripheral tissue demands, leading to decreased cardiac output and tissue perfusion.
• Systolic heart failure manifests as reduced ejection fraction (normal 45-65%). Causes include ischemia, pressure/volume overload from hypertension or valvular disease.
• Diastolic heart failure (HFPEF) occurs when the heart chambers cannot fully relax/expand and fill during diastole. This can be caused by conditions like hypertension.

Cardiac Compensation

• Heart rate and dilatation (overstretching) are compensatory mechanisms that fail to compensate for high rates and overstretching.
• The inability to compensate leads to heart failure.
• Hypertrophy (muscle mass increase) also fails to compensate.

Compensatory Mechanisms

• Compensatory enlargement in the form of cardiac hypertrophy, cardiac dilatation, or both.
• Tachycardia (increased heart rate) due to activation of neurohumoral system (releasing norepinephrine, atrial natriuretic peptide, activating renin-angiotensin-aldosterone mechanism).

Aetiology of Cardiac Hypertrophy

• Right ventricular hypertrophy: Pulmonary stenosis and insufficiency, Tricuspid insufficiency, Mitral stenosis and/or insufficiency, and chronic lung diseases.
• Left ventricular hypertrophy: Systemic hypertension, Aortic stenosis and insufficiency, Mitral insufficiency, Coarctation of the aorta, Left ventricular hypertrophy and failure, congenital anomalies (septic defects and patent ductus arteriosus), and conditions with increased cardiac output. (thyrotoxicosis, anemia, arteriovenous fistulae.)

Causes of Cardiac Failure

• Pulmonary Circulation: A low pressure system (systolic arterial pressure = 24 mmHg, pressure gradient artery/vein = 8 mmHg). Right ventricular mass and coronary blood supply.
• Systemic Circulation: A high pressure system (systolic arterial pressure = 120 mmHg, pressure gradient artery/vein = 90 mmHg). Left ventricular mass and coronary blood supply.
• Main causes of right ventricular failure: Conditions elsewhere in the body causing obstruction to pulmonary blood flow (e.g. lung disease, mitral, stenosis).
• Main causes of left ventricular failure: Ischemic heart disease, systemic hypertension. Additional, less common causes include aortic valve disease, mitral valve incompetence, and congenital heart disease.

Pathophysiology of Symptoms and Signs

• Low output to the lungs is not usually significant unless right ventricular failure is a result of left ventricular failure.
• There is overfilling of the right atrium, systemic veins, and capillaries.
• Chronic venous congestion and oedema also result in cyanosis.
• Increased pulmonary artery pressure and congestion of pulmonary veins and capillaries cause dyspnea.
• Low cardiac output leads to systemic anoxia.

Backward and Forward Heart Failure

• Backward heart failure occurs when a ventricle fails to eject blood normally, increasing end-diastolic volume and pressure in the atria, which then increases pressure in the veins.
• Forward heart failure is caused by diminished cardiac output resulting from impaired myocardial function(reduced systolic function), leading to cardiogenic shock. It results in diminished renal perfusion and activation of the renin-angiotensin-aldosterone system.

Dyspnea in Cardiac Failure

• Acute pulmonary oedema results from fluid accumulation in the lungs, leading to dyspnea and hypoxia.
• Chronic venous congestion of the lungs leads to the lungs becoming bulky, congested, and brownish in colour.

Left Sided Cardiac Failure

• Clinical manifestations arise from decreased left ventricular output, resulting in fluid accumulation in the lungs.
• This includes symptoms like cough, dyspnea, orthopnea, and paroxysmal nocturnal dyspnea.
• Blood stasis in the left heart chambers; secondary left atrial dilation usually accompanies mitral regurg.

Congested Cardiac Failure

• Congestion in the systemic venous circulation arises from right heart failure.
• Reduced left ventricular output, mitral valve incompetence, and increased pulmonary vascular resistance contribute to chronic pulmonary venous congestion.
• Fluid retention results in pleural effusion and ascites.

Right Sided Cardiac Failure

• Right-sided heart failure is affected by upstream of right heart (due to caval and portal venous congestion/reduced cardiac output).
• Blood stasis in right heart chambers, followed by engorgement of portal venous system, systemic venous system, and pleural, pericardial, and peri-toneal effusions and ascites.
• Peripheral edema can affect dependent areas, worsening fluid retention, and leading to a severe, generalised form of edema (anasarca). Renal and brain complications may also arise due to decreased blood flow.

Systemic (Left-Sided) Hypertensive Heart Disease

• Left ventricular hypertrophy without other cardiovascular pathology.
• Hypertension in other organs like the kidney may accompany this condition.
• The major feature is thickening (15mm to 20mm) in the LV wall of the heart which is symmetrical with an increase in heart mass.

Pulmonary (Right-Sided) Hypertensive Heart Disease (Cor Pulmonale)

• Right-side heart disease caused by pulmonary disorders, characterized by right ventricle dilation, or hypertrophy. Occurs acutely from severe pulmonary embolism or chronically - caused by chronic lung diseases and pulmonary vessel diseases.

Myocardial Ischemia

• An imbalance between myocardial supply (perfusion) and cardiac metabolic demands.
• Causes of myocardial ischaemia - Reduced blood flow due to atherosclerosis, coronary artery disease, coronary emboli, myocardial vasculitis, vascular spasm, and conditions - such as anaemia - causing reduced oxygen availability in blood.
• Chronic vascular occlusion, or complete blockage in one or more coronary arteries or branches, occurs in approximately >90% of patients with IHD.
• Acute plaque change is a sudden alteration of a stable plaque of atherosclerosis leading to critical stenosis, through a rupture, erosion, ulceration, or deep haemorrhage and manifest as acute coronary syndromes (unstable angina, acute myocardial infarction, sudden death).

Four Common Clinical Presentations of Myocardial Ischemia

• Angina Pectoris: Episodes of chest discomfort caused by transient myocardial ischaemia.
• Acute Myocardial Infarction (AMI): Myocardial necrosis from prolonged ischaemia (involving anatomic regions as LAD).

Evolution of Acute Myocardial Infarction

• Time sequence of onset and progression of myocardial ischemia, including onset of ATP deletion, loss of contractility, and progression of ischemia necrosis.
• Progression of ischemic necrosis includes Subendocardial zone, Wavefront region, Completed infarct.

Non-transmural (Subendocardial) Infarcts

• Non-transmural infarctions occur when a coronary thrombus resolves before transmural necrosis occurs, involving longer duration of severe hypotension or prolonged ischemic conditions.
• The condition shows fewer chest pain signs, fewer complications, lower fatality compared to transmural infarcts.

Complications (Myocardial Infarction)

• Papillary Muscle Dysfunction, Myocardial Rupture, Arrhythmias, Pericarditis, Dressler Syndrome, Mural Thrombus, Ventricular Aneurysm, Ventricular Remodelling .

Morphological Changes In Myocardial Infarction

• Time sequence of macroscopic and microscopic changes during myocardial infarction.
• Gross changes include various colors of the lesion and gradual transition from initial inflammation to scar tissue
• Microscopic changes show necrosis, inflammatory response, and scar formation

Restoration of Tissue Perfusion

• Reperfusion injury can occur after treatment. Delays in the return of function may sometimes occur due to the reperfusion process.

Chronic IHD with Heart Failure: Ischemic Cardiomyopathy

• Progressive congestive heart failure (due to myocardial damage)
• May show scars (healed infarcts) and mural thrombi.

Sudden Cardiac Death

• Unexpected death from cardiac causes, within 1 to 24 hours.
• Etiologies include arrhythmia caused by ischaemic injury, or due to dilation and alteration in heart chamber conduction systems.

Endocardial Disorders

• Valvular diseases affecting left side of the heart (mitral or aortic valve, rarely combined).
• Stenosis: failure of a valve to open completely during diastole, obstructing blood flow.
• Insufficiency/incompetence: failure of a valve to close completely during systole, resulting in backward blood flow.
• Diseases causing valve deformities - Rheumatic heart disease (RHD), Endocarditis (and complications), Myxomatous degeneration (floppy valve syndrome), and Carcinoid heart disease.

Acute Rheumatic Fever

• Inflammation and Aschoff bodies in all three heart layers, causing pancarditis.
• Valvular vegetations sometimes present

Rheumatic Heart Disease

• Autoimmune disorder that usually follows group A beta-hemolytic streptococcal infections (e.g. tonsillitis / pharyngitis) occurring within 2-3 weeks.
• Resulting inflammatory damage leads to progressive fibrosis of the endocardium and valves, largely causing chronic scarring. The heart is the primary target organ

• Cardiac Manifestations of Right Heart Disease: Pancarditis (affecting all layers of the heart). Rheumatic Endocarditis: Thickening, loss of translucency, valve leaflet cusps involvement. Rheumatic Myocarditis: Tiny pale foci of Aschoff bodies throughout the myocardium, often seen in interventricular septum, left ventricle, and left atrium. Rheumatic Pericarditis: Fibrous/serofibrinous exudate (bread and butter) appearance of the pericardium. • Extracardiac Lesions: –Migratory polyarthritis: Systemic joint pain and swelling that moves from one joint to another. –Subcutaneous nodules: Small, painless nodules on joints, tendons, ligaments, or vertebrae. –Erythema marginatum: Non-pruritic macular rash on trunk and limbs. –Sydenham chorea: Neurological disorder characterized by involuntary, purposeless movements. • Diagnostic Criteria: Presence of two or more major criteria OR one major criterion and two minor criteria.

Chronic Constrictive Pericarditis

• Rare condition characterized by fibrous or fibrocalcific pericardial thickening.
• Results in mechanical interference with heart function, leading to decreased cardiac output.
• Often caused by longstanding conditions such as tuberculous pericarditis or purulent/haemopericarditis.

Chronic / Healed Pericarditis

• Organisation of pericardial inflammation resulting in small fibrous plaques or delicate adhesions.
• Usually does not affect cardiac function but can involve adhesions, obliteration of the pericardial sac and adherence with other parietal layers (mediastinal pericarditis), affecting systolic contractility + workload increment.

Cardiac Neoplasms

• Primary tumours are very rare, with myxoma being the most common benign tumour.
• Metastatic tumours are more common and result from haematogenous or lymphatic spread, possibly from disseminated cancers.

Myxoma

• Most common primary cardiac tumour; found frequently in the left atrium.
• Often single, can be multiple; polypoid, pedunculated (stemmed), and spherical, soft and hemorrhagic, resembling an organizing thrombus on the walls of the heart.
• Macroscopic: Myxoid or mucoid intercellular stroma. Sparse cellularity with stellate-shaped, spindled, and polyhedral cells. Occasional multinucleate tumour giant cells.

Congenital Cardiac Disease

• Anomalies in heart or great vessels, arising from embryogenesis defects between gestational weeks 3-8.
• Significant anomalies may cause stillborn infants, whereas others are compatible with life, presenting in infancy or later in life.
• Some include septal defects, stenotic lesions in valves and vascular pathways, outflow tract anomalies, and anomalous coronary arteries.

Reading Task

• The task is a reading assignment from a specific textbook or website, requiring the student to review various categories of congenital heart diseases.

Specific Types of Infective Endocarditis

• Tuberculous endocarditis: Presence of tubercles on valvular and mural endocardium.
• Syphilitic endocarditis: Aortic valve incompetence.
• Fungal endocarditis: Candida or Aspergillus from IV drug users or those with prosthetic valves.
• Other relevant organisms - Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus viridians, Staphylococcus mutans with predisposing factors including IV drug abusers, prosthetic valves, patients with a previously damaged valve or those who have recently had a dental extraction.

Non-Rheumatic Endocarditis

• Non-bacterial forms:
• Thrombotic (cachectic or marantic): Sterile thrombotic vegetations on heart valves.
• Atypical Verrucous (Libman-Sacks): Fibrin, platelet deposition over thrombi. Etiologies often related to underlying diseases (e.g., systemic lupus erythematosus).

Complications of Endocarditis

• Cardiac complications: Valvular insufficiency/stenosis, ring abscess, suppurative pericarditis, and valvular dehiscence.
• Embolic complications: Involvement of left or right sided lesions of brain, spleen, kidney (left side) or lung infarct or abscess (right side).
• Renal complications: Focal or diffuse glomerulonephritis.

Prosthetic Valves

• Complications: Thromboembolism, structural failure, and infective endocarditis.

Myocarditis

• Inflammation of the heart muscle that can affect any age group.
• Classified as:
  • Myocarditis in Connective Tissue Diseases: Rheumatoid Arthritis, Systemic Lupus Erythematosus, Polyarteritis Nodosa, Dermatomyositis, and Scleroderma.
  • Idiopathic (Fiedler's) Myocarditis: Often with sudden severe cardiac failure or death with no apparent cause.
  • Infective (Viral Myocarditis) - Caused by viral infections such as Influenza, Poliomyelitis, Mononucleosis, Hepatitis, Smallpox, Chickenpox, Measles, Mumps, Rubella, and certain types of Viruses. Suppurative myocarditis: Caused by pyogenic bacteria from septicemia, pyaemia, or from spreading infections

Cardiomyopathy

• A group of myocardial diseases of unknown cause, primarily divided into:
• Idiopathic Dilated Cardiomyopathy: Dilatation of all 4 heart chambers, leading to progressive cardiac failure.
• Idiopathic Restrictive Cardiomyopathy: Restriction in ventricular filling; causes reduction in ventricular volume.
• Idiopathic Hypertrophic Cardiomyopathy: Cardiac enlargement with asymmetrical Hypertrophy; more prominent in the septum.

Pericardial Disorders

• Pleural effusion and haemopericardium: Fluid build-up causes restricted filling when accumulation is too rapid.
• Chronic Pericarditis: Fibrous or fibrocalcific pericardial thickening; results from various causes (tuberculosis, pus, or bleeding), usually from pre-existing processes
• Acute Pericarditis: Inflammatory reactions due to infections (viral, bacterial), autoimmune issues, trauma, or post-surgery, accompanied by chest pain. - Serous, Fibrinous/Serofibrinous, Purulent, Hemorrhagic.