Week 1 - Valve Disorders, Rheumatic Fever & Congenital Heart Diseases Flashcards
Describe the structure of the normal heart valves.
- Transparent (may appear slightly opaque but majority transparent).
- Thin CT layer covered by endocardium.
- Elastic membranes.
- No blood vessels.
Outline rheumatic fever.
- A multisystem autoimmune inflammatory disorder.
- Characterised by inflammatory changes involving the heart, blood vessels, skin (subcutaneous tissue), joints and brain (majority of damage is in the heart).
- Occurs following group A β-haemolytic streptococci infections (GABH/GAS). Usually pharyngitis but also rarely with infections at other sites such as skin.
*Know the difference between RF (heart) and RA (joints): Both are similar, both involve joints however; the major damage is in the heart for RF and in joints for RA.
What are the 2 phases of rheumatic fever?
• Rheumatic fever is the acute form while rheumatic heart disease is the chronic form.
- Acute (ARF): fever, inflammation of heart, skin, joints, brain (inflammation throughout body). Typically in young children.
- Chronic (RHD): scarring of heart valves leading to (mitral) dysfunction. Is specific to heart valves and due to recurrent autoimmune GAS infection (endocarditis only, all other things resolved). Most common cause of mitral stenosis.
• RHD is the cardiac manifestation of RF. It is associated with inflammation of all parts of the heart, but valvular inflammation and scarring produce the most important clinical features (mitral stenosis).
Outline the aetiology of rheumatic fever.
• GAS is common but not everybody develops ARF as a result of infection. 3 factors are required for the development of RF:
- Genetic susceptibility - presence of HLA DR2 & DR3.
- Environmental factor - GABH streptococcus infection.
- Autoimmunity - T cell, ADNase B (autoantibodies produced against capsule M protein).
NOTE: The aetiology is the same 3 factors for all autoimmune disorders - environmental factors (e.g. infection, hormones, drugs, UV radiation) affect the immune background in a genetically susceptible individual causing an autoimmune response.
Describe the pathogenesis of rheumatic fever.
- GAS infection occurs in genetically susceptible children.
- 2-3 weeks later generalised autoimmune reaction occurs as antibodies against the M protein of GAS cross-react with cardiac myosin & sarcolemma membrane protein → fever, erythema, arthritis, pancarditis → “Acute Rheumatic Disease”
NB: the delay of 2-3 weeks is due to time for T cell proliferation to occur (both Ab and T cell response). - Recurrent attacks of GAS infection → fibrous scarring of mitral valve → deformity of valve & chordate tendinae → mitral stenosis & mitral regurgitation → “Rheumatic Heart Disease”
- Multiple repeat attacks of GAS infections in susceptible host (influenced by environmental factors - crowding, nutrition, infections).
- ARF infection triggers molecular mimicry - cross-reacting anti-strep Ab on host antigens causing autoimmunity.
- T cell mediated autoimmune response also occurs - CD4+ T cells that recognise streptococcal peptides can also cross react with host antigens and elicit cytokine mediated inflammatory responses.
- The characteristic 2-3 week delay in symptom onset after infection is explained by the time needed to generate an immune response
- Autoimmunity against tissues in the body e.g. heart - effects pericardium, myocardium and endocardium.
- Repeat attacks of ARF only attack endocardium → chronic damage to valves → destroyed valves replaced by fibrosis → causes stenosis and regurgitation → chronic RHD (years).
Identify the clinical features of rheumatic fever.
• Fever (multisystem inflammation).
• Heart:
- Pancarditis (inflammation of cardia - endocardium, myocardium and pericardium).
• Joints:
- Migratory polyarthritis (mainly involves large joints which are red and swollen due to inflammatory mediators. One joint becomes inflamed then heals, followed by another joint becoming inflamed - cycle repeats).
• Skin:
- Erythema marginatum (multiform red macular skin rash - clear central area with expanding border of inflammation).
- Subcutaneous nodules (small firm painless nodules).
• CNS
- Sydenham chorea (involuntary movements of hands, feet, face).
• Common in children 5-15 years.
• All features due to T cell mediated inflammation. Except endocarditis, all settle without complication.
- Rheumatic heart disease - deforming fibrotic valvular disease (usually of mitral valve)
- Other clinical features include: pericardial friction rub (due to granuloma/inflammation in pericardium), weak heart sounds, tachycardia, arrhythmias, cumulative cardiac damage over decades.
Outline the Jones criteria for the diagnosis of rheumatic fever.
- The patient must have 2x major criteria OR 1x major and 2x minor criteria PLUS evidence of preceding group A streptococcal throat infection (phargyngitis).
- Major criteria:
- Migratory polyarthritis
- Carditis
- Subcutaneous nodules
- Erythema marginatum
- Sydenham chorea
• Minor criteria:
- Fever
- Arthralgia
- High phase reactants
- High ESR (inflammatory marker)
Describe the morphology of rheumatic fever.
Gross • Pancarditis: - Pericarditis - fibrinous. - Myocarditis - T cell inflammation. - Endocarditis - vegetations.
Microscopy • Aschoff body - usually around blood vessels and consist of: - Fibrinoid necrosis. - Macrophages and giant cells. - T lymphocytes.
Explain the formation of pulmonary oedema in rheumatic fever.
- Heart markedly enlarged as all 3 layers involved. Loss of function due to inflammation (cannot push blood out properly → blood accumulates → heart enlarges).
- Enlarged heart with decreased output results in accumulation in lungs (back flow) → pulmonary oedema (opacity in lungs).
- Pulmonary oedema is due to increased hydrostatic pressure in pulmonary capillaries → fluid leaks out → basilar crackles due to accumulation of fluid in lungs (not an infection).
Outline fibrinous pericarditis.
- Bread and butter pericarditis (fibrin adhesions).
- Immune mediated, fibrinous inflammation (all due to T cell mediated inflammation).
- Marked vasodilation and oedema with fibrin deposits in pericardial sac.
- Inflammation of pericardium: Dilation of blood vessels → capillary leakage → fibrinogen leaks out → clots on surface of pericardium causing fibrin threads.
- Pericardium is no longer smooth - does not allow heart to freely move.
- Pericardium exhibits a fibrinous exudate, which generally resolves without the sequelae.
• Pericardial friction rub.
Outline myocarditis.
• Inflammation of myocardium → enlarges heart. Myocardial involvement takes the form of scattered Aschoff bodies within the interstitial connective tissue.
• Aschoff body - collection of T lymphocytes and macrophages around necrosis. Inflammation around blood vessel plus all over myocardium - whole heart inflamed.
• Antibodies coming out of blood vessel so inflammation starts immediately in that area.
- Dark pink deposits (area of inflammation) = broken down collagen (fibrinoid necrosis).
- Surrounded by small black dots = T lymphocytes.
• Ag:Ab reaction stimulates T cells → secrete chemotaxis → recruits macrophages.
• Macrophages also join to form giant cells AKA Anitschkow cells (caterpillar cells) → eat away dead tissue (collagen) due to Ab.
• Anitschkow cells have abundant cytoplasm and central nuclei with chromatin condensed to form a slender, wavy ribbon (caterpillar cells).
• During ARF, Aschoff bodies can be found in any of the 3 layers of the heart (including valves) - hence causes pancarditis.
• Myocarditis - arrhythmias e.g. AF.
Outline endocarditis.
- Vegetations on mitral valve.
- Acute inflammation of valves wherever there is damage. Antibodies to collagen.
- Collagen usually well covered by endocardium. However, edges of valves constantly hitting against each other results in the development of small ulcers which exposes collagen → Antibodies bind to it → inflammation and platelet agglutination on surface of border of valves.
- Microscopy - T lymphocytes, macrophages. T cell mediated inflammation stimulated by antibody deposition.
• Endocarditis - murmur.
Why is the free edge of the mitral valve involved?
- Free edge of valve most exposed to damage due to pressure.
- Mitral valve is exposed to the highest pressures therefore greater damage, followed by aortic valve, which experiences less pressure. The other valves are rarely involved.
What are the complications of rheumatic fever?
- Arrhythmia.
- Cardiac hypertrophy.
- Heart failure.
- Acute rheumatic fever → rheumatic heart disease.
- Mitral stenosis → right ventricular failure (heart failure).
- Mitral regurgitation (due to ulcers around heart valves preventing them closing properly).
Outline the investigations and management of rheumatic fever.
Investigations:
• There are no specific investigations and cultures are usually negative.
• High ASO titre (antistreptolysin O antibodies).
• High Anti-DNAse B titres.
• High acute phase reactants (CRP, SAA, SAP, complements, coagulation) → inflammation.
• The ECG of mitral stenosis shows atrial fibrillation or bifid P waves (these are associated with atrial hypertrophy).
Management:
• Penicillin prophylaxis for patients who have had acute rheumatic fever.
• Medical management for patients with minor valve disease (e.g. anticoagulation, ventricular rate control, diuretics etc.)
• Valve replacement, balloon valvuloplasty for patients with severe valve disease.
Outline the aetiology of rheumatic heart disease.
- The most important consequence of rheumatic fever is rheumatic heart disease - mitral valve deformity.
- Recurrent autoimmune inflammation of heart valves due to GABH Strep causing scarring of valves leading to severe cardiac dysfunction decades later.
- Continued recurrent attacks of autoimmune endocarditis affecting valves (mitral) leading to damage.
- Lifelong antibiotic therapy required to prevent valve damage. Antibiotics are given only after the diagnosis of ARF (not everyone gets it).
Describe the pathogenesis of rheumatic heart disease.
- Characterised by organisation of the acute inflammation and subsequent scarring. Aschoff bodies are replaced by fibrous scar so that these lesions are rarely seen in chronic RHD.
- Repeated autoimmune damage leading to total scarring. Constant inflammation → healing by fibrosis → inflammation → fibrosis - cycle repeats resulting in totally scarred valves.
- Healing also produces angiogenesis factors (wound healing) leading to blood vessels developing in the valves - normally not present.
Describe the morphology of rheumatic heart disease.
Gross
• Most characteristically, valve cusps and leaflets become permanently thickened and retracted. Classically, the mitral valves exhibit:
- Leaflet thickening.
- Commissural fusion.
- Shortening, thickening and fusion of the chordae tendineae.
• Mitral valve stenosis (‘fish mouth’ appearance due to fibrosis - fibrous bridging across the valvular commissures and calcification create ‘fish mouth’. Mitral valve affected due to high pressure.)
• RV hypertrophy (longstanding passive venous congestion gives rise to pulmonary vascular and parenchymal changes typical of left sided heart failure).
Microscopy
• Fibrosis/scarring (destroys the normal leaflet architecture).
• Neovascularisation (normally no blood vessels on valves, suggest healing process).
• Calcification.
Explain how mitral stenosis can lead to atrial fibrillation.
- The most important functional consequence of RHD is valvular stenosis and regurgitation; stenosis tends to predominate.
- The mitral valve is involved in 70% of cases, with combined mitral and aortic disease in another 25%. The tricuspid valve usually is less frequently (and less severely) involved.
- With tight mitral stenosis, the left atrium progressively dilates owing to pressure overload, precipitating AF. The combination of dilation and fibrillation can lead to thrombosis and formation of large mural thrombi is common.
Identify the clinical features of rheumatic heart disease.
- Chronic RHD usually does not manifest itself clinically until years or even decades after the initial episodes of rheumatic fever. At that time, the signs and symptoms of valvular disease depend on which cardiac valve(s) are involved.
- In addition to various cardiac murmurs, cardiac hypertrophy/dilation and CHF, patients with chronic rheumatic heart disease often have arrhythmias (particularly AF in the setting of mitral stenosis) and thromboembolitic complications due to atrial mural thrombi. Furthermore, scarred and deformed valves are more susceptible to infective endocarditis.
- The long-term prognosis is highly variable. In some cases → cycle of valvular deformity, yielding haemodynamic abnormality that generates further deforming fibrosis.
- Surgical repair or replacement of diseased valves has greatly improved the outlook for patients with RHD.
What is mitral facies?
- Livid colour of the cheeks and acral cyanosis. Butterfly lividly erythema on surface of face.
- Pathogenesis: Due to cutaneous vasodilation and chronic hypoxemia.
- Cause: RHD (rarely other, SLE etc).
What are MacCallum plaques?
- Rough fibrous plaques in the left atrium caused by regurgitation of jets of blood flow, due to narrow incompetent mitral valve (MS & MR).
- Abnormal thickening of left atrium’s wall and its endocardial wall above the mitral valve due to fibrosis. Frequently occur in those with regurgitant valvular lesions such as mitral regurgitation. LA most common location.
- Narrow mitral opening → jets eject blood → jets of blood hits atrial wall causing scarring.
Identify the complications of rheumatic heart disease.
• Arrhythmia
• AF → causing thromboembolism.
- Obstruction to mitral valve → excess pressure in atria → excess pressure stimulates AF → stagnation of blood → thromboembolism in LA → can cause infarction/stroke.
• Infective endocarditis
- Granulations are bacterial clumps/colonies growing on abnormal valve. Bacteria and second infection common but valve is abnormal.
• Heart failure
- Due to severe obstruction - not enough to supply body.
Differentiate between ARF and RHD.
- ARF - Acute. Multisystem, autoimmune inflammation. Pancarditis.
- RHD - Chronic. Abnormal valves. Endocarditis only.
Etiological factors → Pancarditis → ARF → usually resolves without complications however, recurrent attacks leads to just endocarditis (valve) → results in RHD → destruction of valves only.
See KFP questions.
Outline congenital heart disease.
• Abnormalities of the heart or great vessels that are present at birth.
• Broad spectrum of malformations:
- Severe - incompatible with intrauterine or perinatal survival.
- Mild - produce only minimal symptoms at birth.
- Unrecognised during life.
• Present with heart failure with/without cyanosis.
• Congenital defects occur in 0.8% of live births - commonest cause of cardiac failure in infants.
• 80% unknown etiology. Idiopathic
• 20% due to alcohol/drugs (teratogens), rubella (viral infections), Down syndrome (genetic - chromosomal disorders), maternal diabetes and vitamin deficiency (e.g. folate) etc.
• 4-9 weeks of gestation is the most crucial period of heart development. Congenital heart disease arises from faulty embryogenesis when major cardiovascular structures develop during this period.
Describe the foetal circulation and 3 vascular shunts.
• Foetal circulation - non-functional lungs.
• Unique cardiovascular modifications seen only during prenatal development include the umbilical arteries and vein and 3 vascular shunts:
- Ductus venosus (liver)
- Foramen ovale
- Ductus arteriosus
• All of these structures are occluded at birth. Defects in the closure of the shunts is the commonest cause of congenital heart disease.
• Maternal blood (oxygenated) → umbilical vein → liver → liver sinusoids to hepatic vein OR ductus venosus (bypasses liver sinusoids) → hepatic vein and ductus venosus empty into IVC (mixes with deoxygenated blood from lower parts of foetus’ body) → right atrium.
• Some of the blood entering the RA flows directly into the LA via foramen ovale, an opening in the interatrial septum loosely closed by a flap of tissue.
• Blood that enters the RV is pumped out into the pulmonary trunk → ductus arteriosus → aorta → umbilical arteries → deoxygenated blood laden with metabolic wastes delivered back to capillaries in the chorionic villi of the placenta.
• These 2 shunts serve to bypass the non-functional lungs. Blood enters the 2 pulmonary bypass shunts because the heart chamber or vessel on the other side of each shunt is a lower-pressure area, owing to the low volume of venous return from the lungs.
Identify the classification of congenital heart disease.
• The various structural anomalies in congenital heart disease can be assigned to 3 major groups based on their haemodynamic and clinical consequences.
- Malformations causing a left to right shunt (acyanotic)
• Atrial Septal Defect (ASD) - commonest clinically
• Ventricular Septal Defect (VSD) - commonest at birth
• Patent Ductus Arteriosus (PDA) - Malformations causing a right to left shunt (cyanotic CHD)
• Tetralogy of Fallot (FT)
• Transposition of Great Arteries (TGA) - Malformations causing obstruction
• Coarctation of the Aorta (CoA)
Outline the clinical features of congenital heart disease.
• Right to left:
- Cyanosis results because the pulmonary circulation is bypassed and poorly oxygenated blood enters the systemic circulation.
- Clinical consequences of severe cyanosis include clubbing of the tips of the fingers and toes (hypertrophic osteoarthropathy), polycythemia (due to hypoxia) and paradoxical embolisation.
• Left to right:
- Low pressure, low resistance pulmonary circulation exposed to increased pressures and volumes. These conditions lead to adaptive changes that increase lung vascular resistance to protect the pulmonary bed, resulting in RV hypertrophy and eventually failure.
- With time, increased pulmonary resistance can also cause shunt reversal (right to left) and late onset cyanosis (causes pulmonary hypertension and secondarily right-sided pressures that exceed those on left). Such reversal of flow and shunting of unoxygenated blood into the systemic circulation is called Eisenmenger syndrome.
• Obstruction:
- Obstruct vascular flow by narrowing the chambers, valves or major blood vessels.
- Complete obstruction is known as atresia.
- In some disorders (e.g. tetralogy of Fallot), an obstruction (pulmonary stenosis) can be associated with a shunt (right to left through a VSD).
- The altered haemodynamics of congenital heart disease usually lead to chamber dilation or wall hypertrophy. However, some defects result in a reduced muscle mass or chamber size.
Describe atrial septal defects.
- Abnormal fixed opening in the atrial septum that allows unrestricted blood flow between the atrial chambers.
- Most common congenital heart disease.
- 3 types, secundum most common (90% are ostium secundum defects in which growth of the septum secundum is insufficient to occlude the second ostium).
- Majority asymptomatic until adulthood.
- Initially cause left to right shunts as a consequence of lower pressures in the pulmonary circulation and right side of heart (well tolerated, no symptoms in childhood).
- Overtime, chronic volume and pressure overloads can cause pulmonary hypertension → heart failure (late/rare).
