Salim Flashcards
Relate laplace law to chamber pressures in the left atrium as a result of mitral stenosis
In mitral stenosis, the pressure in the left atrium rises because it must work harder to push blood through the narrowed valve.
According to Laplace’s law, this increased pressure leads to increased tension on the atrial wall.
In response, the left atrium may undergo hypertrophy to handle the higher tension, which increases its oxygen demand.
Over time, chronic pressure overload causes atrial remodeling, resulting in dilation and weakening of the atrium, which can impair its ability to pump blood effectively and contribute to complications like arrhythmias
Why does angina occur is aortic stenosis
(1) Perfusion of the coronary arteries depends on the pressure difference between Diastolic blood pressure (e.g. 80mmhg) and LVEDP (e.g. 10mmHg). In aortic stenosis, the LVEDP increases which reduces the pressure difference which reduces perfusion of the coronaries.
(2) In severe stenosis, reduced stroke volume caused by the stenotic valve can lead to less blood passing back through the openings of the coronary arteries adjacent to the valve leaflets.
Describe the morphological features of acute and chronic rheumatic heart disease
Acute RHD
(1) Pancarditis with Aschoff body scattering in all layers of the heart
-Pericardial exudate (bread and butter exudate)
-Myocardial connective tissue with scattered aschoff bodies
-Endocardium (valves): fibrin deposition along the closure lines of the valves.
(2) Areas of fibrinoid necrosis can be seen.
Aschoff bodies are aggregates of: plasma cells, lymphocytes and Anitschow cells (large activated macrophages)
Chronic RHD
(1) Aschoff bodies are replaced with fibrous scar tissue
(2) valve cusps are thickened, calcified and have fibrous bridges across the opening - Button hole appearance.
(3) Chordae tendinae are thickened, fused and retracted.
List the 5 major criteria to make a diagnosis of ARF
Evidence of recent GAS infection plus
(1) Carditis
(2) Chorea
(3) Polyarthritis
(4) Erythema marginatum
(5) Sub cut nodules
List 5 minor criteria for ARF diagnosis
(1) Arthralgia
(2) elevated CRP
(3) elevated ESR
(4) Hyperpyrexia (>41.5)
(5) Prolonged PR interval
How is a diagnosis of ARF made
Evidence of recent GAS infection plus
2 major criteria
1 major and 2 minor criteria
list 3 ways to confirm a recent GAS infection
(1) Positive throat culture
(2) Antibody tests
-Antistreptolysin O Titre (ASO)
-Antistreptococcal DNAse B Titre (ADB)
(3) Rapid GAS carbohydrate antigen test.
Describe the pathogenesis of Post-streptococcal glomerulonephritis and how it presents
PSGN manifests approx 1-4 weeks after recovery from GAS infection.
-Antibodies against strep A form immune complexes with Strep antigens (commonly GADPH and Strep endotoxin B).
-These complexes can then lodge in the glomeruli and cause inflammation via complement activation and leukocyte infiltration.
Results in:
-> glomerular hypercellularity due to swelling and proliferation of the mesangial and endothelial cells.
-> IgG deposition in vessel wall
-> Vessel wall necrosis and crescent formation can be seen in more severe cases.
The result is impaired glomerular filtration barrier which presents as nephritic syndrome:
- Oliguria
- Haematuria
- mild proteinuria
- HTN
- Oedema.
Describe the mechanism of action of heparin
Heparin in general binds to Anti-thrombin III, thereby increasing AT III’s affinity for the active sites of Thrombin (IIa) and Xa.
Unfractionated heparin is larger molecule and so can inhibit both Thrombin and Xa. This is because, in order to inactive Thrombin, it requires heparin to bind to both it and AT-III.
LMWH mostly only inhibits Xa, because Xa inhibition only requires binding of heparin to AT-III.
Explain why unfractionated heparin is less predictable than LMWH
Unfractionated heparin (UFH) is less predictable because its elimination follows zero-order kinetics at therapeutic doses. In zero-order kinetics, a constant amount of UFH is eliminated per unit time, regardless of its concentration in the blood. This occurs when the body’s usual elimination pathways become saturated, meaning they cannot handle higher concentrations of the drug. As a result, excess heparin can accumulate in the blood if too high a dose is given, leading to prolonged effects. This accumulation increases UFH’s half-life, further extending its anticoagulant action and making its effects harder to predict.
In contrast, low molecular weight heparin (LMWH) follows first-order kinetics, where a constant percentage of the drug is eliminated per unit time. This means that its half-life remains constant, regardless of the dose, leading to more predictable drug levels and anticoagulant effects in the body.
Opening snap and diastolic rumble is what?
Mitral stenosis.
The snap is caused by forced opening of the mitral valve leaflets caused by increased pressures within the left atrium. The valves are stiff and calcified causing an opening snap sound to be heard. The opening of mitral valve occurs at the beginning of diastole after the 2nd heart sound. Under normal conditions the opening is silent.
The rumble is caused by turbulent blood flow through the stenotic/narrowed valve which creates reverberations/vibrations off the left ventricle wall, heard as a rumble.
The shorter the interval between S2 (aortic valve closure) and the opening snap, the more severe the stenosis as this reflects a higher left atrium pressure that was needed to force open the valve.
Systolic click is what?
Mitral valve prolapse causing mitral regurgitation.
During systole, on ventricular contraction, the mitral valves can billow upwards into the left atrium, pulling on the chordae tendinea/papillary muscles and causing a click sound. It is typically heard in the middle of systole but it depends when during systole the prolapse occurs. To generalise it, it occurs between S1 and S2.
name 2 organisms that commonly cause infective endocarditis and where on the body each can be found
Staph aureus: nostrils, mucous membranes, skin, oropharynx
Strep viridians: oral cavity, nasopharynx, GI tract, female genital tract.
explain what is meant by immunological cross-reactivity
Immunological cross-reactivity refers to when immune components (like antibodies or T-cells) that are designed to recognize one specific antigen also bind to a different antigen because of structural similarity. This can happen between two different pathogens or between a pathogen and unrelated environmental antigens. When this reaction involves the body’s own tissues, it can contribute to autoimmune reactions, which is where molecular mimicry comes into play
List 3 indications for valvular surgery in infective endocarditis
Name 3 surgical options for infective endocarditis
Indications
(1) Heart failure or cardiogenic shock
(2) Embolic complications or high risk of
- Vegetations >10mm
- Highly mobile vegetations
- Afib
- Multi valve involvement
(3) Uncontrolled infection
-persistent positive blood culture
-Enlarging vegetations
-Abscess formation
Surgical options
(1) Total Valve replacement
(2) Partial leaf replacement/Patch repair
(3) Debridement of infective material
(4) Aortic root replacement.
Explain why warfarin may initially cause a hypercoagulable state unless heparin is given concomitantly
This is because warfarin results in depletion of the endogenous anti-coagulant Protein C.
Protein C has a shorter half life than the pre-formed vitamin K dependant clotting factors, therefore protein C levels fall more rapidly than these clotting factors. (it is important to note that warfarin only effects newly formed clotting factors, and those already circulating must undergo natural degradation)
This means that there is an initial imbalance between anticoagulative and procoagulative system which results in a procoagulable state.
This can result in the formation of microthombi which can occlude vasculature and cause warfarin-induced skin/tissue necrosis.
For this reason, concomitant heparin should be given intially until suitable INR is reached.
how does warfarin cause fetal bone deformities?
Through vitamin-k antagonism, warfarin prevents activation of Osteocalcin, a vit-K dependant protein.
Osteocalcin is critical for normal bone mineralisation, structure and development.
(i) craniofacial abnormalities (nasal bridge hypoplasia, microcephaly)
(ii) Stunted limb growth
(iii) Congenital heart defects
list 4 inhibitors and inducers of CYP450
Inhibitors (enhance warfarin effects)
-Antibiotics such as macrolides, fluorquinolones (ciprofoxacin) and Nitroimidazoles (Metronidazole)
-PPI’s
-Anti arrythmics e.g. Amiodarone, a potassium channel inhibitor.
Inducers (reduce warfarin effects)
- Carbamezapine
- Rifampicin
- Alcohol
- Glucocorticoids.
What are the Major duke criteria for IE
Positive blood cultures - At least 1 of the following
(i) Positive for typical I.E causing bacteria in 2 separate blood cultures. (E. Faecalis, Staph aureus, strep viridians, gram -ve HACEK group)
(ii) Persistent bacteremia with IE bacteria
–> 2 samples taken >12 hours apart are +ve
–> 3 or more +ve samples taken at different times with first drawn >1 hour apart
(iii) Single positive culture for Coxiella Burnetti or a very high IgG titre against it (>1:800)
Evidence of endocardial involvement on imaging
-Ultrasound, Cardiac CT, PET.
-Vegetations
-New valvular regurgitation
What are the minor criteria for IE
- Fever (>38 deg)
- Embolic manifestations e.g. conjunctival hemorrhages, janeway lesions, splinter hem, intracranial hem
- Immunological disturbances: Glomerulonephritis, osler nodes, roth spots, rheumatoid factor
- Risk factors: underlying heart disease, IV drug use.
- Blood culture positive for bacteria other than typical I.E-causing bacteria
How can you make a definitive diagnosis of IE?
2 major
1 major, 3 minor
5 minor
What are the normal systolic and diastolic pressures for chambers of the heart
Left ventricle
-Systolic 120mmHg
-Diastolic 10mmHg
Right ventricle
-Systolic 25mmHg
-Diastolic 4mmHg
Left atrium
8-10mmhg
Right atrium
<4mmHg
Describe the pathophysiology of valvular disease in rheumatic fever
Rheumatic fever is primarily a type II hypersensitivity reaction (with type IV components) following infection with group A streptococcal (GAS) beta-hemolytic bacteria.
Antibodies are produced against the bacterial M-protein, but these antibodies and CD4+ T cells cross-react with self-antigens in the heart, including cardiac myosin and valvular endothelium, due to molecular mimicry.
This immune response results in complement activation, leukocyte infiltration, and the release of proinflammatory cytokines, leading to pancarditis—inflammation of the pericardium, myocardium, and endocardium.
In the acute phase, the immune response leads to the deposition of fibrin along the closure lines of the mitral valve, forming small verrucae. Additionally, Aschoff bodies, which are granulomatous lesions, may form in the myocardium.
Over time, with recurrent episodes of rheumatic fever, chronic inflammation causes fibrosis, scarring, thickening of the mitral valve cusps, commissural fusion, and thickening/fusion of the chordae tendineae. This leads to mitral stenosis, though mitral regurgitation can also occur, particularly when the chordae tendineae are involved.
Mitral stenosis occurs due to the narrowing of the valve orifice, impeding blood flow from the left atrium to the left ventricle, while mitral regurgitation can occur in the acute phase due to valvulitis and the resultant failure of the valve to close properly
List 4 underlying causes of mitral regurgitation
- Infective endocarditis
- Papillary muscle rupture
- Chordae tendinae rupture
- Left ventricular dilation
- Calcification of mitral annular ring
- Myxomatous mitral valve (connective tissue disorder causing mitral prolapse)
4 causes of mitral stenosis
- Rheumatic fever
- Congenital stenosis
- Amyloidosis
- SLE
- Atrial myxoma
- Radiotherapy to the chest
List 3 processes that give rise to murmurs
- Stenosis
- Regurgitation
- Septal defects (ASD/VSD or shunts (PDA)
ECG changes in left atrial enlargement?
(1) P-mitrale –> double peaked P wave +/- prolongation in the P wave duration
(2) Atrial fibrillation
-Irregularly irregular rhythm
-Absent P waves
-Narrow QRS tachycardia
ECG changes in LVH
- S wave V1 + R wave V5 or V6 >35mm
- Left axis deviation (Positive deflection leads I, negative deflection leads II, III, aVF)
- Strain pattern in V5 or V6
–> ST depression
–> T wave inversion
List 5 things that can increase the INR of a patient on warfarin
CYP inhibitors
- Macrolides
- Quinolones (ciprofloxacin)
- Amiodarone
- Azole antifungals (fluconazole)
High output states
-Thyrotoxicosis
-Fever
Acute alcohol consumption
Liver disease
name 5 risk factors for IE
- Mechanical heart valve
- HIV
- IV drug use
- Poor dentition
- Indwelling catheter
