Cardiac

Question 1

Explain the pathogenesis of Atherosclerosis

Answer 1

1. Endothelial injury causes accumulation of LDL
2. LDL enters intima and is trapped in sub-intimal space
3. LDL is converted into modified and oxidized LDL causing inflammation
4. Macrophages take up ox/modLDL via scavenger receptors and become** foam cells**
5. Apoptosis of foam cells causes inflammation and cholesterol core of plaque
6. Increase in adhesion molecules on endothelium due to inflammation results in more macrophages and T cells entering the plaque
7. Vascular smooth muscle cells form the fibrous cap, segregating thrombogenic core from lumen

Question 2

What are the cellular components of an atheroscelrotic plaque?

Answer 2

1. Macrophages (with injestion of LDL turn into Foam Cells)
2. Lymphocytes (T>B) : involved in inflammatory process and progession of plaque formation
3. Smooth muscle cells

Question 3

What sites of the aorta are most predisposed to the development of atheromas?

Why?

Answer 3

1. More common in abdominal than thoracic aorta

More common in origins (ostia) of major branches → turbulent blood flow has low/oscillatory shear stress, which is atherogenic

Question 4

What is the definition of stable and unstable angina?

Answer 4

Stable: pain on exertion, predictable, relieved by rest (~70% vessel occlusion)

Unstable: pain at rest also. High likelihood of impending infarction (usually >90% occluded)

Question 5

What is Prinzmetal angina?

Answer 5

Rare, due to coronary artery spasm rather than atherosclerosis (seen in young, japanese women, associated with cocaine use or other vasospastic conditions)

Question 6

How does a atherrosclerotic plaque rupture lead to MI?

Answer 6

Higher risk in unstable atherosclerotic plaques (thin, fibrous cap (often weakened due to inflammation and metalloproteases secreted by macrophages) with thick lipid core)

Rupure –> superimposed platelet activation → thrombosis and vasospasm → occlusive intracoronary thrombus overlying disrupted plaque

Question 7

What is the difference between a plaque rupture and atheroma erosion?

Answer 7

Rupture: exposure of lipid core of plaque into lumne, usually associated with formation of red thrombus

Erosion: exposes prothrombogenic subendothelial basement membrane (usually leads to formation of white plaque

Question 8

When does cardiac ischaemia lead to irreversible cell damage?

Answer 8

Usually after 20-30 minutes after ischaemia

Question 9

Which cardiac vessle is the most common site of MIs?

Answer 9

50% in LAD

40% in RCA
(and 20% in LCx)

Question 10

What part of the heart is supplied by the LAD?

Answer 10

ant wall LV, ant septum, apex

Question 11

What parts of the heart are supplied by the LCx?

Answer 11

lat LV not apex

Question 12

What part of the heart is supplied by the RCA?

Answer 12

lat LV not apex

Question 13

What histological changes are seen 1-6h post-MI?

Answer 13

None

Question 14

What histological changes are seen 6-24h after an MI?

Answer 14

loss of nuclei, homogenous cytoplasm necrotic cell death

Question 15

What histoloigical changes are seen 1-3 days post-MI?

Answer 15

Infiltration of polymorphs then macrophages (clear up debris)

Question 16

What histological changes are seen 1-2 weeks post-MI?

Answer 16

granulation tissue, new blood vessels, myofibroblasts, collagen synthesis

Question 17

What histological changes are seen >2 months after anMI?

Answer 17

strengthening, decellularising scar

Question 18

What are common causes of Heart failure?

Answer 18

• Ischaemic heart disease
• Myocarditis
• Hypertension
• Cardiomyopathy (dilated)

Others include
* Valve disease
* Arrhythmias

Question 19

How does heart failure lead to fluid overload?

Answer 19

Via 2 mechanisms

1. (Show sx of fluid overload): Reduced in Cardiac function –> increased central venous pressure –> signs of increased pressure in lungs (oedema) or liver (nutmet liver)
2. Decreased Cardiac output –> Decreased Arterial Pressure –> activation of RAS –> increased Salt+Water retention –> fluid overload

Question 20

What is cardiomyopathy?

What is the most common sub-type of cardiomyopathy?

Answer 20

Cardiomyopathy are diseases of the heart muscle

The most common sub-type is Dilatead cardiomyopathy

Question 21

How does dilated cardiomyopathy lead to heart failure?

Answer 21

In dilated cardiomyopathy muscle wall is too thin and leads to **systolic dysfunction due to decreased LV contractility and reduced EF ** –> initially LV then RV heart failure

Question 22

What is the aetiology of dilated cardiomyopathy?

Answer 22

Pathophysiology: causative factors lead to decreased myocardial contractility –> increase in pressure remain output –> cardiac remodeling

Primary: Idiopathic (+some very rare gene defects)

Secondary

• alcohol
• Thyroid disease
• Haemochomatosis
• Viral myocarditis

+ and many others

Question 23

How does hypertrophic cardiomyopathy lead to Heart failure?

Answer 23

Thickened myocardium –> smaller ventricle –> Diastolic dysfunction –> heart failure

Question 24

What is the aetiology of hypertrophic cardiomyopathy?

Answer 24

Primary
HCO (Autosomal dominant, most common hereditary heart diseaes)
Storage diseases

Secondary
HTN
Aortic Stenosis
Amyloidosis

Question 25

What is the differnce between Hypertrophic - and Hypertrophic-Obstructive Cardiomyopathy?

Answer 25

Hypertrophic obstructive cardiomyopathy (HOCM) occurs when hypertrophy of the interventricular septum and systolic anterior movement (SAM) of the mitral valve leaflet results in the left ventricular outflow tract (LVOT) obstruction

Question 26

What is genetic HCM? What gene mutation is most commonly affected?

Answer 26

Hypertrohic cardiomyopathy is a genetic autosomal dominant condition 70% are HOCM , 30% HCM (non-onbstructive) Usually caused by mutation in βMHC (β-myosin) gene, but other mutations can also be causative

Question 27

What is restrictive cardiomyopathy? What are some causes of restrictive cardiomyopathy?

Answer 27

Stiffness of the myocardium resulting in decreased diastolic function Many aetiologies Can be sub-devided into **1. Infiltrative** (e.g. Sarcoid, Amyloidosis) **2. Storage**(e.g. haemochromatosis, iron overload) **3. Endomyocardial**(e.g. endomyocardial fibrosis autoimmune disease)

Question 28

What is acute rheumatic fever? What systems are invovled in the development of rheumatic fever?

Answer 28

Multi-system inflammatory disease occuring 2-4 weeks after untreated group A streptococcus infection (GAS) Systems involved are 1. Heart (pericarditis, valvular disorders) 2. Joints: arthritis 3. Skin: erythema marginatum, subcutaneous nodules 4. CNS: Encephalopathy

Question 29

What is rheumatic heart disease?

Answer 29

Rheumatic heart disease refers to two clinical entities: 1. Acute pancarditis as a sequela of GAS infection 2. Chronic cardiac valvular changes as a complication of acute rheumatic fever (usually mitral valve)

Question 30

What is the epidemiology of Acute rheumatic fever?

Answer 30

Peak incidence 5-15 years Less common in the UK now, more common in resource-limited countries

Question 31

What is the pathophysiology of acute rheumatic fever?

Answer 31

Not well understood thought to be molecular mimicry of GAS myosins: development of antibodies against streptococcal M protein → cross-reaction of antibodies with nerve and myocardial proteins (most commonly myosins) due to molecular mimicry → type II hypersensitivity reaction → acute inflammatory sequela

Question 32

How is acute rheumatic fever diagnosed?

Answer 32

1. Evidence of recent GAS infection (throat culture, antigen or antibody testing) 2. Diagnosis via revised Jones criteria (2 Major or 1 Major + 2 Minor)

Question 33

What is the treatment of acute rheumatic fever?

Answer 33

1. Antibiotics agains Group A strep: penicillin V, benzylpenicillin (erythromycin in allergy) 2. Suppression of inflammatory process: NSAIDs (Naproxen) + Prevention with monthyl IM penicillin injections until 10 years after episode OR age of 21

Question 34

How is a sore throat in children due to confimred Group A strep treated?

Answer 34

Has to be treated with abx due to risk of Rheumatic fever: **Phenoxymethylpenicillin** (Given for 5 to 10 days), alternative Clarithromyci If penicillin allergy Avoid amoxicillin because it may cause a widespread maculopapular rash if the tonsillitis is due to infectious mononucleosis

Question 35

Acute rheumatic fever can lead to formation of valvular vagitations due to molecular mimicry. What would the characteristics of the vegetation be?

Answer 35

Small, warty vegetations found along the lines of closure of valve leaflet - ‘verrucae’.

Question 36

A pathologcy cardiac specimin shows Large, irregular masses on valve cusps, extending into the chordae. What is the most likely diagnosis?

Answer 36

Typical presentation of Infective endocarditis --> Colonisation or invasion of heart valves or mural endocardium by microbe

Question 37

What is the most common pathogen causing infective endocarditis? What are the most common valved affected by infective endocarditis?

Answer 37

Most common, regardless of valve: Staph Aureus, other associated with specific risk factors Most common valves: Mitral and aortic, unless IVDU where right side more common

Question 38

What are the diagnostic criteria for diagnosing Infective endocarditis?

Answer 38

Duke Criteria, diganosis when * 2 major * 1 major + 3 minor * 5 minor Major * Positive blood culture growing typical IE organisms or 2 positive cultures >12hrs apart * Evidence of vegetation/abscess on echo or new regurgitant murmur Minor * Risk factor (e.g. prosthetic valve, IVDU, congenital valve abnormalities) * Fever >38 * Thromboembolic phenomena * Immune phenomena * Positive blood cultures not meeting major criteria

Question 39

What antibiotc treatemet is give in infective endocarditis?

Answer 39

Flucloxacillin for MSSA, rifampicin + vancomycin + gentamicin for MRSA. (S. aureus IE is very nasty so make sure there is cover for this If subacute (usually due to other organims, incl. Strep viridans, staph epidermis): Benzylpenicillin + gentamicin; or vancomycin for 4 weeks.

Question 40

What are the most common causes of Aortic stenosis?

Answer 40

1. Calcificaton (old age, aortic sclerosis) 2. Bicuspic aortic valve (congenital)

Question 41

What are causes of aortic regurgitation?

Answer 41

* Infective endocarditis * dissecting aortic aneurysm * LV dilation * connective tissue disease e.g. Marfans, Ank Spon

Question 42

What is the main cause of mitral stenosis?

Answer 42

Rheumatic fever

Question 43

What are the main cases of mitral regurgitation?

Answer 43

Infective endocarditis, connective tissue disease, post-MI, rheumatic fever, left ventricular dilation (functional MR)

Question 44

What are some causes of pericarditis?

Answer 44

1. idiopathic 2. Infectious (usually viral, esp. coxacie B) 3. Miocardial infarction: 1-3 days after as reaction, or weeks to month after (Dresslers syndrome) 4. Others (e.g. uraemia, radiation etc.)

Question 45

What are clinical findings of acute pericarditis?

Answer 45

Pleuritic chest pain, improved on sitting and leaning forward + pericardial friction rub on ausculation +/- pericardial effusions