Histopathology 6 - Vascular and Cardiac pathology Flashcards
- Progression of an atheroma:
- Raised lesion which projects into the lumen (preceded by fatty streak)
- Soft lipid core
- White fibrous cap
Recall the 7 steps of atheroma pathophsyiology
- Endothelial injury - this happens because of the risk factors discussed later. Turbulent blood flow due to hypertension etc also contributes
- LDL enters intima and gets trapped in intimal space
- LDL is converted into oxidised LDL –> inflammation
- Macrophages take up OxLDL via scavenger receptors –> foam cells
- Foam cell apoptosis –> inflammation and cholesterol deposition to form plaque core
- Endothelium expresses more adhesion molecules –> more macrophages and T cells enter plaque
- VSMCs form fibrous cap
What % atheroma of a vessel lumen is considered ‘critical stenosis’?
70%
What is prinzmental angina?
Coronary artery spasm
Which parts of the cardiac muscle are affected by an infarction of the LAD?
Anterior wall of left ventricle, anterior septum and apex
Which parts of the cardiac muscle are affected by an infarction of the RCA?
Posterior wall of left ventricle, posterior septum and posterior wall of right ventricle
Which parts of the cardiac muscle are affected by an infarction of the LCx?
Lateral wall of left ventricle
What are the 4 most important complications of MI?
- Contractile dysfunction (eg cardiogenic shock)
- Arrhythmia >> most common cause of acute death after MI
- Myocardial rupture >> can result in cardiac tamponade
- Pericarditis
What is Dressler’s syndrome?
Pericarditis occuring weeks-months post-MI
autoimmune
What is the average time between MI and myocardial rupture?
4-5 days
What is the prognosis of papillary muscle rupture following MI?
Rubbish - very high mortality
What is the most common cause of sudden cardiac death?
Lethal arrhythmia
What is restrictive cardiomyopathy + causes
Normal size heart but with large atria - due to amyloidosis + sarcoidosis
Recall 3 possible causes of aortic regurgitation
MAIN CAUSE: RHEUMATIC FEVER
Infective endocarditis
Marfan’s
Ankylosing spondylitis
- Rigidity- rheumatic, degenerative
- Destruction- microbial endocarditis
-
Disease of the aortic valve ring
- Dilation means the valve leaflets are insufficient to cover the increased area
- Marfan’s syndrome
- Dissecting aneurysm
- Syphilitic aortitis
- Ankylosing spondylitis
What is Monckeberg atherosclerosis?
Focal calcification of the media of small-medium sized vessels; no associated inflammation
What histological findings would be found within 6 hours of an MI?
Normal histology and normal CK-MB
What histological findings would be found 6 -24 hours following an MI?
Loss of nuclei
Homogenous cytoplasm
Necrotic cell death
What histological findings would be found 1-4 days following an MI?
Infiltration of polymorphs (monocytes + lymphocytes) and macrophages
What histological findings would be found 5-10 days following an MI?
Removal of debris
What histological findings would be found 1-2 weeks following an MI?
Granulation tissue
New blood vessels
Myofibroblasts
Collagen synthesis
What histological findings would be found in the months following an MI?
Strengthening, de-cellularising scar tissue
Recall the possible complications of MI
Mnemonic = PACE MAKERED
Papillary muscle dysfunction/rupture >> mitral regurgitation
Arrhythmia >>> most common cause of acute death after MI
Ccf
Effusion (pericardial)
Mural thrombus
Aneurism (ventricular) >> late complication
(K)ontractile dysfunction >> cardiogenic shock secondary to reduced contractility
Early pericarditis
Rupture of venticular wall/myocardial rupture >> cardiogenic shock
- most common- free wall
- septum- less common: VSD + right to left shunt
- papillary mscule: mitral regurgitation
Elevation of ST segment
Dressler’s syndrome
What types of cardiomyopathy can be caused by sarcoidosis?
Dilated
more commonly restrictive
Which type of cardiomyopathy is associated with alcohol misuse?
Dilated
Is the pathology of cardiomyopathy systolic or diastolic dysfunction in
a) dilated CM
b) hypertrophic CM
c) restrictive CM?
Dilated: systolic
Hypertrophic and restrictive: diastolic
What is the HOCM?
Hypertrophic obstructive CM = septal hypertrophy + Thickening of the heart muscle, usually left ventricular hypertrophy
resulting in an outflow tract obstruction: narrowing of the LV outflow tract
offen causes sudden death
What mutation is associated with Hypertrophic CM?
Beta-myosin heavy chain
- autosomal dominant
(Beta-HMC - HMC is HCM rearranged)
Recall the major criteria for Rheumatic fever diagnosis
CASES
Carditis
Arthritis
Sydenham’s chorea
Erythema marginatum
Subcutaneous nodules
What is the main pathogen in rheumatic fever?
Lancefield group A strep
How is ‘antigenic mimicry’ involved in rheumatic heart fever?
Cell-mediated immunity and antibodies to streptococcal antigen cross-react with myocardial antigens
How are vegetations seen on heart valves in rheumatic fever described?
Small and warty, “verrucae”
beady vegestations,
Aschoff bodies (small giant- cell granulomas),
Anitschkov myoocytes (regenerating myocytes)
What is Libman-Sacks endocarditis
Unknown pathogenesis - associated with SLE and anti-phospholipid syndrome
NON-INFECTIVE form of endocarditis >>> inflammatory endocarditis
Differentiate the likely causative organisms in acute vs subacute infective endocarditis
Acute: Staph aureus/ pyogenes
Subacute: strep viridans/ epidermis/ HACEK/ coxiella/ candida/ mycoplasma
Recall the major and minor Duke criteria for infective endocarditis
Major:
- Pos BC growing typical IE organism OR 2 pos BCs >12hrs apart
- Evidence of vegetation/ abscess on echo or new regurgitant murmur
Minor:
- RF: e.g. prosthetic valve, IVDU, congenital valve abnormalities
- Fever >38
- Thromboembolic phenomena:
- Janeway lesions
- Septic abscesses in lungs/ brain/ spleen/ kidney
- Microemoboli
- Splinter haemorrhage
- Splenomegaly
- Immune phenomena:
- Roth spots
- Osler’s nodes
- Haematuria due to glomerulonephritis
- Pos BCs not meeting major criteria
How many of Duke’s criteria are needed for diagnosis of infective endocarditis?
2 major
1 major and 3 minor
5 minor
What abnormality in the mitral valve might be caused by rheumatic fever vs IE?
RhF: mitral stenosis
IE: mitral regurgitation
How many deaths are caused by coronary heart disease?
men under 75: 25%
women under 75: 16%
Where in the world is ischaemic heart disease increasing?
Japan - because of increase in adoption of the western diet
Definition of atherosclerosis?
Arteriosclerosis charactersed by atheromatous deposits in and fibrosis of inner layer of the arteries
Risk factors for atherosclerosis
Unmodifiable
- genetics - family history is the largest risk factor i.e. familial hypercholestrolaemia
- age - increasing age
- gender - postmenopausal women at higher risk
Modifiable
- smoking
- hyperlipidamiea
- hypertension
- diabetes mellitus
Risk factors are multiplicative
Other risk factors: (commonly in those without any of the above risk factors)
- Inflammation
- Hyperhomocysteinaemia
- Metabolic syndrome
- Lipoprotein (a)
- Haemostasis (procoagulation)
- Lack of exercise
- Stress
- Obesity
important studies
- framingham heart study
- atherosclerosis risk in communities study
What age group is most likely to get MIs?
40-60
What is the earliest change in atherosclerosis? What is it?
Fatty streak
- lipid filled foamy amcorphages
- don’t obstruct lumen flow
- seen in children above the age of 10
*
What is an atheroscleortic plaque?
What is the main difference between fatty streak and atherosclerotic plaque?
Fatty streak - no disturbance to blood flow
Atherosclerotic plaque: disturbs blood flow
Where in arteries do atheroscleortic plaques tend to occur?
At branch points where there is turbulent blood flow
What are the two main consequences of atheroma?
1. obstruction of lumen - stenosis
>70% of occlusion/diameter of <1mm –> critical stenosis–> stable angina –> chronic ischaemic heart disease
(crtical stenosis- demand outgrows the supply)
2. acute plaque change
a) rupture - exposes prothrombogenic plaque contents
b) erosion - exposes prothrombogenic subendothelial basement membrane
c) haemorrhage into the plaque - plaque therefore gets bigger >>>artery occlusion, subsequent ischaemia and death)
Who does acute plaque change occur in?
Can occur in people with mild-moderate stenosis so lots of asymptomatic people with risk of plaque rupture
i.e. plaque does not have to be big to undergo these acute changes : big ones are usually quite stable
What makes plaques vulnerable to rupture
- Lots of foam cells or extracellular fluid
- Thin fibrous cap
- Few smooth muscle cells
- Clusters of inflammatory cells
- Adrenaline increases blood pressure and causes vasoconstriction
- which leads to increased physical stress within the plaque
- Therefore, emotional stress can increase the risk of sudden death
- anything that causes vasoconstriction
- Adrenergic agonists
- Platelet contents
- Reduced endothelial relaxing factors
- Mediators from perivascular cells
- Circadian rhythm
- more likely to infarct in the early morning (6am- noon)
When are you most likely to have an infarction?
6 am to noon
WHat % of IHD is caused by atherosclerosis?
90%
What % stenosis do you need for pain on rest?
% needed for pain on exercise?
90%
75%
What causes acute coronary syndromes?
When stable plaque becomes unstable
This happens because of rupture, erosion or haemorrhage
Generally leads to superimposed thrombus which occludes the lumen further
Types of angina
Stable - comes on with exertion and relieved on rest: no plaque disrupion
Unstable - more frequent and longer lasting pain. present at rest or with lower levels of activity. Due to plaque disruption with superimposed thrombus. Impending MI.
Prinzmetal: due to coronary artery vasospasm - uncommon
What does Non‐reperfused MI show?
Typical ischaemic coagulative necrosis
How quickly does loss of contractility occur after plaque rupture?
Within 60 seconds
heart failure can precede myocyte death (so they could get an arrhythmia and die before any histological changes take place
When does heart failure occur in relation to myocyte death and what is the consequence of this?
Heart failure can precede myocyte death - because loss of contractility occurs within 60 seconds of plaque rupture
This means patient can die before any histological changes take place
When does MI become irreversible?
It is reversible before myocyte death occurs
Once myocyte death occurs it becomes irreversible - usually within 20-30 mins
**obviously, if the patient hasn’t already died before myocyte death occured…*
Which coronary artery is most affected by MI?
LAD - 50%
RCA - 40%
LCx- 10%
Changes wthin first 6 hours of MI
Normal histology
Normal CK-MB
What happens 6-24 hours post MI?
- loss of nuclei
- homogenous cytoplasm
- necrosis
What happens 1-3 days post MI?
- polymorph cells infiltrate (moth-eaten neutrophils eating the damaged myocardium)
- loss of nuclei and striations
- coagulative necrosis
What happens 1-2 weeks following MI?
Granulation tissue
New blood vessels
Myofibroblasts
Collagen synthesis
Over time, macrophages appear
What happens weeks-months after MI?
STrengtheining
decellularising scar formation
WHich type of MI does not cause ST changes?
Subendocardial infarct - does not affect the full thickness
Which factors cause worse prognosis from MI?
- age
- female
- DM
- previous MI
When do half of deaths from MI occur?
Within an hour
Why does reperfusion injury occur?
Reperfusing blood to area of died cardiac cells>>>> oxidative stress, calcium overload and inflammation can cause further injury>>> can lead to arrythmias etc.
Can cause STUNNED MYOCARDIUM: reversible cardiac failure lasting several days
What is the name given to reversible cardiac failure as a result of reperfusion injury?
Stunned myocardium
What is hibernating myocardium?
- The concept that chronic sublethal ischaemia
- → lower metabolism (i.e. hibernating) in myocytes
- which can be reversed with revascularisation
Complications of MI
When do arrythmias occur post MI
First few hours - days
When does persistent pain following MI occur?
12 hours to few days
When does angina following MI occur?
Can be immediate or delayed
When does cardiac failure post MI occur?
Variable
When does mitral incompotenece post MI occur?
First few days
When does pericarditis post MI occur?
2-4 days
When does cardiac rupture post MI occur?
3-5 days
When does mural thrombus post MI occur?
>Week
When does ventricular anueyrsm post MI occur?
>4 weeks
When does Dressler’s syndrome post MI occur?
Weeks to months
When do pulmonary emboli post MI occur?
>1 week
Anterolateral MI leads
aVL, V2, V3, V4, V5, V6
**remove the 1s**
Anterior MI leads
Left Anterior Descending artery
V1-V4
Lateral MI leads
Left Circumflex artery
V5, V6, Lead I, aVL
Inferior MI leads
Right Coronary artery
Lead II, III, aVF
Septal MI leads
V1 and V2
What is sudden cardiac death?
unexpected death from cardiac causes in individuals:
WITHOUT symptomatic heart disease
or early (1 hour) after the onset of symptoms
COMMONLY due to LETHAL ARRYTHMIA: thought to occur due to ischaemia-induced electrical instability
other causes: aortic stenosis, mitral valve prolapse and pulmonary hypertension
Most have underlying atherosclerosis
CHF vs RHF vs LHF
CHF: both sides
RHF: peirpheral oedema and nutmeg liver
LHF: SOB and pulmonary oedema - water logged lungs
MOst common cause of RHF
LHF
Histology of heart failure
LVF = iron laden macrophages
Dilated heart
Scarring and thinning of walls
Fibrosis and replacement of ventricular myocardium with scar tissue
Definition of cardiomyopathy
Intrinsic problems of the heart not due to ischaemic or valvular causes etc.
Histology of rheumatic fever
beady vegetations
Aschoff bodies:
small giant-cell granulomas
Anitschkow myocytes:
Which valves are affected in rheumatic fever?
Most commonly mitral
Followed by aortic
Then tricuspid then pulmonary
Complication of chronic rheumatic valvular disease
Aortic stenosis
Most common cause of aortic stenosis +AGE OF ONSET
Calcific aortic stenosis - impairs the opening and compromises the orifice >>>outflow tract obstruction + REDUCED BLOOD FLOW
occurs in 70s-80s
Main cause of aortic regurgitation
Rheumatic fever
Most likely causative organisms of infective endocarditis
- acute: staph aureus. mostly in IVDU. can occur on healthy or damaged valves
- subacute: strep viridans. usually affects pre-existing damaged valves
Treatment of rheumatic fever
Benzylpenicillin
Treatment of infective endocarditis
Acute: flucloxacillin
Subacute: benzylpencillin
Most commonn location for atheroscleortic anueyrsm
Abdominal region below renal arteries
Types of anuerysms
- saccular: only one side of vessel wall affected
- fusiform: both sides of vessel wall affected
** anuerysms involve all layers of the wall unlike false anueyrsms where only particular layers of the wall are invovled
- False- extravascular haematoma (i.e. a rupture and haematoma that forms)
2 main complications of aneurysms
- rupture: more likely in lower portion (ABDOMINAL) of the aorta
- dissection: more likely in upper portion of the aorta ie aortic arch
can tear and get a false lumen + false lumen causes problems >> Can get blockage and poor flow, leading to ischaemia distally
3 principcal components of atheroscleortic plaques
Cells - including SMC, macrophages and other leukocytes; 2. ECM including collagen; 3. Intracellular and extracellular lipid
WHich part of aorta is more affected by atheroscleorsis ?
**abdominal aorta** - confirm
- An atherosclerotic aneurysm typically occurs in the abdominal portion below the renal arteries
What type of blood flow makes you more suspcetible to atheroscleoriss?
Laminar is protective
Low shear stress is dangerous (especially at origins of major branches–>turbulent blood flow)
Duration of MI that leads to irreversible injjury
20-40 mins
What % of patients develop arrythmia following an MI? and which type of aarythmia is of most concern
90%
*VF: usually in first 24 hours, common cause of sudden death
What complication of MI causes persistent ST elevation?
Ventricular aneurysm
Histology of HCM
Myocyte disarray - arrythmogenic
Large, irregular masses on valve cusps,
extending into the chordae.
Infective endocarditis
Small, warty vegetations found along the heart disease
lines of closure of valve leaflet - ‘verrucae’
Rheumatic heart disease
Small, bland vegetations attached to thrombotic lines of closure. Formed of thrombi.
Non-bacterial thormbotic enodcarditis
Small (up to 2mm), warty vegetations that are sterile and platelet-rich.
Libman Sacks endocarditis
SLE
Acute vs subacute endocarditis
Which valves are affected in chronic hreumatic valve disease?
Mitral>aortic>tricuspid>pulmonary
Mid-systolic click + late systolic murmur
Mitral prolapse
*usually middle aged women, SOB, chest pains
Types of pericarditis
Fibrinous (MI, uraemia)
● Purulent (Staphylococcus)
● Granulomatous (TB)
● Hemorrhagic (tumour, TB, uraemia)
● Fibrous (a.k.a. Constrictive) (arises from any of above)
- Consequences of Atheromatous Plaques:
- Obstruct- keeps growing and blocks the artery
- Rupture- suddenly tear/ rupture
define Angina Pectoris
Transient ischaemia that does NOT produce myocyte necrosis
Myocardial Infarction (MI) define
Death of myocardial muscle due to prolonged ischaemia
describe how the effect of MI depends on severity and duration of injury
Morphological and Microscopic Changes in MI with time
changes in cell type in MI over tim
complication of cardiac failure
- Sudden death (usually due to arrhythmias)
- Arrhythmias
- Systemic emboli (as the heart is not pumping well so its prone to having clots within the walls so they can fly off)
- Pulmonary oedema with superimposed infection (lungs are full of water so more likely to get an infection)
what does this hsow
Dilated Cardiomyopathy
what does this show
Hypertrophic Cardiomyopathy (HOCM)
- There is thickening, shortening and fusion of the chordae tendinae
- The valves look like buttonholes- tight, thick and sclerosed
- Chronic Rheumatic Valvular Disease
which valves are affected in endocarditis
- Left sided >>> damaged valve
- Right sided >>> drugs
- IVDU: more likely to get it on the right side of the heart
- Most people tend to get it on the left side (aortic or mitral) unless they are IVDUs
what type of valves do we have in the heart?
all are tricuspid except for the mitral valve which is bicuspid
