Thrombosis, Cardio Pathology

8/10/2019 Thrombosis, Cardio Pathology

1/12

Health Maintenance and Management APathology

Matt Schiller Page 1 of 12

therosclerosis

Atherosclerosis complex disease of large- and medium-sized arteries (specialised

form of chronic inflammation in response to endothelial injury), characterised by: Focal/Eccentric thickening of tunica intima by inflammatory and fibrotic lesions. Lesions exhibiting lipid deposition, particularly cholesterol and cholesteryl esters.

Fatty streaks Atheromatous/Fibrofatty plaques Complicated lesions

D i s t r i b u

t i o n

Wide and almost randomdistribution

Aorta Coronary arteries Carotid and vertebrobasilar arteries Lower limb arteries Pulmonary arteries (only in pulmonary

hypertension)(Not upper limb arteries)

Same as atheromatous/fibrofatty plaques

F e a

t u r e s

Initial yellow spot of


2/12



Thrombosis

Inhibiting and Predisposing Factors to Thrombosis

Thrombus

solid or semi-solid mass formed from constituents of blood within thevascular system during life (distinct from haemostasis).

Thrombus formation

Factor MechanismIntact endothelial cells Prevent platelet adhesion

Anticoagulant proteins Neutralise active factors in coagulation cascadeFibrinolysis Clearing of fibrin deposits from endothelial surfaces by

plasminogen activator (converts plasminogen to plasmin, whichdegrades fibrin)

Laminar blood flow Central column of cells with plasma layer at edges, removal of

activated clotting factors, and provision of fresh clotting and anti-clotting factorsFactors inhibiting thrombosis

Vessel wall changes Blood flow changes Blood constituents changes Injury to or activation

of endothelium May be exposure of

sub-endothelial layers(notably collagen)

May be due toatherosclerosis,inflammation(vasculitis), or trauma

Turbulence / Highshear forces

Stagnation (due toimmobility, heartfailure, or

arrhythmias)

Clotting factor mutations Inherited anti-clotting agent

deficiency Increased synthesis of

coagulation factors (due to

inflammation, contraceptivepill, or cancer) Hyperviscosity (due to

polycythaemia, dehydration, orshock)

Factors predisposing to thrombosis (Virchows triad)


3/12


4/12



Embolism

Embolism the transportation by the blood of abnormal material and its impaction in a

vessel at a point remote from its entry into the circulation.

Pulmonary Arterial/SystemicOrigin Venous thrombosis

Majority form in deep veins ofcalf

Propagation in direction of flow

Mural thrombosis from left side ofheart (~80%), either:

Secondary to myocardialinfarcts

Related to atrial fibrillationor heart defects

Atherosclerotic plaques

Route

Entering of right heart, thenpulmonary circulation Lodgement in branch of

pulmonary artery (size-dependent)

Obstruction of flow

Movement away from heart (withblood flow)

Lodgement in vessels of matchingsize

Distal ischaemia

Outcome Small most clinically silent Medium may cause

pulmonary infarction (especiallyin conjunction with cardiacfailure)

Large (saddle embolus) maycause sudden death (if >60%of flow obstructed)

Leg ischaemia and gangrene Brain transient ischaemic attach

(TIA) or cerebral infarction Kidney/Spleen wedge-shaped

infarction Gut infarction

Possibleclinicalpresentations

Dyspnoea Haemoptysis Chest pain (in case of saddle

embolus or infarction) Signs and symptoms of

associated DVT Sudden collapse (massive

pulmonary embolism)

(Dependent on site)

Comparison of pulmonary and arterial embolism


5/12


6/12



Myocardial Infarction

Ischaemic Heart Disease

Ischaemic heart disease (IHD)

group of diseases characterised by an inability of thecoronary arteries to deliver sufficient oxygen to meet the demands of the heart(usually due to coronary atherosclerosis).

Decreased supply Increased demand Coronary artery stenosis (due to atherosclerosis) Coronary artery spasm Coronary ostial stenosis (narrowing of mouths of

coronary arteries due to aortitis oratherosclerosis)

Congenital abnormality of coronary artery Coronary arteritis

Aortic stenosis or dissection (dissecting aneurysm)

Anaemia Carbon monoxide poising and

carboxyhaemoglobin Myocardial hypertrophy Tachycardia

Causes of the imbalance between oxygen supply and demand that underlies IHD

Typical pathogenesis of IHD (particularly myocardial infarction): Coronary atherosclerosis. Complicated plaque (rupture, ulceration, and/or haemorrhage). Thrombotic occlusion. Decrease in cross-sectional luminal area (>75%). Critically decreased blood flow.

Important factors determining degree of ischaemia: Plaque location. Vessel narrowing. Collateral circulation. Speed of onset of occlusion (rapid leads to myocardial infarction). Myocardial oxygen supply.

Tissue supplied Common siteof lesionsRelative frequencyof occlusion

Left anteriordescendingbranch (LAD)

Anterior and lateral walls of LV Anterior 2/3 of interventricular

septum

Proximal (first2 cm)

40-60%

Right coronaryartery (RCA)

Inferior and posterior walls ofLV

Posterior 1/3 of interventricularseptum

Posterior wall of RV

Proximal anddistal thirds

30-40%

Left circumflexbranch (LCX)

Lateral wall of LV Proximal (first2 cm)

15-20%

Coronary arteries and their associated atherosclerotic lesions


7/12


8/12



Progression of myocardial necrosis following coronary artery occlusion

Macroscopic Microscopic First 24 hours no visible changes 18-24 hours pallor 2-3 days mottled and circumscribed 3-7 days yellow soft area with hyperaemic

border (granulation tissue and angiogenesis) 6 weeks scar tissue

First 6 hours no visible changes 24 hours loss of myocyte striation

and nuclei, and oedema aroundmuscle

48 hours signs of inflammation

Macroscopic and microscopic features seen following myocardial infarction

Pathological progression following myocardial infarction: Coagulative necrosis. Inflammation (leukocyte infiltration). Ingrowth of granulation tissue (including macrophages, fibroblasts, and new

blood vessels). Diagnosis of myocardial infarction:

Clinical features Electrocardiogram (ECG). Biochemical tests (including serum markers, such as troponins). Nuclear scans (to show decreased perfusion and ischaemia).

Angiography. Possible complications of myocardial infarction: Arrythmias. Cardiac failure (particularly LV). Cardiogenic shock. Extension of infarct. Pericarditis. Thromboembolism. Myocardial rupture. Ventricular aneurysm (usually LV).

Deep venous thrombosis and pulmonary embolism (due to immobility).


9/12



Valvular Heart Disease and Congestive Cardiac Failure

Stenosis and Incompetence

Left RightSemilunar (no tethering) Aortic Pulmonary

Atrioventricular (tethered by chordae tendinae) Mitral TricuspidHeart valves

Normal functions of valves: Seal against regurgitation. Obstruction of free forward-flow.

Stenosis (Obstruction) Incompetence (Regurgitation)Definition Narrowing of orifice Ineffective closure, permitting regurgitationLesion type Always chronic Acute or chronicType of loadon chamber

Pressure Volume

Effect onchamber

Concentric hypertrophy,then dilation

Concurrent eccentric hypertrophy and dilation

Cause Vegetation formation Cusp damage (e.g. hole) Supporting structure damage

D i s e a s e a s s o c i a

t i o n s

Mitral Rheumatic Cusps rheumatic, infective, prolapse

Tensor apparatus

rupture of laxity ofpapillary muscles or chordae tendinae LV dilatation ischaemic, cardiomyopathic Annulus calcification

Aortic Rheumatic Calcific Congenital (bicuspid)

Cusps rheumatic, infective Root degenerative, autoimmune

(vasculitis of vaso vasorum)Tricuspid - Rheumatic

Functional (RV dilatation)Comparison of stenosis and incompetence


10/12



Rheumatic Fever and Infective Endocarditis

Rheumatic fever Infective endocarditisDefinition Acute, inflammatory disease of childhood Colonisation and invasion of one or more

valves and/or mural endocardium bymicroorganisms

Microbiology Following group A beta-haemolyticstreptococcal infection

Commonly streptococci and staphylococci

Pathology Autoimmune injury to heart (andpotentially skin, joints, and/or brain)

Leaflet thickening and retraction Commissural fusion Chordae tendineae thickening and

fusion Calcification Complicating pathology chamber

hypertrophy and dilation

Friable vegetations Tissue destruction of leaflets, apparatus,

and/or annulus

Acute/Chronic Acute and recurrent Chronic/Progressive valvular injury in

majority of cases

Acute or subacute

Clinicalfeatures

Diverse manifestations (diagnosed usingDuckett-Jones criteria)

Fever New or changing murmur Embolic phenomena

Congestive Cardiac Failure Congestive cardiac failure (CCF) impairment of cardiac function causing insufficient

output for the metabolic demand of the body, due to one or both of the following:

Decreased myocardial contractility (systolic dysfunction). Inability to fill cardiac chambers with blood (diastolic dysfunction). Aetiology:

Ischaemic heart disease (especially repeated myocardial infarctions). Cardiomyopathy. Chronic valvular disease.

Event Consequences Atrial fibrillation Embolic phenomenaPulmonary venous congestion Dyspnoea

Orthopnoea (breathing discomfort when flat) Paroxysmal nocturnal dyspnoeaDecreased renal perfusion Activation of renin-angiotensin-aldosterone pathway

Salt and water retention Peripheral oedema

Right heart failure Chronic passive congestion of liver Tender, pulsative hepatomegaly Cardiac cirrhosis

Clinical-pathological correlations of congestive cardiac failure


11/12



Fever

Hyperthermia and Fever

Normal body temperature is 37.2C to 37.5C.

Hyperthemia FeverThermoregulatoryresponses

Altered Normal

Thermal set-point Normal ElevatedPathogenesis Overwhelming of

heat lossmechanisms byinternal and external

heat Impairment of heatloss mechanisms bydisease or drugs

Infection (most commonly) Exogenous pyrogens stimulate cells

to release pro-inflammatorycytokines

Cytokines reach anteriorhypothalamus via circulation andneurones and induce PG-E2production which elevates thermalset-point

Efferent responses: Reduced heat loss

cutaneous vasoconstriction Increased heat production

piloerection, shivering, rigorsMagnitude May exceed 42C Rarely exceed 41CCommonality Less MoreHarmfulness More LessTissue injury andmultiple organfailure

May result Not reported

Advantages and Disadvantages of Fever

Advantages Disadvantages Leads to better prognosis Immune response enhanced Growth of some microorganisms

inhibited by elevatedtemperatures

Use of antipyretics may prolonginfection

Increased metabolic demand: Tissue breakdown Increased carbon dioxide production and

cardiac output Tissue injury from hyperthermia Febrile seizures in children Cognitive deterioration in elderly


12/12



Features of Fever

Stage Thermal set-point Patient experience

Cold Response to elevated thermal set-point (heat preservationand generation) Chills, shivers, andrigorsHot Once body has reached new thermal set-point HeatWet Fall in thermal set-point due to normal diurnal variation in

body temperature (heat loss)Sweating

Typical three stages of fever

Fever is non-specific and systemic, with common constitutional symptoms: Tiredness/Somnolence. Malaise. Myalgia. Arthralgia. Anorexia.

Fever patterns: Variability in body temperature (diurnal variation exaggerated, with heat loss

overnight). Pulse-temperature dissociation

Clinical Evaluation and Treatment of Fever

History Examination Investigations Constitutional

symptoms Localising symptoms Epidemiological clues

Temperature Localising

signs

Non-specific markers of inflammation(leukocyte count, erythrocytesedimentation rate, C-reactive protein)

Detect site of infectionKey aspects of clinical evaluation of fever

Methods for lowering body temperature: Antipyretic drugs (inhibit prostaglandin). Physical interventions (e.g. bathing, sponging, fanning).

No evidence that treatment of fever will: Relieve patient discomfort. Reduce mortality and morbidity. Prevent febrile seizures. Reduce cognitive impairment.

Documents

Thrombosis, Cardio Pathology