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Pathology of Cardiovascular

System

Dr. S.L. [email protected]

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Overview

Review of basics

Ischaemic heart diseases

Coronary artery occlusions

Myocardial infarction

Valvular heart diseases Degenerative valvular diseases

Rheumatic heart disease

Bacterial endocarditis

Shock Hypovoleamic shock

Cardiogenic shock

Septiceamic shock

Anaphylactic shock

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Review

Atherosclerosis

Epidemiology of coronary artery disease

Physiology of the cardiac cycle

Anatomy of the myocardium

Vascular supply of the myocardium

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Taken from Colour Atlas of AnatomyRoden, Yokochi and Lutjen-Drecoll

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Taken from Colour At

of AnatomyRoden,

Yokochi and Lutjen-

Drecoll

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Taken from Colour Atlas ofAnatomyRoden, Yokochi and

Lutjen-Drecoll

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Anatomy of the myocardium

Cardiac muscle cells form a collection of

branching and anastamosing striated muscles.

They make up 90% of the volume of themyocardium.

Unlike skeletal muscles, they contain ten times

more mitochondria per muscle cell. This reflects

their extreme dependence on aerobic metabolism.They do not need to rest!!

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Vascular supply of the

myocardium Predominant blood supply is from the coronary

arteries, which arises from the aorta and runsalong an epicardial route before penetrating themyocardium as intramural arteries.Effectively aone-way street flow and supply.

Coronary arterial blood flow to the myocardiumoccurs during ventricular diastole; when themicrocirculation in the myocardium is notcompressed by cardiac contraction. The one^way

street only flows within a fixed time span.

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Coronary Angiography

L = Left main trunk

A= Anterior descending

C= Circumflex

R= Right coronary

P=Posterior descending

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Areas of supply (perfusion)

The left coronary trunk gives rise to:-

Left Anterior Descending (LAD) and the Left

Circumflex (LCX)

Right Coronary Artery (RCA)

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Areas of perfusion

Left anterior descending (LAD)supplies most ofthe apex of the heart, the anterior wall of the leftventricle and the anterior two-thirds of theventricular septum.

Left circumflex branch supplies the lateral wall ofthe left ventricle.

The right coronary artery in 80% of the populationsupplies the right ventricle, the posterior third ofthe ventricular septum and the posterior-basal wallof the left ventricle. (Right dominant circulation)

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Ischaemic Heart Diseases

This is a generic name for a group ofclosely related syndromes that result from

myocardial ischaemia. In over 90%, this is due to a reduction in

coronary blood flow. (Decrease in supply)

Other conditions arise as a result ofincreases in demand e.g. hypertrophy,shock, increase heart rate, etc.

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Diminished Coronary Perfusion

Fixed coronary obstruction

More than 90% of patients with IHD

One or more lesions that causes at least 75%reduction of the cross-sectional area of at least

one of the major epicardial arteries.

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Coronary atherosclerosis

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Taken from Robbins Pathologic Basis of Disease

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Clinical Manifestations

Angina Pectoris

Myocardial Infarction

Chronic ischaemic heart disease

Progressive heart failure consequent to previous

myocardial infarction.

Sudden Cardiac Death

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Angina Pectoris

This is a symptom complex. Symptomscaused by transient myocardial ischaemia

that falls short of inducing the cellularnecrosis that defines myocardial infarction.

Three variants:-

Stable angina

Prinzmental angina

Unstable angina

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Angina Pectoris

Stable AnginaMost common form.

Chronic stenosing coronary atherosclerosis,

reaching a critical level, leaving the heartvulnerable to increased demand.

Typically relieved by rest or a vasodilator

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Prinzmental Angina

Uncommon pattern

Occurs at rest

Documented to be due to arterial spasm

Unrelated to physical activity, heart rate or

blood pressure.

Generally responds to vasodilators.

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Unstable Angina

Pattern here is the pain occurs with

progressively increasing frequency and

tends to be more prolonged Associated with disruption of the

atherosclerotic plaque, with superimposed

thrombosis, embolisation or spasm. Predictor of Myocardial Infarction

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Effects of ischaemia on myocytes

Onset of ATP Depletion

Loss of contractility

ATP reduced to 50% of normal

To 10% of normal

Irreversible injury

Microvascular injury

Seconds

< 2 minutes

10 minutes

40 minutes

20-40 minutes > 1 hour

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Transmural Infarction

The ischaemic necrosis involves the full or

nearly the full thickness of the ventricular wallin the distribution of a single coronary artery.

Usually associated with chronic coronary

atherosclerosis, acute plaque change and

superimposed completely obstructive

thrombosis.

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Subendocardial infarct

Limited to the inner one-third or at most one

half of the ventricular wallMay extend laterally beyond the perfusion

territory of a single coronary artery

In a majority of cases, there is diffuse stenosingcoronary atherosclerosis.

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Gross changes of myocardial

infarction Gross changes

None to occasional mottling (up to 12 hours)

Dark mottling (12-24 hours)

Central yellow tan with hypereamic border (3-7

days)

Gray white scar (2-8 weeks)

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Varying gross appearance

of myocardial infarction

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Recent and Old Myocardial Infarcts

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Microscopic changes of

myocardial infarct Early coagulation necrosis and oedema;

haemorrhage (4-12 hours)

Pyknosis of nucleic, hypereosinophilia,early neutrophilic infiltrate (12-24 hours)

Coagulation necrosis, interstitial infiltrate of

neutrophils (1-3 days)

Dense collagenous scar (> 2 months)

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Hypereosinophilia

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Coagulative necrosis

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Interstitial infiltration of neutrophils

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Laboratory detection of

myocardial infarction This is based on the measurement of

intracellular macromolecules leaked from

the damaged myocytes into the circulation Creatine kinaseparticularly the MB

isoenzyme

Lactate dehydrogenase

TroponinTroponin 1 and Troponin T

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Other diagnostic tools

ElectrocardiogramQ waves

Echocardiogram

Radioisotope studies

Magnetic Resonance Imaging

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Electrocardiogram (ECG) changes

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Acute effects of myocardial

infarction Contractile dysfunction

Arrhythmias

Cardiac rupture

Pericarditis

Sudden death

Invariably this would be due to a lethal

arrhythmia (asystole or ventricular fibrillation)

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Pathological complications of

myocardial infarction Infarct extension

Mural thrombus

Ventricular aneurysm

Myocardial rupture

Ventricular free wall

Septal

Papillary muscle

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Infarct extension

Diagram from Robbins Pathologic Basis of Disease

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Ruptured

Myocardial

Infarct

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Ruptured Papillary muscle

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Old myocardial infarct showing evidence of

thinning of ventricular wall replaced by fibrous scar

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Fibrous scarring with compensatory hypertrophy of

unaffected ventricular wall

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Ventricular wall

aneurysm

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Anatomy of Heart Valves

Aortic valveCommonly tricuspid semi lunar

valves. Can be congenitally bicuspid.

Mitral valveBi-cuspid flaps supported bychordae tendinae attached to papillary muscles

Pulmonary valvesTricuspid semi lunar valves

Tricuspid valvesTri-cuspid flaps supported by

chordae tendinae.

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Aortic Valves

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Mitral Valves

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Pulmonary

Valves

Tricuspid Valves

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Response to injury

Mechanical injurysuperficial fibrousthickening over preserved architecture.

Inflammationinvariably leads tovascularisation of structure, fibrosis leads todecrease in size/surface area.

Degenerative changesdistortion andincrease in size due to deposits of materialsuch as calcium salts, cholesterol, etc.

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Effects of valvular disease

Stenosistightening of the valvular

opening resulting in decreased flow of

blood through the opening. Incompetenceincomplete closure of the

valvular opening, allowing backflow of

blood through the valvular opening Mixed.

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Effects of valvular disease

Mitral Stenosis

Increased atrial

volume and pressure

Atrial

dilatation

Atrial thrombusCongestion

of lungs

Pulmonary

HypertensionRight Heart

Failure

Systemic

embolisation

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Common valvular diseases

Degenerative

Calcific aortic stenosis

Mitral annular calcificationMyxomatous degeneration of mitral valves

(mitral valve prolapse)

Rheumatic fever and rheumatic heartdisease

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Calcific Aortic Stenosis

Most frequent of all valvular abnormalities

Calcification induced by wear and tear

Onset in the elderly

50s and 60s in congenital bicuspid individuals

70s and 80s in those with previous normal

valves

Heaped up calcified masses

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Aortic Valve Inlet

Looking intothe left

ventricular outlet

Note the three

valvular cuspsand the three

distinct

commissures

(arrows)

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Calcific Aortic Stenosis(3 cusps)

C l ifi Bi id A ti V l

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Calcific Bicuspid Aortic Valve

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Mitral Annular calcification

Degenerative calcific deposits in the ring of

the mitral valve.

Generally does not affect valvular function,but can lead to mitral regurgitation

Source of thrombi and emboli, also prone to

infective endocarditis Most common in women over 60

C l ifi ti f Mit l V l Ri

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Calcification of Mitral Valve Ring


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Mitral Valve Prolapse

Myxomatous degeneration of valve.

Characteristically ballooning of the valvular cuspswith the affected leaflets thickened and rubbery.

Basis for the change unknown but believed to bedue to developmental anomaly of connectivetissue.

Association with Marfans syndrome (a syndromewhereby there is a mutation in the gene encodingfibrillin)

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Mitral Valve

InletViewed

from the leftatrium.

Note bicuspid

valve leaflets.

Slight tenting of

the valve

leaflets

suggestive of

early mitral

valve prolapse.

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Mitral ValveProlapse

Notice

tenting ofvalve leaflet

(arrow)

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Rheumatic fever

Once the most common cause of valvular

heart disease in Hong Kong.

It is an acute immunologically mediated ,multi-system inflammatory disease that

occurs a few weeks after an episode of

Group A (-hemolytic) streptococcalpharyngitis.

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Dia ram from Robbins Patholo ic Basis of Disease

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Rheumatic Valvulitis


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Acute Rheumatic CarditisAschoff Body


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Chronic Rheumatic Valvular

Heart Disease Most important consequence of rheumatic

fever

Inflammatory deformity of valvesAlmost always involve the mitral valve

Involvement of aortic or other valves also

common

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Characteristics of rheumatic

valvular disease Acute phase

Foci of fibrinoid degeneration surrounded bylympocytesAschoff bodies

Most distinctive within the heart, but widelydisseminated.

Pancarditis

Pericarditis Myocarditis

Verrucae vegetations (1-2 mm)

Chronic Rheumatic Disease

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Chronic Rheumatic Disease

of Aortic Valve


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Characteristics of rheumatic

valvular disease Chronic

Leaflet thickening

Commissure fusionShortening, thickening and fusion of chordae

tendinae

Ch i h i i f i l l

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Chronic Rheumatic Disease of Mitral Valve

Vascularisation)


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Infective Endocarditis

Colonisation or invasion of heart valves by

microbiologic agent.

Formation of friable vegetations (composedof thrombotic debris and organisms.

Leads to destruction of underlying cardiac

tissue. Source of infective embolisation

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Infective endocarditis

Most common sites involve the left heartvalves

Tricuspid valves typically involved inintravenous drug abusers

Development of infective endocarditispreventable in patients with valvular

diseases by provision of antibiotic cover forany surgical or dental procedures.

Bacteria Endocarditis

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Bacteria Endocarditis


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The elements of circulationAn effective pump

(The heart)

(Normal blood

vessels)

A clear channel

An effective return

(No peripheral

pooling)

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The elements of circulation

Blood Pressure/Heart Rate

Intact and unblocked

blood vessels

Effective venous andlymphatic return

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The economics of circulation

Di ib i f bl d l i

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Distribution of blood volume in

the circulatory system

Heart 7%

Arteries 13%

Arterioles and capillaries 7%

Veins 64%

Pulmonary vessels 9%

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Body Fluid Compartments

Plasma 3.0L

Interstitial fluid 11.0L

Intracellular fluid 28.L

Blood volume contains both extracellular fluid (plasma) and

intracellular fluid (fluid in RBC). Average blood volume is

about 8% of body weight, approximately 5L (60% plasma

40% RBC)

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What is shock?

A state of generalised hypoperfusion of all cells

and tissues due to reduction in blood volume or

cardiac output or redistribution of blood resulting

in an inadequate effective circulating volume

A systemic (whole body) event resulting from

failure of the circulatory system

It is at first reversible, but if protracted leads toirreversible injury and death.

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Causes of shock

Hypovoleamia

Cardiogenic (pump failure)

Anaphylactic (peripheral pooling) (returnfailure)

Septic (Septiceamic)Complex reasons

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Hypovoleamic shock

Haemorrhage

External (Chop wounds, Gastro-intestinal

bleeding, etc)Internal (Hemoperitoneum due to ruptured

aortic aneurysm, ruptured ectopic pregnancy,

etc.

Fluid loss

Dehydration (low intake or excessive loss)

External loss

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Internal Bleeding

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Internal Bleeding

Effect of volume loss on

Cardiac O tp t and Arterial Press re

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Cardiac Output and Arterial Pressure

Taken from Guyton & HallHuman Physiology and

Mechanisms of Disease

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Stages of hypovoleamic shock

Asymptomatic (< 10%)

Early stage (15-25% loss)

Compensated hypotension Progressive/Advance Stage

Results when no therapeutic intervention is given for

the early stage, compensatory mechanisms become

harmful. Autoregulation mechanisms breakdown. Irreversible shock

Irreversible hypoxic injury to vital organs

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Compensated hypotension

Hypotension (low volume or low cardiac output)

Sympathetico-adrenal stimulation (fight or fright)

Release of catecholaminesresulting in peripheral

vasoconstrictionmaintain BP

Activation of renin-angiotensin-aldosterone system and

increased anti-diuretic hormone release

Fluid retention by kidneys, further vasoconstriction

Impaired renal perfusion and perfusion to other organs

with every effort made to maintain perfusion to brain and

heart (auto-regulation)

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Taken from Guyton & HallHuman Physiology and Mechanisms of Disease

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Splenic Infarct

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Infarct of kidney

Replaced by scarred

tissue

Haemorrhagic infarct of lung

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Haemorrhagic infarct of lung

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Cardiogenic shock

Failure of myocardial pump.

Intrinsicdue to myocardial damage

Extrinsic Due to external pressuree.g. cardiac tamponade

Due to obstructed flowe.g. thrombosis

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Compensated heart failure

Here the situation is one of a compromised cardiacpump which has been compensated by anincrease in right atrial pressure ( increased blood

volume caused by retention of fluid ). Thuscardiac output is maintained.

It may not be noticed as it would have developedgradually over time. However any strain on the

heart, eg sudden increase in exercise would tip thebalance and lead to a decompensated heartfailure.

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Decompensated heart failure

The pump is so damaged that no amount of

fluid retention can maintain the cardiac

output. This failure also means that therenal function cannot return to normal, thus

fluid continues to be retained and the person

gets more and more oedematous with

eventual death. In short, failure of the pump

to pump enough blood to the kidneys.

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Anaphylactic shock

Usually due to prior sensitisation

Exposure to specific antigens

Mediated by histamines, complements andprostaglandins

Vasodilatation of micro-circulation

associated with pooling and fluidextravasation

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Septic shock

Commonly due to gram-negative endotoxin

producing bacteria. May also accompany

gram-ve bacteria. Predisposing factors include:-

Debilitating diseases

Complications of instrumentation and treatmentBurns

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Septic shock

Pathogenesis include:-

Inflammatory reactionvasodilatation mediated by

histamines and complements

Disseminated intravascular coagulopathyactivation

of clotting factors and platelets together with

consumption of clotting factors

Endothelial damageextensive due to endotoxins

Release of interleukin-1 and TNF-alpha (Tumor

necrosis factor alpha) from macrophages

Possible mechanisms of septic shock

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Pathological changes

Hypoxic injury to vital organsinfarction

Necrosis of tissues

Lysis of cells

The extent of pathological changes is dependent

on the duration of decompensation before death.

In acute deaths, often no significant findings are

found.

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Brain

Hypoxic and ischaemic damage

Initially found at boundary zonesMay also be associated with marked cerebral

oedema.

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Heart

Focal myocardial necrosis

Subendocardial infarction (vulnerable region ofblood supply)

If there is pre-existing coronary artery diseases,

may also lead to acute transmural myocardial

infarction

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In cardiogenic shock

Due to previous ischaemic heart diseasesthe

ventricular chambers may well be dilated anddistended. The walls are often thin and may be

replaced by non-elastic fibrous scars

In intrinsic myocardial diseases leading to

pump failure, the myocardium may beunusually thickened and rigid.

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Lungs

Diffuse alveolar damage (adult respiratorydistress syndrome)

Damage to Type 1 pneumocytes and toendothelial cellsoedema as well as hyalinemembrane due to decreased surfactant

production

Haemorrhages, fibrosis, atelectasis andinfection

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Kidneys

Acute tubular necrosisoften associated with

remarkably well preserved glomeruli

Pathophysiology of

Acute Tubular Necrosis

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Acute Tubular

Necrosis,

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Gastrointestinal tract

Mucosal ischaemia, haemorrhage, necrosis,gangrene

Liver

Centrilobular necrosis, fatty degeneration

Adrenal glands

Focal necrosis

Diffuse haemorrhagic destruction

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Pump Failure

Cardiogenic Shock

Vessel injuryPhysical injuries such as wounds,

ruptures of aneurysms, etc

(Hypovoleamic)

Toxins , infection and immune-

complexes (DIC, Anaphylaxis,

Peripheral PoolingHypoalbumineamia,

Ascites, Renal failure,

(Hypovoleamic)

Septiceamic,

Anaphylaxis

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