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Health Maintenance and Management A

Pathology
Atherosclerosis

Distribution

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

Wide and almost random


distribution

Aorta
Coronary arteries
Carotid and vertebrobasilar arteries
Lower limb arteries
Pulmonary arteries (only in pulmonary
hypertension)
(Not upper limb arteries)
Typically raised white to yellow-white
lesions of 3-15 mm diameter
Intimal thickening
Variable amounts of extracellular lipid
Covered by collagenous cap
containing SM
May be central necrosis
Foam cells, other inflammatory cells,
and granulation tissue may be present
at base
Disruption of internal elastic lamina
In advanced plaques:
Atrophy of tunica media
Calcification

Same as atheromatous/
fibrofatty plaques

Features

Sub-clinical, precursor
lesions
First develop in
childhood, with
increasing numbers in
individuals aged 15-35
years
Do not necessarily
progress further, and
may regress
completely

Progressions of fatty streaks


Fibrous plaques tend to be stable and
are unlikely to regress
Lipid-rich plaques can undergo partial
regression
Lipid-rich plaques more prone to
fissure or rupture due to mechanical
properties and weakening by
degradative inflammatory enzymes
Not generally a problem in isolation
(i.e. without complication), except in
case of gradually progressive stenosis

Intraluminal thrombosis
due to obstruction of
endothelial surface
Haemorrhage into
plaques due to rupturing
of intima, and formation
of haematoma in plaque,
producing plaque
enlargement and luminal
occlusion
Embolism of plaque
content
Aneurysmal dilation of
large vessels due to loss
of vessel elasticity
Progression of
atheromatous/fibrofatty
plaques
Can result in ischeamia
of any involved vascular
bed
Mortality primarily from
myocardial ischaemia
(including infarction),
cerebral infarction, and
aneurysm rupture

Illustration

Progression

Initial yellow spot of


<1 mm diameter
Development into a
linear streak
Composed mainly of
foam cells, SM, and
some T lymphocytes
Little extracellular lipid
or fibrosis

Atherosclerotic progression

Matt Schiller

Page 1 of 12

Health Maintenance and Management A

Pathology
Thrombosis
Inhibiting and Predisposing Factors to Thrombosis
Thrombus solid or semi-solid mass formed from constituents of blood within the
vascular system during life (distinct from haemostasis).

Thrombus formation
Factor

Mechanism

Intact endothelial cells


Anticoagulant proteins
Fibrinolysis

Prevent platelet adhesion


Neutralise active factors in coagulation cascade
Clearing of fibrin deposits from endothelial surfaces by
plasminogen activator (converts plasminogen to plasmin, which
degrades fibrin)
Central column of cells with plasma layer at edges, removal of
activated clotting factors, and provision of fresh clotting and anticlotting factors

Laminar blood flow

Factors 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 to
atherosclerosis,
inflammation
(vasculitis), or trauma

Turbulence / High
shear forces
Stagnation (due to
immobility, heart
failure, or
arrhythmias)

Factors predisposing to thrombosis (Virchows triad)

Matt Schiller

Clotting factor mutations


Inherited anti-clotting agent
deficiency
Increased synthesis of
coagulation factors (due to
inflammation, contraceptive
pill, or cancer)
Hyperviscosity (due to
polycythaemia, dehydration, or
shock)

Page 2 of 12

Health Maintenance and Management A

Pathology
Thrombosis Types
Origin

Sites

Morphology

Venous

Arterial

Mural

Primarily due to decreased flow


Originate in deep veins of calf
Predisposing factors:
Immobilisation (decreased
flow)
Post-surgical (pro-coagulation
and immobilisation)
Poor peri-operative care (calf
pressure affects flow and
damages endothelium)
Cancer (pro-coagulation)
Pregnancy (pro-coagulation)
Heart Failure (decreased
flow)
Dehydration (hyperviscosity)
Deep veins of calf

Outcomes (if
not resolved)

Matt Schiller

Adhesion to vessel wall or valve


Propagation in direction of flow
(towards heart)
Occlusion of flow
Laminations

Clinical presentation swollen, red,


tender, and fever
Pulmonary thromboembolism and
infarction

High flow
Injured
endothelium
(especially due
to
atherosclerosis)

Coronary
circulation
(myocardial
infarction)
Cerebral
circulation
(cerebral
infarction)
Femoral arteries
(lower limb
ischaemia)
Laminated
alternative layers of:
Fibrin and
platelets (white)
Increased
numbers of
erythrocytes
(red)
Occlusion
Systemic
embolism

Following myocardial
infarction (decreased
flow, injured
endothelium, and
pro-coagulant effect
of necrotic tissue)
Atrial fibrillation
Valvular damage

Cardiac chambers
(especially left
ventricle and atrium)
Aorta
Damaged valves

Non-occlusive

Systemic embolism

Page 3 of 12

Health Maintenance and Management A

Pathology
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.

Origin

Pulmonary

Arterial/Systemic

Route

Outcome

Possible

clinical

presentations

Venous thrombosis
Majority form in deep veins of
calf
Propagation in direction of flow

Entering of right heart, then


pulmonary circulation
Lodgement in branch of
pulmonary artery (sizedependent)
Obstruction of flow
Small most clinically silent
Medium may cause
pulmonary infarction (especially
in conjunction with cardiac
failure)
Large (saddle embolus) may
cause sudden death (if >60%
of flow obstructed)
Dyspnoea
Haemoptysis
Chest pain (in case of saddle
embolus or infarction)
Signs and symptoms of
associated DVT
Sudden collapse (massive
pulmonary embolism)

Mural thrombosis from left side of


heart (~80%), either:
Secondary to myocardial
infarcts
Related to atrial fibrillation
or heart defects
Atherosclerotic plaques
Movement away from heart (with
blood flow)
Lodgement in vessels of matching
size
Distal ischaemia
Leg ischaemia and gangrene
Brain transient ischaemic attach
(TIA) or cerebral infarction
Kidney/Spleen wedge-shaped
infarction
Gut infarction

(Dependent on site)

Comparison of pulmonary and arterial embolism

Matt Schiller

Page 4 of 12

Health Maintenance and Management A

Pathology
Fat

Cholesterol

Origin/Description

Presentation/Outcome

Usually due to fracture of long bones by trauma

Entry of fat from bone marrow into venous circulation

Mechanical obstruction of vasculature

Endothelial damage with thrombosis


Rupture and fragmentation of atherosclerotic plaque

Amniotic fluid

Rupture of placental membranes, allowing amniotic fluid


(including foetal cells) to enter maternal circulation, which
can cause an allergic reaction (rare, and generally fatal)

Septic

Most commonly from vegetations (organisms and


fibrin) on heart valves (infective endocarditis)
Entry into circulation in small clumps

Air

Often occur in trauma, iatrogenically, or in diving accidents

Decompression
sickness

Passively dissolved nitrogen in blood can form bubbles on


sudden pressure decrease (e.g. when divers rapidly
surface)

Foreign body

Usually occur in intravenous drug users (where drugs are


mixed with other substances)

Dyspnoea
Coma
Generally presents 1-3 days
following injury

Skin symptoms

Gangrene of extremities

Renal failure

Profound respiratory failure

Cardiovascular shock

Convulsions and coma

Excessive bleeding

Disseminated intravascular
coagulation

Dependent on size and site of


lodging

May cause widespread septic


infarcts and/or abscesses

Dependent on whether venous or


arterial, size, and site of lodging

Can cause death if pulmonary


output of heart is blocked

Bends (pain in muscles and


joints)

Chokes (pulmonary
obstruction/haemorrhage)

Staggers (CNS disturbance)


Dependent on size and site of lodging

Other types of embolism

Embolism sites of origin


Matt Schiller

Page 5 of 12

Health Maintenance and Management A

Pathology
Myocardial Infarction
Ischaemic Heart Disease
Ischaemic heart disease (IHD) group of diseases characterised by an inability of the
coronary 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 or
atherosclerosis)
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.

Left anterior
descending
branch (LAD)
Right coronary
artery (RCA)

Tissue supplied

Common site
of lesions

Proximal (first 40-60%


2 cm)

Anterior and lateral walls of LV


Anterior 2/3 of interventricular
septum
Inferior and posterior walls of
LV
Posterior 1/3 of interventricular
septum
Posterior wall of RV
Lateral wall of LV

Proximal and
distal thirds

Relative frequency
of occlusion

30-40%

Left circumflex
Proximal (first 15-20%
branch (LCX)
2 cm)
Coronary arteries and their associated atherosclerotic lesions

Matt Schiller

Page 6 of 12

Health Maintenance and Management A

Pathology
Syndrome

Pathology

Angina
Unstable Angina

Myocardial infarction

Sudden cardiac death

Coronary artery stenosis (>75% occlusion)


Plaque rupture
Mural thrombus
Thromboemboli
Plaque rupture
Occlusive thrombus
Multi-vessel disease
Plaque rupture
Thrombus
Fatal arrhythmia or rapid onset of heart failure

Pathology underlying coronary artery syndromes

Angina Pectoris
Angina pectoris syndrome of episodic, paroxysmal, substernal or precordial chest
pain due to inability of diseased coronary arteries to provide adequate blood for
myocardial oxygenation.

Description

Seriousness

Stable
Only precipitated by exertion
Less
Unstable Increased frequency with less exertion
More
Variant
Not precipitated by exertion, involving coronary artery spasm Most
Clinical types of angina pectoris
Myocardial Infarction

Transmural

Subendocardial

Description

Infarction of entire wall

Commonality
Size and area of
infarct

Most common
Unifocal and large lesion
Distribution of affected
coronary artery
Atheroma and thrombus of
one artery
Possible

Infarction of only part of wall (layer of


muscle just under endocardium)
Least common
Multifocal and small lesions
Circumferential

Cause

Global ischaemia (not just one artery)

Pericarditis
Not possible (not involving pericardial
(complication)
surface)
Aneurysm
Possible
Not possible (whole wall not damaged)
(complication)
Comparison of transmural and subendocardial types of myocardial infarction

Matt Schiller

Page 7 of 12

Health Maintenance and Management A

Pathology

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 around
muscle
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).

Matt Schiller

Page 8 of 12

Health Maintenance and Management A

Pathology
Valvular Heart Disease and Congestive Cardiac Failure
Stenosis and Incompetence

Left

Right

Semilunar (no tethering)


Aortic Pulmonary
Atrioventricular (tethered by chordae tendinae) Mitral Tricuspid
Heart valves

Normal functions of valves:


Seal against regurgitation.
Obstruction of free forward-flow.

Definition
Lesion type
Type of load
on chamber
Effect on
chamber
Cause

Disease associations

Mitral

Aortic
Tricuspid

Stenosis (Obstruction)

Incompetence (Regurgitation)

Narrowing of orifice
Always chronic
Pressure

Ineffective closure, permitting regurgitation


Acute or chronic
Volume

Concentric hypertrophy,
then dilation
Vegetation formation

Concurrent eccentric hypertrophy and dilation

Rheumatic

Rheumatic
Calcific
Congenital (bicuspid)

Comparison of stenosis and incompetence

Matt Schiller

Cusp damage (e.g. hole)


Supporting structure damage
Cusps rheumatic, infective, prolapse
Tensor apparatus rupture of laxity of
papillary muscles or chordae tendinae
LV dilatation ischaemic, cardiomyopathic
Annulus calcification
Cusps rheumatic, infective
Root degenerative, autoimmune
(vasculitis of vaso vasorum)
Rheumatic
Functional (RV dilatation)

Page 9 of 12

Health Maintenance and Management A

Pathology
Rheumatic Fever and Infective Endocarditis
Rheumatic fever

Infective endocarditis

Definition

Acute, inflammatory disease of childhood

Microbiology

Following group A beta-haemolytic


streptococcal infection
Autoimmune injury to heart (and
potentially skin, joints, and/or brain)
Leaflet thickening and retraction
Commissural fusion
Chordae tendineae thickening and
fusion
Calcification
Complicating pathology chamber
hypertrophy and dilation
Acute and recurrent
Chronic/Progressive valvular injury in
majority of cases
Diverse manifestations (diagnosed using
Duckett-Jones criteria)

Colonisation and invasion of one or more


valves and/or mural endocardium by
microorganisms
Commonly streptococci and staphylococci

Pathology

Acute/Chronic
Clinical
features

Friable vegetations
Tissue destruction of leaflets, apparatus,
and/or annulus

Acute or subacute

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 phenomena
Pulmonary venous congestion Dyspnoea
Orthopnoea (breathing discomfort when flat)
Paroxysmal nocturnal dyspnoea
Decreased 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

Matt Schiller

Page 10 of 12

Health Maintenance and Management A

Pathology
Fever
Hyperthermia and Fever
Normal body temperature is 37.2C to 37.5C.

Hyperthemia

Fever

Thermoregulatory
responses
Thermal set-point
Pathogenesis

Altered

Normal

Normal
Overwhelming of
heat loss
mechanisms by
internal and external
heat
Impairment of heat
loss mechanisms by
disease or drugs

Magnitude
Commonality
Harmfulness
Tissue injury and
multiple organ
failure

May exceed 42C


Less
More
May result

Elevated
Infection (most commonly)
Exogenous pyrogens stimulate cells
to release pro-inflammatory
cytokines
Cytokines reach anterior
hypothalamus via circulation and
neurones and induce PG-E2
production which elevates thermal
set-point
Efferent responses:
Reduced heat loss
cutaneous vasoconstriction
Increased heat production
piloerection, shivering, rigors
Rarely exceed 41C
More
Less
Not reported

Advantages and Disadvantages of Fever

Advantages

Disadvantages

Leads to better prognosis


Immune response enhanced
Growth of some microorganisms
inhibited by elevated
temperatures
Use of antipyretics may prolong
infection

Matt Schiller

Increased metabolic demand:


Tissue breakdown
Increased carbon dioxide production and
cardiac output
Tissue injury from hyperthermia
Febrile seizures in children
Cognitive deterioration in elderly

Page 11 of 12

Health Maintenance and Management A

Pathology
Features of Fever

Stage Thermal set-point

Patient experience

Cold

Chills, shivers, and


rigors
Heat
Sweating

Response to elevated thermal set-point (heat preservation


and generation)
Once body has reached new thermal set-point
Fall in thermal set-point due to normal diurnal variation in
body temperature (heat loss)

Hot
Wet

Typical three stages of fever

Fever

Fever

is non-specific and systemic, with common constitutional symptoms:


Tiredness/Somnolence.
Malaise.
Myalgia.
Arthralgia.
Anorexia.
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

Key aspects of clinical evaluation of fever

Non-specific markers of inflammation


(leukocyte count, erythrocyte
sedimentation rate, C-reactive protein)
Detect site of infection

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.

Matt Schiller

Page 12 of 12