HAEMODYNAMIC DISORDERS

BY
PROF. EDMUND MUONIR DER
MBChB, FGCP, FWACP
HOD OF PATH
SoM UDS
TAMALE
 Outline of the lecture:
 Normal Interstitial  Thrombosis
Tissue  Embolism
 Body fluid  Infarction
compartments  Shock
 Oedema
 Haemorrhage
 Normal Interstitial Tissue
• The normal function of parenchymal cells depends
on the integrity of the interstitial tissues that make
up the immediate microenvironment of the cells.
• Components of the interstitial tissue:
 Cells
 Water and electrolytes
Blood vessels
 Ground substance
 Fibrillary elements
 Normal Interstitial Tissue
• The pH and the electrolyte composition of
interstitial tissue are maintained in equilibrium
with that of plasma in capillaries and the
intracellular fluid compartment.
 Body fluid compartments
 Total body water (TBW) is ∼60% (male) and
50% (female) of the body weight in kg.
 Total body weight depends on the age, sex and
degree of obesity, being lower in obese and the
aged.
 TBW is divided into intracellular fluid (ICF): 40%
of the body weight
 Extracellular fluid (ECF): 20% of the body weight
 Body fluid compartments
The ECF is subdivided into two compartments:
 Intravascular: 4%
Extravascular: a) Transcellular (1%) and b)Interstitial (15%)
The fluid balance between the interstitial and the vascular
components are maintain by the Frank Starling's forces.
 Sodium (Na+) is the major extracellular fluid (ECF)
electrolyte
 Potassium (K+) is the major intracellular fluid (ICF)
electrolyte
 Body fluid compartments
 The blood in an individual is made up of cells
and plasma.
 The floor of blood is unidirectional and orderly
(lamina floor), with the cellular elements
within the central axial compartment.
 The components of the blood are maintained
in constant relative proportions by various
forces and the osmotic gradient.
 Body fluid compartments
 There is a balance/equilibrium between those
forces across the blood vessels and the
interstitial compartment.
 This equilibrium depends largely on the
integrity of the blood vessel wall, the diameter
of the vessels and the head pressure gradient.
 HAEMODYNAMICS: LOCALISED

• Fluid exchange through the normal capillary

wall is governed by the balance of opposing
forces:
• 1. Capillary hydrostatic pressure (CHP): Forces
fluid out of the vascular compartment.
• 2. Plasma colloid osmotic pressure (PCOP):
Draws fluid back into the vascular
compartment.
 HAEMODYNAMICS: LOCALISED

• Normally, tissue hydrostatic and colloid

osmotic pressures are near zero and do not
affect this fluid exchange.
• CHP – PCOP = 0 (approximately zero)
• Fluid passes out of the capillary mainly at the
junctions between endothelial cells (pores),
which permit only small non-protein
molecules to pass through (ultrafiltration).
 HAEMODYNAMICS: LOCALISED

• Almost all protein is retained in the vessel.

• The small amount of protein that escapes the
capillary is rapidly removed by the lymphatics
along with any fluid that may not return to the
venules.
 HAEMODYNAMICS: GENERALISED

• Major operating forces:

• Increased total body sodium and water
• Renin-angiotensin-aldosterone system
 Sodium balance depends on the net effect of sodium
filtration (loss) in the glomerulus and sodium
reabsorption in the proximal and distal convoluted
tubules.
 Body fluid compartments
• Any condition or activity that will cause
alterations in the:
 flow and composition of the blood
 impaired vascular integrity
 alteration in the extravascular and
intravascular osmotic gradients
 Will lead to a haemodynamic disorder
 Haemodynamic disorders

 Oedema
 Haemorrhage
 Thrombosis
 Embolism
 Infarction
 Shock
 OEDEMA

• Definition: This is the presence of increased (excess)

fluid in the interstitial space of the extracellular fluid
(ECF) compartment.
• It also includes accumulation of fluid in body cavities
such as:
The pleural cavity (hydrothorax, pleural effusion)
Peritoneal cavity (ascites)
Pericardial cavity (pericardial effusion)
 Anasarca denotes massive oedema of the whole
body, including the body cavities.
 Types of Oedema fluid

• 1. Transudate
Features:
 Protein-poor (<3 g/dL) and cell-poor fluid
 Produces dependent pitting oedema and body cavity effusions
 Low specific gravity
• 2. Exudate
Features:
 Protein-rich (>3 g/dL) and cell-rich (e.g., neutrophils) fluid
 Produces swelling of tissue but no pitting oedema
 High specific gravity
 Types of Oedema fluid
• 3. Lymphedema
Features:
Protein-rich fluid
Non-pitting oedema
• 4. Glycosaminoglycans
Features:
Increase in hyaluronic acid and chondroitin sulfate
Non-pitting oedema called myxedema
 Classification
• Oedema may be classified into:

 1. Localized: Gravity-independent

 2. Generalized: Gravity-dependent.

Commonly occurring around the ankles in ambulatory

patients and the sacral region in bedridden patients.

 Types of localized oedema
• 1. Inflammatory oedema
• Oedema is a cardinal sign of acute inflammatory .
• Inflammatory oedema is caused by increased
capillary permeability, which results in exudation of
fluid and plasma proteins, and increased hydrostatic
pressure due to active dilation of arterioles.
• The extent of oedema is limited by:
 Increased lymphatic flow
 Increase in the interstitial tissue hydrostatic pressure
 Types of localized oedema
• 2. Allergic oedema
• Acute allergic reactions cause local release of vaso-
active substances such as histamine, which cause
increased capillary permeability and dilation and
result in exudation of fluid and oedema.
• Commonly involves the skin, where it produces a
wheal (urticaria, hives).
• Rarely, it may affect the larynx and bronchioles,
causing respiratory obstruction (angioneurotic
oedema).
 Types of localized oedema

• 3. Oedema of Venous Obstruction.

• The effect of venous obstruction depends on the
extent of collateral venous circulation in the area.
• When obstruction of a vein leads to complete
failure of venous drainage, severe oedema and
haemorrhage result from increased hydrostatic
pressure and capillary rupture.
 Types of localized oedema
• 4. Oedema of Lymphatic Obstruction
When lymphatic drainage is obstructed, the small
amount of protein that escapes from the capillary
by pinocytosis and during ultrafiltration is not
removed and accumulates in the interstitial space.
• Over a long period, the interstitial tissue colloid
osmotic pressure increases as the protein
accumulates, and oedema then develops.
• Early lymphatic oedema is a pitting oedema.
 Types of localized oedema
• Over a prolonged period, however, the
oedematous tissue undergoes fibrosis, and the
affected area becomes firm, thickened, and
non-pitting.
• Fibrosis may be associated with marked
epidermal thickening, so that the skin comes
to resemble that of an elephant
(elephantiasis).
 B. types of Generalized Oedema

• 1. Cardiac oedema
• Cardiac failure results in diminished left
ventricular output, which leads to decreased
glomerular filtration pressure and stimulation of
the juxtaglomerular apparatus to secrete renin.
• Renin in turn induces increased aldosterone
production (secondary aldosteronism) by the
angiotensin mechanism leading to retention of
sodium and water and generalized oedema.
 B. types of Generalized Oedema

• Causes:
Left ventricular failure: hypertension, leads
to pulmonary oedema, leads to right sided
heart failure.
Right ventricular failure: COPDS, pulmonary
embolism etc
 B. types of Generalized Oedema

• 2. Oedema of Hypoproteinemia
 Leads to reduced oncotic pressure
• Causes of Hypoproteinemia
 1. Insufficient dietary intake of protein (malnutrition
oedema).
 2.Decreased synthesis of albumin in the liver (hepatic
oedema).
 3. Increased loss of protein in the urine (nephrotic syndrome).
 4. Increased loss from the intestine (protein-losing
enteropathy).
 B. types of Generalized Oedema

• 3. Renal Oedema
• Nephritic syndrome: facial>generalised
• Nephrotic syndrome: generalised
 Clinical Effects of Oedema

• Asymptomatic in most cases.

• Severe and chronic oedema of the skin may be
associated with impaired wound healing and
increased susceptibility to infection.
• Oedema of internal organs is symptomatic:
 oedema of the liver in acute hepatitis and
 oedema of heart failure
 are both associated right upper quadrant pain
caused by over stretching of the liver capsule.
 Clinical Effects of Oedema

• Oedema of the following organs is life-threatening:

• 1. Lungs (Pulmonary oedema)
• The pulmonary circulation functions at low hydrostatic
pressure (<20 mm Hg for pulmonary artery systolic pressure).
• Because this is less than plasma colloid osmotic pressure,
little fluid escapes from the pulmonary capillaries.
• Entry of fluid into the alveoli from the pulmonary capillaries is
called pulmonary oedema.
• This may interfere with gas exchange in the lungs and, when
severe, causes hypoxia and death.
 Clinical Effects of Oedema
• 2.Brain (Cerebral oedema)
• Causes of Cerebral oedema
• 1. Traumatic lesions
• 2. Infections
• 3. Neoplasms
• 4. Vascular accidents.
• The fluid collects mainly in the extracellular
space of the white matter.
 Clinical Effects of Oedema
• Effects of cerebral oedema
• 1. Oedema fluid physically separates neural
connections to cause reversible acute cerebral
dysfunction.
• 2. Increased intracranial pressure produces headache
and oedema of the optic disk (papilloedema).
• 3. Severe increase in intracranial pressure may lead to:
Tentorial herniation
Cause death due to compression of the cardiorespiratory
centers in the brain stem.
 Clinical Effects of Oedema
• 3. Serosa Cavities
• Accumulation of oedema fluid within the
pericardial sac and the pleural cavity may
interfere with normal cardiac function and
expansion of the lung.
• Fluid accumulation in the peritoneal cavity
(ascites) causes abdominal distention but does
not usually interfere with normal function of
abdominal organs
Summary of Pathophysiology of oedema
• Alteration in Starling pressure
– Produces a transudate
– Increased vascular hydrostatic pressure:
Pulmonary oedema in left-sided heart failure
Peripheral pitting edema in right-sided heart failure
Portal hypertension in cirrhosis producing ascites
– Decreased vascular plasma oncotic pressure (hypoalbuminemia):
Malnutrition with decreased protein intake
Cirrhosis with decreased synthesis of albumin
Nephrotic syndrome with increased loss of protein in urine (> 3.5 g/24
hours)
Malabsorption with decreased reabsorption of protein
Summary of Pathophysiology of oedema

– Renal retention of sodium and water

Increases hydrostatic pressure (increased plasma
volume)
Decreases oncotic pressure (dilutional effect on
albumin)
Examples-acute renal failure, glomerulonephritis
 Summary of Pathophysiology of oedema

• Increased vascular permeability

– Produces an exudate
– Example-acute inflammation (e.g., tissue swelling
following a bee sting)
Summary of Pathophysiology of oedema

• Lymphatic obstruction
– Produces lymphedema
– Examples
Lymphedema following modified radical mastectomy
and radiation
Filariasis due to Wuchereria bancrofti
Scrotal and vulvar lymphedema due to
lymphogranuloma venereum
Breast lymphedema due to blockage of subcutaneous
lymphatics by malignant cells
Summary of Pathophysiology of oedema

• Increased synthesis of extracellular matrix

components (e.g., glycosaminoglycans)
T-cell cytokines stimulate fibroblasts to synthesize
glycosaminoglycans.
Example-pretibial myxedema and exophthalmos in
Graves' disease
 HAEMORRHAGE
• Definition: This is discharge of blood out of the vascular
compartment on to the exterior of the body or into nonvascular
body spaces.
• Causes
 1. Trauma
 2. Rupture of atherosclerotic abdominal aorta aneurysm,
congenitally weak cerebral artery anuerysm (berry aneurysm) and
ectopic gestation
 3. Bleeding peptic ulcer
 4.Infections (e.g., pulmonary tuberculosis)
 5. Invasive neoplasms may erode blood vessels and lead to
hemorrhage.
 HAEMORRHAGE
• Some definitions:
• Haematoma: Haemorrhage into soft tissue.
• Haemothorax: Haemorrhage into the pleural
cavity.
• Haemopericardium: Haemorrhage into the
pericardial space.
• Haemoperitoneum: Haemorrhage into the
peritoneal cavity.
• Haemarthrosis: Bleeding into a joint space.
 HAEMORRHAGE
• Petechiae: Pinpoint haemorrhages, usually in
the skin or conjunctiva (<1.0mm)
• This lesion represents the rupture of a
capillary or arteriole and occurs in conjunction
with coagulopathies or vasculitis.
• Petechiae may also be produced by
microemboli from infected heart valves
(bacterial endocarditis)
 HAEMORRHAGE
• Purpura: Diffuse superficial haemorrhages in
the skin, up to 1 cm in diameter.
• Ecchymosis: A larger superficial haemorrhage
in the skin. (1.0cm). A good example of an
ecchymosis is black eye.
 THROMBOSIS

• Thrombosis refers to the formation of a thrombus

in the lumen of a blood vessel of a living person.
• Thrombus is an aggregate of coagulated blood
containing platelets, fibrin, and entrapped cellular
elements, within a vascular lumen.
• A thrombus adheres to vascular endothelium
• Simple blood clot, which reflects only activation
of the coagulation cascade and can form in vitro
or even postmortem.
 Types of THROMBOSIS

 1. Venous

 2. Arterial
 Thrombosis in the Venous System
• Thrombosis in the venous system is
multifactorial.
• Conditions that favour the development of
deep venous thrombosis include (triad):
1.Stasis
2.Injury
3.Hypercoagulability
 Risk factors for thrombosis
• 1. Immobilization after surgery or after leg casting (Major)
• 2.Obesity
• 3. Advanced age
• 4. Previous thrombosis
• 5. Cancer.
• 6. Congestive
• 7. Myocardial infarction
• 8. Atrial fibrillation
• 9. Cardiomyopathy
 Pathology

• Most (>90%) venous thromboses occur in deep veins of the

legs; the rest usually involve pelvic veins.
• Most venous thrombi begin in the calf veins, frequently in
the sinuses above the venous valves.
• Outcome of a venous thrombus:
1. Lysis

2. Organization

3. Propagation

4. Embolization.
 Clinical Features

• Small thrombi are asymptomatic

• Larger thrombi in the iliofemoral system may
cause no symptoms.
• Some patients have calf tenderness, often
associated with forced dorsiflexion of the foot
(Homan sign).
• Occlusive thrombosis of femoral or iliac veins
leads to severe congestion, oedema, and
cyanosis of the lower extremity
 Thrombosis in the Arterial System
• Vessels commonly involved
• 1.The vessels most commonly involved:
Coronary
Cerebral
Mesenteric
 Renal arteries
 Arteries of the lower extremities.
• 2.Less commonly, arterial thrombosis occurs in other disorders:
Arteritis
Trauma
 Blood diseases.
 Possible outcomes of arterial thrombus

 1. Lysis
 2. Propagation
 3. Organization
 4. Canalization
 5. Embolization
 Clinical Features

• 1. Myocardial infarct (heart attack)

• 2. Cerebral infarct (stroke)
• 3. Intestinal infarction
• 4. Kidney infarcts
• 5. Gangrene of the leg
 EMBOLISM

• Definition:
• This is the passage through venous or arterial
circulations of any material that can lodge in a blood
vessel and obstruct its lumen.
• The most common embolus is a thromboembolus
that is, a thrombus formed in one location that
detaches from a vessel wall at its point of origin and
travels to a distant site.
 Pulmonary Arterial Embolism
• Pulmonary arterial embolism is potentially fatal
• It is an important diagnostic and therapeutic challenge.
• Occurs in 1% to 2% of postoperative patients over the age of 40.
• The risk after surgery increases with:
• 1. Advancing age
• 2. Obesity
• 3. Length of operative procedure
• 4. Postoperative infection
• 5. Cancer
• 6. Preexisting venous disease.
 Sources of emboli
• 1. Most pulmonary emboli (90%) arise from deep
veins of the lower extremities; the iliofemoral
veins.
• 2. Pelvic venous plexus
• 3.Right side of the heart.
• 4. Indwelling lines in the systemic venous system
or pulmonary artery.
• The upper extremities are a rare source of
thromboemboli.
 Clinical features of pulmonary embolism

• Acute pulmonary embolism is divided into the

following syndromes:
• 1. Asymptomatic small pulmonary emboli
• 2.Transient dyspnea and tachypnea without
other symptoms
• 3. Pulmonary infarction, with pleuritic chest
pain, haemoptysis, and pleural effusion
• 4. Cardiovascular collapse with sudden death
 Clinical features of pulmonary embolism

• Chronic pulmonary embolism, with numerous

(usually asymptomatic) emboli lodged in small
arteries of the lung, can lead to pulmonary
hypertension and right-sided heart failure
 Massive Pulmonary Embolism

• One of the most dramatic calamities complicating

hospitalization is the sudden collapse and death of a patient.
• Often due to release of a large deep venous thrombus from a
lower extremity.
• Classically, a postoperative patient succumbs upon getting out
of bed for the first time.
• The muscular activity dislodges a thrombus that formed as a
result of the stasis from prolonged bed rest.
• Pulmonary embolism is the most common cause of death
after major orthopedic surgery and is the most frequent non
obstetric cause of postpartum death.
 Locations of pulmonary emboli
• 1. Bifurcation of the main pulmonary artery (saddle
embolus), obstructing blood flow to both lungs
• 2. First branching of the right or left pulmonary
arteries.
• 3. Multiple smaller emboli may lodge in secondary
branches and prove fatal.
• With acute obstruction of more than half of the
pulmonary arterial tree, the patient often experiences
immediate severe hypotension (or shock) and may die
within minutes.
 Locations of pulmonary emboli
• The haemodynamic consequences of such
massive pulmonary embolism are acute right
ventricular failure from sudden obstruction of
outflow and pronounced reduction in left
ventricular cardiac output, secondary to the
loss of right ventricular function.
• The low cardiac output is responsible for the
sudden appearance of severe hypotension.
 INFARCTION
• Definition:
• Infarction is ischaemic tissue or organ necrosis
resulting from occlusion of either its arterial
supply or its venous drainage within the living
body.
• The dead tissue is called an infarct.
• Types:
A. Arterial
B. Venous
 INFARCTION
• Causes
A. Thrombo-embolic events (most common)
B. Other causes of infarction (Less):
 1. Local vasospasm.
 2. Expansion of an atheroma
 3. Extrinsic compression of a vessel.
 4. Twisting of the vessels (e.g. testicular torsion)
 5. Compression of the blood supply by oedema
 6. Entrapment in a hernia sac
 7. Traumatic rupture of the blood vessel.
Factors that condition the development of an infarct

1. The nature of the vascular supply

2. The rate of development of the occlusion
3. The vulnerability of the tissue or organ to hypoxia
4. Oxygen content of blood
5. Pre-existing cardiovascular disease (CCF)
Factors that determine the size of an infarct

• 1.The amount of tissue rendered ischaemic

• 2.The severity and duration of the ischaemia
• 3.The susceptibility of the component cells of the
tissue to ischaemic injury.
• The appearance of an infarct depends on the nature
of the subsequent changes in the dead tissue, and in
particular whether it undergoes coagulative or
colliquative necrosis.
 SHOCK
• Definition:
• Shock is the state of profound circulatory
failure due to reduction either in cardiac
output or in the effective circulating blood
volume resulting in life-threatening hypo-
perfusion and cellular hypoxia of vital organs.
• Shock is not a disease of its own but a
complication of some other disease.
 SHOCK
In shock, all organs are perfused inadequately, as a
result, all tissues suffer (some more, some less) from:
 Lack of oxygen
 Lack of substrates
 Lack of waste removal
 Damage from low flow
 Bacteria (in septic shock)
Concept of inadequate generalized perfusion

• The cardiovascular system can be considered as

consisting of a:
 Pump
 Fluid
 two connected tubes
• Insufficient flow through this system can result from
one of three principal mechanisms.
 1. THE FLUID LEVEL IS LOW – due to loss of blood
volume.
 2. THE PUMP IS WEAK – due to heart malfunction.
 3. THE CONTAINER IS TOO LARGE by vasodilation
(peripheral pooling of blood).
 TYPES OF SHOCK:

1. Hypovolaemic Shock
-Loss of whole blood → haemorrhagic shock
-Loss of plasma alone e.g. severe burns
-Loss of fluid alone by persistent vomiting or
diarrhoea
2. Cardiogenic shock (pump failure)
-Myocardial infarction
-Impaired pulmonary circulation e.g. embolus in
pulmonary artery
 TYPES OF SHOCK:
3. Shock by generalized vasodilatation –
makes the container too large (also called
“distributive shock”)
It occurs in 3 settings
– Septic shock
– Anaphylactic shock
– Neurogenic shock – result as a complication of
general anesthesia or spinal cord injury.
 Clinical features of shock
• These include:
 rapid, shallow breathing
 cold, clammy and cyanotic skin
 constricted veins
 fast shallow pulse
 low blood pressure
 low or nil urine output.
• The patient at this stage may be fully conscious.
 Clinical features of shock
Systemic vasodilatation (hypotension)
Diminished myocardial contractility
Widespread endothelial injury and activation,
causing systemic leukocyte adhesion (leucocyte
plugging) and pulmonary alveolar capillary
damage (adult respiratory distress syndrome
ARDS).
Activation of the coagulation system resulting in
DIC.
 STAGES OF SHOCK

• About 10% of the blood volume can be lost

without a decrease in the blood pressure or cardiac
output; but with greater loss both functions drop
and they reach zero with a blood loss of 35-45%.
• Shock is a progressive disorder that if uncorrected,
leads to death.
 STAGES OF SHOCK
Unless the cause of shock is massive and rapidly fatal, shock
tends to evolve through three general phases:
1. Non-progressive
2. Progressive
 (1 and 2 are reversible)
3. Irreversible phases
• Reversible vrs irreversible shock:
 there is no way to decide whether a given situation of
shock is irreversible or not.
 These stages have been clearly documented in
hypovolaemic shock but are common to other forms of
shock.
 NON-PROGRESSIVE PHASE

• Initial/early: Non-progressive phase:

• Reflex compensatory mechanisms are activated and perfusion
of vital organs is maintained.
• A number of neuro-hormonal mechanisms help maintain
cardiac output and blood pressure
• These include:
1.– baroreceptor reflexes
2. - release of catecholamines
3 - activation of the rennin – angiotensin – aldosterone system
4 - antidiuretic hormone release (vasopressin is also a
vasoconstrictor)
5- generalized sympathetic stimulation.
 NON-PROGRESSIVE PHASE
• The net effect is tachycardia, peripheral vasoconstriction, and
renal conservation of fluid.
• Cutaneous vasoconstriction is responsible for the
characteristic coolness and pallor of skin in well-developed
shock
• Septic shock may initially cause cutaneous vasodilatation and
thus present with warm, flushed skin.
• NB Coronary and cerebral vessels are less sensitive to this
compensatory sympathetic response and thus maintain
relatively normal caliber, blood flow, and oxygen delivery to
their respective vital organs.
 PROGRESSIVE PHASE

• If the underlying causes are not corrected, shock

passes imperceptibly to the PROGRESSIVE PHASE,
during which there is widespread tissue hypoxia.
– In the setting of persistent oxygen deficit, intracellular
aerobic respiration is replaced by anaerobic glycolysis with
excessive production of lactic acid.
– The resultant metabolic lactic acidosis lowers the tissue
pH and blunts the vasomotor response.
• Therefore arterioles dilate, and blood begins to pool
in the microcirculation.
 PROGRESSIVE PHASE
• This peripheral pooling not only worsens the
cardiac output, but also puts endothelial cells
at risk for developing anoxic injury with
subsequent DIC.
• With widespread tissue hypoxia, vital organs
are affected and they begin to fail.
• Clinically the patient at this stage may become
confused, and the urinary output declines.
 IRREVERSIBLE PHASE.

• Unless there is intervention, the process

eventually enters an IRREVERSIBLE PHASE.
• There is widespread cell injury and this is
reflected in lysosomal enzyme leakage, which
further aggravates the shock state.
 VICIOUS CIRCLES IN SHOCK

• Poor perfusion of the heart impairs myocardial

function, with further impairment of cardiac
output, and therefore reduced perfusion of all
organs including the heart itself.
• Poor perfusion of the pancreas induces the
pancreas to produce peptides that further depress
cardiac function; a circulating myocardial
depressant factor (MDF) has actually been
demonstrated in shock patients.
 VICIOUS CIRCLES IN SHOCK

• Poor perfusion of the liver which is the site where

most of the lactic acid is broken down; is now
presented with an excess of it, but being anoxic it
cannot handle it, so that liver becomes a producer
of lactate; this worsens the acidosis, which impairs
cardiovascular function.
• Under these conditions the liver becomes unable
to inactivate all the chemical mediators that flood
the circulation.
 VICIOUS CIRCLES IN SHOCK

• Poor perfusion of the gut causes a

breakdown of the mucosal barrier (the gut is
very sensitive to ischaemia); bacteria reach
the blood, setting the stage for septic shock;
sloughing of the mucosa causes bleeding
and further fluid loss, aggravating the poor
perfusion throughout the body.
 VICIOUS CIRCLES IN SHOCK

• Poor perfusion of the kidneys impairs renal

function and thereby the excretion of acid
metabolites, which worsens the acidosis; reduced
blood perfusion may also lead to tubular necrosis
with further retention of toxic metabolites.
• Poor perfusion of the lungs contributes to the
genesis of the “shock lung” which further impairs
the oxygenation of the blood.
• Capillary plugging by leukocytes creates another
vicious cycle by aggravating the ischaemia.
 The Chemical Mediators of Shock

• Practically all chemical mediators of inflammation have been

found in the blood of shock patients including histamine,
serotonin, kinins and nitric oxide (NO).
• The key is injured tissue – be it tissue injured by poor
perfusion or by the condition that caused the shock (e.g.
trauma).
• Injured cells respond by secreting prostaglandins and
leukotrienes.
• Dying and dead cells can activate complement and also
release lysosomal proteolytic enzymes as well as
thromboplastin; these in turn can activate the kinin,
complement, clotting, and fibrinolytic cascade.
 The Chemical Mediators of Shock

• The complement derived anaphylatoxins (C3a, C4a,

C5a) activate the leukocytes, which respond by
aggregating and producing micro-thrombi (DIC) as
well as sticking to endothelium and causing damage;
correspondingly the number of circulating leukocytes
drops.
• The micro-vascular endothelium is made leaky by
permeability – increasing mediators as well as by
injury due to activated leukocytes.
 The Chemical Mediators of Shock

• Endorphine (vasodilators) seen in shock

patients are responsible for the peripheral
vasodilatation.
• Myocardial Depressant Factor – more than 10
identified in shock patients, majority of which
are produced in the pancreas.
 MORPHOLOGY

• The cellular and tissue changes are essentially those

of hypoxic injury.
• The cellular changes may appear in any tissue but
they are particularly evident in the:
 Brain
 Heart
 Lungs
 Kidneys
 Adrenals
 Gastrointestinal tract.
 MORPHOLOGY
• Brain: Ischaemic encephalopathy.

• Heart:
 -Focal or widespread coagulative necrosis
 - Subendocardial haemorrhages
 - Contraction bands necrosis

• Kidneys – Extensive tubular ischaemic injury (acute tubular

necrosis)
 oliguria
 anuria
 electrolyte disturbances.
 MORPHOLOGY
• Lungs – In shock due to bacterial sepsis and
trauma (lungs are resistant to effects of
hypovolaemic shock) giving rise to diffuse
alveolar damage (shock lung).
• Adrenals – Cortical cell lipid depletion.
• GIT – Haemorrhagic enteropathy i.e. patchy
mucosal h’ges and necrosis.
• Liver – Fatty change, central haemorrhagic
necrosis.
• THE END