SHOCK

DEFINITION :

Shock is a life-threatening clinical syndrome of

cardiovascular collapse characterised by :

- an acute reduction of effective circulating blood

volume (hypotension) and an inadequate perfusion of
cells and tissues (hypoperfusion).

- If uncompensated, these mechanisms may lead to

impaired cellular metabolism and death.
 - The term “initial (or primary) shock” is used for
transient and usually a benign vasovagal attack resulting
from sudden reduction of venous return to the heart caused
by neurogenic vasodilatation and consequent peripheral
pooling of blood e.g. immediately following trauma,
severe pain or emotional overreaction such as due to fear,
sorrow or surprise.

- “true (or secondary) shock” is a circulatory imbalance

between oxygen supply and oxygen requirements at the
cellular level, and is also called as circulatory shock.
- Clinically, patients of primary shock suffer from the
attack lasting for a few seconds or minutes and
develop brief unconsciousness, weakness, sinking
sensation, pale and clammy limbs, weak and rapid
pulse, and low blood pressure.
- Another type of shock which is not due to circulatory
derangement is anaphylactic shock from type 1
immunologic reaction.

- In routine clinical practice, however, true shock is the

form which occurs due to haemodynamic derangements with
hypoperfusion of the cells , this is the type which is
commonly referred to as ‘shock’ if not specified.
CLASSIFICATION AND ETIOLOGY
(CAUSES OF SHOCK) -

1. Hypovolaemic shock :
This form of shock results from inadequate circulatory
blood volume that may be either from the loss of red
cell mass and plasma from haemorrhage, or from the
loss of plasma volume alone.
Hypovolaemic shock can occur with -

 Massive haemorrhage
 Dehydration from vomiting, diarrhoea

 Burns

 Excessive use of diuretics

 Acute pancreatitis
2. Cardiogenic shock :
Acute circulatory failure with sudden fall in cardiac
output due to myocardial pump failure, from acute
diseases of the heart without actual reduction of
blood volume (normovolaemia) results in cardiogenic
shock.
i) Deficient emptying e.g.
a) Myocardial infarction (Intrinsic myocardial damage)
b) Cardiomyopathies
c) Rupture of the heart, ventricle or papillary muscle
d) Cardiac arrhythmias

ii) Deficient filling e.g.

Cardiac tamponade from haemopericardium
iii) Obstruction to the outflow e.g.
a) Pulmonary embolism
b) Ball valve thrombus
c) Tension pneumothorax
d) Dissecting aortic aneurysm
3. Shock associated with systemic inflammation : may be
triggered by variety of insults e.g.

 Microbial infections (septic shock)

 Gram -ve septicemia
 Gram +ve septicemia
 Burns
 Trauma- Shock resulting from trauma is initially
due to hypovolaemia, but even after haemorrhage has been
controlled, these patients continue to suffer loss of plasma
volume into the interstitium of injured tissue.
a) Severe injuries
b) Surgery with marked blood loss
c) Obstetrical trauma

 Pancreatitis
 Septic shock is most frequently triggered by gram
positive bacterial infections, followed by gram negative
bacteria and fungi.

 Hence an older synonym "endotoxic shock" is no longer

appropriate.
OTHER TYPES:

Neurogenic shock : Neurogenic shock results from

causes of interruption of sympathetic vasomotor supply.
 Shock occur in setting of an anesthetic accident
 High Spinal cord injury

 Severe head injury

Anaphylactic shock:
 Occur in IgE mediated hypersensitivity reaction

 In both of these forms of shock, acute vasodilatation leads

to hypotension and tissue hypo-perfusion.
Hypoadrenal shock :
Hypoadrenal shock occurs from unknown adrenal
insufficiency in which the patient fails to respond normally
to the stress of trauma, surgery or illness.
PATHOGENESIS

In general all forms of shock involve 3 deragements:

1. Reduced effective circulating blood volume

It may results from either of mechanisms:
 By actual loss of blood volume as in hypovolaemic shock.
 By decreased cardiac output, without actual loss of blood
(normovolaemia) as occur in cardiogenic shock and septic
shock.
2. Impaired tissue oxygenation :
 Following reduction in effective circulating blood
volume from either of the above mechanism and
from any of the etiologic agents, there is decreased
venous return to heart resulting in decreased
cardiac output.

 Thiscauses reduced supply of oxygen to organs

and tissue and hence tissue anoxia occurs which
causes cellular injury.
3. Release of inflammatory mediators :
 In response to cellular injury, innate immunity of
the body gets activated as a body defense
mechanism and causes release of inflammatory
mediators but eventually these agents themselves
become the cause of cell injury.
 Microbial cell wall constituents combined with
receptors on cells of the innate immune system
triggering the release of proinflammatory mediators
(cytokines); but similar process of release of these
agents takes place in late stages of shock from other
causes.
 Several, proinflammatory mediators are released from
 monocyte macrophages
 other leukocytes
 other body cells

 The most important inflammatory mediarors are

 Tumor necrosis factor  (TNF)
 Interleukin-1 (IL-1)
Pathogenesis of circulatory shock
PATHOGENESIS OF HYPOVOLAEMIC SHOCK

 Hypovolaemic shock occurs from : inadequate circulatory

blood volume (most often from massive hemorrhage)

Decrease cardiac output
 Severity of clinical features depends upon degree of blood
volume loss.
 Major clinical features are
 Increased heart rate
 Low BP
 Low urinary output ( oliguria to anuria)
 Alteration in mental state (agitated to confused to lethargic)

Haemorrhagic shock is divided into 4 types:

 < 1000 ml: Compensated

 1000-1500 ml: Mild

 1500-2000 ml: Moderate

 >2000 ml: Severe

PATHOGENESIS OF CARDIAC SHOCK

 Cardiogenic shock results from severe left

ventricular dysfunction (e.g. acute MI). There is
decreased cardiac output that result in
 Tissue hypo perfusion
 Movement of fluid from pulmonary vascular bed
into pulmonary interstitial space, initially
(interstitial pulmonary edema) later to the
alveolar spaces (alveolar pulmonary edema)
PATHOGENESIS OF SEPTIC SHOCK

 Septic shock ranks first among the causes of death in

ICU.
 Its incidence is rising due to improvement in life
support for critically ill patients as well as increase
in immunocomprised hosts and increasing
prevalence of multidrug resistant organism in
hospital setting.
 Septic is most frequently triggered by gram positive
bacterial infection, followed by gram negative
bacteria and fungi.
Factors believed to play major role in pathophysiology
of septic shock include following:

1. Inflammatory and counter inflammatory responses:

 In sepsis various microbial cell wall constituent
engage receptors on cells on innate immune system
triggering proinflammatory responses.
 Upon activation innate immune cells (Neutrophils
monocyte macrophages) produce - TNF, IL1, IFN-, IL-
12, IL-18, HMG1 (high mobility group box 1 protein)
Reactive oxygen species, PGs and PAF.

 These effector molecule induce endothelial cells to

upregulate adhesion molecule expression and further
stimulate cytokine and chemokine production.
 The complement cascade is also activated by microbial
components results in production of
Anaphylotoxins (C3a, C5a) Contribute
Chemotactic fragments C5a proinflammatory
Opsonins C3b state
 Microbial components can activates coagulation
directly through factor XII.
 Indirectly through altered endoethelial function.

 This enhances development of thrombi.

 The hyperinflammatory state initiated by sepsis also

activates counter regulatory immunosuppresive
mechanism, as a results septic patients may oscillate
between hyperinflammatory and immunosuppresed
states.
2. Endothelial activation and injury :

 The proinflammatory state and endothelial cell

activation associated with sepsis leads to widespread
vascular leakage and tissue edema. Cytokine loosen
endothelial cell junction making vessel leaky and
resulting accumulation of protein rich edema
throughout the body.
 Activated endothelium also increase production of NO and
vasoactive inflammatory mediators (C3a, C5a, PAF), this
leads to vascular smooth muscle relaxation - systemic
hypotension.
3. Induction of procoagulant state
 There is systemic activation of thrombin, and
deposition of fibrin rich thrombi in small vessels
often throughout the body.
 In full blown DIC the consumption of
coagulation factors and platelets is so great that
deficiencies of these factors appear leading to
bleeding and haemorrhage.
4. Metabolic abnormalities:

 Impaired tissue perfusion causes switch from

aerobic to anaerobic glycolysis resulting
metabolic lactic acidosis.

 Lactic acidosis lowers tissue pH which in turn

makes vasomotor response ineffective. This
result in vasodilatation and peripheral pooling of
blood.
5. Organ dysfunction:
 Systemic hypotension
 Interstitial edema
 Small vessel thrombosis
All these decrease the
delivery oxygen and
nutrients to the tissue

 High level of cytokines and secondary mediators

diminish myocardial contractility and cardiac output
and increased vascular permeability and endothelial
injury can lead to ARDS.
 Ultimately these factors can cause failure of multiple
organs particularly kidney, lung, liver and heart
culminating in death.
 Superantigens: are group of secreted bacterial proteins
that can cause a syndrome similar to septic shock (e.g.
toxic shock syndrome).
 Superantigens are polyclonal T-lymphocyte activators
that induce the release of high level of cytokine that
result in variety of clinical manifestations like
 diffuserash
 vasodilatation
 Hypotension
 shock and death
 The net result of above mechanisms is vasodilatation and
increased vascular permeability in septic shock.

 Profound peripheral vasodilatation and pooling of blood causes

hyperdynamic circulation in septic shock, in contrast to
hypovolaemic and cardiogenic shock.

 Increased vascular permeability causes development of

inflammatory oedema.
 Disseminated intravascular coagulation (DIC) is prone to
develop in septic shock due to endothelial cell injury by
toxins.

 Reduced blood flow produces hypotension,

inadequate perfusion of cells and tissues, finally leading to
organ dysfunction.
STAGES OF SHOCK :

 Shock is a progressive disorder that if

uncorrected leads to death.
 The exact mechanism of death from sepsis are
unclear, however organ failure and tissue
hypoxia has a central role.
 In hypovolemic and cardiogenic shock tends to
evolve through 3 general phases unless the insult
is massive and rapidly lethal.
 Non progressive phase / Reversible (Compensated shock)
 Progressive stage

 Irreversible stage
1. Non progressive phase / Reversible (Compensated
shock) -
 A initial phase during which reflex compensatory
mechanisms are activated and perfusion of vital organs
(Brain and Heart) is maintained.

 If the condition that caused the shock is adequately

treated, the compensatory mechanism may be able to
bring about recovery and reestablish the normal
circulation; this is called compensated or reversible shock.
 In non progressive phase of shock, a variety of neurohumoral
mechanism help to maintain cardiac output and blood
pressure.

 These include baroreceptor reflex, catecholamine release

(adrenaline) activation of renin-angiotensin axis, ADH release
and generalized sympathetic stimulation.
 Net effect: Tachycardia
Peripheral vasoconstriction
Renal conservation of fluid

 Cutaneous vasoconstriction is responsible for the

characteristic coolness and pallor of the skin in
well developed shock. Although septic shock
initially causes cutaneous vasodilatation, thus
present with warm, flushed skin.
These compensatory mechanisms are as under :

i) Widespread vasoconstriction. In response to reduced

blood flow (hypotension) and tissue anoxia, the neural and
humoral factors (e.g. baroreceptors, chemoreceptors,
catecholamines, renin, and angiotensin-II) are activated.

-All these bring about vasoconstriction, particularly in the

vessels of the skin and abdominal viscera.
 - Widespread vasoconstriction is a protective mechanism
as it causes increased peripheral resistance, increased
heart rate (tachycardia) and increased blood pressure.

However, in septic shock, there is initial

vasodilatation followed by vasoconstriction.
 - in severe septic shock there is elevated level of
thromboxane A2 which is a potent vasoconstrictor and may
augment the cardiac output along with other sympathetic
mechanisms.

- Clinically cutaneous vasoconstriction is responsible for

cool and pale skin in initial stage of shock.
ii) Fluid conservation by the kidney - In order to
compensate the actual loss of blood volume in
hypovolaemic shock, the following factors may assist in
restoring the blood volume and improve venous return to
the heart :

 Release of aldosterone from hypoxic kidney by

activation of renin-angiotensin-aldosterone mechanism.

 Release of ADH due to decreased effective circulating

blood volume.
 Reduced glomerular filtration rate (GFR) due to arteriolar
constriction.

 Shifting of tissue fluids into the plasma due to lowered

capillary hydrostatic pressure (hypotension).
iii) Stimulation of adrenal medulla : In response to low
cardiac output, adrenal medulla is stimulated to release excess
of catecholamines (epinephrine and non-epinephrine) which
increase heart rate and try to increase cardiac output.
2. Progressive stage: This is a stage when the patient
suffers from some other stress or risk
factors (e.g. pre-existing cardiovascular and lung
disease) besides persistence of the shock so that there is
progressive deterioration.

- characterized by tissue hypoperfusion

- If underlying cause are not corrected, shock passes to

progressive phase during which there is a widespread
tissue hypoxia.
 In case of persistent oxygen deficit, intracellular aerobic
respiration is replaced by anaerobic glycolysis with
excessive production of lactic acid.

 The resulting lactic acidosis lowers tissue pH and

blunts the vasomotor response; arterioles dilate and
blood begins to pool in microcirculation.
 Peripheral pooling not only worsens cardiac output
but also puts endothelial cells at risk of developing
anoxic injury with subsequent DIC with
widespread tissue hypoxia.

 vital organs are affected and begin to fail.

 Clinicallyat this stage the patient develops

confusion and worsening of renal function.
3. Irreversible stage:
- An irreversible stage occurs if cellular and tissue injury
is so severe that even if haemodynamic defects are
corrected survival is not possible.

- When the shock is so severe that in spite of

compensatory mechanisms and despite therapy and
control of etiologic agent which caused the shock, no
recovery takes place, it is called
decompensated or irreversible shock.
Its effects due to widespread cell injury include the following :

i) Progressive vasodilatation. During later stages of shock,

anoxia damages the capillary and venular wall and arterioles
become unresponsive to vasoconstrictors listed above and
begin to dilate.

- Vasodilatation results in peripheral pooling of blood which

further deteriorate the effective circulating
blood volume.
ii) Increased vascular permeability. Anoxic damage to
tissues releases inflammatory mediators which cause
increased vascular permeability.

- This results in escape of fluid from circulation into the

interstitial tissues thus deteriorating effective circulating blood
volume.
iii) Myocardial depressant factor (MDF) –
- Progressive fall in the blood pressure and persistently
reduced blood flow to myocardium causes coronary
insufficiency and myocardial
ischaemia due to release of myocardial depressant factor
(MDF).

- This results in further depression of cardiac function,

reduced cardiac output and decreased blood flow.
iv) Worsening pulmonary hypoperfusion - Further
pulmonary hypoperfusion causes respiratory distress due to
pulmonary oedema, tachypnoea and adult respiratory distress
syndrome (ARDS).
v) Anoxic damage to heart, kidney, brain - Progressive
tissue anoxia causes severe metabolic acidosis due to
anaerobic glycolysis.

- There is release of inflammatory cytokines and

other inflammatory mediators and generation of free radicals.

- Since highly specialised cells of myocardium, proximal

tubular cells of the kidney, and neurons of the CNS are
dependent solely on aerobic respiration for ATP generation,

-there is ischaemic cell death in these tissues.

vi) Hypercoagulability of blood –

Tissue damage in shock activates coagulation cascade with

release of clot promoting factor, thromboplastin and release of
platelet aggregator, ADP, which contributes to slowing of blood-
stream and vascular thrombosis.

- In this way, hypercoagulability of blood with consequent

microthrombi impair the blood flow and
cause further tissue necrosis.
- Clinically, at this stage the patient has features of
coma, worsened heart function and progressive renal
failure due to acute tubular necrosis.

Effects :
- Brain - Hypoxic encephalopathy
- Heart - Focal myocardial necrosis
- Lungs - ARDS
- Kidney - ATN
- Adrenal - Necrosis
- GI - Haemorrhagic gastroenteropathy
- Liver - Necrosis
- Blood - DIC
MORPHOLOGY -
 The cellular and tissue changes induced by
cardiogenic or hypovolemic shock are those of
hypoxic injury.
 Changes can manifest in any tissue although
particularly evident in -
 Brain
 Heart
 Lung
 Kidneys
 Adrenal
 GIT
 Eventually, shock is characterised by multisystem failure.

 The morphologic changes in shock are due to hypoxia

resulting in degeneration and necrosis in various organs.
1. HYPOXIC ENCEPHALOPATHY - Cerebral ischaemia in
compensated shock may produce altered state of consciousness.

However, if the blood pressure falls below 50 mmHg as occurs

in systemic hypotension in prolonged shock and cardiac arrest,
brain suffers from serious ischaemic damage with loss of cortical
functions, coma, and a vegetative state.
Grossly, the area supplied by the most distal branches of the
cerebral arteries suffers from severe ischaemic necrosis which
is usually the border zone between the anterior and middle
cerebral arteries.
Microscopically, the changes are noticeable if ischaemia is
prolonged for 12 to 24 hours.

- Neurons, particularly Purkinje cells, are more prone to develop

the effects of ischaemia.

- The cytoplasm of the affected neurons is intensely eosinophilic

and the nucleus is small pyknotic.

- Dead and dying nerve cells are replaced by gliosis.

2. HEART IN SHOCK - Heart is more vulnerable to the
effects of hypoxia than any other organ.

 Heart is affected in cardiogenic as well as in other forms

of shock.

 There are 2 types of morphologic changes in heart in all

types of shock :

i) Haemorrhages and necrosis - There may be small or

large ischaemic areas or infarcts, particularly located in the
subepicardial and subendocardial region.
ii) Zonal lesions - These are opaque transverse contraction
bands in the myocytes near the intercalated disc.
3. SHOCK LUNG - Lungs due to dual blood supply are
generally not affected by hypovolaemic shock but in septic
shock the morphologic changes in lungs are quite
prominent termed ‘shock lung’.

 Grossly, the lungs are heavy and wet.

 Microscopically, changes of adult respiratory distress
syndrome (ARDS) are seen.

 The changes include –

 congestion

 interstitial and alveolar oedema

 interstitial lymphocytic infiltrate

 alveolar hyaline membranes

 thickening and fibrosis of alveolar septa and

 fibrin and platelet thrombi in the pulmonary

microvasculature.
4. SHOCK KIDNEY - One of the important complications of
shock is irreversible renal injury.

 The renal ischaemia following systemic hypotension is

considered responsible for renal changes in shock.

 The end-result is generally anuria and death.

 Grossly, the kidneys are soft and swollen. Sectioned

surface shows blurred architectural markings.
Microscopically, the tubular lesions are seen at all levels of
nephron and are referred to as acute tubular necrosis (ATN)
which can occur following other causes besides shock.

If extensive muscle injury or intravascular haemolysis are also

associated, brown tubular casts are seen.
5. ADRENALS IN SHOCK - The adrenals show stress
response in shock.

 This includes release of aldosterone in response to hypoxic

kidney, release of glucocorticoids from adrenal cortex and
catecholamines like adrenaline from adrenal medulla.

 In severe shock, acute adrenal haemorrhagic necrosis may

occur.
6.HAEMORRHAGIC GASTROENTEROPATHY –
The hypoperfusion of the alimentary tract in conditions such as
shock and cardiac failure may result in mucosal and mural
infarction called haemorrhagic gastroenteropathy.

 In shock due to burns, acute stress ulcers of the stomach or

duodenum may occur and are known as Curling’s ulcers.
 Grossly, the lesions are multifocal and widely distributed
throughout the bowel.

 The lesions are superficial ulcers, reddish purple in colour.

 The adjoining bowel mucosa is oedematous and

haemorrhagic.
 Microscopically, the involved surface of the bowel shows
dilated and congested vessels and haemorrhagic necrosis of
the mucosa and sometimes submucosa.

 Secondary infection may supervene and condition may

progress into pseudomembranous enterocolitis.
7. LIVER IN SHOCK - Grossly, faint nutmeg appearance is
seen.

 Microscopically, depending upon the time lapse between

injury and cell death, ischaemic shrinkage, hydropic change,
focal necrosis, or fatty change may be seen.

 Liver function may be impaired.

 In
septic shock the development of DIC leads to
widespread deposition of fibrin rich
microthrombi particularly in
Brain
Heart
Lung
Kidney
Adrenal glands
GIT
 The consumption of platelets and coagulation factors
also leads to appearance of petechial haemorrahges on
serosal surfaces and skin.

 With the exception of neuronal and myocyte ischemic

loss, virtually all these tissue may revert back to normal
if individual survives.

 But most patients with irreversible changes due to shock

die before the tissue can recover.
CLINICAL FEATURES

 In hypovolemic and cardiogenic shock the

patient present with
 Hypotension (low BP)
 Weak, rapid pulse (tachycardia)
 Tachyponea
 Cool, clammy, cyanotic skin
 In septic shock,
 Initially skin may be warm and flushed (because of
peripheral vasodilatation)
Life threatening complications in shock are due to
hypoxic cell injury resulting in immunoinflammatory
responses and activation of various cascades (clotting,
complement and kinin).

These include -
 Acute respiratory distress syndrome (ARDS)

 Disseminated intravascular coagulation (DIC)

 Acute renal failure (ARF)

 Multi organ dysfunction syndrome (MODS)

Pulmonary Thromboembolism -

 Pulmonary embolism is the most common and fatal form of

venous thromboembolism in which there is occlusion of
pulmonary arterial tree by thromboemboli.

 Pulmonary thrombosis as such is uncommon and may occur

in pulmonary atherosclerosis and pulmonary hypertension.
ETIOLOGY - Pulmonary emboli are more common in
hospitalised or bed-ridden patients.

The causes are as follows –

i) Thrombi originating from large veins of lower legs (such as

popliteal, femoral and iliac) are the cause in 95% of pulmonary
emboli.

ii) Less common sources include thrombi in varicosities of

superficial veins of the legs, and pelvic veins such as
periprostatic, periovarian, uterine and broad ligament veins.
PATHOGENESIS - Detachment of thrombi from any of the
above-mentioned sites produces a thrombo-embolus that flows
through venous drainage into the larger veins draining into
right side of the heart.

- If the thrombus is large, it is impacted at the bifurcation of

the main pulmonary artery (saddle embolus), or may be found
in the right ventricle or its outflow tract.

-
- More commonly, there are multiple emboli, or a large
embolus may be fragmented into many smaller emboli which
are then impacted in a number of vessels, particularly
affecting the lower lobes of lungs.

- Rarely, paradoxical embolism may occur by passage of an

embolus from right heart into the left heart through atrial or
ventricular septal defect.

- In this way, pulmonary emboli may reach systemic

circulation.
CONSEQUENCES OF PULMONARY EMBOLISM

- Pulmonary embolism occurs more commonly as a

complication in patients of acute or chronic debilitating
diseases who are immobilised for a long duration.

- Women in their reproductive period are at higher risk

such as in late pregnancy, following delivery and with
use of contraceptive pills.
 - The effects of pulmonary embolism depend mainly on
the size of the occluded vessel, the number of emboli, and
on the cardiovascular status of the patient.
i) Sudden death - Massive pulmonary embolism results in
instantaneous death, without occurrence of chest pain or
dyspnoea.

- if the death is somewhat delayed, the clinical features

resemble myocardial infarction i.e. severe chest pain, dyspnoea
and shock.
ii) Acute cor pulmonale - Numerous small emboli may obstruct
most of the pulmonary circulation resulting in acute right heart
failure.

- Another mechanism is by release of vasoconstrictor substances

from platelets or by reflex vasoconstriction of pulmonary
vessels.
iii) Pulmonary infarction. Obstruction of relatively small sized
pulmonary arterial branches may result in pulmonary infarction.

- The clinical features include chest pain due to fibrinous

pleuritis, haemoptysis and dyspnoea due
to reduced functioning pulmonary parenchyma.
iv) Pulmonary haemorrhage- Obstruction of terminal
branches (endarteries) leads to central pulmonary haemorrhage.

The clinical features-

- haemoptysis,
- dyspnoea,
- chest pain
Sometimes, there may be concomitant pulmonary infarction.
v) Resolution - Vast majority of small pulmonary emboli (60-
80%) are resolved by fibrinolytic activity.

- These patients are clinically silent owing to bronchial

circulation so that lung parenchyma is adequately perfused.
vi) Pulmonary hypertension, chronic cor pulmonale and
pulmonary arteriosclerosis – These are the sequelae of
multiple small thromboemboli undergoing healing rather than
resolution.
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