SHOCK

Shock is the final common pathway for a number of lethal clinical events, including:
1- severe hemorrhage,
2- extensive trauma or burns,
3- large myocardial infarction,
4- massive pulmonary embolism,
5- and microbial sepsis.

- shock gives rise to:

1- systemic hypoperfusion; caused either by (1) reduced cardiac output or
(2) by reduced circulating blood volume.

The end results are: (1) hypotension, (2) impaired tissue perfusion,(3) and cellular hypoxia.

• hypoperfusion initially cause only reversible cellular injury,

• persistence of shock eventually causes irreversible tissue injury and the death of the patient.

- Classification of shock :

Type of shock Clinical examples (causes) mechanism

Myocardial infarction
Cardiogenic Failure of myocardial pump resulting from intrinsic
Ventricular rupture
myocardial damage, extrinsic pressure, or obstruction
shock Arrhythmia
to outflow
Cardiac tamponade
Pulmonary embolism

Hypovolemic Hemorrhage
Fluid loss (e.g., vomiting, diarrhea, burns, or trauma) Inadequate blood or plasma volume
shock
- Peripheral vasodilation and pooling of blood;
microbial infection: - gram-negative infections.
- endothelial activation/injury;
- gram-positive
Septic shock - fungal infections
- leukocyte-induced damage;
- disseminated intravascular coagulation;
- activation of cytokine cascades

Less commonly

neurogenic shock may occur in the setting of an anesthetic as a result of loss of vascular tone and peripheral
shock accident or a spinal cord injury pooling of blood

Anaphylactic represents systemic vasodilation and increased acute severe widespread vasodilation results in
shock vascular permeability caused by an tissue hypoperfusion and cellular anoxia.
immunoglobulin E hypersensitivity reaction

- Clinical picture :
- In hypovolemic and cardiogenic shock, the patient presents with:
hypotension; a weak, rapid pulse; tachypnea; and cool, clammy, cyanotic skin.
- In septic shock, , the skin may be warm and flushed as a result of peripheral vasodilation.

- If patients survive the initial complications, they enter a second phase, presented by:
renal insufficiency and marked by a progressive fall in urine output as well as acidosis, and severe fluid and electrolyte imbalances.

The prognosis varies with the origin of shock and its duration:
-healthy patients with hypovolemic shock survive with appropriate management,
-cardiogenic shock associated with extensive myocardial infarction, or gram-negative sepsis carries a mortality rate of 75%.
- Pathogenesis of septic shock :
Most cases of septic shock (approximately 70%) are caused by endotoxin-producing gram-negative bacilli .

Endotoxins are bacterial wall lipopolysaccharides (LPS) consisting of a toxic fatty acid (lipid A) core common to all gram-
negative bacteria, and a complex polysaccharide coat (including O antigen) unique for each species.

Free LPS attaches to a circulating LPS-binding protein, and the complex then binds to a specific receptor (CD14) on

monocytes, macrophages, and neutrophils resulting in intracellular signaling via an associated "Toll-like receptor" protein

4 (TLR-4), resulting in profound activation of mononuclear cells and production of potent effector cytokines such as IL-1

and TNF cytokines act on endothelial cells and have a variety of effects including reduced synthesis of anticoagulation

factors such as tissue factor pathway inhibitor and thrombomodulin.

- TLR-mediated activation helps to trigger the innate immune system to efficiently eradicate invading microbes.

Low levels of LPS Moderate levels of LPS High levels of LPS

1- At low doses, LPS activates : With moderately severe High levels results in :
- monocytes, infections, cytokine-induced
- macrophages, - Systemic vasodilation
secondary effectors (e.g., nitric (hypotension)
- neutrophils; oxide & platelet-activating factor )
- Diminished myocardial
become significant.
2- it can also directly activate complement, thereby contractility
contributing to local eradication of bacteria. - Widespread endothelial injury
In addition, systemic effects of
and activation, causing
TNF and IL-1 include:
Mononuclear phagocytes respond to LPS by systemic leukocyte adhesion
1- fever,
producing TNF, which in turn induces IL-1 synthesis. and diffuse alveolar capillary
2- increased synthesis of
damage in the lung.
acute-phase reactants,
Both TNF and IL-1 act on endothelial cells (and other 3- and increased
cell types) to produce additional cytokines (e.g., IL-6 - Activation of the coagulation
production of circulating
and IL-8) and induce adhesion molecules.
system, resulting in
neutrophils
disseminated intravascular
Thus, the initial release of LPS enhances the local acute inflammatory coagulation (DIC).
response and improves clearance of the infection.

The hypoperfusion resulting from the

combined effects of widespread
vasodilation, myocardial pump failure,
and DIC causes multiorgan system
failure that affects the liver, kidneys,
and central nervous system, among
others.
- Stages of Shock :

Shock is a progressive disorder that if uncorrected leads to death.

Shock tends to evolve through three general stages :

1- An initial nonprogressive stage 2- A progressive stage 3- An irreversible stage

during which reflex compensatory characterized by tissue hypoperfusion that sets in after the body has incurred
mechanisms are activated and and onset of worsening circulatory and cellular and tissue injury so severe that
perfusion of vital organs is maintained metabolic imbalances even if the hemodynamic defects are
corrected, survival is not possible

Nonprogressive phase of shock, various
neurohumoral mechanisms help maintain cardiac
output and blood pressure which includes:
1- baroreceptor reflexes,
2- release of catecholamines,
3- activation of the renin-angiotensin axis,
4- antidiuretic hormone release,
5- generalized sympathetic stimulation.
The net effect is :
- tachycardia,
- peripheral vasoconstriction,
- renal conservation of fluid.
* Cutaneous vasoconstriction, for example, is
responsible for the characteristic coolness and
pallor of skin in shock .
(although septic shock may initially cause cutaneous
vasodilation and thus present with warm, flushed skin).
If the underlying causes are not corrected, shock
passes imperceptibly to the progressive phase:
during which there is widespread tissue hypoxia,
vital organs are affected and begin to fail.
In the setting of persistent oxygen deficit,
intracellular aerobic respiration is replaced by
anaerobic glycolysis, with excessive production
of lactic acid resulting in lactic acidosis
lowers the tissue pH and blood begins to pool in
the microcirculation.
Peripheral pooling not only worsens the cardiac
output but also puts endothelial cells at risk of
developing anoxic injury with subsequent DIC.
the process eventually enters an irreversible
stage:
- Myocardial contractile function worsens, in part
because of nitric oxide synthesis.
- If ischemic bowel allows intestinal flora to enter
the circulation, endotoxic shock may also be
superimposed.
- the patient has complete renal shutdown due
to ischemic acute tubular necrosis.

* Coronary and cerebral vessels are less

sensitive to the sympathetic response and thus
maintain relatively normal caliber, blood flow,
and oxygen delivery to their respective vital
organs.

- Morphology :
• The cellular and tissue changes induced by shock are those of hypoxic injury , due to some combination of
hypoperfusion and microvascular thrombosis.

Since shock is characterized by failure of many organ systems, the cellular changes may appear in any tissue
particularly in: the brain, heart, kidneys, adrenal glands, and gastrointestinal tract.

Fibrin thrombi may be identified in any tissue, although especially in kidney glomeruli.

-The adrenal changes :

in shock are those seen in all forms of stress; essentially there is cortical cell lipid depletion. This reflects not adrenal
exhaustion but instead conversion of the relatively inactive vacuolated cells to metabolically active cells that use stored
lipids for the synthesis of steroids.

-The kidneys:
reveal acute tubular necrosis, so that oliguria, anuria, and electrolyte disturbances dominate the clinical picture.

-The gastrointestinal tract

may mainfest focal mucosal hemorrhage and necrosis.

-The lungs:
are rare affected in pure hypovolemic shock, because they are somewhat resistant to hypoxic injury.
However, when shock is caused by bacterial sepsis or trauma, changes of diffuse alveolar damage may develop.

all tissues may revert to normal if the patient survives.

Unfortunately, most patients with irreversible changes due to severe shock die before the tissues can recover.