PHYSIOLOGY OF

SHOCK

DEFINITION

SHOCK- A physiological state characterized by a

significant, systemic

reduction in tissue perfusion,

resulting in decreased tissue oxygen delivery and

insufficient removal of cellular metabolic products,

resulting in tissue injury.

Shock usually results from inadequate cardiac output.

Two types of factors can severely reduce cardiac

output

Cardiac abnormalities that decrease the ability of the

heart to pump blood

Factors that decrease the venous return which can

be due to

diminished blood volume

decreased vascular tone

obstruction to the blood flow

Classification of shock

Primary Shock: shock that has a neurogenic

basis in which pain and psychic factors affect

the vascular system.

Occurs immediately after an insult.

Secondary shock: shock that occurs sometime

after the injury (6 to 24 hours later).

It is associated with changes in capillary

permeability and subsequent loss of plasma into

the tissue spaces.

Based on etiology classified into

Hypovolemic Shock (decreased blood volume)

Includes- Hemorrhage, trauma, surgery, burns, fluid loss due to

vomiting or diarrhea

Cardiogenic Shock( inadequate output by the diseased heart)

Includes- myocardial infarction, congestive heart failure,

arrhythmias.

Obstructive Shock (obstruction to the blood flow)

Includes- tension pneumothorax, Pulmonary embolism, cardiac

tamponade

Distributive Shock (marked vasodilation, low resistant Shock)

Includes- anaphylaxis, sepsis, Neurogenic, metabolic, psychogenic

shock.

Stages of Shock:

shock tends to evolve through three phases:

An initial non-progressive phase or compensatory stage during

which reflex compensatory mechanisms are activated and

perfusion of vital organs is maintained

A progressive stage characterized by tissue hypo-perfusion and

onset of worsening circulatory and metabolic imbalances,

including acidosis

An irreversible stage that sets in after the body has incurred

cellular and tissue injury so severe that even if the hemodynamic

defects are corrected, survival is not possible

Pathophysiology of Shock

Regardless of etiology, the initial physiologic responses in shock

are driven by tissue hypoperfusion and the developing cellular

energy deficit.

The imbalance between cellular supply and demand leads to

neuroendocrine and inflammatory responses, the magnitude of

which is usually proportional to the degree and duration of shock.

The specific responses will differ based on the etiology of shock, as

certain physiologic responses may be limited by the inciting

pathology

The pathophysiologic responses also vary with time and in

response to resuscitation.

Specific responses in Shock

Neuroendocrine Response

Baroreceptors- elicits powerful sympathetic stimulation of

circulation, producing centrally mediated constriction of peripheral

vessels.

Chemoreceptors-Stimulation results in vasodilation of the coronary

arteries, slowing of the heart rate, and vasoconstriction of the

splanchnic and skeletal circulation.

The sensation of pain from injured tissue is transmitted via the

spinothalamic tracts, resulting in activation of the hypothalamic-

pituitary-adrenal axis, as well as activation of the ANS to induce

direct sympathetic stimulation of the adrenal medulla to release

catechol amines.

Cardiovascular response

Cardiac output, the major determinant of tissue

perfusion, is the product of stroke volume and

heart rate.

Hypovolemia leads to reduced Stroke volume

Tachycardia develops as compensation

Increased myocardial O2 consumption occurs as

a result of the increased workload

Ischemia and infarction worsens

Sepsis, severe tissue trauma, hypothermia, general anesthesia,

and acidemia may all also impair myocardial contractility and

reduce the stroke volume at any given ventricular end-diastolic

volume.

The resistance to ventricular ejection, influenced by the

systemic vascular resistance, is elevated in most forms of shock.

Active venoconstriction as a consequence of adrenergic

activity is an important compensatory mechanism for the

maintenance of venous return and therefore of ventricular filling

during shock.

Microcirculation

Homeostatic vasoconstriction occurs in response to shock

The arteriolar and precapillary sphincter control fails as a result of

hypoxia and the effect of vasodilating agents

The venular channels are less sensitive to hypoxia and resist to

some degree the dilating effect of local metabolites.

Capillary engorgement follows and flow is sluggish or stagnant

microthrombus formation, or the passage of small white

microemboli, can be seen in the postcapillary venules

Capillary dysfunction also occurs secondary to activation of

endothelial cells by circulating inflammatory mediators

generated in septic or traumatic shock

Hormonal Response

Shock stimulates the hypothalamus and pituitary to release ACTH cortisol from adrenal cortex induce a

catabolic state.

Cortisol stimulates gluconeogenesis and insulin resistance

Cortisol also causes retention of sodium and water by the

nephrons of the kidney.

The renin-angiotensin system is activated in shock

producing angiotensin II which is a potent vasoconstrictor

of both splanchnic and peripheral vascular beds.

The pituitary also releases vasopressin or ADH in response to

hypovolemia

Epinephrine, angiotensin II, pain, and hyperglycemia also

increase production of ADH.

ADH acts on the distal tubule and collecting duct of the nephron

to increase water permeability, decrease water and sodium

losses, and preserve intravascular volume

ADH acts as a potent mesenteric vasoconstrictor, shunting

circulating blood away from the splanchnic organs during

hypovolemia.

This may contribute to intestinal ischemia and predispose to

intestinal mucosal barrier dysfunction in shock states.

It also increases hepatic gluconeogenesis and increases hepatic

glycolysis.

Metabolic effects

Decreased Oxygen tension Decreased ATP

production Anerobic metabolism Metabolic

acidosis

Decreased intracellular pH also influences vital cellular

functions such as normal enzyme activity, cell

membrane ion exchange, and cellular metabolic

signaling

Furthermore, acidosis leads to changes in calcium

metabolism and calcium signaling. Compounded,

these changes may lead to irreversible cell injury and

death.

Hepatic glycogenolysis, gluconeogenesis, ketogenesis,

skeletal muscle protein breakdown, and adipose tissue

lipolysis are increased by catecholamines.

Epinephrine induces further release of glucagon, while

inhibiting the pancreatic -cell release of insulin leading

to hyperglycemia and insulin resistance during shock

and injury.

The relative underuse of glucose by peripheral tissues

preserves it for the glucose-dependent organs such as

the heart and brain.

Immune and Inflammatory Responses

Alterations in the activity of the innate host immune

system can be responsible for both the

Development of shock (i.e., septic shock following severe

infection and traumatic shock following tissue injury with

hemorrhage) and

Pathophysiologic sequel of shock such as the

proinflammatory changes seen following hypoperfusion.

The inflammatory and immune responses can arise in

response to trauma, infection, ischemia, toxic, or

autoimmune stimuli.

Following direct tissue injury or infection

There is release of bioactive peptides by neurons in

response to pain

there is release of intracellular molecules by broken

cells, such as heat shock proteins, mitochondrial

peptides, heparan sulfate, high mobility group box 1,

and RNA [damage associated molecular patterns

(DAMP) ]

release of intracellular products from damaged and

injured cells can effects on distant tissues to activate

the inflammatory and immune responses.

Monocytes, macrophages, and T cells release potent

proinflammatory cytokines like Tumor necrosis factor

alpha and interleukins.

TNF- can produce peripheral vasodilation,

activate the release of other cytokines,

induce procoagulant activity, and

stimulate a wide array of cellular metabolic

changes.

IL-1 produces a febrile response to injury by

activating prostaglandins and causes anorexia by

activating the satiety center.

increased IL-2 secretion promotes shock-induced

tissue injury and the development of shock.

IL-6 contributes to lung, liver, and gut injury after

hemorrhagic shock.

IL-6 may play a role in the development of diffuse

alveolar damage and ARDS.

Specific types of Shock

Hypovolumic shock

Loss of blood (hemorrhagic)

External bleeding (wound to the outside)

Internal bleeding (hematoma, hemothorax, hemopertitoneum)

Loss of plasma

Burns

Loss of fluids and electrolytes

External (vomiting, diarrhea, excessive sweating)

Internal ( “third spacing” = pancreatitis, ascitis, bowl obstruction

Mild (loss of < 20% blood volume)

Few external signs in supine young patients

Moderate (loss of 20-40% blood volume)

Patient becomes increasingly anxious and

tachycardic >100 beats/min (sympathetic response)

oliguria

blood pressure may be maintained in supine patient

Severe (loss of > 40% blood volume)

Classic signs of shock appear with hemodynamic

instability

Signs and Symptoms

Low Blood Pressure

Systolic BP is usually below 90 mmHg

Pulse is rapid and weak

Respiration is rapid and shallow

Skin is pale, cool, and clammy

Drowsiness

CARDIOGENIC SHOCK

Pump failure

Secondary to myocardial infarction (most common)

Cardio-myophathy

Acute valvular dysfunction (regurgitations)

Rupture of the ventricular septum

Arrhythmia

Tachyarrhythmia

Bradyarrhythmia

Characteristics of Cardiogenic Shock

Low cardiac output

Peripheral vasoconstriction

Left sided heart failure leads to pulmonary

venous congestion and pulmonary edema

Right sided heart failure leads to systemic

venous congestion and peripheral edema

Signs and symptoms

Major difference between other types of shock is

presence of Pulmonary Edema

Difficulty breathing

Wheezes, Crackles, Rales are heard as fluid levels

increase

Productive cough with white or pink-tinged foamy

sputum

Cyanosis

Altered mentation

Oliguria ( decreased urination)

Obstructive shock

Tension pneumothorax

•Air trapped in pleural space with 1 way valve, air/pressure builds up

•Mediastinum shifted impeding venous return

Cardiac tamponade

•Blood in pericardial sac prevents venous return to and contraction of heart

Pulmonary embolism and Aortic stenosis

Resistance to ejection causes decreased cardiac function

Distributive Shock

Anaphylaxis,

Sepsis,

Neurogenic,

Metabolic ,

Psychogenic shock.

Anaphylactic Shock

A type of distributive shock that results from widespread systemic allergic reaction to an antigen

Antigen exposure

body stimulated to produce IgE antibodies specific to antigen

drugs, bites, contrast, blood, foods, vaccines

Reexposure to antigen

IgE binds to mast cells and basophils

Anaphylactic response

Anaphylactic response

Vasodilatation

Increased vascular permeability

Bronchoconstriction

Increased mucus production

Increased inflammatory mediators recruitment

to sites of antigen interaction

Signs and symptoms

Almost immediate response to inciting antigen

Cutaneous manifestations

urticaria, erythema, pruritis, angioedema

Respiratory compromise

stridor, wheezing, bronchorrhea, respiratory

distress

Circulatory collapse

tachycardia, vasodilation, hypotension

Septic shock

Sepsis is defined as a systemic inflammatory

response to a bacterial infection with bacteriemia

(though blood cultures can be negative)

Severe sepsis is defined by additional end-organ

dysfunction (mortality rate: 25-30%)

Septic shock is defined as sepsis with hypotension

despite fluid resuscitation and evidence of

inadequate tissue perfusion (40-70%)

Initiated by gram-negative (most common) or

gram positive bacteria, fungi, or viruses

infection enters bloodstream and is carried

throughout body

Toxins released overcome compensatory

mechanisms

Can cause dysfunction of one organ system or

cause multiple organ dysfunction

The syndrome of septic shock is characterized by

Systemic vasodilation (hypotension)

Diminished myocardial contractility

Widespread endothelial injury and activation

leading to fluid leakage (capillary leak) resulting in

acute respiratory distress syndrome (ARDS)

Activation of the coagulation cascade leading to

disseminated intravascular coagulation.

Clinically presents in two phases:

“Warm” shock - early phase

hyperdynamic response, Vasodilation

Pink, warm, flushed skin

Increased Heart Rate

Tachypnea

Massive vasodilation

“Cold” shock - late phase

hypodynamic response, Decompensated state

Vasoconstriction

Skin is pale & cold

Tachycardia

Decrease BP

Metabolic and respiratory acidosis with hypoxemia

Neurogenic shock

A type of distributive shock that results from the

sudden loss or suppression of sympathetic tone

or vasomotor tone

Causes massive vasodilatation in the venous

vasculature, leading to venous return to heart

and cardiac output.

Occurs in

Deep general anesthesia

Spinal injury

Brain damage

Pathophysiology

Loss of sympathetic tone (parasympathetic response)

results in massive vasodilatation, inhibition of the

baroreceptor response, and impaired thermo-regulation.

Arterial vasodilatation drop in BP

Decrease in BP & drop in CO impaired tissue perfusion.

Inhibition of baroreceptors no reflex

tachycardia, further compromising tissue perfusion

Psychogenic shock

It is a mental state resulting from an unpleasant

experience generating a vasovagal response

Stages of Shock

Initial non-progressive stage Baro-receptor reflexes

Release of catecholamine

Activation of renin-angiotensin-aldosteron system

ADH release

results in tachycardia, peripheral vasoconstriction (cool skin) and renal fluid conservation

Progressive stage Widespread tissue hypoxia results in anaerobic glycolysis and

Lactate acidosis (pH < 7.35)

Vasodilation with blood pooling in microcirculation

Declined cardiac output

Oligouria

Widespread tissue hypoxia

Irreversible stageWidespread cell injury leading to

Further decreased myocardial contractility

Anuria with tubular necrosis

Ischemic bowl may lead to leakage of bacterial flora

Fluid lung (ARDS)

Postmortem changes

Brain

Show ischemic encephalopathy with initial sweeling

or shrinkage of neurons later nerve cells die and are

replaced by fibrillary gliosis

Kidneys

Ischemia leads to Acute Tubular Necrosis (ATN)

Can be normal in size or enlarged

If extensive muscle injury, peculiar brown tubular

casts are seen

GI tract

The GI tract is at very high risk of infarction. Shock

causes infarction of the GI epithelium

Liver

Fatty changes may be seen

Centrilobular necrosis is common.

Heart

Grossly, subendocardial hemorrhages are

common.

Microscopically, contraction bands are seen in

myocardial cells.

Fatty change – 18 to 24 hrs well marked in 3 to 4

days

Lung

Shock causes release of inflammatory mediators

such as TNF-α. This injures endothelial cells.

Endothelial injury allows leakage of proteinaceous

fluid and neutrophils into the interstitium.

interstitial edema and inflammation common in

shock.

Edema is well discernible after 2 to 3 days

Lungs become heavy, stiff, and hemorrhagic.

Medicolegal Importance

In a person with hemorrhagic diathesis or hemophilia, minor injury produce death from hemorrhage.

Sudden rise of BP in neurogenic shock can precipitate serious complications like –

(a) Intracerebral hemorrhage from rupture of arteriosclerotic cerebral vessels or of berry aneurysm.

(b) Rupture of a dissecting aneurysm of aorta.

Under such conditions even when the deceased received minor trauma before death, the essential cause of death will be underlying disease process.

Minor stimuli or injury over receptic spots may cause sudden death from neurogenic shock.