Acute disturbances of haemodynamic function (shock) Medical Assignment Help

Shock is difficult to define. The term is used to describe acute circulatory failure with inadequate or inappropriately distributed tissue perfusion resulting in generalized cellular hypoxia.


The causes are shown. Very often shock can result from a combination of these factors.


Sympatho-adrenal response to shock

Hypotension stimulates the baroreceptors, and to a lesser extent the chemoreceptors, causing increased sympathetic nervous activity. Later this is augmented by the release of catecholamines from the adrenal medulla. The resulting vasoconstriction, together with increased myocardial contractility and heart rate, helps to restore blood pressure and cardiac output.
Reduction in perfusion of the renal cortex stimulates the juxtaglomerular apparatus to release renin. This converts angiotensinogen to angiotensin I, which is in turn converted in the lungs to the potent vasoconstrictor angiotensin II. Angiotensin II also stimulates secretion of aldosterone by the adrenal cortex, causing sodium and water retention. This helps to restore the circulating volume.

Causes of shock.

Causes of shock.

Neuroendocrine response to shock

RELEASE OF PITUITARY HORMONES: adrenocorticotrophic hormone (ACTH), growth hormone (GH), vasopressin (antidiuretic hormone, ADH) and f3- endorphin. (Endogenous opioid peptides such as f3- endorphin, dynorphin and the enkephalins may be partly responsible for some of the cardiovascular changes.)
RELEASE OF CORTISOL, which causes fluid retention and antagonizes insulin.
RELEASE OF GLUCAGON, which raises blood sugar. Release of mediators
The presence of severe infection (often with bacteraemia or endotoxaemia) or of large areas of devitalized tissue (e.g. following trauma or major surgery) can trigger a massive inflammatory response with systemic activation of leucocytes and release of a variety of potentially damaging ‘mediators’. Although clearly beneficial when targeted against local areas of infection or necrotic tissue, dissemination of this response can produce widespread tissue damage.

Microorganisms and their toxic products

In septic shock the inflammatory cascade is triggered by the presence of microorganisms, their toxic products (e.g. endotoxin) or both in the bloodstream. Endotoxin is a lipopolysaccharide derived from the cell wall of Gramnegative bacteria which is thought to be a particularly important trigger of septic shock.

Activation of complement cascade

One of the many functions of the complement system is to attract and activate leucocytes, which then marginate on to endothelium and release inflammatory mediators such as proteases and toxic oxygen radicals; these can produce local tissue damage. For example, the free radical  superoxide (02-) can participate in a number of chemical reactions, yielding hydrogen peroxide (H202) and hydroxyl radicals (OH-), which can damage cell membranes, interfere with the function of a number of enzyme systems and increase capillary permeability.


Macrophage and lymphocyte-derived cytokines such as the interleukins (ILs) and tumour necrosis factor (TNF) are involved in the pathogenesis of shock. TNF release initiates many of the responses to endotoxin and acts synergistically with IL-l, in part through induction of cyclooxygenase, platelet activating factor (PAF) and nitric oxide synthase.

The sympatho-adrenal response to shock.

The sympatho-adrenal
response to shock.

Platelet -activating factor

This vasoactive lipid is released from various cell populations, such as leucocytes and macrophages, in shock. Its effects, which are caused both directly and through the secondary release of other mediators, include hypotension, increased vascular permeability and platelet  aggregation.

Products of arachidonic acid metabolism

Arachidonic acid, derived from the increased breakdown of membrane phospholipid, is metabolized to form prostaglandins and leukotrienes, which are important inflammatory mediators. Prostaglandins currently thought to be of importance in shock include:
• Prostacyclin, which is a vasodilator and inhibits platelet aggregation
• Thomboxane A2, which causes pulmonary vasoconstriction and activates platelets
• Prostaglandin F2a, which may be responsible for the early phase of pulmonary hypertension commonly seen in experimental septic shock.
Leukotrienes have a variety of effects including reduction in cardiac output, vasoconstriction, increased vascular permeability and platelet activation.

Lysosomal enzymes

These are released in response to hypoxia, ischaemia, sepsis and acidosis. As well as being directly cytotoxic, they can cause myocardial depression and coronary vasoconstriction. Furthermore, lysosomal enzymes can convert inactive kininogens, which are usually combined with {X2-globulin, to vasoactive kinins such as bradykinin. These substances can cause vasodilatation and increased capillary permeability, as well as myocardial depression. They can also activate clotting mechanisms. Endothelium-derived vasoactive mediators Endothelial cells synthesize a number of mediators which contribute to the regulation of blood vessel tone and the fluidity of the blood; these include prostacyclin, endothelin- l and endothelium-derived relaxing factor (EDRF). The latter has now been identified as nitric oxide (NO) which is synthesized from L-arginine under the influence of NO synthases. Increased NO production is responsible for the sustained vasodilatation and hyporeactivity to adrenergic agonists which is seen in septic shock and may also be involved in severe haemorrhagicltraumatic shock. Endothelin-l is a potent vasoconstrictor, but its role in shock is not yet well understood.

Endothelial leucocyte adhesion molecule

This molecule is expressed on endothelial cells after exposure to inflammatory mediators, including TNF, and is involved in the adhesion of polymorphonuclear cells to the endothelium. This is considered to be one of the earliest steps in the cascade of events leading to tissue damage and adhesion molecules may therefore play an important role in the pathogenesis of organ failure.

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