CELL INJURY: CAUSES OF CELL INJURY, MECHANISMS OF REVERSIBLE AND IRREVERSIBLE CELL INJURY.
Causes of cell injury range from gross mechanical external causes to mild endogenous causes as genetic lack of enzymes etc.
Virtually all forms of tissue injuries start with molecular or structural alterations in cells.
Under normal conditions, the cells are in:
❖ homeostastatic „steady“ state
Normal cell is confined to relatively narrow range of functions and structure by its genetic programme to handle normal physiologic demands.
Cells react to adverse influence by
2- sustaining reversible injury
3- suffering irreversible cellular injury- cell death
More excessive stimuli (either physiologic or pathologic) may cause cellular adaptation -in order to reach
❖ altered steady state
- for example, excessive work stress causes an increase in muscle mass that reflects the increase in size of the individual muscle fiber, results in higher level of metabolic activity –and new equilibrium is reached- hypertrophy
- on the other hand- atrophy- is adaptative response in which there is a decrease in the size and function of the cells- and results from a slow long-lasting decrease of blood supply
❖ if the limits of adaptative mechanisms are exceeded or when no adaptative response is possible- cell injury
• Reversible cell injury denotes pathologic changes that can be reversed when the stimulus is removed and the cellular injury has been mild. Cell injury is reversible only up to certain point.
• Irreversible cell injury denotes pathologic changes that are permanent and cause cell death, they cannot be reversed to normal state
for example: if the blood suply to heart muscles is cut off for 10-15 minutes- the myocardial cell experiences injury but it can recover to normal function, if the blood flow is cut off for longer period- the myocardial fiber dies-necrosis
CAUSES OF CELL INJURY
• Hypoxia (= decrease of oxygen supply) -most common cause of cell injury
-occurs usually as a result of ischemia (= loss of blood supply), which occurs for example when arterial flow suffers from atherosclerosis or thrombotic occlusion of arteries - most common cause of hypoxia
-is due to inadequate oxygenation, for example in cardiorespiratory failure
-is caused by loss of oxygen-carrying capacity of the blood, either due to anemia (decreased capacity of the blood for oxygen), or after poisoning with carbon monoxide (CO)= loss of the carrying capacity of the blood
depending on the severity of hypoxia- the cell may undergo
for example: -if femoral artery is narrowed (due to atherosclerotic or atherothrombotic reduction of the lumen of the affected vessel)- skeletal muscles of the leg decrease in size= atrophy. This reduction in size of cell mass may achieve a new balance on the lower level, but severe and prolonged hypoxia will induce severe injury and cell death.
• physical agents - many forms of physical energy may give rise to cell and tissue injury, such as mechanical trauma, extremes of temperature, sudden changes in atmosphere pressure, electromagnetic energy, radiation and electric shock
The most important and frequent in clinical practice are consequences of mechanical forces (traffic accidents).
Changes in atmosphere pressure and hypotermia are relatively uncommon causes of injury, but hypertermia (burns) are encountered more often. Radiation injury- have also assumed importance as potential causes of widespread destruction
• chemical agents -the list of chemicals that may cause cell and tissue injury includes
-poisons-arsenic, cyanide, mercuric salts,etc
-insecticides and herbicides
-alcohol, narcotic drugs
-variety of therapeutic drugs and even oxygen in high concentrations
• infectious agents- these agents range from the submicroscopic...
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