outline causes and pathogenesis of cell injury/death
describe the morphological changes of cell injury/death
Describe the process of apoptosis
Introduction
General considerations……
Adapt or die!
Reaction patterns in a given cell/tissue is often limited
Degree of injury is a function of type, duration and severity of insult
Types of insult - hypoxia
Ischaemia
Local e.g. embolus
Systemic e.g. cardiac failure
Hypoxaemia
Oxygen problems e.g. altitude
Haemoglobin problems e.g. anaemia
Oxidative phosphorylation
E.g. cyanide poisoning
Types of insult - chemical
Many of the common poisons (arsenic, cyanide, mercury) interfere with cellular metabolism. If ATP levels drop below critical levels, affected cells will die.
The list of pharmaceuticals that may have toxic effects on cells is enormous. Some act directly, but most have their effect through breakdown metabolites. Metabolism of alcohol (a type of drug) to acetaldehyde is one example.
E.g. viruses can take over protein translation machinery and subvert it entirely to the production of new virions.
Types of insult - Physical
Direct Physical Effects
Exposure of tissue to extreme heat or cold results in direct injury that is often irreversible, resulting in a pattern of coagulative necrosis (see later).
Sudden changes in pressure can cause cellular disruption (e.g. a hammer blow to the thumb).
Electrical currents can cause direct breakdown of cellular membranes that may be irreversible.
Types of insult –immune
Inflammatory mediators such as interferons and interleukins
can alter both gene expression and cellular metabolism. The effects are designed to help cells combat an infectious process, but the resulting stress to the cells can be highly injurious and sometimes deadly.
Activation of complement
can result in direct attack on a cell's surface membrane.
Cytotoxic T-cells and NK cells
can mediate a direct attack on a target cell's and initiate the self-destruct cascade within a target cell.
Types of insult - nutrition
Dietary insufficiency
of protein, vitamins and/or minerals can lead to injury at the cellular level due to interference in normal metabolic pathways.
Dietary excess
can likewise lead to cellular and tissue alterations that are detrimental e.g. fat is the biggest offender, or excess ingestion of "health supplements"
Death of groups of contiguous cells in tissue or organ
Patterns
Coagulative
Liquefactive
Caseous
Fat necrosis
(gangrene)
(Infarct)
Red/haemorrhagic
White
Coagulative necrosis
Cells have died but the basic shape and architecture of the tissue endures
Most common manifestation of ischaemic necrosis in tissues.
Affected tissue maintains solid consistency.
In most cases the necrotic cells are ultimately removed by inflammatory cells.
The dead cells may be replaced by regeneration from neighboring cells, or by scar (fibrosis).
Coagulative necrosis
Coagulative necrosis
Liquefactive necrosis
Complete dissolution of necrotic tissue.
Most commonly due to massive infiltration by neutrophils (abscess formation).
Release of reactive oxygen species and proteases
Liquefaction is also characteristic of ischaemic necrosis in the brain.
Liquefactive necrosis
Caseous necrosis
Accumulation of amorphous (no structure) debris within an area of necrosis.
Tissue architecture is abolished and viable cells are no longer recognizable.
Characteristically associated with the granulomatous inflammation of tuberculosis. Also seen in some fungal infections.
Caseous necrosis
Caseous necrosis
Fat necrosis
Results from the action of lipases released into adipose tissue.
pancreatitis, trauma.
Free fatty acids accumulate and precipitate as calcium soaps (saponification).
These precipitates are grossly visible as pale yellow/white nodules
Microscopically, the digested fat loses its cellular outlines. There is often local inflammation
Fat necrosis
Gangrene ("gangrenous necrosis")
Not a separate kind of necrosis at all, but a term for necrosis that is advanced and visible grossly.
If there's mostly coagulation necrosis, (i.e., the typical blackening, desiccating foot which dried up before the bacteria could overgrow), we call it dry gangrene.
If there's mostly liquefactive necrosis (i.e., the typical foul-smelling, oozing foot infected with several different kinds of bacteria), or if it's in a wet body cavity, we call it wet gangrene.
Gangrenous necrosis
Infarction
An area of ischaemic necrosis in a tissue or organ
White
Arterial occlusion in most solid tissues
Red/haemorrhagic
Venous occlusion
Loose tissues
Dual blood supply
Previously congested
White infarct
Red infarct
Apoptosis - basics
is a distinct reaction pattern which represents programmed single-cell suicide.
Cells actually expend energy in order to die.
Derived from Greek "falling off" (as for autumn leaves)
Apoptosis is "the physiological way for a cell to die", seen in a variety of normal situations.
