General Veterinary Pathology

Causes and mechanism of reversible and irreversible cell injury

REVERSIBLE AND IRREVERSIBLE CELL INJURY - CAUSES AND MECHANISM

External causes

• Physical causes
• Trauma by cutting objects and blunt objects
• Electrical – Lightning, high frequency current
• Heat - Sun stroke, burns, fever
• Cold - Local tissue freezing, cold shock
• Radiation - UV / X /cosmic radiations
• Pressure - Increased or decreased pressure
• Chemicals
• Nutritional - Excess / deficiency
• Excess - HypervitaminosesA and D
• Deficiency –protein, calorie, vitamins and minerals
• Agrochemicals– nitrates
• Environmental deficiency
• Water –dehydration
• Oxygen –asphyxia
• Sunlight – forvitamin D formation (Hypovitaminosis D)
• Biological toxins
• Bacterial and fungal toxins
• Arthropod and snake venom
• Pesticides –organochlorine compounds
• Biological causes
• Acellular – Viruses, prions
• Prokaryotes – Bacteria, chlamydia, rickettsia,mycoplasma
• Eukaryotes – Protozoa, fungi
• Metazoan parasites – Trematodes, cestodes, nematodesand insects

Internal causes

Genetic causes– mutation of genes to chromosomal defects

The common causes of cell injury

• Hypoxic injury
• Free radical injury
• Chemical injury
• Virus induced injury

Events in ischaemic cell injury

Reversible cell injury is non-lethal and previously referred as degeneration. Irreversible injury causes necrosis or death of the cells. The two patterns found inreversible injury are

• Cellular swelling
• Fatty change

Free radical injury

• Free radicalsare chemical species that have single unpaired electron in the outer orbit.Free radicals are extremely reactive and unstable and enter into reaction with inorganicand organic substances, proteins, lipids or carbohydrates, particularly free radicals react with membrane and nucleic acid. They initiate autocatalytic reactions. Free radicals may be initiated in cells with radiant energy (UV /Xrays), generation of endogenous oxidative reaction or enzymatic metabolism,exogenous chemicals or drugs e.g. Chloroform, carbon tetrachloride
• The oxygen-derived radicals are superoxide, hydrogen peroxide and hydroxide. Thesecause lipid peroxidation, protein damage and DNA damage. The antioxidants(endogenous or exogenous) are helpful in scavenging the free radicals e.g.Vitamin E, sulphur containing amino acids (cystine, methionine), glutathioneand ceruloplasmin.

Chemical injury

• Chemicals can induce cell injury directly by reacting with critical cellular molecules e.g. mercuricchloride poisoning. Mercury binds with sulphydryl group and other proteins andcause increased cell membrane permeability and inhibition of ATPase dependant transport or indirectly by converting chemicals which are not biologicallyactive into reactive toxic metabolite that attack target cells. Mostly reactive free radicals formed can induce membrane damage and can cause direct injury by covalent binding to membrane lipid and protein. e.g. Carbon tetrachloride (CCl₄)poisoning. Carbon tetrachloride is converted to CCl₃ in hepatocyteswhich acts on membrane and generate lipid peroxides. The autocatalytic reactionresults in membrane damage involving rough endoplasmic reticulum, detachment ofribosomes, reduced protein synthesis and fatty liver due to lack of lipidacceptor protein. Lipid peroxidation products can also damage plasma membraneto increase permeability to sodium and water resulting in cell swelling.

Virus induced cell injury

This may be through immune mediated reaction and direct cytopathic effect.

Viruses that induce cellular changes are of two types

• Cytolytic / cytopathic viruses which cause variousdegree of cell injury and cell death.
• Oncogenic viruses which stimulates host cellreplication may produce tumours.