CELL INJURY AND CAUSES

 CELL INJURY

Cell injury is defined as the effect of a variety of stresses due to etiologic agents a cell encounters resulting in changes in its internal and external environment. In general, cells of the body have inbuilt mechanism to deal with changes in environment to an extent. 

The cellular response to stress may vary and depends upon following two variables:

 i) Host factors i.e. the type of cell and tissue involved. 

ii) Factors pertaining to injurious agent i.e. extent and type of cell injury.

CAUSES OF CELL INJURY

A. Genetic Causes

Genetic abnormalities may result in a defect as severe as the congenital malformations associated with Down syndrome, caused by a chromosomal anomaly, or as subtle as the decreased life span of red blood cells caused by a single amino acid substitution in hemoglobin in sickle cell anemia. Genetic defects may cause cell injury because of deficiency of functional proteins, such as enzyme defects in inborn errors of metabolism, or accumulation of damaged DNA or misfolded proteins, both of which trigger cell death when they are beyond repair. Variations in the genetic makeup can also influence the susceptibility of cells to injury by chemicals and other environmental insults.

B. Acquired Causes

1. HYPOXIA AND ISCHAEMIA: Cells of different tissues essentially require oxygen to generate energy and perform metabolic functions. Deficiency of oxygen or hypoxia results in failure to carry out these activities by the cells. Hypoxia is the most common cause of cell injury. Hypoxia may result from the following 2 ways:

following 2 ways: 

 Th e most common mechanism of hypoxic cell injury is by reduced supply of blood to cells due to interruption i.e. ischaemia. 

 Hypoxia may also result from impaired blood supply from causes other than interruption e.g. disorders of oxygen carrying RBCs (e.g. anaemia, carbon monoxide poisoning), heart diseases, lung diseases and increased demand of tissues.

2. PHYSICAL AGENTS;  Physical agents in causation of disease are as under: 

i) mechanical trauma (e.g. road accidents)

 ii) thermal trauma (e.g. by heat and cold) 

iii) electricity

iv) radiation (e.g. ultraviolet and ionizing)

v) rapid changes in atmospheric pressure.

3. CHEMICALS AND DRUGS: An ever-increasing list of chemical agents and drugs may cause cell injury. Important examples include the following:

i) chemical poisons such as cyanide, arsenic, mercury

ii) strong acids and alkali

iii) environmental pollutants

iv) insecticides and pesticides

v) oxygen at high concentrations

vi) hypertonic glucose and salt

vii) social agents such as alcohol and narcotic drugs

viii) therapeutic administration of drugs.

3. MICROBIAL AGENTS: Injuries by microbes include infections caused by bacteria, rickettsiae, viruses, fungi, protozoa, metazoa, and other parasites.

4. IMMUNOLOGIC AGENTS: Immunity is a ‘double-edged sword’—it protects the host against various injurious agents but it may also turn lethal and cause cell injury e.g. 

i) hypersensitivity reactions 

ii) anaphylactic reactions

iii) autoimmune diseases.

5. NUTRITIONAL DERANGEMENTS A deficiency or an excess of nutrients may result in nutritional imbalances.

 Nutritional deficiency diseases may be due to overall deficiency of nutrients (e.g. starvation), of protein calorie (e.g. marasmus, kwashiorkor), of minerals (e.g. anaemia), or of trace elements.

 Nutritional excess is a problem of affluent societies resulting in obesity, atherosclerosis, heart disease and hypertension.

6. AGEING: Cellular ageing or senescence leads to impaired ability of the cells to undergo replication and repair, and ultimately lead to cell death culminating in death of the individual.

7. PSYCHOGENIC DISEASES: There are no specific biochemical or morphologic changes in common acquired mental diseases due to mental stress, strain, anxiety, overwork and frustration e.g. depression, schizophrenia. However, problems of drug addiction, alcoholism, and smoking result in various organic diseases such as liver damage, chronic bronchitis, lung cancer, peptic ulcer, hypertension, ischaemic heart disease etc.

8. IATROGENIC CAUSES:  Although as per Hippocratic oath, every physician is bound not to do or administer anything that causes harm to the patient, there are some diseases as well as deaths attributed to iatrogenic causes (owing to physician). Examples include occurrence of disease or death due to error in judgement by the physician and untoward effects of administered therapy (drugs, radiation). 

9. IDIOPATHIC DISEASES: Idiopathic means “of unknown cause”. Finally, although so much is known about the etiology of diseases, there still remain many diseases for which exact cause is undetermined. For example, most common form of hypertension (90%) is idiopathic (or essential) hypertension. Similarly, exact etiology of many cancers is still incompletely known.