Etiology or cause of cell injuries

Cell Injury

ETIOLOGY OF CELL INJURY:

The causes of cell injury, reversible or irreversible, may be broadly classified into two large groups:

Acquired cause

Genetic cause

A) Acquired cause: Acquired causes of cell injury further categorized as given,

a. Hypoxia and Ischemia

b. Physical agents

c. Chemical agents and drugs

d. Microbial agents

e. Immunologic agents

f. Nutritional derangement

g. Psychological factors

HYPOXIA AND ISCHEMIA:

Cells of different tissues essentially require oxygen to generate energy and perform metabolic function.
Deficiency of oxygen results in hypoxia or anoxia means failure to carry out above activities.
The most common causes for hypoxia are: ischemia, anaemia, CO-poisoning, cardiorespiratory insufficiency and increase demand of tissues.

PHYSICAL AGENTS:

Physical agents for cell injury are:
- Mechanical trauma (e.g., Road accident)
- Thermal trauma (e.g., Heat and cold)
- Electricity
- Radiation (e.g., U.V. radiation)
- Rapid changes in atmosphere pressure.

CHEMICALS AND DRUGS:

Increase level of chemicals and drugs cause the cell injury:
- Chemical poisons such as â€“CN, -As, -Hg etc.
- Strong acids and alkali
- Environmental pollutants
- Insecticides and pesticides
- Oxygen at high concentration
- Hypertonic glucose and salts
- Alcohol and narcotic drugs
- Therapeutic administration of drug

MICROBIAL AGENTS:

Injuries by microbes include infection caused by bacteria, rickettsiae, viruses, fungi, protozoa, metazoa and other parasites.

IMMUNOLOGICAL AGENTS:

Immunity is double edge sword. It means, it protects against various injuries agents but itself may cause cell injury.
Example, Hypersensitivity reactions, Anaphylactic reactions, Autoimmune diseases.

NUTRITIONAL DERANGEMENT:

A deficiency or an excess of nutrients may results in nutritional imbalances.
Nutritional deficiency diseases may be due to overall deficiency of nutrients (starvation), protein calorie (Marasmus, Kwashiorkor), minerals (Anaemia) or of trace elements.
Nutritional excess is a problem of societies results from obesity, in atherosclerosis, heart diseases and hypertension.

PSYCHOLOGICAL FACTORS:

There are number of specific biochemical or morphological changes in common acquired mental diseases due to mental stress, strain, anxiety, overwork and frustration.

Problems of drug addiction, alcoholism and smoking results in various diseases such as liver damage, chronic bronchitis, lung cancer, peptic ulcer, hypertension, ischemic heart diseases etc.

B) Genetic cause: In western countries, genetic defects constitute about 50% total mortality in infancy and childhood, while in developing and under developing countries 95% of infant mortality is occurs.

Genetic cases are such as,
- Developmental defect (Errors in morphogenesis)
- Cytogenic defects (chromosomal abnormalities)
- Single-gene defects (mendelian syndrome)
- Storage diseases (Inborn Errors of metabolism)
- Disorders with multifactorial inheritation.

DEVELOPMENTAL DEFECTS:

Developmental defects are group of abnormalities during fetal life due to errors in morphogenesis.
Certain chemicals, drugs, physical and biological are known to induce suc birt defects are known as teratogens. The study of teratogen is called as teratology. The result of teratogen is formation of defective organ called as mal-formation. It results in following: intrauterine death, intrauterine growth retardation, functional defects, and malformation.
The effect of teratogens in inducing developmental defects are depend upon following factors,
- Variable susceptible to teratogens
- Intrauterine stage
- Dose of teratogen
- Specificy of developmental defect for specific teratogen.
Some clinically important examples are as given,
- Thalidomide malformation: Thalidomide used as sedative by pregnant women in England and Germany in 1960. It results in high incident of limb reduction abnormalities in new born.
- Fetal Hydantoin syndrome: babies born to mother on anti-epileptic treatment wit hydantoin which leads to characteristic facial features and congenital heart defects.
- Fetal alcohol syndrome: Ethanol is potent teratogen. Consumption of alcohol by pregnant mother in first trimester increase the risk of miscarriage; still birth occurs, it leads to growth retardation and mental retardation in the new born.
- Torch Effect: Infection with torch group of organisms (toxoplasa, cytomegalo virus, rubella, herpes simplex) is associated with multisystem anomalies and torch syndrome in the new born. These infection may cause damage to the foetus with following types-ocular effects, sensorineural deafness, cardiac effects, CNS manifestation, thrombocytopenia, hepatospleenomegaly etc.

CYTOGENIC DEFECTS (KERYOTYPIC):

Human germ cells contain 23 chromosomes (haploid or n) while all the nucleated somatic cells contain 23 pairs of chromosomes (diploid or 2n).
They are 44 autosomes and 2 sex chromosomes which are XX or XY.
Karyotype is photography representation of stained preparation of chromosome. Each chromosome is composed of a pair of identical double helix of chromosomal DNA called as chromatids. They are classified on the basis of their length and location of cenromere. Mainly they are, metacentric, submetacentric, acrocentric.
Mainly the abnormalities of chromosomes are divided in to two: Numerical and Structural.
- Numerical: The abnormalities occur due to increase or decrease number of total chromosomes.

1. Polyploidy: It is the term used for number of chromosomes which is the multiple of haploid number. E.g., triploid or 3N (69 chromosomes)

2. Anueploidy: It is not exact multiple number of chromosomes but hypodiploid (2N-1 or monosomy) and hyperdiploid (2N+1 or trisomy)

Down's syndrome: There is trisomy in 21th pair of chromosomes. It occurs due to non dysfunction during meiosis in one of parent. It generally causes mental retardation in new born. It occurs due to a mother over 35 years of age.
Klinfelter's syndrome: Klinfelter syndrome is the trisomy in sex chromosome. Mainly they have 47, XXY karyotype. It results in development of testicular atrophy.

Structural: the abnormalities occurs due to changes in appearance of chromosomes,

1. Deletions: due to cri-du-chat syndrome, cancers

2. Inversions: lead to not any abnormalities.

3. Ring chromosome and Isochromosomes: Turner's syndrome.

SINGLE GENE DEFECTS: (MENDELIAN SYNDROME)

The classic laws of inheritance of characteristics were outlined by Austrian scientist Monk Gregor Mendel in 1866 based on his observation of cross-breeding of red & white garden peas.
Single gene defect follows classic Mendelian patterns of inheritance and are called as mendelian syndrome or disorder.
It is results of mutation of a single gene.
(Mutation is the term applied to permanent changes in DNA of cell. If person have mutated germ cell will be subjected to inheritance of discharacter to the offspring)
Ex, Sickle cell anemia, Î²-Thalassamia.

Sickle Cell Anemia (SCA),

Sickle Cell Anemia is a homozygous state of Hb-S in the RBC in which an abnormal gene is inherited from each parent.
SS is several malignant disorders.
In SCA's Hb (Hb-S), basically genetic defect is the single point mutation in one amino acid out of 146 amino acids of Hb molecules.
There is substitution of valine for glutamic acid at the 6^th position of the β-chain of globin of normal Hb (Hb-A).
Due to SCA, biconcave shape of RBC changes to crescent shape or sickle shape. They cannot pass through narrow passages of blood vessels and leads to rapture of capillary wall.

STORAGE DISEASES (INBORN ERRORS OF METABOLISM)

These errors are introduced during or before birth. In such cases, the new born is containing deficiency or lack of enzymes.
Ex, Glucose-6-dehydrogenase deficiency may cause hemolytic diseases.
Storage of carbohydrate, proteins and lipids take place abnormally.

DISORDERS WITH MULTIFACTORIAL INHERITANCE