BASIC PRINCIPLES OF CELL INJURY AND ADAPTATION

CELL INJURY

DEFINITION:

It is defined as a variety of stresses a cell encounters as a result of changes in its internal

and external environment.

ETIOLOGY and PATHOGENESIS OF CELL INJURY:

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

Acquired cause
Genetic eause
ETIOLOGY AND EXPLANATION
PATHOGENESIS
ACOUIRED CAUSE
HYPOXIA AND Cells of different tissues essentially require oxygen to
ISCHEMIA generate energy and perform metabolic function.
Deficiency of oxygen results in hypoxia or anoxia means
failure to carry out above activities.
T h e most common causes for hypoxia are: 1schemia, anaemia,
CO-poisoning, cardiorespiratory insufficiency and increase
demand of tissues.

PHYSICAL o Mechanical trauma (e.g., Road accident)

AGENTS o Thermal trauma (e.g., Heat and cold)
o Electricity
o Radiation (e.g., U.V. radiation)
Rapid changes in atmosphere pressure.

CHEMICALS AND o Chemical poisons such as aeCN, -As, -Hg etc.

DRUGS o Strong acids and alkali
o Environmental pollutants
o Insecticides and pesticides
o Oxygen at high concentration
o Hypertonic glucose and salts
o Alcohol and narcotic drugs
Therapeutic administration of drug

MICROBIAL Injuries by microbes include infection caused by bacteria, rickettsiae,

AGENTS viruses, fungi, protozoa, metazoa and other parasites.
IMMUNOLOGICAL Immunity is doubleedge sword. It means, it protects against
AGENTS various injuries agents but itself may cause cell injury.
Example, Hypersensitivity reactions, Anaphylactic reactions,
Autoimmune diseases

NUTRITIONAL A deficiency or an excess of nutrients may results in

DERANGEMENT 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 There are number of specific biochemical or morphological

FACTORS 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.

GENETIC CAUSE
DEVELOPMENTAL Developmental defects are group of abnormalities during fetal
DEFECTS 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.
results in following: intrauterine death, intrauterine growth
retardation, functional defects, and malformation.

Examples:

Thalidomide malformation
Fetal Hydantoin syndrome
Fetal alcohol syndrome

CYTOGENIC Human germ cells contain 23 chromosomes (haploid or n)

DEFECTSS while all the nucleated somatic cells contain 23 pairs of
(KERYOTYPIC) 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 doublehelix 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.

SINGLE GENE Single gene defect follows classic Mendelian patterns of

DEFECTS inheritance and are called as mendelian syndrome or disorder.
I t 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, Thalassamia.

MORPHOLOGY OF CELL INJURY:

Cell Injury

Reversible Irreversible
Cell Injury Cell Injury

Cellular Swelling Autolysis &Heterolysis

> Necrosis

Fatty change
Apoptosis
MORPHOLOGY EXPLANATION
Cellular Swelling| it is the result of failure of energydependent ion pumps in the plasma
membrane, leading to an in ability to maintain ionic and fluid homeostasis.
Cellular swelling the first manifestation of almost all forms of cell injury to
cells, is a reversible alteration that may be difficult to appreciate with the
light microscope, but it may be apparent at the level of the whole organ.
Eg: It causes increase in weight of organ.
| Fatty change It occurs in hypoxic injury and in various forms of toxic or metabolic injury
and is manifested by the appearance of small or large lipid vacuoles in the
cytoplasm. It is principally encountered in cells participating in fat
metabolism (e.g., hepatocytes, myocardial cells)andis also reversible.
Other Plasma membrane blebbing and loss of microvilli,
morphological Mitochondrial swelling.
characteristic in Dilation of the ER,
reversible cell Eosinophilia.
injury
Autolysis (i.e. self-digestion) is disintegration of cell by its own hydrolytic enzymes
| liberated from lysosomes.Autolysisis rapid in sometissuesrichin
 hydrolytic enzymes such as in the pancreas, and gastric mucosa;
intermediate in tissues like the heart, liver and kidney; and slow in fibrous
tissue.
Heterolysis It is disintegration of cell by the hydrolytic enzymes liberated from
inflammatory mediators like Neutrophils etc.,
Necrosis It is the type of cell death that is associated with loss of membrane integrity
and leakage of cellular contents resulting in dissolution of cells, largely
resulting from the degradativeaction of enzymes on lethallyinjured cells.
Apoptosis Apoptosis is a pathway of cell death in which cells activate enzymes that
degrade the cells' own nuclear DNA and nuclear and cytoplasmic protein
The plasma membrane of the apoptotic cell remains intact, but the
membrane is altered in such a way that the cell and its fragments become
avid targets for phagocytes.
Apoptotic cell death does not elicit an inflammatory reaction in the host
In contrast to Necrosis, Apoptosis takes place in both physiologic and
pathologic situations. Werethe prior occurs only in pathological conditions.

Reversible Injury Irreversible Injury

mitochondrial
with Few small Severe
Mitochondria) 1Swelling
amorphous densities
membrane swollen & Large
amorphous densities

Intact with few Extensive damage to plasma

Plasma) 2
Blebbing, Blunting. with membrane with loss cellular
Membrane loss of microvillus .organelle

Membrane damaged with

Lysosome) 3 Membrane intact
.vacuoles

Smoothening with
Endoplas mie) 4 Lysis of ER with dilatation
detachments of
Reticulum with detachment of ribosome
ribosome

Nucleus) 5 Clumping of chromatin Pyknosis->Karyorrhexis-

>Karyolysis
Eosinophilic with Fine Shows Course Myelin figure
Cytoplasm) 6
Myelin figure
 ABNORMALITIES IN LIPOPROTEINAEMIA

A lipoprotein is a biochemical assembly that contains both proteins and lipids, bound to
the proteins, which allow fats to move through the water inside and outside cells.

Name Defect Characteristics

Hypolipoproteinemias
|Abetalipoproteinemia No chylomicrons, VLDL, Rare; blood acylglycerols
or LDL are formed low; intestine and liver
because of defect in the accumulate acylglycerols.
loading of apo B with Intestinal malabsorption.
lipid.
Familial alpha- All have low or near Hypertriacylglycerolemia
lipoprotein deficiency absence of HDL. due to absence of apo C-
Tangier disease II, Low LDL levels.
Atherosclerosis in the
Fish-eye disease elderly.
Apo-A-I deficiencies
 Hyperlipoproteinemia
Familial lipoprotein Hypertriacylglycerolemia |Slow clearance of
lipase deficiency (type l) due to deficiencyof LPL,chylomicrons and VLDL.
abnormal LPL, or apo C-II|| Low levels of LDL and
deficiency causing HDL. No increased riskof
inactive LPL. coronary disease.
Familial Defective LDL receptorsElevated LDL levels and
hypercholesterolemia ormutation in ligand hypercholesterolemia,
(type II a) of
region apo B-100. resulting in
atherosclerosisand
coronary disease.
Familial type IlI Deficiency in remnant Increase in chylomicron
hyperlipoproteinemia clearance by the liver is and VLDL remnants,
(broad beta disease, due to abnormality in apo Causes
remnant removal disease, | E. hypercholesterolemia,
familial xanthomas, and
dysbetalipoproteinemia) atherosclerosis,
Familial Overproduction of VLDL High cholesterol, VLDL,
Hypertriacylglycerolemia often associated with Subnormal LDL and
(type IV) glucose intolerance and HDL. Associated with
hyperinsulinemia. Alcoholism, diabetes
mellitus and obesity.
Hepaticlipase deficiency Deficiency of the enzyme Patients have xanthomas
leads to accumulation of and coronary heart
large triacylglycerol-rich disease.
HDL and VLDL remnants
 GLYCOGEN INFILTRATION AND GLYCOGEN STORAGE DISEASES

The abnormal accumulation of glycogen within the cytoplasm of cells is called

Glycogen infiltration.This can be seen in diabetes mellitus and glycogen storage diseases.

. Glycogen is the reserve carbohydrate of the body and is chiefly stored in the liver and
muscles.

SOURCE:

I t synthesis from

Glycogenesis In this the glycogen is synthesised from glucose under the

Influence of enzyme glucogenase.

Glycogenolysis hydrolysis to glucose under the influence of enzyme Phosphorylase.

These processes occur rapidly in the body.

Post- mortem glycogenolysis occurs rapidly 2-3 hrs after the death, in the liver or
muscles.
Glycogen stores of the body are depleted after violent exercise or starvaition.

IDENTIFICATION: he Lapd of Pharn'D

Glycogen can be demonstrated in the liver cells, when a piece of fresh tissue is fixed in
alcohol instead of formol-saline and staining with Best's carmine.

Glycogen storage disease is the result of defects in the processing of glycogen synthesis or
breakdown within muscles, liver, and other cell types

The GSDs can be divided in three main groups:

those affecting liver, those affecting muscle, and those which are generalized.
 Glycpgen
Lysosome
Alpha-1.4- sphorylase Kinase Alpha-
Gucosidase ( G S D Glycogen GSD vil and x xinke
Branching Enzyme
Liver Phosphorylase (GSD VI
Muscle Phosphorylase (GsD V
Slucose Clycogen Synthas
UDPG Debrnching
Enzyme (GsD I)
Glucose-1-P
ini v e r Phosphoglucomutase
GlucosePhosphatase
(GSD)
Glucose Glucose-6-P
Glucose-6-Phosphate
Transporter(GSD IB)
Fructose-6-P
TO DlOOd In brain and musce

hosp nas
Fructose-1,6-P

GSD Typee Enzyme Symptoms Diagnosis Treatment

Deficiency

Type G6PTase Hepatomegaly Liver biopsy cornstarch taken orally

Low blood sugar
Impaired growth
Type ll Debranching Swollen abdomen Liver biopsy protein supplements for
Enzyme Tissue damage abnorma muscle disorder
MUscle weakness structured giycogen

Type IV Branching Growth delay in abnormal iver transplantation

Enzyme childhood
Enlarged liver
structured glycogen
with long outer
chain
Type VI
Tiver Hepatomegaly blood sugar testing Need frequent feedin9
phosphorylase hypoglycaemia Cholesterol to avoid
growth retardation testing hypoglycaemia.
hyperlipidaemia. liver function
Type Ix Phosphorylase enlarged livers and Blood profiling Prevent by toking high
Kinase may have low blood Biopsy of liver carbohydrate diet
sUgar
Iype 0
Gycogen Tiredness Blood tests comstarch toreduce