Riza Novierta Pesik

CAUSES of CELL INJURY :

1.Oxygen Deprivation
2. Physical agents
3. Chemical agents & drugs
4. Infectious agents
5. Immunologic reactions
6. Genetic Derangements
7. Nutritional Imbalances

CELL INJURY & NECROSIS

1.Cellular response, d.o : type of injury, its duration & severity
2.Consequences of cell injury, d.o : type, state & adaptability of the
injured cell
3.Intracellular system (4) :
. maintenance of the integrity of the cell membranes
. aerobic respiration
. protein synthesis
.preservation of the integrity of the genetic apparatus of the cell
4.Injury at one locus leads to wide-ranging secondary effects
5.Morphologic changes of the cell injury become apparent only
after some critical biochemical system within the cell has been
deranged

GENERAL BIOCHEMICAL MECHANISMS :

1. ATP depletion
2. Oxygen&oxygen derived free radicals
3. Intracellular Ca2+ & loss of Ca2+ homeostasis
4. Defects in membrane permeability
5. Irreversible mitochondrial damage

ISCHEMIC & HYPOXIC INJURY

Hypoxia glycolytic energy production can
continue
Ischemia compromises the delivery of
substrates for glycolysis
Ischemia tends to injure tissues faster than
hypoxia

FREE RADICAL-INDUCED CELL INJURY

Initiated within cell by :
1. Absorbtion of radiant energy
2. Enzymatic metabolism of exogenous chemicals
or drugs
3. Reduction-oxidation reactions that occure
during normal metabolic processes
4. Transition metals
5. Nitric oxide (NO)

The Effects to injured cell:

- Lipid peroxidation of membranes
- Oxidative modification of proteins
- Lesions in DNA

CHEMYCAL INJURY

MORPHOLOGY of REVERSIBLE CELL INJURY & NECROSIS

Reversible Injury :
- cellular swelling
- fatty change
Necrosis :
- coagulative necrosis
- liquefactive necrosis
- gangrenous necrosis
- caseous necrosis
- fat necrosis

NECROSIS
Definition :
A spectrum of morfology changes that follow cell death in
living tissue, largely resulting from the progressive
degradative action of enzymes on the lethally injured cell.
Is the result of :
1. Enzymic digestion of the cell : autolysis, heterolysis
2. Denaturation of proteins
The processes require hours to develop, and so there would
be no detectable changes in cell if it caused sudden
death

COAGULATIVE NECROSIS

LIQUEFACTIVE NECROSIS

CASEOUS NECROSIS

FAT NECROSIS

APOPTOSIS
Definition :
Its a form of cell death designed to eliminate unwanted
host cells through activation of coordinated, internally
programmed series of events effected by dedicated set
of gene products

APOPTOSIS OCCURS IN :
1.
2.
3.
4.
5.
6.
7.
8.

Programmed destruction of cells during embryogenesis

Hormone-dependent involution in the adult
Cell deletion in proliferating cell populations
Cell death in tumors
Death of neutrophils during an acute inflamatory response
Death of immune cells
Cell death induced by cytotoxic T cells
Pathologic atrophy in parenchymal organs after duct
obstruction
9. Cell injury in certain viral diseases
10.Cell death produced by a variety of injurious stimuli

SUBCELLULAR RESPONSES TO CELL INJURY

-Lysosomal catabolism
- Induction (hypertrophy) of Smooth Endoplasmic
Reticulum
-Mitochondrial alterations
- Cytoskeletal abnormalities

LYSOSOMAL CATABOLISM

Induction (hypertrophy) of Smooth Endoplasmic

Reticulum

Electron micrograph of liver from phenobarbital-treated rat showing marked

increase in smooth endoplasmic reticulum.
(from Jones AL, Fawcett DW: Hypertrophy of the agranular endoplasmic reticulum in
hamster liver induced by phenobarbital. J Hystochem Cytochem 14:215, 1996. Courtesy
of Dr. Fawcett)

Mitochondrial alterations

Enlarged, abnormally shaped mitochondria from the liver of the patient with alcoholic
cirrhosis. Note also crystaline formations in the mitochondria.

Cytoskeletal abnormalities

A. The liver of alcohol abuse (chronic alcoholism). Hyaline inclusions in the hepatic
parenchyal cell in the center appear as eosinophilic networks disposed about the nuclei.
B. Electron micrograph of alcoholic hyalin. The material is composed of intermediate
(prekeratin) filaments and amorphous matrix.

Riza Novierta Pesik

CELLULAR ADAPTATIONS of GROWTH and DIFFERENTIATION

PHYSIOLOGIC
PATHOLOGIC

- Hyperplasia
- Hypertrophy
- Atrophy
- Metaplasia

HYPERPLASIA
Definition :
constitutes an increase in the number of cells in an organ or
tissue, which may then have increased volume.
Physiologic Hyperplasia :
1. Hormonal hyperplasia
2. Compensatory hyperplasia
Pathologic Hyperplasia :
1. Excessive hormonal stimulation
2. Effects of GFs on target cells
3. Neoplasia

HYPERTROPHY
Definition :
Refers to an increase in the size of cells and, which such change, an
increase in the size of the organ
Hypertrophy physiologic
pathologic

ATROPHY
Definition :
shrinkage in the size of the cell by loss of cell substance
Physiologic :
1. During early development
2. Uterus after parturition

Pathologic, d.o. the basic cause, can be local&general :

1. Decreased workload (atrophic of disuse)
2. Loss of innervation (denervation atrophy)
3. Diminished blood supply
4. Inadequate nutrition
5. Loss of endocrine stimulation
6. Aging (senile atrophy)
7. Pressure

METAPLASIA
Definition :
A reversible change in which one adult cell type
(epithelial or mesenchymal) is replaced by another adult
cell type.

INTRACELLULAR ACCUMULATION
1. A normal cellular constituent accumulated in
excess : water, protein, lipid, carbohydrates
2. An abnormal substance :
- Exogenous : mineral, products of infectious agents
- Endogenous : product of abN synthesis or
metabolism
3. A pigment
Accumulated : transiently/permanently,
harmless/severely toxic,
In cytoplasm(frequenly in lysosomes) /the nucleus

INTRACELLULAR ACCUMULATIONS

INTRACELLULAR ACCUMULATION

General mechanisms of intracellular

accumulation :
1. Abnormal metabolism, as in
fatty change in the liver.
2. Mutation cx alterations in
protein folding & transport, as
in alpha 1-antitrypsin def
iciency
3. Deficyency of critical enzymes
that prevent breakdown of
substrates that accumulate in
lysosomes, as in lysosoma
storage diseases
4. Inability to degrade
phagositosed particles, as in
hemosiderins and carbon
pigment accumulation

STEATOSIS (FATTY CHANGE)

: abN accumulations of triglycerides within

parenchymal cells.
Occurs in : liver, heart, muscle, kidney.

Causes

: toxins
protein malnutrition
DM, obesity, anoxia.
alcohol abuse

FATTY CHANGE

CHOLESTEROLOSIS

Cholesterol-laden macrophages(foam cells)

from a focus of gallblader cholesterolosis. The gallblader mucosa is in
the upper left.

PROTEINS

Protein reabsorbtion droplets in the renal tubular epithelium.

(Courtesy of Dr.Helmut Remke, Dept. Of Pathology, Brigham and
Womens Hospital.)

LIPOFUSCIN GRANULES
in cardiac myocytes (deposits indicated by arrows)

HEMOSIDERIN GRANULES in liver cells

H&E section showing golden-brown, finely granular pigment.

HEMOSIDERIN GRANULES in liver cells

Prusian blue reaction, specific for iron.

PATHOLOGIC CALCIFICATION
Dystrophic Calcification
- in areas of necrosis
- in the atheromas of advanced atherosclerosis
- in aging
- in damaged heart valves

METASTATIC CALCIFICATION
Hypercalcemia
1. Increased secretion of PTH
2. Destruction of bone tissue
3. Vit.D-related disorders
4. Renal failure

HYALINE CHANGE
: it usually

refers to an alteration within cells or in

extracellular space, which gives a
homogeneous, glassy, pink appearance in
routine histologic sections stained with H&E.