PART II

CELLULAR INJURY, ADAPTATION and

CELL DEATH

HOMEOSTASIS
balance

between physiologic demands and the

constraints of cell structure and metabolic
capacity.

CAUSES of Cell Injury:

Oxygen deprivation (HYPOXIA)

Physical Agents

e.g. Ischemia (loss of blood supply); Inadequate

oxygenation(cardiorespiratory failure); Loss of oxygencarrying capacity of the blood (Anemia, carbon monoxide
poisoning)

e.g. Trauma, Heat, Cold, Radiation, Electric shock

Chemical Agents and Drugs

e.g. Alcohol, Narcotics

 Infectious
e.g.

agents

Bacteria, Virus, Fungi, Parasitic

Immunologic
e.g.

Autoimmune disease

Genetic
e.g.

derangements

chromosal alterations, gene mutation

Nutritional
e.g.

reactions

imbalances

lack of specific vitamins/minerals, nutritional excesses

Cellular Responses to INJURY:

Adaptation

Occurs when physiologic or pathologic stressors induce a new state that changes the cell but preserves its
viability in the face of the exogenous stimuli.

HYPERTROPHY
increased in cell mass
HYPERPLASIA
increases in cell number
ATROPHY
decreased in cell mass
METAPLASIA
change from one mature cell type to another

Reversible

Injury

Pathologic cell changes that can be restored to normal if the stimulus is removed or if the
cause of injury is MILD.

Irreversible

Injury

Occurs when the stressors exceed the capacity of the cell to adapt and denotes permanent
pathologic changes that cause cell death.

Cell

Death

Occurs when two morphologic and mechanistic pattern denoted necrosis and apoptosis.

NECROSIS
Common type of cell death , sum of the morphologic changes that follow cell death
in living tissue or organs.
Two (2) Processes underline the Basic Morphologic changes:
1. DENATURATION of protein
2. Enzymatic digestion of organelles and other cytosolic components.

GENERAL Patterns of Necrosis:

A. Coagulative Necrosis
Most common; predominated by protein denaturation with preservation of the cell and tissue
framework.
Hypoxic death in all tissue except the brain
HETEROLYSIS/ AUTOLYSIS

B. Liquefactive Necrosis
Necrotic area is soft and filled with fluid. (e.g. bacterial infections and in the Brain.

C. Gangrenous Necrosis
wet Gangrene
D. Caseous Necrosis
Tuberculous lesions; grossly as soft, friable, cheesy material and microscopically as
amorphous eosinophilic material with cell debris.

E. Fat Necrosis
Seen in adipose tissue; Grossly, these are white, chalky areas (fat saponification)

D. Fibrinoid Necrosis
Pathologic pattern resulting from antigen-antibody deposition in blood vessels.
Microscopically there is bright pink- amorphous material in arterial walls, often with associated
inflammation and thrombosis.

APOPTOSIS

Occurs

when a cell dies by activation of an internal

SUICIDE program, involving an orchestrated
disassembly of cellular components.

PROGRAMMED cell death

To eliminate unwanted cells selectively with minimal

disturbance to surrounding cells and the host

It can be PHYSIOLOGIC or PATHOLOGIC.

AUTOPHAGY
Is

an adaptive response of cells to

nutrient deprivation; selfcannibalization to maintain
viability.

INTRACELLULAR ACCUMULATIONS

Normal endogenous substances produced at normal rate, with the metabolic

rate inadequate to remove it. ( Fat accumulation in liver cells)

An abnormal endogenous substance accumulate because of defective folding

or transport and inadequate degradation.

A normal substance accumulate because of Genetic or Acquired defects in its

metabolism. (Lysosomal storage diseases)

Abnormal exogenous substances may accumulate in normal cells because they

lack the machinery to degrade such substances. ( Macrophages laden with
environmental carbon)

Lipids
- Triglycerides (the most common)

Steatosis
abnormal accumulation of triglyceride within the parenchymal cells due to excessive
entry or defective metabolism and transport.
Increased fatty acids entering the liver (STARVATION, CORTICOSTEROID)
Decreased fatty acid oxidation (HYPOXIA)
Increased triglyceride formation (ALCOHOL)
Cholesterol and cholesterol Esters
Atherosclerosis
Xanthomas
Cholesterolosis
Niemann-Pick disease type C

Proteins
excessive synthesis, absorption or defects in cellular transport
Hyaline Change
refers to any deposit that imparts a homogenous, glassy pink appearance in
H&E stained histologic sections.
Glycogen
commonly stored within cells as a ready energy source
Glycogenoses and DM are example of EXCESSIVE intracellular deposits.
Pigments
colored substances that can be exogenous or endogenous such as melanin or
hemosiderin.
e.g. Melanin (Brown black pigment); Homogentisic acid ( Black pigment, px
with alkaptonuria)

Pathologic Calcification
abnormal tissue deposition of calcium salts.

Dystrophic

Two Forms:

Calcification

MARKER

of prior injury; arises to nonviable tissues in

presence of normal calcium serum levels

Metastatic

Calcification

Hypercalcemia,
Four

can cause renal and lung deficit

principal causes of Metastatic calcification:

Elevated Parathyroid Hormone

Bone destruction

Vitamin D related disorders

Renal failure