This document discusses cell injury and the pathophysiology of cell injury. It describes how cells maintain homeostasis through adaptation but can become injured if adaptive responses are exceeded. The two main patterns of cell injury are necrosis and apoptosis. Cell injury results from depletion of ATP, loss of calcium homeostasis, formation of free radicals, and membrane permeability defects. The accumulation of abnormal substances within cells can also cause injury.

1. Cell INJURY
MR. SOHAN A. PATEL, Dept of Pharmacology
ASSISTANT PROFESSOR,
SMT.S.M.SHAH PHARMACY COLLEGE,
GUJARAT,
sohanpharma@gmail.com

3. INTRODUCTION
• “All organ injuries start with structural or
molecular alterations in cells” concept began by
Virchow in 1800's .
• Structures of living systems are not constant
They are destructured and restored continuously.
• All living organisms absorb and extract proteins,
lipids (fats), carbohydrates, and their components
as well as water, ions, and pigments.

4. 1) Homeostasis
• cells maintain normal structure & function in
response to physiologic demands.

9. • as cells stresses they undergo functional or
structural adaptations to maintain viability /
homeostasis.
• respond to some stimuli by increasing or
decreasing specific organelle content.
• adaptive processes: atrophy, hypertrophy,
hyperplasia and metaplasia.

10. • Cellular Adaptation :

12. Cell Injury

13. cell injury : if limits of the adaptive response are
exceeded or if adaptation not possible, a
sequence of events called cell injury occurs.

15. Two main morphologic patterns:
a. necrosis
b. apoptosis.

17. Necrosis of organs

20. PATHOPHYSIOLOGY OF
CELL INJURY :

22. Cell injury results from different biochemical mechanisms
acting on several essential cellular components

23. Depletion of ATP
• Na+ pump fails Na+ and water enter and K+
is lost
• Glycolysis depletes glycogen and lowers pH
(loss of enzyme activity)
• Ca++ pump fails- Ca++ into cells (toxic)
• Decreased protein synthesis (ribosomes
detach)
• Unfolded protein response

28. Loss of Ca++ Homeostasis
• Extracellular Ca++ is 15X higher than cytosolic
Ca++
• Loss of ATP increases intracellular Ca++
• Increased Ca++ activates phospholipases,
proteases, endonucleases, and ATPases
• Increased Ca++ also increases mitochondrial
permeability triggering apoptosis

30. Free Radical Formation
• Single unpaired electron; highly reactive
• Normal metabolism produces superoxide anion,
hydrogen peroxide and hydroxyl ion; superoxide
is produced in neutrophils
• Reactive oxygen species (ROS) are a type of free
radical
• Excess of ROS within cell leads to oxidative
stress

31. Pathologic Effects of ROS
• Lipid peroxidation leading to membrane
damage
• Protein damage
• DNA damage

33. Major Antioxidants
• Antioxidants block the formation of ROS or
inactivate them
• Antioxidant Enzymes: superoxide dismutase,
catalase, glutathione peroxidase
• Vitamins: A, E, ascorbic acid, glutathione

34. Membrane Permeability Defects
• Plasma membrane
• Mitochondrial membrane
• Lysosomal membrane- release of RNases,
DNases and proteases

36. Cellular swelling
It is an intracytoplasmic accumulation of water
due to incapacity of the cells to maintain the
ionic and fluid homeostasis.

37. Causes
• to cellular hypoxia,

38. Intra cellular accumulation
• Accumulation of abnormal amounts of
various substances due to manifestations of
metabolic derangements in the cell.

39. CATEGORIES:
1. Normal cellular constituents e.g., water,
lipids etc.
2. Abnormal substances
a) Exogenous e.g., mineral or products of
infectious agents
b) Endogenous e.g., products of abnormal
synthesis or metabolism

40. SITES:
a) Cytoplasm (phagolysosomes)
b) Nucleus

41. SOURCE:
Produced by the affected cell .
Produced elsewhere in the body, but stored in
the cell

42. PROCESSES OF ACCUMULATIONS
FOUR PROCESSES
1. Production of a normal endogenous substance
at normal or increased rate, but the rate of
metabolism is inadequate to remove it. e.g., fatty
liver, reabsorption protein droplets in tubules of
kidney

49. • formed by clusters of foamy cells found in the
subepithelial connective tissue of the skin and
in tendons

50. • focal accumulations of cholesterol-laden
macrophages in the lamina propria of
gallbladder
3.CHOLESTEROLOSIS:

54. Calcification
• Calcification is the accumulation of calcium salts
in a body tissue.
• It normally occurs in the formation of bone, but
calcium can be deposited abnormally in soft
tissue, causing it to harden.