Cell injury

1. Cell Injury
Dr Kamran Afzal
MBBS, FCPS, PhD

2. Cell Morphology

3. Cell Physiology
 Cell membrane: Semi-permeable membrane with pumps
for ionic / osmotic homeostasis
 Nucleus: Nucleolus (synthesis of ribosomal RNA)
 Mitochondria: Oxidative phosphorylation (main source of
ATP)
 Endoplasmic reticulum (ER), Ribosomes and Golgi
Apparatus: Protein synthesis and transport
 Lysosome: Endocytosis, phagocytosis and pinocytosis
followed by degradation
 Peroxisome: Catalase and oxidase enzymes, metabolism
of H2O2 fatty acid

4. Cellular Functions
 Movement
 Conductivity
 Metabolic absorption
 Secretion
 Excretion
 Respiration (oxidation)
 Reproduction
 Communication

5. Cell Injury
 A change in cell structure, metabolism, physico-chemical
properties and function which leads to impairment of its
vital activity

6. Main Causes of Cell Injury
 Internal stresses:
 Metabolic imbalances, nutritional deficiencies or excesses
 Genetic abnormalities
 Hypoxia ˃ impairment in aerobic tissue respiration, ischemia ˃
decrease in blood supply
 External stresses:
 Physical agents (mechanical injury, high and low temp,
radiation, electrical shock, sudden fluctuations of the
barometric pressure, acceleration, etc)
 Natural toxins, venoms, infections
 Drugs and chemicals, abundant oxygen, increase in glucose,
high doses of dietary salt, poisons, insecticides, carbon
monoxide, asbestos, social stimulators, e.g. alcohol, narcotics

7. Stages in Cell Injury

8. Reversible Cell Injury
 Occurs when
environmental changes
exceed the capacity of
the cell to maintain
normal homeostasis
 But if the stress is
removed or the cell
withstands the assault
the injury is reversible

9. Irreversible Cell Injury
 If the stress remains
severe, the cell injury
becomes irreversible and
leads to cell death

10. Reversible And Irreversible Cell Injury

11. Mechanisms of Cell Injury
 Defects in membrane permeability
 Mitochondrial damage ˃ Depletion of ATP
 Accumulation of oxygen-derived free radical
(Oxidative stress)
 Influx of intracellular calcium and loss of calcium
homeostasis

12. Mechanisms Of Cell Death
 Physiological, as in cell life cycle
 Necrosis: Morphologic changes seen in dead cells within
living tissue
 Autolysis: Dissolution of dead cells by the cells own
digestive enzymes
 Apoptosis: Programmed cell death
 “Apoptosis is a pathway of cell death that is induced by a
tightly-regulated suicide program in which cells destined
to die activate enzymes that degrade the cell’s own
nuclear DNA and nuclear and cytoplasmic proteins”

13. Cell Injury Signs
 Morphological
 Swelling
 Dystrophy
 Dysplasia
 Necrosis
 Autolysis
 Functional
 Decrease in function
 Cellular
 Increase in permeability
 Cytoplasmic enzymes
leakage to the blood
 Metabolic derangements
 Injury mediators
 Synthesis impairments
 Electrolyte balance
disorders

14. Fatty Change
 Occurs in:
 Hypoxic injury
 Toxic or metabolic injury
 Appearance of lipid vacuoles in the cytoplasm
 Swelling of cells is reversible
 In cells involved in and dependent on fat metabolism
 Hepatocytes
 Myocardial cells

15. Pigmentation
 Endogenous
 Lipofuscin – ageing pigment
 Melanin – in melanocyte
 Hemosiderin – aggregates of ferritin
 Accumulation of bilirubin
Too much produced (e.g., hemolysis)
Not processed (e.g., cirrhosis)
Outflow blocked (e.g., choledocholithiasis)
 Exogenous
 Anthracosis (cigarette smoking; urban living)
 Tattoo

16. Calcification
 Abnormal tissue deposition of calcium salts
 Dystrophic
• Patients have a normal calcium level
• Calcification affects previously damaged tissue
(Ageing or damaged heart valve)
 Metastatic
• Patients have an elevated level of serum calcium
Causes: Hyperparathyroidism, bony metastases, RF
 Atherosclerosis (common)
 Aortic stenosis (uncommon)
- Calcification is not routinely reversible
Tricuspid valve - Calcification

17. Amyloidosis
 A group of diseases characterised by extracellular
depostion of fibrillar proteinaceous substance called
amyloid
 Has morphological appearance, staining properties and
physical structure but with variable protein or biochemical
composition
 Deposits intracellularly and extracellularly

18. Amyloidosis of Heart
 Heart is involved in systemic amyloidosis
 Advanced cases.. restrictive cardiomyopathy, arrhythmias
 Gross: heart enlarged, surface pale, translucent and waxy
Epicardium, endocardium and valves show tiny nodular
deposits of amyloid
 Microscopy: Amyloid deposits in and around coronaries
 In primary amyloidosis, deposits of AL are seen around
myocardial fibres in ring like formations (ring fibres)
 In localised form, deposits are seen in left atrium and
interatrial septum

19. Necrosis
 Result of denaturation of intracellular proteins and
enzymatic digestion of the lethally injured cell
 Necrotic cells are unable to maintain membrane integrity
 Lysosomal enzymes digest the necrotic cells
 Dead cells may ultimately become calcified
 Coagulative
 Liquefactive
 Caseous
 Fat
 Gangrenous
 Fibrinoid

20. Coagulative Necrosis – Kidney
A localized area of coagulative
necrosis is called an infarct
Gangrene - Coagulative
necrosis involving multiple
tissue planes

21. Caseous Necrosis – Tuberculosis
collection of fragmented or lysed cells
and amorphous granular debris
enclosed within a distinctive
inflammatory border
Fat Necrosis – Mesentry
Focal areas of fat destruction,
typically resulting from release of
activated pancreatic lipases

22. Fibrinoid - Artery
When complexes of antigens
and antibodies are deposited
in the walls of arteries
Liquifactive Necrosis – Cerebrum
Digestion of the dead cells, resulting
In transformation of the tissue into a
liquid viscous mass