Reversible cell injury - B. Pharma 2nd Semester Pathophysiology notes pdf

Reversible cell injury

Contents

Reversible cell injury

•       Pathogenesis

•       Morphology

Objectives  

At the end of this lecture, student will be able to

•         Explain the sequence of changes occurring during reversible cell injury

•         Explain the morphology of cell injury

•         Describe the pathogenesis of cell injury due to hypoxia and ischemia

Reversible cell injury

Pathogenesis of reversible cell injury due to hypoxia and ischemia

•       If hypoxia and ischemia is for short duration, the effects are reversible

Sequence of changes occurring during reversible cell injury

• ↓ cellular ATP
• ↓ intracellular pH
• Damage to plasma membrane Na⁺ pump
• ↓ protein synthesis
• Functional consequences
• Ultra structural changes

Decreased cellular ATP

•       ATP required for – Membrane transport

                                     - Protein synthesis

                                     - Lipid synthesis

                                     - Phospholipids metabolism

•       Source of ATP – Aerobic and anaerobic respiration

•       Hypoxia and ischemia limits the supply of oxygen to cells, decreases ATP production

Decreased intracellular pH

•       Low oxygen supply

•       Aerobic respiration by mitochondria fails

•       ATP generation by anaerobic glycolytic pathway

•       Depletion of glycogen

•       Accumulation of lactic acid

•       Low pH of cell

•       Acidosis and clumping of chromatin

Damage to plasma membrane sodium pump

•       Na⁺ /K⁺ ATP ase -  operates at plasma membrane

•       Allows active transport of Na⁺  out of a cell

•       Diffusion of K⁺ into cell after depolarization

•       Low ATP affects Na⁺ pump functioning

•       Outward diffusion of K⁺ ions

•       Intracellular accumulation of Na⁺    

•       Increased intracellular  water -  swelling of affected cell

Decreased protein synthesis

•       Continuation of hypoxia

•       Detachment of ribosome from granular ER

•       Polysomes degraded to monosomes

•       Decreased protein synthesis

Functional consequences

•       Myocardial contractility ceases in 60 sec of coronary occlusion

•       Reversed if circulation restored 

Ultra structural changes

•       Normal structure of ER is affected

•       Membrane bound polyribosome detach from rough ER

•       Swelling of mitochondria

•       Myelin figures appear in cytoplasm

•       Loss of microvilli

•       Reduced synthesis of ribosomal RNA in nucleolus

Morphology of reversible cell injury

Reversible cell injury causes cell degeneration

Cellular swelling

•       Due to influx of Na⁺ ions & H₂O , escape of K⁺ 

•       Common causes  - Bacterial toxins

                                     - Chemicals

                                     - Poisons

                                     - Burns

•       Most affected organs – Kidney, Liver and Heart

•       More vacoules appear

•       ER dilates, ribosomes detach

•       Mitochondrial swelling

Fatty changes

•       Steatosis - Accumulation of fat within parenchymal cells

•       Occurs common in liver

•       In non – fatty tissues – heart skeletal muscles and kidney

Other changes

•       Cytoskeletal changes

•       Lysosomal changes

•       Hypertrophy of smooth ER

•       Intracellular accumulation of protein and glycogen

•       Mitochondrial changes

Summary

•       Hypoxia and ischemia causes cell injury

•       If hypoxia and ischemia is for short duration, cell injury can be reversed

•       Reversible cell injury brings about decreased cellular ATP, intracellular pH, damage to plasma membrane, decreased protein synthesis and ultra-structural changes

•       Reversible cell injury causes cell degeneration