Cell structure and function Cell injury- reversible

1. Cell structure and function Cell injury- reversible

2. Cell is basic structure of life . • Form different Tissues and organs • Stem cells • Epithelial ,Mesenchymal ,Hemtopoeitic cells

4. Cell components • Cell membrane/plasma membrane • Cell cytoskeleton- microtubules, intermediate filaments , microfilaments • Cell cytoplasm and organelles; mitochondria, endoplasmic reticulum,ribosomes Golgi complex, lyzosomes, phagocytic vacuoles , • Nucleus

6. Cell membrane • Trilamellar structure 7.5nm • Mixture of phospholipids, glycolipids, cholestrol, proteins ,carbohydartes. • Functions : selective permeability membrane antigens cell receptor mediated actions

8. Cell cytoskeleton • Microfilaments: 6-8nm , composed of actin and myosin , membrane stability and microvilli • Intermediate filaments : 10nm, cytokeratin,desmin, vimentin, GFAP, neurofilaments • Microtubules : 25nm, composed of tubulin, Eg; cilia, flagella, centriole

9. Mitochondria • Oval structures , 2 layers, outer smooth and inner cristae, and matrix • Function : Production of ATP and store of ATP • Power house of cell

10. Endoplasmic reticulum • Vesicles with communicating channels with nucleus and golgi complex • Smooth & Rough ER • Ribosomes sperical particles on surface of RER. • Monoribosomes, polyribosomes • Free and bound form • main function of protein synthesis .

11. Golgi complex • Lamellated vesicles,sacs near nucleus • Synthesis of carbohydrates , proteins and packing of proteins

12. Lysosomes • Round to oval membrane bound structures • Hydrolytic enzymes • Primary & secondary

13. Nucleus • Nuclear envelope, chromatin , nucleous. • Envelope with ribosomes connected to RER, and nucleopores • Chromatin are thread like structures, 22pairs autosomes and 1 pair of sex chrosomes , • Chromosome with centromere and chromatids DNA & RNA , basic ,acidic and neutral proteins .

14. Watson and Crick 1953 – DNA molecule • Double helix strand spiraly wound around axis of sugar and phophoric acid chains , twisted ladder pattern • 4 nucleotide bases purines- adenine & guanine Pyramidines- cytosine and thymine A=T C=G Nucleous – ribosomal RNA

15. DNA structure

18. Cell function • ATP generation 1.Oxidative phosphorylation 2.glycolysis /glycogenolysis • Protein synthesis • Cellular transport ; Ionic channel regulation , endocytosis , exocytosis , diffusion

19. Cell division & cell cycle

20. Cell injury “Cell injury is defined as a variety of stresses a cell encounters as a result of change in its internal and external environment.”

25. Causes of cell injury • Hypoxia and ischemia • Physical agents • Chemical agents and drugs • Microbial agents • Immunologic agents • Nutritional derangments • Psychological factors

26. Hypoxia and ischemia Hypoxia is the most common cause of cell injury Hypoxic cell injury is by the reduced supply of blood to the cells ; ischemia. oxygen deprivation of tissues ; anemia, carbon monoxide poisoning, cardio respiratory insufficiency and increased demand of tissues.

27. Physical agents Mechanical trauma e.g. road accidents Thermal trauma e.g. heat and cold Electricity Radiation e.g. UV and ionising Rapid changes in atmospheric pressure

28. Chemicals and drugs Chemical poisons such as cyanide, arsenic and mercury Strong acids and alkalis Environmental pollutants Oxygen at high concentrations Hypertonic glucose and salt Alcohol and narcotic drugs

29. Microbial agents Injuries caused by bacteria, viruses, fungi, protozoa and other parasites

30. Immunologic agents Hypersensitivity reactions Anaphylactic reactions Autoimmune reactions

31. Nutritional derangements • Deficiency of overall nutrients e.g. Starvation • Protein deficiency e.g. marasmus, kwashiorkor • Mineral defiency e.g. anemia

32. Underlying factors influencing the type of injury

33. Type, duration and severity of injurious agent Type, duration and severity of the stimulus E.g. small dose of chemical toxin or short duration of ischemia cause reversible cell injury, while large dose of the same chemical agent or persistent ischemia causes cell death.

34. Type, status and adaptability of target cell The type of cell injury as regards to its susceptibility , its nutritional and metabolic status, and adaptation of cell to a hostile environment determine the extent of cell injury E.g. skeletal muscles can withstand hypoxic injury for a longer time while cardiac muscles often suffer irreversible cell injury after 30-60 min of persistent ischemia.

35. Underlying intracellular phenomena • Two biochemical factors underlie to distinguish between reversible and irreversible cell injury • Inability to reverse mitochondrial dysfunction by reperfusion or reoxygenation • Disturbance in membrane function in general and in plasma membrane in particular

36. The sequential changes in reversible cell injury Decreased generation of cellular ATP ATP Is essential for Membrane transport, Protein synthesis, Lipid synthesis Phospholipid metabolism

37. Reduced intracellular Ph Failure of aerobic and anaerobic respiration Rapid depletion of glycogen and accumulation of lactic acid lowers the intracellular pH Intracellular acidosis-clumping of nuclear chromatin

38. Damage to plasma membrane sodium pump Normally in the ATP dependent Na+-K+ pump there is transport of Na+ out of the cell and diffusion of K+ into the cell Therefore lowered ATP increased ATPase activity Na+ is retained within the cell and K+ is diffused out of the cell This results in increased intracellular water accumulation to maintain the iso-osmatic condition (hydropic swelling)

39. Reduced protein synthesis As a result of continued hypoxia Ribosomes are detached from the granular endoplasmic reticulum Polysomes are reduced to monosomes Thus reduced protein synthesis

40. Morphologic consequences All forms of biochemical changes underlying cell injury are expressed in terms of morphologic changes. The morphologic changes of reversible cell injury e.g. hydropic swelling appear earlier than morphologic changes of cell death e.g. myocardial infarction.

41. Morphologic changes • Hydrophic change • Hyaline change • Mucoid change • Fatty change

42. Hydrophic change • Cloudy swelling , cytoplasmicvacuolation and nucleus appears pale • Toxins , burns , chemical poisons etc • Osmotic changes in cell • Kidney , liver, heart and pancreas

43. Hyaline change • Glassy, diffuse pink • Intracellular – hyaline droplets renal cells, zenkers degeneration, mallorys hyaline, Russel bodies, • Extracellular – leiomyomas, old scars, Hyaline arterioscleosis, hyalinised glomeruli

44. Mucoid change • Mucin or mucopolysacharides • Epithelial – catarral inflammation , mucocele , mucin secreting tumors, • Connective tissue mucin – myxoid change in tumors, dermis in myxodema, gaglion of synovium

46. Ultrastructural changes • 1.Plasma membrane alterations, such as blebbing, blunting, and loss of microvilli • 2.Mitochondrial changes, including swelling and the appearance of small amorphous densities   • 3.Dilation of the ER, with detachment of polysomes; intracytoplasmic myelin figures may be present   • 4.Nuclear alterations, with disaggregation of granular and fibrillar elements