Cell structure and function Cell injuryreversible n Cell

Cell structure and function Cell injuryreversible

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

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

Cell membrane n Trilamellar structure 7. 5 nm n Mixture of phospholipids, glycolipids, cholestrol, proteins , carbohydartes. n Functions : selective permeability membrane antigens cell receptor mediated actions

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

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

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

Golgi complex n Lamellated vesicles, sacs near nucleus n Synthesis of carbohydrates , proteins and packing of proteins

Lysosomes Round to oval membrane bound structures n Hydrolytic enzymes n Primary & secondary n

Nucleus n Nuclear envelope, chromatin , nucleous. n Envelope with ribosomes connected to RER, and nucleopores n Chromatin are thread like structures, 22 pairs autosomes and 1 pair of sex chrosomes , n Chromosome with centromere and chromatids

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

DNA structure

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

Cell division & cell cycle

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. ”

ALTERED PHYSIOLOGICAL STIMULI; SOME NONLETHAL INJURIOUS STIMULI CELLULAR ADAPTATIONS n. Increased demand, n. Hyperplasia, hypertrophy increased stimulation (e. g. , by growth factors, hormones) • Decreased nutrients, • Atrophy decreased stimulation • Chronic irritation (physical or chemical) • Metaplasia

METABOLIC ALTERATIONS, GENETIC OR ACQUIRED; CHRONIC INJURY; CUMULATIVE SUBLETHAL INJURY OVER LONG LIFE SPAN INTRACELLULAR ACCUMULATIONS CALCIFICATION CELLULAR AGING

REDUCED OXYGEN SUPPLY; CHEMICAL INJURY; MICROBIAL INFECTION CELL INJURY n Acute and transient n. Acute reversible injury Cellular swelling fatty change • Progressive and severe • Irreversible injury ➙ cell death (including DNA damage) Necrosis Apoptosis

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

Hypoxia and ischemia Hypoxia is the most common cause of cell injury n n 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.

Physical agents n n n 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

Chemicals and drugs n n n 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

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

Immunologic agents n Hypersensitivity reactions n Anaphylactic reactions n Autoimmune reactions

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

Underlying factors influencing the type of injury

Type, duration and severity of injurious agent n Type, duration and severity of the stimulus n 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.

Type, status and adaptability of target cell n 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 n 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

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

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

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

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 n 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)

n 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

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

Morphologic changes n Hydrophic change n Hyaline change n Mucoid change n Fatty change

Hydrophic change n Cloudy swelling , cytoplasmic vacuolation and nucleus appears pale n Toxins , burns , chemical poisons etc n Osmotic changes in cell n Kidney , liver, heart and pancreas

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

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

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