Professional Documents
Culture Documents
Function of normal cells: - Environtment - Supply: O2, Glucose, Amino Acid - Removal of met product: CO2
Cellular Injury
Lethal (Necrosis): - Biochem, structure changes Irreversible - Function (-) clinical disease Differ from Death of individual - Complete & Irreversible cessation of brain function - In legally death many cells and tissue remain viable for transplantation Nonlethal (Degeneration): - Biochem, str abn reversible - Injury persists necrosis
Morphology
Cell shrinkage Chromatin condensation Formation of cytoplasmic blebs and apoptotic bodies Phagocytosis of apoptotic cells or bodies
Apoptosis
Higher grade High level of Apoptosis, High level of proliferation
Apoptosis
= Programmed cell death
Apoptosis
- Health: - Metamorphosis of tadpole to frog - Loss of autoreactive response of T cell in thymus
Necrosis
Cell Damage
-
Reduced oxygen supply Physical agents Chemical agents Toxins Virus Abnormal immunological reaction Genetic abnormalities Downs syndrome
Morphology of Necrosis
A. Early : - normal - 1-3 hrs: EM, - 6-8 hrs: LM
MI, dies within minutes: no structural evidence of nec 2 days: changes are obvious
B. Nucleus: - Pyknosis (deeply basophilic mass) - Karyrrhexis (small basophilic particles) - Karyolysis Rapid: lysis without pyknosis
C. Cytoplasm: - 6 hrs acidophilic - own lysosomes autolysis D. Biockemical: Ca ion influx
Necrosis
= Death of a cell or group of cells severe hypoxia, phy, chem
Necrosis: - Denaturation & Coagulation of protein - digestion o/t cell by released enzymes
Coagulative
Retains cellular outline for several days Nuc (-), Cyto: coagulated, pink, homogen lack of blood supply : Solid: Heart, Spleen, Kidney Virus, toxic chem liver Burn: skin
Coagulative Necrosis
Colliquative Necrosis
Brain & tissue ischemia large amount of fluid: enzyme (lysosomal) autolysis softening: pigmented & turbid fluid. Abscess enzym of pmnl Gangrene: complication of necrosis. Putrefactive org saccharolytic & proteolytic foul, green, black breakdown of Hb. Heterolysis source of enzyme: other than cell itself
Fat Necrosis
Enzymatic Pancreatitis lipase triglycerides glycerol &fatty acid + Ca ions calcium soap chalky white plaques Lipase blood throughout body (cutan fat & bone marrow) Nonenzymatic: - breast & subcutan, abd Trauma ? - Foamy mphage, neut, lcyte - DD. cancer
Fibrinoid Mecrosis Autoimm dis: rheum fever, polyarteritis nodosa, SLE Collagen, smooth muscle of blood vessels Arteriole in malignant hypertension Eosinophilic Hyaline like fibrin Contain : - Ig, compl, albumin, breakdown product of coll & fibrin Gangrene: extensive tiss necrosis 1. Dry gangrene
2. Wet gangrene Severe bac inf superimpose on necrosis Extremities, internal organ Mac: swollen, reddish-black, liquefaction not clearly demarcated difficult to treat surgically Bact fermentation foul odor Mortality > 3. Gas gangrene
Sequels of Necrosis
- Phagocytosis: small numbers of cells - Organisation: large number infl, organisation, fibrous - Deposition of calcium: Tbc caseous nec dystrophic
Free Radicals
- = Mol: single unpaired electron - React & modify lipid (memb), DNAm & protein - OH* = Hydroxyl Radical, O2* = Superoxide Radical
Atrophy
= size or number shrinkage (exp. Old) Causes Gradual ddiminution in blood supply Reduced fuctional activity Interupted nerve supply Endocrine deficiency Pressure
Ageing
? Distinction: True Ageing & Disease complicated Ageing True ageing: ideal invirontment (minimal strress) Main controlling factors = intrinsic, ie genetic - ageing genes in mitochondria - loss of cells ability to divide telomeric shortening) (ends of chromosome)
Protein (structural protein, hormones, receptors, intracellular messengers etc) are encoded along the molecule Gene: - = unit chromosome responsible fo synt of a single specific protein - vary in length: 20,000 base pairs - 50,000 in all the human chr - coding regions (exons), non-coding (introns)
Amyloid Deposition
Waxy: extra cell: around blood ves, basement membrane
Detection
Post mortem: Lugols Iodine: - Amyloid Deep brown - Normal Yellow B I o p s y : - Light mic: - Congo Red: - Amyloid: Red: Apple green birefringence (Polarized light) - Normal: Pale pink: Biref (-) - Immunostaining: P protein
Effects
Kidney
pale, firm, waxy Glo permebility gross proteinuria Nephrotic renal failure
G I Tract
diarrhoe, protein loss Malabsorption, nutritional deficiency
Heart
enlarged cardiac failure
Calcification
1. Dystrophic - Necrotic, not absorbed: - old caseous tbc - dead parasite - old infarct - fat necr pancratitis - old pus - Tissue (slow deg): - fibroid - atheromatous deg - old thrombi - diseased or abn heart valve 2. Metastatic: Ca X phosphate product in blood (hypercalceami)
Endogenous Pigmentation
Iron-Containing Pigment breakdown of Ecyte - Haemosiderin - Bilirubin Iron (spl, liv, BM) + Apoferritin. In plasma, transported by transferrin. Iron within cell excessive deposited brown gran hemosiderin: 2 situations:
Haemoglobin
Intravasc hemolysis urine dull red Acute: eg incomp blo trans) acute renal tubular necrosis Chr : paroxysmal haemoglobinuria Hb reabs
brokendown iron (haemosiderin) tubular epithelium
Haematin (Haemazoin)
Malaria: Hb brown pigment monocyte liv, spl Lipofuscin Yellowish brown lipid: atrophied cells of old age (Wear & tear), heart brown atrophy
Exogenous Pigmentation
Introduced: - Inhalation, ingestion, injection Inhalation: - Coal dust (carbon) black - Stone dust (silica) grey
Pneumoconiosis
Ingestion: silver, lead metalic hue lead blue line: gum (lead+ hydrogen sulphide) carrot: caotene yellowish skin Injection: tattoing
Degenerations Hyaline
Glossy, refractile (HE) Dense collagen: leiomyoma, arteriosclerosis Mallorys hyaline: intracellular: cytoskletal proteins: alc liver
Mucoid
Epit Tumor: secrete mucin degenerate epithel Conn tissue: mucin: mucopolisach (hyaluronic acid) Myxomatous
Cellular Aging
Intrinsic Normal human fibroblast: stop dividing senescent 50 doubling ? Finite number o replication ignorant ? How cells know the number of division theyve undergone
Incompl replication of chr ends (telomere shortening) DNA repl truncated copy of each chr
Clock genes
Genetic timers control the tempo of aging clk1 in Caenorhabditis elegans nematode growth rate Mutated clk-1 rate of development 50% longer life spans
Theory of Aging
1 . Longevity >< rates of mitochondrial generation of superoxide anion radicals 2. Overexp of antioxidative enzymes superoxide dismutase & catalase extends life span 3. Restriction of calori intake lowers steady-state levels of oxidative damage, slows age related changes, and extends the maximal life span.
Oxidative phosphorylation, nucleic acid, enzymatic protein, cell receptor, & transcription factor.
Morphology Irr & abn lobed nuclei Pleomorphic vacuolated mitochondria Endoplasmic reticulum Distorted Golgi apparatus
Werners syndrome
Defective gene product: DNA helicase
A
D A A