Cellular Reactions to Injury.pptx

pathology

1. Haramaya University By: - Dr. Addisu(MD, Assistant professor of pathology) Cellular Reactions to Injury

2. Objectives define adaptive changes know difference between reversible and irreversible injury. describe mechanisms of necrosis types of necrosis and their causes.

3. Introduction cell injury underlies all diseases. in cells exposed to injurious agents the outcomes are;- cell adaptation reversible cell injury irreversible injury & may die by necrosis or apoptosis intracellular accumulation aging the outcome depends on: injurious agent (severity , & duration of the injury) & on the type of the cell.

4. Types of cellular adaptation The types of cellular adaptation include hypertrophy , hyperplasia, atrophy, & metaplasia.

5. 1. Hypertrophy increase in cell size Increased workload leads to increased protein synthesis & increased size & number of intracellular organelles which, in turn, leads to increased cell size which leads to increased size of the organ. physiologic/pathologic e.g -left ventricular hypertrophy in athletes and Hypertension

6. 2. hyperplasia Hyperplasia is an increase in the number of cells in an tissue or organ , usually resulting in increased volume of the organ or tissue. 2.1. physiologic hyperplasia E.g. female breast at puberty and during pregnancy 2.2. pathologic hyperplasia Endometrial hyperplasia (  estrogen) BPH (  androgens) although hyperplasia and hypertrophy are two distinct processes , frequently both occur together, and they may be triggered by the same external stimulus. For instance, hormone-induced growth in the uterus involves both increased numbers of smooth muscle and epithelial cells and the enlargement of these cells.

7. 3. Atrophy decrease in the size of cells . in atrophy cells show autophagic vacuoles from cellular debris and from degraded organelles. Could be physiologic or pathologic Atrophy of notochord, thyroglossal duct Atrophy of uterus after delivery

8. Disuse atrophy (decreased workload) e.g. When a broken limb is immobilized in a plaster cast when a patient is restricted to complete bed rest skeletal muscle fibers decrease in number due to apoptosis, it can also be accompanied by osteoporosis of disuse. denervation under nutrition decreased endocrine stimulation

9. 4. Metaplasia replacement of one differentiated cell by another. 1. Squamous metaplasia columonar cells by squamous cells replaced by squamous cells e.g - bronchial wall metaplasia in smokers 2. Osseous metaplasia This replacement of a connective tissue by bone, for example at sites of injury.

10. Nature and Severity of Injurious Stimulus Cellular Response Altered physiologic stimuli: • Increased demand, increased trophic stimulation (e.g. growth factors, hormones) • Decreased nutrients, stimulation • Chronic irritation (chemical or physical) Cellular adaptations: • Hyperplasia, hypertrophy • Atrophy • Metaplasia Reduced oxygen supply; chemical injury; microbial infection • Acute and transient • Progessive and severe (including DNA damage )   • Mild chronic injury Cell injury : • Acute reversible injury • Irreversible injury ➙ cell death      Necrosis      Apoptosis • Subcellular alterations in various organelles Metabolic alterations, genetic or acquired Intracellular accumulations; calcifications Cumulative sublethal injury over long life span Cellular aging

11. Reversible Cellular Changes and Accumulations Examples : 1 . fatty changes accumulation of triglycerides in side parenchymal cells. It is caused by an imbalance between the uptake, utilization, & secretion of fat. usually seen in the liver, heart, kidneys fatty liver-by alcohol, DM, malnutrition, obesity and poisonings. accumulation mechanisms increased uptake decreased use of fat by cells over production by cells decreased secretion of fat

12. 2. Accumulation of Pigments pigments can be – endogenous : - melanin, bilirubin, hemosiderin, & lipofuscin Exogenous: - carbon A . melanin brownish-black pigment produced by melanocytes in the skin physiological-nevus pathological-in melanoma Decreased melanin pigmentation is seen in albinism & vitiligo .

13. B. Bilirubin yellowish pigment following degradation of hemoglobin Results jaundice: - yellowish discoloration of sclera, skin, mucosa, and internal organs caused by- hemolytic anemia biliary obstruction hepatocellular diseases (genetic or acquired infection)

14. C. Hemosiderin iron containing pigment derived from ferritin. stains as golden-brown amorphous aggregates identified by Prussian blue stain found in macrophages of bone marrow, liver, and spleen as physiologic iron stores Excessive accumulation-2 types 1 . hemosiderosis - primary in tissue macrophages not associated with tissue damage 2. hemochromatosis extensive accumulation leads to tissue damage, scaring and organ dysfunction.

15. cell death can be by two ways- necrosis apoptosis necrosis- cell death following injurious agents cell membrane swelling → rupture → intracellular degradative reactions occur Causes of cell death: hypoxia free radical injury cell membrane damage increased intracellular calcium level

16. A. Hypoxia Hypoxia is a decreased oxygen supply which could be caused by: Ischemia: - decrease blood flow to or from an organ resulting in decreased oxygen as well as nutrient supply. obstruction of arterial blood flow – commonest cause, or by decreased perfusion of tissues by oxygen-carrying blood as occurs in cardiac failure, hypotension, & shock. Anemia: - ↓ oxygen-carrying capacity of red blood cells pulmonary diseases CO poisoning

17. Stages of hypoxia 1. Early (reversible ) results in decreased oxygen phophorulation and ATP synthesis decreased ATP  Failure of the cell membrane Na + – K + pump → cellular swelling ( hydrophic hanges )  large vacuoles in cytoplasm ER swelling, mitochondrial swelling there will be disaggregation of ribosomes and failure of protein synthesis all are reversible if hypoxia is corrected

18. 2. Late (irreversible ) by sever and prolonged injury by massive calcium influx and low PH → activation of enzymes → damage the cell membrane & organelle membrane → cell lysis → detection of intracellular enzymes in peripheral blood Irreversible damage to the mitochondria, cell membranes, & the nucleus mark the point of no return

19. B. Free -Radical Induced Injury any molecule with a single unpaired electron in the outer orbit. E.g superoxide & the hydroxyl radicals Free radicals are formed by normal metabolism, oxygen toxicity, ionizing radiation, & drugs & chemicals, & reperfusion injury. They are degraded by spontaneous decay, intracellular enzymes such as glutathione peroxidase, catalase, or superoxide dismutase, & endogenous substances such as ceruloplasmin or transferrin. Damage occurs when production exceeds degradation  membrane pump damage → ATP depletion and DNA damage [email protected] . reperfusion injury

20. Types of Necrosis Coagulative necrosis Liquefactve necrosis Fat necrosis necrosis Caseous necrosis Gangrenous necrosis

21. 1. COAGULATIVE NECROSIS following sudden interruption of blood vessels e.g. cardiac infarction outline of cells and tissues is kept intact in early stages Ischemia caused by obstruction of vessels lead to coagulative necrosis except in the brain A localized are of necrosis is called infarct

22. 2. LIQUEFACTVE NECROSIS is seen in focal bacterial or, occasionally, fungal infections, because microbes stimulate the accumulation of inflammatory cells and the enzymes of leukocytes digest ("liquefy") the tissue into a liquid viscous mass. If the process was initiated by acute inflammation, the material is frequently creamy yellow and is called pus For unknown reasons, hypoxic death of cells within the central nervous system often evokes liquefactive necrosis.

23. 3.FAT NECROSIS Fat necrosis can be caused by trauma to tissue with high fat content, such as the breast or It can also be caused by acute pancreatitis in which pancreatic enzymes diffuse into the inflamed pancreatic tissue & digest it . The fatty acids released from the digestion form calcium salts (soap formation or dystrophic calcification ). In addition, the elastase enzyme digests the blood vessels & cause the hemorrhage inside the pancreas, hence the name hemorrhagic pancreatitis.

24. 4. CASEOUS NECROSIS cheese like( caseous , white ) – grossly amorphous eosinophilic material on microscopy typical of tuberculosis

25. 5. gangrenous-due to vascular occlusion This is due to vascular occlusion & most often affects the lower extremities and bowel can be : - wet- if followed by infection → liquefaction Dry - only coagulative necrosis NB: necrosis can be followed by inflammation, or dystrophic calcification

26. Apoptosis apoptosis programmed cell death may follow trivial injury death of single cell in clusters apoptotic cells show shrinkage and acidophilia followed by apoptotic bodies occurs as physiologic process e.g .- embryogenesis, menstruation It can also be seen in pathological conditions caused by mild injurious agents. not followed by inflammation or calcification

27. comparison between apoptosis and necrosis Features necrosis apoptosis cell size enlarged reduced Nucleus pykynosis  karyorrhexis  karyolysis chromatin condensation & nuclear fragmentation plasma membrane disrupted intact cell content leakage may leak rarely in apoptotic bodies inflammation frequent no Role pathologic most physiologic

28. pathologic calcification divided in to two: 1. metstatic in hypercalcemia e.g . hyperparathyroidism 2. dystrophic calcification In previously damaged cells , tuberculous lesions, it is also seen in damaged heart valves and atherosclerosis it occurs in normal serum calcium level

29. Reference Mesele Bezabeh et. al, Lecture note, General pathology for health science students, University of Gondar,2005 Robbins and Cotran , Basic.Pathology.8th.Ed Tim D. Spector, John S. Axford ; An introduction to General pathology, 4 th Ed., 1999