2. Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Chapter 1 Cell Pathology

3. 2 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Outline of Cell Pathology   Structure & function of normal cell   Integration & coordination of cell function; response to injury   Reversible; Irreversible   Cell adaptations   Atrophy, hypertrophy, metaplasia, intracellular, accumulation, aging   Cell death   Necrosis, apoptosis

4. 3 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Rudolf Virchow (1821–1902)   Introduced concept of cellular pathology   Considered father of modern cellular pathology  1821- 1902, Berlin, pathologist and statesman, one of the most prominent physicians of the 19th century. He pioneered the modern concept of pathological processes by his application of the cell theory to explain the effects of disease in the organs and tissues of the body. Berlinphysicianspathological processescell theorydiseaseBerlinphysicianspathological processescell theorydisease

5. 4 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Structure & Function of a Cell   Basic unit of life   Nucleus   Cytoplasm   Mitochondria   Ribosome   Endoplasmic reticulum   Golgi apparatus   Lysosome   Cytoskeleton   Plasma membrane

6. 5 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. The Nucleus   Essential component of most living cells   Contains DNA, RNA, nuclear proteins   Major components seen by electron microscope:   Nuclear membrane   Chromatin (during mitosis becomes chromosomes)   Nucleolus

7. 6 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Gene Expression

8. 7 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Plasma Membrane   Forms outer surface of cell   Composed of proteins, lipids, carbohydrates   Bilayer surface   Internal   External

9. 8 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Equilibrium of Cell   Steady state maintained between cell & its surrounding   Equilibrium = homeostasis   External stimuli can alter homeostasis   Imbalance in homeostasis can cause:   Cell injury   Cell death

10. 9 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Steady State (Homeostasis)

11. 10 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. INTRODUCTION WHEN AN INJURY OCCURS IT MUST GO THROUGH 3 STAGES OF HEALING Courtesy of Tracie Yarber

12. 11 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Stage 1: Acute Inflammatory IIIIncrease blood flow to the area that brings cells and chemicals to begin the healing process. PPPPhagocytes- Eat up dead cells. LLLLeukocytes- Infection fighting white blood cells. PPPPlatelets-Carry blood clotting materials. THIS STAGE LASTS FOR ABOUT 2 DAYS Courtesy of Tracie Yarber

13. 12 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Stage 2: Repair  The injured area has been filled with the blood, cells, and chemicals needed to rebuild the injury  Fibroblasts begin building fibers across the injury and form the scar. THIS PROCESS LASTS FROM 6 WEEKS TO 3 MONTHS. Courtesy of Tracie Yarber

14. 13 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Stage 3: Remodeling  Builds tissue strength in the tendons, ligaments and muscles to withstand stress applied to the body. THIS STAGE TAKES UP TO A YEAR OR MORE.

15. 14 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc.CONCLUSION Soft tissue healing requires the tissue to go through 3 stages: Acute Inflammatory Repair Repair Remodeling Remodeling The injury should be healed completely after about a years time.

16. 15 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Cell Injury   Reversible cell injury   Cellular swelling   Irreversible cell injury   Cell death

17. 16 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Reversible Cell Injury

18. 17 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Cellular Swelling   Normal microvilli   Swollen microvilli   Invagination of cell membrane   Swollen mitochondria, dilated RER   Loss of intracellular contact

19. 18 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Cell Membrane Permeability Changes   Regulates flow of sodium (Na) & potassium (K) across membrane   Na+/K+ ATPase pump requires energy produced by mitochondria

20. 19 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Nuclear Changes in Irreversible Cell Injury   Pyknosis: condensation   Karyorrhexis: fragmentation   Karyolysis: dissolution of nuclear structure as result of enzymatic digestion

21. 20 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Causes of Cell Injury  Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply oxygen  means a total depletion in the level of oxygen, an extreme form of hypoxia or "low oxygen".  Anoxia means a total depletion in the level of oxygen, an extreme form of hypoxia or "low oxygen".oxygen   Microbes   Inflammation   Immune reactions   Genetic & metabolic disorders

22. 21 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Major Causes of Hypoxia/Anoxia Hydrogen peroxide linklink Superoxide, is a compound that contains the superoxide anion with the chemical formula O 2 −. anion Hydroxyl radical Free radical and aging The human body is in constant battle to keep from aging. Research suggests that free radical damage to cells leads to the pathological changes associated with aging.

23. 22 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Reperfusion Injury During anoxia, radicals will build up. After a heart attack, if the blood flow is reestablished, then the spreading of these radicals will actually increase the cellular death.

24. 23 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Reperfusion Injury  Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function. tissuebloodischemiaoxygennutrients circulationinflammation oxidative stresstissuebloodischemiaoxygennutrients circulationinflammation oxidative stress

25. 24 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Toxic Cell Injury   Direct toxin: heavy metals (i.e., mercury) disrupt S-S bonds   Indirect toxin: carbon tetrachloride metabolized in liver to form carbon trichloride, which is more toxic

26. 25 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Microbial Pathogens   Bacteria: produce toxins   Viruses: “kill cells from within”   Direct   Indirect

27. 26 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Viral Cell Injury Lytic cycle- Makes new viruses Lysogenic cycle – hides inside the DNA

28. 27 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Cell Adaptations   Occur as result of prolonged exposure to adverse or exaggerated normal stimuli   Main forms of adaptation:   Atrophy means cells wasting away from lack of use. Atrophy   Hypertrophy means swelling of cells. Hypertrophy  means increase in number of cells.  Hyperplasia means increase in number of cells. Hyperplasia   Metaplasia means replacing one cell type with another. Metaplasia  Under some circumstances cells may accumulate abnormal amounts of various substances like lipids or proteins.  Intracellular accumulation: Under some circumstances cells may accumulate abnormal amounts of various substances like lipids or proteins. Intracellular accumulation

29. 28 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Cellular Adaptations

30. 29 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Atrophy   Decrease in size of cell, tissue, organ, or entire body:   Physiologic & predictable: atrophy caused by aging   Pathologic: lack of nutrition, chronic ischemia, denervation, inactivity. This happens when you break an arm and it stays in a cast for 6 – 8 weeks. The muscle atrophies and weakens. Recurrent physical therapy is required to regain the lost muscle mass and tone.

31. 30 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Atrophy of Brain G = gyri, S = sulci

32. 31 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc.ISCHEMIA  In medicine, ischemia, is a restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism (to keep tissue alive) medicinetissuesoxygenglucosecellular metabolismmedicinetissuesoxygenglucosecellular metabolism  Ischemia is generally caused by problems with blood vessels, with resultant damage to or dysfunction of tissue. blood vessels blood vessels

33. 32 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Hypertrophy   Hypertrophy: enlarged cells   Hypertrophy of heart in hypertension   Hypertrophy of skeletal muscles in bodybuilders   Hypertrophy often combined with hyperplasia

34. 33 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Hypertrophy of Left Ventricle

35. 34 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Hyperplasia   Increased number of cells in tissue or organ   Endometrial hyperplasia caused by estrogen   Benign prostatic hyperplasia (BPH) in elderly men   Callus (corn) on hand (in some occupations) or on heels (high-heeled shoes, tight shoes)   Hyperplastic polyps of intestine

36. 35 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Hyperplasia

37. 36 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Intracellular Accumulations   Exogenous materials   Coal particles (anthracosis)   Endogenous metabolites   Hemosiderin   Lipids

38. 37 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Alcohol-Induced Fatty Liver

39. 38 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Death of a Cell   Cell death occurs in two forms: 1. 1. Necrosis: localized death of cells or tissues in living organisms due to disease. 2. 2. Apoptosis: programmed death of single cells within living organisms

40. 39 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Types of Necrosis   Coagulative necrosis: most common form   Liquefactive necrosis: in brain   Caseous necrosis: tuberculosis   Enzymatic fat necrosis: acute pancreatitis

41. 40 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Necrosis

42. 41 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Coagulative Necrosis

43. 42 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Liquefactive Necrosis Often it is associated with focal bacterial or fungal infections. In liquefactive necrosis, the affected cell is completely digested by hydrolytic enzymes, resulting in a soft, circumscribed lesion consisting of pus and the fluid remains of necrotic tissue. Dead leukocytes will remain as a creamy yellow pus. [1] After the removal of cell debris by white blood cells, a fluid filled space is left. It is generally associated with abscess formation and is commonly found in the central nervous system.bacterialfungalhydrolytic [1]white blood cellsabscesscentral nervous system

44. 43 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Caseous necrosis is a form of cell death in which the tissue maintains a cheese-like appearance. The dead tissue appears as a soft and white proteinaceous dead cell mass. Tuberculosis

45. 44 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Dry Gangrene

46. 45 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Calcified Aortic Valve

47. 46 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Necrosis/Apoptosis Apoptosis is the process of programmed cell death (PCD), whereas Necrosis is the premature death of cells and living tissue

48. 47 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Necrosis vs Apoptosis Apoptosis Necrosis NaturalYes caused by infection, toxins, or trauma EffectsBeneficialDetrimental Introduction Apoptosis programmed cell death (PCD) Naturally Necrosis is the premature death of cells and living tissue. result Can prevent tumor formation (homeostasis between cell death rate and mitosis rate) Necrosis results in inflammation, which could become chronic.

49. 48 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Apoptosis

50. 49 Copyright © 2012, 2006, 2000, 1996 by Saunders, an imprint of Elsevier Inc. Apoptosis