1. 1 Altered Cellular and Tissue Biology Chapter 2

2. Mosby items and derived items © 2006 by Mosby, Inc. 2 Cellular Adaptation Physiologic vs. pathogenic Atrophy Hypertrophy Hyperplasia Metaplasia Dysplasia

3. Mosby items and derived items © 2006 by Mosby, Inc. 3 Cellular Adaptation

4. Mosby items and derived items © 2006 by Mosby, Inc. 4 Cellular Adaptation

5. Mosby items and derived items © 2006 by Mosby, Inc. 5 Cellular Injury  Reversible  Irreversible

6. Mosby items and derived items © 2006 by Mosby, Inc. 6 Cellular Injury Mechanisms  Hypoxic injury Ischemia – cut off of blood flow circulation Anoxia – insufficient oxygen can be due to lowered Hb, respiration effects, respiratory poisons Cellular responses  Decrease in ATP, causing failure of sodium-potassium pump and sodium-calcium exchange  Cellular swelling Reperfusion injury

7. Mosby items and derived items © 2006 by Mosby, Inc. 7 Cellular Injury Mechanisms  Free radicals and reactive oxygen species Electrically uncharged atom or group of atoms having an unpaired electron Lipid peroxidation Alteration of proteins Alteration of DNA Mechanisms for the inactivation of free radicals

8. Mosby items and derived items © 2006 by Mosby, Inc. 8 Cellular Injury Mechanisms  Chemical injury Lead – CNS toxin – interferes with neurotransmitters causing hyperactivity. Lead paints and children – anemia & lead toxicity Carbon monoxide – binds irreversibly to Hb Ethanol – cellular toxin kills cells – liver toxin- interrupts protein transport – pickles cells can cause fetal alcohol syndrome Mercury – neurotoxin can cause bone deformities Social or street drugs

9. Mosby items and derived items © 2006 by Mosby, Inc. 9 Unintentional and Intentional Injuries  Blunt force injuries Application of mechanical energy to the body resulting in the tearing, shearing, or crushing of tissues Contusion vs. hematoma – bleeding in skin & underlying layers Abrasion – removal of superficial skin layers Laceration rip, year or puncture of skin & layers Fractures – broken bones

10. Mosby items and derived items © 2006 by Mosby, Inc. 10 Contusions and Hematomas

11. Mosby items and derived items © 2006 by Mosby, Inc. 11 Unintentional and Intentional Injuries  Sharp force injuries Incised wounds Stab wounds Puncture wounds Chopping wounds

12. Mosby items and derived items © 2006 by Mosby, Inc. 12 Unintentional and Intentional Injuries

13. Mosby items and derived items © 2006 by Mosby, Inc. 13 Unintentional and Intentional Injuries  Gunshot wounds Entrance wounds  Contact range entrance wound  Intermediate range entrance wound Tattooing and stippling  Indeterminate range entrance wound Exit wounds  Shored exit wound

14. Mosby items and derived items © 2006 by Mosby, Inc. 14 Gunshot Wounds

15. Mosby items and derived items © 2006 by Mosby, Inc. 15 Unintentional and Intentional Injuries  Asphyxial injuries Caused by a failure of cells to receive or use oxygen Suffocation Strangulation  Hanging, ligature, and manual strangulation Chemical asphyxiants- carbon monoxide, cyanide Drowning

16. Mosby items and derived items © 2006 by Mosby, Inc. 16 Infectious Injury  Pathogenicity of a microorganism – gram neg or positive will determine which antibiotics will work best – anti viral agents for viral infections  Virulence of a microorganism – some strains are more dangerous than others  Disease-producing potential Invasion and destruction Toxin production Production of hypersensitivity reactions

17. Mosby items and derived items © 2006 by Mosby, Inc. 17 Immunologic and Inflammatory Injury  Phagocytic cells – immune cells that engulf and destroy invading microbes and toxins  Immune and inflammatory substances Histamine (chemical released by injured or infected cells that cause local vasodilation), antibodies (endogenous proteins that combat and identify invading cells and toxins), lymphokines (chemical produced by imune cells), complement, and enzymes  Membrane alterations – leakage of cell contents due to the presence of antibodies and histamines

18. Mosby items and derived items © 2006 by Mosby, Inc. 18 Injurious Genetic Factors  Nuclear alterations – mutations and damage to DNA  Alterations in the plasma membrane structure, shape, receptors, or transport mechanisms  Examples of genetic diseases Sickle cell anemia (substitution of one amino acid in Hb structure) and muscular dystrophy (muscle tissue does not function properly

19. Mosby items and derived items © 2006 by Mosby, Inc. 19 Injurious Nutritional Imbalances  Essential nutrients are required for cells to function normally inadequate proteins, carbohydrates, fats, vitamins, minerals  Deficient intake – starvation and improper diets – protein deficiency “kwashiokor” most common, Vitamin B 12 deficiency leads to pernicious anemia  Excessive intake - obesity

20. Mosby items and derived items © 2006 by Mosby, Inc. 20 Temperature Extremes  Hypothermic injury Slows cellular metabolic processes Ice crystal formation and frostbite  Hyperthermic injury Heat cramps Heat exhaustion Heatstroke Protein denaturation

21. Mosby items and derived items © 2006 by Mosby, Inc. 21 Atmospheric Pressure Changes  Sudden increases or decreases in atmospheric pressure Blast injury Nitrogen Narcosis or rapture of the deep Nitrogen gas has a narcotic effect (laughing gas) Decompression sickness or caisson disease  “The bends”

22. Mosby items and derived items © 2006 by Mosby, Inc. 22 Ionizing Radiation  Any form of radiation capable of removing orbital electrons from atoms X-rays, gamma rays, alpha and beta particles Amount of exposure measured in RADS. People who work with X-rays must wear badge that measures dosees of exposure over time  Mechanism of damage – ionization of chemicals and breakage of chemical bonds  Effects of ionizing radiation

23. Mosby items and derived items © 2006 by Mosby, Inc. 23 Ionizing Radiation

24. Mosby items and derived items © 2006 by Mosby, Inc. 24 Cellular Injury  Illumination injury Eyestrain, obscured vision, and cataract formation Caused by light modulation  Mechanical stresses Physical impact or irritation  Noise – sound can cause tisse and organ trauma Acoustic trauma and noise-induced hearing loss – tinnitus very common among performing rock band members

25. Mosby items and derived items © 2006 by Mosby, Inc. 25 Manifestations of Cellular Injury  Cellular accumulations (infiltrations) Water Lipids and carbohydrates Glycogen Proteins

26. Mosby items and derived items © 2006 by Mosby, Inc. 26 Hydropic Degeneration

27. Mosby items and derived items © 2006 by Mosby, Inc. 27 Manifestations of Cellular Injury  Cellular accumulations (infiltrations) Pigments  Melanin, hemoproteins, bilirubin (aging brown spots) Calcium – can cause hardening of cells and altered membrane permeability Urate example is gout where urate crystals form in joints and is very painful

28. Mosby items and derived items © 2006 by Mosby, Inc. 28 Calcium Infiltration

29. Mosby items and derived items © 2006 by Mosby, Inc. 29 Cellular Death  Necrosis – local cell death by autodigestion Sum of cellular changes after local cell death and the process of cellular autodigestion  Processes Karyolysis  Nuclear dissolution and chromatin lysis Pyknosis  Shrinking & Clumping of the nucleus Karyorrhexis  Fragmentation of the nucleus

30. Mosby items and derived items © 2006 by Mosby, Inc. 30 Cellular Death

31. Mosby items and derived items © 2006 by Mosby, Inc. 31 Necrosis  Coagulative necrosis Primarily found in Kidneys, heart, and adrenal glands Protein denaturation and increased intracellular level of Ca

32. Mosby items and derived items © 2006 by Mosby, Inc. 32 Coagulative Necrosis

33. Mosby items and derived items © 2006 by Mosby, Inc. 33 Necrosis  Liquefactive necrosis – common after ischemic events in CNS (stroke) Neurons and glial cells of the brain die and are rich in digestive enzymes Hydrolytic enzymes causes brain tissues to become soft and liquefy – sometimes walled off and form cysts These types of cysts also form after bacterial infection due to actions of phagocytic neutrophils and fluid in cyst is called pus.

34. Mosby items and derived items © 2006 by Mosby, Inc. 34 Liquefactive Necrosis

35. Mosby items and derived items © 2006 by Mosby, Inc. 35 Necrosis  Caseous necrosis Found in Tuberculous pulmonary infection Combination of coagulative and liquefactive necrosis Necrotic debris not completely digested thus tissues appear granular like clumped cheese

36. Mosby items and derived items © 2006 by Mosby, Inc. 36 Caseous Necrosis

37. Mosby items and derived items © 2006 by Mosby, Inc. 37 Necrosis  Fat necrosis Common in Breast, pancreas, and other abdominal organs – breakdown of fats create soaps and referred to as saponification and tissue is opaque or white chalky Action of lipases – break down fats to FA and glycerols

38. Mosby items and derived items © 2006 by Mosby, Inc. 38 Fat Necrosis

39. Mosby items and derived items © 2006 by Mosby, Inc. 39 Necrosis  Gangrenous necrosis Clinical term Dry vs. wet gangrene Gas gangrene

40. Mosby items and derived items © 2006 by Mosby, Inc. 40 Gangrenous Necrosis

41. Mosby items and derived items © 2006 by Mosby, Inc. 41 Apoptosis a type of cell death different from Necrosis in that it is active self destruction of normal and pathologic tissue  Programmed cellular death- found mostly to occur during development of embryo  Mechanisms- specific signaling chemicals send message to cells programmed to die  Necrosis vs. apoptosis- while necrosis usually effects all cells in an area apoptosis effects scattered cells killing the cells shrink quickly and disappear neatly while necrotic cells swell and lyse

42. Mosby items and derived items © 2006 by Mosby, Inc. 42 Apoptosis

43. Mosby items and derived items © 2006 by Mosby, Inc. 43 Aging and Altered Cellular and Tissue Biology  Aging vs. disease tissues all have accumulaion of toxic chemicals and mutation damage over time. Disease can damage and destroys cells quickly due to some pathogenic cause  Normal life span - brain cells live as long as you do and the neurons in CNS once formed by age 6 do not divide. RBC live only 120 days  Gender differences - women live longer than men 78 vs 81 years may be due to genetic superiority

44. Mosby items and derived items © 2006 by Mosby, Inc. 44 Theories of Aging  Accumulation of injurious events – the more exposure to dangerous chemicals and pathogens the faster you age  Genetically controlled program – some of us are destined to live longer due to the genetic program in our cells  Theories Genetic and environmental lifestyle factors Alterations of cellular control mechanisms decreased protein synthesis as you age Degenerative extracellular changes – nutrients and free radicals important

45. Mosby items and derived items © 2006 by Mosby, Inc. 45 Theories of Aging

46. Mosby items and derived items © 2006 by Mosby, Inc. 46 Aging  Cellular aging all cells can replicate 40 – 60 times max and may be why clones do not live as long as parents  Tissue and systemic aging immune function goes down with age and free radicals damage cells speeding aging Frailty – wastin syndrome of aging due to decreased protein synthesis and reduced muscle mass and lowered bone density

47. Mosby items and derived items © 2006 by Mosby, Inc. 47 Somatic Death  Death of an entire person Somatic death with no respiration or circulation  Postmortem changes Algor mortis drop in body temp such that in 24 hrs same as room temp Livor mortis blood settles on lowest tissues due to gravity causing discoloration Rigor mortis – 6 – 12 hours post somatic death stiffening of body due to muscle protein breakdown Postmortem autolysis bloating and swelling of body due to autolysis