Altered Cellular and Tissue Biology

1. Altered Cellular and Tissue Biology Chapter 3

2. Key to Understanding Disease “knowledge of structural and functional reactions of cells and tissues to injurious agents” (including genetic defects)

3. Cellular Adaptation “cells adapt to their environment to escape and protect themselves from injury” • Common • Central part of many disease states

4. Altered Cellular & Tissue Biology canresult from… • Adaption • Injury • Neoplasm • Aging • death

5. Cellular Adaptation • Physiologic verses Pathogenic • Atrophy • Hypertrophy • Hyperplasia • Metaplasia • Dysplasia (atypical hyperplasia)

6. Cellular Adaptation

7. Cellular Adaptation

8. Cell Injury…”BIG PICTURE” • Biochemical Mechanism • ATP depletion • Oxygen & oxygen derived free radicals • Calcium alterations • Defects in membrane permeable

9. Cell Injury • Common forms • Hypoxic injury • Free radicals/reactive oxygen species injury • Chemical injury

11. Cellular Injury - Hypoxia

13. Cellular Injury:Reprofusion

16. Chemical Injury “biochemical interaction with toxic substance” • Direct toxicity – at cell membrane or organelles • Formation of reactive free radicals and lipid peroxidation

17. Chemical Injury

18. Chemical Injury • Poisons – arsenic, cyanide • Air pollutants, insecticides, herbicides • Carbon monoxide – carboxyhemoglobin (300 x O2) • Carbon tetrachloride – Figure 3-9 • Lead – Ca++, Hgb, brain, kidney • Mercury – dental, fish, vaccines • Ethanol – “free radicals” – most organs • Social/street drugs

19. Common Drugs of Abuse • Opioid narcotics • Sedative-hypnotics • Psychomotor stimulants • Phencycielidine-like drugs Table 3-5/6 • Cannabinoids • Hallucinogens • Marijuana • Methamphetamine • Cocaine • Heroin

20. Unintentional and Intentional Injuries • Blunt force injuries “application of mechanical energy to the bodyresulting in tearing, shearing, or crushing of tissues” • Contusion verses hematoma • Abrasion • Laceration • fractures

21. Unintentional and Intentional Injuries • Sharp injuries • Incised wounds • Stab wound • Puncture wound • Chopping wound

22. Unintentional and Intentional Injuries

23. Unintentional and Intentional Injuries

24. Unintentional and Intentional Injuries • Gunshot wounds • Entrance • Exit • Asphyxial Injuries • Suffocation • Strangulation • Chemical – CO, cyanide, hydrogen sulfate • Drowning

25. Infectious Injury • Pathogenicity of a microorganism • Invasion and destruction • Toxin production • Hypersensitivity reaction → damage

26. Immunologic & Inflammatory Injury • Phagocytic cells, antibodies, lymphokines, complement and protease ↓ Cell membrane injury/function ↓ ↑ water ↑ Na+ ↓K+

27. Manifestations of Cellular Injury • Cellular accumulation (infiltrations) • Water – most common • Lipids and carbohydrates – metabolic disorders • Glycogen – metabolic (genetic) disorders • Proteins – renal, B lymphocytes • Pigments – melanin, hemoproteins • Calcium • Urates – gout

28. Hydropic Degeneration

29. Calcium Infiltration

30. Cellular Death • Necrosis • Sum of the cellular changes after local cell death and the process of cellular autodigestion (autolysis)

31. Cellular Death : Nucleus • Processes • Karyolysis – nuclear dissolution, chromatinlysis • Pyknosis – clumping of the nucleus • Karyorrhexis – fragmentation of nucleus

32. Cellular Death

33. Necrosis …” different types in different organs” • Coagulative – hypoxia, kidney, heart, adrenal • Liquefactive – bacterial infections, ischemia – “lipids” • Caseous – tuberculosis – combination coagulative / liquefactive • Fat – breast, pancreas – lipases • Gangrenous – “severe hypoxic injury”

34. Coagulative Necrosis (cont’d)

35. Liquefactive Necrosis:Brain

36. Caseous Necrosis (cont’d)

37. Fat Necrosis: Pancreas

38. Gangrenous Necrosis

39. Aptosis– single cell death • Programmed Cell Death – 10 billion/day – suicide genes • Physiologic – cell deletion during tissue turnover and normal embryonic development, endocrine dependent tissue • Pathologic – intracellular and exogenous events Example: Viral hepatitis, radiation, chemotherapy

42. Theories of Aging • Accumulation of injurious events • Genetically controlled program

45. Somatic Death • Death of the entire person • Postmortem changes • Algor mortis- ↓ temperature 1 – 1.5°F/hr x 24° • Livor mortis – blood settling – gravity • Rigor mortis – muscle stiffening → 12° - ↓ 36 -72° • Postmortem autolysis – release of enzymes and lytic dissolution (microscopic level)