Altered Cellular and Tissue Biology Chapter 3

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

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

Altered Cellular & Tissue Biology can result from… Adaption Injury Neoplasm Aging death

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

Cellular Adaptation

Cellular Adaptation

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

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

Cellular Injury - Hypoxia

Cellular Injury:Reprofusion

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

Chemical Injury

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

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

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

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

Unintentional and Intentional Injuries

Unintentional and Intentional Injuries

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

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

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

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

Hydropic Degeneration

Calcium Infiltration

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

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

Cellular Death

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”

Coagulative Necrosis (cont’d)

Liquefactive Necrosis:Brain

Caseous Necrosis (cont’d)

Fat Necrosis: Pancreas

Gangrenous Necrosis

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

Theories of Aging Accumulation of injurious events Genetically controlled program

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)