ALTERED CELLULAR AND TISSUE BIOLOGYChapter 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

Cellular Adaptation

Physiologic verses Pathogenic Atrophy Hypertrophy Hyperplasia Metaplasia

Dysplasia (atypical hyperplasia)

Cellular Adaptation

Cellular Adaptation

Cell Injury…”BIG PICTURE”

Biochemical Mechanism ATP depletion Oxygen & oxygen derived free radicals Calcium alterations Defects in membrane permeable

Cell Injury

Common forms Hypoxic injury Free radicals/reactive oxygen species

injury Chemical injury

Cellular Injury - Hypoxia

Cellular Injury:Reprofusion

Chemical Injury

“biochemical interaction with toxic substance”

1) Direct toxicity – at cell membrane or organelles

2) 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

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 eventsExample: 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)