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Altered Cellular and Tissue BiologyChapter 2

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Cellular AdaptationPhysiologic vs. pathogenicAtrophyHypertrophyHyperplasiaMetaplasiaDysplasia

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Cellular Adaptation

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Cellular Adaptation

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Cellular Injury Reversible Irreversible

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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

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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

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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

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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

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Contusions and Hematomas

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Unintentional and Intentional Injuries Sharp force injuries

Incised wounds Stab wounds Puncture wounds Chopping wounds

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Unintentional and Intentional Injuries

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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

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Gunshot Wounds

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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

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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

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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

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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

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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

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Temperature Extremes Hypothermic injury

Slows cellular metabolic processes Ice crystal formation and frostbite

Hyperthermic injury Heat cramps Heat exhaustion Heatstroke Protein denaturation

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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”

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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

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Ionizing Radiation

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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

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Manifestations of Cellular Injury Cellular accumulations (infiltrations)

Water Lipids and carbohydrates Glycogen Proteins

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Hydropic Degeneration

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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

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Calcium Infiltration

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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

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Cellular Death

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Necrosis Coagulative necrosis

Primarily found in Kidneys, heart, and adrenal glands

Protein denaturation and increased intracellular level of Ca

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Coagulative Necrosis

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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.

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Liquefactive Necrosis

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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

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Caseous Necrosis

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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

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Fat Necrosis

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Necrosis Gangrenous necrosis

Clinical term Dry vs. wet gangrene Gas gangrene

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Gangrenous Necrosis

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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

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Apoptosis

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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

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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

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Theories of Aging

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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

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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