Altered Cellular and Tissue Biology

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Altered Cellular and Tissue Biology

• Chapter 2

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Cellular Adaptation
Physiologic vs. pathogenic Atrophy Hypertrophy Hyp
erplasia Metaplasia Dysplasia
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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