Cell Injury and Its Causes
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Cell Injury and Its Causes

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What is the primary effect of hypoxia on cellular respiration?

  • Activation of aerobic respiration
  • Inhibition of oxidative phosphorylation (correct)
  • Increased intracellular potassium
  • Increased production of ATP
  • Reversible injury leads to an increase in intracellular sodium and a decrease in intracellular potassium.

    True

    What happens to ribosomes during reversible injury?

    They detach from the rough endoplasmic reticulum (RER).

    The accumulation of _____ and lactic acid during hypoxia results in reduced intracellular pH.

    <p>inorganic phosphates</p> Signup and view all the answers

    Which of the following enzymes is NOT activated in response to calcium influx during ischemia?

    <p>Catalases</p> Signup and view all the answers

    What is the result of prolonged hypoxia on the cytoskeleton?

    <p>It disappears, leading to loss of ultrastructural features.</p> Signup and view all the answers

    Match the injuries to their characteristics:

    <p>Reversible Injury = Acute cellular swelling and metabolic disturbances Irreversible Injury = Severe damage and loss of cellular structures Hypoxia = Decreased ATP and stimulation of anaerobic glycolysis Reperfusion Injury = Release of toxic oxygen radicals</p> Signup and view all the answers

    The accumulation of calcium particles indicates reversible injury.

    <p>False</p> Signup and view all the answers

    Which type of cell death is characterized by swelling and breakdown of organelles?

    <p>Necrosis</p> Signup and view all the answers

    Apoptosis can occur under pathological conditions only.

    <p>False</p> Signup and view all the answers

    What is the primary cause of hypoxic cell injury?

    <p>Inadequate oxygenation of the blood</p> Signup and view all the answers

    ________ agents such as trauma, extremes of temperature, and radiation can lead to cell injury.

    <p>Physical</p> Signup and view all the answers

    Match the following causes of cell injury with their descriptions:

    <p>Hypoxia = Inadequate oxygenation of blood Genetic defects = Conditions like Down's syndrome Nutritional imbalances = Vitamin deficiencies and protein-calorie insufficiency Microbiologic agents = Infections from viruses to tapeworms</p> Signup and view all the answers

    Which intracellular system is NOT explicitly mentioned as vulnerable to injury?

    <p>Cellular enzyme activity</p> Signup and view all the answers

    Calcium levels in the cytosol are maintained at high levels to support cellular functions.

    <p>False</p> Signup and view all the answers

    Name one effect of aging on cells.

    <p>Increased vulnerability to injury</p> Signup and view all the answers

    Which of the following is NOT a condition in which free radicals are implicated?

    <p>Rheumatoid arthritis</p> Signup and view all the answers

    Free radicals have a stable configuration due to their unpaired electron.

    <p>False</p> Signup and view all the answers

    Identify one mechanism by which chemical injury occurs.

    <p>Combining with a critical molecular component or cellular organelle.</p> Signup and view all the answers

    The enzymatic catabolism of oxygenous chemicals can lead to the formation of _____ free radicals.

    <p>toxic</p> Signup and view all the answers

    Match the free radical with its effect on cell components:

    <p>Lipid peroxidation = Plasma membranes Thymine reaction = DNA Protein cross-linking = Proteins Hydroxyl radical = Cellular components</p> Signup and view all the answers

    What is one of the enzymatic processes that generate superoxide radicals?

    <p>Xanthine oxidase activity</p> Signup and view all the answers

    Hydropic changes indicate irreversible cell injury.

    <p>False</p> Signup and view all the answers

    Name one reactive species generated through the reduction-oxidation reactions.

    <p>Superoxide radical</p> Signup and view all the answers

    Which of the following conditions is NOT a cause of fatty change (steatosis)?

    <p>Excessive exercise</p> Signup and view all the answers

    What term is used to describe the accumulation of fat within macrophages of subcutaneous connective tissues?

    <p>Xanthomas</p> Signup and view all the answers

    Fatty change is irreversible and often leads to permanent damage to the liver.

    <p>False</p> Signup and view all the answers

    An abnormal accumulation of calcium salts in tissues is referred to as __________.

    <p>pathologic calcification</p> Signup and view all the answers

    Match the following types of deposits with their characteristics:

    <p>Fatty Change = Abnormal accumulation of triglycerides Hemosiderin = Iron-derived granular pigment Cholesterol = Lipids in macrophages during atherosclerosis Glycogen = Vacuoles seen in abnormal glucose metabolism</p> Signup and view all the answers

    What is dystrophic calcification associated with?

    <p>Normal serum calcium levels</p> Signup and view all the answers

    Which of the following cells may be stuffed with lipid due to necrotic cell debris?

    <p>Macrophages</p> Signup and view all the answers

    Excess fatty acid oxidation is a cause of fatty change in tissues.

    <p>False</p> Signup and view all the answers

    Metastatic calcification can occur in normal tissues during hypocalcemia.

    <p>False</p> Signup and view all the answers

    List one cause of hypercalcemia.

    <p>Hyperparathyroidism</p> Signup and view all the answers

    What type of change occurs in the liver during fatty change as seen under a light microscope?

    <p>Small vacuoles displacing the nucleus</p> Signup and view all the answers

    Dystrophic calcification is often found in ____ areas of necrosis.

    <p>advanced atherosclerosis</p> Signup and view all the answers

    Match the following terms to their descriptions:

    <p>Atrophy = Shrinkage in cell size Hypertrophy = Increase in cell size Dystrophic calcification = Deposition in dead tissues Metastatic calcification = Occurs in normal tissues with hypercalcemia</p> Signup and view all the answers

    Which of the following is a characteristic of hypertrophy?

    <p>Increased organ size due to cell enlargement</p> Signup and view all the answers

    Atrophic cells are dead cells.

    <p>False</p> Signup and view all the answers

    What is the biochemical change associated with atrophy?

    <p>Decreased synthesis and increased catabolism</p> Signup and view all the answers

    Study Notes

    Cell Injury

    • Cells maintain a narrow range of physiological activities.
    • When adaptation mechanisms are exceeded, cell injury occurs.
    • Two main patterns of cell death:
      • Necrosis: Cell swelling, protein denaturation, and organellar breakdown.
      • Apoptosis: Programmed cell death, occurring under normal or physiological conditions.

    Causes of Cell Injury

    • Hypoxia: Diminishes aerobic respiration, distinct from ischemia (also causes hypoxic cell injury). Occurs with inadequate oxygenation of the blood.
    • Physical agents: Trauma, temperature extremes, radiation, electric shock, atmospheric pressure changes.
    • Chemicals and drugs: Alter membrane permeability, osmotic homeostasis, or enzyme integrity.
    • Microbiologic agents: Viruses, parasites.
    • Immunologic reactions: Immune system attacks can cause cell injury, e.g., anaphylaxis.
    • Genetic defects: E.g., Down's syndrome, sickle cell anemia.
    • Nutritional imbalances: Protein-calorie deficiency, vitamin deficiencies, diets high in animal fat.
    • Aging: Cellular processes gradually decline.

    Mechanisms of Cell Injury

    • Four vulnerable intracellular systems:
      • Cell membrane integrity (ionic and osmotic regulation).
      • Aerobic respiration.
      • Protein synthesis.
      • Genetic apparatus.
    • Cytosolic free calcium is maintained at low levels by ATP-dependent transporters.
    • Ischemia or toxins increase intracellular calcium, activating enzymes:
      • Phospholipases (degrade membranes).
      • Proteases (protein breakdown).
      • ATPases (ATP depletion).
      • Endonucleases (DNA fragmentation).
      • Oxygen free radicals are key mediators of cell death.

    Ischemic and Hypoxic Injury

    • Reversible Injury:

      • Reduced ATP leads to:
        • Influx of calcium.
        • Sodium pump dysfunction.
        • Intracellular sodium accumulation.
        • Potassium loss.
        • Cell swelling.
        • Accumulation of metabolites (inorganic phosphates, lactic acid, purine nucleotides).
        • Increased anaerobic glycolysis, glycogen depletion.
        • Reduced intracellular pH.
        • Reduced protein synthesis.
        • Loss of cytoskeletal features.
    • Irreversible Injury:

      • Severe mitochondrial vacuolization and calcium accumulation.
      • Extensive plasma membrane damage.
      • Lysosomal swelling.
      • Calcium-mediated injury during reperfusion.
      • Loss of proteins from hyperpermeable membranes.
      • Lysosomal enzyme release and intracellular degradation.
      • Formation of myelin figures.

    Mechanisms of Irreversible Injury:

    • Progressive loss of membrane phospholipids.
    • Cytoskeletal abnormalities.
    • Toxic oxygen radicals from reperfusion.
    • Lipid breakdown products.

    Free Radical Mediation of Cell Injury

    • Free radicals are unstable molecules with unpaired electrons.

    • Generated by:

      • Absorption of radiant energy.
      • Redox reactions.
      • Enzymatic catabolism of chemicals.
    • React with:

      • Plasma membranes (lipid peroxidation).
      • DNA.
      • Proteins.

    Chemical Injury

    • Two Mechanisms:

      • Direct combination with a critical molecule or organelle.
      • Conversion to toxic metabolites (often by P-450 oxidases in the SER).
    • Example: Carbon tetrachloride (CCl4) is converted to CCl3. in the liver, resulting in membrane peroxidation, ER damage, and fatty liver change.

    Patterns of Acute Cell Injury

    • Reversible Cell Injury: Light microscopic changes:

      • Cell swelling.
      • Abnormal exogenous substance deposits.
    • Fatty Change (Steatosis):

      • Accumulation of triglycerides in parenchymal cells.
      • Occurs in the liver, heart, muscle, kidney.
      • Causes: toxins, diabetes, malnutrition, obesity, anoxia.
      • Excess triglycerides may result from defects in fatty acid entry or lipoprotein synthesis.

    Cholesterol and Cholesterol Esters

    • Macrophages in contact with lipid debris become filled with lipid, forming "foamy cells."
    • Atherosclerosis: Smooth muscle cells and macrophages are filled with cholesterol and cholesterol esters.
    • Xanthomas: Accumulations of fat within macrophages in subcutaneous tissues, appearing as nodules.

    Proteins

    • Less common accumulation, e.g., in glomerular diseases with proteinuria.

    Glycogen

    • Accumulation in cases of glucose or glycogen metabolism disorders, appearing as vacuoles.

    Pigments

    • Colored substances, exogenous or endogenous.
      • Melanin: Accumulates in basal cells of the epidermis or dermal macrophages.
      • Hemosiderin: A hemoglobin-derived pigment, golden-brown, accumulates with iron excess.

    Pathologic Calcification

    • Abnormal calcium salt accumulation.
    • Dystrophic calcification: Occurs in dead or dying tissues despite normal calcium levels, evident in atheromas, injured arteries, and aging tissue.
    • Metastatic Calcification: Occurs in normal tissues with hypercalcemia. Causes:
      • Endocrine disorders (hyperparathyroidism).
      • Bone catabolism (multiple myeloma, cancer).
      • Vitamin D intoxication, milk alkali syndrome.
      • Sarcoidosis.
      • Renal failure.

    Cellular Adaptations of Growth and Differentiation

    • Physiologic Adaptations: Responses to normal stimuli (hormones, chemicals).
    • Pathologic Adaptations: Allow cells to modulate their environment and avoid injury.

    Atrophy

    • Shrinkage in cell size due to loss of cell substance.
    • Causes:
      • Reduced workload
      • Loss of innervation
      • Diminished blood supply
      • Inadequate nutrition
      • Loss of endocrine stimulation
      • Aging
    • Cells become smaller to survive with reduced resources.
    • Biochemically: Decreased synthesis, increased catabolism.

    Hypertrophy

    • Increase in cell size due to increased synthesis of structural proteins and organelles.
    • Results in an increase in organ size.

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