pathophysiology chapter 4
TRANSCRIPT
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CELL INJURY, AGING, AND DEATH
Chapter 4
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REVERSIBLE CELL INJURY• Hydropic swelling: cellular swelling due to
accumulation of water• First manifestation of most forms of reversible cell
injury• Results from malfunction of sodium-potassium
pump with accumulation of sodium ions within the cell
• Any injury that results in loss of energy (ATP) will also result in swelling
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REVERSIBLE CELL INJURY (CONT.)
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REVERSIBLE CELL INJURY• Hydropic swelling: cellular swelling due to
accumulation of water• Characterized by large, pale
cytoplasm; dilated endoplasmic reticulum; and swollen mitochondria
• Generalized swelling of cells in organs can lead to increase in size and weight, indicated by “megaly”
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REVERSIBLE CELL INJURY (CONT.)
Intracellular Accumulations• Excess accumulations of substances in cells
may lead to cellular injury due to toxicity, immune response, and/or taking up cellular space
• Characterized by:• Excessive amounts of normal intracellular
substance
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REVERSIBLE CELL INJURY (CONT.)
Intracellular Accumulations• Characterized by
• Accumulation of abnormal substances secondary to faulty metabolism or synthesis
• Accumulation of pigments or particles that cell is unable to degrade
• Common site of accumulation is liver
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REVERSIBLE CELL INJURY (CONT.)
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REVERSIBLE CELL INJURY (CONT.)
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REVERSIBLE CELL INJURY (CONT.)
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REVERSIBLE CELL INJURY (CONT.)
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CELLULAR ADAPTATION• Atrophy: cells shrink and reduce their
differentiated functions in response to normal and injurious factors• General causes
• Disuse• Denervation• Ischemia• Nutrient starvation• Interruption of endocrine signals• Persistent cell injury• Aging
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CELLULAR ADAPTATION (CONT.)
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CELLULAR ADAPTATION (CONT.)• Hypertrophy: increase in cell mass
accompanied by an augmented functional capacity in response to physiologic and pathophysiologic demands
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CELLULAR ADAPTATION (CONT.)
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CELLULAR ADAPTATION (CONT.)• Hyperplasia: increase in functional capacity
related to an increase in cell number due to mitotic division• Usually in response to increased physiologic
demands or hormonal stimulation
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CELLULAR ADAPTATION (CONT.)• Metaplasia: replacement of one
differentiated cell type with another• Most often as an adaptation to persistent injury,
with replacement of a cell type that is better suited to tolerate injurious stimulation
• Fully reversible when injurious stimulation is removed
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CELLULAR ADAPTATION (CONT.)• Dysplasia: disorganized appearance of cells
because of abnormal variations in size, shape, and arrangement• Represents an adaptive effort gone astray• Significant potential to transform into cancerous
cells, thus referred to as preneoplastic lesions
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IRREVERSIBLE CELL INJURYNecrosis• Usually occurs as a consequence of
ischemia or toxic injury• Characterized by cell rupture, spilling of
contents into extracellular fluid, and inflammation
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IRREVERSIBLE CELL INJURY (CONT.)
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IRREVERSIBLE CELL INJURY (CONT.)
Four Types of Tissue Necrosis• Coagulative (most common type): process
that begins with ischemia and ends with degradation of plasma membrane
• Liquefactive: occurs with dissolution of dead cells, liquification of lysosomal enzymes, and formation of abscess or cyst from dissolved dead tissue
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IRREVERSIBLE CELL INJURY (CONT.)
Four Types of Tissue Necrosis• Fat necrosis
• Death of adipose tissue• Usually the result of trauma or pancreatitis• Appears as a chalky white area of tissue
• Caseous necrosis• Characteristic of lung damage secondary to tuberculosis• Resembles clumpy cheese
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IRREVERSIBLE CELL INJURY (CONT.)
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IRREVERSIBLE CELL INJURY (CONT.)
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IRREVERSIBLE CELL INJURY (CONT.)
Gangrene• Cellular death in a large area of tissue• Results from interruption of blood supply to
a particular part of the body• Dry gangrene
• Form of coagulative necrosis characterized by blackened, dry, wrinkled tissue separated by a line of demarcation from healthy tissue
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IRREVERSIBLE CELL INJURY (CONT.)
Gangrene• Wet gangrene
• Form of liquefactive necrosis• Typically found in internal organs
• Gas gangrene• Results from infection of necrotic tissue by
anaerobic bacteria (Clostridium), which is characterized by formation of gas bubbles in damaged muscle tissue
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IRREVERSIBLE CELL INJURY (CONT.)
Apoptosis• Occurs in response to injury that does not
directly kill the cell, but triggers intracellular cascades that activate a cellular suicide response
• Not always a pathologic process• Does not cause inflammation
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IRREVERSIBLE CELL INJURY (CONT.)
Two Types of Environmental or ExtrinsicSignals May Induce Apoptosis• Withdrawal of “survival” signals that
normally suppress apoptotic pathways, such as observed with cancer cells
• Extracellular signals, such as the Fas ligand, bind to the cell and trigger death cascade through activation of “death receptors”
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IRREVERSIBLE CELL INJURY (CONT.)
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IRREVERSIBLE CELL INJURY (CONT.)
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IRREVERSIBLE CELL INJURY (CONT.)
• Apoptosis can also be triggered by intrinsic pathways• In response to severe cell damage, a protein (p53,
which is normally low in the body) will increase in response to cellular DNA damage, triggering the cell’s own death
• Involves numerous intracellular signals and enzymes
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IRREVERSIBLE CELL INJURY (CONT.)
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ETIOLOGY OF CELLULAR INJURYIschemia and Hypoxic Injury• Tissue hypoxia is most often caused by
ischemia• Ischemia is the most common cause of cell
injury and injures cells faster than hypoxia alone
• Combination of disruption of oxygen supply with accumulation of metabolic waste
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ETIOLOGY OF CELLULAR INJURY (CONT.)
Gangrene• Cellular events lead to lactic acidosis
• Cellular proteins and enzymes become more dysfunctional
• Up to a point, ischemic injury is reversible, but cell death occurs when plasma, mitochondrial, and lysosomal membranes are critically damaged
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ETIOLOGY OF CELLULAR INJURY (CONT.)
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ETIOLOGY OF CELLULAR INJURY (CONT.)
Nutritional Injury• Adequate amounts of fats, carbohydrates,
proteins, vitamins, and minerals are essential for normal cellular function
• Certain cell types more susceptible to injury than others
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ETIOLOGY OF CELLULAR INJURY (CONT.)
Nutritional Injury• Nutritional deficiencies may result from Poor intake Altered absorption Impaired distribution by circulatory
system Inefficient cellular uptake
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ETIOLOGY OF CELLULAR INJURY (CONT.)
Nutritional Injury• Common causes of malnutrition
• Poverty• Chronic alcoholism• Acute and/or chronic illness• Self-imposed dietary restrictions• Malabsorption syndromes
• Nutritional excesses primarily result from excessive intake
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ETIOLOGY OF CELLULAR INJURY (CONT.)
Infectious and Immunologic Injury• Bacteria and viruses can injure cells in a
variety of ways depending on it’s virulence• Added injury may occur indirectly by
triggering body’s immune response
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ETIOLOGY OF CELLULAR INJURY (CONT.)
Chemical Injury• Toxic chemicals or poisons can cause
cellular injury both indirectly and by becoming metabolized into reactive chemicals by the body
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ETIOLOGY OF CELLULAR INJURY (CONT.)
Physical and Mechanical Injury• Factors
• Extremes in temperature• Abrupt changes in atmospheric pressure• Mechanical deformation• Electricity• Ionizing radiation
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ETIOLOGY OF CELLULAR INJURY (CONT.)
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ETIOLOGY OF CELLULAR INJURY (CONT.)
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ETIOLOGY OF CELLULAR INJURY (CONT.)
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CELLULAR AGINGCellular Basis of Aging • Cumulative result of progressive decline in
proliferation and reparative capacity of cells combined with exposure to environmental factors that cause accumulation of cellular and molecular damage
• Responsible mechanisms include DNA damage, reduced proliferation capacity of stem cells, and accumulation of metabolic damage
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CELLULAR AGING (CONT.)
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CELLULAR AGING (CONT.)Physiologic Changes of Aging• Age-related decrease in functional reserve• Inability to adapt to environmental demand
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SOMATIC DEATH• Death of the entire organism• No inflammation or immunologic response
occurs prior to death• General features include cessation of
respirations and heartbeat
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SOMATIC DEATH (CONT.)• Presence of stiffened muscles throughout
body after death (rigor mortis) eventually leads to release of lytic enzymes in body tissues, postmortem autolysis
• Determination of “brain death” as proof of somatic death
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