PathoPhysiology Chapter 4

1. CELL INJURY, AGING, AND DEATH
Chapter 4
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2. 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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3. REVERSIBLE CELL INJURY (CONT.)
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4. 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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5. 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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6. 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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7. REVERSIBLE CELL INJURY (CONT.)
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8. REVERSIBLE CELL INJURY (CONT.)
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9. REVERSIBLE CELL INJURY
(CONT.)
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10. REVERSIBLE CELL INJURY
(CONT.)
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11. 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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12. CELLULAR ADAPTATION
(CONT.)
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13. 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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14. CELLULAR ADAPTATION
(CONT.)
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15. 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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16. 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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17. 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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18. IRREVERSIBLE CELL INJURY
Necrosis
• 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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19. IRREVERSIBLE CELL INJURY
(CONT.)
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20. 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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21. 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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22. IRREVERSIBLE CELL INJURY
(CONT.)
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23. IRREVERSIBLE CELL INJURY
(CONT.)
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24. 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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25. 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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26. 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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27. IRREVERSIBLE CELL INJURY
(CONT.)
Two Types of Environmental or Extrinsic
Signals 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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28. IRREVERSIBLE CELL INJURY
(CONT.)
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29. IRREVERSIBLE CELL INJURY
(CONT.)
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30. 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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31. IRREVERSIBLE CELL INJURY
(CONT.)
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32. ETIOLOGY OF CELLULAR
INJURY
Ischemia 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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33. 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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34. ETIOLOGY OF CELLULAR
INJURY (CONT.)
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35. 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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36. 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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37. 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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38. 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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39. 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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40. 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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41. ETIOLOGY OF CELLULAR
INJURY (CONT.)
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42. ETIOLOGY OF CELLULAR
INJURY (CONT.)
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43. ETIOLOGY OF CELLULAR
INJURY (CONT.)
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44. CELLULAR AGING
Cellular 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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45. CELLULAR AGING (CONT.)
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46. CELLULAR AGING (CONT.)
Physiologic Changes of Aging
• Age-related decrease in functional reserve
• Inability to adapt to environmental demand
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47. 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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48. 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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