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Pathology CoursePathology Course
Chapter 1Chapter 1
Section 1.2
Cell Injury and Death
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TopicsTopics
y Apoptosis vs. Necrosisy Causes of Cell Injury
Tissue Hypoxia
x
Causes of Hypoxiax Mechanism of Cell Death by Tissue Hypoxia
Free Radicals
yMorphology of Cell Injury and Death
y Patterns of Necrosis
y Apoptosis
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Apoptosis vs. NecrosisApoptosis vs. Necrosis
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Apoptosis vs. NecrosisApoptosis vs. Necrosis
Apoptosis is an active, nice clean process whereas necrosis is a total mess.
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Causes of Cell InjuryCauses of Cell Injury
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When does cell injury occur?When does cell injury occur?
Cell injury occurs either when it causespersistent stress that cannot be tolerated
by the cell through adaptation, or when
the agent is intrinsically injurious.
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Causes of Cell InjuryCauses of Cell Injury
Causes ofcell
injury
Tissuehypoxia
Chemicals
Physicalinjury
Infectiousagents
Immunereactions
Nutrition
Geneticdiseases
Aging
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HypoxiaHypoxia
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HypoxiaHypoxia
Hypoxia is a decrease in the
oxygenation of tissues.
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Causes of HypoxiaCauses of Hypoxia
Hypoxia
Ischemia HypoxemiaHemoglobin
abnormalities
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IschemiaIschemia
Ischemia is a decrease in the
blood flow to an organ.
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IschemiaIschemia
The most common cause of ischemia is a thrombus
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IschemiaIschemia
Another cause of ischemia is shock (a decrease in cardiac output)
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HypoxemiaHypoxemia
Hypoxemia in a decrease in
the oxygenation of blood.
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HemoglobinAbnormalitiesHemoglobinAbnormalities
Hypoxemia
Respiratoryacidosis
Respiratorydistress syndrome
Increased deadspace in lung
Interstitial lungdiseases
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HypoxemiaHypoxemia
Respiratory acidosis causes hypoxemia because as the concentration of CO2goes up, that of O2 goes down (as the total pressure must remain at 760
mmHg).
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HypoxemiaHypoxemia
Infant respiratory distress syndrome (hyaline membrane disease) causes hypoxemia
because of inadequate oxygenation of blood in the alveoli.
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HypoxemiaHypoxemia
Another cause of hypoxemia is alveolar dead space. This means that air reaches the
alveoli but there is no perfusion (due to an embolus, etc.)
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HypoxemiaHypoxemia
Another cause of hypoxemia is pulmonary edema. This causes hypoxia because there is
decreased oxygenation of blood when passing through the alveoli.
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HypoxemiaHypoxemia
Another cause of hypoxemia is pulmonary edema. This causes hypoxia because there is
decreased oxygenation of blood when passing through the alveoli.
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HypoxemiaHypoxemia
Sarcoidosis is a granulomatous disease that commonly affects the lungs.
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HemoglobinAbnormalitiesHemoglobinAbnormalities
Hemoglobin
abnormlities
Anemia CO poisoning et emoglobinemia
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Structure of HemoglobinStructure of Hemoglobin
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Structure of HemoglobinStructure of Hemoglobin
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AnemiaAnemia
Anemia is a decrease in hemoglobin level. This decreases the capacity of blood to carry
oxygen to tissues, thus causing hypoxia.
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AnemiaAnemia
One of the signs of anemia is pallor of the conjunctivae.
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CO PoisoningCO Poisoning
Another hemoglobin abnormality is CO poisoning, which displaces oxygen from
hemoglobin, thus causing hypoxia.
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CO PoisoningCO Poisoning
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CO PoisoningCO Poisoning
CO poisoning gives cherry-red color on the skin (from the
carboxyhemoglobin).This masks the cyanosis from the hypoxia.
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MethemoglobinemiaMethemoglobinemia
Methemoglobin has ferric iron instead of ferrous iron.This reduces its capacity to bind
oxygen. Normally there is methemoglobin reductase in red cells to reduce this abnormal
form back to normal hemoglobin.
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MethemoglobinemiaMethemoglobinemia
There is a rare inherited disorder of methemoglobin reductase deficiency in which the
individuals have around half of their hemoglobin in the form of methemoglobin.They
compensate by polycythemia, though.
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MethemoglobinemiaMethemoglobinemia
What do you think is the immediate treatment for methemoglobinemia?
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MethemoglobinemiaMethemoglobinemia
Why is methemoglobinemia common inAIDS patients?
Because they commonly have infection withPneumocystis cariniiand the treatment of choice for this
infection is cotrimoxazole (which causes methemoglobinemia).
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MethemoglobinemiaMethemoglobinemia
Apatient with leprosy may get methemoglobinemia from being treated with
dapsone (because it oxidizes the iron in heme).
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Mechanism of Cell Death in HypoxiaMechanism of Cell Death in Hypoxia
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Mechanism of Cell Death in HypoxiaMechanism of Cell Death in Hypoxia
Hypoxia will inactivate the Na+/K+ATPase pump, causing a buildup of sodium
inside the cell.
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Mechanism of Cell Death in HypoxiaMechanism of Cell Death in Hypoxia
A rise in inctracellular sodium concentration will impair the Na+/Ca2+
exchange pump, thus causing a buildup of calcium in the cell.
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Mechanism of Cell Death in HypoxiaMechanism of Cell Death in Hypoxia
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Free RadicalsFree Radicals
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Free RadicalsFree Radicals
Free radicals are compounds with an unpaired
electron in outer orbit.T
hus they are highlyreactive.
Ischemiareperfusioninjury
Ionizingradiation
Iron overload Paracetamol
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Free RadicalsFree Radicals
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Ischemia Reperfusion InjuryIschemia Reperfusion Injury
If ischemia is followed by reperfusion, the excess flow of oxygen to the tissue can help
form a large amount of oxygen free radicals can cause more tissue damage.
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Ionizing RadiationIonizing Radiation
Ionizing radiation contains free radicals that can damage DNA in several ways.Thus,
even though they can be used for treating cancer, they can also cause cancer.
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Iron OverloadIron Overload
Iron can generate hydroxyl radicals in the Fenton reaction. That is why iron
overload states can be dangerous in forming a lot of free radicals.
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AcetaminophenAcetaminophen
Paracetamol (acetaminophen, or Ac in the image above) can be converted
into a free radical if taken in large doses.
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Morphology of Cell Injury and DeathMorphology of Cell Injury and Death
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Threshold of InjuryThreshold of Injury
A threshold separates reversible from irreversible injury.
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Reversible InjuryReversible Injury
ReversibleInjury
Blebbing ofmembrane
Swelling ofER
Swelling ofmitochondria
hromatinclum ing
Amor housdensities
Se aration ofribosomes
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Morphology of Cell Injury and DeathMorphology of Cell Injury and Death
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Threshold of Irreversible InjuryThreshold of Irreversible Injury
Irreversibleinjury
Mitochondrialdysfunction
Membranedisruption
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Morphology of Cell Injury and DeathMorphology of Cell Injury and Death
The renal tubules on the left are normal.The ones in the center are in progressive injury
and necrosis. Notice the increased eosinophilia of some of the cells.
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Patterns of NecrosisPatterns of Necrosis
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CoagulativeCoagulative NecrosisNecrosis
Renal infarct on top, normal myocardium on lower left,MI on lower right
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LiquefactiveLiquefactive NecrosisNecrosis
Liquefactive necrosis of the brain
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CaseousCaseous NecrosisNecrosis
Caseous necrosis in a lung with tuberculosis
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Gangrenous NecrosisGangrenous Necrosis
Dry gangrene of the left foot from a frostbite
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Gangrenous NecrosisGangrenous Necrosis
Occlusion of blood supply to the lower limb from diabetes caused dry gangrene, but
then a superimposed infection changed it into wet gangrene.
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Fat NecrosisFat Necrosis
Enzymatic fat necrosis of the pancreas; notice the white chalky deposits of calcium.
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FibrinoidFibrinoid NecrosisNecrosis
Fibrinoid necrosis in the wall of an artery; this occurs in some forms of vasculitis, like
polyarteritis nodosa.
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ApoptosisApoptosis
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ApoptosisApoptosis
Overview of mechanisms and morphology of apoptosis
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ApoptosisApoptosis
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ApoptosisApoptosis
An apoptotic cell showing increased eosinophilia and nuclear clumping
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Mechanisms ofMechanisms of
ApoptosisApoptosis
Intrinsic (mitochondrial)
pathway for activating
apoptosis
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MechanismsMechanisms
ofApoptosisofApoptosis
Extrinsic (death receptor-
initiated) pathway ofapoptosis
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IncreasedApoptosisIncreasedApoptosis
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DecreasedApoptosisDecreasedApoptosis
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Necrosis vs.ApoptosisNecrosis vs.Apoptosis
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