N212 PATHOPHYSIOLOGY EXAM 1 COMPREHENSIVE STUDY
GUIDE LATEST VERSION 2026/2027
C
Cellular Function | Inflammation | Fluid & Electrolytes | Acid-Base Balance | Genetics |
Immunity
UNIT 1: CELLULAR ADAPTATION & INJURY
A. Normal Cell Function
Cells maintain homeostasis through regulated metabolism, membrane integrity, and
organelle coordination. Understanding deviations from normal function is the foundation
of pathophysiology.
Cellular Organelles and Pathophysiologic Relevance
• Nucleus — contains DNA; site of transcription; nuclear envelope disruption signals
irreversible injury
• Mitochondria — ATP production via oxidative phosphorylation; first organelle to
show hypoxic injury; release cytochrome c triggering apoptosis
• Endoplasmic Reticulum (ER) — protein synthesis (rough) and lipid synthesis
(smooth); ER stress triggers unfolded protein response (UPR)
• Lysosomes — contain hydrolytic enzymes; lysosomal rupture releases enzymes
causing cellular autolysis
• Plasma Membrane — maintains ionic gradients via Na+/K+ ATPase; injury causes
loss of ion regulation
B. Cellular Adaptation Responses
Cells adapt to stress by altering their size, number, or type. Adaptations may be
physiologic (normal) or pathologic (disease states).
Hypertrophy: Increase in cell SIZE (not number) due to increased workload. Example:
Cardiac hypertrophy in hypertension; skeletal muscle with exercise.
Hyperplasia: Increase in cell NUMBER due to increased demand. Example:
Endometrial hyperplasia from excess estrogen; callus formation.
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,Atrophy: Decrease in cell SIZE and/or number due to reduced workload, ischemia,
denervation, or malnutrition. Example: Muscle wasting in prolonged bed rest.
Metaplasia: REVERSIBLE replacement of one differentiated cell type with another.
Example: Squamous metaplasia of bronchial epithelium in smokers; Barrett esophagus
(squamous → columnar).
Dysplasia: Abnormal change in cell SIZE, shape, and organization. Premalignant; may
progress to neoplasia. Example: Cervical dysplasia on Pap smear.
Aplasia: Failure of cells to develop; absent or underdeveloped organ. Example: Aplastic
anemia — failure of bone marrow stem cells.
Hypoplasia: Incomplete development of an organ/tissue — fewer cells than normal but
cells are morphologically normal.
Clinical Note: The key exam distinction: Hypertrophy = bigger cells; Hyperplasia =
more cells; Metaplasia = different cell type (reversible); Dysplasia = disordered cells
(premalignant).
C. Cell Injury & Death
Causes of Cell Injury
• Hypoxia/Ischemia — most common; deprivation of O2; reduces ATP production
• Physical agents — trauma, temperature extremes, radiation, electrical injury
• Chemical agents/drugs — toxins, heavy metals, medications
• Infectious agents — bacteria, viruses, fungi, parasites
• Immunologic mechanisms — autoimmune reactions, hypersensitivity
• Genetic factors — enzyme defects, structural protein defects
• Nutritional imbalances — deficiencies or excesses
Reversible vs. Irreversible Injury
Reversible Injury: Cell can return to normal if stimulus removed. Signs: cellular swelling
(hydropic change), fatty change, loss of microvilli, plasma membrane blebbing.
Irreversible Injury: Cell death occurs. Key markers: Mitochondrial permeability transition
(MPT) pore opening; inability to restore membrane integrity; lysosomal swelling.
Types of Cell Death
Necrosis: PATHOLOGIC cell death. Passive, releases cellular contents → inflammation.
Types include coagulative, liquefactive, caseous, fat necrosis, and gangrenous necrosis.
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, Apoptosis: PROGRAMMED (planned) cell death. Orderly process; phagocytosis
without inflammation; essential for normal development. Triggered by caspase
activation.
Coagulative Necrosis: Most common type. Cell outline preserved; cytoplasm becomes
eosinophilic/protein-rich. Seen in ischemic infarcts (except brain). Example: Myocardial
infarction.
Liquefactive Necrosis: Hydrolytic enzymes dissolve necrotic tissue into liquid mass.
Brain infarcts and bacterial abscesses. Example: Stroke, Staphylococcal abscess.
Caseous Necrosis: Combination of coagulative and liquefactive; cheese-like appearance.
Classic for Mycobacterium tuberculosis. Central necrosis within granulomas.
Fat Necrosis: Enzymatic fat destruction; saponification. Classic in acute pancreatitis
(lipase release).
Gangrenous Necrosis: Dry gangrene = coagulative; Wet gangrene = liquefactive +
bacterial infection. Common in ischemic limbs.
Clinical Note: Apoptosis vs. Necrosis: Apoptosis = orderly, no inflammation, normal
development or DNA damage. Necrosis = uncontrolled, inflammatory response,
pathologic stimulus. High-yield exam distinction.
D. Free Radicals and Oxidative Stress
Free Radical: Atom or molecule with unpaired electron in outer orbital; highly reactive;
causes lipid peroxidation, protein oxidation, DNA strand breaks.
Reactive Oxygen Species (ROS): O2 derivatives (superoxide, hydrogen peroxide,
hydroxyl radical). Major source of oxidative injury in ischemia-reperfusion.
• Sources of free radicals: Normal metabolism, ischemia-reperfusion, radiation,
drugs/toxins, inflammation
• Defense mechanisms: Superoxide dismutase (SOD), catalase, glutathione
peroxidase, Vitamins C and E
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GUIDE LATEST VERSION 2026/2027
C
Cellular Function | Inflammation | Fluid & Electrolytes | Acid-Base Balance | Genetics |
Immunity
UNIT 1: CELLULAR ADAPTATION & INJURY
A. Normal Cell Function
Cells maintain homeostasis through regulated metabolism, membrane integrity, and
organelle coordination. Understanding deviations from normal function is the foundation
of pathophysiology.
Cellular Organelles and Pathophysiologic Relevance
• Nucleus — contains DNA; site of transcription; nuclear envelope disruption signals
irreversible injury
• Mitochondria — ATP production via oxidative phosphorylation; first organelle to
show hypoxic injury; release cytochrome c triggering apoptosis
• Endoplasmic Reticulum (ER) — protein synthesis (rough) and lipid synthesis
(smooth); ER stress triggers unfolded protein response (UPR)
• Lysosomes — contain hydrolytic enzymes; lysosomal rupture releases enzymes
causing cellular autolysis
• Plasma Membrane — maintains ionic gradients via Na+/K+ ATPase; injury causes
loss of ion regulation
B. Cellular Adaptation Responses
Cells adapt to stress by altering their size, number, or type. Adaptations may be
physiologic (normal) or pathologic (disease states).
Hypertrophy: Increase in cell SIZE (not number) due to increased workload. Example:
Cardiac hypertrophy in hypertension; skeletal muscle with exercise.
Hyperplasia: Increase in cell NUMBER due to increased demand. Example:
Endometrial hyperplasia from excess estrogen; callus formation.
Page 1 of 24
,Atrophy: Decrease in cell SIZE and/or number due to reduced workload, ischemia,
denervation, or malnutrition. Example: Muscle wasting in prolonged bed rest.
Metaplasia: REVERSIBLE replacement of one differentiated cell type with another.
Example: Squamous metaplasia of bronchial epithelium in smokers; Barrett esophagus
(squamous → columnar).
Dysplasia: Abnormal change in cell SIZE, shape, and organization. Premalignant; may
progress to neoplasia. Example: Cervical dysplasia on Pap smear.
Aplasia: Failure of cells to develop; absent or underdeveloped organ. Example: Aplastic
anemia — failure of bone marrow stem cells.
Hypoplasia: Incomplete development of an organ/tissue — fewer cells than normal but
cells are morphologically normal.
Clinical Note: The key exam distinction: Hypertrophy = bigger cells; Hyperplasia =
more cells; Metaplasia = different cell type (reversible); Dysplasia = disordered cells
(premalignant).
C. Cell Injury & Death
Causes of Cell Injury
• Hypoxia/Ischemia — most common; deprivation of O2; reduces ATP production
• Physical agents — trauma, temperature extremes, radiation, electrical injury
• Chemical agents/drugs — toxins, heavy metals, medications
• Infectious agents — bacteria, viruses, fungi, parasites
• Immunologic mechanisms — autoimmune reactions, hypersensitivity
• Genetic factors — enzyme defects, structural protein defects
• Nutritional imbalances — deficiencies or excesses
Reversible vs. Irreversible Injury
Reversible Injury: Cell can return to normal if stimulus removed. Signs: cellular swelling
(hydropic change), fatty change, loss of microvilli, plasma membrane blebbing.
Irreversible Injury: Cell death occurs. Key markers: Mitochondrial permeability transition
(MPT) pore opening; inability to restore membrane integrity; lysosomal swelling.
Types of Cell Death
Necrosis: PATHOLOGIC cell death. Passive, releases cellular contents → inflammation.
Types include coagulative, liquefactive, caseous, fat necrosis, and gangrenous necrosis.
Page 2 of 24
, Apoptosis: PROGRAMMED (planned) cell death. Orderly process; phagocytosis
without inflammation; essential for normal development. Triggered by caspase
activation.
Coagulative Necrosis: Most common type. Cell outline preserved; cytoplasm becomes
eosinophilic/protein-rich. Seen in ischemic infarcts (except brain). Example: Myocardial
infarction.
Liquefactive Necrosis: Hydrolytic enzymes dissolve necrotic tissue into liquid mass.
Brain infarcts and bacterial abscesses. Example: Stroke, Staphylococcal abscess.
Caseous Necrosis: Combination of coagulative and liquefactive; cheese-like appearance.
Classic for Mycobacterium tuberculosis. Central necrosis within granulomas.
Fat Necrosis: Enzymatic fat destruction; saponification. Classic in acute pancreatitis
(lipase release).
Gangrenous Necrosis: Dry gangrene = coagulative; Wet gangrene = liquefactive +
bacterial infection. Common in ischemic limbs.
Clinical Note: Apoptosis vs. Necrosis: Apoptosis = orderly, no inflammation, normal
development or DNA damage. Necrosis = uncontrolled, inflammatory response,
pathologic stimulus. High-yield exam distinction.
D. Free Radicals and Oxidative Stress
Free Radical: Atom or molecule with unpaired electron in outer orbital; highly reactive;
causes lipid peroxidation, protein oxidation, DNA strand breaks.
Reactive Oxygen Species (ROS): O2 derivatives (superoxide, hydrogen peroxide,
hydroxyl radical). Major source of oxidative injury in ischemia-reperfusion.
• Sources of free radicals: Normal metabolism, ischemia-reperfusion, radiation,
drugs/toxins, inflammation
• Defense mechanisms: Superoxide dismutase (SOD), catalase, glutathione
peroxidase, Vitamins C and E
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