Chapter 2 - Cellular Injury and Adaptation Flashcards
Most common cause of cell injury
Hypoxia
Major mechanisms leading to hypoxia
Ischemia, cardiopulmonary failure, and decreased oxygen-carrying capacity of the blood (e.g., anemia)
Vitamin deficiencies: A
Night blindness, squa- mous metaplasia, immune deficiency
Vitamin deficiencies: C
Scurvy
Vitamin deficiencies: D
Rickets and osteomalacia
Vitamin deficiencies: K
Bleeding diathesis
Vitamin deficiencies: B12
megaloblastic anemia, neuropathy, and spinal cord degeneration),
Vitamin deficiencies: folate (B9)
Megaloblastic anemia and neural tube defects
Vitamin deficiencies: Niacin (B3)
Pellagra (diarrhea, dermatitis, and dementia)
Critical intracellular targets that are susceptible to injury
DNA
Production of ATP via aerobic respiration
Cell membranes
Protein synthesis
Damage to DNA, proteins, lipid membranes, and circulating lipids (LDL) can be caused by Oxygen-derived free radicals, which are:
Superoxide anion (O2 –)
Hydroxyl radical (OH•)
Hydrogen peroxide (H2O2).
ATP depletion can cause … and increase …
Disruption of Na+/K+ or Ca++ pumps
Anaerobic glycolysis that leads to a decrease in cellular pH
Influx of calcium can cause problems because calcium is a second messenger, which can activate a wide spectrum of enzymes, like…
Proteases (protein breakdown), ATPases (contributes to ATP depletion), phospholipases (cell membrane injury) and endonucleases (DNA damage)
Mitochondrial dysfunction causes…
Decreased oxidative phosphorylation and ATP production
Formation of mitochondrial permeability transition (MPT) channels
Release of cytochrome c (a trigger for apoptosis).
Protective factors against free radicals include:
• Antioxidants
Vitamins A, E, and C
• Superoxide dismutase
Superoxide → hydrogen peroxide
• Glutathione peroxidase
Hydroxyl ions or hydrogen peroxide → water
• Catalase
Hydrogen peroxide → oxygen and water
Myocardial injury rises the levels of
Troponin
CPK-MB
Lactate dehydrogenase (LDH)
Features of Reversible cell injury:
Decreased synthesis of ATP by oxidative phosphorylation.
Decreased function of Na+K+ATPase membrane pumps, which in turn causes influx of Na+ and water, efflux of K+, cellular swelling (hydropic swelling), and swelling of the endoplasmic reticulum
Switch to anaerobic glycolysis
Decreased protein synthesis leads to detachment of ribosomes from the rough endoplasmic reticulum
Plasma-membrane blebs and myelin figures
Features of Irreversible cell injury:
Severe membrane damage with a massive influx of calcium and efflux of intracellular enzymes and proteins
Marked mitochondrial dysfunction
Rupture of the lysosomes → activation of acid hydrolases → autolysis
Nuclear changes seen in Irreversible cell injury:
Pyknosis (degeneration and condensation of nuclear chromatin)
Karyorrhexis (nuclear fragmentation)
Karyolysis (dissolution of the nucleus)
Morphologic types of necrosis: concept
Cell death in living tissue, often with an inflammatory response
Most common form of necrosis, most often due to ischemic injury (infarct):
Coagulative necrosis
Coagulative necrosis, is caused by…
Denaturing of proteins within the cytoplasm
In coagulative necrosis, microscopic examination shows…
Loss of the nucleus but preservation of cellular shape
Coagulative necrosis does not occur in the…
Brain
Liquefaction necrosis is caused by…
Hydrolytic enzymes, leading to autolysis (release of proteolytic enzymes from injured cells) and heterolysis (release of proteolytic enzymes from inflammatory cells).
Liquefaction necrosis occurs in…
Abscesses, brain infarcts, and pancreatic necrosis
Caseous necrosis gross appearance is:
soft, friable and “cheese-like”
Caseous necrosis is characteristic of…
Granulomatous diseases
Fat necrosis is caused by…
action of lipases on adipocytes
it’s characteristic of acute pancreatitis
Fat necrosis: gross examination
Chalky white appearance.
Fibrinoid necrosis is a form of necrotic…
connective tissue that histologically resembles fibrin
On microscopic examination fibrinoid necrosis has an…
Eosinophilic (pink) homogeneous appearance
Fibrinoid necrosis is often due to…
Acute immunologic injury and vascular hypertensive damage
Dry gangrene has … for the microscopic pattern
Coagulative necrosis
Wet gangrene has … for the microscopic pattern
Liquefactive necrosis
Apoptosis: concept
Programmed cell death without inflammatory response.
Apoptosis: in morphologic appearance…
the cell shrinks in size and has dense eosinophilic cytoplasm
Nuclear changes in apoptosis
Pyknosis and karyorrhexis
Stimuli for apoptosis include
Cell injury and DNA damage,
Lack of hormones, cytokines, or growth factors
Receptor-ligand signals: Fas binding → Fas ligand; tumor necrosis factor (TNF) → TNF receptor 1 (TNFR1)
Function of Protein bcl-2
Inhibiting apoptosis
How does the Protein bcl-2 inhibit apoptosis?
Preventing release of Cytochrome C from mitochondria
Binding pro-apoptotic protease activating factor (Apaf-1)
Function of protein p53
Stimulates apoptosis
How does the protein p53 stimulate apoptosis?
Arresting the cell cycle
If DNA repair is impossible, p53 stimulates apoptosis.
Protein p53 is elavated by…
DNA injury
Execution of apoptosis is mediated by…
a cascade of caspases (cysteine aspartic acid proteases).
Function of caspases in apoptosis
Digest nuclear and cytoskeletal proteins
activate endonucleases
Physiologic examples of apoptosis:
Embryogenesis
Menstrual cycle
Selective death of lymphocytes
Pathologic examples of apoptosis:
Viral diseases (viral hepatitis [Councilman body])
Graft-versus-host disease
Cystic fibrosis (duct obstruction and pancreatic atrophy).
Atrophy: concept
Decrease in cell size and functional ability
Causes of atrophy
Decreased workload/disuse (immobilization)
Ischemia (atherosclerosis)
Lack of hormonal or neural stimulation
Malnutrition
Aging
Atrophy: Light microscopic examination shows…
Small shrunken cells with lipofuscin granules
Atrophy: Electron microscopy shows…
Decreased intracellular components and autophagosomes.
Hypertrophy: concept
Increase in cell size and functional ability due to increased synthesis of intracellular components
Cell types that are unable to exhibit hyperplasia:
Nerve, cardiac, skeletal muscle cells
Increased expression of growth-promoting genes (proto-oncogenes) is related to…
Hyperplasia
Metaplasia: concept
Reversible change of one fully differentiated cell type to another
Pathologic accumulation: Russell bodies
Intracytoplasmic accumulation of immunoglobulins in plasma cells
Lipofuscin
Perinuclear yellow-brown pigment
Due to indigestible material within lysosomes
Common in the liver and heart
Melanin is derived from…
Tyrosine found in melanocytes and substantia nigra
Hemosiderin
Golden yellow-brown granular pigment found in areas of hemorrhage or bruises
Examples of intracellular hyaline:
Renal proximal tubule protein reabsorption droplets
Russell bodies
Mallory’s hyaline (alcoholic)
Examples of extracellular hyaline:
Hyaline arteriolosclerosis
Amyloid
Hyaline membrane disease of the newborn
Examples of Dystrophic calcification:
Fat necrosis (saponification)
Psammoma bodies (laminated calcifications that occur in meningiomas and papillary carcinomas of the thyroid and ovary)
Mönckeberg medial calcific sclerosis in arterial walls
Atherosclerotic plaques.
Dystrophic calcification is the precipitation of calcium phosphate in…
Dying or necrotic tissues
Metastatic calcification is the precipitation of calcium phosphate in…
Normal tissue due to hypercalcemia
Causes of hypercalcemia:
Hyperparathyroidism
Renal failure
Paraneoplastic syndrome
vitamin D intoxication
Milk-alkali syndrome
Sarcoidosis
Paget disease
Multiple myeloma
