Pathology Flashcards
Atrophy
Shrinkage of cell by loss of substance
Reasons for atrophy
Disuse, inadequate nutrients, lack of endocrine stimulus, poor blood supply, denervation, aging
Hypertrophy
Increase in SIZE of cell –> increasing organ size
Grows by creating more stuff (lipids, proteins glycogen, anabolic reactions)
Hyperplasia
Increase in NUMBER of cells
Reasons for hypertrophy and hyperplasia
Increased functional demand
Increase, work demand, metabolic demand, excess endocrine stimulus
Metaplasia
Replacement of one cell type with another cell type, usually less differentiated
Reasons for metaplasia
Increased capacity for tissue survival, persisting injury
Loss of normal cell function
Maintained if compromised–> Dysplasia
Causes of Cell Injury
Oxygen deprivation Chemical agents Infectious agents Immunologic reactions Genetic factors Nutritional imbalances Physical agents Radiation Calcium Aging
Oxygen Deprivation Categories
Ischemia- Tissue isnt receiving enough oxygen
Hypoxia- Cells are deprived
Anoxia- Complete loss of oxygen/blood
What negative outcomes occur due to hypoxia?
Decreases ATP
Failure of sodium-potassium pump, calcium pump
Hydropic degeneration –> Cellular swelling, membrane loses ability to regulate ion permeability
Reduced pH
Mitochondrial swelling
If not corrected cell will lyse
Reperfusion Injury
Rapid restoration of blood flow to ischemic tissue
Most damage occurs from mitochondrial dysfunction and subsequent free radical production
-Lipid peroxidation
-Alteration of DNA and proteins
Creation of Reactive Oxygen Species
Reduction of molecular oxygen creates superoxide O2-
Superoxide Dismutase creates H2O2
Hydrogen peroxide can then be converted to water by Catalase or Glutathione (Antioxidant enzyme)
If hydrogen peroxide is not converted it will form a hydroxyl radical
Asphyxial Injuries
Failure to receive or use oxygen
Suffocation, strangulation, chemical (CO and propane), drowning
What causes negative affects due to Calcium? And how is this propagated in the cell?
Ischemia and toxins increase intracellular Calcium in the Mitochondria, and smooth ER
Results in activation of cellular enzymes
Phospholipase & protease –> Membrane damage
Endonuclease –> Nuclear damage
ATPase–> reduced ATP
How can aging injure the cell
Environmental and metabolic insults –> DNA damage –> Mutations
Telomere shortening –> Decreased cell replication –> cell loss
Abnormal protein homeostasis –> Decrease functional proteins –> Decrease cell functions
What can accumulate in a cell due to injury?
Lipid (triglycerides, cholesterol) Protein Glycogen Water Pigments (melanin bilirubin) Calcium (calcified heart valves) Urate (deposits in joints)
What are features of reversible cell injury?
Cellular swelling Fatty change (TG accumulate due to excessive intake, defective transport) Altered ion flux Mitochondrial swelling Pynknosis Membrane alterations (blebbing)
Features of Irreversible Cell Injury
Same as reversible plus…
Increased eosinophilia
Greater nuclear changes
Necrosis
Cell death associated with loss of cell integrity and leakage of cell contents eliciting local damage (inflammation)
Apoptosis
Cell activates enzymes that degrade clls DNA, nuclear and cytoplasmic proteins.
Membrane remains intact and is phagocytosed, no inflammation
Necrosis Nuclear changes
Pyknosis - Clumping of chromatin in the nucleus
Karyorrhexis- Fragmentation of nucleus
Karyolysis- Nuclear dissolution and chromatin lysis
Necrosis Calcification occurs because
Dead cells can be degraded into fatty acids which bind calcium, resulting in calcification
Dystrophic Calcification
Can happen in any necrosis
Likely to occur with atheroma with atherosclerosis (atrioventricular valves)
Metabolic Calcification
Consequence of hypercalcemia
Can occur in any tissue
Bone destruction, Vit D disorders, renal failure
Patterns of Tissue Necrosis (6)
Coagulative Necrosis Liquefactive Necrosis Caseous Necrosis Fat Necrosis Fibrinoid Necrosis Gangrenous Necrosis
Coagulative Necrosis occurs in? Result from?
Kidneys, heart, spleen, and adrenal gland
Protein denaturation
-Albumin changes into an opaque state
Liquefactive Necrosis
Neurons and glial cells
Hydrolytic enzymes
Caseous Necrosis
Combination of coagulative and liquefactive
Often enclosed in granuloma
Fat necrosis
Pancreas, breast, abdominal organs
Action of lipases (saponification)
FFA + Calcium
Fibrinoid Necrosis
Arteries
Complexes of antigens and antibodies are deposited on the walls of arteries
Gangrenous Necrosis, 2 types
Result of hypoxia, limbs not organs
Dry
-Insufficient blood, coagulative, dry, crusty, black
Wet
-Infection, liquefactive, cold, swollen, black, foul odor, pus
Apoptosis Cell Morphology
Cell shrinkage, pyknosis, apoptotic bodies
Causes of Apoptosis, Physiologic
During embryogenesis Hormone deprivation Proliferating populations End of usefulness Elimination of WBC
Causes of Apoptosis, Pathologic
DNA damage
Accrual of misfolded proteins
Injury from infection
Apoptosis, Intrinsic path
Mitochondrial, depends on mito membrane permeability
Injurious stimuli (loss of growth factor, DNA damage, protein misfolding)
BCL-2 inhibition –> BAX/BAK activation–> Cytochrome C leaves mito–>Caspases activated
Apoptosis, Extrinsic
Death receptor activated by TNF–> caspases
What do caspases cause?
Nuclear fragmentation
Cytoplasmic blebbing
Formation of apoptotic bodies
Phagocytosis of bodies
Autophagy
Lysosomal digestion of cells components
Survival in times of starvation
Excessive autophagy will activate apoptosis
