cellular adaptations, cell injury, cell death Flashcards
cell adaptations
-hyperplasia- increase in NUMBER of cells
-hypertrophy- increase in SIZE of cells
-metaplasia- reversible change in which one differentiated cell is replaced by another cell type
-atrophy- reduction in size of organ d/t decrease in cell SIZE and NUMBER
reversible injury vs irreversible injury
-reversible- cell injury
-irreversible- necrosis/apoptosis
cell death
-IRREVERSIBLE
-necrosis- denaturation of cell proteins, leakage, nucleus disintegrates
-apoptosis
-irreversible mitochondrial dysfunction = necrosis
-diff types:
-coagulative- solid organs, cellular outline maintained, nucleus dissolves (kidney, heart, liver)
-localized area of coagulative necrosis = infarct
-liquefactive- brain
-fatty- breast, any fat
-caseous- (cheese)- granulomas, e.g. tuberculosis
-gangrene- extremities, bowel, non-specific -> wet and dry
-fibrinoid- usually in vasculitis, rheumatioid non-specific
hypertrophy
-!!increase in SIZE of cells -> increase in size of the organ
-NO new cells, just larger cells
-increased cellular protein production
-*Cells able to divide may also undergo hyperplasia (increase number of cells)
-Permanent cells (striated muscle, nerve tissue, cardiac muscle) can only undergo hypertrophy
-types:
-physiologic- uterus during pregnancy
-pathological- heart secondary to aortic stenosis or HTN
hyperplasia
-INCREASE IN NUMBER OF CELLS
-Physiologic hyperplasia – increase in glandular epithelium of breast at puberty and pregnancy
-also with enlargement (hypertrophy) of the glandular epithelial cells
-Pathologic hyperplasia- excessive hormones or growth factors acting on target cells
-endometrial hyperplasia
atrophy is secondary to
-Decrease in size of cells
-secondary to:
-DECREASED WORKLOAD
-DENERVATION
-DECREASED BLOOD FLOW
-DECREASED NUTRITION
-AGING (involution)
-PRESSURE
metaplasia
-can lead to cancer
-Replacement of one differentiated (mature, adult) cell by another cell type
-Reversible, but if persists can lead to dysplasia
-MC is columnar to squamous
-Results from either:
-reprogramming of local tissue stem cells OR
-colonization by differentiated cell populations from adjacent sites
-Stimulated by signals generated by cytokines, growth factors, and ECM components in cells’ environment
-ex- columnar epithelium -> makes mucus to protect against acid -> squamous protects
metaplasia examples chart
-columnar epithelium - produces mucus to protect against acid
-squamous is protective
- Barrett’s esophagus
- Muscles in a body builder
- Enlarged heart from aortic stenosis
- Post-menopausal uterus lining
-A. Physiologic hypertrophy
-B. Pathologic hypertrophy
-C. Atrophy
-D. Metaplasia
-1. D
-2. A
-3. B
-4. C
-A. Physiologic hypertrophy
-B. Pathologic hypertrophy
-C. Atrophy
-D. Metaplasia
what causes cell injury/death
-1. Hypoxia: reducing aerobic oxidative respiration
-What causes hypoxia?
-reduced blood flow (ischemia)
-low oxygenation of blood from cardiorespiratory failure
-decreased oxygen-carrying capacity (anemia, carbon monoxide poisoning and severe blood loss)
-2. Physical Agents (temperature (burns and deep cold), sudden changes in atmospheric pressure, radiation, electric shock)
-Chemical Agents and Drugs
-Infectious Agents
-Immunologic Reactions
-Genetic Abnormalities
-Nutritional Imbalances
reversible changes
-Ischemia
-REDUCED oxidative phosphorylation
-ATP depletion/ loss or reduction of Na+/K+ pump.
-Cellular “SWELLING” -> edema
process of cell injury to cell death
-Damage to mitochondria -> decreased oxidative phosphorylation and ATP
-Reduced Na/K -> swelling (reversible)
-Increase anaerobic glycolysis -> Decrease in protein synthesis
-!!Failure of CA pump—-Ca enters cell causing membrane and nuclear damage by activating phospholipases, proteases, endonuclease, and ATPases
-Denaturation of intracellular proteins, enzymatic digestion of cell, contents leak out and elicit inflammation
-irreversible mitochondrial dysfunction = necrosis
!coagulative necorsis
-more common bc it happens in solid organs (anything with solid wall too)
-Cell outlines preserved -> but nucleus disappears!
-Increased eosinophilia (pink) seen at first because of denatured cytoplasmic proteins
-Local area of coagulative necrosis – infarct!
-Heart, kidney, solid organs
liquefactive necrosis
-brain
-Digestion of dead cells resulting in liquid, viscous mass
-Occurs in abscesses (bacteria)
-Neutrophils release lysosomal enzymes -> digest -> protein degradation
gangrene necrosis
-Not specific pattern of cell death, but term commonly used in clinical practice
-Ex: limb, generally lower leg, that has lost its blood supply and has undergone necrosis (typically coagulative necrosis) involving multiple tissue planes
-When its a bacterial infection -> more liquefactive necrosis because of degradative enzymes in bacteria and attracted leukocytes (wet gangrene)
fibrinoid necrosis
-Special form of vascular damage usually seen in immune reactions!! involving blood vessels
-Usually when complexes of antigens and antibodies are deposited in the walls of arteries
-!!Deposits of these immune complexes, along with plasma proteins that has leaked out of vessels, result in -> bright pink and amorphous appearance in H&E stains called “fibrinoid” (fibrin-like) by pathologists!
caseous necrosis
-TB
-Caseous (cheeselike) - friable white appearance of area of necrosis
-Histology shows necrotizing granulomas
fatty necrosis
-destruction of fat
-Example: Acute pancreatitis
-pancreatic enzymes leak out from acinar cells
-fatty acids combine with Ca (saponification) creating insoluble salts which appear as chalky-white area
-can be caused by Infections, viruses, trauma, ischemia and toxins -> damage pancreas causing enzymes to be released
-Breast tissues can also have fat necrosis triggered by trauma
-Gross appearance: soft chalky-white area on the pancreas.
-Microscopic. Anucleated adipocytes with pinker cytoplasm containing amorphous mass of necrotic material; may see inflammation
- Heart Ischemia
- Stroke
- Reversible injury
- Irreversible injury
- Infarct
A. Necrosis
B. Swelling
C. Coagulative necrosis
D. Nucleus disintegration
E. Liquefactive necrosis
-1. C
-2. E
-3. B
-4. A
-5. A or C
A. Necrosis
B. Swelling
C. Coagulative necrosis
D. Nucleus disintegration
E. Liquefactive necrosis
apoptosis vs necrosis
-APOPTOSIS (“normal” death) -> NORMAL
-can be pathologic OR normal
-ATP needed
-membrane integrity sustained -> little leakage -> NO INFLAMMATION
-NECROSIS (“premature” or “untimely” death due to “causes”) -> PATHOLOGIC
-always pathologic
-no ATP
-leaks debris -> inflammation
-many cells involved in area
apoptosis
-2 pathways converge on caspase activation: the mitochondrial (intrinsic) pathway and death receptor pathway – the initiation phase of apoptosis
-MORPHOLOGY:
-DEcrease in cell size, i.e., shrinkage
-INcrease in chromatin concentration -> hyperchromasia, pyknosis -> karyorhexis -> karyolysis
-INcrease in membrane “blebs”
-Phagocytosis
-BIOCHEMISTRY:
-Protein Digestion (Caspases)
-DNA breakdown
-Phagocytic Recognition
normal vs pathologic apoptosis
-NORMAL:
-Embryogenesis- webs on fingers
-Hormonal “Involution”- menstrual cycle
-Cell population control, e.g., “crypts”
-Post Inflammatory “Clean-up”
-Elimination of “HARMFUL” cells- tumor cells
-Cytotoxic T-Cells cleaning up
-PATHOLOGIC:
-“Toxic” effect on cells, e.g., chemicals, pathogens
-Duct obstruction
-Tumor cells
-Apoptosis/Necrosis spectrum
intracellular accumulations
-Lipids
-“Hyaline” = any “proteinaceous” pink “glassy” substance
-Glycogen
-Pigments (EX-ogenous, END-ogenous)
-Calcium
intracellular accumulations: lipids
-ALL lipids are yellow grossly and WASHED out (clear) microscopically
-cholesterol
-fatty liver -> MC due to alcohol, diabetes, and obesity
intracellular accumulations: pigments
-EXogenous- tattoo, anthracosis* (black stuff in lungs)
-ENDogenous- similar in appearance (hemosiderin, melanin, lipofucsin, bile),they are all golden yellowish brown on “routine” Hematoxylin & Eosin (H&E) stains
intracellular accumulations: lipofuscin
-finely granular yellow-brown pigment granules composed of lipid-containing residues of lysosomal digestion.
-“wear and tear” pigment
-pigment of aging
-cells getting old
-Commonly found in the:
-liver
-kidney
-heart muscle
-retina
-adrenals
-nerve cells
-ganglion cells
intracellular accumulations: pathologic calcification
-Dystrophic Calcification:
-Normal serum calcium but Ca deposits in areas of necrosis
-Calcium can be intracellular, extracellular or both
-Calcium deposition on abnormal tissue
-Metastatic Calcification
-Normal tissue, hypercalcemia is usually present
-No specific relationship to malignancy
-4 major causes
-(1) hyperparathyroidism
-(2) bone destruction (e.g. tumors)
-(3) Vitamin D disorders
-(4) renal failure
-Seen especially in kidney, lung, gastric mucosa
Apoptosis does not elicit inflammation.
However, what happens when a cell becomes necrotic?
inflammation!