What are the four aspects of disease? Which is the most important?
series of changes that accompany cell death, largely from degradative action of enzymes on lethally injured cells
Swelling of ER and clumping of chromatin are typically considered [reversible/irreversible] damage.
How can ischemia affect a cell?
-decreased oxphos leads to decreased ATP
-dec. ATP leads to Na pump inaction, inc. glycolysis
-Na pump inaction leads to inc. cytosolic Na, inc. glycolysis leads to lactic acid buildup
-inc. cytosolic Na leads to swelling, activation of -ases; lactic acid buildup decreases cellular pH, inactivating proteins
-ribosomes detach, chromatin clumps up, cell membrane blebs
How does free radical generation fit into necrosis?
-ROSs are sometimes a byproduct of oxphos
-with mitochondrial damage, ROSs become more numerous and can cause more damage, exacerbating any pathogenesis already stressing the cell
What molecules are important for free radical neutralization?
What causes eosinophilic changes within a cell?
binding of eosin by denatured proteins
loss of glycogen
What is coagulative necrosis? Where and how does it occur? What injury is it characteristic of?
-component cells are dead but the basic tissue architecture is preserved for a while
-everywhere but the brain; hypoxic death of tissue
What is liquefactive necrosis? What injury is it characteristic of?
-area of digested tissue due to enzymes of leukoctyes and inflammatory cells
-bacterial, fungal infx; hypoxic death in the brain
What is caseous necrosis? What disease is it associated with?
-cheesy consistency substance produced by fragmented or lysed cells within the core of a granuloma
What are the characteristics of "gangrenous" necrosis?
combination of coagulation and liquefaction necrosis
What is fat necrosis? What does it typically result from?
-focal areas of fat destruction
-acute pancreatitis (pancreatic lipases and enzymes leak from the pancreas)
What is fibrinoid necrosis? What reaction is it associated with?
-deposits of ICs and fibrin (leaked from vascular cells) on the walls of arteries
How do heterophagy and autophagy differ?
h: lysosome fusion with endocytotic vacuole
a: lysosome fusion with self vacuole
What is lipofuscin? What does it signify?
-undegraded remnants of lipid peroxidation
-"wear and tear" of a cell
Increased ER is a result of what?
What does it mean for tolerance of drugs oxidized via the same system?
What can cause mitochondrial numbers to increase in cells? Decrease?
hypertrophy (need for more energy to perform action)
atrophy (less energy required to perform action)
What is a Mallory body? What is it composed of?
-an alcoholic hyaline
-cytoplasmic inclusion of liver cells
-composed of ubiquinated intermediate filaments
What are some major accumulations that can occur in cells?
What disease is associated with rapid steatosis, causing fat to accumulate within fat?
Accumulation of cholesterol can lead to groups of what type of cells? What can these cells cause?
-foam cells (macrophages filled with lipids)
What is hemosiderin? In which cell does it typically accumulate? When and why?
-excess iron becomes ferritin, ferritin complexes with itself (and denatured self) to form hemosiderin
-after a bruise/contusion, phagocytosis of RBCs and hemoglobin
What are siderophages? What do they indicate?
-heart failure cells
-left heart failure, pulmonary edema
How are siderophages created in heart failure?
-failing left ventricle cannot keep up with blood load from the pulmonary vein
-blood backs up, creating pressure on alveolar capillaries
-RBCs leak out and are ingested by alveolar macrophages, creating hemosiderin within the macrophages
How do dystrophic and metastatic calcification differ?
d: calcium deposition within dead or dying tissues; occurs in the absence of Ca metabolic derangements
m: deposition of Ca salts in normal tissues; reflects some derangement of Ca metabolism (hypercalcemia)
What is the pathogenesis leading to calcification of tissues?
-initiation: extracellular (vesicles of Ca); intracellular (mitos of dying cells)
-propagation: dependent on [Ca2+] and [PO4-]; crystal formation
-end-result: creating crystalline calcium phosphate
What are the targets of dystrophic and metastatic calcification?
d: atheromas, aging heart valves, TB lymph nodes
m: interstitium of all tissues
What stain is used to identify amyloid accumulations? What are they and what diseases are they associated with?
-eosinophilic glassy amorphous deposit from any cause
-variety of diseases: MM, RA, Alz, among others
What are labile cells? Examples?
cell that multiply continuously throughout life
epithelium and stem cells
What are stable cells? Examples?
cell that can respond and regenerate in response to damage, though in a limited fashion
parenchymal cells, SMCs
What is compensatory hyperplasia?
regeneration of cells to replace damaged cells, as in after a partial hepatectomy
Atrophy results as a response to:
decreased workload, loss of innervation, diminished blood supply, inadequate nutrition, aging
Metaplasia is a stepping stone to these two more sinister types of cell growth:
What is a form of dysplasia often found along mucus membranes of habitual tobacco users?
What three things occur during chronic inflammation?
attempts at repair
What is the difference between transudate and exudate?
t: low protein plasma ultrafiltrate, lower SG
e: high protein and cell debris, higher SG
In leukocyte rolling, what molecules select the type of leukocyte and what molecules move the leukocyte through the endothelium?
What is margination?
the accumulation and adhesion of leukocytes to the epithelial cells of blood vessel walls at the site of injury in early inflammation
Which selectins are involved in the rolling of leukocytes at the site of injury?
What are some examples of exogenous and endogenous chemotactic factors?
ex: soluble bacteria products
en: C5a, C3a, leukotriene B4, IL-8, PAF
How can leukocytes induce tissue injury?
-by releasing lysosomal enzymes into the extracellular space during phagocytosis
-release of ROSs and products of AA metabolism
What is LAD-1? What is it the absence of?
leukocyte adhesion deficiency-1; integrins, resulting in PMNs that can roll but do not stick
What causes Chediak-Higashi syndrome?
microtubule polymerization defect which leads to a decrease in phagocytosis
What three major systems interact with each other to control inflammation?
What does DAF do? Inability to express DAF results in:
destabilizes convertases in the complement system; paroxysmal nocturnal hemoglobinuria
What 4 things does bradykinin cause in inflammation?
increased vascular permeability
smooth muscle contraction
pain on injection
What four things activate Factor XII?
collagen & basement membrane
These two proteins antagonize each other in vasodilation/constriction and promotion/inhibition of platelet aggregation:
Which does which actions?
PGI2 - vasodilation, inhibits platelet aggregation
TXA2 - vasoconstriction, promotes platelet aggregation
Cyclooxygenase is responsible for the creation of which 3 major products?
Of lipooxygenase/cyclooxygenase, which is related to:
spasm (vase, broncho)
What molecule is 100-100,000x stronger than histamine in increasing permeability and vasodilation?
What are some major effector functions of NO?
decreased platelet aggregation
mast cell inhibition
decreased regulation of leukocyte recruitment