104 terms

3: Pathology

1-56: Cell Injury 57-69: Cell Adaptation 70-104: Inflammation
STUDY
PLAY
What are the four aspects of disease? Which is the most important?
etiology
pathogenesis
morphology
clinical significance*
hypertrophy
increase in size
hyperplasia
increase in number
atrophy
loss of size and function
metaplasia
change of tissue type
ischemia
loss of blood flow
hypoxia
loss of oxygenation
apoptosis
programmed cell death
necrosis
series of changes that accompany cell death, largely from degradative action of enzymes on lethally injured cells
pinocytosis
endocytosis of small particles
phagocytosis
engulfing of solid particles
heterophagy
degradation of extracellular components
autophagy
degradation of own compartments through lysosomes
Swelling of ER and clumping of chromatin are typically considered [reversible/irreversible] damage.
reversible
Is it possible to have hypoxia without ischemia?
yes: anemia, CO poisoning, pneumonia, etc.
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
-necrosis
Swollen ER is a result of:
active ionic transport failure
What is hydropic degeneration?
a reversible condition in which cells have become swollen with fluid
What are two major sites for calcifications to occur?
blood vessels, breasts
What other cell is typically present during cellular necrosis?
PMN
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?
SOD
glutathione peroxidase
Vitamin C
catalase
pyknosis
irreversible chromatin condensation
karyorrhexis
destructive fragmentation of nucleus
karyolysis
complete dissolution of chromatin matter
Denaturation is associated with ____ necrosis
coagulative
Enzymatic degradation is associated with ____ necrosis
liquefaction
What causes eosinophilic changes within a cell?
binding of eosin by denatured proteins
loss of glycogen
membrane disruption
debris
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
-infarction
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
-TB
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
-immunologic
What can fat necrosis cause to form within a breast?
calcifications
What genes are activated to control apoptosis?
Bcl-2, c-myc, p53
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?
toxin/drug exposure
increased tolerance
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 happens in Chediak-Higashi syndrome?
microtubule defect resulting in decrease in phagocytosis
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?
fat
cholesterol
proteins
glycogen
pigments
What disease is associated with rapid steatosis, causing fat to accumulate within fat?
Reye's syndrome
Accumulation of cholesterol can lead to groups of what type of cells? What can these cells cause?
-foam cells (macrophages filled with lipids)
-atherosclerosis, xanthomas
Of all the accumulations, which is most common?
cholesterol
Where does proteinuria tend to have accumulations?
proximal tubular epithelial cells
What type of accumulation causes lung tissue to turn black?
anthracosis - carbon stains
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
-macrophages
-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 is the most common cause of hypercalcemia?
primary hyperparathyroidism
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?
-Congo red
-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 are some examples of physiologic hyperplasia? How is it induced?
breast, uterus; hormones
What is compensatory hyperplasia?
regeneration of cells to replace damaged cells, as in after a partial hepatectomy
What is an example of virus that induces hyperplasia?
papillomavirus in cervical cancer
What is an example of physiologic hypertrophy?
uterus during pregnancy
Hypertrophy results as a response to:
increased functional demand
Atrophy results as a response to:
decreased workload, loss of innervation, diminished blood supply, inadequate nutrition, aging
What is metaplasia? Is it reversible?
change in which one cell type is replaced by another
yes
In which patients will bronchial squamous metaplasia occur?
smokers
Metaplasia is a stepping stone to these two more sinister types of cell growth:
dysplasia, neoplasia
What is dysplasia?
growth of morphologically different cells due to atypical cytologic alterations
What is a form of dysplasia often found along mucus membranes of habitual tobacco users?
leukoplakia
What three things occur during chronic inflammation?
active inflammation
tissue destruction
attempts at repair
What are the 5 signs of acute inflammation?
calor
rubor
tumor
dolor
functio laesa
What is the "triple response of Lewis"?
red line, wheal, flare
In which type of vessel does vascular permeability occur?
venule
In which type of vessel does vasodilation occur?
arteriole
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?
selectins
integrins
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?
E-endothelial
L-leukocyte
P-platelets
Adhesion during leukocyte migration is mediated by these two proteins:
ICAM-1, VCAM-1
What two proteins mediate diapedesis of leukocytes between endothelial cells?
PECAM-1, ICAM-1
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 is defective in people with chronic granulomatous disease?
NADPH oxidase
What three major systems interact with each other to control inflammation?
complements
kinins
coagulation/fibrinolysis
How do C5a and C3a affect vascular dilation and permeability?
increase them, similar to histamine
Which AA metabolism pathway does C5a activate?
lipoxygenase
Which complement proteins trigger mast cells to release histamine?
C3a, C5a, C4a
What does DAF do? Inability to express DAF results in:
destabilizes convertases in the complement system; paroxysmal nocturnal hemoglobinuria
C1 inhibitor deficiency causes:
hereditary angioneurotic edema
What 4 things does bradykinin cause in inflammation?
increased vascular permeability
arteriolar dilatation
smooth muscle contraction
pain on injection
What four things activate Factor XII?
plasmin
kallikrein
collagen & basement membrane
activated platelets
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
Lipoxygenase is responsible for the creation of which 3 major products?
5-HETE
5-HPETE
leukotrienes
Cyclooxygenase is responsible for the creation of which 3 major products?
prostaglandins
prostacyclin
thromboxane A2
Of lipooxygenase/cyclooxygenase, which is related to:
platelet aggregation
vasodilation/constriction
spasm (vase, broncho)
p: cyc
v/c: cyc
s: lipo
What molecule is 100-100,000x stronger than histamine in increasing permeability and vasodilation?
plate-activating factor
PAF enhances leukocyte ... :
adhesion, chemotaxis, degranulation, and oxidative burst
Cytokine production:
macrophages
T-cells
m: IL-1, TNFa
T: TNFb
Which cytokines are responsible for acute phase responses?
IL-1, TNF, IL-6
What is the cause of cachexia in cancer?
increased amounts of TNFa
What are some major effector functions of NO?
vasodilation
decreased platelet aggregation
mast cell inhibition
decreased regulation of leukocyte recruitment
Chronic inflammation is characterized by the infiltration of what type of cell?
mononuclear leukocytes