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Pathobio Exam 1
Set 2: Cellular Alterations 1 & 2
115
Pathology
Graduate
10/05/2011

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Term
def

Hyperplasia
Definition
increased number of cells => increased tissue volume
Term
What 3 stimuli can cause hyperplasia?
Definition
1) hormones
2) GF
3) cytokines
Term
What is the mechanism of cell proliferation in hyperplasia?
Definition
usually increased transcription of genes encoding GF & receptors and cell cycle promotors. Also, there's occasional recruitment of stem cells.
Term
What induces glandular epithelial cell proliferation in female breast in puberty & pregnancy?
Definition
hormones
Term
What induces smooth muscle cell proliferation in uterus in pregnancy?
Definition
hormones
Term
When might hyperplasia be compensatory?
Definition
Partial hepatectomy (regeneration of liver needed)
unilateral nephrectomy (enlargement of contralateral kidney)
Term
What causes the endometrium in the uterus undergo hyperplasia?
Definition
prolonged unopposed estrogen stimulation
Term
Where is hyperplasia seen in wound healing & repair?
Definition
in CT
Term
Where does HPV cause hyperplasia?
Definition
epithelium
Term
def

Hypertrophy
Definition
increased cell size due to increased synthesis of cellular components => increased tissue volume
Term
Can hypertrophy or hyperplasia been seen in non-mitotic cells?
Definition
hypertrophy only.

hyperplasia can only been seen in cells with mitotic capability.
Term
What 2 stimuli can cause hypertrophy?
Definition
1) hormones
2) increased workload
Term
Where is hypertrophy seen in pregnancy?
Definition
increased uterine smooth muscle cell size
Term
What causes hypertophy in skeletal muscle cells of weightlifters?
Definition
increased workload
Term
When is hypertrophy seen in cardiac myocytes?
Definition
increased workload due to hypertension or stenotic outflow valve
Term
What 2 signals cause hypertrophy in cardiac myocytes?
Definition
mechanical & trophic
Term
What does the heart do in response to increased workload?
Definition
increase transcription or re-express fetal genes to increase synthesis of proteins to increase cardiac function & decrease workload
Term
def

Atrophy
Definition
decreased cell size due to decreased cellular components => decreased tissue volume
Term
What 8 stimuli can cause atrophy?
Definition
1) decreased workload
2) denervation
3) decreased vascular supply
4) malnutrition
5) decreased hormonal stimuli
6) aging
7) compression
8) cytokines

note: some of these can occur simulaneously
Term
Why do we not have some of our embryologic structures as adults?
Definition
atrophy
Term
What in the postpartum mother atrophies?
Definition
uterus
Term
What in the postmenopausal female atrophies?
Definition
endometrium
Term
What can atrophy after a spinal cord trauma?
Definition
limb muscle
Term
What can cause cerebral atrophy?
Definition
decreased blood flow & aging
Term
What atrophies due to starvation (malnutrition)?
Definition
skeletal muscle
Term
How does atrophy occur?
Definition
increased destruction of cellular components by lysosomes & proteasomes => incrased autophagic vacuoles
Term
What may atrophy be accompanying?
Definition
apoptosis/necrosis => fatty infiltration
Term
def

Metaplasia
Definition
replacement of one mature cell type by another
Term
What stimuli initiates metaplasia?
Definition
chronic tissue trauma/irritation
Term
How does chronic tissue trauma/irritation cause metaplasia?
Definition
leads to signals by cytokines, GF & ECM components => transcriptional change => differentiation towards a new cell
Term
What epithelial metaplasia does cigarette smoke cause to the epithelium of the RT?
Definition
pseudostratified, ciliated, columnar epi => stratified squamous
Term
What epithelial metaplasia does gastroesophageal reflux cause to the epithelium of the lower esophagus?
Definition
stratified squamous => gastric & intestinal-type glandular epi.
Term
What CT metaplasia can be seen after trauma to skeletal muscle?
Definition
myosis ossificans
(skeletal muscle => bone)
Term
What are the 2 normal functions of lysosomes?
Definition
heterophagy
autophagy
Term
Which cells do most of the lysosomal heterophagy?
Definition
neutrophils & macrophages
Term
def

Heterophagy
Definition
endocytosis of extracellular maerial => fusion of lysosome to form phagolysosome => enzymatic degradation
Term
def

Autophagy
Definition
collection of injured or unnecessary intracellular material to vacuoles => fusion with lysosomes to form autophagolysosomes => enzymatic digestion
Term
What happens when a lysosome is functioning abnormally?
Definition
enzymatic dysfunction => excess accumulation of lysosomal contents & potential cellular injury
Term
What can lead to enhanced smooth ER metabolism?
Definition
chronic exposure to certain agents metabolized by smooth ER => increased smooth ER synthesis => enhanced metabolism
Term
What alterations can cellular mitochondria see?
Definition
Hypertrophy (increased #)
Atrophy (decreased #)
Genetic metabolic disease
Aquired disorder
Term
What 3 cellular components can have alterations in the cytoskeleton?
Definition
Microtubules
Thin Filaments
Intermediate Filaments
Term
Which of the cytoskeleton cellular components that can have alterations, which can occur both genetically or aquired?
Definition
Mirotubules & Intermediate filaments

(thin filament alterations are due to aquired alterations secondary to toxins)
Term
In what cellular reaction rate imbalances will there be an accumulation of normal endogenous substances?
Definition
if production/absorption rate > metabolic/removal rate
Term
In what cellular reaction defects will there be an accumulation of normal or abnormal endogenous substances?
Definition
alterted synthesis/metabolism/transport
Term
When what in the cell is lacking will there be an accumulation of abnormal exogenous substances?
Definition
lack of cellular metabolic/secretory pathways
Term
What is the liver lipid?
Definition
triglycerides
Term
What causes fatty deposits in the liver?
Definition
1) stravation => fatty acid uptake from adipose 2) protein malnutrition & CCl4 toxicity => decreased apoprotein synthesis => decreased lipoprotein export 3) damage due to alcholism, DM, obesity, hypoxia => triglyceride production/removal alterations
Term
How are triglycerides removed from the liver?
Definition
Added to apoproteins to form lipoproteins
Term
How are trigylcerides formed in the liver?
Definition
from a fatty acid precursor
Term
What are the 2 fates of fatty acids in the liver?
Definition
become triglycerides or catabolism (to ketones, phospholipids, or cholesterol)
Term
What gross changes are seen in a fatty liver(steatosis)?
Definition
enlarged, greasy & yellow
Term
Microscopically, what is seen in a steatotic liver in an H&E stain?
Definition
clear vesicular cytoplasmic vacuoles in the parenchymal cells
Term
Microscopically, what is seen in a steatotic liver in an oil red-O stain?
Definition
vacuoles stain red
Term
What gross change is seen in tissue with high cholesterol content?
Definition
yellow discoloration
Term
What microscopic change is seen in a tissue with excess cholesterol & cholesterol esters?
Definition
foam cells (round with clear bubbly cytoplasm)
Term
How do atherosclerotic plaques look microscopically?
Definition
clear clefts
Term
How do xanthomas due to hyperlipidemia look?
Definition
Masses that are often subcutaneous
Term
When is cholesterolosis in the subepithelium of the gallbladder seen?
Definition
with cholesterol-predominant gallstones
Term
How do protein deposits look microscopically?
Definition
variably-sized, pink, cytoplasmic globules
Term
What causes proteinuria?
Definition
increased protein reabsorption by the proximal renal tubular epithelial cells
Term
What causes Russell bodies is plasma?
Definition
increased Ig production
Term
What causes α1-antitrypsin protein in ER of hepatocytes?
Definition
mutations in the α1-antitrypsin gene => abnormal protein => decreased intracellular transport & secretion
Term
How does glycogen accumulation look microscopically in an H&E stain?
Definition
small, clear, cytoplasmic vacuoles
Term
How does glycogen accumulation look microscopically in a PAS stain?
Definition
vacuoles stain magenta
Term
Why does glycogen accumulate in DM?
Definition
abnormal glucose metabolism
Term
What inherited enzyme deficiencies can lead to glycogen accumulation?
Definition
glycogen storage diseases due to abnormal glycogen metabolism
Term
What type of pigments are unable to be degraded and persist in phagolysosomes?
Definition
exogenous pigments
Term
What 2 exogenous pigments can persist?
Definition
carbon
tattooing pigments
Term
What permanant pigment is seen due to carbon?
Definition
black granular pigment in the cytoplasm of macrophages
Term
def

Anthracosis
Definition
black granular pigment caused by carbon in the cytoplasm of macrophages in lungs & hilar lymph nodes
Term
How can carbon cause anthracosis?
Definition
inhalation of carbon dust => phagocytosis of alveolar macrophages
Term
How does tattoo pigment become permanent?
Definition
phagocytosis by dermal macrophages
Term
What are the 4 endogenous pigments that can accumulate?
Definition
lipofuscin
melanin
bilirubin
hemosiderin
Term
def

Lipofuscin
Definition
"wear & tear pigment"

indigestible phospholipis/protein remnant within autophagolysosomes
Term
What causes lipofuscin?
Definition
free radical injury => subcellular membrane lipid peroxidation
Term
What does lipofuscin look like microscopically?
Definition
perinuclear, finely granular, yellow-brown pigment with long-lived cells
Term
Where is lipofuscin especially prominent?
Definition
tissue atrophy
Term
What produces the brown-black pigment of melanin?
Definition
melanocytes
Term
How is bilirubin derived?
Definition
from the porphyrin ring of hemoglobin
Term
What are the 2 components that hemoglobin is broken down into?
Definition
Heme & globin
Term
What are the 2 components that heme is broken down into?
Definition
prophyrin ring & Fe
Term
What does the porphyrin ring break down into?
Definition
biliverdin (open chain) => unconjugated bilirubin
Term
Where is unconjugated bilirubin found?
Definition
blood plasma - tightly bound to albumin
Term
How do hepatocytes remove unconjugated bilirubin?
Definition
conjugate it to bilirubin glucuronides
Term
Where is unconjugated bilirubin excreted from?
Definition
biliary system
Term
Where is hemoglobin broken down into unconjugated bilirubin?
Definition
mononuclear phagocytes
Term
What happens to the aa of globin?
Definition
exported & recycled
Term
What happens to the Fe of heme?
Definition
transported to the bone marrow by transferrin & recycled
Term
Why must bilirubin be conjugated?
Definition
To become water-soluble for excretion
Term
How do serum unconjugated bilirubin levels increase?
Definition
1) increased RBS destruction => increased production
2) hepatocyte dysfunction => decreased bilirubin conjugation
Term
How does hepatocyte dysfunction occur?
Definition
genetic or acquired
Term
How do serum conjugated bilirubin levels increase?
Definition
1) hepatocyte dysfunction => decreased bilirubin secretion
2) cholestasis (biliary tract obstruction) => decrased excretion
Term
What can cause intrahepatic choestasis?
Definition
space-occupying leisons in the liver, destruction of intrahepatic bile ducts, cirrhosis, hepatic injury/swelling, medication
Term
What can cause extrahepatic cholestasis?
Definition
gallstones in biliary tract, internal compromise or external compression of common bile duct
Term
How do we test for cholestasis?
Definition
test for increased alkaline phosphatase (though conjugated bilirubin is also increased, it's a much less sensitive test)
Term
What does cholestasis look like mircoscopically?
Definition
smooth, green to golden-brown, globular pigment most commonly found in the liver
Term
def

Hemosiderin
Definition
intracellular, end-stage storage form of excess iron
Term
What are the 2 fates of intracellular iron?
Definition
Used or stored
Term
What does iron combine with prior to storage?
Definition
apoferritin
Term
What does iron combined with apoferritin form?
Definition
ferritin micelles
Term
How is hemosiderin formed?
Definition
Excess ferritin aggregates to form clusters & are engulfed by lysosomes & degraded
Term
What causes excess hemosiderin formation?
Definition
1) increased absorption of dietary iron
2) increased degredation of hemoglobin
3) parenteral iron excess
Term
Where does increased absorption of dietary iron accumulate?
Definition
parenchymal cells (esp. pancreas, liver, and heart)
Term
Where does increased degradation of hemoglobin accumulate?
Definition
mononuclear phagocytes (macrophages)
Term
What can cause increased degradation of hemoglobin?
Definition
localized breakdown of RBCs (hemorrhage)
systemic RBC destruction (hemolytic anemia)
Term
Where does parenteral iron excess accumulate?
Definition
macrophages
Term
What is seen microscopically in hemosiderin accumulation in an H&E stain?
Definition
coarsely granular, rusty-orange/brown, refractile, sytoplasmic pigment
Term
What is seen microscopically in hemosiderin accumulation in a Prussian Blue stain?
Definition
granules stain deep blue
Term
What 4 serum lab tests are there to assess iron status?
Definition
1) ferritin
2) iron
3) transferrin - iron-bindind capacity
4) % transferrin saturation
Term
Where is transferrin synthesized?
Definition
liver
Term
Function

Transferrin
Definition
binds/transports all plasma iron
Term
How do you calculate % trasnferrin saturation?
Definition
serum iron/IBC (iron-binding capacity)
Term
What % of the transferrin iron-binding sites are normally filled?
Definition
1/3
Term
How is iron excreted?
Definition
There is no physiological excretion mechanism
Term
Where does the majority (75%) of all iron absorbed per day go to?
Definition
bone marrow for RBC/hemoglobin synthesis
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