Goljan Cell Injury Flashcards

Terms Definitions
Uncouplers
thermogenin, dinitrophenol
Dysplasia
disordered cell growth
Permanent cells
cannot divide
BCL2 gene
antiapoptosis gene
BAX gene
apoptosis gene
MetHb Rx
IV methylene blue
CO and CN poisoning
house fires
Metaplasia/Hyperplasi in some cases may progress to...
dysplasia
Diffusion defect
Interstitial fibrosis, pulmonary edema
I-cell disease
defect in post-translational modification of lysosomal enzymes
What do phagolysosomes contain?
lysosomal enzymes
Lysosomal storage disease
↓ lysosomal enzymes
Caspases
group of cysteine proteases; activation induces apoptosis
Ubiquitin
marker for intermediate filament degradation
Fibrinoid necrosis
necrosis of immune-mediated dz
what is apoptosis
programed cell death
Best neutralizer of hydroxyl FRs
Vitamin C
Most common cause of fatty change
alcohol
CO poisoning
Normal Hb and PaO2, ↓SaO2
Hypoxia
inadequate oxidation of tissues (same definintion as shock)
define anemia
decrease in hemoglobin

no hypoxemia in a patient w/ anemia (PO2 and and O2 sat are normal, because breathing is normal), but don't carry much oxygen so get tissue hypoxia
Name the substrate of TG synthesis
Glycerol 3-Phosphate
O2 content
= (Hb x SaO2) + PaO2
Two metals that generate hydroxyl FRs?
Iron, Copper
Cellular features of apoptosis
deeply eosinophilic cytoplasm; pyknotic nucleus
Microscopic - indistinct outlines of cells w/in dead tissue and abscence of nuclie of cells, what type of necrosis is this?
coagulation necrosis
VHY
This type of calcification occurs in necrotic tissue?

Two good examples ae atherosclerotic plaques and calcification in the pancreas
Dystrophic calcification
(know all about these, ***VHY)
Causes of tissue hypoxia
Ischemia
hypoxemia
respiratory acidosis
ventilation defects
perfusion defects
diffusion defect
Hemoglobin related things
(anemia, CO, methemoglobin)
problems w/ cytocrome oxidase
uncoupling agents
left shifted curve
VHY
sluffing of the renal papilla and/or the inability to concentrate urine caused by acetaminophen toxicity is called? Mechanism was already described
analgesic nephropathy
VHY
Kids w/ respiratory distress syndrome can get what two types of injury from being given to much oxygen
Retinopathy of prematurity

bronchopulmonary dysplasia
VHY**
Where in the liver does acetaminophen toxicity occur
Central vein
VHY
what is the marker for intermediate filament degredation?
Ubiquitin
TP53 suppressor gene
guardian of the cell, promotes apoptosis if DNA is damaged
What happens to serum ferritin in iron deficiency anemia?
Hemorrhagic infarctions occure in which organs?
lung, small bowel, testicle
Features of atrophy
autophagic vacuoles, ↑ lipofuscin in cells
Pale infarctions occur in which organs?
heart, kidney, spleen
Womnen damages her pendulace breast from running, what type of necrosis?
Non-enzymatic fat necrosis
What are two important causes of hypercalcemia
primary hyperparathyroidism

Malignancy-induced hypercalcemia (medullary carcinoma of thryoid, MEN diseases)
Daltons law
sum of the partial pressueres of gasses must equal 760 (Oxygen, CO2 and Nitrogen)

Note: nitrogen is fixed
Drug that forms FRs in the liver and kidney?
Acetaminophen
Name two drugs that disrupt tubulin syntheisis in G₂ Phase
Etoposide, Bleomycin B
VHY**
In this disease hydrolytic enzymes are not marked w/ mannose 6-phosphate so they cannot be packeged into...

Symptoms of the disease include psycomotor disease and mental retardation
I-cell disease (inclusion cell), hydorlyitc enzymes are not put into LYSOSOMES (whichi s necessary to degrade complex substrates)...undigested substrates accumulate as large inclusion in the cytosol
VHY
In a nut shell what type of tissue/cell degeneration can result from tissue hypoxia?
Coagulation necrosis
VHY:
patient presenst w/ neutropenia, oculocutaneous albinism and is especially susceptible to staph infections, Dx

What is the pathophysiology
Patient has Chediak-Higashi syndrome (CHS)

Leukocyte defect in chemotaxis, degranulation and killing - (inability of the primary lysozome to fuse w/ phagosomes and produce secondary phaogolysosoemes which is how the bacteria are killed)
What does reperfusion injury involve?
superoxide FRs and ↑ cytosolic Ca2+
Features of Chédiak-Higashi syndrome
giant lysosomal granules ; defect in formation of phagolysosomes
What happens when you have a ventilation defect but you still have perfusion?
Intrapulmonary shunt is created
IF partial pressure of oxygen is decreased what will happen to oxygen saturation?
It has to decrease
what left shifts the oxygen saturation curve
CO, Methemoglobin, Fetal-hemoglobin, Alkalosis, dec. 2,3 BPG
Patient w/ hypoxemia, gave 100% oxygen and the PO2 did not increase what does it mean?
Intrapulmonary SHUNT (massive ventilation defect), if its a kid then hyaline membrane disease if adult ARDS
Mullerian inhibitory factor inhibits the formation of?

How does it do it?
uterus, cervix, upper 1/3 of vagina

Activates caspases tha cause apoptosis of these structures
VHY
How do signals initiate apoptosis?
activating caspases - group of cysteine proteases
VHY
ALL infarctions produce what type tissue necrosis?

VHY:
What is the one exception
Coagulation necrosis - gross manifestation secondary to occlusion of the vessel

an infection will cause the same thing to the brain.

Cerebral infarction produces liquifactive necrosis (hardley has any structure)- get a cystic space
VHY
This product is the ferritin degredation product?
Hemosiderin - gold brown pigment
What is liquifactive necrosis?

What is the mechanism
Necrotic tissue that softens and becomes liquified

Lysosomal enzymes of necrotic tissue or neutrophils is released intot he tissue
Wolfian duct structures, how are theses structures destroyed in the female
epididimis, vas deferens,

singal caspsases which tell the cell to undergo apoptosis
Segment of renal cortex most susceptible to hypoxia?
straight portion of the proximal tubule
VHY
pateint has fever, night sweats and weight loss?

Type of necrosis
TB - most common cause

Caseous necrosis
VHY
In this type of necrosis you have preservation of the structural outline of dead cells, what is the mechanism?
COAGULATION NECROSIS

Denaturing of enzymes and structural protiens (inactivation of enzymes that cause dissolution (autolysis))
VHY
what is the first and second most common cuase of infarction of the bowel
1.addhesions from previous surgery
2.indirect inguinal hernia sack (will be a small section of bowel trapped)
VHY
What is the usual cuase of liquifactive necrosis
Acute inflammation related to neutrophil infiltration.
VHY
Someone comes out of the Rocky Mountatains and he is cyanotic, they give 100% oxygen but cyanosis is not improved, what is the diagonis, primary and scondary treatment
Methemoglobinemia (assume he was drinking water in the mountains which has lots of nitrates and can cause methemoglobin to form)

IV - methylene blue

Secondary - vitamin C (reducing agent)
VHY
why are alcoholics so
suceptible to heat stroke on a hot day?

What is a common side effect of aspirin?
Beceause both are uncoupling agents they can produce hyperthermia
VHY
Left shift in oxygen curve (can't release oxygen),
dec. in oxygen saturation (can't bind oxygen)
inhibition of the cytocrome oxidase are all caused by?
Carbone monoxide poisioning

The whole system shuts down
VHY
CN and CO both inhibit?
Cytocrome oxidase (last enzyme in the oxidative phosphorylation pathway before transfers the electron to Oxygen)

3 C's all like each other
Abscence of a thymus and tetani is what disease?
Di-george (apoptosis destroyed the thymus)
VHY
What is the number one cause of fluminant hepatits caused by a drug, what is the MOA
Acetaminophen (tylenol) produces free radicals, this happens when the CYP 450 changes it upon metabolism
VHY
What drugs can cause methemoglobinemia?

What toxicities can these drugs have?
Dapsone - sulfa drug (used in treating leporasy, used on USMLE), other sulfa drugs (Trimethylprim-sulfamethaxazol, primaquine)

NITRO durgs (nitroglycerin, and nitroprusside)

Produce methemoglobin and can produce hemolytic anemia in people w/ G6PD.
Patinet presents w/ palpable purpura (e.g. Henoch-Schonlein purpura, would be of the lower extremity), what is the type of hypersensitivity , and type of necrosis?
That is a small vessel vasculitis, type III hypersensitivity

FIBRINOID NECROSIS
VHY
What is the pathogeneisis of how damage results from immune complexes
It deposits and activtes the compliment system - C5A is produced and attracts nuetrophils...they do the damage
second most common cause of hypoxia
HYPOXEMIA - causes hypoxia (not same as hypoxia), deals w/ partial pressure of oxygen, when decreased it is called hypoxemia
What is the most common cause of aortic stenosis and what is the mechanism
bicuspid aortic stenosis

they get damaged because two are doing the work of three and DYSTROPHIC CALCIFICATION OCCURS
MOST COMMON CAUSE OF TISsue HYPOXIA
Ischemia define:

Most common cause of ischemia
decrease in arterial blood flow (NOT VENOUS)

Thrombis to a muscular artery (myocardial infarction) -produces tissue hypoxia
↑ Ca2+ in cytosol d/t impaired calcium ATPase pump
"point of no return" ; activates enzymes
What happens to calcium during tissue hypoxia

*VHY* What happens w/ Ca2+ reentry into the mitochondria
calcium enters the cell (becasue pump is shut down to keep it out)

inc. in mitochondrial permeability w/ the release of CYTOCHROME C - ACTIVATES APOPTOSIS
VHY**
what is the most common cause of fatty change to the liver (cytosolic accumulation of TG's)?

What is the mechanism
Alcohol

Increase NADH in the cell during the metabolism of the alcohol, accelerates the conversion of DHAP to glycerol 3-phosphate which is the substrate for TG formation
How do the vinka alkaloids and colchicine interfere w/ the cell cycle
They bind to tubulin in microtubles preventing the assembly into mitotic spindles
How do acetaminophen and aspirin do to your
free radicals destroy the renal medulla (destroying renal tubules)

Aspirin - blocks vasodilator PGE2 made at the afferent arteriole

allowing angiotensin II to control blood flow to the kidney
What are two important causes of hyprphosphatemia
renal failure (thats why they need dialysis)

Primary hypothyroidism
VHY
What is the damage of the tissue in reperfusion injury caused by? (e.g. when using a thrombolytic to dissolve a clot and blood enters the tissue again)
Oxygen free radicals and cytoosolic Ca2+
What happens if you block the hepatic vein what happnes?

What happens to the liver if you block the portal vein?
Bud chiari syndrome - get congested liver

NOTHING
What enzyme is elevted in actue pancreatitis?

What is the underlying cause
amylase

LIPASE AS WELL, IT IS MORE SPECIFIC, it is activated by alcohol
What area of the liver is the most sensitive to oxygen deprivation?

This is the same area that is effected in acetaminophen toxicity because it combat oxygen free radicals w/ low levles of oxygen
CENTRAL VEIN (ZONE 3) you will see fatty change
What happens if you ↑ Alveolar PCO2 ?
= ↓ alveolar PO2 = ↓ PaO2 = ↓ SaO2
/ 85
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