Pathoma Chapter 1C Flashcards
Anemia leading to decreased O2 carrying capacity.
(decrease in RBC mass) PaO2 normal; SaO2 normal
Carbon monoxide poisoning
CO binds hemoglobin more avidly than oxygen
What is the PaO2 and SaO2 for carbon monoxide poisoning?
PaO2 normal; SaO2 decreased
Exposures for Carbon monoxide poisoning
include smoke from fires and exhaust from cars or gas heaters.
Classic finding for Carbon monoxide poisoning
cherry-red appearance of skin.
Early sign of exposure for Carbon monoxide poisoning
headache; significant exposure leads to coma and death.
What is Methemoglobinemia?
Iron in heme is oxidized to Fe3+ which cannot bind oxygen
PaO2 and SaO2 for Methemoglobinemia?
PaO2 normal; SaO2 decreased
Methemoglobinemia is Seen with?
oxidant stress (eg sulfa and nitrate drugs) or in newborns
Classic finding for Methemoglobinemia?
cyanosis with chocolate-colored blood.
Treatment for Methemoglobinemia?
intravenous methylene blue, which helps reduce Fe3+ back to Fe2+ state.
Hypoxia results in low ATP how?
impairs oxidative phosphorylation resulting in decreased ATP.
Low ATP disrupts what?
key cellular functions including 1. Na/K pump 2. Ca2+ pump 3. Aerobic glycolysis
Disruption of Na/K pump results in what?
sodium and water buildup in the cell
Disruption of Ca2+ pump results in what?
Ca2+ buildup in the cytosol of the cell
Disruption of Aerobic glycolysis results in what?
switch to anaerobic glycolysis. Lactic acid buildup results in low pH, which denatures proteins and precipitates DMA.
The hallmark of reversible injury is
cellular swelling.
Cytosol swelling results in
loss or microvilli and membrane blebbing.
Swelling of the rough endoplasmic reticulum (RER) results in
dissociation of ribosomes and decreased protein synthesis.
The hallmark of irreversible injury is
membrane damage.
Plasma membrane damage results in
- Cytosolic enzymes leaking into the serum {e.g cardiac troponin) 2. Additional calcium entering into the cell
Mitochondrial membrane damage results in
- Loss of the electron transport chain (inner mitochondrial membrane) 2. Cytochrome c leaking into cytosol (activates apoptosis)
Lysosome membrane damage results in
hydrolytic enzymes leaking into the cytosol, which in turn, are activated by the high intracellular calcium.
The end result of irreversible injury is
cell death.
The morphologic hallmark of cell death is
loss of the nucleus,
loss of the nucleus occurs via
nuclear condensation (pyknosis), fragmentation (karyorrhexis), and dissolution (karyolysis)
The two mechanisms of cell death are
necrosis and apoptosis.
NECROSIS
A. Death of large groups of cells followed by acute inflammation B. Due to some underlying pathologic process; never physiologic C. Divided into several types based on gross features
GROSS PATTERNS OF NECROSIS
A. Coagulative necrosis, B. liquefactive necrosis, C. Gangrenous necrosis D. Caseous necrosis E. Fat necrosis F. Fibrinoid necrosis
What is Coagulative necrosis?
Necrotic tissue that remains firm, cell shape and organ structure are preserved by coagulation of proteins, but the nucleus disappears
Coagulative necrosis is Characteristic of?
ischemic infarction of any organ except the brain
Area of infarcted tissue for Coagulative necrosis?
It is often wedge-shaped (pointing to focus of vascular occlusion) and pale.
What is Red infarction
arises if blood re-enters a loosely organized tissue (e.g. pulmonary or testicular infarction)
What is Liquefactive necrosis?
Necrotic tissue that becomes liquefied; enzymatic lysis of cells and protein results in liquefaction.
Liquefactive necrosis is Characteristic of?
Brain infarction, abscess, pancreatitis
What type of necrosis for brain infarction?
Liquefactive necrosis - Proteolytic enzymes from microglial cells liquefy the brain.
What type of necrosis for abscess?
Liquefactive necrosis - proteolytic enzymes from neutrophils liquefy tissue
What type of necrosis for pancreatitis?
Liquefactive necrosis - Proteolytic enzymes from pancreas liquefy parenchyma.
What is Gangrenous necrosis?
Coagulative necrosis that resembles mummified tissue (dry gangrene)
Gangrenous necrosis is characteristic of?
ischemia of lower limb and GI tract
What is wet gangrene?
superimposed infection of dead tissues occurs, then liquefactive necrosis ensues (wet gangrene).
What is Caseous necrosis?
Soft and friable necrotic tissue with cottage cheese-like appearance. It’s a combination of coagulative and liquefactive necrosis
What is caseous necrosis characteristic of?
granulomatous inflammation due to tuberculous or fungal infection
What is fat necrosis?
Necrotic adipose tissue with chalky-white appearance due to deposition of calcium
What is fat necrosis characteristic of?
trauma to fat (eg. breast) and pancreatitis-mediated damage of peripancreatic fat
Fat necrosis and saponification
Fatty acids released by trauma (eg to breast) or lipase (eg pancreatitis) join with calcium via a process called saponification which is an example of dystrophic calcification in which calcium deposits on dead tissues.
dystrophic calcification
the necrotic tissue acts as a nidus for calcification in the setting of normal serum calcium and phosphate
Dystrophic calcification vs metastatic calcification
high serum calcium or phosphate levels lead to calcium deposition in normal tissues (eg. hyperparathyroidism leading to nephrocalcinosis)
Fibrinoid necrosis
Necrotic damage to blood vessel wall, Leaking of proteins (including fibrin) into vessel wall results in bright pink staining of the wall microscopically
What is fibrinoid necrosis characteristic of?
malignant hypertension and vasculitis
What is apoptosis?
Energy (ATP)-dependent, genetically programmed cell death involving single cells or small groups of cells.
Examples of apoptosis include
- Endometrial shedding during menstrual cycle 2. Removal of cells during embryogenesis 3. CD8+ T cell-mediated killing of virally infected cells
Morphology of apoptosis
- Dying cell shrinks, leading cytoplasm to become more eosinophilic (pink) 2. Nucleus condenses (pyknosis) and fragments (karyorrhexis).
Apoptotic bodies
fall from the cell and are removed by macrophages; apoptosis is not followed by inflammation
Apoptosis is mediated by
caspases that activate proteases and endonucleases
Proteases
break down the cytoskeleton.
Endonucleases
break down DNA,
How are caspases activated?
- Intrinsic mitochondrial pathway 2. Extrinsic receptor-ligand pathway 3. Cytotoxic CD8+ Tcell-mediated pathway
What is the main molecule in the intrinsic mitochondrial pathway?
Bcl2
