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181 Cards in this Set
- Front
- Back
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What is the term for programmed cell death?
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Apoptosis
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What does apoptosis require?
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- ATP
- Activation of cytosolic caspases |
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What are the morphologic characteristics of cells undergoing apoptosis?
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- Eosinophilic cytoplasm
- Cell shrinkage - Nuclear shrinkage (pyknosis) and basophilia - Membrane blebbing - Nuclear fragmentation (karyorrhexis) - Formation of apoptotic bodies (which are phagocytosed) |
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What is the term for nuclear shrinkage?
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Pyknosis
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What is the term for nuclear fragmentation?
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Karyorrhexis
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What is a sensitive indicator of apoptosis?
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DNA laddering
- During karyorrhexis (nuclear fragmentation), endonucleases cleave at internucleosomal regions - Yields 180-bp fragments |
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How does radiation therapy cause apoptosis? What cells are affected?
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- Radiation causes apoptosis of tumors and surrounding tissue via free radical formation and dsDNA breakage
- Rapidly dividing cells (eg, skin and GI mucosa) are very susceptible to radiation therapy induced apoptosis |
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What are the pathways that cause apoptosis?
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- Intrinsic pathway
- Extrinsic pathway: ligand receptor interactions (Fas-FasL) and immune cell (cytotoxic T-cell release of perforin and granzyme B) |
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What is the purpose of the intrinsic pathway of apoptosis? When is it used?
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Involved in tissue remodeling in embryogenesis
- Occurs when a regulating factor is withdrawn from a proliferating cell population (eg, ↓ IL-2 after completed immunologic reaction → apoptosis of proliferating effector cells) - Also after exposure to injurious stimuli (eg, radiation, toxins, hypoxia) |
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What happens during the Intrinsic Pathway of Apoptosis?
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- Changes in proportions of anti-apoptotic factors (Bcl-2) and pro-apoptotic factors (BAX and BAK)
- Leads to ↑ mitochondrial permeability - Cytochrome C released from mitochondria into cytoplasm - Cytochrome C activates cytosolic Caspases leading to cellular breakdown |
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What are the anti-apoptotic factors involved in the intrinsic pathway of apoptosis?
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Bcl-2
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What are the pro-apoptotic factors involved in the intrinsic pathway of apoptosis?
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BAX and BAK
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What is the action of Bcl-2?
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Anti-apoptotic
- Prevents cytochrome C release from mitochondria by binding to and inhibiting Apaf-1 - Apaf-1 normally induces the activation of Caspases - If Bcl-2 is overexpressed (eg, follicular lymphoma), then Apaf-1 is overly inhibited, leading to ↓ Caspase activation and tumorigenesis |
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What happens in the Fas pathway for apoptosis? What is its role?
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Extrinsic Pathway
- Fas-FasL interaction is necessary in thymic medullary negative selection - Fas is aka CD95 and when FasL binds, multiple Fas molecules coalesce, forming a binding site for a death domain containing adaptor protein FADD - FADD binds inactive Caspases, activating them, leading to cellular breakdown |
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What are the implications of mutations in Fas?
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Increases numbers of circulating self-reacting lymphocytes due to failure of clonal deletion (usually involved in thymic medullary negative selection)
*Basis of autoimmune disorders* |
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What is the molecular basis of autoimmune disorders?
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Defective Fas-FasL interaction (important for thymic medullary negative selection)
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What causes necrosis?
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Enzymatic degradation and protein denaturation of a cell resulting from exogenous injury
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What happens during necrosis?
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- Intracellular components leak
- Inflammation |
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How does apoptosis compare to necrosis?
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Both result in death of cell(s), but necrosis causes inflammation
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What are the types of necrosis?
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- Coagulative
- Liquefactive - Caseous - Fatty - Fibrinoid - Gangrenous |
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Which type of necrosis occurs in the heart, liver, and kidney? Characteristics?
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Coagulative Necrosis
- Occurs in tissues supplied by end-arteries - Increased cytoplasmic binding of acidophilic dye - Proteins denature first, followed by enzymatic degradation |
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Which type of necrosis occurs in the brain and bacterial abscesses? Characteristics?
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Liquefactive Necrosis
- Occurs in CNS due to high fat content - In contract to coagulative necrosis, enzymatic degradation due to release of lysosomal enzymes occurs before proteins denature |
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Which type of necrosis occurs with TB, systemic fungi, and Nocardia infections?
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Caseous Necrosis
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Which type of necrosis occurs in the pancreas and breast? Characteristics?
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Fatty Necrosis
- Enzymatic: pancreatitis - saponification - Non-enzymatic: breast trauma - Calcium deposits appear dark blue on staining |
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Which type of necrosis occurs in the vessels? Characteristics?
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Fibrinoid Necrosis
- Vasculitides (eg, Henoch-Schönlein purpura, Churg-Strauss syndrome) - Malignant hypertension - Amorphous and pink on H&E |
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Which type of necrosis occurs in the limbs and GI tract? Characteristics?
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Gangrenous Necrosis
- Dry (ischemic coagulative) - Wet (infection) |
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What are the characteristics of Coagulative Necrosis?
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- Heart liver, kidney (occurs in tissues supplied by end-arteries
- Increased cytoplasmic binding of acidophilic dye - Proteins denature first, followed by enzymatic degradation |
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What are the characteristics of Liquefactive Necrosis?
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- Brain and bacterial abscesses
- Occurs in CNS due to high fat content - Enzymatic degradation by release of lysosomal enzymes occurs before proteins denature |
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What are the causes of Caseous Necrosis?
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- TB
- Systemic fungi - Nocardia |
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What are the characteristics of Fatty Necrosis?
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- Enzymatic (pancreatitis - saponification)
- Non-enzymatic (eg, breast tissue) - Calcium deposits appear dark blue on staining |
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What are the characteristics of Fibrinoid Necrosis?
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- Vasculitides (eg, Henoch-Schönlein purpura, Churg-Strauss syndrome)
- Malignant hypertension - Amoprhous and pink on H&E |
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What are the characteristics of Gangrenous Necrosis?
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- Common in limbs and GI tract
- Dry (ischemic coagulative) - Wet (infection) |
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What are the characteristics of reversible cell injury?
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Reversible with O2
- ATP depletion - Cellular / mitochondrial swelling (↓ ATP → ↓ activity of Na+/K+ pumps) - Nuclear chromatin clumping - ↓ Glycogen - Fatty change - Ribosomal / polysomal detachment (↓ protein synthesis) - Membrane blebbing |
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What happens to the size of cells / mitochondria during reversible cell injury?
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Cellular / mitochondrial swelling (↓ ATP → ↓ activity of Na+/K+ pumps)
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What are the characteristics of irreversible cell injury?
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- Nuclear pyknosis, karyorrhexis, karyolysis
- Plasma membrane damage (degradation of membrane phospholipid) - Lysosomal rupture - Mitochondrial permeability / vacuolization; phosopholipid-containing amorphous densities within mitochondria (swelling alone is reversible) |
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Which organs are susceptible to hypoxia / ischemia and infarction?
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- Brain
- Heart - Kidney - Liver - Colon |
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Which areas of the brain are most susceptible to hypoxia / ischemia and infarction?
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Boundary / watershed areas
- ACA / MCA - MCA / PCA These areas receive dual blood supply from most distal branches of 2 arteries, which protects these areas from single-vessel focal blockage; however they are susceptible to ischemia from systemic hyperperfusion |
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Specifically, which cells are most susceptible to the effects of hypoxia in the brain?
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Hypoxic ischemic encephalopathy (HIE) affects:
- Pyramidal cells of hippocampus - Purkinje cells of cerebellum |
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Which area of the heart is most susceptible to hypoxia / ischemia and infarction?
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Subendocardium (LV)
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Which areas of the kidney are most susceptible to hypoxia / ischemia and infarction?
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- Straight segment of proximal tubule (medulla)
- Thick ascending limb (medulla) |
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Which area of the liver is most susceptible to hypoxia / ischemia and infarction?
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Area round central vein (zone III)
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Which areas of the colon are most susceptible to hypoxia / ischemia and infarction?
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- Splenic flexure
- Rectum These areas receive dual blood supply from most distal branches of 2 arteries, which protects these areas from single-vessel focal blockage; however they are susceptible to ischemia from systemic hyperperfusion |
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What causes reperfusion injury?
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Free radicals
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What are the types of infarcts?
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Red (left) vs Pale (right)
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What are the characteristics of "red infarcts"?
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- Red (hemorrhagic) infarcts occur in loose tissues with multiple blood supplies (left)
- Liver, lungs, intestine - Red = Reperfusion (injury is due to damage by free radicals) |
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What are the characteristics of "pale infarcts"?
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- Pale infarcts occur in solid tissues with a single blood supply (right)
- Heart, kidney, spleen |
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What is the first sign of shock?
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Tachycardia
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What is shock in the setting of DIC secondary to?
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Secondary to trauma - likely due to sepsis
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What are the types of shock?
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- Distributive
- Hypovolemic / cardiogenic |
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What type of shock occurs due to high-output failure?
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Distributive Shock
- ↓ TPR - ↑ CO - ↑ Venous Return |
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What type of shock occurs due to low-output failure?
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Hypovolemic / Cardiogenic Shock
- ↑ TPR - ↓ CO - ↓ Venous Return |
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What is the relative pulmonary capillary wedge pressure (PCWP) in the different types of shock?
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- Distributive: ↓
- Hypovolemic: ↓ - Cardiogenic: ↑ |
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What type of shock is associated with vasodilation? Symptoms associated with this?
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Distributive - warm, dry skin
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What type of shock is associated with vasoconstriction? Symptoms associated with this?
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Hypovolemic & Cardiogenic
- Cold, clammy patient |
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How do IV fluids affect distributive shock?
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Failure to ↑ BP with IV fluids
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How do IV fluids affect hypovolemic / cardiogenic shock?
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Blood pressure restored with IV fluids
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Which type of shock can not restore the BP with IV fluids?
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Distributive shock
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Which type of shock has a BP that can be restored by IV fluids?
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Hypovolemic / Cardiogenic shock
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What happens with atrophy?
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Reduction in the size and / or number of cells
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What can cause atrophy?
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- ↓ Endogenous hormones (eg, post menopausal ovaries)
- ↑ Exogenous hormones (eg, factitious thyrotoxicosis, steroid use) - ↓ Innervation (eg, motor neuron damage) - ↓ Blood flow / nutrients - ↓ Metabolic demand (eg, prolonged hospitalization, paralysis) - ↑ Pressure (eg, nephrolithiasis) - Occlusion of secretory ducts (eg, cystic fibrosis) |
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How can the levels of hormones lead to atrophy? Examples?
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- ↓ Endogenous hormones (eg, post-menopausal ovaries)
- ↑ Exogenous hormones (eg, factitious thyrotoxicosis, steroid use) |
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How can a change in innervation lead to atrophy? Example?
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↓ Innervation (eg, motor neuron damage)
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How can a change in blood flow / nutrients lead to atrophy?
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↓ Blood flow / nutrients
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How can a change in metabolic demand lead to atrophy? Examples?
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↓ Metabolic demand (eg, prolonged hospitalization or paralysis)
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How can a change in pressure lead to atrophy? Example?
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↑ Pressure (eg, nephrolithiasis)
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How can a change in secretory ducts lead to atrophy? Example?
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Occlusion of secretory ducts (eg, cystic fibrosis)
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What are the signs of inflammation?
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- Rubor (redness)
- Dolor (pain) - Calor (heat) - Tumor (swelling) - Functio laesa (loss of function) |
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What happens to the vascular component with inflammation?
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↑ Vascular permeability, vasodilation, and endothelial injury
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What happens to the cellular component with inflammation?
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Neutrophils extravasate from circulation to injured tissue to participate in inflammation through phagocytosis, degranulation, and inflammatory mediator release
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What are the effects of neutrophils in inflammation?
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- Phagocytosis
- Degranulation - Inflammatory mediator release |
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What mediates acute cellular inflammation?
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- Neutrophils
- Eosinophils - Antibodies |
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What is the time course of acute inflammation?
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Rapid onset (seconds to minutes) - lasts minutes to days
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What are the potential outcomes of acute inflammation?
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- Complete resolution
- Abscess formation - Progression to chronic inflammation |
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What mediates chronic cellular inflammation?
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- Mononuclear cells
- Fibroblasts |
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What characterizes chronic cellular inflammation?
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- Persistent destruction and repair
- Associated with blood vessel proliferation and fibrosis |
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What is a granuloma made of?
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Nodular collection of epithelioid macrophages and giant cells
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What are the potential outcomes of chronic inflammation?
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- Scarring
- Amyloidosis |
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What is the term for the process involving the cell body following axonal injury?
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Chromatolysis
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What is Chromatolysis?
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- Process involving the cell body following axonal injury
- Changes reflect ↑ protein synthesis in effort to repair damaged axon |
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What are the characteristics of Chromatolysis?
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- Round cellular swelling
- Displacement of nucleus to periphery - Dispersion of Nissl substance throughout cytoplasm |
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What are the types of "calcification"?
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- Dystrophic calcification
- Metastatic calcification |
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What is the term for calcium deposition in tissues secondary to necrosis?
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Dystrophic Calcification
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Where does dystrophic calcification occur?
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Tissues with necrosis
- Tends to be localized (eg, on heart valves) |
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What is dystrophic calcification associated with?
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- TB (lungs and pericardium)
- Liquefactive necrosis of chronic abscesses - Fat necrosis - Infarcts and thrombi - Schistosomiasis - Mönckeberg arteriolosclerosis - Congenital CMV + Toxoplasmosis - Psamomma bodies |
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What is the relationship of dystrophic calcification to the level of calcium in the serum?
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Not directly associated with hypercalcemia (ie, patients are usually normocalcemic)
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Where does metastatic calcification occur?
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Widespread (ie, diffuse and metastatic) deposition in normal tissue
- Predominantly in interstitial tissues of kidney, lungs, and gastric mucosa |
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What causes metastatic calcification?
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Deposits in normal tissue secondary to:
- Hypercalcemia (eg, primary hyperthyroidism, sarcoidosis, hypervitaminosis D) - High calcium-phosphate product (eg, chronic renal failure + secondary hyperthyroidism, long-term dialysis, calciphylaxis, warfarin) |
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What can cause hypercalcemia leading to metastatic calcification?
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- Primary hyperparathyroidism
- Sarcoidosis - Hypervitaminosis D |
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What can cause high calcium-phosphate product leading to metastatic calcification?
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- Chronic renal failure + secondary hyperparathyroidism
- Long-term dialysis - Calciphylaxis - Warfarin |
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What are the characteristics of the kidney, lungs, and gastric mucosa that favors metastatic calcification? How promotes deposition?
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- These tissues lose acid quickly
- ↑ pH favors deposition |
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What are the levels of calcium in patients with metastatic calcification?
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Patients are usually not normocalcemic
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What is the most common location for leukocyte extravasation?
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Post-capillary venules (sites of tissue injury and inflammation)
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What are the four steps of leukocyte extravasation?
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1. Margination and rolling
2. Tight-binding 3. Diapedesis 4. Migration |
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What mediates the first step of leukocyte extravasation?
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Margination and Rolling:
- E-selectin binds Sialyl-Lewis - P-selectin binds Sialyl-Lewis - GlyCAM-1, CD34 bind L-selectin |
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What mediates the second step of leukocyte extravasation, after margination and rolling?
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Tight-Binding
- ICAM-1 (CD54) binds CD11/18 integrins (LFA-1, Mac-1) - VCAM-1 (CD106) binds VLA-4 integrin |
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What mediates the third step of leukocyte extravasation, after tight-binding?
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Diapedesis - leukocyte travels between endothelial cells and exits blood vessel
- PECAM-1 (CD31) binds PECAM-1 (CD31) |
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What mediates the fourth step of leukocyte extravasation, after diapedesis?
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Migration - leukocyte travels through interstitium to site of injury or infection guided by chemotactic signals
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What chemotactic products are release in response to bacteria to stimulate leukocyte migration?
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- C5a
- IL-8 - LTB4 - Kallikrein - Platelet-actvating factor |
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What mediates margination and rolling in leukocyte extravasation?
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Vasculature / stroma:
- E-selectin - P-selectin - GlyCAM-1, CD34 Leukocyte: - Sialyl-Lewis - L-selectin |
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What mediates tight binding in leukocyte extravasation?
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Vasculature / stroma:
- ICAM-1 (CD54) - VCAM-1 (CD106) Leukocyte: - CD11/18 integrins (LFA-1, Mac-1) - VLA-4 integrin |
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What is the term for when a leukocyte travels between endothelial cells to exit a blood vessel?
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Diapedesis
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What mediates diapedesis in leukocyte extravasation?
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PECAM-1 (CD31) on both vasculature/stroma and leukocytes
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How do free radicals damage cells?
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- Lipid peroxidation
- Protein modification - DNA breakage |
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What can initiate free radical damage?
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- Radiation exposure (eg, cancer therapy)
- Metabolism of drugs (phase I) - Redox reactions - Nitric oxide - Transition metals - Leukocyte oxidative burst |
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What enzymes can eliminate free radicals?
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- Catalase
- Superoxide dismutase - Glutathione peroxidase |
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Besides enzymes, what else can eliminate free radicals?
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- Spontaneous decay
- Antioxidants (eg, vitamins A, C, and E) |
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What pathologies are caused by free radical injury?
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- Retinopathy of prematurity
- Bronchopulmonary dysplasia - Carbon tetrachloride, leading to liver necrosis (fatty change) - Acetaminophen overdose (fulminant hepatitis, renal papillary necrosis) - Iron overload (hemochromatosis) - Reperfusion injury (eg, superoxide), especially after thrombolytic therapy |
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What free radical damage is associated with prematurity?
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Retinopathy
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How can the lungs be affected by free radical damage?
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Bronchopulmonary Dysplasia
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What are the effects of carbon tetrachloride?
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Free radical damage → liver necrosis (fatty change)
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What are the free radical effects of acetaminophen overdose?
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Overdose → fulminant hepatitis and renal papillary necrosis
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What mediates reperfusion injury?
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Superoxide, especially after thrombolytic therapy
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What is the most common pulmonary complication after exposure to fire?
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Inhalation Injury:
- Inhalation of products of combustion (eg, carbon particles, toxic fumes) → chemical tracheobronchitis, edema, and pneumonia |
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How long does it take for wound healing to get a majority of the tensile strength back to the tissue? What percentage of tensile strength?
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Takes ~3 months following wound formation to get 70-80% of the tensile strength back (little additional strength will be regained after that)
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What are the pathologic types of scars?
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- Hypertrophic scars
- Keloid scars |
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Which type of scar has greater collagen synthesis?
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- Keloid Scars: ↑↑↑ collagen synthesis
- Hypertrophic Scars: ↑ collagen synthesis |
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What is the arrangement of collagen in hypertrophic vs keloid scars?
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- Hypertrophic: parallel collagen
- Keloid: disorganized collagen |
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What is the extent of a hypertrophic vs keloid scars?
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- Hypertrophic: confined to borders of original wound
- Keloid: extends beyond the borders of the original wound |
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Do hypertrophic scars tend to recur following resection? vs keloid scars?
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- Hypertrophic scars infrequently recur following resection
- Keloid scars frequently recur following resection |
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What types of scars are these? Characteristics?
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Keloid Scars
- ↑ collagen synthesis - Parallel collagen arrangement - Scar is confined to borders of original wound - Infrequently recurs following resection |
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What types of scars are these? Characteristics?
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Keloid Scars
- ↑↑↑ collagen synthesis - Disorganized collagen arrangement - Scar extends beyond the borders of the original wound - Frequently recurs following resection |
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Who is at higher risk for keloid scars?
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African-Americans
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What are the tissue mediators of wound healing?
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- PDGF
- FGF - EGF - TGF-β - Metalloproteinases |
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What is the source of PDGF? Function?
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PDGF is secreted by activated platelets and macrophages
- Induces vascular remodeling and smooth muscle cell migration - Stimulates fibroblast growth for collagen synthesis |
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What is the function of FGF?
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Stimulates all aspects of angiogenesis
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What is the function of EGF?
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Stimulates cell growth via tyrosine kinases (eg, EGFR as expressed by ERBB2)
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What is the function of TGF-β?
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- Angiogenesis
- Fibrosis - Cell cycle arrest |
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What is the function of metalloproteinases?
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Tissue remodeling
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What factor induces vascular remodeling and smooth muscle cell migration?
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PDGF (from activated platelets and macrophages)
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What factor stimulates fibroblast growth for collagen synthesis?
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PDGF (from activated platelets and macrophages)
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What factor stimulates all aspects of angiogenesis?
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FGF
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What factor stimulates cell growth via tyrosine kinases?
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EGF - via EGFR, as expressed by ERBB2
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What enzyme is involved in tissue remodeling?
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Metalloproteinases
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What are the phases of wound healing?
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1. Inflammatory (immediate)
2. Proliferative (2-3 days after wound) 3. Remodeling (1 week after wound) |
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What is the immediate phase of wound healing? Mediators?
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Inflammatory Phase
- Mediated by platelets, neutrophils, macrophages |
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What is the phase of wound healing that occurs 2-3 days after a wound? Mediators?
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Proliferative Phase
- Fibroblasts - Myofibroblasts - Endothelial cells - Keratinocytes - Macrophages |
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What is the phase of wound healing that occurs 1 week after a wound? Mediators?
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Remodeling Phase
- Fibroblasts |
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What are the characteristics of the inflammatory phase of wound healing?
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Immediately after wound:
- Clot formation - ↑ Vessel permeability and neutrophil migration into tissues - Macrophages clear debris 2 days later |
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What are the characteristics of the proliferative phase of wound healing?
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2-3 days after wound
- Deposition of granulation tissue and collagen - Angiogenesis - Epithelial cell proliferation - Dissolution of clot - Wound contraction (mediated by myofibroblasts) |
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What are the characteristics of the remodeling phase of wound healing?
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1 week after wound
- Type III collagen replaced by type I collagen - Increased tensile strength of tissue |
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What bugs/pathologies can cause granulomas?
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- Bartonella henselae (cat scratch)
- Berylliosis - Churg-Strauss syndrome - Crohn disease - Francisella tularensis - Fungal infections (eg, histoplasmosis, blastomycosis) - Granulomatosis with polyangiitis (Wegener) - Listeria monocytogenes (granulomatosis infantisepticemia) - M. leprae (leprosy; Hansen disease) - M. tuberculosis - Treponema pallidum (tertiary syphilis) - Sarcoidosis - Schistosomiasis |
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What mediates the formation of a granuloma?
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- Th1 cells secrete γ-interferon, activating macrophages
- Macrophages release TNF-α, which induces and maintains granuloma formation |
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What can the side effects of anti-TNF drugs be?
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Cause sequestering granulomas to breakdown, leading to disseminated disease
(TNF-α maintains granuloma formation) |
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Which mediator activates macrophages? Source?
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γ-Interferon from Th1 cells
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What mediator from macrophages induces and maintains granuloma formation?
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TNF-α
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What do you need to check for before starting anti-TNF therapy? Why?
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Latent Tuberculosis
- Anti-TNF drugs can cause sequestering granulomas to breakdown, leading to disseminated disease |
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Which is thicker/thinner: exudate or transudate?
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- Exudate (thick)
- Transudate (thin) |
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What are the contents of an exudate?
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- Cellular
- Protein rich |
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What are the contents of an transudate?
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- Hypocellular
- Protein-poor |
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What is the relative specific gravity in an exudate vs transudate?
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- Exudate: >1.020 (thick)
- Transudate: <1.012 (thin) |
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What can cause an exudate?
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- Lymphatic obstruction
- Inflammation / infection - Malignancy |
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What can cause a transudate?
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- ↑ Hydrostatic pressure (eg, CHF)
- ↓ Oncotic pressure (eg, cirrhosis) - Na+ retention |
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What is the Erythrocyte Sedimentation Rate a reflection of?
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- Products of inflammation (eg, fibrinogen) coat RBCs and cause aggregation
- When aggregated, RBCs fall at a faster rate within the test tube |
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What can cause increased ESR?
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- Most anemias
- Infections - Inflammation (eg, temporal arteritis) - Cancer (eg, multiple myeloma) - Pregnancy - Autoimmune disorders (eg, SLE) |
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What can cause decreased ESR?
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- Sickle cell (altered shape)
- Polycythemia (↑ RBCs "dilute" aggregation factors) - CHF (unknown) |
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What is one of the leading causes of fatality from toxicologic agents in children?
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Iron poisoning
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What is the mechanism of iron poisoning?
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Cell death due to peroxidation of membrane lipids
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What are the acute symptoms of iron poisoning?
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- Nausea
- Vomiting - Gastric bleeding - Lethargy |
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What are the chronic symptoms of iron poisoning?
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- Metabolic acidosis
- Scarring leading to GI obstruction |
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How do you treat a patient with iron poisoning?
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Chelation:
- IV deferoxamine - Oral deferasirox Dialysis |
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What is the term for the abnormal aggregation of proteins (or their fragments) into β-pleated sheet structures? Implications?
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Amyloidosis → damage and apoptosis
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What are the common types of Amyloidsosi?
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- AL (primary)
- AA (secondary) - Dialysis-related - Heritable - Age-related (senile) systemic - Organ specific |
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What causes AL (primary) amyloidosis? Associated with?
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- Deposition of proteins from Ig Light chains
- Can occur as a plasma cell disorder or associated with multiple myeloma |
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What are the extent of the effects of AL (primary) amyloidosis?
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Often affects multiple organ systems, including:
- Renal (nephrotic syndrome) - Cardiac (restrictive cardiomyopathy, arrhythmia) - Hematologic (easy bruising) - GI (hepatomegaly) - Neurologic (neuropathy) |
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What causes AA (secondary) amyloidosis? Associated with?
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Seen with chronic conditions:
- Rheumatoid arthritis - IBD - Spondyloarthropathy - Protracted infection Often multisystem |
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What is AA (secondary) amyloidosis composed of?
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Fibrils composed of serum Amyloid A
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What are the extent of the effects of AA (secondary) amyloidosis?
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Often multisystem involvement like AL amyloidosis
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How does dialysis relate to amyloidosis?
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Dialysis-Related Amyloidosis:
- Fibrils composed of β2-microglobulin in patients with ESRD and/or on long-term dialysis |
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How might dialysis-related amyloidosis present?
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Carpal tunnel syndrome
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What is the amyloidosis in patients on dialysis composed of?
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β2-microglobulin
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What are the characteristics of heritable amyloidosis? Cause?
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Heterogenous group of disorders
- Example is ATTR neurologic / cardiac amyloidosis due to transthyretin (TTR or prealbumin) gene mutation |
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What causes age-related (senile) systemic amyloidosis?
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Deposition of normal (wild-type) transthyretin (TTR) in myocardium and other sites
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How does the rate of cardiac dysfunction compare in age-related amyloidosis and AL amyloidosis?
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Age-related amyloidosis has a slower progression of cardiac dysfunction relative to AL amyloidosis
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What is the most important form of organ-specific amyloidosis? Cause?
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Alzheimer Disease
- Deposition of amyloid-β protein cleaved from amyloid precursor protein (APP) |
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What type of amyloidosis is associated with T2DM? Cause?
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Islet Amyloid Polypeptide (IAPP) - type of organ-specific amyloidosis
- Commonly seen in T2DM - Caused by deposition of amylin in pancreatic islets |
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What type of disease is caused by deposition of amylin in the pancreatic islets?
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Islet Amyloid Polypeptide (IAPP) - organ-specific amyloidosis commonly seen in patients with T2DM
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What does this image show?
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Amyloidosis:
- Congo red stain shows amyloid deposits within vessel walls |
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What does this image show?
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Amyloidosis
- Congo red stain shows apple green birefringence under polarized light |
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What is the name of the yellow-brown "wear and tear" pigment associated with normal aging?
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Lipofuscin
- Macrophages with granular yellow-brown pigment |
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What is the cause of Lipofuscin deposition in macrophages?
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Formed by oxidation and polymerization of auto-phagocytosed organellar membranes
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Where will you find Lipofuscin in an autopsy of an elderly person?
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- Heart
- Liver - Kidney - Eye - Other organs |
