Cellular Accumulations Flashcards
Inherited form of AA Amyloidosis
Familial Mediterranean Fever
Can involve transthyretin (TTR) protein
Stain for hemosiderin
Prussian Blue
Bilirubin Accumulation
Yellow-green pigment that’s a result of heme breakdown
Causes Jaundice in skin and Icterus in Eye
Immune disorders and malignancies that cause AA Amyloidosis
- Rheymatoid arthritis
- Crohn’s Disease/UC
- Medullary Carcinoma of the Thyroid and Renal Cell Carcinoma
Protein Accumulation in Kidney
In some glomerular disease, large amounts of proteins are lost to “leaky” glomerular basement membrane
Protein accumulates as discrete pink droplets within cytoplasm of proximal tubule cells
Alpha-1-Antitrypsin Disease
Abnormally folded Alpha-1-Antitrypsin cannot be exported from endoplasmic reticulum in the liver, where it accumulates
Is required in the lung because it degrades elastase, so lack of this enzyme causes emphysema
Accumulation of cholesterol
Cells other than hepatocytes have no way of metabolizing cholesterol, so it is stored within them indefinitely
Macrophages ingeest large amounts of it and become Foamy
Foamy macrophages accumulate and cause atherosclerosis
Pathology caused by excess Iron
- Lipid peroxidation via free radical generation
- DNA damage from free radicals
- Stimulation of collagen synthesis
Fates of Fatty Acids in liver
- Be oxidized to ketones
- Used to synthesize phospholipids
- Used to create cholesterol esters
- Be esterified to create triglicerides
Metastatic Calcification:
Definition and Examples
High serum levels of calcium cause deposition of calcium salts in viable tissue
Typically accumulates in cells with alkaline environments because they secrete acid (gastric mucosa, kidneys)
Examples:
- Hypersecretion of PTH
- Destruction of Bone
- Vitamin D poisioning
Normal Iron Metabolism and Accumulation
Iron is first stored bound to ferritin within phagocytic cells, and later transported via transferrin in the blood to the liver
Digestion of ferritin forms hemosiderin, a brown intracellular pigment
There is no physioloigc way to rid the body of excess iron
Pathologic Calcification
Involves necrosis and irriversibly injured mitochondria
Accumulation of triglicerides can occur when:
- Increased delivery of Fatty Acids (Ethalon or Diabetes)
- Decreased oxidation of Fatty Acids (hypoxia, ethanol, toxins)
- Reduced apoprotein availability (CCL4, malnutrition)
Mechanisms of Amyloid formation
- Mutation of a gene resulting in abnormally folded protein
- Normal protein with intrinsic tendency to form amyloids given enough time or high enough concentration
- Abnormal metabolism of a normal protein
Accumulation of exogenous pigments
Carbon accumulation in dust cells
Tattoo ink ingested by macrophages in connective tissue
Mallory’s hyalin
Normal protein that’s damaged during injury, resulting in an undigestable accumulation within a cell
Usually Cytokeratin accumulations within liver cells due to ethanol poisioning
Lipofuscin Accumulation
Yellow-brown pigment composed of polymers of lipids and protein that is thought to be the final product of peroxidation
Found in aging myocardial cells and hepatocytes
AA Amyloidosis
Associated with acute and chronic inflammatory disorders
Characterized by accumulation of serum AA protein that is abnormally processed by macrophages and deposited as amyloid
Amyloid and Alzheimer’s
Amyloid deposits in cerebral plaques and blood vessels of Alzheimer’s patients form ß-amyloid protein
Diseases that have microvascualr fat deposits
- Reye’s Syndrome
- Fatty Liver of Pregnancy
Process of Copper metabolism
Excreted through the biliary system
Dystrophic Calcification
Definition and examples
Occurs with deposition of calcium in necrotic or chronically traumatized tissue
Associated with normal serum levels of calcium
Examples:
- Fat necrosis
- Coagulation, caseous, or liquefactive necrosis
- Atherosclerosis
- Aortic Stenosis (damaged heart valves)
Dialysis-Associated Amyloidosis
ß2-microglobulin accumulates because it does not pass through dialysis membrane
Results in destructive arthropathy
Amyloidosis
Abnormal proteinaceous deposit in extracelular space
Characterized by ß-Pleated sheats
Hyaline (or glassy-pink) stain on H&E
Diseases that lead to excess iron
- Diseases that cause ineffective hematopoesis or that require numerous transfusions (lots of RBC lysis)
- Genetic hemochromatosis involving too much uptake of iron
Mechanisms of how substances accumulate within cells
- Normal endogenous substance produced at increased rate
- Abnormal protein does not fold correctly so it accumulates
- Inactivating enzymes mutated so intermediates in a metabolic pathway accumulate
- Injury or damage results in alteration of an intracellular constituent that cannot be removed
- Abnormal exogenous substance is taken up and retained
Wilson’s Disease
Autosomal Recessive disorder marked by toxic levels of copper in liver and brain
Involves inability to excrete copper into canniculi resulting in accumulation into hepatocytes and regurgitation into circulation
Stain for Amyloid
Congo Red
AL Amyloidosis
Amyloid deposits formed by abnormal immunoglobin light chains
Associated with Multiple Myeloma (excess production of parts of antibodies)
Deposit in heart (where they restrict contraction) and glomeruli (where they allow protein leakage)
