Cellular Accumulations Flashcards Preview

Foundations of Disease and Therapy > Cellular Accumulations > Flashcards

Flashcards in Cellular Accumulations Deck (29):

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

  1. Rheymatoid arthritis
  2. Crohn's Disease/UC
  3. 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

  1. Lipid peroxidation via free radical generation
  2. DNA damage from free radicals
  3. Stimulation of collagen synthesis 


Fates of Fatty Acids in liver

  1. Be oxidized to ketones
  2. Used to synthesize phospholipids
  3. Used to create cholesterol esters
  4. 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)


  1. Hypersecretion of PTH
  2. Destruction of Bone
  3. 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:

  1. Increased delivery of Fatty Acids (Ethalon or Diabetes)
  2. Decreased oxidation of Fatty Acids (hypoxia, ethanol, toxins)
  3. Reduced apoprotein availability (CCL4, malnutrition) 


Mechanisms of Amyloid formation

  1. Mutation of a gene resulting in abnormally folded protein
  2. Normal protein with intrinsic tendency to form amyloids given enough time or high enough concentration
  3. 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 

  1. Reye's Syndrome
  2. 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


  1. Fat necrosis
  2. Coagulation, caseous, or liquefactive necrosis
  3. Atherosclerosis 
  4. Aortic Stenosis (damaged heart valves)


Dialysis-Associated Amyloidosis

ß2-microglobulin accumulates because it does not pass through dialysis membrane

Results in destructive arthropathy 



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

  1. Diseases that cause ineffective hematopoesis or that require numerous transfusions (lots of RBC lysis)
  2. Genetic hemochromatosis involving too much uptake of iron 


Mechanisms of how substances accumulate within cells 

  1. Normal endogenous substance produced at increased rate
  2. Abnormal protein does not fold correctly so it accumulates
  3. Inactivating enzymes mutated so intermediates in a metabolic pathway accumulate 
  4. Injury or damage results in alteration of an intracellular constituent that cannot be removed 
  5. 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)