Intracellular accumilations

Yodit Getahun, MD
Cellular accumilations
• Substances can accumulate in cells as a result of damage to the cell
• As a result of an intrinsic abnormality in metabolic function (e.g.
genetic disease)
• As a result of Inadequate removal of a normal substance
e.g. Fatty change
• As a result of deposition and accumulation of an abnormal exogenous
substance
e.g. carbon, Silica, and Asbestos
Cont’d
• Substances that commonly accumulate are
lipofuscin
calcium
protein
iron
fat, cholesterol, glycogen, and pigments
Lipofuscin
• Wear-and-tear pigment
• A product of lipid peroxidation, which accumulates in lysosomes as
the cell ages
• Most common organs where lipofuscin accumulates are the heart and
liver
• Causes brown discoloration to organ
• Microscopically:- Finely granular, yellow-brown pigment which often
surrounds the nucleus
Lipofuscin pigment
Calcium
• Two types :- metastatic calcification and dystrophic calcification
metastatic calcification:
• Patients who have hypercalcemia have deposition of the calcium
within normal or abnormal tissue
• Increased parathyroid hormone (PTH) by a parathyroid adenoma
or parathyroid gland hyperplasia
• Destruction of bone by tumors
• Vitamin D intoxication, or renal failure
• Sarcoidosis, where macrophages activate vitamin D precursor
cont’d
dystrophic calcification:
• Patients who have normal levels of calcium have deposition of the
calcium only within abnormal tissue, such as necrotic tissue

* Commonly affected by calcium accumulation: Vasculature, kidneys,

and lungs
* Gross morphology of calcium accumulation: Hard yellow nodules.
* Microscopic morphology of calcium accumulation: Chunky, smooth,
purple granules.
Dystrophic calcification of a tricuspid aortic valve
Protein
• Accumulations often involve intermediate filaments
• Mallory hyaline in the liver : associated with alchohol
• Neurofibrillary tangles seen in Alzheimer disease.
Fatty liver with Mallory hyaline
Iron
• Two forms of iron accumulation: Hemosiderosis and hemochromatosis
1. Hemosiderosis:
• Accumulation of iron in organs without resultant side effects
• The iron pigment is frequently within macrophages
• Hemosiderin is a term used for aggregates of ferritin micelles: stains
positive with a Prussian blue stain
Cont’d
2. Hemochromatosis
• Accumulation of iron in parenchymal cells resulting in side effects,
including congestive heart failure, diabetes mellitus (from damage to
the pancreas), and cirrhosis
• Hemochromatosis can be acquired or hereditary
• Most common organs affected are the liver, skin, pancreas, and heart
• Microscopically: Chunky, yellow-brown granules
Hemosiderin within Kupffer cells in the liver. The hemosiderosis in this patient resulted
from extravascular hemolysis.
Fat
• Accumulation of fat AKA steatosis
• Most common organs affected are the liver, kidney, heart, and skeletal
muscle.
• Gross : Yellow discoloration of an organ
• Microscopic morphology of steatosis: One or several clear vacuoles
within the cell.
• Steatosis can indicate reversible damage or may be the sign of an
intrinsic abnormality in fat metabolism
Steatosis of the liver
Cholesterol
• Mostly affects Blood vessels (by the process of atherosclerosis) or at
sites of hemorrhage
• Cholesterol accumulates within phagocytic cells
Glycogen
• Glycogen accumulates as part of glycogen storage disorders (genetic
diseases with a defect in enzymatic pathway of glycogen, such as
McArdle syndrome
• McArdle disease (GSD 5) is a rare, genetic muscle disorder. It results
from deficiency or absence of an enzyme called myophosphorylase, a
key substance that the muscles need to break down glycogen into
sugar (glucose) for energy
• The most common organs affected are liver and skeletal muscle
Pigments
■ Exogenous pigments:
• Tattoos and anthracotic pigment, which is carbonaceous debris from
urban dwelling or cigarette smoking
■ Endogenous pigments:
• Melanin : brown black pigment
• Bilirubin : major pigment in bile
Anthracosis of the lung
Jaundice = increased level of bilirubin
Cholestasis within a cirrhotic liver