Intracellular accumulation

Presenter Amon
Facilitator Prof Amos Mwakigonja
 Intracellular accumulation

• Under some circumstances cells may

accumulate abnormal amounts of various
substances, which may be harmless or
associated with varying degrees of injury.

• The substance may be located in the

cytoplasm, within organelles (typically
lysosomes).
• Accumulation may be transiently or
permanently
• Harmless Vs harmful
• Produced within the cell Vs mere storage
• Indicates cellular metabolic derangement.
• ↑↑Normal cellular constituents, abnormal
substances or Pigments
Normal cellular constituents:
– Water
– Lipids
– Proteins
– carbohydrates
Abnormal substances (endogenous or
exogenous
- Carbon particles
- Silica particles
 Mechanism
1. Normal/increased production of
endogenous substance but decreased
metabolism to remove it – fatty liver due to
accumulation of triglycerides, protein
droplets in renal tubule cell due to increased
reabsorption in case of proteinuria.
2. Normal/abnormal endogenous product due
to defect whether genetic or acquired- defect
in packaging , transport or secretion.
e.g. storage disease- defect in enzyme for lipid
metabolism.
 3. Accumulation of exogenous substance-
because the cell have no enzyme to degrade it
or ability to transport it.
- carbon particles, silica
 Steatosis (Fatty change)
• Abnormal accumulation of Triglycerides within
parenchymal cells.
• Often seen in the liver -major organ of
metabolism and other organs like heart,
skeletal muscles, kidneys etc..
• Causes of steatosis
– Protein malnutrition/ starvation
– DM
– Obesity `
– Alcohol (abuse)
– Anoxia
• Source of triglycerides in hepatocytes
– Free fat acids from adipose tissue
– Fat acids from diets
– Synthesis within hepatocytes
Liver- FA are esterified to triglycerides 
cholesterol, phospholipids or ketone bodies
Release of triglycerides from hepatocytes require
association with apoproteins.
↑↑ triglycerides may result from defect in this
pathway
• Alcohol induce mitochondrial and microsomal
functional defects.
• Protein malnutrition ↓↓ protein synthesis
• Anoxia=extreme form of hypoxia. inhibits fatty
acid oxidation
• Starvation ↑↑ mobilization from peripheral
tissues
• Morphology:
- Fatty change is often seen in liver and heart
- Organ appear large, yellow and soft
- Micro:
- starts as membrane bound vacuoles.
- Coalesce of vacuoles to form large clear space
which displacing nucleus to the peripheral.
 cholesterol
• Synthesis is tightly controlled
• Cell use cholesterol for synthesis of cell
membrane
• Cholesterol accumulation manifests as
intracellular vacuoles in several conditions;
Atherosclerosis-
– (smooth MS) in intimal of aorta and other large
blood vessels.
– Cell have foamy appearance (foamy cells)
 – Accumulation of foamy cells cholesterol
laden ateromas which are yellow in color
– Some cell rapture and release cholesterol
into extracellular space forming cholesterol
crystals.
Inflammation and necrosis: foamy MQs-
engulfed cholesterol from membrane of dead
cells.
 PROTEINS
• Appear as round eosinophilic vacuoles in the
cytoplasm.
• By EM may be fibrillar, amorphous or crystalline.
Reabsorption droplets in proximal renal tubules:
- assoc. with increased urine from the renal
glomerulus.
- Appear as pink hyaline droplets in the cytoplasm
- Metabolised and disappear when proteinuria
stops.
 GLYCOGEN
• Defects in glucose or glycogen metabolism
• Appear as clear vacuoles in the cell cytoplasm.
• Commonly found in:
– Epithelia cell of convoluted renal tubules in DM pt
– Genetic disorders – glycogen storage diseases
where there is defect in enzymes for break down
or synthesis of glycogen
 PIGMENTS
• Colored substances
• Categorized as endogenous or exogenous
Exogenous pigments
- Carbon or coal dust
- Carbon particles are trapped in alveoli 
engulfed  regional Ln
- Black coloration of lungs is called anthracosis
• Endogenous pigments
• Lipofuscin- insoluble pigment (wear and tear,
aging pigment)
– Polymers of lipid and phospholipids complexed with
protein
– Not injurious to the cell
– Seen in cells undergoing slow regressive changes
– Common in liver and heart of aging pts, pt with severe
malnutrition or cancer cachexia
• Melanin
• Brown-black pigment formed from oxidation of
tyrosin to dihydroxyphenylalanin by the enzyme
tyrosinase in melanocytes

• Hemosiderin- hemoglobin-derived golden yellow

to brown.
• Derived from stored iron
• Formed where there is excess iron
• Normally can be seen in bone marrow, liver
and spleen (all are engaged in active
breakdown of RBCs)
Reference;
1.Robbins basic pathology 9th edition.
2.Harsh Mohan textbook of pathology.