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Abnormal Intracellular

Depositions
Prof. Ung
Pathology
Year 2
Pathways of abnormal intracellular
accumulations

1. A normal substance is produced at a normal or an


increased rate, but the metabolic rate is inadequate
to remove it.
 E.g. fatty change in the liver
2. A normal or an abnormal endogenous substance
accumulates because of genetic or acquired defects
in its folding, packaging, transport, or secretion.
 E.g. alpha-1-trypsin deficiency
3. An inherited defect in an enzyme may result in
failure to degrade a metabolite.
 E.g. storage diseases
4. An abnormal exogenous substance is deposited
and accumulates because the cell has neither the
enzymatic machinery to degrade the substance not
the ability to transport it to other sites.
 Accumulations of carbon particles
Fatty change

• Fatty change refers to any abnormal


accumulation of triglycerides within parenchymal
cells.
• Sites : • Causes
I. The liver I. Toxins
II. Heart II. Protein malnutrition
III. Diabetes mellitus
III. Skeletal muscle IV. Obesity
IV. Kidney V. Anoxia

• Most common cause:


I. Alcohol abuse
II. Diabetes associated with obesity
Mechanisms

I. Hepatotoxins ( e.g.. alcohol ) alter


mitochondrial and SER function and thus inhibit
fatty acid oxidation.
II. Carbon tetrachloride and protein malnutrition
decrease the synthesis of apoprotein.
III. Anoxia inhibits fatty acid oxidation
IV. Starvation increases fatty acid mobilization from
peripheral stores.
Morphology

Liver
• Gross- enlarge, 3 to 6 kg, bright, yellow , soft ,
greasy
• Microscopic- small fat vacuoles in the cytoplasm
around the nucleus,
• Later stage, the vacuoles coalesce to create
clear spaces that displace the nuleus to the cell
periphery
• Fatty cyst
• The significance of fatty change depends on the
cause and severity of the accumulation.
• When it may have no effect on cellular function.
• In the severe form, fatty change may precede
cell death.
• E.g. nonalcoholic steatohepatitis
Pigments
• Pigments are coloured substances that are either
exogenous, coming from outside the body, or
endogenous, synthesized within the body itself.

Exogenous pigment

• Most common- carbon


• Anthracosis
• Heavy accumulation can lead to
– emphysema
– coal workers’ pneumoconiosis
Endogenous pigments
• Lipofuscin
• Melanin
• Hemosiderin

Lipofuscin pigment

• Wear-and-tear pigment
• Insoluble brownish-yellow granular intracellular
material
• Heart, liver, brain
• Age or atrophy
Melanin
• Brown-black pigment produced in melanocytes
• Epidermis
• Screen against harmful UV radiation
Hemosiderin
• Hemoglobin-derived granular pigment
• Golden yellow to brown
• Local or systemic excess of iron
• Identified by the Prussian blue histochemical reaction
• Local excess
• E.g. common bruise
• Systemic excess
• E.g. hemosiderosis
Pathologic calcification

• It implies the abnormal deposition of calcium


salts, together with smaller amount of iron,
magnesium, and other minerals.
• Types :
• 1. Dystrophic calcification
• 2. Metastatic calcification
Dystrophic calcification

• Encountered in areas of necrosis of any type

• E.g. the atheromas of advanced atherosclerosis

• Insignificant past cell injury

• Cause of organ dysfunction

• E.g. the aortic valves_ causing aortic stenosis


Metastatic calcification

• Metastatic calcification can occur in normal tissues


whenever there is hypercalcemia.
• Major causes of hypercalcemia :
1. Increased secretion of parathyroid hormone
 E.g. primary parathyroid tumors
2. Destruction of bone due to the effects of accelerated
turnover, immobilization, or tumors
 E.g. Paget disease, multiple myeloma, leukaemia
3. Vitamin D-related disorders
 E.g. vitamin D intoxication, sarcoidosis
4. Renal failure
• Can occur widely throughout the body
• The interstitial tissues of the vasculature, kidneys,
lungs, and gastric mucosa
• Massive deposits-organ damage
• E.g. nephrocalcinosis