Lecture - 4 –
Dr. Ali Zeki
General pathology
Intracellular accumulation:
Mechanisms:
1- Normal endogenous substance produced in normal or excess rate, but the
metabolic rate of the cell is inadequate to remove it ex. (fatty changes).
2- Normal or abnormal endogenous substance accumulate due to genetic or
acquired defect in metabolism , transport and excretion ex. (storage disease and ᾀanti-tripsin deficiency .
3- An abnormal exogenous substance is deposit and accumulate because the cell
has neither the enzymatic machinery to degrade this substance , nor the ability to
transport it into other sites, ex. (carbon particles accumulate in lung of the
smokers).
Lipid accumulation:
1- fatty changes (steatosis):
It refers to any abnormal accumulation of triglyceride within paranchymal cells, its
most often seen in the liver (hepatocytes), since this is the major organ involved in
fat metabolism, but it can also seen in heart, skeletal muscles and kidney. Mild
fatty changes do not affect cell function but more sever fatty changes can impair
cellular function.
Free fatty acid metabolism :
Any defects in metabolic pathway of fatty acid metabolism lead to fatty changes.
 Common causes of fatty changes are
1- Alcoholism, act as hepatotoxin affect normal metabolism of hepatocytes.
2- Protein malnutrition, decrease synthesis of apoprotein.
3- Diabetes mellitus, increase fatty acid mobilization.
4- Obesity.
6- Anoxia, inhibits fatty acid oxidation.
 Morphology of liver fatty changes:
Grossly:
mild fatty changes exhibit no gross morphological changes but sever type shows
increase in weight of the liver (3-6)kg, and liver appear bright yellowish in color,
soft and greasy in texture.
Microscopically:
Fatty accumulation appears as clear small vacuoles in the cytoplasm around the
nucleus of hepatocytes, as the process progresses, the vacuoles coalesce creating
clear spaces that push the nucleus to the periphery of the cell.
Stains: Oil – Red O (orange color).
Deferential diagnosis: a- glycogen stained Red with PAS.
b- water vacuoles take no stain.
2- cholesterol and cholesterol ester:
Intracellular accumulation of cholesterol seen in several pathologic process like:
Atherosclerosis: deposition of cholesterol within smooth muscle of aorta and large
arteries .
Xanthomas: accumulation of cholesterol in connective tissue of the skin.
Protein accumulation:
The intracellular accumulation of proteins appear as rounded, eosinophilic droplets
seen within the cytoplasm.
It can be seen in the following conditions:
1- Renal Tubules in patients with sever protein uria.
2- Accumulation of immunoglobulins in plasma cell seen as eosinophilic
inclusions called Russell bodies.
Glycogen accumulation:
Glycogen is energy store of the cell, intracellular deposits of glycogen seen in
patients with abnormality in either glucose or glycogen metabolism.
Glycogen accumulates within cells in a group of genetic diseases call glycogen
storage diseases.
Special stain used to demonstarate the glycogen deposits within the cell is PAS
(Periodic Acid Schiff Stain), this stain give rose to violet color to the glycogen.
Pigments accumulation:
1- Exogenousnts pigments:
carbon particles when inhaled it is phagocytosed by alveolar macrophages and
pass through lymphatic channels to regional LNs. This appear grossly as black
spots at the lung parenchyma ( anthracosis ), and also at hilar LNs.
In the heavy and prolonged exposure to carbon particles lung develop Emphysema
and fibroblastic reaction and this condition called ( coal worker's pneumoconiosis).
2- Endogenous pigments :
a- Lipofusin pigment :
its insoluble brownish – yellow granules intracellular material that accumulate in (
heart, liver and brain), it represent complex of lipid and protein result from
catalyzed peroxidation of poly unsaturated lipid of cell membranes
b- Melanin pigment:
its brown – black pigment produced by melanocytes which present mainly at the
epidermis of the skin, can accumulate in keratenocytes and also in dermal
maqcrophages.
c- Hemosiderin pigment:
it is a hemoglobin-derived granular pigment that is golden-yellow to brown in
color and accumulate in tissues when there is local or systemic excess of iron. local
excesses of iron result from hemorrhage and best example is the bruise at site of
trauma, while if the excess of iron is systemic like in hemolytic anemia and blood
transfusion, the hemosiderin is deposited in many organs and tissue leading to a
condition called hemosiderosis.
Pathological calcification :
it implies the abnormal deposition of calcium salts, and divided into the following:
1- Dystrophic calcification.
When deposition occur in areas of necrosis, and it occur in with normal serum
level of calcium, common example seen in atheromas of advanced atherosclerosis,
and cuspal calcification in congenital bicuspid aortic valve which result in aortic
stenosis in elderly.
2- Metastasis calcification
It can occur in normal tissue whenever there is hyperclacemia, so four major
causes of hypercalcemia are:
1- Hyperparathyroidism.
2- Bone destruction, (Paget disease, multiple myloma, and leukemia).
3- Vitamin D intoxication.
4- Renal failure.
Common sites for metastatic calcification are (kidney and lung).
Morphology :
 Gross appearance:
Fine white granules or clumps felt as gritty deposits.
 Microscopical appearance:
Intracellular and / or extracellular Basophilic, granular deposits.