Cell injury : Intracellular accumulations

Intracellular accumulations

1. Learning objectives Intracellular accumulations Fatty change Proteins Carbohydrates pigments

2. Intracellular accumulations

3. Intracellular accumulations Manifestation of metabolic derangement Accumulation may be transient & reversible or permanent. Effects: range from harmless to toxic Three categories

4. Accumulations of Constituents of Normal Cell metabolism Accumulations of Abnormal substances of abnormal Cell metabolism Accumulations of pigments Fats Proteins Carbohydrates Storage diseases Inborn errors of metabolism Endogenous pigments Exogenous pigments ACCUMULATIONS

5. Mechanisms of intracellular accumulations Alpha 1 antitrypsin deficiency

6. FATTY CHANGE Steatosis Fatty metamorphosis Intracellular accumulation of neutral fat(triglycerides) within the parenchymal cells. Common in liver Can occur in heart, skeletal muscle and kidneys.

7. Causes of fatty liver - ALCHOL ABUSE - DIABETES MELLITUS - OBESITY - PROTIEN MALNUTRION (starvation) -DRUGS/TOXINS -ANOXIA -PREGNANCY

8. Excessive entry of lipids into the liver Enhanced fatty acid synthesis by hepatocytes Decreased oxidation of fatty acids by mitochondria Increased esterification of fatty acids to triglycerides Decreased apoprotein synthesis Impaired lipoprotein excretion

9. Size Capsule Margins Color GROSS

10. Fat stains Can be demonstrated in fresh unfixed tissue by frozen section

11. Other Lipid Accumulations Cholesterol and cholesterol esters In atherosclerosis, cholesterol accumulates in smooth muscle cells and macrophages in the intima of arteries In hereditary hyperlipemia, cholesterol accumulates in macrophages, usually under the skin, forming tumor-like structures known as xanthomas

12. Intracellular Accumulation of Proteins

13. Excesses exceeding capacity of cell to metabolize Defects in protein folding , rendering them vulnerable to intracellular aggregation: Synthesis and secretion of excessive protein Nephrotic syndrome, defined by 24 hr. urine protein > 3.5 gms . manifested as cytoplasmic protein droplets in renal tubular epithelium Monoclonal immunoglobulins in serum and/or urine, due to bone marrow containing excess numbers of neoplastic plasma cells Eg : Myeloma Inherited metabolic disease, PiZZ genotype (1/7000 persons), resulting in < 10% normal plasma levels of alpha 1 - antitrypsin with accumulations of protein in hepatocytes

14. Intracellular Accumulation of Proteins Primarily in epithelial cells of the proximal convoluted tubules of the kidney and in plasma cells In the kidney , this excessive accumulation occurs subsequent to leakage of proteins from glomeruli into the glomerular filtrate Plasma cells – RUSSEL BODIES Alpha 1 antitrypsin deficiency Mallory body or alcholic hyalin

15. Intracellular Accumulation of Glycogen Glycogen Infiltration and Glycogen Storage Glycogen appears as clear vacuoles in the cytoplasm of cells Hyperglycemia Epithelial cells of the distal portion of the proximal convoluted tubule and in the loop of Henle in the kidney Leukocytes within inflamed or necrotic tissue Liver Cardiac muscle fibers

16. Intra cellular accumulations Pigments

17. Pigments are colored substances, some of which are normal constituents of cells (e.g., melanin), whereas others are abnormal and accumulate in cells only under special circumstances Exogenous Endogenous

18. EXOGENOUS ENDOGENOUS Carbon – coal dust Anthracosis Coal workers pneumoconiosis Tattooing India ink, carbon Ingested Argyria : silver Lead carotenemia Lipofuschin Melanin Hemosiderin

19. Exogenous pigments Carbon (anthracosis) Coal dust (pneumoconiosis) Lung: pick up by alveolar macrophages regional lymph nods blackening the tissues of the lungs (anthracosis )

20. Here is anthracotic pigment in macrophages in a hilar lymph node The black streaks seen between lobules of lung beneath the pleural surface are due to accumulation of anthracotic pigment.

21. EXOGENOUS ENDOGENOUS Carbon – coal dust Anthracosis Coal workers pneumoconiosis Tattooing India ink, carbon Ingested Argyria : silver Lead carotenemia Melanin Hemosiderin Lipofuschin

22. Lipofuschin Insoluble pigment, also known as lipochrome or wear-and-tear pigment Composed of polymers of lipids and phospholipids in complex with protein Not injurious to the cell or its functions Telltale sign of free radical injury and lipid peroxidation

23. In sections it appears as a yellow-brown, finely granular cytoplasmic, often perinuclear, pigment Seen in liver and heart of ageing patients Patients with severe malnutrition Cancer cachexia

24. EXOGENOUS ENDOGENOUS Carbon – coal dust Anthracosis Coal workers pneumoconiosis Tattooing India ink, carbon Ingested Argyria : silver Lead carotenemia Lipofuschin Melanin Hemosiderin

25. Melanin Endogenous, non-hemoglobin-derived, brown-black pigment Only endogenous brown-black pigment Formed when the enzyme tyrosinase catalyzes the oxidation of tyrosine to dihydroxyphenylalanine in melanocytes and dendritic cells.

26. DISORDERS OF MELANIN PIGMENTATION HYPER PIGMENTATION HYPO PIGMENTATION

27. HYPER PIGMENTATION GENERALISED LOCALISED Addisons disease Chloasma Café au lait spots Peutz jeghers syndrome Melanosis coli Nevi and tumors

28. HYPO PIGMENTATION GENERALISED LOCALISED Albinism Vitiligo

29. EXOGENOUS ENDOGENOUS Carbon – coal dust Anthracosis Coal workers pneumoconiosis Tattooing India ink, carbon Ingested Argyria : silver Lead carotenemia Lipofuschin Melanin Hemosiderin

30. Hemosiderin Hemoglobin-derived, golden yellow-to-brown, granular or crystalline pigment Major storage forms of iron Hemosiderin pigment represents aggregates of ferritin micelles Small amounts of hemosiderin can be seen in the mononuclear phagocytes of the bone marrow, spleen, and liver, which are actively engaged in red cell breakdown.

31. Excess of iron LOCAL SYSTEMIC Common bruise Acquired Hemosiderosis Hemolytic disorders Blood transfusion Iatrogenic Heriditary hemochromatosis Increased absorption Excessive dietary intake.

32. Iron pigment appears as a coarse, golden, granular pigment lying within the cell's cytoplasm

33. Perls prussian blue stain

34. The brown coarsely granular material in macrophages in this alveolus is hemosiderin that has accumulated as a result of the breakdown of RBC's and release of the iron in heme. The macrophages clear up this debris, which is eventually recycled.

35. EXOGENOUS ENDOGENOUS Carbon – coal dust Anthracosis Coal workers pneumoconiosis Tattooing India ink, carbon Ingested Argyria : silver Lead carotenemia Lipofuschin Melanin Hemosiderin

36. Summary Intracellular accumulations Fatty change Proteins Carbohydrates pigments

37. Thank you.