Intracellular Accumulations and pigment s.pptx

Intracellular pigment accumulation

1. G e n e r a l P a t h o l o g y L e c t u r e s 3 I n t r a c e l l u l a r A c c u m u l a t i o n s & Calcifications D r . E m a d I b r a h i m Osman

2. Under some circumstances cells may accumulate abnormal amounts of various substances, which may be harmless or associated with varying degrees of injury . T hese subtances are either produced by the cell or produce out side the cell . The sites of accumulation within the cell:- The cytoplasm. The organelles ( lysosomes ). The nucleus

3. Pathways of abnormal intracellular accumulations :- 1. A normal substance is produced at a normal or an increased rate, but there is inadequate removal . Example:- fatty change in the liver. 2 . Accumulation of an abnormal endogenous substance as a result of genetic or acquired defects in its folding, packaging, transport, or secretion, as with certain mutated forms of α1-antitrypsin 3 . Failure to degrade a metabolite due to inherited enzyme deficiencies. The resulting disorders are called storage diseases . Example:- glycogen storage diseases 4 . An abnormal exogenous substance is deposited and accumulates because the cell has neither the enzymatic machinery to degrade the substance nor the ability to transport it to other sites. Example carbon and silica .

4. Mechanisms of intracellular accumulation

5. 1- Fatty Change ( Steatosis ) Fatty change refers to any abnormal accumulation of triglycerides within parenchymal cells. Sites:- liver ( common site), heart, skeletal muscle, kidney, and other organs. Causes:- Toxins ( alcohol), protein malnutrition, diabetes mellitus, obesity, and anoxia

6. Alcohol abuse and diabetes associated with obesity are the most common causes of fatty change in the liver (fatty liver) in industrialized nations. When mild it may have no effect on cellular function. More severe fatty change may transiently impair cellular function. fatty change is reversible , unless some vital intracellular process is irreversibly impaired .

7. Morphology : With increasing accumulation, the organ enlarges and becomes progressively yellow. In any site, fatty accumulation appears as clear vacuoles within parenchymal cells.

8. 2- Cholesterol and Cholesteryl Esters : Cholesterol metabolism is tightly regulated to ensure normal cell membrane synthesis without intracellular accumulation. Phagocytic cells may become overloaded with lipid in several different pathologic processes. Macrophages may be filled with m e m brane -bound vacuoles of lipid, result in foamy appearance to their cytoplasm ( foam cells ).

9. Examples : In atherosclerosis , smooth muscle cells and macrophages are filled with lipid vacuoles give atherosclerotic plaques their characteristic yellow color and contribute to the pathogenesis of the lesion.

10. In hyperlipidemic syndromes , macrophages accumulate intracellular cholesterol; when present in the subepithelial connective tissue of skin they form masses called xanthomas .

11. xanthomas

12. 3 - Proteins Less common than lipid accumulations; Ocurrs in disorders with heavy protein leakage across the glomerular filter ( nephrotic syndrome), there is a much larger reabsorption of the protein by tubular cells . The process is reversible. accumulation of newly synthesized immunoglobulins that may occur in the RER of some plasma cells, forming rounded, eosinophilic Russell bodies.

13. 4 - Glycogen Due to abnormalities in the metabolism of either glucose or glycogen. In poorly controlled diabetes mellitus,glycogen accumulates in renal tubular epithelium, cardiac myocytes , and β cells of the islets of Langerhans Glycogen also accumulates within cells in a group of closely related genetic disorders collectively referred to as glycogen storage diseases .

14. 5 - Pigments Pigments are colored substances that are either exogenous, or endogenous. The most common exogenous pigments:- Aggregates of the carbons that pigment and blacken the draining lymph nodes and pulmonary parenchyma ( anthracosis ).

15. Lipofuscin ( brown pigment ) or "wear-and-tear pigment," is an insoluble brownish-yellow granular intracellular material that accumulates in a variety of tissues (particularly the heart, liver, and brain) as a function of age or atrophy. Lipofuscin represents complexes of lipid and protein that derive from the free radical-catalyzed peroxidation of polyunsaturated lipids.

16. Melanin:- Is an endogenous, brown-black pigment produced in melanocytes . Adjacent basal keratinocytes in the skin can accumulate the pigment (e.g., in freckles),

17. Hemosiderin :- Is a hemoglobin-derived granular pigment that is golden yellow to brown and accumulates in tissues when there is a local or systemic excess of iron Either:- Physiological:- normal in the mononuclear phagocytes of the bone marrow, spleen, and liver.

18. Pathological:- at the site of hemorrhage, the red cell debris is phagocytosed by macrophages. hemosiderin is deposited in many organs and tissues, a condition called hemosiderosis Hemosiderosis occurs in the setting of: (1) increased absorption of dietary iron. (2) impaired utilization of iron. (3) hemolytic anemias . (4) transfusions

19. H ereditary hemochromatosis : - there is tissue injury including liver fibrosis, heart failure, and diabetes mellitus ( bronze Diabetes ) .

20. PATHOLOGIC CALCIFICATION

21. Pathologic Calcification it implies the abnormal deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals. There are two types of calciffication :- Dystrophic calcification. Metastatic calcification.

22. Dystrophic calcification: - It occurs in normal serum levels of calcium. It encountered in areas of cell injury and necrosis .

23. Morphology calcium salts are grossly seen as fine white granules or clumps. Histologically, calcification appears as intracellular and/or extracellular basophilic deposits.

24. Hyalinized fibroadenoma with stromal calcification.

25. The pathogenesis:- initiation (or nucleation) . propagation.

26. (1)Initiation (or nucleation): Initiation of intracellular calcification occurs in the mitochondria of dead or dying cells that have lost their ability to regulate intracellular calcium.

27. (2)Propagation : After initiation, propagation of crystal formation occurs. This is dependent on the concentration of Ca 2+ and PO 4 - in the extracellular spaces, the presence of mineral inhibitors, and the degree of collagenization , which enhances the rate of crystal growth.

28. Metastatic Calcification:- occurs in normal tissues whenever there is hypercalcemia . The four major causes of hypercalcemia are: Increased secretion of parathyroid hormone. Destruction of bone due to the effects of accelerated turnover (Paget disease), immobilization, or tumors. Vitamin D intoxication. Renal failure, in which phosphate retention leads to secondary hyperparathyroidism.

29. Morphology:- can occur widely throughout the body but principally affects the interstitial tissues of the vasculature, kidneys, lungs, and gastric mucosa. massive deposits in the kidney ( nephrocalcinosis ) can cause renal damage.

30. T h e E n d T h a n k s