Intracell accumulation final

intracellular accumulation in pathophysiology

1. PRESENTATION ON: Intracellular Accumulation Presented by: Mohammad Muztaba Asst. Professor(Jr.) Department of Pharmacology Bhavdiya institute sibar sohawal Ayodhya

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

3. Accumulations of Constituents of Normal Cell metabolism Accumulations of Abnormal substances of abnormal Cell metabolism Accumulations of pigments Fats Proteins Carbohydrat e s Storage diseases Inborn errors of metabolism E ndogenous pigments E x oge n ous pigments ACCUMULATIONS

4. Intracellular accumulations 4 different intracellular accumulations Lipids Steatosis Cholesterol and CholesterolEsters Proteins Gl y cog e n Pigments

5. 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.

6. Causes of fatty liver - ALCHOL ABUSE ( alcohol dependence) - DIABETES MELLITUS OBESITY ( Obesity  is a condition in which a person has excess body fat) - PROTIEN MALNUTRION ( starvation suffering or death caused by lack of food. ) -DRUGS/TOXINS -ANOXIA -PREGNANCY

7. Excessive entry of lipids into the liver Enhanced fatty acid synthesis by hepatocytes Decreased oxidation of fatty acids by mitochondria Increased e s te r if i c a ti o n of fatty acids to triglycerides Decreased apo p rotein synthesis Impaired lipoprotein excretion

8. an example of fatty liver smooth surface: important distinction from other liver diseases where livers develop irregular surfaces cut surface is shiny: greasy and yellow

9. 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

10. Intracellular Lipid Accumulation Cholesterol and cholesterol esters Atheros c lero s is Xanthomas Cholesterolosis common causes of many diseases less common lipid storage disease Xanthomas : Cluster of f oam cells in subepithelial connective tissues of skin & in tendons producing tumorous masses. Atherosclerosis: Smooth muscles cells & macrophages filled with cholesterol & cholesterol ester forming foam cells within intimae layer of vessels. Accumulations of foam cells Like cholesterol

11. Xant h oma lipid ccumulation in the dermis knobby appearance--> clue that the patient may have defect in lipid metabolism

12. Ch o lesterolosis ciliated epithelium accumulation of lipid in gall bladder submucosa --may be an indicator of other underlying diseases

13. Intracellular Protein Accumulations Defective intracellular transport and secretion Excessive amounts of normal proteins (Multiple myeloma -Russell Bodies) accumulation of mucin (Cystic fibrosis) proliferation of plasma cells, causing accumulation of immunoglobin Defect in protein folding; defect in intracellular transport & secretion ER stress induced by unfolded & missfolded protein accumulation in ER aggregation of abnormal or missfolded proteins in tissues

14. M o rph o l o g y : Round eosinophilic droplets, vacuoles or aggregates in cytoplasm. May be amorphous or crystaline. Example : amyloidosis

15. Excessive normal proteins (Russell bodies) PathGuy normal plasma cell Russell body

16. Defective intracellular transport and secretion (Cystic fibrosis) trachea thick tenacious mucus in airway

17. Intra cellular accumulations GLYCOGEN Abnormal metabolism of glucose or glycogen result in excessive intracellular accumulation of glycogen Example… uncontrolled diabetes mellitus (main example of abnormal glucose metabolism

18. Intra cellular accumulations Pigments

19. DEFINITION Pigments are coloured substances, some of which are normal constituents of cells (e.g., melanin), whereas others are abnormal and accumulate in cells only under special circumstances Pigments can be exogenous , coming from outside the body , or endogenous , synthesized within the body itself.

20. A. ENDOGENOUS PIGMENTS B. EXOGENOUS PIGMENTS 1.Inhaled pigments 3.Injected pigments Melanin Melanin-like pigment Alkaptonuria Dubin-Johnson syndrome Haemoprotein-derived pigments Haemosiderin Acid haematin (Haemozoin) Bilirubin Porphyrins Lipofuscin (Wear and tear pigment)

21. Exogenous pigments Exogenous pigments are the pigments introduced into the body from outside such as by inhalation, ingestion or inoculation.

22. Exogenous pigments Carbon ( anthracosis accumulation of carbon in the lungs   ) Coal dust (pneumoconiosis) Lu n g: pick up by alveol a r macrop h ag e s regional lymph nods blackening the tissues of the lungs (anthracosis )

23. 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.

24. Injected Pigments (Tattooing) Pigments like India ink, cinnabar and carbon are introduced into the dermis in the process of tattooing where the pigment is taken up by macrophages and lies permanently in the connective tissue. The examples of injected pigments are Prolonged use of ointments containing mercury, and tattooing by pricking the skin with dyes.

25. Lipofus c hin fine yellow-brown pigment granules composed of lipid-containing residues of liposomal digestion . found in the liver, kidney, heart muscle, retina, adrenals, nerve cells, and ganglion cells

26. Melan i n The pigment that gives human skin, hair, and eyes their color.   Melanin  is produced by cells called melanocytes. Melanin is group of natural pigments found in most organisms. Melanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino acid tyrosine, is followed by polymerization

27. DISORDERS OF MELANIN PIGMENTATION HYPER PIGMENTATION HYPO PI G MEN T A T I ON

28. HYPER PIGMENTATION GENERALISED 1. 1 . A d d iso n s d i s e a s e 2. 2. Chloasma LOCALISED Peutz jeghers S yndrome Melanosis coli

29. HYPO PI G MEN T A T I ON GENER A L I SED Albinism L O C A L I SED Vitiligo

30. Hemos i derin Hemoglobin-derived, golden yellow-to-brown, granular or crystalline pigment Major storage forms of iron Hemosiderin  or haemosiderin is an iron-storage complex. It is only found within cells (as opposed to circulating in blood) and appears to be a complex of ferritin ,( Ferritin is a universal intracellular protein that stores iron  ) denatured ferritin and other material. The iron within deposits of  hemosiderin  is very poorly available to supply iron when needed. Excess of iron

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