Lecture 6: Intracellular Accumulations: Pigments & Pathological Calcification PDF

Lecture 6 Intracellular accumulations: Pigments & Pathological calcification Year/Level: D2 / Semester 1 Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students will be able to 1. Di...

Lecture 6 Intracellular accumulations: Pigments & Pathological calcification Year/Level: D2 / Semester 1 Dr Mohammad Shahid Iqbal M.D Assistant Professor of Pathology 1 Learning Outcomes By the end of this lecture, the students will be able to 1. Discuss the pigments and their associated disorders 2. Describe the etiopathogenesis and types of pathological calcification 2  Pigments Pigments are colored substances that are either: Exogenous, coming from outside the body, Endogenous, synthesized within the body itself. Some of which are normal constituents of cells (e.g., melanin), whereas others are abnormal and accumulate in cells only under special circumstances.  The Accumulations of Pigments Pigments can be exogenous or endogenous. Exogenous pigments include carbon. Endogenous pigments include melanin, bilirubin, hemosiderin, & lipofuscin. Tattooing is a form of localized, exogenous pigmentation of the skin. These pigments can accumulate inside cells in different situations.  Exogenous Pigment: Carbon Introduced into the body from outside by ingestion, inhalation or inoculation. Most common inhaled pigment is carbon (coal dust), When inhaled, it is phagocytosed by alveolar macrophages and transported through lymphatic channels to the regional lymph nodes. Anthracosis (in lung) - Accumulation of carbon, black pigment. Exogenous pigment: Anthracosis.  Endogenous Pigments include: a) Melanin. b) Bilirubin c) Hemosiderin. d) Lipofuscin.  Melanin Brownish-black pigment produced in melanocytes located in the epidermis. Acts as a screen against harmful ultraviolet radiation. Although melanocytes are the only source of melanin, adjacent basal keratinocytes and dermal macrophages in the skin can accumulate the pigment Eg: Freckles  Melanin Increased melanin pigmentation is caused by: - Sun tanning. - Certain diseases e.g., nevus, or malignant melanoma. Decreased melanin pigmentation is seen in: - Vitiligo – loss of pigment producing melanocytes within the epidermis. - Albinism – melanocytes are present but no melanin is produced because of a lack or defect in tyrosinase enzyme. Melanoma  Hemosiderin Hemoglobin-derived. Golden yellow-to-brown, granular pigment. One of the major storage forms of iron. Iron is normally carried by specific transport proteins, transferrins. Stored in association with a protein, apoferritin, to form ferritin micelles. Ferritin is a constituent of most cell types. When there is a local or systemic excess of iron → ferritin forms hemosiderin granules. Hemosiderin pigment represents aggregates of ferritin micelles.  Hemosiderin Identified by its staining reaction (blue color) with the Prussian blue dye. Accumulates in tissues when there is a local or systemic excess of iron. Hemosiderin accumulation is usually pathologic. However, it exists normally in small amounts within tissue macrophages of the bone marrow, liver, & spleen as physiologic iron stores; where there is extensive red cell breakdown.  (c) Hemosiderin This excess accumulation is divided into 2 types: (1) Hemosiderosis: when accumulation of hemosiderin is primarily within tissue macrophages & is not associated with tissue damage. (2) Hemochromatosis: when there is more extensive accumulation of hemosiderin (Iron), often within parenchymal cells, which leads to tissue damage, scarring & organ dysfunction, including liver fibrosis, heart failure, and diabetes mellitus. Hemosiderosis occurs in the setting of: 1. Increased absorption of dietary iron. 2. Impaired utilization of iron. 3. Hemolytic anemias. 4. Transfusions (the transfused red cells constitute an exogenous load of iron).  Hemosiderin Granules in Liver Cells. The iron ions of hemoglobin accumulate as The iron can be unambiguously identified by golden-yellow hemosiderin. the Prussian blue histochemical reaction A B Hemosiderin granules in liver cells. A, H&E section showing golden-brown, finely granular pigment. B, Prussian blue reaction, specific for iron.  (d) Lipofuscin Lipofuscin (“wear and tear” pigment) is an insoluble brownish-yellow granular intracellular material. Consists of lipids and phospholipids in complex with protein. Derived from the free radical-catalyzed peroxidation of polyunsaturated lipids of subcellular membranes. Not injurious to the cell or its functions, but is important as a marker of past free-radical injury.  (d) Lipofuscin Seen in a variety of tissues (the heart, liver, and brain) as a function of age or atrophy. The brown pigment when present in large amounts, imparts an appearance to the tissue that is called brown atrophy. In tissue sections, it appears as a: - Yellow-brown. - Finely granular intracytoplasmic - Often perinuclear pigment.  Lipofuscin Granules in a Cardiac Myocyte. A B Lipofuscin granules in a cardiac myocyte. A, Light microscopy (deposits indicated by arrows). B, Electron microscopy. Note the perinuclear, intralysosomal location. By electron microscopy, the pigment appears as perinuclear electron-dense granules  Pathologic Calcification A common process in a wide variety of disease states. Abnormal deposition of calcium salts, together with smaller amounts of iron, magnesium, and other minerals. Two forms: (1) Dystrophic calcification. (2) Metastatic calcification.  (1) Dystrophic Calcification Deposition of calcium salts in dead or degenerated tissues. Occurs with normal calcium metabolism and normal serum calcium. Seen in : ▪ Arteries in Atherosclerosis. ▪ Damaged heart valves. ▪ Necrosis Dystrophic Calcification in the Wall of the Stomach. At the far left is an artery with calcification in its wall. There are also irregular bluish-purple deposits of calcium in the submucosa. Calcium is more likely to be deposited in tissues that are damaged.  (2) Metastatic Calcification. Deposition of calcium salts is in vital tissues. Calcium metabolism is abnormal. Serum calcium is high (hypercalcemia), usually a consequence of parathyroid hormone excess. May occurs in normal tissues. Seen in interstitial tissues of blood vessels, stomach, kidneys, lungs. Morphology similar to that in dystrophic Calcification.  Metastatic Calcification: Principle Causes 1. Increased secretion of parathyroid hormone, as occurs in hyperparathyroidism resulting from parathyroid tumors. 2. Destruction of bone tissue, as occurs with primary tumors of bone narrow (e.g., multiple myeloma). 3. Vitamin D-related disorders, including Vitamin D intoxication and systemic sarcoidosis. 4. Associated with renal failure, which cause secondary hyperparathyroidism.  The General Morphology of Pathologic Calcification Grossly : Fine white granules or clumps, gritty deposits. Microscopically (H & E) : calcification appears as intracellular and/or extracellular deeply basophilic, irregular, granular clumps. Special stains for calcium : 1. Von-Kossa-black, 2. Alizarin red s-red  References 1. Robbins and Cotran Pathologic Basis of Disease; 10th ed. 2021 2. HarshMohan Textbook of Pathology. 7th edition. 27