Patho - 4th Asessment - Pigment Disorders - 5 Feb 2007

Disorders of Pigment and other deposits Dr. Francis

GLYCOGEN ACCUMULATION Glycogen normally is present in the livers of people in the fed state , and is abundant if the patient with an IV line infusing glucose ("dextrose“) In hyperglycemia, it is common to see glycogen in • hepatic nuclei • pancreatic beta cells • proximal tubular epithelial cells These accumulations are probably harmless Glycogen also accumulates within the cells in genetic disorders, referred to as the glycogen storage diseases

glycogen storage diseases

ACCUMULATIONS OF COMPLEX LIPIDS AND CARBOHYDRATES Result from inborn errors of metabolism Substance is stored in lysosomes Eventually enough accumulates to compromise organ function – – – – –

Gaucher's: Tay-Sachs‘ Niemann-Pick's Hunter's, Hurler's Fabry's

glucocerebroside ganglioside sphingomyelin mucopolysaccharide ceramide trihexose

Gaucher's Disease

PIGMENTS • Pigments are colored substances, normal or abnormal and collect in cells • Pigments can be either exogenous or endogenous • Soluble pigments do not appear in tissue • They include – carotene – bilirubin (except in bile plugs) – urochrome

• Insoluble pigments inside cells are typically stored in phagolysosomes

Carbon • Carbon particles enter our bodies in smoke and soot • Carbon settles in macrophages, where it remains indefinitely. • Carbon in the lungs and nearby lymph nodes is called "anthracosis” • Carbon pigment is usually inert • Heavey deposits could be associated with lung fibrosis and emphysema

Lipofuscin (* "lipochrome"; "fuscus" is Latin for brown) •

Composed of polymers of lipids, phospholipids and protein

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Derived from lipid peroxidation of polyunsaturated lipids of subcellular membranes

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Lipofuscin is normally present in: – – – – –

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Interstitial cells of the testis, Epithelial cells of the epididymis and seminal vesicles Cardiac nuclei Earwax pigment

Lipofuscin becomes more abundant during – normal aging – severe malnutrition – cancer cachexia

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"Brown atrophy" is simply atrophy where the lipofuscin is visible grossly

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By age 90, the heart may contain 30% lipofuscin by weight.

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"Ceroid" is lipofuscin that has become acid-fast and autofluorescent

Lipofuscin ( lipochrome)

Melanosis coli • A condition with a pigment found within macrophages in the mucosa of the colon • typical seen in people using laxatives • Results from apoptosis of colonic epithelial cells digested by macrophages. • Chemical nature of melanosis coli pigment unknown

Hemosiderin •

Iron is normally carried by transferrins

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In cells, it is stored in association with apoferritin, to form ferritin micelles

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Ferritin is a constituent of most cell types

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When there is excess of iron, ferritin forms hemosiderin granules

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Hemosiderin granules are easily seen with the light microscope

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Lack of stainable iron of course indicates systemic iron deficiency

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Under normal conditions, small amounts of hemosiderin can be seen in the mononuclear phagocytes of – Bone marrow – Spleen – Liver

Hemosiderin Localized accumulations of iron ("local hemosiderosis"): • Longstanding congestion (lungs, leg veins) • Massive hemorrhage • Repeated minor injury

Hemosiderin •

In systemic overload of iron, hemosiderin is deposited in many organs and tissues

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Condition called hemosiderosis

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Seen with: 1. 2. 3. 4.

Increased absorption of dietary iron Impaired use of iron Hemolytic anemias Blood transfusions

Hemosiderin •

In systemic hemosiderosis, it is found at first in the mononuclear phagocytes of – – – –

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With progressive accumulation, parenchymal cells throughout the body – – – –

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Liver Bone marrow Spleen Lymph nodes

Liver: Cirrohosi Pancreas: Diabetes Mellitus Heart: Heart failure Endocrine organs: Hormone deficiencies

Iron can be visualized in tissues by the Prussian blue reaction

PIGMENTS Copper pigment: Deposited in the liver and/or basal ganglia in Wilson's disease Homogentisic acid polymer: Hereditary arthritis syndrome "alkaptonuria" accumulate and breaks down into black pigment in cartilages (nose, ears), joints Called “Ochronosis".

PIGMENTS Hemozoin: • This is a ferric iron pigment that looks like hemosiderin • Formed by the break-down of hemoglobin of RBC • Does not exhibit the Prussian Blue reaction because the iron is sequestered by protein. • It is seen in RE cells in malaria • Plasmodia protect themselves from free iron-heme complex by converting it into this substance

CALCIFICATION • Calcium salts (hydroxides, phosphatehydroxides) are deposited. • Calcium salts stain dark blue on H&E. • Special stains: – Von Kossa – Alizarin red

Calcification Dystrophic calcification This is calcification that takes place locally, in the presence of normal overall calcium-phosphorus metabolism. Dystrophic calcification is seen in: – – – – – –

Malformed or damaged cardiac valves Caseous granulomas Scars (surgical, myocardial) Certain tumors contain "psammoma bodies" Advanced atherosclerotic plaques Uterine fibroids (smooth m

Calcification Metastatic calcification: Calcification that takes place with elevated serum calcium and/or phosphate ion concentration High blood calcium is usually due to: – – – –

Cancer destroying bone High PTH levels Sarcoidosis vitamin D abuse

High blood phosphate is almost always due to kidney failure

Calcification Metastatic calcification:

Metastatic calcification occurs in: – – – –

Alveolar walls Gastric fundic epithelium Basement membranes of certain renal tubules Walls of small blood vessels

Metastatic calcification is usually harmless

Melanin • • •

From Greek "melos", The principal pigment of human skin. A complex polymerized 5,6-dihydroxyindole and other tyrosine metabolites.

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Skin color gene is MC1R binds melanocyte-stimulating hormone and determines both depth of pigment

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Melanin is seen in melanocytes and their tumors: – Common "moles", – Malignant melanomas)

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Melanin in urine indicates extensive malignant melanoma

Melanin Albinism Failure of body to produce or distribute melanin pigment, called, because of one of several genetic defects Type 1 albinism • Defect in the metabolism of tyrosine lead to failure in converting this amino acid to melanin. • This is due to a genetic defect in tyrosinase Type 2 albinism • Defect in the "P" gene. • Subjects have slight pigmentation at birth •

Most severe form of albinism (called oculocutaneous albinism)

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Hermansky-Pudlak syndrome is a form of albinism associated with a bleeding Disorder, lung and bowel diseases. Ocular albinism also occurs

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