ExamQ. 54 - Endogenous pigments

Lipofuscin "definition":

- "Wear and tear" pigment after age or atrophy - Granules represent indigestible material resulting from free-radical mediated lipid peroxidation - Insoluble brownish-yellow granular material

Endogenous is again divided into:

- *Autogenous* (formed within the organism) - *Hematogenous* (from hemoglobin)

4 causes of hemosiderosis:

- *Incr absorption* (primary hemosiderosis/hemochromatosis) - *Impaired utilization* - *Hemolytic anemias* (large breakdown of RBC→ iron is free) - *Transfusions* (pool" of iron, there is 4 extra Fe pr RBC we add to the body!)

Occupational toxin pigments - examples:

- Anthracotic pigments - Plumbism - Chalcosis

Iatrogenic pigments - examples:

- Argyria: silver - Amalgam: mercury - Carotene - Tetracycline --> Bone and teeth in children. Yellow discoloration.

Hematin:

- Blackish-brown - Oxidized heme (ferric iron) - Develops in an upper GIT hemorrhage when the hemoglobin comes into contact with HCl. - Needed for Haemoph.influenza can grow --> That's why vomited blood is black (vomiting = hematemesis).

Hematozoidin:

- Brown-gray - Formed by Plasmodium (malaria parasite) in RBC parasitism - Stored in reticuloendothelial system (=mononuclar phagocyte system) - Partially crystallization of hematin - A blue to blackish-brown compound formed in theoxidation of hemoglobin and containing ferric iron.

Name three exogenous types of pigments:

- Cosmetic pigments - Occupational toxin pigments - Iatrogenic pigments

Lipochrome in DN:

- DM: yellowish coloration of skull, palms → xanthosis diabetica -

Typical findings/places of hematin:

- Found in gangrenous tissue changes - Found in the foam of bleeding peptic ulcers

Staining used for lipofuscin?

- Gommory - PAS - Sudan black

Hemosiderin - short definition:

- Iron storage complex - Hb derived - Accumulate when there is local/systemic excess of iron (e.g bruises, bleeding)

Diseases associated with melanin:

- Leukoderma (localized loss of pigmentation) burns/inflammations - Hyper/Hypopigmentation - Albinism. - Vitiligo (depigmentation of sections of the skin. Occurs when melanocytes die or are unable to function) What about melanoma??

Bilirubin - short definition:

- Major pigment found in bile (non iron containing). - It is derived from porphyrin ring of the heme moiety of hemoglobin

Hereditary hemochromatosis:

- More extensive iron accumulation - Tissue injury: liver fibrosis, heart failure, DM. - NOT connected with bleeding. - Connected with high inntake of Fe2+. - The normal role of hepcidin is disrupted and your body absorbs more iron. Hepcidin normally inhibit iron absorbtion.

Types of melanin:

- Neuromelanin - Oculocutaneous melanin - Eumelanin - Pheomelanin. Melanin are small granulocytes in normal melanocytes.

Hematoidin:

- Nonferrous - Red-brown - Contain pyrrole (indirect bilirubin) - When macrophages cannot reach the inner RBC in the center of the hemorrhage → Hb disintegration, iron release, crystallization of residual material containing pyrrole rings - Chemically identical with bilirubin, but formed in the tissues from hemoglobin, particularly under conditions of reduced oxygen tension.

Biliverdin - short definition:

- Results from the breakdown of the heme moiety of hemoglobin in erythrocytes - Green color

Lipochrome is ingested with _____ and how does the eyes look?

- The food in the form of beta carotene (precursor→ Lycopin). - Normal in eyes

Brown atrophy:

- When lipofuscin is present in large amounts - Apoptotic breakdown of cells → bodies with lipofuscin remains - Enhanced autophagy (elimination of parts of cell within the cell)

What color is seen in bilirubin pigment, and what stain is used to detect it?

- Yellow - Hall stain

BILIRUBIN

-->

BILIVERDIN

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CEROID

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ENDOGENOUS PIGMENTS (divided into autogenous and hematogenous)

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EXOGENOUS PIGMENTS

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HEMATOGENOUS PIGMENTS

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HEMOSIDERIN

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HOMOGENTISIC ACID

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LIPOCHROME

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LIPOFUSCIN

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MELANIN

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OTHER HEMATOGENOUS PIGMENTS

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Name 6 hematogenous pigments:

1. Hemosiderin 2. Hematin 3. Hematozoidin 4. Hematoidin 5. Bilirubin 6. Biliverdin

Give me 5 examples of autogenous pigments (they are formed within the organism):

1. Lipofuscin 2. Ceroid 3. Lipochrome 4. Melanin 5. Homogentisic acid

Icterus - rubin icterus:

= hepatocellular icterus

Homogentisic acid - short definition:

A black pigment that occurs in patients with ochronosis (a rare metabolic disease - the accumulation of homogentisic acid in connective tissues).

Hemosiderin accumulates when?

Accummulate when there is local/systemic excess of iron (e.g. bruise, bleeding)

Porphyria:

Accumulation of precursors to heme, lead to a purple pigment when exposed to sunlight

Chrysocyanosis:

After administration of colloid gold

Another disorder that almost always accompanies ochronosis:

Alkaptonuria, in which homogentisic acid is excreted by the kidneys. The urine of these patients, if allowed to stand for some hours in air, turns black due to oxidation of homogentisic acid.

Hematozoidin is also called:

Also called ferriheme, oxyheme , oxyhemochromogen

Lipochrome is very alike an iatrogenic pigment:

Carotene

Most common affected tissues of homog.acid accumulation:

Cartilages, capsules of joints, ligaments and tendons

FYI:

Ceroid is a golden, waxy pigment appearing in the cirrhotic livers of some individuals, in the GItract, in the nervouse system, and in the muscles. It is an insoluble, acid-fast, sudanophilic pigment.

Statement: Hemosiderosis causes damage, but organ can still function.

False, NO damage!

Statement: Homogentisic acid is melanin-like and is only deposited intracellularly.

False, both extra and intra

FYI:

Formation of lipid pigments increases with cell age. In older persons, hepatocytes in the central lobe and myocardial cells are characterized by yellowish brown lipofuscin granules.

Explain how heme in transferritin is made into hemosiderin:

Heme is transported by *transferritin*, stored in cells in association with *apoferritin* → *ferritin micelles*. Large aggregates of ferritin micelles → *hemosiderin*

Hemtaogenous pigments are based on one "main pigment": Not sure if it can be called a pigment:-p

Hemoglobin

What is systemic overload of iron called? Esp. in blood and endocrine organs!

Hemosiderosis = hemosiderin deposition in many organs and tissues - "bronzing".

Hemosiderosis is related to:

Increased hemolysis

Macrophages in colonic lamina propria is connected with:

Inflammation

Are lipofuscin found intra- or extracellular?

Intra

Is it intra- or extracellularly?

Intracellular within macrophages (siderophages, kuppfer cells)

What type of hereditary disorder is ochronosis, and what is causing it?

It is an autosomal recessive disorder. There is deficiency of an oxidase enzyme required for breakdown of homogentisic acid which then accumulates in the tissues and is excreted in the urine. Intermediate of aromatic acids..

Pruritus means:

Itching

Its normal formation and excretion are vital to health, and ______ is a common clinical disorder caused by excess of this pigment within cells and tissues.

Jaundice

If extensive accumulation of anthracosis pigment is combined with silica →?

Leads to fibrotization.

How can left sided heart failure cause hemosiderin?

Left sided heart failure → Stasis in lungs → Macrophages → Hemosiderin

Ceroid is a type of what other pigment?

Lipofuscin

Lipofuscin accumulates especially in:

Liver, brain and heart

How is it "made"?

Macrophages break down senescent erythrocytes and break the heme down into *biliverdin*, which normally rapidly reduces to free bilirubin. Biliverdin is seen briefly in some bruises as a green color. Its breakdown into bilirubin in bruises, leads to a yellowish color.

FYI:

Not a pigment, but in blood plasma, *haptoglobin* binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity.

Hemosiderin is stained with:

Pearl's = Prussian blue/Berliner blue - stains iron

Formation of a bruise:

RBCs - Hb (red) → biliverdin (green) → bilirubin (yellow) → hemosiderin (yellow-brown)

Pigments:

Substance that has its own color - visible by naked eye or under microscope that is unstained. Can be Exogenous and endogenous

Cosmetic pigments - examples:

Tattoos and traumatic tattoo • Pigment promotes inflammation initially - but becomes inert • May occur slight fibrotization • Don't play paintball. The painting can be permanent.

Statement: Lipofuscin is NOT injurious to the cell, but can tell about past free-radical injury

True

Statement: Hemosiderin is normally present in bone marrow?

True

Plumbism:

• Chronic lead poisoning. • Produce halo-like deposits in the gingiva.

Chalicosis:

• Exhaust gases containing copper and dust from copper processing industry. • Green discoloration of the hair.

Other info about ceroid:

• Increased lipid turnover in macrophages → homogenous appearance. • Stains with Zeihl neelson. • In the liver, in resorption phase of acute viral hepatitis. • It's the clean up pigment. Occurs in macrophages after heterophagy

Anthracosis (coal dust):

• Nodular black discoloration of the lungs, dust within the tissue. • Interstitial deposition, subpleural localization. • The substances are *phagocytozed* by macrophages and removed via lymphvessels. • No change in function.