1

Pathologic pigmentation

Pigments

Forms:• Endogenous pigments

– haemoglobinogenous pigments

• haemoglobin

– szulfmethaemoglobin, haemiglobin, carbon-monoxid-haemoglobin, formaldehyde pigment, haematin

• haemosiderin

• haematoidin and bilirubin

• porphyrin

– anhaemoglobinogenous (autochtonous) pigments

• Exogenous pigments

2

Topics

• 31. Pathologic pigmentation caused by

hemoglobin and haemosiderin

• 32. Pathologic pigmentation caused by

hematoidin, and bilirubin

• 33. Pathologic pigmentation caused by

porphyrins

• 34. Pathologic pigmentation caused by melanin,

lipofuscin, and ceroid

• 35. Exogenous pigments

• 36. Concretions (lithiasis) and pseudoconcretions

31. Pigmentation caused by haemoglobin

and haemosiderin

• Haemoglobin– Haemolysis haemoglobinaemia

– Haemoglobin cylinders in renal tubuli

(benzidine +)

• Causes of haemolysis:– Autointoxication

– Chemicals (arsenic, cupper, phenol, trichlorethane)

– Drugs(sulphonamides, atebrin, phenacetin)

– Physical effects(radiation, thermal injuries)

– Bacteria, viruses, parasites (Babesia)

– plant poisons

Hemoglobin forms:

• Sulfhaemoglobin (H2S): greenish fades

• Methaemoglobin (Fe++, - Fe+++): dark brown

• Carboxi-haemoglobin (CO-intoxication)

– cherry pink discoloration, clearly visible in brain

3

• Hemosiderin

– Brown, amorphous, granular, iron-containing pigment

– Develops in RES cells (macrophages)

– Siderin: injection of iron-dextran preparates

– Histology:

• Prussian blue (Perl’s reaction)

• Turnbull’s technique

– Local haemorrhages: siderophor cells

– Pseudomelanosis: hemosiderin + H2S

(putrefaction)

Hemosiderin

– Pseudomelanosis: hemosiderin + H2S (putrefaction)

4

32. Pigmentation caused by hematoidin

and bilirubin

• Hematoidin

– Brownish pigment

– Old haemorrhages

– Iron free derivate of haem!

– Needle-shaped or rhomboid crystals

• Bilirubin (biliverdin: oxydized): bile pigment

– RHS (MPS) cells (indirect bilirubin)

– Liver cells (direct bilirubin – conjugated to

glucuronic acid)

Simultaneous presence of haematoidin and haemosiderin

in subcutaneous tissue

Jaundice - icterus

• Bilirubin in tissues: solute and

precipitated to proteins

• Staining the tissues yellow

(conjunctiva, sclera, intima of blood

vessels…)

• Bird liver: green (biliverdin)

• Staining:

– Forsgren method (reddish-blue)

5

Jaundice - icterus

• Posthepatic

• (stagnation or resorption)

– Obstruction to the outflow of bile (bilirubin I)

– In the blood and urine: bilirubin II

• Prehepatic (hyperfunctional or hemolytic)

– Intensive haemolysis

– (bilirubin I in blood)

– Icterus neonatorum

• Hepatic (toxic or retention)

– (bilirubin I and bilirubin II)

– In the urine: bilirubin II, urobilinogen

– Cell necrosis

Intrahepatic accumulation of bilirubin

Cholelithiasis ( posthepatic icterus)

HE; 200x

HE; 600x

33. Pathologic pigmentation

caused by porphyrins

6

Porphyria

• Porphyrin

– Haem synthesis

– Protoporphyrin + Fe + globulin = Hb

– Porphyrin synthesis: liver + bone marrow

– Affinity to bone

– Photosensitization

– Brownish-violet, fluorescence under UV light

– Uro- and coproporphyrin = excreted with urine and faeces

– Hereditary porphyria

– Toxicoses: lead, arsenic, CCl4, benzene, anilin

• coproporphyrin

Porphyria

• Hereditary

• Toxicoses (Pb, As, anilin etc.)

• Spongy bones are coloured

• Dental cement brown

• Dentin pink, reddish-brown

• Enamel: white

• Cartilage, ligaments, tendons:

uncoloured

7

40. HGCE - Pyometra complex

34. Pathologic pigmentation caused by

melanin, lipofuscin and ceroid

Autochton pigments

Pigments

Forms:• Endogenous pigments

– haemoglobinogenous pigments

• haemoglobin

– szulfmethaemoglobin, haemiglobin, carbon-monoxid-haemoglobin, formaldehyde pigment, haematin

• haemosiderin

• haematoidin and bilirubin

• porphyrin

– anhaemoglobinogenous (autochtonous) pigments

• Exogenous pigments

Anhaemoglobinogen pigments

• melanin

• lipofuscin

• ceroid

• ceroid-like pigment

34. Pigmentation caused by melanin,

lipofuscin and ceroid

Melanin

• Insoluble in water, acids, fat solvents

• Solubile in K-OH, Na-OH

• H2O2 – bleach

• Ectodermal origin cells produce it

• Tyrosinase enzyme initiatesmelanin synthesis

• Melanocyte-stimulating hormone (MSH) stimulates, but also ACTH has influence on the pigmentation

• Brownish-blackish pigment – no iron

Autochtonous (non hemoglobinogen

pigments)

8

Melanocyte

Melanin

• Produced by: melanocytes

• Stored by: melanophags

tirozin

Tirozinase (oxidation)

melanin

Hypophysis (MSH, ACTH)

Under physiological conditions

• skin– epidermis, corium

• during pregnancy– nipples, face, middle line if the belly (chloasma gravidarum)

• eye– retina, iris, chorioid

• ganglion cells– nucleus niger

• leptomenings

• mucous membrane of the oral cavity

• mammary gland in special swine breeds (Berkshire)

• Serous membrane of reptils and some birds

9

• Hyperpigmentatio

– Radiation, arsenic treatment

– Naevi (naevus pigmentosus)

– Focal melanosis

– Melanoma

– Acanthosis nigricans

– Addison’s disease

• Hypopigmentatio– Leukoderma (surgical

treatment)

– Vitiligo (pigmentfree area)

• Albinismus

Three variations of abnormal pigmentation

Melanosis maculosa

Melanoma benignum

(melanocytoma)

10

Acanthosis nigricans

• Disease of unknown origin

• Hyperpigmentation of the axillae, ventral thorax, inguinal and circum-anal region

• Uneven proliferation of the epithelial cells in stratum spinosum

• Skin thickened, surface uneven

• Velvety touch

Hypopigmentation

• Age

• Vitiligo (hamartia)

• Leukoderma (focal absence after injury)

• Trophoneurotic problems– dourine in horses

• Trypanosoma equiperdum infection

– depigmented areas

• pale areas after maceration

• Albinism– pathological absence of melanin

– congenital in rodents

11

• Lipofuscin

Golden-brown pigment

protein + lipids, no iron

Formed in lysosomes

Ageing cells

Autooxidation of unsaturated lipids

all three germ layer cells may contain

insoluble in water, acid, alkali

Liver, kidney tubuli, adrenal gland,

chorioid plexus, muscle cells

EM: dense, amorphous autophagosomes

+ granules and lipids

Lipofuscin in heart muscle

cellsLipofuscin containing histiocytes

12

• Brown bowel syndrome

– Dogs

– Diarrheal diseases

– Steatorrhea

– Pancreatic acinar deficiency

– Malabsorption

– Intestine: brown

• Smooth muscle cells

• Neuronal ceroid lipofuscinosis

– English setter, cattle, sheep, cat

– Intracellular accumulation

– Progressive loss of cells in the

brain and the cerebral function

• Ceroid

– Lipogenous pigment

– Partially oxidized and polymerized unsaturated

fatty acid bound to proteins

– Produced in macrophages and hepatocytes

– Ziehl-Neelsen positive

• Yellow fat disease

– Alcohol soluble - icterus

– Ether soluble - yellow fat disease

Ceroid-like pigment

yellow

Appearance

• lipocytes

• macrophages

• MPS-cells

• The fat tissue is yellow

– yellow fat disease

– cause: high amount if unsaturated fatty acid in the feed

13

Ochronosis (alkaptonuria)

• inherited disturbance of the protein

metabolism (tyrosine, phenilalanine)

amino acids (aromatic)

homogentisic-acid

oxidation colored substance

• Cartilage, tendons, ligaments become greenish

• The bones do not get discolorated

Pigments

Forms:• Endogenous pigments

– haemoglobinogenous pigments

• haemoglobin

– szulfmethaemoglobin, haemiglobin, carbon-monoxid-haemoglobin, formaldehyde pigment, haematin

• haemosiderin

• haematoidin and bilirubin

• porphyrin

– anhaemoglobinogenous (autochtonous) pigments

• Exogenous pigments

35. Exogenous pigments

• Anthracosis– Phagocytic activity against fine coal

• Pneumoconiosis– Siderosis (Fe), Chalicosis (CaCO3),

– Silicosis, asbestosis, tabacosis…

• Tattooing

• Pseudoicterus– karotinoids

• Medicines– Trypanblue

– Silver preparations (argyria)…

14

Exogen pigments

• Either colored or non-colored

• Enter the body

– Aerogenously• pneumoconiosis

– Per os (enterogen)• Food, plants (common madder - alizarin)

– Skin wound (tattooing)

– Parenteral way

• In the lungs

– Alveolar macrophages + histiocytes

– Gets to the regional lymph node

15

Exogen pigmentsPowders, chemicals, drugs, feed particles

• soot, dust = anthracosis

• quartz = silicosis

• iron = siderosis

• lime, whiting = chalicosis

• asbestos = asbestosis

• tobacco = tabacosis

• silver products = argyrosis

• karotin = karotinosis (pseudoicterus)

• Any substance in the lung - pneumoconiosis

16

Exogen pigments

Drug, feed

• blackberry = skin, tendons

• pannage = fascia, mesenteric lymphnodes

• alizarin = osteogenesis

– madder (Rubia tinctorum)

– fine red dyeplant

– used to colour fabric and timber

• picric acid = yellow

• tripaflavin = yellow

• trypan blue = tendons

Lithiasis, calculus formation

• Solid substances

– From secretions of certain organs

– Lined by mucous membranes

• Reason for the precipitation

– Increased concentration of crystalloids

– Decreased protective colloid content

• Lithogenous material + binding material → Microlith

• calculus, sediment

36. Concretions and pseudoconcretions

Predisposing factors

Lithogenous material in increased amount

• Metabolic disorders

• Nutritional factors

Inflammation of hollow organs

• Changes in the pH

• Enzymatic destruction of the colloids

• Desquamation of the epithelial cells

Stasis of excretions

Composition of different

concretions

• Calcium-carbonate

– Food is contaminated with limestones

• Phosphate calculi

– Feeding with forage, bran

• Oxalate stones

– High amount of fodder beet

• Cystine or xanthine stones

– Due to metabolic disorders in urinary tract

Structure

• Microlith – crystallization centre

– Foreign body, fibrin, necrotic cells

• Lithogenous material

– Salts of organic or inorganic acids

– Cholestrol, bilirubin, cystine, xanthine

• Binding material

– Protein or mucous like

• Concentric layering

17

Localization

• Mainly in the urinary tract– Pelvis of the kidney, urinary bladder

• besides that– ducts of the salivary glands

– ducts of the pancreas

– gallbladder, biliary ducts

– intestines

– oral cavity (dental plaque, tartar)

• Liths in the large intestine of the horses– Composition: magnesium-ammonium-phosphate

– high amount of forage, bran = magnesium(II)-phosphate

– during putrefaction of proteins ammonium is produced

18

Concentric layering

„Enveloped stone”

„Facetted stones”

Uroliths from the renal

pelvis of a horse

19

Stone in the urinary

bladder of a dog

Sialolith from the parotid gland

of a horse

Sialolith in human

submadibular gland

Sand deposition, horseEnterolith, horse, large intestine

20

Concrements

• Size of the stones

– differ

• What happens with the stones?

– small concretions exit from the lumen

– in some cases dissolve

– in other cases break into smaller pieces

– stay in the organ constantly

• Harmful effects

– Stenosis or complete obstruction of the lumen

– Mechanical trauma (rough surface)

– Heavy stones cause pressure, atrophy, necrosis

Pseudoconcretions

• Inspissation of content

• Impaction of foreign materials

• Types:

– Simple solidification of the excretions

• Fossae of the tonsils, prepuce, guttural pouch, bronchi, oviduct

• Secondary calcification

– Knotted animal hair (zootrichobezoars)

• Effect of the movements of the stomach (Ru, sus, ca, oryct)

• Bones, fur, fish-scale – in predators

– Knotted plant elements (phytotrichobezoars)

• Straw, barley chaff (horse, birds)

– Conglobates

• Undigested non-food fragments and foreign bodies

Inspissation of the intestinal content

Obstipation (coprolith)

Zootrichobezoars

21

Zootrichobezoar in stomach, swine Zootrichobezoar in stomach, swine

Phytotrichobezoars

barley chaff bezoar, pig

Phytotrichobezoar in large intestine

Conglobate in the gizzard of day-old poultry

Conglobates

22

Pseudoconcretions formed from eggs

• Multifactorial disease

– The egg gets stuck in the oviduct

– new eggs are also formed

– abnormal decomposition of the eggs start

– fibrin accumulates between the eggs

– results in inflammation

– the wall of the oviduct gets reconstructed…..

Pseudoconcretion from eggs

Consequences

• Local irritation

• Pressure

– resulting in atrophy, necrosis, ulceration

• Narrowing, impacting the lumen of the organ

– painful spasm

– ileus

• Causing disorders of the passage

– obstruction, gas accumulation (tympany)