Pigments, Infiltrates Flashcards
What are 3 things an increase in pigment cause?
Anthracosis, melanosis, lipofuscin
What are 2 things a decrease in pigment causes?
Albinism, acquired depigmentation
What are 2 types of normal cells producing pigment and what species are they found in?
Chromatophores -> birds, fish, reptiles
Melanin -> birds, mammals
What are 3 types of chromatophore?
Xanthophore, erythrophore, iridophore
What is intracellular accumulation?
Accumulation of abnormal amounts of substance -> can be normal but excessive or abnormal (endogenous or exogenous)
What are 2 causes of intracellular accumulations?
Inherited or acquired
What are 3 types of abnormal intracellular accumulations? (what do they do)
- Normal excessive -> rate of metabolism not enough to remove
- Normal or abnormal endogenous accumulation -> accumulates due to defect in its metabolism, packaging or transortation
- Abnormal exogenous -> accumulates eg carbon inhalation
What is an example of a disorder caused by exogenous pigements? What is the histology associated with this?
Anthracosis -> accumulation of carbon in lungs + lymph nodes
Carbon phagocytosed by macrophages and cant be degraded
Histology -> fine blue/black granules in macrophages in airways
What are 2 examples of a disorder caused by endogenous pigements?
Melanosis (excess) and albinism (deficiency)
What enzyme is associated with albinism and how do acquired deficiencies occur?
Tyrosinase
Can get acquired deficiency due to copper deficiency not allowing enzyme to function
What is melanosis and what are the types?
Generalised -> Induced by UV
Localised -> lung, liver, meninges, maternal caruncles - angus cattle have melanin everywhere
Congenital naevi -> dermal accumulations of melanoblasts (moles)
How does soft tissue calcinosis form?
Cacinogenic plants contain steroidal glycoside - this hydrolyses and has vitamin D3 activity
Creates excessive Ca2+ binding protein -> increases GIT absorption -> hypercalcaemia + soft tissue calcificiation
What does lipid accumulation occur and where is it most common?
Liver (also in kidney and skeletal muscle)
Causes large lipid vacuoles in parenchymal cells and pale liver
What does accumulation of protein cause?
Resorption droplets in proximal convoluted tubules of the kidney -> proteinuria (brown colour due to haemoglobin) -> hyaline droplets in cytoplasm of those cells
Or excessive normal secretion causes immunoglobulins in plasma cells (russell bodies)
What does glycogen accumulation cause?
Hepatocytes and respiratory epithelium in newborns -> cells with central nucleus and clear cytoplasm
Liver will be pale
What are 2 lipopigments?
Ceroid and Lipofuscin
What are lipopigments derived from?
Lipid-peroxidation products of membrane polyunsaturated FA’s - accumulate in lysosomes in cells which do not divide (neurons, muscle, skin)
What does ceroid accumulation result from and cause?
Results from peroxidation of fat deposits
Yellow pigment
Ovine white liver disease - ceroid accumulates in hepatocytes then sinusoidal cells
What causes accumulation of lipofuscin and what does it cause?
Derived from lipid peroxidation of membrane unsaturated FA -> accumulation in lysosomes of cells that dont divide (neurons, muslce, skin)
Yellow brown granular pigment - does not affect cell function
What is lipofuscin accumulation associated with?
Aging -> generation of free radicals as byproducts of metabolism
Prevented by vitamin E -> inhibits peroxidation by incorporating into lipid bilayer
What is lipofuscinosis?
In dogs -> brown dog gut
Gut smooth muscle atrophy and myocyte cytoplasm full of lipofuscin
What is haemosiderin and how does it form?
Yellow brown granular pigment containing ferric iron (Fe3+) mostly derived from breakdown of haemoglobin
- erythrocyte phagocytosis after haemorrhage
- Haemolytic anaemias and ovine mycoplasma ovis infection
Where does haemosiderin accumulate?
Macrophages, sites of haemorrhage or fixed marcophages in hepatocytes/spleen/renal tubular cells
What does haemosiderin cause grossly?
Brown discolouration of tissue
How is excess Fe dealt with?
No mechanism to excrete, only can be scavenged (can get toxicity)
What is hepcidin and what does it do?
Peptide hormone produced by the liver
Inhibits Fe transport by binding to + degrading fe2+ channel ferroprotin on enterocytes, hepatocytes and macrophages
Controls intake and release from cells
What are 3 steps of haemoglobin breakdown?
- Globin chains degraded to aa and reutilised for protein synthesis
- Fe converted to ferritin -> may accumulate as haemosiderin
- Haeme -> biliverdin -> free bilirubin (in resident tissue macrophages)
Happens in bruise/spleen
How is bilirubin excreted?
Hepatocytes convert free bilirubin to conjugated bilirubin (soluble and non-toxic)
Conjugated bilirubin excreted in bile and discharged into the intestine
What is icterus and what does it result from?
Jaundice -> accumulation of bilirubin
What are 3 types of jaundice?
Haemolytic (prehepatic)
Toxic (Hepatic)
Obstructive (post-hepatic)
What do birds and reptiles do that differs to mammals in regard to bilirubin?
They make biliverdin and excrete it (only small amount of bilirubin as lipid based antioxidant)
How do fetuses get rid of bilirubin?
Through the placenta (lipid based)
Couldnt get rid of biliverdin as it is water based
What is haemolytic icterus?
Pre-hepatic jaundice
Increased breakdwon of erythrocytes -> may be haemoglobinaemia, haemoglobinuria and increase in unconjugated bilirubin in the blood
Hepatic system overloaded
What happens in hepatic icterus?
Hepatic jaundice
damage to hepatocytes canot conjugate or excrete bilirubin -> increased free bilirubin in blood with no evidence of haemolysis
May be increased urobilinogen as may not be re-excreted by damaged liver
What is obstructive icterus?
Obstruction of excretion of conjugated bilirubin due to blockage of bile ducts
Increased conjugated bilirubin in blood
Reduced serum and urine urobilinogen with pale faeces
What is amyloidosis and what are the two broad types?
Amyloid proteins abnormally deposited in organs or tissue
15 types classified by protein precursors from which amyloid fibril is derived
Pattern of amyloid can be systemic (vessels affected) or localised
What are 3 types of systemic amyloidosis?
Primary amyloidosis
Amyloid protein: light chains
Reactive amyloidosis
what is primary amyloidosis?
Associated with multiple myeloma
Malignant plasma cells synthesise excessive immunoglobulin light chains
What is amyloid protein light chain amyloidosis?
Accumulate in tissue and pass in urine
What is reactive amyloidosis?
Associated with chronic inflammation autoimmune disease
A persistent systemic acute phase response - extra serum amuloid A or inflammatoru proteins deposit in tissues
What are the types of renal amyloidosis?
If in renal glomeruli -> protein loss in urine
If interstitial amyloidosis in medulla -> glomerulus is working but cannot concentrate urine
What is feline pancreatic amyloidosis?
Islet amyloid polypeptide secrete by beta islet cells along with insulin -> insulin disrupted
What happens in Alzheimers?
Cerebral cortex gets foci of degenerate axons and neurites surrounding core of amyloid fibrils
How do crystals form?
Ingested by plants containing oxalate - accumulate of calcium oxalate crystals mostly in kidney tubules and sometimes CNS
What is gout?
Uric acid or urate crystals deposited in tissues
What is pathological calcification and what are two types?
Dystrophic mineralisation - found in areas of necrosis wher Ca precipitates
Metastatic mineralisation - normal tissues with hypercalcaemia - destriuction of bone, increase PTH secretion, renal failure + vitamin D toxicity
How do lysosomal storage diseases happen?
Partial or lack of lysosomal hydrolase -> substrates stored
Mostly autosomal recessive
How do lysosomal storage diseases happen?
Partial or lack of lysosomal hydrolase -> substrates stored
Mostly autosomal recessive
what is alpha mannosidosis and how does it start?
Autosomal recessive a-mannose deficiency in lysosomes
Mannose containing oligosaccharides accumulate + neurons + epithelial cells vacuolated
Aquired by toxic plants containing swainsonine that inhibits a mannosidase
What is glycogenoses?
Glycogen accumulates in lysosomes of skeletal and cardiac muscle, liver and CNS
Swollen + vacuolated cytoplasm
Inherited deficinecy of lysosomal a,1,4-glucosidase
What is galactocerebrosidosis
Cell leukodystrophy of cairn terriers and poll dorset
Deficnecy of enzyme -> accumlation of galacotocerebrosides in myelin sheath
= decrease myelin formation
Lipid accumulates in oligodendroglia and globoid cells in perivascular areas in CNS