Lecture 18: Pigments, Infiltrates & Storage Disease Flashcards
Exogenous Pigments
Tattoos- good ones don’t fade coz they immobilise macrophages
Carbon- Anthracosis: blackening of lungs due to inhaled carbon particles (smoke & soot). Carbon doesn’t bleach. Macrophages go to the LNs and interstitium
ANTHRACOSIS is the local accumulation of black carbon particles in the lungs and draining lymph nodes following long-term exposure to polluted air. The carbon is taken up and held by macrophages. There is rarely a change in the gross appearance when carbon is present. Histologically it appears as blue-black fine granules within macrophages around airways and lymphatics in the lungs.
Melanin
MELANIN is a naturally-occurring brown pigment in the skin, hair etc. It is produced in melanocytes
Tyrosine –> Tyrosinase + melanin (Cu2+ dependant)
Its function is protect against Uv radiation. Melanin is thought to capture the free radicals generated in the skin during injury.
-It can be shed by melanocytes and phagocytksed by macrophages, which are the termed Melanophages
Lipofuscin
LIPOFUSCIN is commonly known as a ‘wear and tear’ pigment and appears as a faint yellow-brown on H&E. The brown colouration leads to condemnation of organs at slaughter due to ‘brown atrophy’. It consists of complexes of lipid-protein substances thought to be derived from the peroxidation of membrane lipids.
Haemosiderin
-yellow brown iron containing pigment derived from breakdown of haemoglobin
-found in abnormal quantities with haemorrhage in liver/spleen and kidneys
-can cause brown discolouration of tissue
Clinical: resulting iron accumulation is damaging especially to liver by damaging DNA predisposing cancer
What are the 3 types of jaundice?
What is bilirubin
Bilirubin comes from breakdown of haeme and is an orange pigment
- excess amounts causes yellow discolouration of tissue (best seen on sclera)
- free bilirubin is toxic and insoluble in aqueous solutions
- conjugate bilirubin is soluble and non toxic (non conjugate needs to be changed in the liver to make it non-toxic) water soluble and excreted as bile.
3 causes:
- Haemolytic–> increased breakdown of erythrocytes and an increase in free bilirubin in the blood. The hepatic system is overloaded.
- Toxic–> damage to the liver so hepatocytes can’t conjugate and excrete bilirubin. So increase in free bilirubin in blood
- Obstructive–> where there is an obstruction to the excretion of conjugate bile due to blockage of bile duct system. Can occur in the liver or bile duct itself.
- there is increased conjugated bilirubin in the blood, pale faeces.
Refer to slide 10–> should probe listen to the lecture on it
Photosensitivity
Type 1 (primary)–> photodynamic agent is ingested, injected or absorbed- common in humans
type 2 (aberrant metabolism)–> porphyrins = endogenous pigments arising from inherited/ acquired defective functions of enzymes involved in haeme synthesis. Cattle, cats and humans
Type 3 (secondary/ hepatogenous)–> phylloerythrin (a porphyrin) derives from the breakdown of chlorophyll by GIT microorganisms. It is normally absorbed into the circulation and is effectively excreted by the liver into the bile. Failure to do so due to hepatic dysfunction or bile duct lesions increases circulating phylloerythrin. May also be jaundiced!
Type IV (idiopathic) – either the photodynamic agent or its pathogenesis is unknown
Amyloid
amyloid is an extracellular deposit and when present in large amounts can cause organs to be large, pale and waxy
- the forms of amyloid are classified biochemically according to the protein pre-cursors from which the amyloid fibril is derived.
- Amyloid is an insoluble beta-pleated sheet, deposited extracellularly, and resistant to proteolysis, which can arise from various different compounds.
Reactive amyloid (AA)–> often in kidney, liver and spleen. often assoisated with a persistent inflammatory disease. The molecule in this case is serum amyloid A, produce in the liver as part of the acute phase response to inflammation forming a beta-pleated sheet.
Immune (Amyloid AL) arises from neoplasm of plasma cells e.g. multiple myeloma. The molecule is formed from light chains of immunoglobulin, also forming an insoluble beta-sheet.
Amyloidosis can be a post mortem finding only, particularly in the spleen. However its deposition cause pressure necrosis and atrophy of tissue.
Lysosomal storage Disease
slide 15
- involve the accumulation of some macromolecular substance, usually due to the inadequate production of a specific catabolic enzyme.
- due to a genetic deficiency of a particular enzyme which breaks down macromolecules.
The type of defect in the gene may be due to:
- A fault in the operator gene and the allele may be totally switched off
- a fault in the regulator gene so the allele may produce a greatly reduced quantity of enzyme
- A base change in the structural gene may produce a defective enzyme with reduced activity
important: the abnormal quantities of cellular material accumulate within the secondary lysosomes.
Lysosomes–> small cytoplasmic bodies which have max activity at acid pH and are involved in intracellular digestion of macromolecules.
- Involved in cell turnover
- after breakdown residual material may accumulate within cells but they don’t cause any real functional impairments to the cell
Crystals
17
The ingestion of certain plants containing OXALATE, results in the accumulation of calcium oxalate crystals in the kidney tubules and sometimes in the CNS. The patient usually dies of hypocalcaemia or acute renal failure.
GOUT is a disease were URIC ACID are deposited in tissues, particularly around joints. The crystals start a low grade chronic inflammatory reaction with enlargement and distortion of joints.
Fat and Glycogen
18
Metabolic disorders (and alcohol consupmption) can lead to increased fat or glycogen deposition.
- liver is commonly affected (swollen, fragile, pale and grossly)
- the cytoplasm shows vacuolation such that it is clear (commonly seen in diabetes)
