Learning Objectives Wk 10 Vincent is Off Colour
Marty Roebuck
Pathology of Pigments and Depositions
1. Outline the sources and characteristics of common pigments including
bilirubin, lipofuscin and haemosiderin.
Bilirubin:
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Major end product of haemoglobin degradation (red blood cell (RBC) lifespan = 120 days)
This occurs in liver (Kupffer cells), spleen and bone marrow (macrophages).
This action by tissue macrophages is referred to as reticuloendothelial system
Haemoglobin molecule:
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Iron portion : passed back into blood to be carried by transferrin either to bone marrow for
production of new blood cells or to the liver and other tissues for storage in the form of ferritin.
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Porphyrin portion : converted by macrophages – series of stages: biliverdin → free or unconjugated
bilirubin → released into blood, binds with plasma albumin (also in interstitial fluids) → liver.
Once in liver: Unconjugated bilirubin→ passes through hepatic cell membrane → released from
plasma albumin → conjugated (joined) with glucuronic acid (80% = bilirubin glucuronide), sulphate
(10% = bilirubin sulphate), +others (10%), excreted in bile via canaliculi → intestines – mostly
deconjugated here to colourless urobilinogens → 20% urobilinogens reabsorbed in
ileum/colon→liver (bile) or kidney (urine) → faeces = urobilinogens + intact pigment.
Lipofuscin.
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Latin – (fuscus,brown)
Insoluble pigment, also known as “wear and tear pigment” (Robbins and Cottran, Pathologic
basis of Disease, p36)
Is not injurious to the cell or its functions.
Sign of free radical injury and lipid peroxidation
Seen in cells undergoing slow, regressive changes – prominent in liver and heart of aging patients
or patients with severe malnutrition and cancer cachexia
Haemosiderin.
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Haemoglobin-derived, golden yellow-to-brown, granular or crystalline pigment that serves as
one of the major storage forms of iron.
This pigment represents aggregates of ferrin micelles, where iron is carried by specific transport
proteins (transferrins) and stored in association with another protein (apoferritin).
Haemosiderin can be seen via light microscope in the mononuclear phagocytes of the bone
marrow, spleen and liver which are actively engaged in red cell breakdown (see Bilirubin, above)
Accumulates when excess iron arises – eg from local tissue haemorrhage ( as in bruising).
Systemic overload may also occur – eg ↑ dietary iron absorption, ↑ iron released from
erythrocytes (haemolytic anaemia). This can cause deposition in many organs and tissues which
can be damaging – a condition called haemosiderosis.
2. Differentiate jaundice from cholestasis.
Jaundice:
 Yellow discolouration of the skin. (in sclera = “icterus”)
 Occurs when the equilibrium between bilirubin production and clearance is disturbed.
 This causes either conjugated or unconjugated hyperbilirubinaemia – see 3. Below.
Haemolytic Jaundice: (Guyton p 841)
Caused by:
- Haemolysis of red blood cells (rbc’s).
- Liver excretory function NOT impaired.
- RBC’s haemolysed so rapidly → hepatic cells can’t excrete bilirubin as quickly as it is
formed → plasma bilirubin ↑ to > normal.
- Rate of formation of urobilinogen in intestine ↑, reabsorbed into blood, excreted
in urine.
Obstructive Jaundice: (Guyton p 841)
Caused by:
- Obstruction of bile ducts or liver disease
- Gallstone or cancer blocks common bile duct or:
- Hepatic cell damage (hepatitis)
Unconjugated Bilirubin → liver → conjugated→ bilirubin returns to blood,
probably by rupture of congested bile canaliculi → emptying of bile into
lymph leaving liver→ conjugated bilirubin in plasma > unconjugated
Cholestasis:
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Denotes a pathologic condition of impaired bile flow caused by extrahepatic or intrahepatic
obstruction of bile channels or by defects in hepatocyte bile secretion.
Intrahepatic: Hepatocyte damage, swelling eg - hepatitis, drugs, excessive alcohol consumption.
Extrahepatic: Gall stones, duct abnormalities – eg cancer.
3. Outline causes of conjugated and unconjugated hyperbilirubinaemia.
Normal serum bilirubin = 0.2-1.2mg/dl
Jaundice (>3mg/dl approx.) occurs when the equilibrium between bilirubin production and clearance is
disturbed by:
a)
b)
c)
Excessive extrahepatic production of bilirubin
Reduced hepatocyte uptake
Impaired conjugation
a,b,c – will cause unconjugated hyperbilirubinaemia
d)
e)
Decreased hepatocellular excretion
Impaired bile flow
d,e – will produce predominantly conjugated hyper bilirubinaemia
4. Be aware of other pathologic tissue depositions e.g. calcium, amyloid, urates.
Calcium Deposition.
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Often deposited at sites of cell death, resulting in pathologic calcification – abnormal tissue
deposition of calcium salts + iron, magnesium + other mineral salts. 2 Types of deposition:
a) Dystrophic deposition:
 Occurs locally in dying, necrotic tissues.
 Formation of crystalline calcium phosphate mineral.
 Often a cause of organ dysfunction.
 eg – calcific valvular disease, atherosclerosis.
b) Metastatic Calcification:
 may occur in normal tissues whenever there is hypercalcaemia due to:
o ↑ parathyroid hormone secretion → bone resorption
o Destruction of bone tissue, secondary to: bone marrow tumours, diffuse
skeletal metastasis (eg breast cancer), accelerated bone turnover (Pagets
disease), immobilisation.
o Vitamin D disorders
o Renal failure → phosphate retention
o
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Amyloid Deposition
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+ less common “other” – aluminium intoxication, milk alkali syndrome
(excessive calcium ingestion)
Principally affects interstitial tissues of gastric mucosa, kidneys, lungs, systemic
arteries and pulmonary veins.
(see Robbins and Cottran p 249-255)
Amyloid – “pathological proteinaceous substance, deposited in the extracellular
space in various tissues and organs of the body in a wide variety of clinical settings”
(Robbins and Cottran. P249)
Amyloidosis – Pathogenesis probably related to abnormal protein folding. Also,
immunological abnormalities associated with some forms of amyloidosis.
Proteins deposited as fibrils in extracellular tissue and disrupt normal function in
organs such as kidney (ischaemia, vascular narrowing) liver (encroachment on space
of Disse, hepatocytes, sinusoids), spleen and heart (pressure atrophy of myocardial
muscle fibres).
Should not be considered a single disease, rather it is a group of diseases having in
common the deposition of similar proteins.
Histologic diagnosis based on staining characteristics.
Clinical manifestations at first are often entirely non-specific – weakness, weight
loss, light-headedness or syncope. Specific findings appear later – renal, cardiac,
gastrointestinal involvement.
Urate Deposition
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Urate = a salt derived from uric acid = end product of purine metabolism. Plasma levels of
uric acid = production V excretion.
Hyperuricaemia can cause deposition of urate in various tissues resulting in dysfunction
In the urinary tract - uric acid stones = urolithiasis
In the kidney - either acute or chronic nephropathy.
Crystallisation of urates within and about joints = gouty arthritis