Pigments, Infiltrates and Storage Diseases

Pigments, Infiltrates and Storage Diseases are a result of the accumulation of either a normal substance in abnormal amounts or an abnormal substance inside cells or between them. These diseases can be inherited or acquired and may cause organ dysfunction but in some cases are incidental findings. In this post we’ll take a look at haemosiderosis, anthracosis, lipofuscinosis, amyloidosis, and hyperbilirubinaemia.We'll also look at how storage diseases, in particular: lysosomal storage diseases, work.

Infiltrations and Pigmentations
Pigmentations

Pigments can either be exogenous or endogenous. Examples of exogenous pigments include tattoo inks and carbon pollutants. Endogenous pigments can be physiological or pathological and include: haemosiderin, bilirubin, melanin and lipofuscin.

Exogenous

Anthracosis refers to the local accumulation of black carbon particles in the lungs and draining lymph nodes as a result of long-term exposure to polluted air. The carbon is taken up by macrophages which then travel to the lymph nodes and interstitium. The carbon is inert and so it has no effect on the function of the organ. Histologically, anthracosis is seen as blue-black fine granules within macrophages around airways and lymphatics in the lungs. Anthracosis is not a pathological disease and is instead usually an incidental finding.

Endogenous

Lipofuscin is known as the ‘wear and tear’ pigment and appears as a feint yellow-brown colour histologically under the haematoxylin and eosin stain. This compound consists of complexes of lipid-protein substances that are derived from the peroxidation of lipids in cell membranes. The presence of lipofuscin is associated with:

·         Aging: continuous exposure throughout life to environmental factors generates free radicals

·         Diets high in fat

·         Vitamin E deficiency: Vit E is incorporated into the membrane and helps to prevent peroxidation.

Lipofuscin will accumulate in non-dividing cells as well as liver cells. In addition, it may accumulate in muscle cells such is seen in alimentary lipofuscinosis.

Haemosiderin is a yellow-brown iron containing pigment derived from the breakdown of haemoglobin. Abnormal quantities of haemosiderin may accumulate within macrophages, at sites of haemorrhage as well as in the liver, spleen or kidney. The accumulations may result in haemosiderosis which, grossly, can cause a brown discoloration of the tissue.

Haemochromatosis is a group of genetic defects which cause generalised abnormal storage or abnormal increase in absorption of iron. This is always pathological and leads to tissue damage.

Amyloid is an extracellular deposit and when present in large amounts can cause organs to be large, pale and waxy. Generally, amyloid is an insoluble beta-pleated sheet which is deposited extracellularly and is resistant to proteolysis. It may arise from several different compounds.

Amyloidosis is the abnormal accumulation of amyloid. Systemic forms of amyloidosis is cause amyloid deposits in many tissues (usually the kidney, liver and spleen). The reactive form of amyloidosis affects the kidney liver and spleen and is often associated with a persistent inflammatory disease. Immune amyloid is a result of the neoplasm of plasma cells.

Bilirubin is an orange pigment derived from the breakdown of heme. In excess amounts it causes tissues to appear yellow and this is known as jaundice or icterus and this is seen in the sclera, mucous membranes or the aorta’s lining. There are three forms of icterus:

1.       Haemolytic: this is when there is an increased breakdown of erythrocytes. There may be haemoglobinaemia, haemoglobinurea and increase in unconjugated bilirubin in the blood.

2.       Toxic: this is where there is damage to the liver so that hepatocytes are unable to conjugate bilirubin (bilirubin is toxic in its unconjugated form). As a result of this there is an increase in free bilirubin in the blood with no evidence of haemolysis.

3.       Obstructive: this is where there is obstruction to the excretion of conjugated bile as a result of blockage of the bile duct system. This causes an increase in the amount of conjugated bilirubin in the blood. In addition, there may be no or reduced amounts of serum, urine urobilinogen and pale faeces.

Storage Diseases

Storage diseases involve the accumulation of a macromolecular substance in a tissue and this is due to the inadequate production of a specific catabolic enzyme.

This is usually the result of homozygous autosomal recessive patterns of transmission of a familial genetic defect. The defect in the gene may be due to:

·         A fault in the operator gene and the allele may be switched off

·         A fault in the regulator gene so that 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.

Lysosomal Storage Disease

These diseases are the most important group of storage diseases. It involves the accumulation of abnormal quantities of cellular material within secondary lysosomes.

Lysosomes are small bodies with the cytoplasm that contain about 40 hydrolytic enzymes enclosed within a membrane. Lysosomes are responsible for the turnover of macromolecules within the cell. When these macromolecules are broken down in the lysosome, residual material may accumulate within the cell. Clinically many lysosomal storage diseases show neurological changes.

That's all for now, if you have any questions please let me know :)