The deposition of material in tissues ranges from being completely physiologically normal and healthy (ie. melanin deposition in the skin protecting against UV damage) to being abnormal and pathological (ie. amyloidosis, calcification, abnormal pigmentation, jaundice, etc.). In this blog post I will focus on the abnormal deposition of material in tissues, briefly describing the different processes, identifying their basic common ground and how in general, it seems to me, the deposition of material seems to be a possible response, or mode of action, of the body to try to safely store material when faced with high levels of it in the blood.
Amyloid is an abnormal protein material that consists of a number of chemically different proteins that are all fibrillar and arranged in ß-pleated sheets, it is believed that it is this physio-chemical characteristic that accounts for amyloid behaviour in the body. (Rippey, 1994) The table below clearly outlines the different types of amyloid, their associated diseases and sites of deposition.
Amyloid deposits itself in the extracellular space of various organs and tissues and eventually hinders their function, even though amyloid itself is inert and does not cause an inflammatory response. For example, by restricting movement of the cardiac muscle, causing ischaemia by the narrowing of blood vessels (Kyle, 2001), causing proteinuria by increasing glomerular permeability, and causing atrophy and destruction in organs by increasing pressure on parenchymal cells. (Rippey, 1994) The protein pieces that form amyloid share in common becoming insoluble in water and are not proteolysed to be reused or excreted – they aggregate to form plaques and are deposited instead. This fact jumped out at me when I read this chapter and it was the first clue I had in considering the common ground between the materials discussed in this post. The video below demonstrates this process with regards to Alzheimer’s disease as a result of amyloid deposition in the brain. (Alzheimer’s Disease Education & Referral Centre, 2010)
When calcium is deposited in tissues other than the bones and teeth, where it is normally found, it is termed heterotropic calcification, of which there are two main types. Dystropic calcification occurs when there is no calcium metabolism abnormality and there is a deposition of calcium salts in degenerate or dead tissue such as areas of caseous necrosis and fat necrosis, around dead parasites, in thrombi forming phleboliths, in scar tissue and in tumours. (Rippey, 1994) Metastatic calcification occurs when there is a disturbance in calcium metabolism and there is usually hypercalcaemia. There are high serum levels of calcium and the calcium salts are deposited in tissues such as renal tubules, stomach wall, joints, lung alveoli, artery walls and the cornea instead of being excreted. It can also lead to the formation of calculi in hollow organs or ducts such as the pelvis, ureter or bladder of the urinary tract, or the gall bladder. (Rippey, 1994) Two common causes of hypercalcaemia are malignancy and hyperparathyroidism,less common causes are vitamin D intoxication, familial hypocalciuric hypercalcaemia and sarcoidosis. (Waters, 2009) In this case the body’s normal paths of deposition and excretion of calcium are blocked by pathological hormone signals and so it must deposit the calcium extracellularly to try and lower calcium levels in the blood – in a very general way this seemed similar to amyloid deposition to me and was my second clue. The images above, to the left shows dystrophic calcification of the aortic valve with stenosis, and to the right shows intervertebral disc calcification.
Pigmentation in the human body takes many forms. Exogenous pigments such as dust will cause a blackening of the lungs due to inhaled carbon particles accumulating in the macrophages there. Endogenous pigments such as melanin, a brown pigment produced by melanocytes, gives natural colour to our skin, iris and hair; and lipofuscin, a golden brown pigment thought to be created by free radical injury and lipid peroxidation of cell membranes and so result from cell injury and death in a tissue, particularly found in the heart. (Rippey, 1994) The video below shows lipofuscin accumulation within the retinal pigment epithelium. The image above shows melanin formation within a melanocyte and its transferral to a keratinocyte. Particularly evident in everyday life are the pigments derived from haemoglobin breakdown, nearly all of which can be seen in a bruise. The escape of red blood cells into tissues after the damaging act causes the initial redish-blue colour, followed by the formation of biliverdin causing a greenish colour, then yellow with the formation of bilirubin, and finally only haemosiderin is left causing a brownish black colour, until this is also absorbed by the body. (Rippey, 1994)
Haemosiderosis is abnormal deposition of haemosiderin, storing iron, in organs and tissues of the body. This is caused by an iron overload of the body as the body does not have a method of excreting iron to manage iron levels – this is seen particularly in haemochromatosis. (Rippey, 1994) The image to the right is a histological sample of idiopathic pulmonary haemosiderosis, showing haemosiderin-laden macrophages in the alveolar spaces and was my third clue.
Jaundice is the accumulation of bilirubin in tissues and interstitial fluid of the body due to high levels of total serum bilirubin – it is a sign of many different diseases and is not a disease itself. (Rippey, 1994) The diagram to the right outlines bilirubin metabolism. (Aras, 2012) If jaundice is due to an accumulation of unconjugated bilirubin it could be because of an overproduction of bilirubin due to excessive haemolysis, decreased hepatic uptake due to viral hepatitis, or decreased bilirubin conjugation due to a hereditary lack of glucuronyl transferase. (Rippey, 1994) If jaundice is due to an accumulation of conjugated bilirubin it could be because of extrahepatic biliary obstruction due to gallstones, impaired canalicular bile flow due to viral hepatitis, or decreased cellular secretion of conjugated bilirubin due to hereditary conditions. (Rippey, 1994) Jaundice is reversible except, under certain circumstances, high levels of total serum bilirubin may be toxic to the central nervous system of healthy term newborns and may cause neurologic impairment. (Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia, 1994) This occurs when all the albumin in the body has been used to bind to the excessive levels of unconjugated bilirubin and there is not enough – the excess bilirubin can then penetrate the blood-brain barrier, be deposited in the extracellular brain tissue, staining the tissue and causing damage to the neurons. (Rippey, 1994) This was my final clue!
For myself, the abnormal deposition of material in tissues mentioned above seem to share the common ground of the material starting out as part of normal physiological processes in the body. Then, due to various aetiologies there develops abnormally high levels of the material in the blood and the body is unable to metabolise or excrete the substance sufficiently, or not at all, and so the next option for the body is to deposit the material out of the way, so to say, in the various body tissues and extracellular spaces in order for it not to hinder normal functioning too much. However, over time the build up of abnormal material deposition becomes too much for the body to cope with and pathological symptoms occur. I think it is important to understand these pathological processes within the larger concept of learning about human disease because they are nearly all irreversible, are often not clinically visible until the deposition has built up to significant levels within the body and mostly because they are all important signs of a deeper pathological aetiology that would need to be investigated.
Alzheimer’s Disease Education & Referral Centre, 2010. Inside the Brain: Unraveling the Mystery of Alzheimer’s Disease. Available at: <http://www.youtube.com/watch?NR=1&feature=endscreen&v=NjgBnx1jVIU> [Accessed 1 March 2013].
Aras, H., 2012. All About Jaundice. [online] Slide Share. Available at: <http://www.slideshare.net/ozhenaras/all-about-jaundice> [Accessed 1 March 2013]. Slide 5.
[Dystrophic calcification of the aortic valve] n.d. [image online] Available at: <http://quizlet.com/13172006/pathology-test-1-w-pics-flash-cards/> [Accessed 1 March 2013].
HDEngineering, 2012. SPECTRALIS BluePeak – Blue Laser Autofluorescence – Lipofuscin Accumulation Over Time. Available at: <http://www.youtube.com/watch?v=M-oZh6U_GZk> [Accessed 1 March 2013].
[Idiopathic pulmonary haemosiderosis] n.d. [image online] Available at: <http://www.brown.edu/Courses/Digital_Path/systemic_path/pulmonary/iph.html> [Accessed 1 March 2013].
[Intervertebral disc calcification] 2010. [image online] Available at: <http://radiologyinthai.blogspot.com/2010/08/intervertebral-disc-calcification.html> [Accessed 1 March 2013].
Kyle, R.A., 2001. Amyloidosis: a convoluted story. British Journal of Haematology, 114, pg 529-538.
Provisional Committee for Quality Improvement and Subcommittee on Hyperbilirubinemia, 1994. Practice Parameter: Management of Hyperbilirubinemia in the Healthy Term New Born. Pediactrics, 94(4), pg 558-565.
Rippey, J.J., 1994. General Pathology. Johannesburg: Witwatersrand University Press.
Waters, M., 2009. Hypercalcaemia. InnovAiT: The Royal College of General Practitioners Journal for Associates in Training, 2(12), pg 698-701.