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==Introduction==
==Introduction==
Heinz bodies are inclusion bodies that form within erythrocytes as a result of '''oxidative injury''' to the cell. Named after Robert Heinz, the German physician who first described them, they consist of precipitated haemoglobin and their presence can result in premature phagocytosis of erythrocytes <ref name="Schalm">Weiss, D and Wardrop, K (eds) (2010) '''Schalm's Veterinary Haematology, Sixth edition''' Wiley-Blackwell p. 134</ref>
'''Heinz bodies''' are inclusion bodies that form within erythrocytes as a result of '''oxidative injury''' to the cell. Named after Robert Heinz, the German physician who first described them, they consist of precipitated haemoglobin and their presence can result in premature phagocytosis of erythrocytes <ref name="Schalm">Weiss, D and Wardrop, K (eds) (2010) '''Schalm's Veterinary Haematology, Sixth edition''' Wiley-Blackwell p. 134</ref>
===Structure of haemoglobin===
===Structure of haemoglobin===
Haemoglobin is a conjugated protein consisting of four globin chains, each of which contains a heme group. Its structure allows it to combine reversibly with oxygen and is thus very important in the transportation of oxygen to tissues. Normally the iron within the heme group is in the ferrous (2+) form, the form able to combine with oxygen.
Haemoglobin is a conjugated protein consisting of four globin chains, each of which contains a heme group. Its structure allows it to combine reversibly with oxygen and is thus very important in the transportation of oxygen to tissues. Normally the iron within the heme group is in the ferrous (2+) form, the form able to combine with oxygen.
===Oxidative damage to haemoglobin===
=====Pathophysiology of oxidative damage to haemoglobin===
Oxygen can produce reactive free radicals such as hydrogen peroxide. These substances are generated under normal physiologic conditions and there are enzyme mechanisms to prevent damage to the cell. When these mechanisms are overwhelmed, oxidative damage occurs. As erythrocytes have no organelles they are unable to synthesise proteins and so have limited ability to repair themselves.<ref name="Schalm"></ref> The damaged cells have highly rigid membranes and so are more likely to be removed from circulation <ref name="CVT"></ref>
Oxidation results in three major changes to the haemoglobin molecules:
* '''Heinz bodies''' are produced when the sylfhydral groups in the '''globin part of the haemoglobin molecule''' undergoes oxidation, causing the molecule to become unstable. Heinz bodies are formed when the damaged haemoglobin molecules coalesce. <ref name="CVT">Bonagura, J and Kirk, R (eds) (1995) '''Kirk's Current Veterinary Therapy XII''' WB Saunders, p. 444</ref>
* '''Heinz bodies''' are produced when the sylfhydral groups in the '''globin part of the haemoglobin molecule''' undergoes oxidation, causing the molecule to become unstable. Heinz bodies are formed when the damaged haemoglobin molecules coalesce. <ref name="CVT">Bonagura, J and Kirk, R (eds) (1995) '''Kirk's Current Veterinary Therapy XII''' WB Saunders, p. 444</ref> In most species, Heinz bodies can be removed from erythrocytes by the spleen.
* '''Methaemoglobinaemia''' formation occurs when the '''iron in the haemoglobin molecule''' is oxidised to the ferric (3+) state. In normal circumstances the methaemoglobin reductase enzyme reduces ferric (3+) back to ferrous (2+) but this system can become overwhelmed in some circumstances.<ref name="CVT"></ref>
* '''Methaemoglobinaemia''' formation occurs when the '''iron in the haemoglobin molecule''' is oxidised to the ferric (3+) state. In normal circumstances the methaemoglobin reductase enzyme reduces ferric (3+) back to ferrous (2+) but this system can become overwhelmed in some circumstances.<ref name="CVT"></ref> This is the only form of oxidative damage which is reversible.
* '''Eccentrocytes'''
* '''Eccentrocytes''' have their haemoglobin concentrated on one side of the cell, causing the opposite side of the cell to appear clear. They are probably formed
when there is damage to the erythrocyte membrane.
This article will cover only Heinz bodies in detail.
Cats, dogs, horses and ruminants can all suffer from Heinz body anaemias but they are clinically significant mainly in the cat and dog.
Cats, dogs, horses and ruminants can all suffer from Heinz body anaemias but they are clinically significant mainly in the cat and dog.
Cats
===Cats===
Feline erythrocytes are particularly susceptible to oxidative damage because they have eight highly reactive sulfhydryl groups, as opposed to two
Feline erythrocytes are particularly susceptible to oxidative damage as they have eight highly reactive sulfhydryl groups, as opposed to two
less reactive ones in other species.
less reactive ones in other species. In addition, the cat spleen is less efficient in the removal of Heinz bodies from erythrocytes. These two characteristics mean that cats may have 5-10% of erythrocytes containing Heinz bodies under normal circumstances and makes them very susceptible to developing clinical signs of toxicity on exposure to oxidative substances.
*
* Paracetamol (known as acetominophen in the US) - cats have a low level of N-acetyltransferase enzymes, which prevents them from metabolising the drug to non-toxic substances. They are also relatively deficient in methaemoglobin reductase and methaemoglobinaemia is also a feature of paracetamol toxicity in cats.
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