Changes

Oxidation results in three major changes to the haemoglobin molecules:  

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> In most species, Heinz bodies can be removed from erythrocytes by the spleen.

* '''Heinz bodies''' are produced when the sulfhydral 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> This is the only form of oxidative damage which is reversible.

* '''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. Methaemoglobin is a brownish compound formed by the oxidation of iron in haemoglobin from the ferrous to the ferric state. When present in quantity it leads to a muddy cyanotic discolouration of mucous membranes. Usually it accounts for less than 1.1% of haemoglobin. It is increased due to oxidative damage caused by toxins which may also cause Heinz body and eccentrocyte formation. Methaemoglobinaemia results from either increased production due to oxidative injury or decreased reduction of methaemoglobin to Hb. Congenital methaemoglobinaemia has been reported due to deficiency of the RBC enzyme NADH-methaemoglobin reductase. References: [[NationWide Laboratories]]

This article will cover only Heinz bodies in detail.

This article will cover only Heinz bodies in detail.

==Substances causing Heinz body formation==

==Substances causing Heinz body formation==

===Cats===

===Cats===

* Paracetamol (acetominophen) - cats have a low level of N-acetyltransferase enzymes, which prevents them from metabolising the drug to non-toxic substances as humans do.  (ref name="ACVIM"> McConkey SE , Cribb A . The molecular mechanism of acetaminophen in dogs and cats. In: Proceedings of the 26th Annual American College of Veterinary Internal Medicine Meeting 2008, pp. 610 – 612 </ref>. They are also relatively deficient in methaemoglobin reductase and methaemoglobinaemia is also a feature of paracetamol toxicity in cats.  

* Paracetamol (acetominophen) - cats have a low level of N-acetyltransferase enzymes, which prevents them from metabolising the drug to non-toxic substances as humans do.  <ref name="ACVIM"> McConkey SE , Cribb A . The molecular mechanism of acetaminophen in dogs and cats. In: Proceedings of the 26th Annual American College of Veterinary Internal Medicine Meeting 2008, pp. 610 – 612 </ref>. They are also relatively deficient in methaemoglobin reductase and methaemoglobinaemia is also a feature of paracetamol toxicity in cats.  

* Diabetes mellitus - there is increased production of radicals resulting from various disease-induced metabolic compromises. Ketoacidotic cats have significantly higher numbers of Heinz bodies than non-ketoacidotic patients. (<ref name="DM"> Christopher M, Broussard J, Peterson M., (1995). '''Heinz body formation

* Diabetes mellitus - there is increased production of radicals resulting from various disease-induced metabolic compromises. Ketoacidotic cats have significantly higher numbers of Heinz bodies than non-ketoacidotic patients. <ref name="DM"> Christopher M, Broussard J, Peterson M., (1995). '''Heinz body formation associated with ketoacidosis in diabetic cats'''.J Vet Intern Med, Vol 9: p. 24 – 31.</ref>

associated with ketoacidosis in diabetic cats'''.J Vet Intern Med, Vol 9: p. 24 – 31.</ref>

* Hyperthyroidism - one study found increased numbers of Heinz bodies in hyperthyroid cats but patients were not significantly anaemic. (<ref name="Christopher"> Christopher M, (1989). '''Relation of endogenous Heinz bodies to disease and anemia in cats: 120 cases (1978 – 1987)'''. J Am Vet Med Assoc, Vol 194 pp. 1089-1095</ref>

* Hyperthyroidism - one study found increased numbers of Heinz bodies in hyperthyroid cats but patients were not significantly anaemic. <ref name="Christopher"> Christopher M, (1989). '''Relation of endogenous Heinz bodies to disease and anemia in cats: 120 cases (1978 – 1987)'''. J Am Vet Med Assoc, Vol 194 pp. 1089-1095</ref>

* Lymphoma - an increased percentage of Heinz bodies has been linked with lymphoma in cats. <ref name="Christopher"></ref>

* Lymphoma - an increased percentage of Heinz bodies has been linked with lymphoma in cats. <ref name="Christopher"></ref>

===Dogs===

===Dogs===

* Onions/garlic - contain oxidative agents which are active in raw, cooked and dehydrated forms. Heinz body anaemias are most common in small breeds, suggesting a dose relationship and in breeds with naturally high levels of potassium, such as Akitas and Shar-Peis.  <ref name="Schalm"></ref>

* Onions/garlic - contain oxidative agents which are active in raw, cooked and dehydrated forms. Heinz body anaemias are most common in small breeds, suggesting a dose relationship and in breeds with naturally high levels of potassium, such as Akitas and Shar-Peis.  <ref name="Schalm"></ref>

===Horses===

===Horses===

* Dried red maple leaves - contain gallic acid, which may be involved in Heinz body formation.  <ref name="maple>Alward A, Corriher C, Barton M, et al. (2006) Red maple (Acer rubrum) leaf toxicosis in horses: a retrospective study of 32 cases. '''J Vet Intern Med''' 20: 1197 – 1201</ref>

* Dried red maple leaves - contain gallic acid, which may be involved in Heinz body formation.  <ref name="maple">Alward A, Corriher C, Barton M, et al. (2006) Red maple (Acer rubrum) leaf toxicosis in horses: a retrospective study of 32 cases. '''J Vet Intern Med''' 20: 1197 – 1201</ref>

* Garlic - can be used as an antifungal agent in stock feed.

* Garlic - can be used as an antifungal agent in stock feed.

==Laboratory findings==

==Laboratory findings==

Heinz bodies are frequently missed on routine blood films as they tend not to stain well. However they are easily seen on slides stained with new methylene blue. <ref name="CVT"></ref>

Heinz bodies are frequently missed on routine blood films as they tend not to stain well. However they are easily seen on slides stained with new methylene blue and with Wright-Giemsa stain. <ref name="CVT"></ref>

 

Cats may have up to

Dogs do not normally have Heinz bodies present in their circulation and therefore if they are identified the patient history should be reviewed to try to pinpoint the oxidant exposure.

[[Category:Anaemia]]

[[Category:Anaemia|8]]