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| ==What is Vitamin K (Menaquinone-7, MK-7)?== | | ==What is Vitamin K (Menaquinone-7, MK-7)?== |
− | Vitamin K is category of '''essential fat-soluble vitamins''' that consist of napthaquinone rings with aliphatic side-chains. They are found naturally-occurring in the diet as one of two forms: '''plant-derived vitamin K<sub>1</sub> (phylloquinone) or animal-derived vitamin K<sub>2</sub> (menaquinone-7 or MK-7)''', the latter is derived from bacterial synthesis in the gastrointestinal tract. Vitamin K<sub>3</sub> (menadione) is a synthetic compound, often used as a dietary supplement in animal feeds<ref name="NRC">National Research Council (NRC). Vitamins. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p.210-212.</ref>. However this form of vitamin K (menadione) is not biologically active, until it is converted to vitamin K<sub>2</sub> (MK-7) by intestinal microbes prior to absorption. Vitamin K is incorporated into mixed micelles along with dietary [[Fat Overview - Nutrition|fat]] and absorbed by [[Diffusion - Physiology|diffusion]] across the mucosal surface of the [[Small Intestine Overview - Anatomy & Physiology|small intestine]]. Once in the enterocytes, absorbed vitamin K is incorporated into chylomicrons and released into the [[Lymphatic System Overview - Anatomy & Physiology|lymphatics]] for transport to the [[Liver - Anatomy & Physiology|liver]]. Vitamin K is primarily excreted through [[Bile acids|bile]] in faeces, though significant amounts are also lost through urine. | + | Vitamin K is category of '''[[Nutrition Glossary#Essential Nutrients|essential]] fat-soluble vitamins''' that consist of napthaquinone rings with aliphatic side-chains. They are found naturally-occurring in the diet as one of two forms: '''plant-derived vitamin K<sub>1</sub> (phylloquinone) or animal-derived vitamin K<sub>2</sub> (menaquinone-7 or MK-7)''', the latter is derived from bacterial synthesis in the gastrointestinal tract. Vitamin K<sub>3</sub> (menadione) is a synthetic compound, often used as a dietary supplement in animal feeds<ref name="NRC">National Research Council (NRC). Vitamins. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p.210-212.</ref>. However this form of vitamin K (menadione) is not biologically active, until it is converted to vitamin K<sub>2</sub> (MK-7) by intestinal microbes prior to absorption. Vitamin K is incorporated into mixed micelles along with dietary [[Fat Overview - Nutrition|fat]] and absorbed by [[Diffusion - Physiology|diffusion]] across the mucosal surface of the [[Small Intestine Overview - Anatomy & Physiology|small intestine]]. Once in the enterocytes, absorbed vitamin K is incorporated into chylomicrons and released into the [[Lymphatic System Overview - Anatomy & Physiology|lymphatics]] for transport to the [[Liver - Anatomy & Physiology|liver]]. Vitamin K is primarily excreted through [[Bile acids|bile]] in faeces, though significant amounts are also lost through urine. |
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| ==Why is it Important?== | | ==Why is it Important?== |
− | Vitamin K is important for normal blood clotting and [[Bone & Cartilage Development - Anatomy & Physiology|bone formation]]. Under normal circumstances endogenous production of vitamin K bacterial synthesis in the gastrointestinal tract is sufficient to meet metabolic requirements. | + | Vitamin K is important for [[Normal Mechanisms of Haemostatic Control|normal blood clotting]] and [[Bone & Cartilage Development - Anatomy & Physiology|bone formation]]. Under normal circumstances endogenous production of vitamin K bacterial synthesis in the gastrointestinal tract is sufficient to meet metabolic requirements. |
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| ==Roles in the Body== | | ==Roles in the Body== |
− | #'''Coagulation Factors''': The aliphatic side-chain on MK-7 serves as a substrate for γ-glutamyl carboxylase, which results in carboxylation of glutamyl residues on prothrombin (i.e., factor II), as well as the glutamyl residues on coagulation factors VII, IX, X<ref>Suttie JW. Vitamin K. In Biochemical and physiological aspects of human nutrition. 2000 Philadelphia, PA: WB Saunders Company p.568-583.</ref>. This carboxylation facilitates Ca<sup>2+</sup> binding and activation of these proteins, which initiates the coagulation cascade<ref>Winter RL, et al. Aortic thrombosis in dogs: presentation, therapy, and outcome in 26 cases. J Vet Cardiol 2012;14:333-342.</ref>. Decarboxylated MK-7 forms a vitamin-K-epoxide that must be recycled through reaction with a vitamin-K-epoxide reductase in the liver. | + | #'''Coagulation Factors''': The aliphatic side-chain on MK-7 serves as a substrate for γ-glutamyl carboxylase, which results in carboxylation of glutamyl residues on prothrombin (i.e. factor II), as well as the glutamyl residues on coagulation factors VII, IX, X<ref>Suttie JW. Vitamin K. In Biochemical and physiological aspects of human nutrition. 2000 Philadelphia, PA: WB Saunders Company p.568-583.</ref>. This carboxylation facilitates Ca<sup>2+</sup> binding and activation of these proteins, which initiates the coagulation cascade<ref>Winter RL, et al. Aortic thrombosis in dogs: presentation, therapy, and outcome in 26 cases. J Vet Cardiol 2012;14:333-342.</ref>. Decarboxylated MK-7 forms a vitamin-K-epoxide that must be recycled through reaction with a vitamin-K-epoxide reductase in the liver. |
− | #'''Bone Health''': Osteocalcin is secreted by [[osteoblasts]] and is the second most abundant protein in bone<ref>Neve A, et al. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 2013;228:1149-1153.</ref>. Glutamyl residues on osteocalcin are carboxylated by vitamin-K-dependant carboxylase enzymes and allow Ca<sup>2+</sup> binding and subsequent formation of hydroxyapatite in bone. | + | #'''Bone Health''': Osteocalcin is secreted by [[osteoblasts]] and is the second most abundant protein in bone<ref>Neve A, et al. Osteocalcin: skeletal and extra-skeletal effects. J Cell Physiol 2013;228:1149-1153.</ref>. Glutamyl residues on osteocalcin are carboxylated by vitamin-K-dependant carboxylase enzymes and allow Ca<sup>2+</sup> binding and subsequent formation of hydroxyapatite in bone. |
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| ==Consequences of Vitamin K Deficiency== | | ==Consequences of Vitamin K Deficiency== |
| ====Dogs:==== | | ====Dogs:==== |
− | Clinical signs of vitamin K deficiency include prolonged bleeding times that can progress to internal [[haemorrhage]] and death if not treated. Because of adequate microbial synthesis, naturally occurring vitamin K deficiencies have not been reported in dogs. Relative deficiencies can occur due to vitamin K antagonist exposure (i.e., [[Anticoagulant Rodenticide Toxicity|warfarin toxicity]])<ref>Clark WT and Halliwell REW. The treatment of vitamin K preparation of warfarin poisoning in dogs. Vet Rec 1963;75:1210-1213.</ref> or in animals with synthetic liver failure. | + | Clinical signs of vitamin K deficiency include prolonged bleeding times that can progress to internal [[haemorrhage]] and death if not treated. Because of adequate microbial synthesis, naturally occurring vitamin K deficiencies have not been reported in dogs. Relative deficiencies can occur due to vitamin K antagonist exposure (i.e. [[Anticoagulant Rodenticide Toxicity|warfarin toxicity]])<ref>Clark WT and Halliwell REW. The treatment of vitamin K preparation of warfarin poisoning in dogs. Vet Rec 1963;75:1210-1213.</ref> or in animals with synthetic liver failure. |
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| ====Cats:==== | | ====Cats:==== |
− | Clinical signs of vitamin K deficiency in kittens and adult cats include prolonged bleeding times, internal haemorrhage, and death. Congenital defects in γ-glutamyl carboxylase have been described in Devon Rex cats<ref>Soute BA, et al. Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats. Thromb Haemost 1992;68:521-525.</ref>, and the feeding of fish-based diets does not support adequate microbial vitamin K synthesis<ref>Strieker MJ, et al. Vitamin K deficiency in cats fed commercial fish-based diets. J Small Anim Pract 1996;37:322-326.</ref> and can result in a vitamin K deficiency unless supplemental vitamin K is added to the diet. Relative deficiencies can occur in cats due to vitamin K antagonist exposure (i.e., warfarin toxicity) or in animals with chronic liver or intestinal disease<ref>Center SA, et al. Proteins invoked by vitamin K absence and clotting times in clinically ill cats. JVIM 2000 14:292-297.</ref>. | + | Clinical signs of vitamin K deficiency in kittens and adult cats include prolonged bleeding times, internal haemorrhage, and death. Congenital defects in γ-glutamyl carboxylase have been described in Devon Rex cats<ref>Soute BA, et al. Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats. Thromb Haemost 1992;68:521-525.</ref>, and the feeding of fish-based diets does not support adequate microbial vitamin K synthesis<ref>Strieker MJ, et al. Vitamin K deficiency in cats fed commercial fish-based diets. J Small Anim Pract 1996;37:322-326.</ref> and can result in a vitamin K deficiency unless supplemental vitamin K is added to the diet. Relative deficiencies can occur in cats due to vitamin K antagonist exposure (i.e. warfarin toxicity) or in animals with chronic [[Liver - Pathology|liver]] or [[:Category:Intestines, Small and Large - Pathology|intestinal disease]]<ref>Center SA, et al. Proteins invoked by vitamin K absence and clotting times in clinically ill cats. JVIM 2000 14:292-297.</ref>. |
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| == Toxicity == | | == Toxicity == |
− | There are no published reports of MK-7 and phylloquinone toxicity in dogs and cats and oral menadione has only been shown to be toxic when given at 1000x the requirement<ref name="NRC"/>. Conversely, parenteral menadione is toxic in all species and can cause haemolytic [[Regenerative and Non-Regenerative Anaemias|anaemia]] at low dosages and should not be given<ref name="NRC"/>. | + | There are no published reports of MK-7 and phylloquinone toxicity in dogs and cats and oral menadione has only been shown to be toxic when given at 1000x the requirement<ref name="NRC"/>. Conversely, '''parenteral menadione is toxic''' in all species and can cause haemolytic [[Regenerative and Non-Regenerative Anaemias|anaemia]] at low dosages and should not be given<ref name="NRC"/>. |
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| == Dietary Sources == | | == Dietary Sources == |
− | Vitamin K is found in varied concentrations in all foodstuffs. Liver has higher concentrations of MK-7 than other animal proteins such as muscle meat, dairy, and eggs. Phylloquinone is concentrated in the leaves of dark-green vegetables (e.g., spinach, kale, broccoli) as well as pulses (i.e., legumes), while cereal grains and other fruits and vegetables have lower concentrations of phylloquinone. Menadione is used as a vitamin K supplement in commercial dog and cat foods. | + | Vitamin K is found in varied concentrations in all foodstuffs. Liver has higher concentrations of MK-7 than other animal proteins such as muscle meat, dairy, and eggs. Phylloquinone is concentrated in the leaves of dark-green vegetables (e.g. spinach, kale, broccoli) as well as pulses (i.e. legumes), while cereal grains and other fruits and vegetables have lower concentrations of phylloquinone. Menadione is used as a vitamin K supplement in commercial dog and cat foods. |
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| == Diagnosing Vitamin K Deficiency == | | == Diagnosing Vitamin K Deficiency == |
− | A true deficiency of Vitamin K is rarely encountered in clinical practice; a relative deficiency resulting from intoxication with a Vitamin K antagonist (e.g., Warfarin) is more likely. A clinical suspicion arises when animals have bleeding tendencies (e.g., haemorrhage) compatible clinical signs and prolongation of [[Coagulation Tests#Prothrombin Time|prothrombin time (PT)]] and possibly activated partial thromboplastin time (aPTT). Measuring elevated levels of Proteins Induced by Vitamin K Antagonism (PIVKA) is a sensitive indicator for vitamin K deficiency and enables confirmation of the diagnosis; however, PIVKA is not a direct vitamin K test but simply a more sensitive assay for PT<ref>Mount ME, et al. Use of a test for proteins induced by vitamin K absence or antagonism in diagnosis of anticoagulant poisoning in dogs: 325 cases (1987-1997). JAVMA 2003;222:194-198.</ref>. | + | A true deficiency of Vitamin K is rarely encountered in clinical practice; a relative deficiency resulting from intoxication with a Vitamin K antagonist (e.g. Warfarin) is more likely. A clinical suspicion arises when animals have bleeding tendencies (e.g. haemorrhage) compatible clinical signs and prolongation of [[Coagulation Tests#Prothrombin Time|prothrombin time (PT)]] and possibly [[Coagulation Tests#Activated Partial Thromboplastin Time|activated partial thromboplastin time (aPTT)]]. Measuring elevated levels of Proteins Induced by Vitamin K Antagonism (PIVKA) is a sensitive indicator for vitamin K deficiency and enables confirmation of the diagnosis; however, PIVKA is not a direct vitamin K test but simply a more sensitive assay for PT<ref>Mount ME, et al. Use of a test for proteins induced by vitamin K absence or antagonism in diagnosis of anticoagulant poisoning in dogs: 325 cases (1987-1997). JAVMA 2003;222:194-198.</ref>. |
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| ==References== | | ==References== |
| <references/> | | <references/> |
| + | <br> |
| + | {{Reviewed Nutrition 1 |
| + | |date = 22 May 2015}} |
| + | {{Waltham}} |
| + | {{OpenPages}} |
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| [[Category:Vitamins]] | | [[Category:Vitamins]] |
− | [[Category:To Do - Nutrition]]
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− | [[Category:To Do - Nutrition preMars]]
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