Changes

==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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ binding and subsequent formation of hydroxyapatite in bone.

==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.

 

====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>.

== 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"/>.

== 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.

== 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>.

==References==

==References==

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[[Category:Vitamins]]

[[Category:Vitamins]]