PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN Haemostasis An efficient

PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Haemostasis An efficient Mechanism is functional to maintain the circulation as a transport system. l It prevents blood loss from damaged vessels. l It also prevents cessation of blood flow due to thrombosis. l Haemostasis depends upon interaction between the vessel walls , platelets and clotting factors. l PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Mechanism It occurs in two phases primary and secondary. l In primary the damaged vessel constricts and platelets aggregates to form platlet plug. l In secondary phase plugs get secure by fibrin clot net work formed by the activation of clotting factors. l PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

What are Clotting Factors ? l l l Clotting factors are proteins , synthesized mainly by liver. Factor II , VII , IX and X are vitamin K dependent. These factors are rich in Glutamic acid, which require carboxylation. The enzyme required for this carboxylation is Glutamic acid carboxylase It is Vit. K dependent PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Vitamin K Also known as anti hemeregic factor PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Vitamin K The name vitamin K , has been derived from Danish word “Koagulation” since it has important role in blood clotting. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

FORMS OF Vitamin K exists in two forms. 1. Vit K-1 (phyllo quinone) in green plants 2. Vit K-2 (menaquinone) in animals and (Produced by intestinal bacteria) 3. Vit K 3 ( Menadione ) is the synthetic form of this vitamin and is most commonly used. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Food sources PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Food sources/ Stability ANIMAL SOURCES l Liver l Kidney STABILITY It is heat stable but can be destroyed by acids, alkalis and irradiation PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Requirements l Its requirement is not well established in adults, but it is suggested that 20 -100 µg/day is sufficient to meet its daily needs. l It is advised to administer a single, prophylactic dose of 1 mg of vitamin K 1 to a newborn, on the first day of life. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Recommended Daily Allowance l l l l Age Group Adequate Intake 0 -6 months 2. 0 micrograms/day 7 -12 months 2. 5 micrograms/day 1 -3 years 30 micrograms/day 4 -8 55 micrograms/day 9 -13 60 micrograms/day Girls 14 -18 75 micrograms/day Women 19 and up 90 micrograms/day Preg. / BFeeding 75 micrograms/day PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Absorption and metabolism About half of the Vit K required is derived from dietary sources specially green leafy vegetables, and about half is synthesized by the gut flora. As it is fat soluble, requires the presence of bile for its absorption, which occurs mostly in the upper part of the small intestine. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

METABOLISM OF VITAMIN K 1. 70% of Vit. K 3 ( menadione) excreted in urine in 24 hr in the form of sulphate, phosphate and glucuronic acid conjugate. 2. Small % excreted in faces as glucuronic acid conjugate. 3. Vit K 2 and K 3 undergo slower metabolism to shorten the side chain to 5 - 7 carbons carboxylate. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

SYMPTOMS OF VITAMIN K DEFICIENCY 1. 2. 3. Uncontrolled internal bleeding. Cartilage calcification and malformation of developing bone. Deposition of insoluble calcium salts in the arterial vessel walls. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Factors needed to prevent vitamin K deficiency: a. Normal diet containing the vitamin. b. Presence of bile in the intestine. c. A normal intestinal uptake or absorption. d. A normal liver i. e. no interference with vitamin K metabolism or use of vitamin K antagonists therapeutically or accidently. e. Heavy alcohol consumption impairs the liver’s ability to produce vitamin K-dependent coagulation factors and impair recycling of vitamin K. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Functions l Vitamin K is essential for the maintenance of the normal levels of various blood-clotting factors, specially prothrombin, factor VII, factor IX, and factor x. l These proteins are synthesized in the liver in their inactive forms (zymogen) and get converted to their biologically active forms with the help of vitamin K. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Role in Gamma-carboxylation l Formation of the clotting factors requires the vitamin K-dependent carboxylation of glutamic acid residues. l This forms a mature clotting factor that contains γ-carboxyglutamate (Gla) and is capable of subsequent activation. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Functions l Has a role in osteocalcein and C-reactive proteins synthesis and activation l Other physiologic functions include electron transport, growth and photosynthesis. l Advanced liver damage, as caused by cancer or Cirrhosis, causes prothrombin deficiency that cannot be alleviated by the administration of Vit K PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Deficiency Symptoms l Deficiency of vitamin K is seen in the newborns, due to their sterile intestine, particularly in premature infants who show reduced levels of vitamin K, prothrombin, and Christmas factor. l Common deficiency symptoms include cutaneous and intramuscular hemorrhages with bluish-red coloration in different parts of the body. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Causes of deficiency Deficiency of Vit K can be caused by : 1. Elimination of sources from diet. 2. Suppression of growth of the intestinal microflora by antibiotics Use for a long period. 3. With impaired lipid absorption such as that resulting from the use of mineral oil as a laxative. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Drug Interactions l l l Many drugs can interfere with the effects of vitamin K. Antacids. Laxatives. Blood Thinners like Aspirin Antibiotics and sulfonamides Drugs for cancer, Seizures and High Cholesterol PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Vitamin K antagonists l The anticoagulants dicumarol and warfarin act as antivitamins for vitamin K, due to their structural similarities with vitamin K 1. l They act as competitive inhibitors for the enzymes, which are concerned with the activation of prothrombin and other coagulation factors, and require vitamin K for their activation. PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN

Vitamin K Cycle PESHAWAR MEDICAL COLLEGE NWFP PAKISTAN