Vitamins Flashcards
1
Q
Hypervitaminosis A
A
- acute toxicity raised ICP
- Sx: headache, nausea, projectile vomiting
- Dry & pruritic skin (itchy skin)
- enlarged liver
- pregnancy: spontaneous abortions & congenital malformations in fetus
2
Q
Deficiency of Vit. A
A
Causes:
- fat free diets (fad diets)
- malabsorption of fats can also lead to deficiency Sx:
- night blindness
- Xerophthalmia:
- dryness of conjunctive & cornea
- Bitot’s spots
- Keratomalacia: corneal erosion
- increased risk of pulm infections: loss of muco-ciliary epithelium
- immune deficiency
- skin metaplasia with hyperkeratinisation
- increased predisposition to formation of renal & urinary stones
3
Q
Clinical uses of Vit. A
A
- Routine injection of Vit. A given with measles vaccine and also in clinical cases of measles as it helps to reduce the severeity of the disease
- Role on leukemia rx: trans form given along with chemotherapy in Acute Promyelocytic Leukemia
- Rx of acne & psoriasis: topical application
4
Q
Sources & Fx of Vit. A
A
Sources
- animal derived: liver, kidney, egg yolks, fish, milk, butter
- plant derived: yellow vegetables (carrots, squash) & green leafy veg.
- Kerotene: Pro-vit Fx Vision: component of rhodopsin (visual pigment). Visual cycle requires isomerization b/w cis & trans retinal
- Retinol: transport & storage form
- Retinal: component of visual pigment
- Retinoic Acid: active in epithelial differentiation & growth
- Maintenance of specialized epithelia, especially mucous secreting cells
- Growth
- Repro
- Immunity: stimulation of immune system to generate immunity against infection
5
Q
Absorption & Transport of Vit. A
A
- Diet contains retinol esters
- Hydrolysis by intestinal mucosa releasing retinol & free fatty acids
- Re-esterification & secretion in chylomicrons which are taken up by the liver where it is stored
- Plasma retinol binding protein in the liver transports to extra hepatic tissues
- Tissues contain cell retinol binding protein that carries retinoic acid to the nucleus
6
Q
Retinoids MOA
A
- retinol enters the target cell & is oxidised to retinoic acid in the cytosol
- from the cytosol, the retinoic acid moves into the nucleus with the help of cell retinoid binding proteins
- retinoic acid binds to intranuclear receptor forming an activated receptor complex
- retinoic acid-receptor complex binds to chromatin activating gene transcription
7
Q
Biochemical Events in vision
A
- retinol transported to the retina & enters the retinal pigment cells
- esterified to form a retinyl ester - storage form
- ester can be hydrolysed to form 11-cis retinol - oxidised to 11-cis retinal
- 11-cis retinal enters the rod cell where it combines with opsin to form rhodopsin (visual pigment)
- absorption of a photon of light catalyses the isomerization of 11-cis-retinal to all-trans-retinal triggering a cascade of events, leading to the generation of an electrical signal to the optic nerve which is interpreed as vision
8
Q
Metabolism of Vit. D
A
- Ergocalciferol (D2): found in plants
- Cholecalciferol (D3): found in animal tissues
- precursor of cholecalciferol synthesis in skin is 7-dehydrocholesterol (intermediate in cholesterol synthesis) in presence of sunlight.
- 1,25 Dihydroxycholecalciferol (calcitriol) is most active form:
- 25-hydroxycholecalciferol 1-hydroxylase aka alpha1-hydroxylase: converts 25-hydroxycholecalciferol -> 1, 25 dihydroxycholecalciferol
- Low plasma Ca2+ & PTH stimulate 25-hydroxycholecalciferol 1-hydroxylase
9
Q
Vit. D. Fx
A
Actions
- essential fx of Vit. D is maintenance of normal plasma Ca2+ & phosphorous levels. on the intestine: stimulates intestinal absorption of Ca2+ & PO43- by increased synthesis of specific Ca2+ binding proteins. PO4+ absorption is increased through the action of PTH Bone: stimulates the mobilisation of Ca2+ on PO43-from bone in presence of PTH
- Kidneys: Vit. D stimulates parathyroid dependent reabsorption of Ca2+ from the distal renal tubules &inhibits Ca2+ excretion by stimulating parathyroid dependent Ca2+ reabsorption.
10
Q
Vit. D sources & deficiency
A
Sources endogenous production in presence of UV radiation in sunlight - decreased by melanin and high solar protection factor sunblocks fortified cereals & dairy products fish oil egg yolks Causes
- nutritional deficiency: decreased intake/fat malabsorption
- inadequate exposure to sunlight
- Rickets
- Osteomalacia
11
Q
Vit. E structure & Fx
A
Sructure
- 8 naturally occuring tocopherols
- alpha-tocopherol is most active Fx
- most important role is anti-oxidant
- prevents peroxidation of lipids in conjuction with Selenium
- scavenges free radical generated
12
Q
Vit. E deficiency
A
Dietary deficiency of Vit. E is very rare since it’s abundant in foods. Occurs in association with:
- malabsorption of fat: cholestasis, pancreatic enzyme deficiency, CF
- relatively more common in premature infants with an immature GI tract
- Abetalipoproteinemia
- rare autosomal recessive syndrome of impaired Vit. E metabolism Sx:
- Hemolytic anemia: oxidative injury by superoxide radicals generated during oxygenation of Hb
- reduced DTR (Areflexia) & gait problems due to axonal degeneration
13
Q
Vit. K metabolism & Fx
A
- in humans, it is synthesized by the intestinal bacterial flora exists in 2 naturally occuring forms
- Phylloquinone (plants): dietary source
- Menaquinone (bacteria): intestine Vit. K is active in its Reduced form
- Epoxide Reductase (liver): converts inactive Vit. K -> Active epoxide Fx principal role of Vit. K is inpost-translation mod by various clotting factors including:
- Prothrombin
- VII
- IX
- X
- Protein C & S
- Vit. K serves as cofactor for liver microsomal gamma carboxylase
- Vit. K dependent carboxylation of glutamate residues leads of formation of mature clotthing factors (gamma-carboxy-glutamyl (Gla) residues & is capable of subsequent activation
- gamma-carboxylation allows Ca2+ binding b/c of 2 adjacent -ve charged carboxylate groups
- clotting factor Ca2+ complex can then bind to phospholipids on the platelet membrane
14
Q
Vit. K sources & Fx
A
Sources
- most Vit. K recycled by liver which converts the oxidised form to the reduced form
- endogenous intestinal bacterial flora readily synthesise the vit and so the daily dietary requirement is low
- foods rich in Vit. K include cabbage, cauliflower, spinach, egg yolk & liver Deficiency Neonates:
- newborns have sterile intestines as bacterial flora have not developed & therefore cannot synthesise Vit. K Hemorrhagic disease of the newborn
- bleeding at various sites in the body including skin, umbilicus & viscera
- Intracranial bleeding: most serious complication
- do not confuse w/ Rh incompatibility
- Rx: im injection of Vit. K for all newborns Adults Vit. K deficiency seen in cases of:
- fat malabsorption
- prolonged use of broad spectrum antibiotics
- diffuse liver disease which interferes with storage of Vit. K Vit. K toxicity manifests as:
- hemolytic anemia & jaundice
- hematuria
- melena (blood in stools)
- ecchymoses (brusiing)
- bleeding from gums Warfarin:
- Vit. K receptor antagonist
- MOA: blocks the activity of liver epoxide reductase & prevent regeneration of reduced Vit. K
- Rx for Pt with thrombo-embolic disease.
15
Q
Vit. C fx
A
- required for Iron absorption; reduces Iron to the ferrous state in stomach
- very important anti-oxidant; direct scavenger of free radicals; regenerates anti-oxidant form of Vit. E
16
Q
Scurvy (Vit. C def)
A
- Fragile blood vessels - perifollicular hemorrhages (base of hair follicles)
- sore, spongy, bleeding gums
- loose teeth
- bleeding into joints
- frequent bruising
- impaired wound healing
17
Q
Vit. B1 (Thiamine) Fx
A
- active form: TPP (Thiamine pyrophosphate) Fx:
- oxidative decarboxylation of alpha keto acids; helps to maintain neural membranes & nl nerve conduction
- acts as a cofactor for transketolase in HMS
18
Q
Vit. B1 sources & deficiency
A
Sources
- widely available in diet
- thiamine deficient foods are polished rice, white flour & white sugar Thiamine deficiency Beri-beri:
- polished rice is the major diet component
- Dry: polyneuropathy: disruption of motor, sensory and reflex arcs; could progress to paralysis
- Wet: cardiovascular sx & peripheral neuropathy Wernicke-Korsakoff syndrome:
- associated with chronic alcoholism = poor diet
- ophthalmoplegia & nystagmus; paralysis of extra-ocular muscles
- ataxia
- confusion, disorientation
- memory loss and confabulation
- Dx: increase in erythrocyte Transketolase activity on addiction of TPP
19
Q
Vit. B2 (Riboflavin) Fx
A
Active forms
- Flavin mononucleotide (FMN)
- Flavin Dinucleotide (FAD)
- participate in oxidation - reduction rxn
20
Q
Vit. B2 sources & deficiency
A
Sources
- widely distributed in meat, dairy products & veg Riboflavin Deficiency
- primary deficiency still occurs in developing countries
- lack of green veg.
- frequently accompanies other vit deficiencies Sx
- Cheilosis: areas of pallor, cracks & fissures at the angles of the mouth
- Pt describes “eating something salty & corners of mouth burn”
- Glossitis: inflammation & atrophy of the tongue
- facial dermatitis
21
Q
Vit. B3 (niacin)
A
Active forms:
- NAD+
- NADP+ Fx
- act as co-enzymes in oxidation reduction rxn
- NAD: dehydrogenases
- NADP: dehydrogenation rxn especially in the HMS cycle Uses
- niacin inhibits lipolysis in the adipose tissue & greatly reduces production of free fatty acids; Rx of Type IIb hyperlipoproteinemia
22
Q
Vit. B3 defiency
A
Pellagra
- seen in alcoholics
- deits rich in maize/corn
- can result from both Niacin or Trp deficiency
- Dermatitis
- Diarrhea
- Dementia
23
Q
Biotin fx & deficiency
A
- prosthetic group for most carboxylation rxn
- inherited deficiency of incorporation of biotin in these enzymes results in manifestations of biotin deficiency (multiple carboxylase deficiency)
- Biotin supplementation improves sx in many children with multiple carboxylase deficiency enzymes requiring biotin are:
- Pyruvate carboxylase
- Acetyl-CoA carboxylase
- Propionyl-CoA carboxylase
- Avidin inhibits biotin absorption
24
Q
Vit. B6 (pyridoxine)
A
- collective term for: pyridoxine, pyridoxal, pyridoxamine serve as precursors for PLP which act as co-enzyme for:
- Transamination: aa metabolism
- Decarboxylation: synthesis of NT
- Condensation: heme synthesis, i.e. ALA Synthase
- Conversion of homocysteine to cysteine
25
Q
Vit. B6 (pyridoxine) deficiency
A
- not very common Isoniazid (anti-TB drug) inactivates pyridoxine
- pyridoxine supplements are given as a part of anti-TB regimes Sx
- microcytic anemia (ALA synthase)
- peripheral neuropathy
- increased risk of cardiovascular disease (high levels of plasma homocysteine)
- seizures may occur
26
Q
Trace elements & enzymes
A
- Manganese: pyruvate carboxylase, mitochondrial SOD
- Molybdenum: xanthine oxidase
- Selenium: glutathione peroxidase
- Zinc: more than 100 enzymes
27
Q
Copper Fx & metabolism
A
important co-factor in redox rxn Cytochrome C
- part of complex IV
- inhibited by CN
- SOD Lysyl oxidase
- synthesis of collagen Tyrosinase
- melanin synthesis Dopamine beta-hydroxylase
- NT synthesis
- Copper forms ceruloplasmin aka Ferroxidase in the liver, which apart from being a copper transport protein, helps in Iron metabolism Metabolism
- 50% of ingested copper is absorbed in stomach & upper small intestine and the rest is excreted in feces
- ingested copper is absorbed in the stomach & instestine; transported to the liver bound to albumin
- in hepatocytes, it is used to form Ceruloplasmin which is secreted into plasma
- aged Ceruloplasmin is taken up by the liver from the plasma, endocytosed & degraded and copper is secreted into bile
28
Q
Copper deficiency
A
Sx:
- microcytic anemia (smaller RBC)
- degradation of vascular tissue
- defects in hair
- includes Menke’s syndrome & Wilson’s disease
29
Q
Menke’s syndrome
A
- X-linked disease (only boys) resulting in a defect in copper mobilisation from intestine causing copper deficiency
- kinky hair syndrome
- mental retardation
- fatal in infancy
30
Q
Wilson’s disease
A
- AR disorder of copper metabolism
- defect in copper transporting ATPase which is needed to attach copper to Ceruloplasmin & help in its biliary excretion -> accumulates in liver, brain, & eye
- gene for Wilson disease located on chromosome 13; over 30 mutations have been id Sx:
- commonest presentation is acute or chronic liver disease
- presents around >6 y
- neuropsych manifestations & frank psychosis Dx:
- decreased serum Ceruloplasmin
- increased Urinary excretion of copper; specific for Wilson’s disease
- increased hepatic copper content; also seen in Menke’s Rx:
- chelation
- Zn blocks uptake of copper from intestine and is used in conjunction with chelators
- ammonium tetrahiomolybdate: investigation drug which acts both as chelating agen and to block absorption of copper from gut
- avoidance of food with high copper contents link chocolate, nuts, liver
31
Q
Iron Fx & metabolism
A
Fx
- required for redox rxn & heme synthesis Metabolism
- absorption from diet; regulated by body iron stores & sensed by HFE
- iron can be absorbed only in the ferrous form
- any iron in the ferric form is changed to ferrous form by action of pH and Vit C in stomach -> no milk before iron tablets because it neutralizes some the stomach acid
- Ceruloplasmin (ferroxidase) participates in the release of ferrous iron from the intestinal cells and helps to convert it to ferric iron
- transferrin is the transport protein for iron
- ferritin & hemosiderin are the storage forms of iron in the liver
32
Q
Iron deficiencies
A
Causes
- dietary lack
- impaired absorption: tannates decrease absorption.
- increased requirement: pregnancy
- chronic blood loss Iron deficiency anemia: induces a hypochromic microcytic anemia. Sx include
- brittle nails
- alopecia
- pica: appetite for soil
- weakness & pallor
- fatigue
33
Q
Heriditary Hemochromatosis & Iron toxicitiy
A
- AR disorder causing excessive absorption of Iron
- defect in HFE gene leading loss of sensing mechanisms on basolateral surface of intestinal crypot cell iron sensor
- excessive accumulation of iron in the parenchymal organs, most importantly liver & pancreas excessive iron appears to be directly toxic to tissues by:
- lipid peroxidation via iron catalyzed free radical rxn
- DNA damage Clinical Sx
- cirrhosis
- diabetes
- cardiac dysfunction
- acute synovitis (inflammation of joint synovial linings)
- brownish skin pigmentation
- very high levels of serum iron & ferritin
- iron content of unfixed liver tissue dramatically increased
- Pt treated by regular phlebotomy have a nl life expectancy
34
Q
Nutritional anemias
A
Microcytic (
- Iron, copper or pyridoxine deficiency Normocytic (MCV 80-100)
- protein-calorie malnutrition Macrocytic (MCV>100)
- aka megaloblastic
- Vit. B12 or Folate deficiency
