Vitamins Flashcards Preview

Biochem Diseases > Vitamins > Flashcards

Flashcards in Vitamins Deck (34)
Loading 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 in post-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 (<80 MCV)

  • Iron, copper or pyridoxine deficiency

Normocytic (MCV 80-100)

  • protein-calorie malnutrition

Macrocytic (MCV>100)

  • aka megaloblastic
  • Vit. B12 or Folate deficiency