401 Exam 3

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ejstave
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401 Exam 3
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2012-04-20 00:11:45
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Exam 3 starting with Vitamin A and ending with
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  1. Preformed Vit A
    • Retinol (alcohol)
    • Retinal (aldehyde)
    • Retinoic Acid (RA)
  2. Provitamin A
    • Carotenoids that can be converted to retinol
    • -Beta- carotene, beta-cryptoxanthin, lycopene, canthaxanthin, lutein
  3. Vit A sources
    • Free retinol
    • -not present in food
    • -present as precursor fatty acid esters (i.e. retinyl palmitate)
    • *animal products including egg yolks, butter, whole
    • milk, liver and fish liver oils
    • Carotenoids
    • -red, orange and yellow pigments made by plants
    • -beta carotene is pigment w/ greatest Vit A activity
  4. Retinol activity equivalent (RAE)
    -12micrograms beta carotene or 24 microg other carotenoids= 1 RAE
  5. Vitamin A Digestion and Absorption
    • -often complexed to PTN (release requires pepsin in stomach and proteases in SI)
    • -release from fatty acids (esterase abd lipases)
    • -released carotenoids and retinols in SI are incorporated into micelles
  6. Vitamin A amount of absorption
    • 70-90% of retinol absorbed
    • 20-50% of carotenoids absorbed
  7. Vitamin A within enterocyte
    • -Beta carotene can be converted to retinal and then be reduced to retinol or oxidized to RA
    • -Retinol is acetylated (reesterified to RE)
  8. Re-esterification
    • -Primary pathway involves cellular retinol-binding protein (CRBP) II
    • -CRBP II binds both retinal and retinol
    • -Non-specific ptn may also bind retinol when in high amounts
    • *re-ester requires acyl CoA retinol acyl transferase
    • (ARAT)
  9. CRBP II
    • binds both retinal and retinol
    • -directs the reduction of retinal to retinol
    • -directs the esterification of retinol to retinyl esters
    • *lecithin retinol acyl transferase (LRAT) transfers acyl
    • group to form retinyl palmitate
  10. Vitamin A transport
    • CMs
    • -removal of RE, retinol and carotenoids on route to liver by extrahepatic tissues
    • *bone marrow, blood cells, spleen, adipose, muscle,
    • lungs, kidneys
    • CM remnants removed by liver
  11. Vitamin A in the liver
    • Retinyl Esters
    • -hydrolyzed to free retinol
    • -retinol binds with CRBP
    • -enzymatic metabolism

    • Retinol not metabolized or transported out
    • -stored as RE primarily in stellate cells
  12. Vitamin A enzymatic metabolism
    • -esterification by LRAT or ARAT
    • -oxidation of retinol to retinal
    • -phosphorylation of retinol to retinyl phosphate
  13. Retinol export from liver
    • -dependent upon synthesis and secretion of retinol binding ptns (RBP)
    • -RBP binds retinol (from stellate cells) (holo RBP)
    • -complex secreted in plasma
  14. Vitamin A in plasma
    • -holo-RBP interacts with transthyretin (TTR)
    • -RBP-TTR complex circulates in plasma
    • -Retinol can be taken up from complex
  15. Uptake of retinol by cells
    • -retinol removed leaving behind RBP-TTR
    • -RBP-TTR then dissociate
    • *apo-RBP catabolized by kidney
  16. How is retinoic acid made?
    • by individual cells
    • -in cytoplasm, RA binds to cellular retinoic acid-binding ptns (CRABPs)
    • *prevent catabolism and direct usage
  17. Vitamin A functs
    • Visual cycle (retinal)
    • Cell differentiation (retinoic acid)
    • ROH essential for reproductive process
    • Immune system (for T-lymph funct, antibody response)
    • Bone developement
    • Antioxidants (Beta carotene)
    • Embryonic developement
    • Maintenance of normal structure and function of epithelial cells
    • Growth
  18. Vit A in Bone developement
    -Vit A deficiency results in excessive deposition of bone by osteoblasts and reduced number of osteclasts
  19. Vitamin A in antioxidant funct
    -possess ability to react with and inactivate free-redical reactions in membrane systems and possibly in solution (plasma/cytoplasm)

    -prevent oxidation of LDL-C
  20. Cellular differentiation-retinoic acid
    functs as a hormone to affect gene expression

    RA or 9-cis RA taken into nucleus bound to CRABP
  21. Cellular differentiation in nucleus.
    • -RA or 9-cis RA binds to RAR (RA receptors)
    • -9-cis RA binds to RXR (retinoid receptors)
    • -RAR-RXR dimerization permits interaction with specific nucleotide sequences of DNA (genes)
    • *regulates transcription to RNA and translation to protein
  22. Vitamin A in embryonic developement
    may signal morphogenesis-evolution and developement
  23. Vitamin A in maintenance of normal structure and funct of epithelial cells
    • epithelial cells found in lungs, trachea, skin, cornea, and GI tract
    • *directs the differentiation of keratinocytes into mature
    • epidermal cells
    • *also directs keratin synthesis
    • *directs differentiation of epithelial keratinizaing cells
    • in mucus-secreting cells in vitro
  24. Vitamin A in growth
    Vit A deficiency results in poor growth

    • admin of ROH or RA can stimulae impaired growth
    • *particularly growth of epithelal cells
    • *stimulate the # of specific receptors for GF
  25. Vitamin A nutrient-nutrient interactions:
    Vitamin E
    • Vit E
    • -is needed for cleavage of beta carotene into retinal
    • -may protect substrate and product from oxidation
  26. Vitamin A nutrient-nutrient interactions:
    Excessive Vitamin A
    May prohibit both Vitamin E and K absorption
  27. Vitamin A nutrient-nutrient interactions:
    Protein status
    transport and use of the vitamin depends on several vitamin A binding proteins
  28. Vitamin A nutrient-nutrient interactions:
    Zinc
    • Zinc deficiency interferes with Vitamin A metabolism
    • -decreased food intake
    • -reduction in synthesis of RBP
    • -decreased mobilization of ROH from its storage as RE
    • -alcohol dehydrogenase requires Zn
  29. Vitamin A nutrient-nutrient interactions
    Vitamin A def. may result in microcytic anemia

    Vit A may affect iron metabolism or storage or differentiation of RBC
  30. Vitamin A excretion
    • -oxidize RA to a variety of matabolites
    • *excreted via bile into feces (70% of vit A metabolites)
    • * urinary excretion accounts for remaining 30%
  31. Vit A RDA
    • -900 micrograms for males
    • -700 for women

    -UL=3000 micrograms/d (preformed vit only)
  32. Vitamin A deficiency
    • -common in developing companies
    • *inadequate intake is common in children <5yo

    • -increased mortality
    • *anorexia, retarded growth, increased susceptibility to infections, keratinization of epithelial cells of skin with failure of normal differentiation
  33. Vitamin A deficiency problems
    • Night blindness
    • Xerophthalmia
    • Corneal ulceration/keratomalacia
  34. Who is at risk for Vitamin A deficiency?
    • -Those with increased needs
    • *fat malabsorption, intestinal parasites, protein def.,
    • chronic nephritis
    • -Measles
    • *depresses Vit A status
    • *WHO and UNICEF recommend supplements for children with measles or living in countries where measles in prevalent
  35. Night blindness
    impaired production of rhodopsin in rods (reversible)
  36. Xeropthalmis
    • Reversible
    • -abnormal dryness and thickening of conjunctiva and cornea of eyes.
    • *conjunctival change include disappearane of goblet cells, enlargement and keratinaization of epithelial cells
    • *Bitot's spots-white accumulations of sloughed cells; accumulate over the keritinized epithelial cells
  37. Corneal ulceration/keratomalacia
    softening and necrosis of cornea

    -irreversible
  38. Vitamin A Toxicity
    • In adults
    • -dry, itchy skin, bone and muscle pain, conjunctivitis, cirrhosis

    • -100,000 IU/d for short period=toxic
    • -25,000-50,000 IU/d= toxic
    • -10,000 IU/d avoids toxicity in most
    • Bet carotene is non toxic
  39. Clinical assessment of Vitamin A
    Bitot's spots

    Measurment of dark adaptation threshold

    Electroretinograms to measure the level of rhodospin and its rate of regeneration
  40. Assessment of Vitamin A
    • Plasma ROH concentration
    • -more accurate if tissue stores exhausted
    • Measurement of changes in plasma ROH concentration before and 5 hours after oral admin of RE in oils
    • -process referred to as Relative Dose Response
  41. Vitamin D forms
    • Vitamin D3 (cholecalciferol, D2
    • Active form is 1,25- (OH)2 D3 (calcitriol)
  42. Process of Vitamin D
    • Cholesterol ->
    • 7-dehydrocholesterol ->
    • Previtamin D3 ->
    • Vitamin D3 (cholecaciferol) ->
    • 25-OH Vitamin D3 ->
    • 1,25 (OH) 2 Vitamin D3 (calcitriol)
  43. Vitamin D sources
    • Sunlight
    • Animal
    • -eggs, butter, liver, fatty fish
    • -fortified products like milk and margarine
    • Plants, ergosterol can be activated by irradiation to from ergocalciferol (Vit D2 or ercalciol)
  44. VItamin D through sunlight
    -7-dehydrocholesterol is made in sebaceous glands of skin and secreted onto the surface and then reabsorbed into various layers of skin

    • -exposure to sunlight
    • *converts some of 7-dehydrocholesterol to previtamin D3
  45. DIetary Vitamin D Absorption
    bile salts, micelle, incorporation into CMs

    ~50% is absorbed
  46. Vitamin D transport
    • -CMs transport ~40%
    • *some holecalciferol may be transferred from CM to DBP and delivered to extrahepatic tissues
    • -~60% of cholecalciferol is transported by DBP
    • *skin+ diet (DBP=Vit D binding protein)
    • -Both go to liver
    • *extrahepatic tissues remove Vit D3 en route
  47. Vitamin D in the Liver
    • -Hydroxylated at carbon 25 to form 25-OH D3
    • -Most gets secreted in blood and taken to kidney by DBP
  48. Vitamin D in Kidneys
    Second hydroxylation occurs at 1 position forming 1,25- (OH)2-d3 (calcitriol)

    Active form of Vitamin
  49. Vitamin D3 in the kidney
    • -1-hydroxylase is regulated by many factors
    • *PTH and low blood Ca++ stimulate
    • *high dietary P intake decreases
    • *sufficient amounts of calcitriol inhibit activity
    • 1.)24 hydroxylase is stimulated
    • 2.)may be involved in bone mineralization or
    • represent a step in degradation process
  50. Vitamin D functions?
    read in book!
  51. Calcitrol in Kidneys
    works with PTH in increasing calcium and phosphorus reabsorption
  52. Calcitrol and bone
    • Works with PTH in directing mobilization of Ca++ and P from bone to mnormalized blood Ca++ levels
    • -may be mediated by calcitriol-induced cell differentiation of hemopoietic cells to osteclasts
    • -or may be mediated by calcitriol-induced increases of osteoclast activity
  53. Osteoclasts
    mediate bone resorption
  54. Calcitonin
    -hormone produced by thyroid gland

    -released when blood calium levels rise above normal

    -promotes mineralization of calcium and phosphorus in bones
  55. Calcitonin Regulation
    • Elevated serum calcitriol and elevated serum Ca++ cause decrease in PTH through feedback loops
    • -elevated serum calcium inhibits PTH secretion
    • -calcitriol decreases transciption of the gene for preparathyroid hormone
    • *interacts with Vit D receptors
  56. Osteocalcin
    • Protein found in bone matrix and dentine
    • -secreted by osteblasts
    • -associated with new bone formation

    *Calcitriol may be important, along with Vit K, in the synthesis of osteocalcin
  57. Calcitriol and Cell differentiation
    • Cell differentiation
    • -triggers differentiation of stem cells to osteoclasts
    • *may also induce release of osteoblast-derived resorption factors that stimulate osteclast activity
  58. Evidence that calcitriol inhibits...
    cancer cell proliferation and growth and stimulates epidermal cell differentiation, while preventing proliferation
  59. Two characteristics of cancer cells
    • -lack of differentiation (specialization)
    • -rapid growth or proliferation
  60. Many tumors have been found to contain __________ receptors
    • Vitamin D receptors (VDR)
    • -breats, lung, skin, colon, bone
  61. Vit D and cancer
    1,25 (OH) 2D induces cell differentiation and/or inhibit proliferation of a number of cancerous and noncancerous cell types maintained in cell culture
  62. Geographic cancer and Vit D
    • Geographic distribution of colon and breast can. is similar to gegraphic distribution of rickets.
    • -decreased sunlight exposure and diminished vitamin D nutritional status may be related to an increased risk
  63. Autoimmune diseases and there targeted tissue
    • Insulin dependent diabetes mellitus
    • -beta cells of the pancreas
    • Multiple sclerosis
    • -myelin producing cells of CNS
    • Pheumatoid arthritis
    • -collagen producing cells of the joints
  64. Vitamin D interactions with other nutrients
    Ca, P, Vit K
  65. Vitamin D excretion
    • -converted to 1,24,25- (OH)3D3 and then further catabolized and excreted in bile
    • -feces major route of excretion
    • -<5% of metabolites are excreted in urine
  66. Vitamin D DRI/RDA 2010
    • -in 2010 the Food and Nutrition Board of the institute of Medicine set a Recommended Dietary Allowance based on the amount of Vit D needed for bone health
    • -based on age
    • -adults 19-50=15 mcg
    • -UL adults 19 y and older = 100 mcg
  67. Vitamin deficiency
    Rickets in infants and children

    Osteomalacia (soft bone) in adults
  68. Rickets
    • failure of bone to mineralize
    • -long bones of legs bow
    • -knees knock as weight-bearing activities begin (walking)
    • -spine becomes curved and pelvic and thoracic deformities
  69. Osteomalacia
    • -impaired Ca absorption
    • -mineralization of bone is impaired
    • -bone matrix becoes demineralization- bone pain and softening
  70. Risk factor of D def.
    Obesity
  71. Certain diseases/conditions increase risk of vit d def.
    • -fat malabsorption
    • -disorders affecting parathyroid gland, liver and/or kidney
    • -infants on breast milk
    • -aging may reduce synthesis of cholecalciferol
    • -lack of sunlight (location, dark skin, burka)
    • -diet, vegan, lacto-veg.
  72. Vitamin D toxicity
    • NOT due to excessive exposure to sunlight
    • -doses of 10,000 IU/d may result in hypercalcemia
    • *calcification of soft tissues (kidney, heart, lungs, blood vessels)
    • *HTN, anorexia, nausea, renal failure, death
  73. Biological forms/oxidation states
    Ca2+, divalent cation

    Calcium Phosphate Hydroxyapatite
  74. Diets rich in calcium
    3 or more servings milk/dairy foods

    calcum-fortified foods

    Calcium/vitamin D supplements
  75. Foods rich in other bone healthy nutrients
    • 5 or more servings vegetables and fruit
    • -potassium, magnesium, zinc, copper
    • -vitamin K and vitamin C
  76. Calcium recommendations
    • DRI/RDA
    • 19-50 yo= 1,000 mg Ca
    • 51-70= male 1000, females 1200
    • >70= 1200 mg

    UL-2,500 mg
  77. Calcium rich foods
    • milk, yougurt, buttermilk, cheese
    • Canned salmon with bones
    • calcium fortified foods
    • -OJ, soy drinks
    • -breakfast cereals, cereal bars
    • tofu made w/ Ca sulfate
  78. Who needs Calcium/VitD supplements
    • -Lactose intolerant or allergic to milk
    • -avoid milk/dairy
    • -on strict wt loss diet
    • -over 50 yo
    • -not enough sun exposure
    • -long term steroid therapy
  79. Calcium Digestion/Absorption
    • -Absorbed via active (vit D, PTH)
    • -also passive, paracellular, nonsaturable
    • -in upper part of sm. intestine (ileum)
    • -large intestine, bacteria release Ca from fermentable fibers (pectin)
  80. How much Calcium is digested and absorbed?
    • about 30% for adults
    • about 75% for children
  81. Enhances Ca bioavailability?
  82. physiological needs
    • acidity of GI tract
    • Lactose, other sugars, protein
    • vitamin D
  83. Inhibits Ca bioavailability?
    • nonfermentable fibers, decrease transit time
    • fermentable fibers, binds
    • phylates (legumes, nuts, cereals) binds
    • oxalates (veg, fruits, nuts, tea) chelates
    • unabsorbed fat (steatorrhea)
    • excess P or Mg 2+, menopause, age
  84. Nutrients/substances enhancing calcium absorption
    • Vit D
    • sugars and sugar alcohols
    • protein
  85. Nutrients/substances inhibiting calcium absorption
    • fiber
    • phytate
    • oxalate
    • excessive divalent cations
    • unabsorbed fatty acids
  86. Nutrients whose absorption may be inhibited by excessive calcium
    • iron
    • fatty acids
  87. Calcium transportation
    • -ionized form (60%)
    • -protein-bound (aprox 40% albumin)
  88. Calcium Excretion
    • Feces- unabsorbed and endogenous Ca
    • Urine
    • Sweat (small amounts)
  89. Calcium Metabolic Roles
    • 1. bones formation and maintenance
    • -cortical bones:dinse, compact
    • -trabecular bone: spongy, inner matrix
    • -bone strength: bone mineral density test
  90. Bone remodeling
    -remove old, build new, 15-30% of the bone is rebuilt each year
  91. Osteoblast cells
    • bone cells that secrete a collagen matrix that forms the support structure of bone
    • they then secrete bone mineral, which strengthens the bone
  92. Osteoclast cells
    bone cells that constantly break down the bone network
  93. Calcium Functions
    • -Metabolic roles
    • -formation of dentin
    • -blood clotting
    • -muscle contraction
    • -phosphorylase kinase activate phosphatase
    • -nerve conduction
    • -regulation of intracellular membrane transport
  94. Calcium deficiency conditions
    • -osteoporosis
    • -rickets/osteomalacia
  95. Ca def. signs/symptoms
    • -impaired dentition
    • -impaired skeletal developement
    • -elevated blood pressure??
  96. Building bones
    • Calcium is deposited
    • -during childhood, teen and young adult years
    • -when consume enough Ca and Vit D
    • Calcium is withdrawn
    • -during older adult years
    • -when do not consume enough Ca and Vit D
  97. Osteoporosis
    • Porous bones
    • -bones have lost Ca and other minerals
    • -bones are fragile
    • -bones fracture easily
  98. Osteoporosis Risk factors
    • Female
    • Increasing age
    • Thin, small bones-BMI<19
    • Caucasian or asian
    • Fam Hx
    • High sodium
    • High protein intake
    • Abnormal menstrual hx
    • Have has an eating disorder or times of strict dieting
    • Medical conditions
    • Medication use
  99. Medical risk factors
    • bone fraccture after 40
    • rheumatoid arthritie
    • thyroid disorder
    • parathyroid disorder
    • poorly controlled T1DM
    • lactose intolerance
    • digestion disorders
  100. Osteoporosis Lifestyle risk factors
    • inactive lifestyle
    • dt low in Ca
    • little sun exposure and diet low in Vit D
    • few fruits and vegetables
    • drink excess alcohol
    • current or former smoker
    • lots of caffeine
    • high sodium and protein
  101. Ca toxicity
    • -disruption of normal parathyroid function may result in increase blood Ca++
    • -hypercalcemia is a condition called Ca rigor
    • -excess Ca++ may interfere with absorption of Zn
    • Increased risk of urinary stone formation in susceptible indivs

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