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134 Cards in this Set
- Front
- Back
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atopy
- definition - biochemical differences in individual |
predisposition to localized reactions to certain allergens
atopic individuals have higher serum levels of IgE and more IL-4 producing T cells |
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mechanism of Type I HSR
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allergen presentation by DC to CD4+ T cells
--> differentiation to Th2 cells --> secretion of IL-4, IL-5, IL-13 |
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IL-4
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activation of IgE secreting B lymphocytes
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IL-5
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activation of eosinophils
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IL-13
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promotes IgE secretion & epithelial mucus secretion
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4 effects of histamine
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increased vascular permeability
vasodilation contraction of extravascular smooth muscle increased glandular secretions |
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LTC4 and LTD4 effects
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increased vascular permeability
bronchial smooth muscle contraction |
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LTB4 effects
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chemotactic for PMNs, eosinophils, monocytes
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eosinophil function in Type 1 HSR
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produce major basic protein (MBP) & eosinophil cationic protein (ECP)
toxic to epithelial cells |
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Type II HSR, aka:
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Ab-mediated
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4 mechanisms of Type II hypersensitivity
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opsonization and phagocytosis
opsonization and cell lysis w/ ADCC & complement (MAC) complement- and FcR- mediated inflammation Ab-mediated cellular dysfunction |
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describe opsonization & phagocytosis
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IgM & IgG bind to cells, activate complement
generate C3b, C3b binds receptors on phagocytes Fc region of IgG recognized by phagocytes |
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ADCC
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cells coated w/ low concentrations of IgG recognized by Fc receptors on PMNs, eosinophils, Mphages, and NK cells
--> toxin-mediated cell lysis |
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disease examples of opsonization-mediated cell death
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transfusion reactions
certain drug reactions autoimmune hemolytic anemia, agranulocytosis or thrombocytopenia |
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complement- or FcR mediated inflammation
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IgM and IgG bound to ECM proteins activate complement
generate C5a recruit PMNs, etc release of enzymes, ROIs --> tissue damage |
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Goodpasture syndrome
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Type II HSR
Abs vs. basement proteins of renal glomeruli & pulmonary alveoli --> glomerulnephritis & alveolitis |
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Ab mediated cellular dysfunction
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Abs against cell surface receptors impair or dysregulate function w/o causing cell injury or inflammation
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Myasthenia gravis
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Ab-mediated celular dysfunction
Abs vs. AChR of skeletal muscle impairs NMJ transmission muscle weakness |
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Type III HSR
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immune complex-mediated
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general mechanism type III HSR
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Ag-Ab complexes deposited in tissues, incite inflammation
complexes formed in circulation |
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localized Type III HSR
-definition - three locations of deposit and corresponding disease |
complexes deposited in particular organs:
kidneys - glomerulonephritis joints - arthritis cutaneous blood vessels - vasculitis |
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generalized/systemic Type III HSR
- definition - mechanism |
complexes deposited in many organs:
complexes form in circulation bind to circulating WBCs thru FcRs or thru C3b receptors activated WBCs release vasoactive mediators --> allow complexes to deposit in vessel wall --> inflammatory response & further activation of complement (C5a, C3a) vasculitis |
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C5a
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chemotactic for PMNs and Mphages
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C3a
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increased vacular permeability
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Type IV HSR
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cell-mediated
initiated by Ag-activated (sensitized) T cells |
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2 mechanisms of Type IV HSR
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delayed type HSR
T cell-mediated cytotoxicity |
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DTH
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CD4+ T cells + Ag/MHC II complex --> Th1 cells
Th1 --> IFN --> activated Mphages |
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IL-12 role in DTH
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influences CD4+ T cell --> Th1
activates memory Th1 cells upon subsequent exposure to Ag produced by APCs |
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role of Mphages in DTH
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secrete TNF, IL-1, chemokines --> inflammation
--> IL-12 --> amplify Th1 response secrete TNF & lymphotoxin --> activation of vascular endothelium --> WBC extravasation secrete GFs --> stimulate fibroblasts & collagen synthesis |
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Type IV HSR disease examples
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tuberculin reaction in the skin of individuals previously sensitizes to or infects w/ M. Tuberculosis
reactions to intracellular microbes such as fungi, protozoa and parasites |
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histopathology of DTH
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granulomatous inflammation
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2 mechanisms of CTL-mediated killing
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perforin-granzyme-dependent
- perforins --> osmotic lysis - granzymes --> apoptosis Fas-FasL |
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CTL-mediated killing important in which three pathologies?
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viral-infected cells
neoplastic cells w/ tumor Ags graft rejection |
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In most HSR, the underlying cause of tissue damage is what?
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inflammation
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genetic predisposing factors to autoimmunity
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susceptiblity genes (certain MHC alleles)
- e.g.: defective eliminiation of self-reacting T cells in thymus during development - e.g.: defective development of Tregs |
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environmental predisposing factors to autoimmunity
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infection (e.g.: molecular mimicry)
trauma drugs |
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epitope spreading in autoimmunity
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initial autoimmune response may damage self-Ags and expose new epitopes of the Ags normally concealed from the immune system
--> activation of new auto-reactive lymphocytes & spreading of disease |
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categorization of autoimmune ds
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Type II - Ab-mediated
Type III - immune complex-mediated Type IV - T cell mediated (in parallel w/ HSR) |
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examples of Type II autoimmune ds
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rheumatic fever
Graves' hyperthyroidism Guillain-Barré syndrome |
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Examples of Type III autoimmune ds
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SLE
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Examples of Type IV autoimmune ds
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Type I DM
MS rheumatoid arthritis |
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amyloid
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group of morphologically similar proteins w/ various chemical compositions
deposited extracellularly in various tissue and organs may cause pressure atrophy or degeneration of surrounding cells --> organ dysfunction |
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histologic appearance of amyloid
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amorphous
eosinophilic hyaline extracellular |
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ultrastructural appearance of amyloid
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nonbranching fibrils
arranged in bundles in random meshwork fibrils aggregated in cross-beta-pleated sheets |
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3 common locations of amyloid deposits
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kidney - renal glomeruli
spleen - lymphoid follicles and/or walls of sinuses/CT framework of red pulp liver - spaces of Disse |
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chemical nature of amyloid
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95% fibril proteins
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3 most common types of amyoid proteins
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AL (amyloid light chain)
AA (amyloid associated) A-beta (beta amyloid protein) |
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amyloid light chain
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composed of Ig light chains synthesized by plasma cells
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amyloid associated protein
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derived from SAA (Serum amyloid associated protein), an APP syntheized by hepatocytes
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A-beta amyoid
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core of cerebral plaques
in cerebral blood vessel walls in Alzheimer's disease |
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transthyretin
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less common amyloid protein
normal serum protein that binds and tranports thyroxin and retinol mutant form deposited in group of genetic disorders - "familial amyloid polyneuropathies" normal transthyretin is deposited in heart of elderly pts |
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Amyloidosis classifications
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localized - one organ
generalized/systemic - multiple organ involvement |
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Systemic forms of amyloidosis
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primary
secondary or reactive |
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Primary systemic amyloidosis
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associated with immunocyte dyscrasias (unspecified disorder of the blood) - e.g.: multiple myeloma
AL type amyloid - most common malignant B cells produce excessive amounts of single Ig --> monoclonal gammopathy Bence Jones proteins in serum and urine |
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Bence Jones proteins
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characteristic of primary systemic amyloidosis
Ig light chains found in serum and urine |
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Secondary or reactive systemic amyloidosis
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2* to chronic inflammatory condition --> infectious or noninfectious
may also occur in association w/ certain neoplastic conditions |
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localized forms of amyloidosis
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nodular deposits
amyloidosis of aging - transthyretin deposits in heart |
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pathogensis of amyloidosis
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all forms result from abnormal folding of proteins, which then aggregate
aggregation --> formation of insoluble fibrils --> extracellular deposition in tissues |
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proteins that form amyloid are either ____ or ____
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normal proteins which fold imporperly when produced in excess
or mutated proteins which are structurally unstable |
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what usually happens to misfolded proteins?
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degraded intracellularly by proteasomes
degrades extracellularly by Mphages |
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Triple burden of malnutrition
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hunger - energy and protein deficiencies
hidden hunger - specific nutrient deficiencies excessive net energy intake - overweight/obesity |
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6 effects of malnutrition
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lymphoid atrophy - reduced size of thymus and spleen
decreased phagocytic activity decreased number T cells impaired lymphokine production depressed integrity of skin and mucosal surfaces impaired complement activation |
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Immune effects of vitamin A deficiency
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reduced...
WBC numbers lymphoid tissue weights T cell function NK cell numbers complement activation |
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Immune effects of vitamin B deficienies
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reduced...
lymphocyte number lymphoid tissue weights Ab responses phagocyte function T cell proliferation |
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Effects of iron deficiency
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reduced cytotoxic activity of phagocytes and proliferation of Th cells
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Effects of zinc deficiency
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reduced T cell development and function
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Effects of infection on nutrient supplies in body
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causes protein catabolism and negative nitrogen balance
increases resting energy metabolism redistributes trace elements like iron and zinc increases vitamin utilization and excretion |
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Effects of infection on vitamin A
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reduces serum vitamin A concentrations, precipitating xerophtalmia
xerophtalmia = night blindness, corneal dryness, etc. |
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effects of infection on serum iron
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sequesters serum iron in reticuloendothelial system
phagocytes release lactoferrin |
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effects of infection on zinc
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decreases plama zinc concentration due to redistribution of metal to the liver
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iron deficiency anemia is associated with ___% of maternal deaths worldwide
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22%
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causes of maternal anemia
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low dietary intake of iron
porr absorption of iron malaria hookworm high fertility other micronutrient deficiencies diarrhea, HIV/AIDS, other infectious diseases |
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consequences of maternal anemia
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increased maternal & perinatal mortality
incrased numbers of preterm birth and/or low birthweight impaired cognitive development reduced work productivity |
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supplements for disease prevention:
neural tube defects |
folic acid
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supplements for disease prevention:
heart disease |
folate
vitamins B6, B12 Vitamin C vitamin E niacin |
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supplements for disease prevention:
osteoporosis |
calcium
vitamin D & K |
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supplements for disease prevention:
cancer |
beta carotene
selenium folate vitamins B6, B12 vitamin C vitamin E niacin Zn iron |
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5 characteristics of vitamins
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organic compounds
involved in release of energy from carbs, fats, and proteins by functioning as co-enzymes do not yield energy themselves function both dependently and independently one vitamin cannot substitute for another |
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In animals, preforemed vitamin A usually exists...
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retinol
retinyl carotenoids cryptoxanthin |
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In plants, vitamin A exists in its _______, i.e.:
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precursor form: provitamin A, carotenoids, and cryptoxanthin
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active component of vitamin A
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transretinol
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ingested forms
- from animal products - from plants |
animals: palmitate, acetate vitamin A (retinol)
plants: carotenoids |
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functions of vitamin A in normal vision
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formation of rhodopsin (retinal pigment) from retinal and opsin
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functions of vitamin A in epithelial cells
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normal integrity and groth of epithelial cells moistening linings of eye, resp, GI and GU tracts
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other functions of vitamin A
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collagen production
normal reproduction promotion of cellular differentiation |
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vitamin A utlization pathway
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ingest carotenoids
converted to retinol, then retinal in gut for transport absorption occurs in ileum and requires bile salts stored in liver as retinyl ester |
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vitamin A deficiency signs and symptoms
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night blindess
xerophthalmia - fail to produce tears pale conjunctiva decrased growth rate in children poor wound healing, loss epithelial integrity |
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vitamin A toxicity symptoms
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flaky, itchy, peeling rashes
teratogenic effects HA, irrritability, alopecia, muscle and bone pain blurred vision |
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risks for vitamin A toxicity
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pregnancy
increases risk lung CA in high risk groups (smokers, etc.) alcohol |
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activation of vitamin D
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undergoes 25-hydroxylation in the liver, followed by 1-hydroxylation in the kidneys
--> 1,25 (OH)2-D3 |
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functions of vitamin D
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increase calcium absorption
increase bone calcification and reabsorption maintain calcium, phosphate and bone homeostasis |
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sources of vitamin D
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fish liver oils, fatty ofish, egg yolks
sunlight conversion in skin |
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vitamin D deficiencies
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children: delayed growth and/or rickets
adults: osteomalacia and//or osteoporosis |
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risk of osteoporosis begins in ____
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adolescence
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forms of vitamin E
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tocopherals and tocotrienols
active form: alpha-tocopherol |
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vitamin E utilization
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absorbed with fats via lymphatic system
transported in lipoproteins |
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vitamin E function
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chain breaking antioxidant, preventing futher auto-oxidation of lipids
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vitamin E deficiency
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rare: most commonly due to severe malabsorption
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dietary sources of vitamin E
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veggie oils
nuts margarine mayonnaise |
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niacin utilization
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synthesized de novo from tryptophan
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niacin functions
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co-enzyme involved in energy metabolism
hydrogen receptor and donor: NAD, NADP, NADH, NADPH involved in lipid metabolism |
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dietary sources of niacin
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meat, fish, eggs, enriched breads and cereals
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niacin deficiency:
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pellagra: dermatitis, dementia, diarrhea, death
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treating hyperlipidemia with niacin
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nicotinic acid lowers serum LDL and TGs
raises HDL side effects: flushing, itching, HA, nausea, hyperuricemia, abnormal liver function, hyperglycemia |
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functions of vitamin K
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co-factor for synthesis of prothromin and other proteins in clotting cascade
serves as co-factor in gamma-carboxylation of glutamyl residues on bone proteins |
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vitamin K utiliztion
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synthesized by bacteria in small intestine
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vitmain K dietary sources
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dark green leafy veggies
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etiology of deficiency
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malabsorption syndrome
biliary obstruction oral sulfa drugs or ABS |
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vitamin K deficiency
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prolonged clotting time and hemorrhage in newborns
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vitamin K prevents
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low bone mineral density
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folic acid (folate) utilization
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absorption occurs in proximal jejunem
enters enterohepatic circulation and binds albumin serum folate levels reflect v. recent dietary ingestion - normal levels don't R/O deficiency taken up by cellular folate receptors, 5-CH3-THF is converted to THF by vitamin B12-dependent methionine synthase |
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THF
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tetrahydrofolate
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THF metabolism is dependent on which vitamin?
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B12
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functions of folate
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synthesis of purine and pyrimidines and RBCS in conjuction with vit. B12
thymidine synthesis amino acid modifications and conversions |
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folate deficiency
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megaloblastic/macrocytic anemia (blockage of erthyrogenic pathway)
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role of folate in prevention of cardiovascular ds
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cofactor and substrate in homocysteine metabolism, converting methionine to cysteine
strong inverse association btw homocystein and folate levels |
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role of folate in preventing neural tube defects
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essential during first trimester of pregnancy
1 mg/day usu. supplemented |
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populations at risk for folate deficiency
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alcoholics
low produce intake low grain product intake (US grain fortified w/ folate) |
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thiamin function
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co-enzyme in energy function
required for nerve conduction thiamin pyrophosphate and pyruvate decarboxylase convert pyruvate to acetyl CoA |
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diatery sources of thiamin
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meats
eggs wheat germ cereals nuts and legumes |
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thiamin deficiency
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Beri Beri
seen in populations consuming only polished rice alcohol inhibits thiamin absorption in the gut |
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earliest symptoms of thiamin deficiency
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anorexia, fatique depression, irritablity, poor memory, inability to concentrate
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advanced thiamin deficiency
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peripheral neuropathy
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Wernicke's encephalopathy
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thiamin deficiency
ophthalmoplegia nystagmus ataxia |
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Korsakoff's psychosis
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memory defect
confabulation |
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functions of vitamin C
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collagen formation
antioxidant increase in non-heme iron absorption co-factor for cytochrome P 450 enzymes |
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conditions requiring increased vitamin C
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severe burns
fractures PNA rheumatic fever TB surgery cigarette smoking |
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condition requiring decreased vitamin C
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oxalate kidney stones
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vitamin C deficiency
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related to defects in collagen:
petechia ecchymosis bleeding gums hyperkeratosis arthalgia impaired wound healing joint effucions weakness, fatigue impaired bone growth in children |
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vitamin B12
form: utiliation: dietary sources functions: |
B12:
cyanocobalamin - synthesized by microorganisms - requires intrinsic factor for absorption in ileum - stored in ileum meats, fish, eggs, milk required for DNA synthesis and hematopoeisus |
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B12 deficiency
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megalobaslic anemia
pancytopenia neurological (long-term) |
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How are nutrient minerals classified?
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based on content in body
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calcium supplements
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calcium carbonate - fairly well absorbed when taken with food
calcium citrate - not as well absorbed calcium gluconate - not well absorbed |
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Difference btw RDA and DRI
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RDA - focused on avoiding vitamin deficiencies, rather than maintaining health
DRI focused more on health promotion and disease prevention |
