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Nutrition & Trace Elements Flashcards

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1
Q

In what form in iron stored in the body?

A

Ferritin:
24 subunit protein – MW ~450 kD
Binds up to 4500 Fe3+ as hydroxyphosphate
Present in most cells, esp. liver, spleen, marrow
Readily mobilized as needed

Hemosiderin:
Insoluble complex derived from ferritin
Decreased apoferritin content
Releases iron less readily than ferritin

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2
Q

Iron is part of what 5 important things in the body?

A

1 Hemoglobin (2500 mg)
2 Myoglobin (130 mg)
3 Enzymes, cytochromes (8 mg)
4 Transferrin, plasma (3 mg)

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3
Q

In a typical diet 10-20 mg/day is available yet only 5-10% of that is absorbed. Where does iron absorption take place?

A

Absorbed in duodenum and jejunum only as Fe2+

Gastric reducing environment (e.g., vitamin C) helpful

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4
Q

How is iron transported within plasma and why?

A

Free unbound iron is toxic. So it is bound and transported very transferrin.

Transferrin:
ß-globulin glycoprotein
MW 79.5 kD
Two Fe3+ binding sites per molecule
Trf is in excess; Fe saturation 20-50% typically
—–Specific Trf receptor for tissue uptake

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5
Q

How is serum iron measured? What type of specimen can be used?

A

Specimen: serum or heparinized plasma
Principle:
Fe3+ is released from binding proteins by acidification
Fe3+—> Fe2+ by ascorbate or other reducing agent
Fe2+ binds to ferrozine, ferene, or bathophenanthroline and is measured with a spectrophotometer
Usually not affected by hemolysis
Heme iron not released in assay
Test should also include iron-binding capacity
Reference Interval:
Male 65-170 mcg/dL
Female 50-170 mcg/dL
Diurnal variation (high in am, low in pm)

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6
Q

How is transferrin measured?

A

Immunoassay (nephelometry or turbidimetry)

Reference interval 200-320 mg/dL

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7
Q

What is TIBC? How is it measured?

A

TIBC-Total Iron Binding Capacity (semi-automated):

Add excess Fe3+ to sample and equilibrate
Complex non-bound iron (e.g., MgCO3) and separate
Measure Trf-bound iron (as in total iron)
Reference interval: 175-400 mcg/dL (iron)

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8
Q

What is UIBC? How is it measured?

A

UIBC-Unsaturated Iron Binding Capacity (automated)

Add excess Fe3+ to sample and equilibrate
Measure unbound iron only (no acidification)
TIBC = UIBC + serum iron
UIBC = Added iron-measured iron
Do not report UIBC results, only TIBC (& percent saturation)

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9
Q

How is Transferrin Saturation and Transferrin itself calculated?

A

Transferrin Saturation = Fe ÷ TIBC (or Trf)
—Usually expressed as a percent

Transferrin (mg/dL) ≈ 0.8 x TIBC (mcg Fe/dL)

TIBC reference interval: 175-400 mcg/dL
Trf Sat’n reference interval: 15-60% (TIBC)

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10
Q

Serum ferritin is ______ to stored iron and will _____ as iron stores______.

A

directly proportional.
decrease.
deplete.

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11
Q

What are the tree stages of iron deficiency anemia?

A

Stage 1 : Iron DEPLETION
Depletion of iron stores marked by ferritin decrease
Normal serum iron and TIBC (ferritin maintains serum levels)
No anemia
Normal RBC morphology

Stage 2: Iron-deficient Erythropoiesis
Decreased iron available for erythropoiesis (stores depleted)
Decreased ferritin, serum iron, Trf sat’n; increase in TIBC (Trf)
No anemia; RBC slightly microcytic, no hypochromia, inc. RDW

Stage 3 : Iron DEFICIENCY ANEMIA
Decrease in ferritin, iron, Trf sat’n; increase in TIBC (Trf)
Decrease in hemoglobin, MCV, MCH, MCHC; inc. RDW
Microcytic, hypochromic anemia

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12
Q

Describe the pathogensis of anemia due to chronic disease.

A

Inflammatory cytokines induce hepcidin production by the liver
Hepcidin prevents iron release from enterocytes and macrophages
Low available iron interferes with bacterial growth

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13
Q

What role does copper play in the body?

A

Enzyme cofactor – esp. redox enzymes

Bound to ceruloplasmin (α2-globulin)

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14
Q

Copper deficiency leads to…?

A

Deficiency:
Microcytic, hypochromic anemia
Neutropenia

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15
Q

Copper excess is called…?

A

Excess: Wilson’s disease
Copper deposition in tissues, esp. liver and brain
Decreased ceruloplasmin and serum Cu, plus elevated urine Cu

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16
Q

How is copper measured?

A

Measure Cu by atomic absorption, ceruloplasmin by immunoassay (nephelometry or turbidimetry)

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17
Q

What are the fat soluble vitamins?

A

A: carotene, retinol, retinal, retinoic acid
Vision
Epithelial cell stability

D: cholecalciferol
Ca2+ absorption

E: tocopherols
Antioxidant, free radical scavenger

K: phylloquinones, menaquinones
Synthesis of clotting factors II, VII, IX, X, C and S
Cofactor for enzymatic formation of γ-carboxyglutamate

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18
Q

Fat soluble vitamins are readily stored in the body and deficiency slowly develops. What can cause it?

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A

Decreased dietary intake
Decreased absorption
Biliary deficiency
Intestinal malabsorption

19
Q

Which vitamin is commonly measured? How?

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A

(Vitamin D) by HPLC
Vitamin D: LC-MS/MS or immunoassay

—-Immunoassay:
Must measure both D3 and D2 equally
Must displace from binding protein - (D3 bound tighter)
—–LC-MS/MS: preferred method but more expensive
Reference intervals controversial:
80->150 ng/mL seen)

20
Q

Vitamin D absorption/conversion can be inhibited by…?

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A

Dec. by pigmented skin, low sun angle (high latitude, winter)

21
Q

Where is Vitamin D mostly found?

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A

primarily in milk (added), cod liver oil, multi-vitamins, and supplements

22
Q

UV light converts 7-dehydrocholesterol to what?

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A

vitamin D3—-cholecalciferol

23
Q

How is Vitamin D metabolized?

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A

UV light + 7-dehydrocholesterol in skin——->Vitamin D3

Vitamin D3 to liver—–>25(OH) Vitamin D

In Kidney 25(OH)Vitamin D—->1,25(OH)2 Vitamin D (ACTIVE METABOLITE!!!)—–>Tissue specific Vitamin D response

24
Q

What is Vitamin D2

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A

Ergocalciferol from ergosterol UV irradiation
Of plant origin (yeast and mushrooms)
Identical hydoxylations as D3 (1- and 25-)
1,25 diOH D2 has same action as D3
Possible shorter half-life
More common form of pharmaceutical vitamin D (in U.S.)
OTC supplements are usually D3

25
Actions of Vitamin D?
Raise calcium levels: - --Increases GI (duodenal) Ca absorption - --Stimulates osteoclast precursors to become mature osteoclasts (break down bone) - --Stimulates osteoblasts to influence osteoclast bone resorption Immune modulation, …? ---All cells have vitamin D receptors but few have calcium responses
26
What is the best marker for vitamin D status?
Best marker of vitamin D status is 25-OH D (cf case) | ----Pts w/ renal disease may req. 1,25-diOH D measurement
27
What is Vitamin B1?
Thiamine (B1) - --α-ketoacid deHase cofactor (Pyr, α-KG) - --Beriberi & Wernicke’s encephalopathy (alcoholics) - --Measure in whole blood, not plasma - -----Transketolase enzyme assay historical surrogate
28
What is Vitamin B2?
Riboflavin (B2) | ----Dehydrogenase enzyme cofactor
29
What is Vitamin B3?
Niacin (B3) – nicotinic acid - ---Required for NAD+ and NADP+ - ----Pellagra results from deficiency
30
What is Vitamin B6?
Pyridoxine (B6) - Cofactor in >60 enzymes - Aminotransferases (ALT, AST) - ---Provide glucogenic substrates - Tryptophan metabolism - Catecholamine synthesis Excess can lead to peripheral neuropathy
31
What is Vitamin B12?
Corrin ring w/ Co+ coordination atom Involved in one carbon transfers Thymidine synthesis (DNA) Primary sources are meat and dairy (bacterial) Absorption requires: ----Low gastric pH to dissociate B12 from food -----Intrinsic factor (IF, stomach) for ileal absorption Transported in blood by transcobalamins
32
How is Vitamin B12 measured?
Immunoassay or intrinsic factor binding assay -----Use IF as binder in competitive assay Reference interval: 180-900 pg/mL -Definite deficiency
33
What causes Vitamin B12 deficiency?
Decreased gastric acidity -------Atrophy or proton pump inhibitors (e.g., Prilosec) Decreased intrinsic factor -------Anti-intrinsic factor antibodies (pernicious anemia) Malabsorption --------Pancreatic insufficiency, celiac dz, Crohn’s dz Decreased intake (vegetarians)
34
Vitamin B12 deficiency results in....?
Results in macrocytic anemia (reversible) ----Macrocytosis, hypersegmented PMN nuclei Irreversible neuropathy possible Treat by IM injections (if PA)
35
What is Folate?
A water soluble vitamin needed in the synthesis of DNA. - Primarily plant derived - Involved in one carbon transfers - Measure by immuno- or ligand-binding assay - Serum – may reflect recent diet, therefore reduced utility - Reference interval: >3.0 ng/mL, deficient 280 ng/mL, def.
36
What is Heme?
``` Fe-containing prosthetic group in: Hemoglobin Myoglobin Cytochromes Peroxidase Catalase ```
37
What color are porphyrinogens?
Colorless.
38
In Heme synthesis what is the rate limiting step?
1) ALA Synthase, inhibited by heme
39
Give an overview of heme synthesis.
Succinyl CoA---->ALA---->Porphobilinogen----->Uro---->Copro------------------------>Proto---->heme decreasing polarity of side chains-----> Urine: ALA PBG URO COPRO Stool: PROTO and COPRO (oxidation in urine and stool forms color)
40
What are porphyrias?
Rare disorders of partial enzyme deficiencies - Genetic or acquired - Dec. heme production reduces inhibition of ALA synthase, precursors accumulate ``` Clinical manifestations: Neurologic – usually acute presentation ---Abdominal pain, psychiatric --------Early precursor (ALA, PBG) accumulation Photosensitivity – usually more chronic ---Skin reactions, erythema, blistering ------Porphyrin(ogen) accumulation ```
41
How are Porphyrias diagnosed?
Urinary PBG if acute, neurological symptoms - ---Collect during an attack - ----If negative, acute porphyria unlikely - ----ALA dehydratase (PBG synthase) def. very rare (
42
Macronutrition: What can we make and what must we get from diet?
We can make carbohydrate We can make essential lipids (chol) Essential amino acids must be in diet We do not recycle nitrogen very well
43
What does Nitrogen balance mean?
Relationship of nitrogen intake to excretion Negative nitrogen balance – excretion exceeds intake Indicates muscle catabolism is providing nitrogen needs
44
What is enteral and parental feeding?
``` Enteral feeding (“stomach tube) ---Preferred ``` Parenteral feeding (IV) - --Peripheral – usually short term - --Total (TPN) - central line, usually longer or more critical patient - --Solutions may be high in glucose (5-10%) & lipid - --------Consider effect on blood samples drawn

Clinical Chemistry (9 decks)

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