Midterm 2 Section 4

Question 1

Healthy erythropoiesis

Answer 1

red blood cell production
RBC made in bone marrow from stem cells
Main steps:
1) cells divide, and hemoglobin synthesis begins
2) nucleus migrates with organelles and leaves cell
3) circulates for 120 days or so without nucleus and then dies

Question 2

Microcytic anemia erthyropoiesis

Answer 2

1) cells divide
2) without iron hemoglobin synthesis is impaired
3) creates small (microcytic), pale (hypochromic) RBCs and less are made

Question 3

signs and symptoms of iron deficiency anemia
Hemoglobin and hematocrit levels to diagnose

Answer 3

tiredness, decreased work performance, decreased childhood development (psychomotor and intellectual), increased lead poisoning susceptibility

Men Hgb > 140 g/L
Women Hgb > 120 g/L
Hematocrit HCT 40% blood volume is normal
Can also test for free protoporphyrin circulating (indicates lack of hemoglobin to fill it)

Question 4

iron deficiency anemia stats

Answer 4

50% of women and children, 25% men in developing countries

7-12% deficient in developed countries

Question 5

iron functions

Answer 5

binds oxygen for transfer as part of the heme group in hemoglobin/myoglobin
electron transport in cellular respiration cytochrome complex
can be oxidized in reactive oxidative species protection such as peroxidase, myeloperoxidase, and catalase
functions in some metalloenzymes

Question 6

hemoglobin vs myoglobin

Answer 6

hemoglobin - transport of oxygen to tissues
contains 4 heme subunits
myoglobin - muscle storage of oxygen
contains 1 heme subunit

Question 7

where is iron bound in hemoglobin?

Answer 7

protoporphyrin when combined with an iron atom, forms heme, the oxygen-bearing prosthetic group of the red blood pigment hemoglobin.

Question 8

DMT

Answer 8

divalent metal transporter
divalent cations are Ca, Zn, Pb, and Mg

Question 9

ferrous vs ferric

Answer 9

ferrous - Fe 2+ (reduced)
ferric - Fe 3+ (oxidized)

Question 10

Iron metabolism

Answer 10

1) Ferrous iron enters intestinal epithelial cells
2) Inside cell it is bound by transferrin and oxidized to ferric iron and escorted to tissues such as bone marrow for RBC production
3) In tissues it is converted back to Fe 2+ and added to protoporphyrin to make heme and then hemoglobin in RBCs
4) RBCs circulate and then die, iron is Fe 2+ is recycled in the liver, reconverted to Fe3+ for binding to transferrin or stored as Fe 3+
5) Heme is excreted as bilirubin in bile, or bound by albumin and excreted in urine

Question 11

bioavailability of iron

Answer 11

15%, RDA is what is needed in the diet, not the amount that is metabolically active

Question 12

ferritin and how to measure levels

Answer 12

protein that binds Fe3+ for storage in the liver
can be measured in blood plasma

Question 13

Sequential changes with iron deficiency development

Answer 13

1) Depletion of iron stores - plasma ferritin decreases

2) changes in iron transport: increased intestinal absorption efficiency, transferrin binding capacity and transferrin receptors, decreased transferrin saturation %

3) Defective erythropoiesis: decreased plasma iron, FEP (free erythrocyte protoporphyrin)

4) Iron deficiency anemia: microcytic hypochromic erythrocytes and associated behavioral signs

Question 14

Bloodwork Stages of Anemia

Answer 14

Stage 1) increasing concentration of transferrin to pick up more iron but protoporphyrin saturation index will go down, in bone marrow increased transferrin receptors, increasing absorption percentage

Stage 2) Not enough iron to bind all protoporphyrin - free protoporphyrin (Free Erythrocyte Protoporphyrin)

Stage 3) Shows as low hemoglobin and low hematocrit, mean cell volume (small cells, microcytic), hypochromic anemia

Question 15

Causes of iron deficiency

Answer 15

Decreased intake
Inhibition of absorption by mineral interactions and inhibitors
Increased red cell mass development like in pregnancy
Increased blood loss: hemolysis, occult, heavy menstruation

Question 16

Good sources of iron

Answer 16

Fortified foods: processed grains
Elemental iron: pinto beans, peanut butter, sunflower seeds, parsley, tofu, prune juice
Heme iron: clams, liver, meat, fish, eggs

Question 17

heme and non-heme iron intake
factors that increase iron absorption

Answer 17

25% absorbed from heme sources, 10% of dietary intake
1-50% absorbed from non-heme sources, 90% of dietary intake

increased by sugars, vitamin C, and acids (including amino acids)
decreased by Ca, P, phytates, oxalates, polyphenols, tannins, EDTA

Question 18

iron UL
RDA for men vs women

Answer 18

45mg/day
18mg for women (33 if vegan), 8mg for men (14 if vegan)
27mg for pregnancy, 11mg if on oral contraceptives

Question 19

iron supplements should be

Answer 19

not above 10mg (constipating)
ferrous sulphonate or gluconate

Question 20

indicators of deficiency vs over-supply of iron

Answer 20

low saturation of transferrin indicates deficiency due to increased transferrin synthesis
high saturation of transferrin indicates excess

Question 21

daily iron losses

Answer 21

men 1mg/day
women 1.4 mg/day (premenopausal)
lost through sweat, urine, feces, skin and menstruation/bleeding

Question 22

what can cause iron toxicity?

Answer 22

megadoses of vitamin C over 5g reduces bound ferric iron to Fe2+ and frees it creating Fenton reaction

hemochromatosis

Question 23

hemochromatosis

Answer 23

autosomal recessive genetic disorder, affects men more, defective hepcidin production increases iron release from intestinal epithelial cells
- iron is deposited as hemosiderin in liver causes cirrhosis
- treatment is phlebotomy or desferroxamine

Question 24

megaloblastic anemia

Answer 24

larger than normal, irregularly shaped RBC that are unable to divide, keep growing and don’t excrete nucleus due to folate or B12 deficiency
cannot carry oxygen efficiently
slow to develop due to B12 stores
considered 1° deficiency

Question 25

parts of folate structure

Answer 25

dihydropteridin ring, PABA, glutamate

Question 26

Folate metabolism

Answer 26

1) folate is naturally occurring as folate polyglutamate (folate monoglutamate/folic acid in supplements and fortified foods)
2) In the intestine the polyglutamate tail is removed and folate is methylated
3) B12 activates folate by demethylating and methylating itself, therefore also activating B12
4) both are now available as coenzymes for DNA synthesis

Question 27

folate sources

Answer 27

brightly colored fruits and veg and legumes and fortified processed grain foods
ex. dark leafy vegetables, lentils, pinto beans, asparagus, broccoli, tomato

Question 28

B12 structure

Answer 28

cobalamin contains cobalt in the center

Question 29

absorption of B12

Answer 29

HCl and pepsin release B12 from dietary proteins
gastric cells secrete intrinsic factor which binds B12 for absorption in SI
Lack of intrinsic factor can be secondary deficiency

Question 30

Folate/B12 activation cycle

Answer 30

Folate trap (methylated), B12 demethylates and converts homocysteine to methionine activating folate
activated folate acts as coenzyme in DNA synthesis
NADPH (by riboflavin FAD) methylates folate again

no B12 means no activation of folate and no DNA synthesis which leads to megaloblasts

Question 31

pernicious anemia

Answer 31

low intrinsic factor production due to aging or poor gut health
or neurological component
B12 is not recognized for absorption
leads to megaloblasts but is NOT the same as megaloblastic anemia
cannot be fixed with diet or supplemental changes, only B12 injection or nasal spray
considered 2° deficiency

Question 32

Side effects of folate deficiency

Answer 32

megaloblastic anemia
neural tube defects
decline in cognitive functions/alzheimer’s
elevated homocysteine CVD risk

Question 33

what forms the neural tube in a developing fetus?
when does the neural tube close?

Answer 33

primitive streak forms the neural tube which closes at 6 weeks (4 weeks after conception) in a healthy fetus

Question 34

types of neural tube defects

Answer 34

spina bifida - outpouching of nerves from spinal cord

anecephaly - brain is partially or completely absent (can be lethal)

encephalocoele - brain and skull are malformed

Question 35

risk factors for neural tube defects

Answer 35

3/1000 live births
preconceptional folate status
genetics
Northern european or hungarian ancestry
if it occurs once, 20x more likely to occur again

Question 36

neural tube defect prevention

Answer 36

400ug per day for 1 month prior to conception, and continue through first trimester
4000ug per day for previous NTD to prevent another
you can really only get 200ug from the diet only

Question 37

folate supplementation benefits

Answer 37

decrease cognitive decline (Alzheimer’s), decrease risk of stroke and depression
decreases homocysteine levels
decreases megaloblastic anemia
decreases neural tube defects

Question 38

what is homocysteine
how to decrease homocysteine levels

Answer 38

intermediate compound that in excess causes oxidative stress, can damage arterial walls and increase risk of CVD/stroke

B12/folate - activation also results in conversion to methionine
B6 - conversion to cysteine, aminotransferase cofactor

Question 39

when does the government fortify with a nutrient

Answer 39

to correct widespread nutritional deficiency
to restore nutrients lost in processing
to add nutrients normally supplied in the food the product replaces
questions: can you reach the people who need it? can you fix the problem without endangering others?

Question 40

how does folate supplementation mask B12 deficiency

Answer 40

additional folate will fix megaloblastic anemia
cannot fix irreversible neurological problems from B12 deficiency
RBC issue is fixed but neurological issues continue untreated