Blood

Question 1

Where do formed elements in blood come from?

Answer 1

Pluripotent stem cell

WBC, RBC, platelets

Question 2

What can cause cyanosis?

Answer 2

Cyanosis: lips/fingertips/skin turn blue

Cause: lot of Hb that doesn’t have O2 bound

Question 3

Hematocrit

Answer 3

Hematocrit=% of blood that is cells

normal: men=40-50%
women=35-45%

-after menopause, women’s levels go to what men’s areo

Question 4

What does hypoxia, low O2 delivery to kidney’s signal?

Answer 4

↑ HIF (TF for erythropoietin) → makes erythropoietin → more RBC’s

*erythropoiesis (making RBC)=occurs in bone marrow

Question 5

What does the kidney do?

Answer 5

Senses O2 levels in tissues

If low O2 to KIDNEY→ kidney gets more HIF→ ↑ erythropoietin (EPO)

*HIF is destroyed by O2, so high O2 will destroy HIF and thus body won’t make more RBC/erythropoietin (EPO)

Question 6

Erythropoietin (EPO)

Answer 6

“We’re in a hurry and need RBC’s!!!”

A peptide hormone (travels in blood) secreted by the kidneys that increases the rate of production of red blood cells in response to falling levels of oxygen in the tissues

Receptor: in JAK2/STAT5 pathway→ “growth”

• Acts on stem cells→ ↑ differentiation→proerythroblasts→RBC
• ↑ maturation rate (makes mature faster)
• ↑ transferrin (transport protein for Fe) & its receptor

Question 7

Not enough Fe→

Answer 7

microcytic anemia (RBC's will be smaller)
hypochromic (too little color)

Question 8

Vit B12 & Folic acid deficiency

Answer 8

Macrocytic anemia (bigger-can’t divide normally and spend more time in growth phase)

Question 9

B12 deficiency

Answer 9

Pernicious anemia

megaloblastic macrocytic anemia

Lack of B12 b/c of lack of intrinsic factor (made by stomach, from same cells that make gastric acid)

Protects B12 from digestion: B12 needs to get through stomach to intestine for absorption

Cause: gastric mucosa destroyed via auto-immune mechanism)

• Elderly, Northern Europeans
• Testing: CBC test will show macrocytic, nomochromic anemia

Question 10

Folate

Answer 10

• Cooking destroys it (green beens)
• Alcohol inhibits liver from mobilizing folic acid
• Pregnant women need supplements

Question 11

O2 Capacity and O2 Content

Answer 11

“available seats in a room”

Amt of O2 that can be carried in blood assuming every heme has O2 bound to it

Hb (hemoglobin) carries 1.34 mL O2/100 mL blood
(100 mL=1 deciliter (1 dL) )

SO……

(1.34 mL O2/g Hb) (15 g Hb/dL blood)= 20.1 mL O2/dL blood=OXYGEN CAPACITY

O2 CONTENT: how much O2 is actually there. “150 people in a room”

-Need O2 % saturation (will be given)

Content=capacity x % saturation
=20.1 mL O2/dL x 95%= 19.1 mL O2/dL

*Normal O2 content=at least 90%

Question 12

What is a symptom of low O2?

Answer 12

Confusion

Question 13

Where do RBC get ATP?

Answer 13

Via anaerobic glycolysis

They don’t have mitochondria
*ATP needed for membrane flexibility, maintaine Fe 2+ state, prevent oxidation of Hb, ion transport (ATPase)

Question 14

Hb A1C=

Answer 14

Glucose sticks to Hb

Question 15

Fe in Hb

Answer 15

Iron (Fe) is recycled

Heme broken down to bilirubin

Question 16

What can cause anemia?

Answer 16

↓ RBC
↓ Hb content
↓ Folate/B12
↓ Fe
Bone marrow damage (b/c no stem cells)
Kidney damage (loss of EPO)

Effects: too little O2

Question 17

Polycythemia

Answer 17

Too many RBC’s (blood doping)

Effects: more O2 carrying content but thicker blood and heart thus has to work harder (blood is like honey)

Question 18

Polycythemia vera (primary polycythemia)

Answer 18

• No EPO signal

- Bone marrow is making RBC when there isn’t a need

Question 19

Large amounts of Fe 3+ in blood is called what?

Answer 19

methemoglobinemia

Question 20

Sickle cell disease

Answer 20

RBC is deformed (hemoglobin defect)

Hb defect at AA#6 where valine(hydrophobic-wants to be on inside) is used instead of glutamic acid

-Hemolytic anemia
Symptoms: pain, organ damage, strokes, ↑ infections

Question 21

What affects Hb?

Answer 21

2,3-BPG =(altitude) reduces affinity (→ shift)

↓ pH=↓affinity (→ shift)

HbF (fetal) (fetus doesn’t have binding site) ← shift

Question 22

Fe deficiency

Answer 22

Anemia (you test for ferritin (not Fe)

• poor diet
• menstruation
• hypochromic microcytic

Treatment: supplements

Fe 3+=damage

Question 23

Transport Fe in Enterocyte

Answer 23

1. Fe 3+→Fe 2+ via Dcytb
2. Into enterocyte via DMT1
3. On backside of cell, ferroportin sends it out of cell into blood via Hephestin → Fe 3+ → transferrin (Fe content is regulated by absorption via Hepcidin)

Question 24

Pyridoxine responsive anemia

Answer 24

B6 deficiency

Question 25

E7

Answer 25

distal histidine

Question 26

F8

Answer 26

Proximal (bound to heme). Involved in changing conformation when O2 binds

Question 27

Hereditary Hemochromatosis

Answer 27

Helps w/ signal or High or Low Fe

Organ dysfunction due to Fe overload: cirrhosis, arthritis, skin pigmentation

Genetic definition: classical HH

• autosomal recessive
• Mutations in HFE gene (common mutation=C282Y)..involved in regulation of Fe absorption

Question 28

Hepcidin

Answer 28

• Regulated by Hfe
• Regulates export/import of Fe to bone marrow
• Binds to channel (ferroportin) that Fe goes through to get outside

-↑ hepcidin= ↓ferroportin = ↓Fe

Question 29

Hfe and Hepcidin

Answer 29

Hfe controls Hepcidin

-If Hfe is mutation, it can’t bind TFR2→can’t turn on hepcidin expression → lots of ferroportin → Fe overdose

Question 30

Fe deficiency smear test

Answer 30

Blood smear should be hypochromic, microcytic
Low serum ferritin
Serum ferritin=high (Hfe mutation)

Question 31

Fole and B12 deficiency

Answer 31

Megaloblastic macrocytic anemia (large RBC but normal Hb content)

Results from diminished DNA synthesis in making RBC in bone marrow

Blood smear: macrocytic, normochromic cells (nothing wrong with Fe)

Question 32

Eating folic acid

Answer 32

When you eat folic acid → methyl form and needs B12 (to demethylate)

Lot of folate can mask B12 deficiency

B12 not available=folate stuck as methyl-THF (folate trap)

Question 33

B12 absorption

Answer 33

1. B12 binds R-binder proteins in stomach (gastric mucosa cells)
2. Proteases degrade R-binder in duodenum, releasing B12 (“hand-off”)
3. Intrinsic factor carries B12 to ileum → receptors bring B12 into body

• B12 deficiency more common in elderly (their GI tract)
• Common mutation/defect=Intrinsic factor→ B12 will just go into poop

Question 34

Schilling Test

Answer 34

Vit B12 deficiency: diet or absorption problem?

1. Given labeled and unlabeled B12
   2a. Labeled: saturates body so radioactive form is urinated out. If in urine→then patient absorbed B12 (DIET is answer)
   2b. If you don’t find B12 in urine→repeat but add intrinsic factor. If you find B12 in urine → due to INTRINSIC FACTOR/ABSORPTION