Blood Flashcards
Where do formed elements in blood come from?
Pluripotent stem cell
WBC, RBC, platelets
What can cause cyanosis?
Cyanosis: lips/fingertips/skin turn blue
Cause: lot of Hb that doesn’t have O2 bound
Hematocrit
Hematocrit=% of blood that is cells
normal: men=40-50%
women=35-45%
-after menopause, women’s levels go to what men’s areo
What does hypoxia, low O2 delivery to kidney’s signal?
↑ HIF (TF for erythropoietin) → makes erythropoietin → more RBC’s
*erythropoiesis (making RBC)=occurs in bone marrow
What does the kidney do?
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)
Erythropoietin (EPO)
“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
Not enough Fe→
microcytic anemia (RBC's will be smaller) hypochromic (too little color)
Vit B12 & Folic acid deficiency
Macrocytic anemia (bigger-can’t divide normally and spend more time in growth phase)
B12 deficiency
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
Folate
- Cooking destroys it (green beens)
- Alcohol inhibits liver from mobilizing folic acid
- Pregnant women need supplements
O2 Capacity and O2 Content
“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%
What is a symptom of low O2?
Confusion
Where do RBC get ATP?
Via anaerobic glycolysis
They don’t have mitochondria
*ATP needed for membrane flexibility, maintaine Fe 2+ state, prevent oxidation of Hb, ion transport (ATPase)
Hb A1C=
Glucose sticks to Hb
Fe in Hb
Iron (Fe) is recycled
Heme broken down to bilirubin
What can cause anemia?
↓ RBC ↓ Hb content ↓ Folate/B12 ↓ Fe Bone marrow damage (b/c no stem cells) Kidney damage (loss of EPO)
Effects: too little O2
Polycythemia
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)
Polycythemia vera (primary polycythemia)
- No EPO signal
- Bone marrow is making RBC when there isn’t a need
Large amounts of Fe 3+ in blood is called what?
methemoglobinemia
Sickle cell disease
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
What affects Hb?
2,3-BPG =(altitude) reduces affinity (→ shift)
↓ pH=↓affinity (→ shift)
HbF (fetal) (fetus doesn’t have binding site) ← shift
Fe deficiency
Anemia (you test for ferritin (not Fe)
- poor diet
- menstruation
- hypochromic microcytic
Treatment: supplements
Fe 3+=damage
Transport Fe in Enterocyte
- Fe 3+→Fe 2+ via Dcytb
- Into enterocyte via DMT1
- 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)
Pyridoxine responsive anemia
B6 deficiency
E7
distal histidine
F8
Proximal (bound to heme). Involved in changing conformation when O2 binds
Hereditary Hemochromatosis
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
Hepcidin
- 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
Hfe and Hepcidin
Hfe controls Hepcidin
-If Hfe is mutation, it can’t bind TFR2→can’t turn on hepcidin expression → lots of ferroportin → Fe overdose
Fe deficiency smear test
Blood smear should be hypochromic, microcytic
Low serum ferritin
Serum ferritin=high (Hfe mutation)
Fole and B12 deficiency
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)
Eating folic acid
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)
B12 absorption
- B12 binds R-binder proteins in stomach (gastric mucosa cells)
- Proteases degrade R-binder in duodenum, releasing B12 (“hand-off”)
- 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
Schilling Test
Vit B12 deficiency: diet or absorption problem?
- 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
