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Flashcards in Anemia Deck (109)
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1

Hemoglobin Structure

Tetramer composed of two unlike pairs of globin polypeptide chains (one pair of alpha-globin and one pair of non-alpha globin)

2

Oxygen in its Ferrous vs Ferric form

Ferrous = Fe+2 (reduced) BIND O2
Ferric = Fe+3 (oxidized) CAN'T bind O2
Iron is reduced from ferric to ferrous by Cytochrome Reductase

3

Allostery of Hemoglobin

When O2 binds to hemoglobin at one site, hemoglobin changes in configuration, which alters the binding affinity of additional O2

4

Taut form of Hemoglobin

Deoxygenated form, under conditions where oxygen concentration is low (none of the 4 binding sites are occupied). T-configuration is present due to inter- and intra-salt bonds, H-bonding, and hydrophobic interactions

5

Relaxed form of Hemoglobin

Oxygenated form. As oxygen becomes more available, 1 oxygen binds, configuration changes and other sites have higher binding affinity. Breaking of salt bonds lead to R-conformation

6

Neumonic for %oxygen saturation with various pO2

mmHg/%
30-60, 60-90, 40-75 (100-98)

7

How does pH affect the hemoglobin dissociation curve?

Low pH = decreased O2 affinity = shift to right
High pH = increased O2 affinity = shift to left
Known as BOHR EFFECT

8

How does CO2 concentration affect the hemoglobin dissociation curve

CO2 + H20 >> carbonic acid >> bicarbonate and H+
This leads to a lower pH, initiating Bohr Effect. O2 will be unloaded in tissues with high metabolism (more CO2=more acidic=less O2 affinity)

9

How does Temperature affect the hemoglobin dissociation curve?

Higher Temp = Lower O2 affinity

10

How does 2,3-BPG concentration affect the hemoglobin dissociation curve?

Increase in BPG = Lower O2 affinity
(BPG is the product of anaerobic glycolytic pathway)

11

Hemoglobin vs Myoglobin

Myoglobin is a MONOMER and cannot undergo allosteric regulation. Has very high O2 affinity at very low O2 concentrations. Good for STORAGE

12

What are conditions that would create a Right-shift on hemoglobin dissociation curve?

Functional abnormal hemoglobin variants
Increase in BPG: High altitude, Pulmonary hypoxemia, Severe anemia, Congestive heart failure, Hepatic cirrhosis

13

What conditions would create a Left-shift on hemoglobin dissociation curve?

Functionally abnormal hemoglobin variants
CO poisoning
Decrease in BPG: Septic shock, Severe acidosis, Blood transfusion of stored blood, BPG-mutase deficiency

14

Alpha-like globin chains

4 gene copies on chromosome 16

15

Beta-like globin chians

2 gene copies on chromosome 11

16

Fetal Hemoglobin

Have distinct hemoglobin with high O2 affinity:
At 4-14 weeks gestation: Gower I, Gower II, Portland
At 8 weeks gestation: Fetal hemoglobin. Binds BPG poorly, putting the hemoglobin in a permanent relaxed state. Also increase in Bohr Effect

17

Hemoglobin at birth

65-95% HbF and 20% HbA

18

Hemoglobin after age 5

96-97% HbA
2% HbA2
1% HbF

19

HbA2

Functions much like HbA, has the same Bohr effect, same response to Bohr effect. Is more heat stable and has slightly higher O2 affinity

20

Hemoglobin Variants

More than 500 identified, ~200 are clinically significant
Most common HbS, HbC, HbE. Can lead to unstable hemoglobins or with altered O2 affinity

21

High Affinity Hemoglobin

Hemoglobin Chesapeake: single point mutation. Erythrocytosis because O2 delivery is reduced

22

Low Affinity Hemoglobin

Presents with cyanosis and mild anemia

23

Unstable Hemoglobin

Spontaneously denature, may or may not bind O2
Ex: Hemoglobin Zurich (single point mutation, increases O2 binding). Also Hemoglobin Koln (mutation in Beta-chein, increase O2 affinity. Mild anemia, reticulocytosis, splenomegaly). Finally, Hemoglobin Poole (mutation in gamma chain, infants with hemolytic anemia that resolves in a few months)

24

Methemoglobinemia

Fe+3 (ferric) cannot carry oxygen. The curve shifts to the left and p50 drops. Can be acquired (drugs and chemicals) or genetic (homozygous, think of the inbred blue-skinned family in KY). No treatment is needed for genetic, only cosmetic. For acquired, the higher the methoglobin level the more severe the symptoms (above 70% not compatible with life.

25

CO poisoning

240x more affinity to hemoglobin than O2. Normally have 3% CO, smokers have 10-15%. Causes curve to shift left. Leads to headache, malaise, nausea, dizziness., coma, MI. NOT cyanotic, instead is "cherry red"

26

Basic definition of Anemia, and the measurements to define it

Insufficient red cell mass to adequately deliver oxygen to peripheral tissues. Measure Hemoglobin concentration, Hematocrit, RBC count. Values will differ based on age, gender and geography

27

Reticulocyte Count

Is the percentage of reticulocytes with 1,000 RBC are counted. An increase in RBC destruction (or loss of blood) will raise the Reticulocyte count

28

Know the chart of Anemia by heart, OK?

OK!

29

Symptoms of Anemia

Shortness of breath, fatigue, rapid heart rate, dizziness, pain with exercise, pallor

30

Where do you find iron in the body?

Most iron is in hemoglobin, but about 25% is stored in Ferritin and Hemosiderin