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Hematology Lecture 11
Hematology Lecture 11 Red Cell Metabolism III
81
Biology
Undergraduate 3
11/28/2014

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Term
Name the 7 Globin Chains
Definition
Alpha (α)
Beta (β)
Zeta (ς)
Delta (δ)
Epsilon (ε)
Gamma-A (γA)
Gamma-G (γG)
Term
Globin synthesis is directed by ____ genetic loci per haploid genome
Definition
Eight
Term
These genetic loci/haploid genome produce 7 different types of globin chains
Definition
Term
Globin chain synthesis occurs on ____ ____ during the _____ to _____ stages
Definition
RBC Ribosomes
Pronormoblast
Reticulocyte
Term
Which Genes will be found on Chromosome 16?
Definition
Zeta (embryonic)
Alpha
Term
Which Genes will be found on Chromosome 11?
Definition
Epsilon (embryonic)
Gamma
Delta
Beta
Term
Activation of globin gene progresses from ____ to ____ on Chromosome 16
Definition
Zeta
Alpha
Term
Activation of globin gene progresses from ____ to ____, ____, and ____ on chromosome 11
Definition
Epsilon
Gamma
Delta
Beta
Term
Epsilon and zeta chains normally only appear during ______ development
Definition
embryonic
Term
Epsilon and zeta chains may be produced up to _____ months following conception
Definition
3
Term
True or False:
Embryonic Hemoglobin - Alpha chains are always present
Definition
True
Term
What are the 3 Embryonic Hemoglobins?
Definition
Hemoglobin Gower 1 (Zeta2, epsilon2)
Hemoglobin Gower 2 (alpha2, epsilon2)
Hemoglobin Portland(zeta2, gamma2)
Term
In Fetal Hemoglobin - Production of gamma chains is active from the ____ _____ ____ until ___ ____ postnatally
Definition
third fetal month
1 year
Term
Fetal hemoglobin is:
Definition
alpha2, gamma2
Term
By age 2, Hemoglobin _____ is less than 2% of total hemoglobin
Definition
F
Term
_____ _____ production rises gradually prenatally and reaches adult percentages between 3 – 6 months postnatally
Definition
Beta Chain
Term
All normal adult hemoglobins are formed as
Definition
Tetramers
Term
These tetramers consist of what?
Definition
2 alpha chains
2 non-alpha chains – beta, delta, or gamma
Hydrogen bonds and salt bridges
Term
Hemoglobin _____ consists of Alpha and Beta and 96% of Adult/30% of Newborn
Definition
A
Term
Hemoglobin ____ consists of Alpha and Delta and 3% of Adult, 1% of Newborn
Definition
A2
Term
Hemoglobin ____ consists of Alpha and Gamma and 1% of Adult/70% of Newborn
Definition
F
Term
Heme is inserted into the _____ chains
Definition
Globin
Term
True or False:
In Normal Hemoglobin the order of Amino Acid is Very Important
Definition
True
Term
True or False:
If amino acid sequence changes, can cause the hemoglobin not to coil and red cell is no longer pliable
Definition
True
Term
_____ ____ have a simple AA change
Definition
Sickle Cells
Term
One of the most important controls of hemoglobin affinity for oxygen is the RBC ______ ______ ______
Definition
organic phosphate 2,3-diphosphoglycerate (2,3-BPG)/(2,3-DPG)
Term
Where is 2,3-BPG produced?
Definition
In the Leubering-Rapaport Shunt
Term
Deoxyhemoglobin
Definition
When 2,3-BPG is part of the hemoglobin molecule, it widens the space between the beta chains, forming an anionic salt bridge
Term
Oxyhemoglobin
Definition
When 2,3-BPG is absent, the salt bridge is broken and the hemoglobin molecule will carry more oxygen
Term
Which of the following has a LOWER affinity for oxygen?
Oxyhemoglobin or Deoxyhemoglobin
Definition
Deoxyhemoglobin
Term
Why does Deoxyhemoglobin have a lower affinity for oxygen?
Definition
This is due to formation of the salt bridge
Term
Which of the following has a HIGHER affinity for oxygen?
Oxyhemoglobin or Deoxyhemoglobin
Definition
Oxyhemoglobin
Term
Why does Oxyhemoglobin have a higher affinity for oxygen?
Definition
Salt bridges are broken, Beta chains are pulled together, 2,3-DPG is expelled
Term
What determines the proportion of oxygen that is released to the tissues or loaded onto the cell at a given oxygen pressure?
Definition
Hemoglobin affinity for oxygen
Term
Increased oxygen affinity means the hemoglobin has a ...
Definition
Higher affinity for oxygen
Term
Does Hemoglobin with a high affinity for Oxygen want to give up Oxygen?
Definition
No
Term
When will Hemoglobin release oxygen more readily?
Definition
When Hemoglobin has a low affinity for oxygen
Term
Oxygen affinity of hemoglobin is usually expressed as the PO2 at which ______ of the hemoglobin is saturated with oxygen
Definition
50%
Term
P50 is normally about ____ mm Hg
Definition
26
Term
If hemoglobin-oxygen saturation is plotted versus the partial pressure of oxygen (PO2), a ____ _____ results
Definition
sigmoid curve
Term
This sigmoid curve is known as:
Definition
Hemoglobin-Oxygen Dissociation Curve
Term
Normally in the lungs, the oxygen tension is almost _____ saturated
Definition
100%
Term
As RBC’s circulate, oxygen is released when PO2 drops to ____ mm Hg
Definition
40
Term
When the PO2 drops to 40 mm Hg, how much of oxygen is released?
Definition
25%
Term
Right Shift
Definition
Oxygen affinity is decreased
More oxygen is released to the tissues
Term
5 Causes of Right Shift:
Definition
Hypoxia (reduction of oxygen supply to tissues)
Increased 2,3-BPG
Anemia
Acidosis
Fever
Term
Left Shift
Definition
Decreased oxygen delivered to tissues
Only 12% is released at 40 mmHg
Term
5 Causes of Left Shift:
Definition
Decreased 2,3-BPG
Alkalosis
Increased quantity of abnormal hemoglobin
Multiple transfusions
Fetal hemoglobin
Term
Shift in Hemoglobin-Oxygen Dissociation Curve:

Left Shift
Definition
pH increases
Temperature decreases
2,3-BPG decreases
Term
Shift in Hemoglobin-Oxygen Dissociation Curve:

Right Shift
Definition
pH decreases
Temperature increases
2,3-BPG increases
Term
Acquired Nonfunctional Hemoglobins
Definition
These molecules have been altered
Compromised oxygen transport
Term
Acquired Nonfunctional Hemoglobins Cause (2)
Definition
Hypoxia
Cyanosis
Term
Hypoxia
Definition
inadequate amount of oxygen at tissue level
Term
Cyanosis
Definition
bluish color of skin due to presence of high amounts of deoxyhemoglobin in blood
Term
3 Acquired Nonfunctional Hemoglobins
Definition
Carboxyhemoglobin
Methemoglobin
Sulhemoglobin
Term
Carboxyhemoglobin
Definition
Occurs when hemoglobin is exposed to carbon monoxide
Can be fatal
Hemoglobin’s affinity for carbon monoxide is >200 times greater than affinity for oxygen
Smokers can have up to 12%
Term
Methemoglobin
Definition
Hemoglobin with iron in the ferric (Fe+3) state
Incapable of combining with oxygen
Increased levels are formed when exposed to certain oxidizing chemicals or drugs
Infants are more susceptible to methemoglobin production
Term
True or False:
Infants are more susceptible to methemoglobin production
Definition
True
Term
Why are infants are more susceptible to methemoglobin production?
Definition
HbF more readily converts
Term
Sulfhemoglobin
Definition
An irreversible change in the hemoglobin molecule
Sulfur atom combines with each of the four heme groups
Binds to the oxygen
Term
Sulfhemoglobin - Hemoglobin molecule has an affinity for oxygen only ______ that of normal hemoglobin
Definition
1/100
Term
Aging is characterized by a decline in _____ _____ _____ and ______
Definition
cellular enzyme systems
pathways
Term
Aging leads to decreased _____ production
Definition
ATP
Term
Aging - Cell also loses the ability to maintain ___, ______, and _____ ______
Definition
shape
deformability
membrane integrity
Term
As RBCs age:
_______ enzymes decrease in activity
Definition
Glycolytic
Term
As RBCs age:
Cells become ____, ____, or _____
Definition
Spherocytic
Rigid
Burr
Term
Aged RBCs are removed by _______ or ____ ____
Definition
Macrophages
RE System
Term
______ returns iron to bone marrow or liver (stored as ferritin)
Definition
Transferrin
Term
______ is broken down and AA recycled
Definition
Globin
Term
_____ ____ is broken down to Toxic Bilirubin
Definition
Protoporphyrin
Term
Bilirubin is conjugated in the liver to make it ____ ____ and ______
Definition
More soluble
excretable
Term
_______ is excreted in the stool and a small amount is excreted in kidney
Definition
Urobilinogen
Term
About 90% of aged erythrocyte destruction is ________
Definition
Extravascular
Term
~90% of aged erythrocyte destruction:
____, _____, _____, ____ _____
Definition
Histiocytes
spleen
liver
bone marrow
Term
10% of Erythrocyte destruction is ______
Definition
Intravascular
Term
RBC ruptures in the blood vessels and ________ is released directly into the _________
Definition
hemoglobin
bloodstream
Term
Intravascular Hemolysis-
After the red cells rupture, the ____ ____ or ____ ____ are picked up by haptoglobin
Becomes a larger molecule that cannot be excreted by the kidney
Definition
alpha dimers
beta dimers
Term
Intravascular Hemolysis :
Prevents ___ ___
Definition
Kidney Damage
Term
Intravascular Hemolysis :
______ takes the dimers to the liver where it is converted to bilirubin
Definition
Haptoglobin
Term
_____ cell differential of WBCs
Definition
100
Term
What analysis is performed on a blood smear other than a 100 cell differential of WBCs?
Definition
RBC Morphology examined
Platelet Estimation performed
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