HEMATOLOGY 1 MIDTERMS

Hemoglobin

One of the most studied proteins in the body due to the ability to easily isolate it from red blood cells.

95%

comprises approximately ____ of the cytoplasmic content of RBCs

34 g/dL

concentration of hemoglobin in RBCs is approximately

64,000 Dalton

molecular weight is approximately

Lungs to Tissue

main function

Acid-base balance

Contribute ______ balance by binding and releasing hydrogen ions and transport NO, regulator of vascular tone

X-ray crystallography

Hemoglobin was first protein structure was described using ________

2 different pairs of polypeptide chain and 4 heme groups

Hemoglobin consist of

Protoporphyrin IX

Consist of ring carbon, hydrogen and nitrogen atoms called

Ferrous Iron (Fe2+)

Central atom of divalent ____________ with reversibly combines with one oxygen molecule

Ferric Ion (Fe3+)

Ferrous iron oxidized to ______ and they can no longer bind with oxygen

Four globin chains

How many globin chains comprising each hemoglobin molecule

Primary, secondary, tertiary and quaternary protein stucture

Hemoglobin molecule can be described by its ______

Primary structure

Refers to the amino acid sequence of the polypeptide chains

Secondary structure

Refers to chain arrangements in helices and nonhelices

Tertiary structure

arrangement of helices into a pretzel-like configuration

Quaternary structure

Also called tetramer, describes the complete hemoglobin molecule which is spherical has, 4 heme group attached to 4 polypeptide chains and may carry u to 4 molecules of oxygen

Hemoglobin A

Predominant hemoglobin, composed of 2 a-globin chains and 2 B-globin chains

Glycated

Small percentage of this hemoglobin is _______-, a post translation modification formed by the non enzymatic biding of various sugars to globin chain amino groups over the life span of the RBCs

Hb A1c

Most characterized glycated hemoglobins

N-terminal valine of B-chain

Hb A1c attaches to the _________

4-6%

HbA circulates in A1c form

Mitochondria and cytoplasm

Heme biosynthesis occurs in _________, ________ of bone marrow precursors, pronormoblast through circulating Erythrocyte

Mature erythrocyte

Can no longer make hemoglobin

Glycine and succinyl coenzyme A (CoA)

Heme biosynthesis begins with the condensation of

aminolevulinate synthase

condensation of glycine and succinyl coenzyme A (CoA) in the mitochondria which is catalyzed by _________

Aminolevulinic acid (ALA)

aminolevulinate synthase to form

aminolevulinic acid dehydratase

converts aminolevulinic acid (ALA) to porphobilinogen (PBG)

hydroxylmethylbilane

porphobilinogen (PBG) undergo several transformations in the cytoplasm, it will convert into ______________

PBG deaminase enzyme

The porphobilinogen (PBG) undergo several transformations in the cytoplasm, it will convert into hydroxylmethylbilane with the help of ________

Uroporphyrinogen III

hydroxylmethylbilane converts to _________

Uroporphyrinogen III synthase

hydroxylmethylbilane converts to Uroporphyrinogen III with the help of ______

Coproporphyrinogen III

converted into ______________ with he help of Uroporphyrinogen decarboxylase.

Coproporphyrinogen III

final step of production of heme, which will start from the conversion of ________

Protoporphyrinogen IX

conversion of Coproporphyrinogen III to ___________

coproporphyrinogen oxidase

Conversion of Coproporphyrinogen III to Protoporphyrinogen IX with the help of _____

Cytoplasm

Heme will leave the mitochondria to join the globin chains in the __________

Chromosome 16

α- and ζ- globin genes are on the short arm of chromosome

Chromosome 11

ε-,γ-,δ- and β- globin gene cluster is on the short arm of chromosome

erythroid precursors

production of globin chains takes place in ___________ from the pronormoblast through the polychromatic erythrocyte.

Ribosomes of Cytoplasm.

Transcription of globin genes and translation of mRNA to the globin polypeptide chain occurs in the ________

Release

After translation is complete, the chains are ________ from the ribosomes in the cytoplasm.

Alpha chain

Positive charge has a high affinity for B chain

Beta chain

Negative charge attracted to alpha chain

Gamma globin chain

the next higher affinity

Delta chain

After gamma globin affinity

Heterodimer

After the release of globin from ribosomes, each globin chain binds to a heme molecule, then forms _____

Tetramer

Two heterodimer the combine to form a ________

Gower I

2 zeta 2 epsilon

Gower II

2 alpha 2 epsilon

Portland

2 zeta 2 gamma

HbF

2 alpha 2 gamma

A1

2 alpha 2 beta

A2

2 alpha 2 delta

Intrauterine

GI, GII, Portland

HbF, A1, A2

Newborn and adult

92-95%

conc. HbA

2-3%

HbA2

1-2%

HbF

Second and third trimester

During the ______________ of fetal life and at birth, HbF is the predominant hemoglobin.

HbA

The major hemoglobin present from 6 months of age through adulthood

glycine and succinyl CoA

The rate restriction in heme synthesis is the initial reaction of ________________ to form ALA, catalyzed by ALA synthase.

Globin synthesis

Interaction between the transcription of DNA sequences and soluble transcription factor are the ones that controlled the _________.

peritubular cells

Tissue, when there is an insufficient quantity of hemoglobin or if the hemoglobin molecule is defective in transporting oxygen, it is detected by the _______ of the kidney in which the production of EPO will increase

14-18 g/dL

Men

12-15 g/dL

Women

16.5-21.5 g/dL

Newborns

Oxygen Transport

• The function of hemoglobin is to readily bind oxygen molecules in the lung, which requires high oxygen affinity; to transport oxygen; to efficiently unload oxygen to tissues, which requires low oxygen affinity.

• During oxygenation, each of the four heme atoms will reversibly bind to one oxygen molecule.

1.34 mL

Oxygen: hemoglobin concentration

P50 value

• defined in terms of amount of oxygen needed to saturate 50% of hemoglobin

• relationship is describe by the oxygen dissociation curve of hemoglobin, which plots the percent oxygen saturation of hemoglobin versus the PO2.

Sigmoidal

the curve

Saturated Hemoglobin

High oxygen tension in lungs = High hemoglobin oxygen affinity

Rapidly release oxygen

Low oxygen tension in lungs = Low hemoglobin oxygen affinity

PO2

27 mmHg, 50% oxygen saturation of the hemoglobin molecule

96% - 100%

In arterial oxygen, the hemoglobin saturation is

Bohr effect

PO2 shifts of the curve to the left and right occur if there are changes in the pH of the blood. A shift in the curve due to change in pH is termed ____, facilitates the ability of hemoglobin to exchange oxygen and carbon dioxide.

Shift to the left

50% oxygen saturation of the hemoglobin occurs at a PO2 of less than 27mmHg.

Shift to the right

50% oxygen saturation of the hemoglobin occurs at a PO2 of higher than 27mmHg

higher oxygen saturation

Shift to the left

lower oxygen saturation

Shift to the right

Left shift curve

D: P50, 2-3 DPG, PCO2, Temp
I: O2, pH

Right shift curve

I: P50, 2-3 DPG, PCO2, Temp
D: O2, pH

Low Temperature, Alkalosis, Multiple blood transfusion depleted 2-3 DPG

Clinical condition in Left Shift Curve

Increase body temperature, Acidosis, Increase 2-3 DPG due to hypoxia conditions (high altitude, pulmonary insufficiency, CHF, Severe anemia)

Clinical condition in Right Shift Curve

Myoglobin

present in cardiac and skeletal muscle, binds oxygen with greater affinity than hemoglobin it’s a hyperbolic curve that it releases oxygen only at low partial pressure meaning it is not as effective as hemoglobin in releasing oxygen to the tissue.

damaged to the muscle in myocardial infarction, trauma, or severe muscle injury

Myoglobin is release in plasma when

Kidney

Myoglobin is normally excreted in

Renal failure

Myoglobin is elevated when there is

Blood

Myoglobin in urine produces positive result on the urine dipstick test for

19 to 21 mmHg

HbF has a P50 of

HbF

disadvantage in that, it delivers oxygen less readilty to tissues which the bone marrow compensates by producing more RBCs to ensure adequate oxygenation of the tissues that is why the RBC count, hb concentration and hct of newborn are higher than adult it will gradually decrease to normal physiologic levels by 6 months of age.

Chloride shift

To maintain the electroneutrality, the chloride diffuses from the plasma into the cell across the membrane this is called

Nitric Oxide Transport

third function of hemoglobin are binding, t=inactivation and transport of nitric oxide (NO).

Carbondioxide Transport

Second important hemoglobin function

vascular endothelial cells

Nitric oxide, secreted in _________ and causes relaxation of the vascular wall smooth muscle and vasodilation.

hypoxic microvascular areas

Hemoglobin preserves and transport nitric oxide to ________, which stimulates vasodilation and increase blood flow, which helps the hemoglobin to work with other system in regulating local blood flow to microvascular areas by binding and inactivating nitric oxide.

Dyshemoglobin

Dysfunctional hemoglobins that are unable to transport oxygen. It forms and may accumulate totoxic levels, after exposure to certain drugs or environmental chemical and gasses. Most cases are acquired, and some are cases are hereditary

Methhemoglobin

Formed by the reversible oxidation of heme iron to the ferric iron state. Cannot carry oxygen because the oxidized ferric iron cannot bind it.

decreased

Increase of this dyshemoglobin results in _________ delivery of oxygen to the tissues.

25%

generally asymptomatic