Chapter 4 - HEMOGLOBIN (Functions, Components, Synthesis, Types, Forms) Flashcards by Arriane Cyrel (MTI)

Respiratory pigment found in the red cells

HEMOGLOBIN

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A conjugated protein synthesized in the RBCS

HEMOGLOBIN

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It represents more than 1% of the total body weight and It occupies 28% of the red cell mass.

HEMOGLOBIN

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HEMOGLOBIN Function:

Transports oxygen from the lungs where the oxygen tension is high, to the tissues, where the oxygen tension is low.

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HEMOGLOBIN also binds to other substances such as (?).

hydrogen ions (which determine pH of the blood), carbon dioxide and 2,3 diphosphoglycerate (2,3-DPG)

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These substances do not bind to hemoglobin at the oxygen-binding sites, however, binding of these substances to hemoglobin affects the (?).

affinity of hemoglobin to oxygen

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Conversely, binding of (?) causes changes in the structure of the hemoglobin molecule thus affecting its ability to bind other gases or substances

oxygen to hemoglobin

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How is CO2 transported in the blood (plasma and red cells?)

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As CO2 enters the blood, it combines with H2O to form (?), a relatively weak acid, which dissociates into (?).

carbonic acid (H2CO3)

H+ and HCO3 -

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Blood acidity is minimally affected by the released (?)because blood proteins, especially hemoglobin, are effective buffering agents.

H+ ions

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The conversion of CO2 to H2CO3 is catalyzed by (?), an enzyme present inside the RBCs.

carbonic anhydrase

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Because the enzyme is present only in the RBCs, (?) accumulates to a much greater extent within the red cells than in the plasma.

HCO3

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The capacity of blood to carry (?) - is enhanced by an ion transport system inside the RBC membrane that simultaneously moves a HCO3 - out of the cell and in exchange for a chloride ion.

CO2 as HCO3

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The simultaneous exchange of these 2 ions, known as the (?), permits the plasma to be used as a storage site for bicarbonate without changing the electrical charge of either the plasma or the red blood cell.

chloride shift

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is a curve that plots the proportion of hemoglobin in its saturated form on the Y axis against the prevailing oxygen tension on the X axis.

oxygen dissociation curve/oxyhemoglobin dissociation curve (ODC)

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This relates oxygen saturation and partial pressure of O2 in the blood (PO2)

oxygen dissociation curve/oxyhemoglobin dissociation curve (ODC)

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determined by hemoglobin affinity for oxygen.

oxygen dissociation curve/oxyhemoglobin dissociation curve (ODC)

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Explain the influence/effect of Bohr effect, Haldane effect, 2, 3, DPG and chloride on the affinity of hemoglobin to oxygen

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Blood temp

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Blood pH (Bohr Effect)

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RBC 2,3 DPG

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CO2 (Haldane Effect)

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Hb F

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Abnormal Hbs

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HEMOGLOBIN COMPOSITION:

1. 1 Globin 2. 4 Heme

inorganic iron groups that assist in binding O2

Heme

each iron atom can bind and then release an oxygen molecule

Heme

nitrogenous substance formed in the mitochondrion

Protoporphyrin IX

a salt produced in the Rapoport-Luebering shunt in the RBCs.

2,3 Diphosphoglycerate (DPG)

Composed of 2 sets (dimer) of 2 different polypeptide chains

GLOBIN Chains

The spatial arrangement of each alpha-beta pair is symmetrical

GLOBIN Chains

Contacts between the subunits are by means of H-bonds

GLOBIN Chains

Differences in the globin chain relate both to the sequence and to the number of amino acids in the chain.

GLOBIN Chains

141

Alpha

Beta Delta Gamma Epsilon

146

Gower-1

2 zeta 2 epsilon

Gower-2

2 alpha 2 epsilon

Portland

2 zeta 2 gamma

Hb A

2 alpha 2 beta

Hb A2

2 alpha 2 delta

Hb F

2 alpha 2 gamma

TYPES OF HEMOGLOBIN

: Major normal adult hemoglobin (97%)

Hb A1

: Major Hb of the fetus and the newborn

Hb F

Has high affinity to O2

Hb F

Resistant to both acid elution and alkali denaturation

Hb F

After birth, smaller amounts of(?) are produced

HbF

= HbF is less than 8%

6 months

= HbF less than 2%

After age 2 years

= less than 1%

Adults

Accounts for 1.5 % - 3.5 % of normal adult Hb

Hb A2

Increased in some -Thalassemias, hyperthyroidism and in some cases of megaloblastic anemia

Hb A2

= analogue of alpha-chain

zeta chain

= counterpart of the gamma, beta, and delta chains

epsilon chain

EMBRYONIC HEMOGLOBINS

Hb Gower I Hb Gower II Hb Portland

FORMS of HEMOGLOBIN NORMAL ABNORMAL

Formed when the RBCs pass through the alveolar capillaries of the lungs

Oxyhemoglobin (HbO2)

The O2 is loosely bound and unstable for easier release into the tissues

Oxyhemoglobin (HbO2)

Gives a scarlet red/bright red color

Oxyhemoglobin (HbO2)

Reduced form

Deoxyhemoglobin (HbCO2)

Hemoglobin with CO2 (carbaminohemoglobin)

Deoxyhemoglobin (HbCO2)

Gives a dark red color

Deoxyhemoglobin (HbCO2)

Hemoglobin with CO (affinity of CO to hb is 200 x greater than the affinity of O2)

Carboxyhemoglobin (HbCO)

Imparts a cherry red in color

Carboxyhemoglobin (HbCO)

Absorption wavelength: 576 nm

Carboxyhemoglobin (HbCO)

Critical Value: 5g /100 ml (May cause irreversible tissue changes when increased)

Carboxyhemoglobin (HbCO)

Treatment: administration of hyperbaric O2

Carboxyhemoglobin (HbCO)

Rapid Tests for HbCO :

1. NaOH test: red color 2. Dilution test (addition of water): cherry red 3. Tannic Acid test: red precipitate

: red color : cherry red : red precipitate

1. NaOH test 2. Dilution test (addition of water) 3. Tannic Acid test

Iron (Fe++) is oxidized into its Fe+++ form

Methemoglobin/Hemiglobin (Hi)

Normally makes up 1.5%

Methemoglobin/Hemiglobin (Hi)

Approximately 0.5% - 3% of the total body Hb is spontaneously converted to Hi daily

Methemoglobin/Hemiglobin (Hi)

Conveys a chocolate brown color

Methemoglobin/Hemiglobin (Hi)

Absorption wavelength: 630 635 nm

Methemoglobin/Hemiglobin (Hi)

Methemoglobin/Hemiglobin (Hi) Screening tests:

Aeration: blood retains its color Addition of 1% MB: blood turns red

Maintenance of Hemoglobin in the Normal Reduced state (Fe++): Production of reduced (?) in the presence of methemoglobin reductase (diaphorase) reduced (?) in the presence of Glucose-6-PO4 dehydrogenase (?) and its associated enzymes

Diphosphopyridine dinucleotide (DPNH) Triphosphopyridine nucleotide (TPNH) Glutathione

: blood retains its color : blood turns red

Aeration Addition of 1% MB

Conditions of Methemoglobinemia:

: commonly attributed to NADH-Methemoglobin reductase deficiency/Diaphorase deficiency

a. Inherited (enzyme deficiency)

: results of various amino acid substitutions in the globin chain that directly affect the heme group.

b. Inherited M

: effects of chemical or therapeutic agents (aniline dyes, nitrate-rich water and foodstuffs)

c. Acquired

Formed when organic sulfides combine with Hb

Sulfhemoglobin (SHb)

Observed in patients taking in oxidant drugs (phenacetin & acetanilid, sulfonamides)

Sulfhemoglobin (SHb)

Irreversible once formed

Sulfhemoglobin (SHb)

NOT normally present in the blood

Sulfhemoglobin (SHb)

Imparts a greenish color

Sulfhemoglobin (SHb)

Absorption wavelength: 600 - 620 nm

Sulfhemoglobin (SHb)

Reference Values for Hemoglobin Male: Female: At Birth:

140 175 g/L 123 153 g/L 150 200 g/L

Increased Hb

Polycythemia Dehydration

Decreased Hb

All anemia Leukemia Oligochromia

Physiologic Variations: After 50 years of age = (?) Higher in the (?) and lower in the (?) Lower if (?) Increased in (?); high altitude

slight decrease morning; evening lying down smokers

Other forms of Hemoglobin:

Formed when ferricyanide is added to the Fe++ of a normal Hb

Cyanmethemoglobin

The most stable among the Hb pigments

Cyanmethemoglobin

Absorption wavelength: 540 nm

Cyanmethemoglobin

What are the glycosylated hemoglobins?

is elevated 2 3 folds in patients with diabetes mellitus.

Hb AIc

It is used as an index of metabolic control in diabetes during the preceding 2 - 3 mons.

Hb AIc

Disorders Related with Abnormal Hemoglobins

diverse group of genetic disorders characterized by a primary, quantitative reduction in globin chain synthesis for hemoglobin.

THALASSEMIA

1. Silent carrier

Alpha Thalassemia

2. Thalassemia trait/A-Thal minor

Alpha Thalassemia

3. Hb H disease

Alpha Thalassemia

4. Barts Hdrops fetalis

Alpha Thalassemia

1. Beta Thalassemia Major/Cooles anemia

Beta Thalassemias

2. Beta Thalassemia Intermedia

Beta Thalassemias

3. Beta Thalassemia Minor/Cooles trait

Beta Thalassemias

conditions characterized by qualitative structural abnormalities of the globin polypeptide chains that result from alteration of the DNA genetic code for those chains

HEMOGLOBINOPATHIES

Structural abnormalities may involve amino acid

HEMOGLOBINOPATHIES

HEMOGLOBINOPATHIES (hemoglobin variants)

1. Substitution 2. Deletion 3. Fusion 4. Elongation

Examples with Nomenclature: 1. Substitution 2. Deletion 3. Fusion 4. Elongation

The most well-known hb variant characterized by substitution of glutamic acid by valine on the 6th amino acid posiion of he b-chain.

Hb S (Sicking hb)

What are the effects of the glutamic acid substitution by valine on the 6th position of the β-chain in the Hb S molecule?

Read the sickle cell crises. Be able to enumerate and discuss them.

FUNCTIONAL CLASSIFICATION OF HEMOGLOBIN VARIANTS

Hb M Boston a258Tyrb2

Hemoglobins associated with methemoglobinemia and cyanosis

Hb M Iwate 287Tyr2

Hemoglobins associated with methemoglobinemia and cyanosis

Hb M Saskatoon 2263Tyr

Hemoglobins associated with methemoglobinemia and cyanosis

Hb M Milwaukee 2267Glu

Hemoglobins associated with methemoglobinemia and cyanosis

Hb M Hde Park 2292Tyr

Hemoglobins associated with methemoglobinemia and cyanosis

Hb FM Osaka 2263Tyr

Hemoglobins associated with methemoglobinemia and cyanosis

Hb FM Fort Riple 2292Tyr

Hemoglobins associated with methemoglobinemia and cyanosis

Hb Chesapeake 292Leu2

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb J Capetown 292Gln2

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Malmo 2297Gln

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Yakima 2299His

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Kempse 2299Asn

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Y psi (Ypsilanti) 2299Tyr

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Hiroshima 22146Asp

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Rainier 22145Cys

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Bethesda 22145His

Hemoglobins associated with Increased Oxygen affinity and polycythemia

Hb Kansas 22102Thr

Hemoglobins associated with Decreased Oxygen affinity and polycythemia

Hb Titusville 294Asn2

Hemoglobins associated with Decreased Oxygen affinity and polycythemia

Hb Providence 2282Asn

Hemoglobins associated with Decreased Oxygen affinity and polycythemia

Hb Agenogi 2290Lys

Hemoglobins associated with Decreased Oxygen affinity and polycythemia

Hb Beth Israel 22102Ser

Hemoglobins associated with Decreased Oxygen affinity and polycythemia

Hb Yoshiuka 22108Asp

Hemoglobins associated with Decreased Oxygen affinity and polycythemia

Hb Bibba 2136Pro2