L3 HEMA - Hemoglobin

Hemoglobin

↳ Iron bearing protein contained within RBCs.

.

↳ Synthesized by the young erythroblast from the polychromatic normoblast stage up to reticulocytes stage.

.

↳ 1 gram of Hb can carry 1.34 mL of oxygen; carries 3.47 mg of iron.

Iron

polychromatic

reticulocytes

1.34

3.47 mg

HEMOGLOBIN:

.

↳ ________ bearing protein contained within RBCs.

.

↳ Synthesized by the young erythroblast from the __________________ normoblast stage up to _________________ stage.

.

↳ 1 gram of Hb can carry _____ mL of oxygen; carries ______ of iron.

Heme Biosynthesis

Globin Biosynthesis

2 Composition of Hemoglobin

Heme Biosynthesis

COMPOSITION OF HEMOGLOBIN:

.

↳ Occurs in the mitochondria.

mitochondria

HEME BIOSYNTHESIS:

.

↳ Occurs in the _________________.

Globin Biosynthesis

COMPOSITION OF HEMOGLOBIN:

.

↳ Occurs in the ribosomes.

ribosomes

GLOBIN BIOSYNTHESIS:

.

↳ Occurs in the _______________.

Primary Structure

Secondary Structure of Globin

Tertiary Structure of Globin

Quaternary Structure of Globin

4 Structure of Hemoglobin

Primary Structure

STRUCTURE OF HEMOGLOBIN:

.

↳ Refers to the amino acid sequence of the various chain types.

.

…..➙ Numbering from the N-terminal identifies the position of individual amino acids.

.

…..➙ The identity and position of these amino acids cannot be changed without causing gross impairment to molecular function.

amino acid

position

identity

molecular

PRIMARY STRUCTURE:

.

↳ Refers to the _______________ sequence of the various chain types.

.

…..➙ Numbering from the N-terminal identifies the _____________ of individual amino acids.

.

…..➙ The _____________ and position of these amino acids cannot be changed without causing gross impairment to ________________ function.

Secondary Structure of Globin

STRUCTURE OF HEMOGLOBIN:

.

↳ It comprises nine non-helical sections joined by eight helical sections.

.

…..➙ Helical sections (more on alpha chain) are identified by the letters A-H while the non-helical sections (beta chains) are identified by a pair of letters corresponding to the adjacent helices.

nine

eight

alpha

adjacent

SECONDARY STRUCTURE OF GLOBIN:

.

↳ It comprises _____ non-helical sections joined by _________ helical sections.

.

…..➙ Helical sections (more on _________ chain) are identified by the letters A-H while the non-helical sections (beta chains) are identified by a pair of letters corresponding to the _____________ helices.

Tertiary Structure of Globin

STRUCTURE OF HEMOGLOBIN:

.

↳ Arrangement of the helices into 3D structure.

.

…..➙ The tertiary folding of each globin chain forms the approximate sphere.

.

…..➙ The intra-molecular bonds which give rise to the helical parts impart considerable structure rigidity, causing chain folding to occur in the non-helical parts.

3D

sphere

intra

rigidity

non-helical

TERTIARY STRUCTURE OF GLOBIN:

.

↳ Arrangement of the helices into ____ structure.

.

…..➙ The tertiary folding of each globin chain forms the approximate __________.

.

…..➙ The _________-molecular bonds which give rise to the helical parts impart considerable structure ____________, causing chain folding to occur in the _______________ parts.

Quaternary Structure of Globin

STRUCTURE OF HEMOGLOBIN:

.

↳ Has 4 subunits arranged tetrahedrally.

.

…..➙ In adult Hb, there are different contact areas.

4

tetrahedrally

contact

QUATERNARY STRUCTURE OF GLOBIN:

.

↳ Has __ subunits arranged __________________.

.

…..➙ In adult Hb, there are different __________ areas.

Alpha and Zeta

GENETIC INHERITANCE (GLOBIN):

.

↳ Amino Acids = 141

.

↳ Chromosomes = 16

141

16

ALPHA AND ZETA:

.

↳ Amino Acids = ____

.

↳ Chromosomes = ___

Beta, Gamma, Delta and Epsilon

GENETIC INHERITANCE (GLOBIN):

.

↳ Amino Acids = 146

.

↳ Chromosomes = 11

146

11

BETA, GAMMA, DELTA AND EPSILON:

.

↳ Amino Acids = ____

.

↳ Chromosomes = ___

Oxyhemoglobin Dissociation Curve

↳ Graphically describe the relationship between oxygen content (percent or saturation) and partial pressure of oxygen (pO2).

oxygen

pressure

OXYHEMOGLOBIN DISSOCIATION CURVE:

.

↳ Graphically describe the relationship between __________ content (percent or saturation) and partial ______________ of oxygen (pO2).

pO2 (Partial Pressure of Oxygen)

P50 Value

% O2 Saturation

3 Variables

pO2 (Partial Pressure of Oxygen)

VARIABLES:

.

↳ The amount of oxygen needed to saturate 50% of Hb (Reference Value: 27 mmHg).

50

27 mmHg

pO2 (PARTIAL PRESSURE OF OXYGEN):

.

↳ The amount of oxygen needed to saturate ____% of Hb (Reference Value: ______________).

P50 Value

VARIABLES:

.

↳ Indicates the oxygen tension at which 50% of Hb are saturated.

.

↳ 26.52 or 27 mmHg for WB under accepted standard conditions of pH 7.4 and temperature of 37.5 ℃.

tension

saturated

26.52

7.4

P50 VALUE:

.

↳ Indicates the oxygen ___________ at which 50% of Hb are _______________.

.

↳ _______ or 27 mmHg for WB under accepted standard conditions of pH ___ and temperature of 37.5 ℃.

% O2 Saturation

VARIABLES:

.

↳ Oxygen content of hemoglobin.

hemoglobin

% O2 SATURATION:

.

↳ Oxygen content of _________________.

Oxygen Affinity

↳ The ability of hemoglobin to bind or release oxygen. Expressed in terms of the oxygen tension at which hemoglobin is 50% saturated with oxygen.

release

tension

50

OXYGEN AFFINITY:

.

↳ The ability of hemoglobin to bind or ___________ oxygen. Expressed in terms of the oxygen ___________ at which hemoglobin is _____% saturated with oxygen.

Bohr Effect

↳ pH (Alaklosis) = ⬆ Hb affinity for O2 (L)

.

↳ pH (Acidosis) = 🠫 Hb Affinity for O2 (R)

Alkalosis

R

BOHR EFFECT:

.

↳ pH (__________) = ⬆ Hb affinity for O2 (L)

.

↳ pH (Acidosis) = 🠫 Hb Affinity for O2 (___)

Normal Hemoglobin

Abnormal Hemoglobin

Abnormal Hemoglobin Pigments or Derivatives

3 Hemoglobin Classification

Embryonic Hemoglobin

Fetal Hemoglobin

Hemoglobin A / A1 (HbA or HbA1)

Hemoglobin A2 (HbA2)

Hemoglobin A3 (HbA3)

Glycosylated Hemoglobin / HbA1C

6 Terms under Normal Hemoglobin

(EH, FH, HA, HA2, HA3, GH)

Embryonic Hemoglobin

UNDER NORMAL HEMOGLOBIN:

.

↳ Found in normal human embryos and fetuses with a gestational age of less than three months.

fetuses

three

EMBRYONIC HEMOGLOBIN:

.

↳ Found in normal human embryos and __________ with a gestational age of less than _________ months.

Hb-Gower 1

Hb-Gower 2

Hb-Portland-1

Hb-Portland-2

4 Terms under Embryonic Hemoglobin

Hb-Gower 1

UNDER EMBRYONIC HEMOGLOBIN:

.

➙ Composed of 2 zeta and 2 epsilon globin chains.

zeta

globin

HB-GOWER 1:

.

➙ Composed of 2 _______ and 2 epsilon __________ chains.

Hb-Gower 2

UNDER EMBRYONIC HEMOGLOBIN:

.

➙ Composed of 2 alpha and 2 epsilon.

alpha

HB-GOWER 2:

.

➙ Composed of 2 _________ and 2 epsilon.

Hb-Portland-1

UNDER EMBRYONIC HEMOGLOBIN:

.

➙ Composed of 2 zeta and 2 gamma.

gamma

HB-PORTLAND-1:

.

➙ Composed of 2 zeta and 2 ___________.

Hb-Portland-2

UNDER EMBRYONIC HEMOGLOBIN:

.

➙ Composed of 2 zeta and 2 beta.

beta

HB-PORTLAND-2:

.

➙ Composed of 2 zeta and 2 ______.

Fetal Hemoglobin

UNDER NORMAL HEMOGLOBIN:

.

↳ Is the major Hb of the fetuses and newborns.

.

…..➙ It is composed of 2 alpha and 2 gamma chains.

.

…..➙ Produced 4 months after conception.

newborns

gamma

months

FETAL HEMOGLOBIN:

.

↳ Is the major Hb of the fetuses and _______________.

.

…..➙ It is composed of 2 alpha and 2 _________ chains.

.

…..➙ Produced 4 __________ after conception.

Hemoglobin A / A1

UNDER NORMAL HEMOGLOBIN:

.

↳ The normal adult hemoglobin.

.

…..➙ Produced after 1 year and onwards.

.

…..➙ Composed of 2 alpha and 2 beta chain; Alpha chains (consists of 141 amino acids) is encoded in chromosome 16 while beta chain (consists of 146 amino acids) is in chromosome 11.

adult

1

beta

141

11

HEMOGLOBIN A / A1:

.

↳ The normal ________ hemoglobin.

.

…..➙ Produced after __ year and onwards.

.

…..➙ Composed of 2 alpha and 2 _______ chain; Alpha chains (consists of _______ amino acids) is encoded in chromosome 16 while beta chain (consists of 146 amino acids) is in chromosome ____.

Hemoglobin A2 (HbA2)

UNDER NORMAL HEMOGLOBIN:

.

↳ Constitutes 1.5 - 3.5% of total Hb.

.

…..➙ Composed of 2 alpha and 2 delta chains.

.

…..➙ If the level is more than 4.5%, then there may be beta thalassemia traits.

3.5

delta

4.5

thalassemia

HEMOGLOBIN A2 (HBA2):

.

↳ Constitutes 1.5 - ____% of total Hb.

.

…..➙ Composed of 2 alpha and 2 ________ chains.

.

…..➙ If the level is more than ____%, then there may be beta _______________ traits.

Hemoglobin A3 (HbA3)

UNDER NORMAL HEMOGLOBIN:

.

↳ Degradation product of Hb12.

.

…..➙ Composed of 2 alpha and 2 delta chains.

Hb12

alpha

HEMOGLOBIN A3 (HBA3):

.

↳ Degradation product of ______.

.

…..➙ Composed of 2 ________ and 2 delta chains.

Glycosylated Hemoglobin / HbA1C

UNDER NORMAL HEMOGLOBIN:

.

↳ Produced throughout the life of the erythrocyte.

.

…..➙ Glycosylation of hemoglobin increases linearly over the 120-day lifespan of RBCs.

.

…..➙ Used as an index of metabolic control of diabetes during the preceding 2-3 months.

erythrocyte

120

metabolic

months

GLYCOSYLATED HEMOGLOBIN / HBA1C:

.

↳ Produced throughout the life of the ___________________.

.

…..➙ Glycosylation of hemoglobin increases linearly over the ______-day lifespan of RBCs.

.

…..➙ Used as an index of _________________ control of diabetes during the preceding 2-3 _________.

Hemoglobin S

Hemoglobin C

Hemoglobin D

Hemoglobin G

Hemoglobin E

Hemoglobin H

Hemoglobin Bart's

Hemoglobin Sydney

Hemoglobin Milwaukee

Hemoglobin Bristol

10 Terms under Abnormal Hemoglobin

(HS, HC, HD, HG, HE, HH, HB, HS, HM, HB)

Hemoglobin S

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Homozygous (SS) = Sickle Cell Anemia

.

↳ Heterozygous (Ss) = Sickle Cell Trait

.

↳ Glutamic Acid is replaced by Valine at the 6th position of the beta chain.

Homozygous

Trait

Glutamic

6th

beta

HEMOGLOBIN S:

.

↳ _________________ (SS) = Sickle Cell Anemia

.

↳ Heterozygous (Ss) = Sickle Cell _______

.

↳ ____________ Acid is replaced by Valine at the ____ position of the _______ chain.

Hemoglobin C

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Glutamic Acid is replaced by a Lysine in B6.

.

↳ Target cells are often seen.

.

↳ Often in combination with HbS.

Lysine

Target

HbS

HEMOGLOBIN C:

.

↳ Glutamic Acid is replaced by a ___________ in B6.

.

↳ ___________ cells are often seen.

.

↳ Often in combination with ______.

Hemoglobin D

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Most frequent variants are HbD Punjab and HbD Los Angeles.

.

↳ Glutamic Acid in the 121st beta chain is substituted by glutamine.

Punjab

121st

glutamine

HEMOGLOBIN D:

.

↳ Most frequent variants are HbD ____________ and HbD Los Angeles.

.

↳ Glutamic Acid in the _______ beta chain is substituted by _______________.

Hemoglobin G

UNDER ABNORMAL HEMOGLOBIN:

.

↳ The most common variant in American blacks is the HbG-Philadelphia.

.

↳ Few target cells on blood films with those who have homozygous for HbD.

blacks

Philadelphia

homozygous

HEMOGLOBIN G:

.

↳ The most common variant in American ________ is the HbG-________________.

.

↳ Few target cells on blood films with those who have _________________ for HbD.

Hemoglobin E

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Same electrophoretic mobility as HbA2 and resembles thalassemia trait.

.

↳ Second most hemoglobinopathy in the United States next to S and C.

.

↳ Most common in the Philippines and Southeast Asia.

.

↳ Glutamic Acid is substituted by Lysine in position 26 in the beta chains.

electrophoretic

thalassemia

hemoglobinopathy

Southeast

Lysine

26

HEMOGLOBIN E:

.

↳ Same ____________________ mobility as HbA2 and resembles _________________ trait.

.

↳ Second most ____________________________ in the United States next to S and C.

.

↳ Most common in the Philippines and ________________ Asia.

.

↳ Glutamic Acid is substituted by ___________ in position ___ in the beta chains.

Hemoglobin H

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Consists of 4 beta chains.

.

↳ Associated with a chain disease and with thalassemia minor.

4

chain

minor

HEMOGLOBIN H:

.

↳ Consists of ___ beta chains.

.

↳ Associated with a _________ disease and with thalassemia _________.

Hemoglobin Bart's

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Abnormal variant of HbF.

.

↳ Consists of 4 gamma chains.

Abnormal

gamma

HEMOGLOBIN BART'S:

.

↳ ______________ variant of HbF.

.

↳ Consists of 4 _________ chains.

Hemoglobin Sydney

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Alanine substitute for Valine at position E11 in the beta chain.

Valine

E11

HEMOGLOBIN SYDNEY:

.

↳ Alanine substitute for _________ at position ____ in the beta chain.

Hemoglobin Milwaukee

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Glutamic Acid substitutes Valine at position E11 in the beta chain.

Glutamic

beta

HEMOGLOBIN MILWAUKEE:

.

↳ _____________ Acid substitutes Valine at position E11 in the _______ chain.

Hemoglobin Bristol

UNDER ABNORMAL HEMOGLOBIN:

.

↳ Aspartic Acid substitute for Valine in the beta chain.

Aspartic

HEMOGLOBIN BRISTOL:

.

↳ _____________ Acid substitute for Valine in the beta chain.

Carboxyhemoglobin

Methemoglobin

Sulhemoglobin

3 Terms under Abnormal Hemoglobin Pigments or Derivatives

(C, M, S)

Carboxyhemoglobin

UNDER ABNORMAL HEMOGLOBIN PIGMENTS OR DERIVATIVES:

.

↳ Formed by a combination of Hb and carbon monoxide.

.

↳ Reversible.

.

↳ Found in the blood of tobacco smokers in concentrations of 1-10%.

.

↳ Symptoms of headache, nausea, dizziness, and muscular weakness will occur at levels of 20-30%.

monoxide

Reversible

tobacco

10

muscular

30

CARBOXYHEMOGLOBIN:

.

↳ Formed by a combination of Hb and carbon _______________.

.

↳ ________________.

.

↳ Found in the blood of ____________ smokers in concentrations of 1-____%.

.

↳ Symptoms of headache, nausea, dizziness, and ____________ weakness will occur at levels of 20-____%.

Methemoglobin

UNDER ABNORMAL HEMOGLOBIN PIGMENTS OR DERIVATIVES:

.

↳ Type of Hb in which the ferrous ion has been oxidized to the ferric state.

.

↳ It may be acquired or inherited.

.

↳ Reversible.

.

↳ Normally present in the blood concentrations of 1-2%.

.

↳ Cyanoses will be manifested at 10%.

ferrous

ferric

inherited

1-2

Cyanoses

METHEMOGLOBIN:

.

↳ Type of Hb in which the ___________ ion has been oxidized to the __________ state.

.

↳ It may be acquired or _________________.

.

↳ Reversible

.

↳ Normally present in the blood concentrations of ____%.

.

↳ ______________ will be manifested at 10%.

Sulhemoglobin

UNDER ABNORMAL HEMOGLOBIN PIGMENTS OR DERIVATIVES:

.

↳ Not normally found in the blood.

.

↳ Irreversible.

.

↳ Formed by the action of certain drugs and chemicals such as sulphonamides and aromatic amines.

.

↳ Seen in patients with severe constipation, bacteremia due to C. Perfringens and enterogenous cyanosis.

blood

Irreversible

chemicals

v

bacteremia

entero

SULHEMOGLOBIN:

.

↳ Not normally found in the __________.

.

↳ ________________.

.

↳ Formed by the action of certain drugs and ______________ such as sulphonamides and _____________ amines.

.

↳ Seen in patients with severe constipation, _______________ due to C. Perfringens and __________genous cyanosis.

Shaking

Katayama's Test

Gas Chromatography & Spectroscopic Method

Spectrophotometric Method

Examination of Plasma or Serum for Methemalbumin (Fairley's Pigment)

Determination of Fetal Hemoglobin

6 Tests for Abnormal Hemoglobin Derivatives and Abnormal Hemoglobins

(S, KT, GCSM, SM, EPSM, DFH)

Shaking

TEST FOR ABNORMAL HEMOGLOBIN DERIVATIVES AND ABNORMAL HEMOGLOBINS:

.

↳ Whole blood is shaken in the air for 15 minutes.

.

…..➙ Bright Red = HbO2

.

…..➙ Chocolate Brown = Hi (Methemoglobin)

.

…..➙ Cherry Red = HbCO (Carboxyhemoglobin)

.

…..➙ Mauve Lavender = SHb (Sulfhemoglobin)

15

SHAKING:

.

↳ Whole blood is shaken in the air for ____ minutes.

Bright Red

UNDER SHAKING:

.

➙ HbO2

Chocolate Brown

UNDER SHAKING:

.

➙ Hi (Methemoglobin)

Cherry Red

UNDER SHAKING:

.

➙ HbCO (Carboxyhemoglobin)

Mauve Lavender

UNDER SHAKING:

.

➙ SHb (Sulfhemoglobin)

Katayama's Test

TEST FOR ABNORMAL HEMOGLOBIN DERIVATIVES AND ABNORMAL HEMOGLOBINS:

.

↳ Method for carboxyhemoglobin.

.

↳ Detects as little as 10% saturation.

.

↳ Blood + Ammonium Sulfide

.

…..➙ Rose Red = (+) HbCO

.

…..➙ Greenish Brown = (-) HbCO

carboxy

10

Sulfide

Rose

Brown

KATAYAMA'S TEST:

.

↳ Method for ___________hemoglobin.

.

↳ Detects as little as ____% saturation.

.

↳ Blood + Ammonium ___________

.

…..➙ _________ Red = (+) HbCO

.

…..➙ Greenish __________ = (-) HbCO

Gas Chromatography & Spectroscopic Method

TEST FOR ABNORMAL HEMOGLOBIN DERIVATIVES AND ABNORMAL HEMOGLOBINS:

.

↳ Can detect carboxyhemoglobin or chemical adducts by measuring light absorption shifts or separating gases from blood samples.

chemical

light

gases

GAS CHROMATOGRAPHY & SPECTROSCOPIC METHOD:

.

↳ Can detect carboxyhemoglobin or ___________ adducts by measuring ________ absorption shifts or separating __________ from blood samples.

Spectrophotometric Method

TEST FOR ABNORMAL HEMOGLOBIN DERIVATIVES AND ABNORMAL HEMOGLOBINS:

.

↳ Hb pigments have a characteristic absorption band.

.

…..➙ HbCO = 555 nm

.

…..➙ Hi = 630 nm

.

…..➙ SHb = 620 nm

absorption

SPECTROPHOTOMETRIC METHOD:

.

↳ Hb pigments have a characteristic ______________ band.

555 nm

UNDER SPECTROPHOTOMETRIC METHOD:

.

➙ HbCO

630 nm

UNDER SPECTROPHOTOMETRIC METHOD:

.

➙ Hi

620 nm

UNDER SPECTROPHOTOMETRIC METHOD:

.

➙ SHb