CHAPTER 4 PART 2 Flashcards
Production of reduced Diphosphopyridine dinucleotide (DPNH) in the presence of
methemoglobin reductase (diaphorase)
Production of reduced Triphosphopyridine nucleotide (TPNH) in the presence of
Glucose-6-PO4 dehydrogenase → Reduced Glutathione
o Increase production
Inherited Enzyme Deficiency
o NADH-Methemoglobin reductase deficiency or Diaphorase deficiency
Inherited Enzyme Deficiency
Results of various amino acid substitutions in the globin chain that directly affect the heme group.
Inherited M
Inherited M Acquired: Chemical or therapeutic agents
(aniline dyes, NO3, NO2, antimalarial drugs, sulfonamides)
Inherited M Therapy:
Ascorbic Acid & Methylthioninium Cl
Org. sulfides + Hb oxidant drugs (phenacetin & acetanilid, sulfonamides)
Sulfhemoglobin
Hb oxidant drugs
(phenacetin & acetanilid, sulfonamides)
IRREVERSIBLE
Sulfhemoglobin
Sulfhemoglobin + CO -
Carboxysulfhemoglobin
Sulfhemoglobin
Sulfhemoglobin Critical value:
0.5 g/100 ml
mauve-lavender (when its stained) Heinz bodies (central stippling)
Sulfhemoglobin
Absorption: 600-620 nm
Sulfhemoglobin
ferricyanide + Fe3+ of Hb
Cyanmethemoglobin (HCN)
The most stable among the pigments
Cyanmethemoglobin (HCN)
Absorption wavelength: 540 nm
Cyanmethemoglobin (HCN)
“fast hemoglobins”
GLYCOSYLATED HEMOGLOBIN
irreversibly glycosylated at 1 or both N-terminal valines (or
lysine) of the B-chains
GLYCOSYLATED HEMOGLOBIN
HbA1a, HbA1b, Hb A1c
GLYCOSYLATED HEMOGLOBIN
is elevated 2 - 3 fold in patients with diabetes mellitus.
Hb A1c
Increased Hb
Polycythemia
Dehydration (burns, diarrhea)
Decreased Hb
All anemia
Leukemia
After 50 years of age =
slight decrease
(?) in the morning and (¿) in the evening
Higher
lower
(?) if lying down
Lower
in smokers: high altitude
Increased
Determines the proportion of O2, released to the tissues or loaded onto the cell at a given oxygen pressure.
OXYGEN AFFINITY
means hemoglobin has an increased affinity for O2, so it binds more and does not want to give it up
Increases in oxygen affinity
Decreases in oxygen affinity, cause.
O2 to be released
FACTORS AFFECTING HEMOGLOBIN AFFINITY FOR OXYGEN
- Blood (Body) Temperature
- Blood pH
- Level2,3–DPG
- Carbon Dioxide (Haldane Effect)
- Fetal Hb
- Abnormal Hb
• Hgb has less attraction or affinity for 02
Right-Shift
•Hgb willing to release Oz to totissue. tissue
Right-Shift
•Hgb has more attraction for O2
Left shift
Hgb less willing to release O2 to tissues
Left shift
•Alterations in blood pH, shifts oxygen dissociation curve
Bohr Effect
•In acidic pH, the curve shifts to the right
Bohr Effect
•Results in an enhanced capacity to release O2 where it is needed
Bohr Effect
• Uptake of oxygen will release carbon dioxide
Haldane Effect
And losing of oxygen will increase affinity for carbon dioxide
Haldane Effect
(quantitative defect)
Thalassemic (quantitative defect) disorders
(qualitative defect)
Hemoglobinopathies
decreased or non-existent production of one or more globin chain type.
Thalassemic disorders
• Alpha
• Beta
• Alpha and Beta
• Alpha (Asians)
• Beta (mediteranean)
• Alpha and Beta (African)
Result from the alteration of the DNA genetic code for the chains → hemoglobin variants
Hemoglobinopathies
– changes 1 or more amino acids in the sequence
- Substitution
– changes in the part of Hb
- Deletion
– joins the DNA sequence
- Addition/Elongation
– joins another amino acid in the sequence
- Fusion
amino acid substitution
Hemoglobin S
No HbA is produced
Hemoglobin S
Sickling occurs when O2, is reduced at the tissue level.
Hemoglobin S
The Hb S molecule polymerizes leading to the formation of
(?) which cause the cells to become rigid.
tactoid crystals
gene has provided resistance from Plasmodium falciparum
Hemoglobin S
Hemoglobin S
Polymorphism in Hb genes
(Hb S, Hb E and B- Thalassemia, G-
6PD def.)
protects individuals from developing severe falciparum malaria.
Hemoglobin S
Hemoglobin S Inheritance:
- Homozygous (SS)- visible
- Heterozygous (AS)-not visible
o Anemia is usually severe
Sickle Cell Anemia (SS)
o increase RDW
Sickle Cell Anemia (SS)
Sickle Cell Anemia (SS)
o Blood Smear:
Polychromasia, Sickle cells, target cells, ovalocytes, schistocytes; Howell-Jolly & Pappenheimer bodies
o Retarded Growth and sexual maturation
Sickle Cell Anemia (SS)
Sickle Cell Anemia (SS)
o Hbs
o HbF
o Hb A2, Normal
80-90%
10-20%
1.5-3.5%
o Any situation that produces excessive deoxygenation of RBCs
Sickle Cell Crises
Sickle Cell Crises o Eg.
Vasoocclusive crises
o Hb A compensates for Hb S
Sickle Cell Trait
o Patients usually have no symptoms unless in cases of
extreme tissue hypoxia
Sickle Cell Trait
Sickle Cell Trait o HbS
30-45%
Hb s-Thalassemia
Hb S-a
Hb S-B
Other Sickling Hbs same amino acid substitution as HbS with additional unique 6-substitution
Hb C-Harlem; C-Ziguinchor; S-Travis
Screening test: sickling hemoglobin
DITHIONITE SOLUBILITY TUBE TEST
Red cells are lysed by (?) allowing hb to escape.
saponin
binds with oxygen
Sodium dithionite
polymerizes and forms a precipitate
Deoxygenated hb S
make the solution turbid.
Tactoids
Turbidity: against a
newsprint/reader card with thin black lines.
Turbidity:
(+) HbS
TEST FOR UNSTABLE HbS
- Isopropanol Pot Test
- Heat Denaturation/Instability Test (50°C for 3 hrs.)
- Heinz bodies training (Wright Stain)
N/N anemia with numerous target cells
Hb C Disease (CC)
: hexagonal or rod-shaped crystals; blunt
ends; rigid cells
Hb CC crystals
RBCs – slightly hypochromic, target cells
HbC Trait (AC)
Milder than Hb SS
Hemoglobin SC disease
“pocketbook” cells
Hemoglobin SC disease
: with fingerlike projections.
Hb SC crystals
Methemoglobin and congenital cyanosis
Hemoglobin M
Amino acid substitution: not protected from oxidation of
iron
Hemoglobin M
Cyanosis, Blood: chocolate brown; Heinz bodies
Hemoglobin M
