Hematology Hemoglobin Lecture

Hemoglobin

Primary Oxygen-Carrying proteins of RBCs

HBA, HBA2, and HBF

The hemoglobin electrophoreisis

Heme

Iron-containing prosthetic group

Globin

The protein chains (A, B, etc)

Heme structure

A ring of carbon, hydrogen, and nitrogen atoms with 1 atom of ferrous iron in the center

A

Alpha Chain

B

Beta chains

Γ

Gamma chains

Δ

Delta chains

141 amino acids

A on chromosome 16 with…

146 amino acids

B on chromosome 11 with…

Primary protein structure

Amino acid sequence of polypeptide chains

Secondary structure

Chain arrangements in Helices and Nonhelices

Tertiary Strucutre

Arrangement of helices into a pretzel like configuration (3D structure)

Quaternary structure (Tetramer)

Complete hemoglobin molecules

Glycinated hemoglobin

Post translation modification formed by nonenzymatic binding of various sugars to globin chain amino groups of the life span of the RBC

HBA1c

nORMALLY ABOUT 4-6% BUT HIGHER IN UNCONTROLLED Diabetes mellitius

Pronormoblast

Where hemoglobin synthesis begins

Ribosomes in cytoplasm

Where globin biosynthesis begins

Embryonic > Fetal > Adult

Developmental regulation

Hemoglobin Assembly

Heme + Globin assembled into tetramers, where each globin chain bind to heme molecule forming a heterodimer

HBA

2 alpha, 2 beta chains

HBA2

2 alpha,, 2 delta chains

HBF

2 alpha, 2 gamma chains

Hemoglobin ontogeny

Fetal hemoglobin

HBF

Adult hemoglobin

HBA, HBA2

Alas

Rate limiting that regulates heme

Causes of Cell Damage

Excess globin chauin, protoporphyrinx IX, or iron accumaltes

Globin Regulation

Highly regulated to ensure balance; controlled at translation when MRNA codes for globin chain

13.5-18 g/dL

Hemoglobin reference range for men

12-16 g/dL

Hemoglobin reference range for women

16.5-21.5 g/dL

Hemoglobin reference range for newborns

1.34ml

The amount of oxygen carried by each gram of hemoglobin

1/3rbc

The space hemoglobin takes up in a rbc

Rule of 3

HGB * 3 = HCT ± 3; HCT/3 = HGB ± 3

Hemoglobin-oxygen dissociation curve

Affinity for oxygen is related to the partial pressure of oxygen

Low affinity

Oxygen at low oxygen tension

High affinity

Oxygen at high oxygen tension

Carbonic acid

Made form carbon dioxide diffusing into RBCs and water; then dissociates to release hydrogen and bicarbonate

Nitric Oxide Transport

Hemoglob binds, inactivates and transports nitric oxide that is secreted by vascular endothelial cells which causes relaxatio of vascular wall smooth muscle and vasodilation

Oxygen curve normal

PO2 ~ 27mmHG; 50% oxygen saturation; P50

Oxygen curve shift left

P50 <27 MMHG; higher oxygen affinity

Oxygen curve shift right

P50 >27mmHG; lower oxygen affinity

Myoglobin

Oxygen binding heme protein with greater affinity for oxygen than hemoglobin. Oxygen released only at very low partial pressure

Hemoglobin F

Higher affinity for oxygen resulting in a left shift of oxygen dissociation curve due to weakened ability to bind 2,3-DPG

Dyshemoglobins

Nonfunctional HB derivatives

Methehmoglobin

Hemoglobin with ferric iron; cannot bind to oxygen

Acquired Methemoglobin

Causes cyanosis; removal from toxic agent may suffice in treatment

Hereditary methemoglobin

HGM compromised 30-50% with no effective treatment; elevations occur in those who are homozygous or compound heterozygous

Sulfhemoglobin

Sulfur incorporated into HB; irreversible; ineffective in oxygen transport; presents with cyanosis

Carboxyhemoglobin

HB binds to carbon monoxide; 240*affinity vs oxygen (shift left); CO poisoning; 40% of this results in coma, seizure, hypotension, cardiac arrythmias, pulmonary edema, and death; cherry red blood and skin

Cyanmethemoglobin

Reference method for hemoglobin measurement; lysing agent frees hemoglobin from RBC; measured at 540NM spectrophotometrically