Transcript PowerPoint: Hemoglobin

MLAB 1415- Hematology
Keri Brophy-Martinez
Chapter 6: Hemoglobin
Hemoglobin
 What is it?
Iron- bearing protein which is the main component of the RBC
 Gives the red cell its color
 Synthesis
 Majority synthesized at the polychromatophilic normoblast stage
 Regulation
 Stimulated by tissue hypoxia
 Hypoxia causes the kidneys to increase production of EPO, which
increases RBC and hemoglobin production
 Function
 Carry oxygen from the lungs to the tissues
 Remove CO2
 Buffering action, maintains blood pH as it changes from
oxyhemoglobin (carrying O2) to deoxyhemoglobin ( without O2)

Hemoglobin Reference Ranges
 Adults


Male 14-17.4 g/dL
Female12-16.0 g/dL
 Children


Birth 13.5-20.0 g/mL
6-12 years 11.5-15.5 g/mL
**Refer to inside cover of text for other age
ranges
Structure
 4 polypeptide
Subunits

Heme group


Porphyrin ring
Ferrous iron
 Globin chain


2 Alpha Chains
2 Beta chains
Hemoglobin Synthesis
 Synthesis


Occurs in the mitochondria of developing red cells
as they mature in the bone marrow
Processes necessary for normal synthesis
 Adequate iron supply & delivery
 Adequate synthesis of protoporphyrins
 Adequate globin synthesis
Heme Synthesis
 Chain of Events
 Iron delivery & supply
 Iron is delivered to the
reticulocyte by
transferrin
 Synthesis of
protoporphyrins
 Occurs in the
mitochondria of RBC
precursors
 Mediated by EPO and
vitamin B6
 Protoporphyrin + iron =
heme
Globin Synthesis
 Chain of Events
 The rate of globin synthesis is
proportional to the rate of
porphyrin
synthesis.

Proper globin synthesis
depends on genes. The precise
order of amino acids in the
globin chains is critical to the
structure and function of
hemoglobin.

Chain designations are as
follows
 Alpha α, beta β, delta δ,
epsilon ε, gamma γ, zetaζ
Normal hemoglobins
Embryonic
Hemoglobins
• Gower 1- zeta
(2), epsilon (2)
• Gower 2- alpha
(2), epsilon (2)
• Portland-Zeta
(2), gamma (2)
Fetal
hemoglobin
• Hemoglobin Falpha(2),
gamma (2)
Adult
hemoglobins
• Hemoglobin Aalpha (2), beta
(2)
• ~95%
• Hemoglobin
A2- alpha(2),
delta(2)
• ~1.5-3.7%
• Hemoglobin Falpha(2),
gamma (2)
• <2 %
Hemoglobin Synthesis
Oxygen transport
 The amount of O2 bound to hemoglobin and
released to tissues depends on PO2 and
PCO2, but also the affinity of hemoglobin for
O2.
 Oxyhemoglobin: hemoglobin with oxygen
 Deoxyhemoglobin: hemoglobin without
oxygen
 Oxygen affinity is the ease with which
hemoglobin binds and releases oxygen.
Oxygen Affinity
 Determines the proportion of O2 released to
the tissues or loaded onto the cell at a given
oxygen pressure.
 Increases in oxygen affinity means
hemoglobin has an increased affinity for O2,
so it binds more. However, it does not want
to give it up.
 Decreases in oxygen affinity, cause O2 to be
released.
Bohr Effect
 Alterations in blood pH, shifts oxygen
dissociation curve
 In acidic pH, the curve shifts to the right
 Results in an enhanced capacity to release
O2 where it is needed
Oxygen Dissociation Curve
 Right-Shift
 Hgb has less attraction
for O2
 Hgb willing to release
O2 to tissue
 Examples: anemia,
acidosis
 Even though there
may be less RBC’s,
they act more
efficiently to deliver O2
to target
Oxygen Dissociation Curve
 Left shift
 Hgb has more
attraction for O2
 Hgb less willing to
release O2 to tissue
 Examples: presence
of abnormal Hgb’s,
alkalosis
Carbon Dioxide Transport
 Three mechanisms of transport



Dissolution in the plasma
Formation of bicarbonic acid
Binding to carbaminohemoglobin
Nonfunctional hemoglobins
 What do they do?

Hypoxia


Inadequate amount of O2 in the blood
Cyanosis


Presence of > 5 g/dl deoxyhemoglobin in blood
Patient appears blue
Nonfunctional hemoglobins

Carboxyhemoglobin




Methemoglobin




Oxygen molecules bound to heme are replaced by carbon monoxide.
Slightly increased levels of carboxyhemoglobin are present in heavy
smokers and as a result of environmental pollution.
Can revert to oxyhemoglobin.
Iron in the hemoglobin molecule is in the ferric (Fe3) state instead of the
ferrous (Fe2) state. Incapable of combining with oxygen.
Can occur as a result of strong oxidative drugs or to an enzyme
deficiency (more discussion to follow).
Can revert to oxyhemoglobin
Sulfhemoglobin



Hemoglobin molecule contains sulfur.
Caused by certain sulfur-containing drugs or chronic constipation.
Cannot revert to oxyhemoglobin and may cause death.
References
 McKenzie, S. B. (2010). Clinical Laboratory
Hematology (2nd ed.). Upper Saddle River,
NJ: Pearson Education, Inc..