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Essentials
Iron oxygen carrying pigment
Folic acid (B9) - required for nucleoprotein
synthesis and maintenance in erythropoiesis
Vitamin B6, B12
ERYTHROPOIETIN
CELLULAR CHANGES
Cellular changes that occur during erythroid differentiation include
1. a decrease in cell size
2. condensation of nuclear chromatin
3. a decrease in nuclear diameter
4. an accumulation of hemoglobin in the cytoplasm (increased
acidophilia)
5. a decline in ribosome numbers in the cytoplasm (decreased
basophilia)
6. ejection of the nucleus.
STAGES OF ERYTHROPOIESIS
1. Proerythroblast unipotential stem cells
2. Basophillic erythroblast synthesise hemoglobin
3. Prochromatophillic erythroblasts synthesise hemoglobin
4. Normoblasts extrusion of pyknotic (degenerated/dead) nucleus
5. Reticulocytes
maturation to RBC in 24-48 hours
digestion of their remaining organelles and assumption of the biconcave shape.
RETICULOCYTES
Reticulocytes are the first non-nucleated red cell, which contains
ribosomal material in the cytoplasm.
It has a faint blue tinge polychromasia
They lose their ribosomal material and mature over 3 days,
subsequently release into the circulation.
Failure of this mechanism will result in reduced membrane flexibility of the RBC
and causes leakiness; and oxidation of Hb molecule producing methaemoglobin
and precipitation of globin chains as Heinz bodies localised on the inside of the
membrane.
Heinz bodies are found in G6PD deficiency,
NADPH deficiency, alpha thalassaemia,
chronic liver disease, hypersplenism.
Hemoglobin F is
unable to bind 2,3
DPG and has a left-
shifted curve this
ensures oxygenation
of the fetus blood.
HEMOGLOBIN SYNTHESIS
Trauma to the RBC membrane that causes the cell contents, chiefly
hemoglobin, to spill directly into plasma.
Approximately 10% to 20% of normal RBC destruction is
intravascular, secondary to turbulence and anatomic restrictions in the
vasculature.
IRON SALVAGE
1. By binding to haptoglobin, hemoglobin avoids filtration at the
glomerulus and is saved from urinary loss. The complex is carried
to the liver, where the haptoglobin-hemoglobin complex is bound
to macrophage receptors and internalized into the macrophage.
2. A secondary mechanism of iron salvage involves hemopexin. In
hemoglobin that is not bound by haptoglobin, the iron becomes
oxidized, forming methemoglobin. The heme molecule (actually
metheme) dissociates from the globin and binds to another liver-
produced plasma protein, hemopexin. This binding also saves the
iron from urinary loss and prevents oxidation of cell membranes.
Hemopexin-metheme binds to hepatocyte receptors and is
internalized.
EXTRAVASCULAR DESTRUCTION
Macrophages in the spleen, liver and
bone marrow (reticuloendothelial
system) remove the senescent RBC from
circulation.
Any reduction in cell deformability
makes their entrance difficult to the
spleen, resulting in splenic sequestration
and phagocytosis.
HEMOLYTIC ANEMIA
INTRODUCTION
Anemia can result from increased
red cell destruction, impaired red
cell production or blood loss.
In hemolytic anemia, the primary
focus would be in the context of red
cell destruction.
Hemolytic anemia is defined as
anemia due to a shortened survival
of circulating red blood cells (RBCs)
due to their premature destruction.
RBC undergoing hemolysis can occur
either intravascularly or
extravascularly (e.g. spleen).
INTRAVASCULAR VS EXTRAVASCULAR
CLINICAL FINDINGS
Intravascular Extravascular
Hemoglobinemia Jaundice
Hemoglobinuria Reduced levels of haptoglobin
Hemosiderinuria Elevated levels f LDH
Unconjugated hyperbilirubinemia Splenomegaly
Jaundice
Massive Acute tubular necrosis
Reduced haptoglobin levels
High levels of LDH
REFERENCE
http://accessmedicine.mhmedical.com.ezproxy.lib.monash.edu.au/cont
ent.aspx?sectionid=42045308&bookid=563&jumpsectionID=420464
59&Resultclick=2
https://clinicalgate.com/introduction-to-increased-destruction-of-
erythrocytes/
Kumar and Clark, 8th Edition
Davidsons Principles and Practice of Medicine, 22nd Edition