3.1 ERYTHROKINETICS Flashcards
Dynamics of RBC production and destruction
ERYTHROKINETICS
Collection of all stages of RBC throughout the body in the BM, PB, vascular spaces within
organs
Erythron
refers only to the cells in circulation
RBC mass
STIMULUS TO RED BLOOD CELL PRODUCTION
HYPOXIA
Primary oxygen-sensing system LOC
Peritubular fibroblast of the kidney
Ability to sense whether there is adequate O2 supply to the tissues; once inadequacy of
O2 supply is detected, they influence/trigger EPO production
Primary oxygen-sensing system
First human hematopoietic growth factor to be identified
Erythropoietin
Gene for EPO is located at
chromosome 7
EPO Mediated by
GATA1
primary source of EPO
Kidneys (peritubular interstitial cells)
also secretes EPO (10%-15%) | primary source of EPO in the unborn
Liver
Thermostable, nondialyzable, glycoprotein hormone that has carbohydrate unit & terminal
sialic acid unit
EPO Structure
EPO MW
34 kD
Promotes early release of reticulocytes from the BM
SHIFT/ STRESS RETICS
major way in which EPO increases RBC mass
Prevents apoptotic cell death
ERYTHROCYTE DESTRUCTION
ERYPTOSIS
process of cellular aging
Senescence
Changes that occur as the RBC ages
Alteration in the membrane
↓ ATP levels
↑ calcium
Appearance of senescent antigen
↓ pH
Alteration in the membrane is caused by
loss of sialic acid and lipids
↓ ATP levels due to loss of
glycolytic enzymes
This makes RBCs more susceptible to destruction
Appearance of senescent antigen
This promotes iron oxidation
↓ pH
Extravascular Hemolysis
Macrophage-Mediated Hemolysis
Fragmentation or Intravascular Hemolysis
Mechanical Hemolysis
RBC destruction outside blood vessel by splenic macrophage
Macrophage-Mediated Hemolysis
90% of aged red cell destruction
Macrophage-Mediated Hemolysis
- ↑ total bilirubin and indirect
(unconjugated) bilirubin - Slightly ↑ lactate dehydrogenase activity
- Sightly ↓ haptoglobin and hemopexin
- Slightly ↑ free hemoglobin
Serum samples of Macrophage-Mediated Hemolysis
- ↑ total bilirubin and indirect
(unconjugated) bilirubin - ↑ lactate dehydrogenase activity
- ↓ haptoglobin and hemopexin
- ↑ free hemoglobin
Serum of Mechanical Hemolysis
- ↑ urobilinogen
- Free hemoglobin: Negative
- Methemoglobin: Negative
Urine sample of Macrophage-Mediated Hemolysis
- ↑ urobilinogen
- Free hemoglobin: Positive
- Methemoglobin: Positive
Urine sample of Mechanical Hemolysis
- Spherocytes are often present
Macrophage-Mediated Hemolysis
Associated with Rh incompatibility
Macrophage-Mediated Hemolysis
RBC rupture within the blood vessel
Mechanical Hemolysis
10% of aged red cell destruction
Mechanical Hemolysis
Schistocytes are often present
Mechanical Hemolysis
Associated with ABO incompatibility
Mechanical Hemolysis
In intravascular hemolysis, the rupture of RBCs results in the release of RBC contents (particularly hemoglobin) which leads to the presence of
free plasma hemoglobin.
Three ways to salvage free plasma hemoglobin:
binding of haptoglobin to free plasma
hemoglobin
binding of hemopexin to metheme
metheme binds to albumin (temporarily)
Heme portion of methemoglobin is called
metheme/hemin
