Physiology
Basic Cellular
Where in the body is most erythropoietin produced:
Answer:
The glycoprotein hormone erythropoietin (EPO) promotes the production of red cells. About 90% of erythropoietin is produced in the peritubular complex of the kidney and 10% in the liver and other organs. Erythropoietin secretion is stimulated by reduced O2 supply to the kidney receptor. Thus the principal stimuli to red cell production are tissue hypoxia and reduced haemoglobin concentration (anaemia). Increased pathological secretion may occur in polycystic kidney disease and renal cell carcinoma. Decreased secretion may occur in advanced chronic kidney disease or in polycythaemia vera. Recombinant erythropoietin is available for treating anaemia in end-stage chronic kidney disease.Red Blood Cells
Physiology / Basic Cellular / Blood and Blood Flow
Last Updated: 4th August 2019
Erythropoietin
The glycoprotein hormone erythropoietin (EPO) promotes the production of red cells. About 90% of erythropoietin is produced in the peritubular complex of the kidney and 10% in the liver and other organs. Erythropoietin secretion is stimulated by reduced O2 supply to the kidney receptor. Thus the principal stimuli to red cell production are tissue hypoxia and reduced haemoglobin concentration (anaemia). Increased pathological secretion may occur in polycystic kidney disease and renal cell carcinoma. Decreased secretion may occur in advanced chronic kidney disease or in polycythaemia vera. Recombinant erythropoietin is available for treating anaemia in end-stage chronic kidney disease.
Red Cell Production
Red blood cells are formed from committed stem cells in a process called erythropoiesis which occurs in the bone marrow in adults, and the liver and spleen in the foetus. Erythropoietin increases the number of committed stem cells and promotes production of red cells. Stem cells differentiate into erythroblasts (early normoblasts) which are relatively large and nucleated. As differentiation proceeds, the cells shrink and haemoglobin is synthesised, which requires iron, folate and vitamin B12. In the late normoblast the nucleus breaks up and disappears and the reticulocyte is formed.
About 2 x 1011 red cells are produced from the marrow each day. The spleen also holds a reserve of red cells that can be released following blood loss.
Reticulocytes
Reticulocytes do not have a cell nucleus, but they have a network of ribosomal RNA which allows continued synthesis of haemoglobin. Normally about 1 - 2% of circulating red cells are reticulocytes, which are characterised by their slightly larger size compared to mature erythrocytes and cresyl blue staining (due to residual RNA).
The reticulocyte count is a measure of new red cell production by the bone marrow. It is raised after haemorrhage or haemolysis when extra red cell production is needed. It is low if the marrow is incapable of normal red cell production, for example in:
- General bone marrow failure (e.g. malignant infiltration, aplastic anaemia)
- Impaired red blood cell production (e.g. deficiency of iron, vitamin B12 or folate)
- Lack of erythropoietin stimulus (e.g. chronic kidney disease)
- Chronic systemic disease
An isolated reticulocytosis without anaemia is relatively common as a direct toxic effect of alcohol.
Erythrocytes
The reticulocytes are released from the marrow into the peripheral blood, where after about 1 - 2 days, they lose their remaining ribosomes and become mature erythrocytes, at which point haemoglobin synthesis can no longer take place.
Mature erythrocytes are biconcave discs with no nucleus, ribosomes or mitochondria but with the ability to generate energy as ATP by the anaerobic glycolytic pathway. The red cell membrane consists of a bipolar lipid layer with a membrane skeleton of penetrating and integral proteins anchoring carbohydrate surface antigens. The shape and flexibility of red cells allows them to deform easily and pass through capillaries.
Erythrocytes have a normal lifespan of about 120 days.
Red Cell Degradation
Senescent red cells are destroyed extravascularly by macrophages in the reticuloendothelial system (in the bone marrow, liver and spleen).
Approximately 10 - 15% of developing erythroblasts die within the marrow without producing mature cells; this is termed ineffective erythropoiesis and may be more marked in certain disease.
![By OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons](https://primary-cdn.frcemsuccess.com/wp-content/uploads/2018/09/1905_Erythrocyte_Life_Cycle.jpg)
Lifecycle of a Red Blood Cell. (Image by OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons)
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
