Physiology chapters
Plasma proteins and erythropoiesis
The composition of blood and the jobs of the plasma proteins, the stages of red cell development from stem cell to mature erythrocyte, how erythropoietin and nutrients control production, and the fate of old red cells.
- Plasma proteins are albumin (oncotic pressure, transport), globulins (immunity, transport) and fibrinogen (clotting); albumin and most globulins and fibrinogen are made in the liver.
- Red cells develop in the bone marrow through pronormoblast → normoblasts → reticulocyte → erythrocyte, losing the nucleus along the way.
- Production is driven by erythropoietin from the kidney in response to low tissue oxygen; it needs iron, vitamin B12 and folate.
On this page
Overview
Blood is made of cells (red cells, white cells and platelets) suspended in plasma.
- Cells make up about 45% of blood volume (the haematocrit) in men, a little less in women.
- Plasma makes up about 55%. It is about 91% water, with proteins, electrolytes, nutrients, hormones and waste.
Serum is plasma without the clotting factors (the fluid left after blood clots).
Plasma proteins
Normal total plasma protein is about 6–8 g/dL.
| Protein | Normal level (approx.) | Main functions |
|---|---|---|
| Albumin | 3.5–5 g/dL | Oncotic pressure (about 80% of it); carries bilirubin, fatty acids, hormones, calcium and drugs; buffer |
| Globulins (α, β, γ) | 2–3.5 g/dL | α and β: transport (transferrin, caeruloplasmin, lipoproteins); γ-globulins (immunoglobulins): immunity |
| Fibrinogen | 0.2–0.4 g/dL | Clotting (converted to fibrin) |
Where they are made
- Albumin, fibrinogen and most α and β globulins: the liver.
- Immunoglobulins (γ-globulins): plasma cells (from B lymphocytes).
Albumin is the main source of plasma oncotic pressure, which holds fluid inside capillaries. Low albumin (liver disease, nephrotic syndrome, malnutrition) causes oedema.
Other functions of plasma proteins
- Act as a buffer for pH.
- Provide a protein reserve in starvation.
- Contribute to blood viscosity.
- Fibrinogen and globulins raise the erythrocyte sedimentation rate (ESR) by making red cells stack (rouleaux).
Sites of blood cell formation
| Stage of life | Main site |
|---|---|
| Early embryo | Yolk sac |
| Middle of fetal life | Liver (and spleen) |
| Late fetal life onward | Bone marrow |
In children, almost all bones make blood. By adulthood, active (red) marrow is found mainly in flat bones: vertebrae, sternum, ribs, skull, pelvis, and the upper ends of the femur and humerus.
All blood cells come from a single type of pluripotent haematopoietic stem cell.
Stages of erythropoiesis
- Pronormoblast (proerythroblast): large cell, large nucleus; starts making haemoglobin.
- Early (basophilic) normoblast: cytoplasm stains blue (many ribosomes).
- Intermediate (polychromatic) normoblast: haemoglobin starts to build up.
- Late (orthochromatic) normoblast: cytoplasm full of haemoglobin; the nucleus shrinks and is pushed out.
- Reticulocyte: no nucleus but a network of remaining ribosomes. It leaves the marrow and matures in the blood in about 1–2 days. Normally about 1% of red cells.
- Erythrocyte: mature biconcave disc, about 7.8 µm across, no nucleus or mitochondria.
The whole process takes about 5–7 days.
The nucleus is lost at the late normoblast stage. A raised reticulocyte count shows the marrow is producing more red cells (after bleeding or haemolysis).
Regulation of erythropoiesis
Erythropoietin
- Stimulus: low tissue oxygenation (anaemia, high altitude, lung disease, heart failure).
- Source: about 90% from the kidney (peritubular interstitial cells), the rest mainly from the liver.
- Effect: stimulates stem cells to form pronormoblasts and speeds every stage of red cell production.
Kidney disease causes anaemia because erythropoietin production falls. Synthetic erythropoietin is used to treat it.
Testosterone also stimulates red cell production, which is one reason haemoglobin is higher in men.
Nutrients needed
- Iron: for haemoglobin. Absorbed in the duodenum, carried by transferrin, stored as ferritin.
- Vitamin B12 and folic acid: needed for DNA synthesis. Without them, cells grow but cannot divide properly, so they become large (megaloblastic) and fragile.
- Also protein, vitamin C, copper and others.
Vitamin B12 needs intrinsic factor from the parietal cells of the stomach to be absorbed in the terminal ileum.
Iron deficiency gives small, pale (microcytic, hypochromic) cells. B12 or folate deficiency gives large (macrocytic, megaloblastic) cells.
Haemoglobin
Each haemoglobin molecule has four haem groups (iron in the ferrous, Fe2+ state) and four globin chains. Adult HbA is α2β2; fetal HbF is α2γ2.
Normal haemoglobin is about 15 g/dL in men and 14 g/dL in women.
Destruction of red cells
Red cells live about 120 days. Old cells become rigid and are removed by macrophages, mainly in the spleen (and liver and marrow).
- Iron is recycled.
- Globin is broken into amino acids.
- Haem is turned into biliverdin, then bilirubin, which is carried by albumin to the liver and excreted in bile.
Clinical relevance
Anaemia of chronic kidney disease
How it happens: loss of erythropoietin-producing cells.
What you see: normocytic anaemia, corrected by erythropoietin injections.
Pernicious anaemia
How it happens: autoimmune destruction of parietal cells; no intrinsic factor, so B12 is not absorbed.
What you see: megaloblastic anaemia and nerve damage (subacute combined degeneration).
Polycythaemia
How it happens: secondary to chronic hypoxia (altitude, lung disease) through erythropoietin, or primary (polycythaemia vera, a marrow disorder with low erythropoietin).
What you see: high haematocrit, thick blood, headaches and clotting risk.
Expect: the functions of each plasma protein and where they are made, the main protein for oncotic pressure, the sites of haematopoiesis at each age, the stages of erythropoiesis and where the nucleus is lost, the source and stimulus of erythropoietin, the roles of iron, B12 and folate, and red cell lifespan and breakdown.
Quick revision
- Plasma protein 6–8 g/dL; albumin gives most oncotic pressure.
- Liver makes albumin and fibrinogen; plasma cells make immunoglobulins.
- Yolk sac → liver and spleen → bone marrow.
- Pronormoblast → normoblasts → reticulocyte → erythrocyte; nucleus lost at late normoblast.
- Erythropoietin: kidney (about 90%); stimulus is low tissue O2.
- B12 and folate: DNA synthesis; deficiency gives megaloblasts.
- Red cell lifespan 120 days; removed in the spleen.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
Which plasma protein is most important for oncotic pressure?
Albumin, which provides about 80% of plasma oncotic pressure.
Where is erythropoietin produced?
About 90% in the kidney and most of the rest in the liver.
What is a reticulocyte?
A young red cell without a nucleus that still contains some ribosomes; it matures in the blood within one to two days.
How long does a red blood cell live?
About 120 days.