Blood Production Structure Function Anaemia Notes

Semester 2

Case 7: Giving and Receiving

• What is the normal composition of blood?

Refer to anatomy workbook for general outline.

Whole Blood = 46-63% plasma, 37-54% formed elements.

Plasma = 92% water, 7% plasma proteins, 1% other solutes.

Formed elements = 99.9% RBC, <0.1% WBC, <0.1% platelets.

Extended notes:

{1} Plasma Proteins

Albumins: Constitute roughly 60% of the plasma proteins. They are major contributors to the osmotic pressure of plasma. They are also important in the transport of fatty acids, thyroid hormones, some steroid hormones, etc.

Globulins: Constitute about 35% of the plasma proteins. Antibodies (AKA. Immunoglobulins) attack foreign proteins & pathogens. Transport globulins bind small ions, hormones, & compounds that might otherwise be lost at the kidneys or that have very low solubility in water.

Fibrinogen: Constitutes roughly 4% of plasma proteins. Under certain conditions, fibrinogen molecules interact, forming large, insoluble strands of fibrin. Fibrin provides the basic structure for a blood clot.

Other plasma proteins: Make up the remaining 1%. Examples include insulin, prolactin, TSH, FSH, and LH.

Formed Elements

Hematocrit = The % of whole blood volume contributed by formed elements. Adult males = 46%, and adult females = 42%. The sex difference in Hematocrit primarily reflects the fact that androgens stimulate red blood cell production, whereas oestrogens do not. Hematocrit can increase due to dehydration, or after EPO stimulation. It can decrease as a result of internal bleeding or problems with RBC production.

[2] RBC:Platelet:WBC = 700:40:1.

• Where is blood formed & how does this vary between the foetus, child & adult?

In bone marrow failure e.g. leukaemia, haematopoiesis again takes place in other areas of the body. AKA: Extramedullary haematopoiesis. – liver, spleen, thymus, etc.

Stromal cells, including yellow bone marrow, provide the microenvironment for haematopoiesis to occur. They, for example, secrete growth factors and express adhesion molecules. The stromal matrix provides physical support for haematopoietic cells.

Foetal Hb has 2 alpha chains & 2 gamma chains. There is increasing synthesis of beta chains from 13 weeks of gestation, and at term there is 80% Hb F and 20% Hb A, which contains 2 alpha chains & 2 beta chains. The switch from Hb F to Hb A occurs after birth when the genes for gamma chain production are further suppressed and there is rapid increase in the synthesis of beta chains. Less than 1% of Hb F is produced after 6 months of life. Hb A₂, which contains 2 alpha chains and 2 delta chains, comprises about 2% of adult haemoglobin.

• How is blood formed?

[2] Blood is composed of plasma and formed elements.

Plasma

The liver synthesises & releases >90% of the plasma proteins, including ALL albumins & fibrinogen, MOST globulins, and various prohormones. It is for this reason that liver disorders can alter the composition and functional properties of blood.

Antibodies are produced by plasma cells, which are derived from lymphocytes.

Peptide hormones are produced in a variety of endocrine organs.

Formed Elements

The formed elements are produced via the process of haematopoiesis.

Blood cells have various lifespans, so need to be produced at various rates.

Platelets: 9-10 days.

RBCs: 120 days.

WBCs: A few days to a few years.

RBCs and platelets are produced at the same rate. However, RBCs have a much larger lifespan, so there are more present in the blood.

Two populations of pluripotent stem cells are responsible for the production of all of the different types of formed elements. These are myeloid stem cells and lymphoid stem cells. Lymphoid stem cells only give rise to lymphocytes. Myeloid stem cells give rise to every other blood cell type – RBCs, platelets, neutrophils, basophils, & eosinophils.

Haematopoietic Stem Cells

All blood cells originate in bone marrow! They are capable of differentiating into any blood cell type. They become specialised and produce more mature cell types from a precursor. Haematopoietic stem cells give rise to different progenitor cells (myeloid & lymphoid stem cells). They look similar to small/medium lymphocytes, and are identified using immunological testing for CD34+ and DC38+ markers.

Erythropoiesis

Proerythroblasts are large cells with cytoplasm that stains dark blue. They give rise to normoblasts, which are smaller cells whose cytoplasm starts to stain lighter blue. Late normoblasts have extruded nucleus (they get ready to rid their nuclei). Normoblasts then become reticulocytes, which contain some ribosomal RNA, and circulate in peripheral blood for 1-2 days. (An increased number of reticulocytes suggest the body is trying to produce more RBCs, for example in anaemia.) In mature RBCs, RNA is lost. 1000million erythrocytes are replaced every day!

Thrombopoiesis

Endomitosis occurs in myeloid cells to produce megakaryoblasts. This is when nuclear content (chromosomes) increases, but cells don’t divide. The cells become larger & polyploid. At a certain point, endomitosis stops, cytoplasm becomes more granular, and megakaryocytes fragment. This process takes 2-3 days. After 9-10 days, they are broken down if they haven’t been used. Each megakaryocyte produces roughly 4000 platelets.

Monopoiesis

A myeloid stem cell differentiates into a monoblast, which then becomes a promonocyte. Promonocytes are large cells with indented nuclei that are only found in bone marrow. These become monocytes. Monocytes have a kidney-shaped nucleus. They are the largest blood cells. Monocytes remain in circulation for 20-40 hours in peripheral blood. They then migrate to tissues & mature into macrophages, which...

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