Blood: Circulating Life
Blood is a fluid that is made up of plasma and elements, which includes erythrocytes, leukocytes and platelets. At times the plasma volume and concentration can be affected as in fluid and electrolyte imbalances, but other times blood coagulation can have its disorders.
When elements are produced in the blood, we call this hemopoiesis. Hemopoiesis takes place through mitosis and differentiation of daughter cells. The cells specialize to produce a specific function. Most of the hemopoiesis happens in red bone marrow (about 2 liters of red marrow is in an adult’s skeleton). Formed element has very little reproductive abilities.
Stem cells are able to differentiate into all hemopoietic cells, or even form new stem cells. Progenitor cells are derived from stem cells but can’t self-renew themselves, so are said to be commited to a cell line.
Erythropoises, red blood cell formation, happens through mitosis. Then hemoglobin synthesis happens, followed by loss of organelles. The reticulocyte is finally a mature erythrocyte once cytoplasmic RNA is lost. It lasts about 120 days before removal in spleen, liver or marrow. Twenty five billion are lost every day, so production is about just as high.
Leukopoiesis happens in granulocytes and moncytes, with migration of lymphocyte progenitors to lymphoid tissue. We have about 7 million of these white blood cells in each milliliter of blood.
Thrombopoiesis produces thrombocytes, or platelets, from marro megakaryocytes. It happens through fragmentation as cytoplasm fragments are shedded from the megakaryocyte. There’s about 250 million platelets per milliliter.
Coagulation of blood is a response that occurs to block blood loss and basically is a turning of fluid blood to a gel so it stops flowing. The gel is a blood clot. It’s created with long protein filaments that become a tangled mesh next to wherever damage happened. The filaments are made of fibrin, derived from fibrinogen, which is split by thrombin, an enzyme derived from prothrombin. The thrombin also activates factor XIII to create crosslinking of fibrin filaments.
Prothrombin is activated to produce thrombin by a cascade of events that are a result of clotting factors. The clotting factors hang out in the plasma, but are only activated when endothelial cells or fibroblasts at a damaged sites have membrane changes that spills out tissue factor, or tissue thromboplastin.
Tissue factor activates the extrinsic pathway, clotting factors activate, and fibrin starts coagulation. The thrombin also stimulates another cascade called intrinsic pathway, which triggers even larger amounts of fibrin production.
Calcium is required for coagulation but only a little bit so a calcium deficiency is unlikely to affect response. The calcium is taken up by chelating agents . The liver contributes fibrinogen, prothrombin and clotting factors in a way that requires vitamin K.
A bleeding disorder can occur when there are issues with platelet or clotting factors. Thrombocytopenia is a condition that occurs when there aren’t enough platelets.
Clotting factor disorders can include Von Willebrand’s disease when a factor interferes with platelet binding or hemophilia when there are deficiencies in clotting factors.
Impaired hepatic synthes occurs when liver cannot produce enough clotting factors such as due to deficiency of vitamin K or if liver damage causes abnormal clotting factors to be produced.
Sometimes bleeding disorders can occur from small blood vessels as in vascular purpura, which is a blood vessel abnormality.
When there are too many erythrocytes, we have polycythemia; and when there are too few, we have anemia.
Anemia can happen due to little oxygen transport, iron deficiency, B12 deficiency, folic acid deficiency, or due to hemolysis because of abnormal blood cells (sickle cell, thalassemia).
Polycythemia can involve overproduction of red blood cells in the marrow. Smokers can suffer secondary polycythemia when inhaling carbon monoxide because it binds to hemoglobin causing compromised oxygen delivery, which can trigger increased erythrocyte production.
Like in erythrocytes, there may be too many leukocytes (leukocytosis) or too few (leukopenia).
Leukopenia usually happens because of neutropenia, when white cells are depleted because of infection or not enough production from marrow because of anti-tumor drugs or radiation.
Leukocytosis happens when there’s increased demand to a inflammation.
Leukemia is a cancer that results when a leukocyte precursor turns into a malignant tumor, then spill to the blood.
Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.