Haemotology Flashcards
Diapedesis
Reticulocytes pass from bone marrow into blood capillaries by squeezing through pores of endothelial membrane
Neutrophils and monocytes also enter tissue via diapedesis
Cytokines such as Tumour Necrosis Factor (TNF) stimulate the expression of selectin. As the leukocytes roll along the capillary wall, the selectin binds to the leukocytes, slowing it down and allowing it to squeeze through the activated endothelial membrane. Once inside the interstitial fluid, they migrate along a chemostatic gradient towards the site of injury or infection.
Erythrocytes
Biconcave
Non nucleated
Carries Oxygen and carbon dioxide
Haematopoiesis
Haematopoiesis is the process of producing blood cells.
for self-renewal of blood cells and the long term reconstitution of blood.
blood cells begin in the bone marrow from a single type of cell called the pluripotential haematopoietic stem cell.
As these cells reproduce, a portion of them remains exactly like the original pluripotential cells and is retained in the bone marrow to maintain a supply of these.
Most of the others differentiate and mature to form other cell types. This process is controlled by many growth factors, differentiation inducers and cytokines.
Leukocytes
are formed from the early differentiation of the pluripotential haematopoietic stem cell: the myelocytic (myeloid) and the lymphocytic (lymphocytes) lineages.
An increase in the amount of cytokines or presence of inflammation will increase leukocyte production.
Granulocytes and monocytes
The granulocytes and monocytes are formed only in the bone marrow (medullary), and are stored within the marrow until they are needed in the circulatory system. Granulocytes are the main defence against bacterial infection
Lymphocytes and plasma
The lymphocytes and plasma cells are produced and stored mainly in the various lymphogenous tissues (extra-medullary) – especially the lymph glands, spleen and thymus.
Platelets and megakaryocytes
Megakaryocytes, which fragment to form platelets, are also formed in the bone marrow. Thrombopoietin (TPO) is a haemopoietic cytokine that is responsible for their production.
Erythropoiesis
principal stimulus for erythrocyte production is hypoxia – low O2 tension in the blood. Hypoxia causes a marked increase in erythropoietin production, and the erythropoietin in turn enhances RBC production until hypoxia is relieved. Renal tubular epithelial cells secrete erythropoietin during hypoxia, directly or under the stimulation of norepinephrine, epinephrine and other prostaglandins
Erythropoietin
Erythropoietin stimulates the production of proerythroblasts from the haematopoietic stem cells in the bone marrow, and causes these cells to pass more rapidly through the different erythroblastic stages than they normally do. During erythropoiesis, plasma haemoglobin levels decrease as it is taken up by developing RBCs.
B12 and folate
Both folate and vitamin B12 is essential for DNA synthesis. Lack of either causes abnormal and diminished DNA and, consequently, failure of nuclear maturation and cell division.
the erythroblastic cells of the bone marrow, fail to proliferate, produce mainly larger than normal RBCs called macrocytes.
Macrocytes have a flimsy membrane, and is often irregular, large and oval, causing them to have a short life span compared to normal RBCs.
o DNA synthesis needs adenosine, guanine, cytosine and thymidine – these come from dATP, dGTP, dTTP etc.
o To make dTTP you need B12 and folate à deficiency of these means thymidine can’t be made so can’t make DNA è can’t make new cells
o Problems appear in cells that divide + get replaced lots i.e. epithelial surfaces of mouth, gonoads and bone marrow
o Bone marrow problems mean you get abnormal blood cells
o B12 comes from meats, eggs, dairy
o Folic acid comes from leafy green vegetables
o B12:
§ Parietal cells of stomach make intrinsic factor
§ IF binds to B12 à combo binds to receptors in ileum to be absorbed
§ Causes of deficiency à not enough in diet, pernicious anaemia (autoimmune disorder where parietal cells or IF destroyed by antibodies), malabsorption
Iron
Iron in diet is absorbed in duodenum
o Haem iron (Fe2+, ferrous iron) from animals is better absorbed than Fe3+ (ferric iron)
o Fe3+ needs to be reduced to Fe2+ to be absorbed
o Phytates in food reduce iron absorption
o High iron levels in body are toxic à excess iron can’t be excreted
Iron is transported in the form of transferrin
in the plasma to areas of the body where it is needed. Transferrin binds strongly to with receptors in the cell membranes of erythroblasts in the bone marrow. Together with its bound iron, it is ingested into the erythroblasts by endocytosis. There the transferrin transfers the iron directly to mitochondria where heme is synthesized.
Hepcidin
In duodenum à ferroportin on enterocytes transfers iron from cell into bloodstream
o Erythropoietin inhibits hepcidin à to ensure sufficient supply of iron to bone marrow when demand for erythrocytes is high
o If body Fe stores are high à inflammatory response in body à liver makes hepcidin
o Hepcidin degrades ferroportin so any iron absorbed by enterocytes is bound by protein ferritin and kept in enterocyte until it dies
o Inflammation can cause low levels of iron in blood, leading to anaemia
Anemia
Deficiency of haemoglobin in the blood, caused by either too few RBCs or too little haemoglobin.
Blood loss anemia
Aplastic anemia
Hypochromic,microcytic anemia
Polychromic, macrocytic (megaloblastic) anemia
Haemolytic anemia
Aplastic anemia
Lack of functioning bone marrow (Bone marrow aplasia)
Hypochromic microcytic anemia
Iron deficiency anemia): Lack of iron causes RBCs that are produced to be smaller than normal and have too little hemoglobin inside them.
Decreased MCH and MCV
Decreased ferretin and bone marrow iron levels; increased transferrin levels
Megaloblastic anemia
Polychromic macrocytic
Folate, vitamin B12 deficiency results in erythroblasts being unable to proliferate rapidly enough to form normal numbers of RBCs, causing RBCs formed to be oversized, have odd shapes and fragile membranes, which rupture easily.
Haemolytic anemia
Abnormalities of RBCs make the cells fragile, such that they rupture easily as they go through capillaries. The life span of the RBCs are so short that the cells are destroyed faster than they can be formed and serious anemia results. Usually due to heredity and autoimmunity.
Anisocytosis
More variation in size than normal RBC
Poikilocytosis
More variations in shape than normal RBC
Target cells
cells w/accumulation of Hb in centre of central pallor, found in obstructive jaundice, liver disease, haemoglobinopathies and hyposplenism
Polycythaemia
too many red cells in circulation, Hb, RBC and Hct are all increased
o Blood doping or over transfusion
o Appropriately increased erythropoietin à e.g. as result of hypoxia
o Inappropriate erythropoietin synthesis or use à e.g. from renal tumour secretions
o Independent of erythropoietin à polycythaemia vera – intrinsic bone marrow disorder (myeloproliferative neoplasm) leading to hyper viscosity (thick blood) – drugs given to reduce bone marrow production of red cell
Effects of polycythemia on function of the circulatory system
Blood flow through the peripheral blood vessels is often very sluggish. Rate of venous return to the heart is decreased due to increased blood viscosity; but is neutralized by the increase in blood volume. Arterial pressure is regulated by pressure-regulating mechanisms, but should regulations fail, hypertension develops.
Effects of anemia on circulatory system
Blood viscosity may fall due to anemia, such that resistance to blood flow in the peripheral blood vessels is decreased. Moreover, hypoxia resulting from diminished transport of oxygen by the blood causes the peripheral tissue blood vessels to dilate, allowing a further increase in return of blood to the heart. Hence, one of the major effects of anemia is greatly increased cardiac output, as well as increased pumping workload on the heart. During exercise, which greatly increases demand for oxygen, extreme tissue hypoxia results, and acute cardiac failure ensues.
