Blood Physiology Allison Gourley and Susan Rutherford

Define Haematopoesis Production of mature blood cells Red, white, platelets

Where does haematopoiesis occur? [3] Yolk sac (trimester one) Liver and spleen (trimester two) Red marrow (trimester three onwards)

Where does haematopoiesis occur? [3] Yolk sac (trimester one) Liver and spleen (trimester two) Red marrow (trimester three onwards) Where is red marrow found? [2] Flat bones: pelvis, sternum, ribs, scapula, cranium Epiphyseal ends of long bones: femur, humerus

Myeloid stem cell (GEMM) Lymphoid stem cell Multipotent hematopoietic stem cell What are the two different types of stem cells that arise from

Myeloid stem cell B-lymphoblast T-lymphoblast B-cells T-cells Lymphoid Stem Cell Plasma cells Multipotent hematopoietic stem cell 14 days What types of cells are produced from the myeloid cell line? RBC, Platelets, Neutrophils, Macrophages, Eosinophils, Mast cells

What controls haematopoiesis? [2] Local cell-to-cell contacts Growth factors (Now, name the 2 growth factors involved) Paracrine (G-CSF) or endocrine (EPO) Control proliferation, differentiation, maturation

EPO speeds erythropoiesis by what two mechanisms? Increases rate of mitoses Decreases maturation time What four things are required? [4] EPO, iron, folic acid, vitB12

Steps of erythropoiesis? Name some of the changes that occur to the cell during erythropoiesis: Decrease in cell size Haemoglobin production Loss of organelles Acquires an eosinophilic cytoplasm Extrusion of nucleus Acquisition of a biconcave disc

Four reasons for an erythrocyte being a biconcave disc? [4] Increase surface area Minimise distance (for diffusion) Increase flexibility Minimal tension with cell swelling

What is polycythaemia? Too many erythrocytes Opposite: anaemia

What is the pathogenesis of sickle cell anaemia? Autosomal recessive Point mutation of HbS leads to extensive membrane damage, producing an irreversibly sickled cell resulting in haemolysis

Where in the body is iron found? Haemoglobin Circulating, bound to transferrin Hepatocytes Macrophages Intracellular stores – ferritin and haemosiderin

What marker would you measure to investigate a patient’s iron stores? Ferritin: Circulating levels reflect iron stores

What are 3 causes of iron deficiency? 1.Increased demand 2.Inadequate absorption 3.Blood loss

Describe the stages leading to iron deficiency anaemia Net loss of iron Exhaustion of iron stores Decreased serum iron Compensatory increase in iron binding capacity Saturation of transferrin <15% leading to reduced iron delivery to bone marrow Iron deficiency anaemia Initial Compensation and effect Continues End result

Describe the passage of vitamin B12 through the body 1.Vitamin B12 ingested 2.Is bound R protein in salivary fluid 3.Binds to intrinsic factor in the duodenum 4.Absorbed in terminal ileum

What is the only indispensible function of the stomach?

What is pernicious anaemia? Autoimmune destruction of gastric parietal cells leading to lack of intrinsic factor and hence, B12 deficiency

What is the most common cause of vitamin B12 deficiency? Malabsorption NB. Rarely due to insufficient intake

What are some other causes of B12 deficiency? Gastric causes e.g. gastrectomy Intestinal causes e.g. malabsorption, ileal resection, Crohn’s disease (remember effect on terminal ileum), HIV, radiotherapy Some drugs e.g. anticonvulsants

Give 4 causes of folic acid deficiency 1.Insufficient intake 2.Malabsorption 3.Drugs e.g alcohol, anticonvulsants 4.Increased demand (leading to higher turnover)

What are the body’s physiological responses to anaemia? (4) Decreased affinity of Hb for oxygen Redistribute blood flow (withdraw supply to skin and kidneys, increase plasma volume from interstitial fluid) Increase reticulocyte count Increase cardiac output (only if severe)

What is the name for having too many WBCs? Why might this happen? Leukocytosis Increased production in marrow E.g. infection, paraneoplastic syndrome, CML Increased release from marrow stores E.g. infection, hypoxia Decreased margination E.g. exercise, catecholamines Decreased extravasation into tissues E.g. glucocorticoids

What is the name for having too few WBCs? Why might this happen? Leukopaenia Suppression of haematopoeitic stem cells Suppression of committed granulocytic precursors Ineffective haematopoeisis Increased peripheral utilisation

Types of anaemia and examples of their causes Normocytic, normochromic Acute blood loss Anaemia of chronic disease Haemolytic anaemia Microcytic, hypochromic Iron deficiency Thalassaemia Macrocytic, normochromic Vitamin B12 deficiency Folate deficiency Pernicious anaemia (accounts for 80% of this type)