Haemopoiesis, the Spleen and Bone Marrow

Question 1

What is haemopoiesis

Answer 1

Process by which blood cells are formed

Question 2

Where does haemopoiesis take place

Answer 2

In the bone marrow, mainly in pelvis, sternum, skull, ribs and vertebrae

Question 3

What cell is in the bone marrow that differentiates into blood cells

Answer 3

Haemopoietic stem cell (multipotential)

Question 4

What are the five main lineage pathways arising from haemopoietic stem cells

Answer 4

Thrombopoiesis

Granulopoiesis

Monocytopoiesis

Lymphopoiesis

Erythropoiesis

Question 5

What is thrombopoiesis

Answer 5

Production of platelets - platelets are membrane bound fragments which bud off from megakaryocytes

Megakaryocyte formation is driven by thrombopoietin (TPO)

Question 6

What are the cells produced by granulopoiesis

Answer 6

Granulocytes - basophils, neutrophils and eosinophils

Question 7

What is granulopoiesis

Answer 7

Production of granulocytes from myeloblast cells

Myeloblast cells airse from common myeloid progenitor cells

Question 8

What is the function of neutrophils

Answer 8

Migrate to areas of inflammation by chemotaxis where they phagocytose invading microbe and destroy them by respiratory burst

Question 9

What is the function of eosinophils

Answer 9

Phagocytose microbes and are associated with immune response to multicellular parasites

Question 10

What is the function of basophils

Answer 10

Role similar to eosinophils in parasitic infections and allergy

Question 11

What is monocytopoiesis

Answer 11

Production of monocytes from myeloblast cells

Myeloblast cells airse from common myeloid progenitor

Question 12

What is lymphopoiesis

Answer 12

Production of B and T lymphocytes from small lymphocytes which arise from common lymphoid progenitors

Question 13

How do B lymphocytes develop

Answer 13

Start development in foetal liver and bone marrow

During development, immunoglobulin genes rearrange to allow production of antibodies with wide range of specificities

Final maturation of B-cells requires exposure to antigen in lymph nodes

Question 14

How do T lymphocytes develop

Answer 14

T-lymphocyte progenitors arise from foetal liver and migrate to thymus gland early in gestation

Immature T-cells undergo rearrangement of T-cell receptor genes resulting in ability to produce wide range of T-cell receptors

Question 15

What is erythropoiesis

Answer 15

Process by which erythrocytes are produced in the bone marrow

Question 16

What hormone drives erythropoiesis and where is it produced

Answer 16

Erythropoietin

Produced by the kidneys

Question 17

What factors cause an increased erythropoietin production

Answer 17

Hypoxia caused by:

Decreased RBC count

Decreased Hb

Decreased oxygen availability

Question 18

What is the function of erythropoietin

Answer 18

Inhibit apoptosis of CFU-E (colony-forming units of erythroid cell line) progenitor cells

Allow these cells to develop, proliferate and differentiate

Question 19

How do erythrocytes develop

Answer 19

Nucleated erythroblasts extrude their nuclei and most organelle forming reticulocytes

Reticulocytes are released into circulation where they extrude remaining organelle to form erythrocytes

Question 20

What proteins are found in the erythrocyte cell membrane

Answer 20

Spectrin

Ankyrin

Band 3

Protein 4.2

Question 21

What is the function of the proteins found in the RBC membrane

Answer 21

Facilitate vertical interactions with cell cytoskeleton and are essential in maintaining the RBCs biconcave shape and deformability

Question 22

What disease is associated with a mutation in RBC membrane proteins

Answer 22

Hereditary spherocytosis

Question 23

What is the spleen split into and what cells go into the different parts

Answer 23

Red pulp - sinuses lined by endothelial macrophages and cords. RBCs pass through red pulp

White pulp - structure similar to lyphoid follicles. White cells and plasma passes through here

Question 24

What is the spleen’s functions

Answer 24

Sequestration and phagocytosis

Blood pooling

Extremedullary haemopoiesis

Immunological functions - antibody synthesis, removal of antibody-coated bacteria

Red pulp removes old RBCs and metabolises Hb

Question 25

What causes splenomegaly

Answer 25

Haemolytic anaemia Infiltration by leukaemias and lymphomas Accumulation of waste products of metabolism Infections like malaria, schistosomiasis, HIV, glandular fever due to EBV Chronic myeloid leukaemia Myelofibrosis Liver cirrhosis with portal hypertension Myeloproliferative disorders

Question 26

What is generally the aetiology behind splenomegaly

Answer 26

Typically due to increased workload

Question 27

What risks are there with hyposplenism or having a splenectomy

Answer 27

Overwhelming sepsis Infection by encapsulated bacteria

Question 28

What are the causes of hyposplenism

Answer 28

Underlying disease causing destruction of spleen tissue - sickle-cell disease, coeliac disease Splenectomy

Question 29

What would you seen in the blood film of a patient with hyposplenism and why

Answer 29

Howell-Jolly bodies - DNA remnants in circulating erythrocytes These are present as they are not removed due to the hyposplenism

Question 30

What is the RES

Answer 30

The reticuloendothelial system A network of cell located throughout the body and is part of a larger immune system Role is to remove dead or damaged cells and identify and destroy foreign antigens in the blood

Question 31

What function does the spleen have in the RES

Answer 31

Filters blood to remove damaged and old cells from circulation Hb is removed from senescent erythrocytes and recylced with the globin portion being degraded to amino acids and haem portion metabolised to bilirubin

Question 32

Describe the process by which bilirubin is removed from the body

Answer 32

Bilirubin is conjugated in the liver and secreted in bile Bacteria in colon deconjugate and metabolise bilirubin into urobilinogen which is oxidised to form urobilin and stercobilin Small amount of urobilinogen is reabsorbed and processed by kidneys to give yellow colour

Question 33

What is the term for a low number of blood cells

Answer 33

Cytopenia

Question 34

What is the term for a low number of red cells

Answer 34

Anaemia

Question 35

What is the term for a low number of white cells

Answer 35

Leucopenia

Question 36

What is the term for a low number of neutrophils

Answer 36

Neutropenia

Question 37

What is the term for a low number of platelets

Answer 37

Thrombocytopenia

Question 38

What is the term for a low number of RBCs, WBCs and platelets

Answer 38

Pancytopenia

Question 39

What endings denote an increase in the number of cells

Answer 39

...cytosis or ...philia

Question 40

What is hypersplenism

Answer 40

Low blood count due to pooling of blood in an enlarged spleen

Question 41

What controls neutrophil development and what does it do

Answer 41

G-CSF hormone which causes: * Increased neutrophil production * Decreased time to release mature neutrophils * Enhanced chemotaxis * Enhanced phagocytosis and pathogen destruction

Question 42

What are the causes of neutrophilia

Answer 42

Actue inflammation Haemorrhage Smoking Cancer Tissue damage Drugs Cytokines Metabolic/endocrine disorders Myeloproliferative diseases

Question 43

What are the causes of neutropenia

Answer 43

Increased removal/use - splenic pooling, sepsis, immune destruction Benign ethnic neutropenia Cyclic netropenia Reduced production - B12/folate deficiency, infiltration of bone marrow by malignancy/fibrosis, aplastic anaemia, drugs, viral infections, congenital disorders

Question 44

What are the potential consequences of neutropenia

Answer 44

Severe bacterial/fungal infection Mucosal ulceration Neutropenic sepsis

Question 45

What are the causes of monocytosis

Answer 45

Chronic inflammatory conditions Chronic infections Carcinoma Myeloproliferative disorders

Question 46

What are the causes of eosinophilia

Answer 46

Allergic diseases Drug hypersensitivity Parasite infection Acute lymphoblastic leukaemia, acute myeloid leukaemia, eosinophilic leukaemia Hodgkin lymphoma Myeloproliferative disorders

Question 47

What are the causes of basophilia

Answer 47

Immediate hypersensitivity reactions RA Ulcerative colitis Myeloproliferative disorders - systemic mastocytosis

Question 48

What are the causes of lymphocytosis

Answer 48

Viral infections (especially in children) Bacterail infections Stress related Post splenectomy Smoking Lymphoproliferative disorders - chronic lymphocyte leukaemia, lymphoma