5. Haemopoeisis, Spleen And Bone Marrow

Question 1

Where does the production of blood cells occur?

Answer 1

Bone marrow
In adult: pelvis, sternum, skull, ribs, vertebrae
In infant: extensive throughout skeleton

Question 2

What is differentiation of haemopoietic stem cells determined by?

Answer 2

Hormones
Transcription factors
Interactions with non-haemopoietic cell types

Question 3

What is the role of erythropoietin?

Answer 3

Secreted by kidney and stimulates red blood cell production

Question 4

What is the role of thrombopoietin?

Answer 4

Produced by liver and kidney and regulates production of platelets

Question 5

What are the 2 progenitor cell types?

Answer 5

Common myeloid

Common lymphoid

Question 6

What do common myeloid progenitors differentiate into?

Answer 6

Megakaryocytes (platelets)
Erythrocytes
Myeloblasts

Question 7

What do myeloblasts differentiate into?

Answer 7

Basophils
Neutrophils
Eosinophils
Monocytes -> macrophage

Question 8

What do common lymphoid progenitors differentiate into?

Answer 8

Small lymphocytes

Question 9

What do small lymphocytes differentiate into?

Answer 9

B lymphocytes

T lymphocytes

Question 10

What are the features of haemopoietic stem cells?

Answer 10

Capable of self-renewal

Given appropriate stimuli can differentiate into variety of specialised cells

Question 11

What is extramedullary haematopoiesis?

Answer 11

In pathological conditions such as myelofibrosis or thalassaemia haemopoietic stem ells can mobilise into circulating blood to colonise other tissues

Question 12

What is the reticuloendothelial system (RES)?

Answer 12

Part of immune system and made up of monocytes in blood and a network of tissues which contain phagocytic cells

Question 13

What is the role of the RES?

Answer 13

To remove dead or damaged cells and identify and destroy foreign antigens in blood and tissues

Question 14

What are the main organs of the RES?

Answer 14

Spleen and liver

RES cells in spleen dispose of blood cells

Question 15

What are the functions of the spleen in adults?

Answer 15

Sequestration and phagocytosis
Blood pooling (platelets and RBC can be rapidly mobilised during bleeding)
Extramedullary haemopoeisis
Immunological function

Question 16

What can cause splenomegaly?

Answer 16

Back pressure - portal hypertension in liver disease
Over work (red or white pulp)
Extramedullary haemopoeisis
Expanding as infiltrated by cells (cancer)
Expanding as infiltrated by other material

Question 17

What is hypersplenism?

Answer 17

Low blood counts occur due to pooling of blood in enlarged spleen

Question 18

What is hyposplenism?

Answer 18

Lack of functioning splenic tissue

Question 19

What can cause hyposplenism?

Answer 19

Splenectomy
Sickle cell disease
Gastrointestinal diseases (coeliac, Crohns, ulcerative colitis)
Autoimmune diseases (systemic lupus, rheumatoid arthritis)

Question 20

What are Howell Jolly bodies?

Answer 20

RBC with DNA remnants - normally removed by spleen

Question 21

What are patients with hyposplenism at risk of?

Answer 21

Sepsis from encapsulated bacteria
E.g. streptococcus pneumonia, haemophilus influenzae, meningococcus
Patients must be immunised and given life long antibiotic prophylaxis

Question 22

What happens when there are changes to the RBC plasma membrane?

Answer 22

Causes cell to become less derformable and more fragile

Question 23

What proteins are involved in hereditary spherocytosis?

Answer 23

Spectrin
Ankyrin
Band 3
Protein 4.2

Question 24

What is spectrin?

Answer 24

Actin crosslinking and molecular scaffold protein that links plasma membrane to actin cytoskeleton

Question 25

What is ankyrin?

Answer 25

Links integral membrane proteins to the underlying spectrin-actin cytoskeleton

Question 26

What is band 3 protein?

Answer 26

Facilitates chloride and bicarbonate exchange across membrane and also involve in physical linkage of membrane to cytoskeleton (binds wit ankyrin and protein 4.2?

Question 27

What is protein 4.2?

Answer 27

ATP-binding protein which may regulate the association of band 3 with ankyrin

Question 28

Describe the degradation of haem

Answer 28

Senescent RBC engulfed by macrophage in reticuloendothelial system Haem is recycled as Fe2+ or converted to bilirubin Unconjugated bilirubin transported in blood bound to albumin Some bilirubin taken up by liver ad conjugated with glucuronic acid Conjugated bilirubin secreted in bile into duodenum Either into faeces or reabsorbed and excreted in urine

Question 29

What is the conjugated form of bilirubin?

Answer 29

Bilirubin diglucoronide

Question 30

What form of bilirubin is in faeces?

Answer 30

Stercobilin

Question 31

What form of bilirubin is in urine?

Answer 31

Urobilin

Question 32

What is cytopenia?

Answer 32

A reduction in the number of blood cells

Question 33

What does ...cytosis or ...philia at the end of a word mean?

Answer 33

An increase in the number of blood cells

Question 34

What are neutrophils?

Answer 34

First-responder phagocyte Most common white cel Essential part of innate immune system Circulate in bloodstream and invade tissues (lifespan 1-4 days)

Question 35

What is the maturation of neutrophils controlled by?

Answer 35

The hormone G-CSF, a glycoproteins growth factor and cytokine

Question 36

What does G-CSF do?

Answer 36

Increases production of neutrophils Speeds up releas of mature cells from BM Enhances chemotaxis Enhances phagocytosis and killing of pathogens

Question 37

When is recombinant G-CSF administered?

Answer 37

When more neutrophils are needed | E.g. a patient with severe neutropenia and sepsis after chemotherapy

Question 38

What is neutrophilia?

Answer 38

An increase in the absolute number of circulating neutrophils

Question 39

What can cause neutrophilia?

Answer 39

``` Infection Tissue damage Smoking Myeloproliferative diseases Cancer Acute haemorrhage ```

Question 40

How does acute haemorrhage cause neutrophilia?

Answer 40

Neutrophils usually stick to endothelial cells of vessels | These are released in haemorrhage increasing the number of circulating neutrophils

Question 41

What are the consequences of neutropenia?

Answer 41

Severe life threatening bacterial infection Severe life threatening fungal infection Mucosal ulceration

Question 42

What causes reduced production of neutrophils and therefore neutropenia?

Answer 42

``` B12/folate deficiency Aplastic anaemia Viral infection Congential Drugs Radiation ```

Question 43

What causes increased removal or use of neutrophils and therefore neutropenia?

Answer 43

Immune destruction Sepsis Splenic pooling

Question 44

What are the features of monocytes?

Answer 44

Largest cells in blood In tissues differentiate into macrophages or dendritic cells Phagocytose microorganism and breakdown/remove cellular debris Antigen presenting role to lymphocytes Defence against chronic bacterial infections

Question 45

What are the causes of monocytosis?

Answer 45

Bacterial infection Inflammatory conditions Carcinoma Myeloproliferative disorders and leukaemias

Question 46

What are the features of eosinophils?

Answer 46

Responsible for immune response against multicellular parasites Mediator of allergic responses Granules contain array of cytotoxic proteins Phagocytosis of antigen-antibody complexes

Question 47

What are the common causes of eosinophilia?

Answer 47

Allergic diseases Parasitic infection Drug hypersensitivity Skin diseases

Question 48

What are basophils?

Answer 48

Large dense granules containing histamine, heparin, hyaluronic acid, serotonin Granules stain deep blue Active in allergic reactions and inflammatory conditions

Question 49

What are the 3 types of lymphocytes?

Answer 49

Bc ells T cells Natural killer cells

Question 50

What can cause lymphocytosis?

Answer 50

``` Viral infections Bacterial infections Stress related: MI/cardiac arrest Post splenectomy Smoking Leukaemia Lymphoma ```