5. Haemopoiesis Flashcards
What is haemopoiesis?
Production of mature blood cells and platelets
Where does production of blood cells occur?
Production of blood cells occurs in the bone marrow
Where is bone marrow found in children and adults?
- Bone marrow extensive throughout the skeleton in infant
- More limited distribution in adulthood - It can be found in the axial skeleton; pelvis, sternum, skull, ribs and vertebrae.
What is the process by which bone marrow can be extracted?
Bone marrow can be exctracted using a trephine biopsy to allow examination
What is the differentiation of haemopoietic stem cells in bone marrow Determined by?
- Hormones
- Transcription factors
- Interactions with non-haemopoietic cell types (e.g.endothelial cells)
What is erythropoietin?
Erythropoietin is a hormone secreted by kidney and stimulates red blood cell production
What is thrombopoietin?
Thrombopoietin is a hormone produced by liver and kidney and regulates production of platelets.
What is the function of Haemopoietic stem cells (HPSCs)?
- Capable of self-renewal (more than any other adult tissue)
* Given appropriate stimuli can differentiate into variety of specialised cells
Are Haemopoietic stem cells found in the plasma ?
HSPCs are never normally found in the blood - their presence indicates pathology
In which condition would HSPCs be found in the plasma?
In pathological conditions e.g. myelofibrosis or thalassaemia HSPCs can mobilize into circulating blood to colonise other tissues (extramedullary hematopoiesis)
What are the Sources of HSPC?
- Bone marrow aspiration (rarely done)
- GCSF mobilised peripheral blood stem cells (collected by leucopharesis)
- Umbilical cord stem cells
What is the Reticuloendothelial system (RES)?
Part of immune system and made up of monocytes in blood and a network of tissues which contain phagocytic cells
What is the function of Reticuloendothelial system (RES).
Role to remove dead or damaged cells and identify and destroy foreign antigens in blood and tissues.
What are the main organs of the Reticuloendothelial system (RES)?
Main organs are spleen and liver
Give the function of RES cells in the spleen
RES cells in spleen dispose of blood cells, in particular damaged or old red cells
What are the 2 types of pulp in the spleen?
Red pulp: sinuses lined by endothelial macrophages and cords
White pulp: similar structure to lymphoid follicles
What are the functions of the spleen?
• Sequestration and phagocytosis - old/abnormal red cells removed by macrophages
• Blood pooling - platelets and red cells can be rapidly mobilised during bleeding
• Extramedullary haemopoiesis - pluripotential stem cells
proliferate during haematological stress or if marrow fails (e.g. in myelofibrosis)
• Immunological function - 25% of T cells and 15% of B cells are present in spleen
How does blood enter the spleen?
Blood enters via the splenic artery
Where does white blood cells and red blood cells pass through in the spleen?
- White cells and plasma preferentially pass through the white pulp - where foreign material is taken to stimulate immune system
- Red cells preferentially pass through the red pulp
Why would the spleen grow(splenomegaly)?
• Back pressure as fibrosis of liver makes it hard for blood to flow through which increases pressure in splenic artery - portal hypertension in liver disease
• Over work (red or white pulp)
• Reverting to what it used to do- extramedullary haemopoiesis
• Expanding as infiltrated by cells
> Cancer cells of blood origin e.g. leukaemia
>Other cancer metastases
• Expanding as infiltrated by other material
> Sarcoidosis (granulomas)
How is examination of the spleen done?
- It is never normal for the spleen to be palpable below the costal margin
- Start to palpate in Right Iliac Fossa (RIF) or may miss massive splenomegaly
- Feel for spleen edge moving towards your hand on inspiration
- Feel for the splenic notch
- Measure in cm from costal margin in mid- clavicular line
What can multipotential hematopoietic stem cells differentiate into?
Common myeloid progenitor and common lymphoid progenitor
What can common myeloid progenitors differentiate into?
Megakaryocytes
Erythrocytes
Myeloblasts
What can common lymphoid progenitors differentiate into?
Small lymphocytes
In which tissues are the following macrophages found? Kupffer cell Tissue histiocyte Microglia Peritoneal macrophage Red Pulp Macrophage Langerhans cell
Kupffer cel l= Liver Tissue histiocyte = Connective tissue Microglia = Central nervous system Peritoneal macrophage= Peritoneal cavity Red Pulp Macrophage = Spleen Langerhans cell = Skin and Mucosa
Give causes of massive, moderate and mild splenomegaly
Massive
• Chronic myeloid leukaemia• Myelofibrosis • Malaria
• Schistosomiasis
Moderate – as above, plus
• Lymphoma • Leukaemias • Myeloproliferative disorders
• Liver cirrhosis with portal hypertension
• Infections such as Glandular Fever
Mild – as above, plus • Infectious hepatitis • Endocarditis
• Infiltrative disorders such as sarcoidosis
• Autoimmune diseases such as AIHA, ITP, SLE
Hypersplenism definition
Hypersplenism refers to overactivity of the spleen causing the spleen to remove blood components at an excessive rate.
An enlarged spleen means more blood can pool in the spleen which cause blood levels to be low as more of the blood is pooling in the spleen and less is in circulation. - results in low blood count
What is the Effect of splenomegaly on daily life of the patient
Risk of rupture if spleen enlarged and no longer protected by rib cage - Need to Avoid contact sports and vigorous activity
Hyposplenism definition
Lack of functioning splenic tissue
What are the causes of Hyposplenism?
• Splenectomy May be required due to splenic rupture from trauma or because of cancer • Sickle cell disease In older children and adults due to multiple infarcts & fibrosis • Gastrointestinal diseases > Coeliac disease > Crohn’s disease > Ulcerative colitis • Autoimmune disorders > Systemic lupus > Rheumatoid arthritis > Hashimoto’s disease
What are Patients with hyposplenism at risk of? How can the risk be reduced?
Patients with hyposplenism are at risk of sepsis
from encapsulated bacteria e.g.
• Streptococcus pneumonia
• Haemophilus influenzae
• Meningococcus
Patients must be immunised and given life long antibiotic prophylaxis
What is visible in blood in hyposplenism?
Howell Jolly bodies (DNA remnants) - Red cells containing these inclusion bodies would normally be removed by a fully functioning spleen. Thus their presence indicates that the spleen is not functioning properly
What are vital statistic of erythrocytes?
• RBC (Red Blood Cell Count) How Many?
4.4 - 5.9 x 1012/l
• Hb (Haemoglobin) How effective?
13.5 - 16.7 g/dl
• MCV (Mean Corpuscular Volume) How large?
80 - 100fl
• Biconcave flexible disc ~8mm diameter Shape?
What are the functions of Erythrocytes?
• Deliver oxygen to tissues • Carry haemoglobin • Maintain haemoglobin in its reduced (ferrous) state • Maintain osmotic equilibrium • Generate energy
Structure of haemoglobin
Haemoglobin is a tetramer of 2 pairs of globin chains
each with its own haem group which contains iron.
What is the Position of globin genes in chromosomes
Globin gene clusters on Ch 11 & 16.
At what age during the life span is there the switch from fetal to adult Hb?
The switch from fetal to adult Hb occurs at ~3-6 months of age
What are the 2 configuration of Hb?
The relaxed R state
The tight T state
How can RBC change shape?
RBCs change shape by changing the components of the cell membrane.
Why is it important for the RBC to be able to change shape?
This is because as a part of their role RBCs are constantly having to squeeze into small areas, this means that they’re have to be flexible to bend and fit into small areas or else they’ll break down forcing themselves into these tight areas.
