Bone Marrow and Blood Cells Flashcards
Where does haemopoiesis take place in a 0-2 month old foetus?
The yolk sac
Where does haemopoiesis take place in a 2-5 month old foetus?
Liver and spleen
Where does haemopoiesis take place in a 5-9 month old foetus?
Bone marrow
Where does haemopoiesis take place after birth?
Bone marrow
In the bone marrow of which bones does haemopoiesis take place in infants?
Most bones
In the bone marrow of which bones does haemopoiesis take place in adults?
Vertebrae
Ribs
Sternum
Sacrum and pelvis
Proximal end of femur
What is bone marrow?
Soft, spongy, gelatinous tissue found in the hollow space in the interior of bones
What does bone marrow consist of?
Stem cells supported by stroma
What is produced in bone marrow?
Red blood cells
Platelets
Most white blood cells
What are the two different types of bone marrow?
Red marrow
Yellow marrow
What tissue is the main constituent of red marrow?
Haemopoietic tissue
What tissue is the main constituent of yellow marrow?
Fatty tissue
All marrow is what type at birth?
Red marrow
What proportion of marrow is red marrow in adulthood?
Half
What happens to half of the bodies red marrow between birth and adulthood?
It is converted to yellow marrow
How can bone marrow be examined histologically?
By taking a trephine biopsy of the marrow in the pelvis
What is the starting cell for haemopoiesis?
Multipotent haemopoietic stem cell
What cells can a multipotent haemopoietic stem cell become differentiate into?
Common myeloid progenitor
Common lymphoid progenitor
A common myeloid progenitor cell can eventually differentiate into which mature blood cells?
Platelets
Erythrocytes (RBC)
Mast cell
Basophil
Neutrophil
Eosinophil
Macrophage
Under the influence of what hormone does a common myeloid progenitor cell begin differentiating to platelets?
Thrombopoietin
Thrombopoietin causes common myeloid cells to differentiate into which cell initially?
Megakaryocytes
How do megakaryocytes become platelets?
Increase in size
Replicate DNA
Platelets bud from cytoplasm
What causes megakaryocytes to produce platelets?
Thrombopoietin
What causes common myeloid progenitor cells to differentiate into red blood cells?
Erythropoietin
During the process of erythropoiesis, what cells form before becoming a red blood cell?
Proerythroblast
Early normoblast
Intermediate normoblast
Late normoblast (nucleated red cell)
Reticulocyte
Erythrocytes
What percentage of new circulating red blood cells are reticulocytes?
1%
How long before a reticulocyte matures to an erythrocyte?
1-2 days
What is the lifespan of an erythrocyte?
~120 days
What process occurs first in the production of erythrocytes?
Haemoglobinisation of cytoplasm
What process occurs secondly in production of erythrocytes?
Nuclear maturation
What process occurs lastly in the formation of erythrocytes?
Nuclear extrusion
What two different types of tissue does the spleen consist of?
Red pulp
White pulp
Describe the structure of red pulp
Sinuses lined by endothelial macrophages and cords
Describe the structure of white pulp
Similar structure to lymphoid follicles
How does blood enter the spleen?
Via the splenic artery
The splenic artery is a branch of what?
The celiac trunk
Name the other branches of the celiac trunk (not including the splenic artery)
Left gastric artery
Common hepatic artery
White cells and plasma preferentially pass through which tissue of the kidney?
White pulp
Red blood cells preferentially pass through which tissue of the kidney?
Red pulp
What can red pulp do with red blood cells?
Sequester them
List the 4 main functions of the spleen
Sequestration and phagocytosis
Blood pooling
Extramedullary haemopoiesis
Immunological function
Explain sequestering and phagocytosis in relation to the spleen
Old/abnormal red blood cells can be sequestered by the red pulp and removed by phagocytosis
Explain the spleens blood pooling function
Platelets and red blood cells can be rapidly mobilised by the spleen during bleeding
Explain the spleens extramedullary haemopoiesis function
Pluripotent stem cells proliferate during haematological stress or if the marrow fails (e.g. myelofibrosis)
Explain the spleens immunological function
25% of T cells and 15% of B cells are present in the spleen
What is an enlarged spleen known as?
Splenomegaly
How can splenomegaly be defined on examination?
Feeling the spleen below the costal margin
How is the splenomegaly palpated for?
Start palpating in the right iliac fossa ( to avoid missing massive splenomegaly) and move diagonally
You will feel an enlarged spleen edge move towards your hand on inspiration
Feel for the splenic notch
Measure in cm the distance from the costal margin in the mid-clavicular line
Give reasons for splenomegaly
Back pressure of blood
Over working red pulp
Over working white pulp
Conducting extramedullary haemopoiesis
Expansion due to infiltration by malignant cells (of blood origin e.g. leukaemia or metastases)
Expansion due to infiltration by other material
What can cause back pressure of blood in the spleen?
Portal hypertension in liver disease
What conditions can cause massive splenomegaly?
Chronic myeloid leukaemia
Myelofibrosis
Chronic malaria
Schistosomiasis
What conditions can cause moderate splenomegaly?
As with massive, PLUS:
Lymphoproliferative disorders
Myeloproliferative disorders
Liver cirrhosis with portal hypertension
Infections such as glandular fever
What conditions can cause mild splenomegaly?
As with massive and moderate, PLUS:
Hepatitis
Endocarditis
Sarcoidosis
SLE
What changes to blood count can occur as a result of splenomegaly?
Pancytopenia or thrombocytopenia
Define thrombocytopenia
Low platelet count
Why can pancytopenia and thrombocytopenia occur in splenomegaly?
There can be increased pooling of blood within the enlarged spleen
What is increased pooling of blood in the spleen known as?
Hypersplenism
What is at risk of occurring when the spleen is enlarged?
Rupturing of the spleen
Why is spleen rupture a risk in splenomegaly?
As the spleen is no longer protected by the rib cage
Define hyposplenism
Lack of functioning splenic tissue
What can cause hyposplenism?
Splenectomy
Sickle cell disease in older children and adults (due to multiple infarcts of the spleen followed by fibrosis)
Coeliac disease
What is seen on a blood film in people with hyposplenism?
Howell Jolly bodies
What are patients with hyposplenism at risk of?
Overwhelming sepsis
People with hyposplenism are particularly at risk from sepsis caused by which types of organisms?
Encapsulated organisms
E.g. pneumococcus, haemophilus influenzae, and meningococcus
Define cytopenia
Reduction in the number of blood cells
Give 5 different forms of cytopenia
Anaemia
Leucopenia
Neutropenia
Thrombocytopenia
Pancytopenia
Anaemia is a low count of which cell?
Red blood cell
Leucopenia is a low count of which cell?
White blood cells
Neutropenia is a low count of which cell?
Neutrophils
Thrombocytopenia is a low count of which cell?
Platelets
Pancytopenia is a low count of which cells?
Red blood cells, white blood cells, and platelets
Thrombocytopenia can generally caused by an increase and decrease in what?
Increased removal or use
Decreased production
What can cause increase removal or use of platelets?
Immune destruction
Non-immune destruction
Splenic pooling
Many drugs
What is the most common auto-immune cause of thrombocytopenia?
Immune thrombocytopenic purpura (ITP)
What immunity related problems can thrombocytopenia occur secondary to?
SLE
Lymphoma
CLL
How can thrombocytopenia due to immune destruction be treated?
Immunosuppression (corticosteroids or pooled human immunoglobulin)
What treatment will not work in thrombocytopenia due to immune destruction?
Platelets transfusion
Why will platelet transfusion not work to treat thrombocytopenia due to immune destruction?
Because the transfused platelets will be destroyed also
What non-immunity related causes can cause thrombocytopenia ?
Microangiopathic haemolytic states
Cardiopulmonary bypass surgery
What can cause reduced production of platelets?
B12/folate deficiency
Infiltration of bone marrow by cancer/fibrosis
Aplastic anaemia
Drugs - chemotherapy, co-trimoxazole
Viruses - HIV, EBV, CMV, viral hepatitis
What can happen as a result of thrombocytopenia?
Easy bruising
Petechiae, purpura
Mucosal bleeding
Severe bleeding after trauma or procedures
Intracranial haemorrhage
Numerically define neutropenia
Neutrophil count <1.5x10^9/L
Neutropenia can generally be caused by an increase and decrease in what?
Increased removal or use of neutrophils
Decreased production of neutrophils
What can cause increased removal or use of neutrophils?
Splenic pooling
Sepsis
Immune destruction
What can cause reduced production of neutrophils?
B12/folate deficiency
Infiltration of bone marrow
Aplastic anaemia
Radiation
Drugs
Viral infection
Congenital disorders
What drugs can cause neutropenia?
Chemotherapy
Antibiotics
Anti-epileptics
Psychotropic drugs
Rituximab
What can happen as a consequence of neutropenia?
Severe life threatening bacterial infection
Severe life threatening fungal infection
Mucosal ulceration
Is neutropenic sepsis worrying?
YES - it’s a medical emergency
What should be given immediately to someone with neutropenic sepsis?
IV antibiotics
Pancytopenia can generally be caused by an increase and decrease in what?
Reduced production of blood cells
Increased removal of blood cells
What can cause increased removal of RBCs, WBCs and platelets?
Splenic pooling due to hypersplenism
What can cause reduced production induced pancytopenia?
B12/folate deficiency
Bone marrow infiltration by malignancy
Marrow fibrosis
Aplastic anaemia
Radiation
Drugs
Viruses
Congenital bone marrow failure
What is aplastic anaemia?
Pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate and with no increase in reticulin (fibrosis)
What kinds of malignancy can cause pancytopnenia?
Haematological malignancy
Non-haematological malignancy
What haematological malignancies can cause pancytopenia?
Acute and chronic leukaemia
Lymphoma
Myeloma
Myelofibrosis
What non-haematological malignancies can cause pancytopenia?
Prostate
Breast
Lung
What are the symptoms of pancytopenia?
Symptoms of anaemia
Symptoms of thrombocytopenia
Symptoms of neutropenia
Symptoms of underlying cause
What are the symptoms of anaemia?
Fatigue
Dizziness
Chest pain
SoB
What are the symptoms of thrombocytopenia?
Bleeding
Bruising
What are the symptoms of neutropenia?
Infection
Ulcers
Fevers
