Haematopoesis - Unit 2 Flashcards
What is the composition of blood and plasma?
What is haematopoesis, where does it occur?
-Formation and development of blood cells
-Bone marrow in adults, various sites of the developing embryo
What part of the body has the richest amount of bone marrow? How much red and yellow bone marrow do we have at both and as an adult?
-Hips and spine
-At birth 100% is red marrow, in an adult ~50% is red. Yellow can revert to red if the demand is high enough.
Where do we find red bone marrow?
-Red Marrow is found in the flat bones as well as the metaphyseal and epiphyseal ends of long bones (femur, tibia and humerus)
What happens if the demand for a particular component changes?
-Bone marrow will start to produce more of this cell
What are the stages of cell development in haematopoiesis?
- 1) Haematopoietic stem cell
> Multipotent so continues to self renew but can also differentiate into any of the haematopoietic cell types - 2) Common progenitors
> Oligopotent so can self renew and differentiate into a subset of cell types - 3) Commited progenitors
> Can differentiate into only one cell type through many intermediate stages - 4) Mature cells
How does a ligand initiate haematopoesis? What are the 2 ways a signal can be sent?
Name the important 9 factors?
What are SCF? What are Interleukins ?
-(SCF) is the colony stimulating factor which enables the production of haematopoietic stem cells . It is produced by endothelial cells and fibroblasts in the bone marrow. It promotes survival and proliferation
-Interleukins determine which major branch a cell will differentiate to
How are megakaryocytes and erythrocytes formed?
What is special about BFU/CFU?
-Same progenitor (Megakaryocyte-erythroid progenitor) but are induced by different factors, both of which are secreted by organs. As the cells differentiate they become more like their mature cell and less proliferative.
> Burst forming units (BFU) are highly proliferative
> Colony forming units (CFU) are more differentiated
How is thrombopoiesis regulated?
-The production of platelets is regulated by their own levels in the blood stream
1. Thrombopoietin is produced by the liver and kidney
2. It signals to the bone marrow to increase platelet production
3. Mature platelets bind to free TPO in the blood stream and internalise and degrade it, decreasing TPO levels
- Low platelet levels = high TPO → increased platelet production
- High platelet levels = less TPO → decreased platelet production, less signalling to bone marrow
What are the stages in erythrocyte development?
How are RBCs removed and broken down?
- Over an RBCs lifetime, they become misshaped and damaged, which is recognised by macrophages from the spleen, bone marrow and liver
- RBCs are engulfed and removed from circulation by macrophages
- RBCs components are broken down; Hb is broken down into:
> Heme
Further broken down into:
- Bilirubin which is taken up by the liver for excretion
- Iron which returns to blood stream
> Globin : Further broken down into amino acids which return to blood stream
How is erythropoiesis regulated?
What is : (Clinical measures of blood)
-HCT
-RBC
-HGB
-WBC
-PLT
-MCV
-MCH
-MCHC
-RDW
What can cause anaemia? What symptoms are there?
-a condition in which there is a deficiency of red cells or haemoglobin in the blood
> Increased destruction of RBC
> Loss of blood
> Decreased production of RBC
> Defects in haemoglobin
-Results in fatigue, breathlessness, pale complexion, palpitations.
Insufficient iron intake is often a common cause as iron is needed to produce haemoglobin.
What nutritional deficiencies cause anaemia?
-Iron
-Folate
-Vitamin B12
What is Sickle cell, Aplastic anaemia and Thalassemia?
Sickle cell - Prevent oxygen reaching tissue
Aplastic anaemia - Look normal don’t make enough
Thalassemia - Inability to produce haemoglobin
Lymphopoeisis?
-Immune cells production
-Making of WBC - Leukocytes
-Circular round big nucleus
Granulopoiesis?
-Granulocyte production
-Making of WBC - Leukocytes
- Myeloid pathway
-Distorted curved nucleus
What is Leukaemia? What are the 2 ways to classify?
-A malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leucocytes
>Can occur in the myeloid (myeloid leukaemia) and lymphoid (lymphoblastic leukaemia) cells
>Acute is proliferation of immature cells (blasts) and is quick and can be often fatal particularly in older patients. >20% blasts visible in the blood (usually 1-2%)
Chronic is slow growing, involves more mature cells which don’t function properly and a prolonged disease course. Very few blasts visible
What effects/symptoms does leukaemia have?
- Excessive cell proliferation of one of the immature blood cells in the bone marrow; Causes an imbalance of blood cell types in the bone marrow, can lead to the Hematopoietic stem cells pool being depleted.
- Blast Cells are non functional their accumulation in the bone marrow disturbs normal haematopoiesis leading to neutropenia, anaemia and thrombocytopenia
> Anaemia, Infection, bleeding, swelling of lymph nodes
Leukaemia risk factors ?
Exposure to radiation
Some chemicals (occupational hazards)
Smoking
Genetic causes (other associated conditions)
Past chemotherapy
Blood Disorders
Auto immune conditions
Viruses
How does chromosome translocation cause leukaemia? (A-9 / B-22)
-Causes ALWAYS on tyrosine kinase which drives cell proliferation
What is the treatment for Leukaemia?
Chemotherapy for Leukaemia has several phases (some just have two phases)
Induction – First stage aimed at killing as many cells as possible. At this point other treatments may also be given to treat symptoms e.g. blood transfusion.
Consolidation – Aims to kill any remaining leukaemia cells
Maintenance – Regular doses of chemotherapy to prevent relapse of the leukaemia
The choice of chemotherapy varies between the types and can be specifically tailored for an individual patient
As well as starting chemotherapy many patients will be given a blood transfusion and antibiotics
