Session 6 - Haemopoesis, the spleen and bone marrow Flashcards
Understand and explain the basics of haemopoiesis:
What is haemopoiesis?
Haemopoiesis is the process by which blood cells are formed.
It involves specification of blood cell lineages, and proliferation, to maintain an adequate number of cells in the circulation
Where does haemopoiesis occur before and after birth?
- Early embryo –process begins in the vasculature of the yolk sac before shifting to the embryonic liver by ~week 5-8 gestation
- After birth–sole site of haemopoiesis is in bone marrow
Understand and explain the basics of haemopoiesis:
What is haemopoiesis driven by?
Haemopoetic stem cells
Describe where the production of blood cells occurs in adults and infants
- In adults = limited distribution (pelvis, sternum, skull, ribs, vertebrae)
- In infant = extensive throughout skeleton
Name the 5 major lineage pathways that arise from haemopoetic stem cells
- Thrombopoiesis
- Erythropoeisis
- Granulopoeisis
- Monocytopoeisis
- Lymphopoeisis
What determines the differentiation of haemopoeitic stem cells into different lineages?
- Hormones
- Transcription factors
- Interactions with non-haemopoetic cell types (e.g. endothelial cells)
Describe the pathways that lead to the production of different blood types
Name 2 important hormones in haemopoeisis
1) Erythropoietin
2) Thrombopoietin
What is Erythropoietin secreted by and what does it do?
- Secreted by kidney
- Stimulates red blood cell production
What is Thrombopoietin secreted by and what does it do?
- Produced by liver and kidney
- Regulates production of platelets
Describe the process of thrombopoiesis
-Thrombopoiesis results in the ultimate formation of platelets involved in clot formation
- Platelets have no nuclei and are membrane bound fragments of cytoplasm that bud off from megakaryocytes
What is another name for platelets?
Thrombocytes
Describe the process of granulopoiesis
Granulopoiesis is the process by whichgranulocytes arise from myeloblast cells which in turn arise from common myeloid progenitor cells
Identify the three granulocytes
Describe the process of monocytopoiesis
Monocytopoiesisis the process which leads to the production of monocytes (andsubsequently, macrophages)
What do monocytes do?
Monocytes circulate in the blood for ~1-3 days before moving into tissues where they differentiate into macrophages or dendritic cells
Describe the process of lymphopoiesis
Lymphopoiesisis the process in which lymphocytes develop from a common lymphoid progenitor cell
Identify some lymphocytes
- B cells
- T cells
- Natural killer cells
Describe the process of erythropoiesis
Erythropoiesis is the process by which red blood cells are produced from a common myeloid progenitor cell in the bone marrow
What is another name for red blood cells?
Erythrocytes
Describe the function of erythrocytes (6)
- Transports oxygen to tissues around the body and transports CO2 to your lungs for you to exhale
Describe the function of T - lymphocytes (5)
- Major component of the adaptive immune system
- Directly killing infected host cells
- Activating other immune cells
- Producing cytokines
- Regulating the immune response
Describe the function of B - lymphocytes (3)
- Form part of the adaptive immune response by producing antibodies
- And presenting antigens to T cells
- Once activated, they can mature into plasma cells or memory B lymphocytes
Describe the functions of Thrombocytes (2)
- Plugging and repairing damaged blood vessels, thus preventing blood loss
- Participate in the cascade of events that lead to blood clotting by triggering the release of a series of coagulation factors
Describe the function of Monocytes (5)
- Monocytes circulate in the blood for 1-3 days before moving into tissues where they differentiate into macrophages or dendritic cells
- Normally largest cells in blood
- Phagocytose microorganisms and breakdown/remove cellular debris
- Antigen presenting role to lymphocytes
- Important in defence against chronic bacterial infections (e.g. tuberculosis) and chronic fungal infections
Describe the function of Macrophages
- The front line in fighting viruses, bacteria, fungi and protozoa that enter your body
- Macrophage cells surround the invading microbe and ingest and kill it with toxic enzymes within the cell
- They also help to remove dead cells from the tissues and bloodstream
Describe the function of neutrophils
- Phagocytose and destroy foreign organisms First-responder phagocyte
- Most common white cell
- Essential part of innate immune
system - Circulate in bloodstream & invade
tissues – live for 1-4 days
Describe the function of eosinophils
- Effector cells
- Actions against parasitic infections and involved in many different immune responses
- Pathalogiclly take part in allergic reactions
Describe the function of basophils
- Least common and large
- Active in allergic reactions and inflammatory conditions
- Large dense granules containing histamine, heparin, hyaluronic acid, serotonin
- Granules stain deep blue to purple and often so numerus they mask nucleus-
- Circulating leucocytes that contain histamine, which they release as part of the immune response
Describe the role of the spleen
- Sequestration and phagocytosis old/abnormal red cells removed by macrophages (They are removed, broken down and have their contents recycled)
(In other words, it acts as a blood filter - red pulp removes old red cells and metabolises the haemoglobin, and white pulp synthesises anti bodies and removes antibody-coated bacteria and blood cells)
- Blood pooling - Spleen contains a reservoir of platelets and red cells, which can rapidly be mobilised during a period of bleeding, in order to minimise blood loss
- Extramedullary haemopoiesis (haemopoeises outside the bone marrow):
If the bone marrow every becomes infected, such that it’s not a very good microenvironment for the haemopoetic system to develop, the haemopoetic stem cells can come out of circulation, seed in the spleen and you can get haemopoetic tissue in the spleen. Pluripotential stem cells proliferate during haematological stress or if marrow fails (e.g. in myelofibrosis), hence patients with myelofibrosis sometimes have a big spleen. - Immunological function 25% of T cells and 15% of B cells are present in spleen e.g. red cells perform phagocytosis of opsonised bacteria by macrophages and also antigen presenting cells may enter white pulp , resulting in activation of the T-lymphocytes stored there
Understand the causes of splenomegaly
- Back pressure- portal hypertension in liver disease
- Over work (red or white pulp)
- Reverting to what it used to do-
extramedullary haemopoiesis in the spleen - Expanding as infiltrated by cells
- Cancer cells of blood origin e.g. leukaemia
- Other cancer metastases
- Expanding as infiltrated by other
material - Sarcoidosis (granulomas)
Learn either explanation:
Enlargement of the spleen (splenomegaly) is typically associated with an increased workload, for example in haemolytic anaemia where an increased number of defective red cells are removed from the circulation. Other causes include congestion due to portal hypertension in liver diseases which (increases back pressure), infiltration by leukaemias and lymphomas and expansion due to accumulation of waste products of metabolism (e.g. in Gaucher’s disease, a defect in the beta-glucosidase enzyme which catalyses the breakdown of glucocerebroside (a constituent of red and white blood cell membranes), causes glucocerebroside to accumulate in fibrils). Some infectious diseases are also characterised by splenomegaly, most notably malaria, schistosomiasis, HIV and glandular fever caused by Epstein Barr virus.
Name infections that lead to 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
Understand the clinical significance of splenomegaly
Describe what can occur in hypersplenism
- When the spleen enlarges, the patient’s blood count can appear low and they may look anaemic, might have a low white cell count and might have a low platelet count
- Not because the bone marrow is not producing cells, but rather most of the cells will go into the spleen (there is greater splenic pooling)
Clinical significance:
- An enlarged spleen is no longer protected by the rib cage so it is at risk of rupture
- Therefore, avoid contact sports and vigorous activity
What should people with splenomegaly avoid and why?
- As clinicians, you need to warn patients with splenomegaly to be very careful:
- They should avoid contact sports and vigorous contact activity
- This is because there is a risk of rupture if your spleen is enlarged and no longer protected by the crib cage
What are the dangers of rupturing your spleen?
- You can lose a huge amount of blood into your abdomen, usually a hidden bleed to begin with
What is hyposplenism?
Lack of functioning splenic tissue/reduced splenic function
Give some causes of hyposplenism
What would a blood film of a patient with hyposplenism contain ?
- Howell-Jolly bodies (DNA remnants found in circulating erythrocytes)
Why are Howell Jolly bodies a good indication of hyposplenism?
- During erythroopoeiss, erythroblasts normally expel their nucle, but in some cases, a small portion of DNA remains
- Red cells containing these inclusion bodies, will normally be removed by a fully functioning spleen, so the presence of Howell Jolly bodies is a good indicator of reduced splenic function
What are patients with hyposplenism at risk of and why, and what action must be taken as a result?
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
Explain the concepts of a normal range and be able to assess whether a laboratory test is likely to be normal or abnormal.
Summary:
Normal range is estimated from volunteers and includes 95% of the healthy population (can vary from region to region).
Remember, 2.5% normal values sit below the range and 2.5% normal values sit above the range.
Normal range can change with: age, sex, ethnicity or co-morbidities
For understanding:
Put simply, an abnormal result is one which falls outside the normal range of values or is drastically different to a previous result.
A normal range is a set of values within which a healthy patient should fall(for normal ranges, please refer to Figure 1 NB that normal ranges can vary between laboratories).
However, a normal range is by no means a perfect measure. The normal range will only include values for 95% of the normal healthy population. Therefore, 2.5% of the population will lie outside of the normal range without any pathology.
Therefore it is extremely important to not be blinkered by any blood tests. Blood tests should only be used as an adjunct to a good history and examination and should always be interpreted in the clinical context of the patient and in relation to any previous blood results.
The normal range also changes for different populations, and can be affected by; age, sex, ethnicity and co-morbidities.
A blood result may be abnormal if it shows a large change as blood values should not usually change physiologically.
If a result is unexpected the blood test should always be repeated as there are several sources of errors in processing a FBC:
Describe the clinical significance of hyposplenism
Clinical significance:
- Risk of sepsis from encapsulated bacteria
- Patients need to be immunised and given long life antibiotic prophylaxis
What are reticulocytes? (4)
- Immature RBC’s
- They have just been released from the bone marrow into the blood
- They have lost their nucleus and are one step away from becoming a mature red cell
- We identify them based on the fact that they have quite a lot of RNA in them and their size
How are reticulocytes counted?
- Using special stain or fluorescent dyes which bind to ribosomal RNA (rRNA is not present in more mature red cells)
What is the reticulocyte count test important for?
OR
Explain the significance of the reticulocyte count
- Very useful test in evaluating different kinds of anaemia
- Telling you if its something you need to be massively concerned about or generally concerned about
Increased reticulocyte count:
- Indicates that there is recent loss of RBCs and the body is compensating by producing new RBCs (reticulocytes)
e.g. haemolytic anaemia, response to EPO etc.
Decreased reticulocyte count:
- Either due to haematinic deficiency (doesn’t have the components to make RBCs)
- Bone marrow deficiency
Give 4 causes of decreased reticulocyte count
- Haemantic deficiency (not enough iron)
- Bone marrow failure
- Parvovirus infection
- Aplastic anaemia
Give 6 causes of increased reticulocyte count
- Haemolytic anaemia (red cell destruction)
- Recent blood loss (bleeding)
- Response to iron, Vit B12, folate replacement
- Response to EPO (when patients get given EPO)
- Recovery from bone marrow suppression
- High altitudes
Name the types of blood cells and what an increase and decrease in the cell type is called
Be familiar with the teminology used to describe erythrocytes
Check slides for more - lecture 2
Explain the meaning and possible clinical significance of the terms that are frequently used to describe abnormalities in a blood count or film
CHECK LECTURE AND WORKBOOK
Display an understanding of how a FBC is analysed
DISCUSSION BOARD
Understand the terms used to describe blood cell parameters and appearance
Lecture and workbook?
Name some RBC Inclusions and describe them
See lecture for images
Be able to assess whether a laboratory test is likely to be normal or abnormal.
You will be given the normal range in brackets in examination questions involving laboratory tests.
For example:
The patient had a platelet count of 396 x 109/L (140 - 400)
