1. Physiology of Blood Cells and Haematological Terminology Flashcards
What are all blood cells derived from and where do they originate?
Blood cells of all types originate in the bone marrow
They are ultimately derived from multipotent haematopoietic stem cells
What do pluripotent stem cells give rise to?
Lymphoid stem cells
Multipotent myeloid stem cells/precursors
From both of these, red cells, granulocytes, monocytes and platelets are derived
What can a multi potent lymphoid-myeloid stem cell differentiate into?
• There are TWO branches in the differentiation:
○ Multipotent Myeloid Stem Cell/Precursor
• Granulocyte-monocyte (neutrophils, eosinophils and basophils)
• Erythroid
• Megakaryocyte
○ Lymphoid Stem Cell
• T cells
• B cells
• NK cells
What are the characteristics of haematopoietic stem cells and why are they important?
- Ability to self-renew and produce mature progeny – it protects the ability of the bone marrow to produce differentiated progeny for the lifespan of the individual
- It has the ability to divide into two cells with different characteristics, one another stem cell and the other a cell capable of differentiating to mature progeny
How are erythrocytes initially produced?
• The multipotent myeloid stem cell/precursor can give rise to the proerythroblast (this is the first cell in the erythroid lineage)
• This then gives rise to erythroblasts (cells with nuclei) and then erythrocytes/red cells (without nuclei)
NOTE: the ending blast indicates that the cell is a precursor
Outline the normal erythrocyte maturation process
The proerythroblast is a large cell and its chromosomes are widespread showing that it is still an early cell
This divides into two early erythroblasts which divide into two intermediate erythroblasts which divide into two late erythroblasts
These early cells are classified based on the appearance of their cytoplasm.
How does the colour of the erythroblasts change as they mature?
As the red cells differentiate, the colour of the cytoplasm goes from dark blue to a more pink colour
This is because the mature red cell is completely pink
Why is erythropoietin important and how is it made?
• Normal erythropoiesis requires the presence of erythropoietin
• Erythropoietin is synthesised mainly in the kidneys, in response to hypoxia (but also sometimes anaemia as both reduce the amount of oxygen delivered to the kidneys)
• Erythropoietin is also partly made in the liver
• Process:
○ Hypoxia is detected by the kidneys
○ This leads to an increase in erythropoietin synthesis
○ This increases bone marrow activity
○ This leads to an increase in red cell production
Wher does erythropoietin production take place?
Mainly from juxtatubular interstitial cells in the KIDNEYS
A small amount of erythropoietin is produced in the LIVER by hepatocytes and interstitial cells
What is the lifespan of erythrocytes and how are they destroyed?
The red cells are ultimately destroyed by phagocytic cells (macrophages) in the SPLEEN but can also be anywhere else in the body
How do white cells come about and what is needed for this?
- The multipotent haemopoietic stem cell can also give rise to a myeloblast, which in turn can give rise to granulocytes and monocytes
- Cytokines and various interleukins are needed
Outline the granulocyte maturation process
- Each cell divides into 2
- Myeloblasts divide into promyelocytes which have primary granules. Pale area adjacent to the nucleus is the golgi zone where the granules are produced
- Myelocytes have primary and secondary granules (so two different colours)
- Band form is an immature neutrophil which matures through condensation of the chromatin and lobulation of the nucleus to form a mature neutrophil
Outline the main characteristics and function of neutrophils
• The neutrophil survives 7-10 hours in the circulation before migrating into the tissues where it has its main effect but it can also have an effect in the bloodstream
• Its main function is defence against infection
It phagocytoses and kills microorganisms
How can a neutrophil get out of the bloodstream?
It becomes adhesive so sticks to the endothelium. This is due to changes on the endothelium or the neutrophil. Rolls along endothelium, escapes via diapedesis, migrates through tissues in response to chemokines then undergoes phagocytosis in tissues
Outline the main characteristic of eosinophils
- Spends less time in the circulation than neutrophils
- Bigger granules and more brightly staining than the neutrophil (usually orangy red)
- Its main function is defence against PARASITIC infection
- Important in allergic responses
- It only has TWO lobes in its nucleus
Outline the characteristics of basophils
Have a role in ALLERGIC RESPONSES
In basophils there are often so many dark blue dots that you don’t even see the nucleus
Outline the characteristics of monocytes
- These spend several days in the circulation
- They are large cells with a kidney bean shaped nucleus
- Monocytes migrate to the tissues where they develop into macrophages (also called histiocytes) and other specialised cell types that have a phagocytic function
- Macrophages also store and release IRON through the breakdown of haemoglobin. It can be released again for erythropoeisis
- Finely granular cytoplasm and a large lobulated nuclei
Outline the characteristics of platelets
- Multipotent haematopoietic stem cells can also give rise to megakaryocytes and then to platelets
- It has a granular cytoplasm so the platelet produced also has granules which are needed for platelet function
- Platelets survive about 10 days in the circulation – so if someone is bleeding and has a lack of platelets then they can be given platelets through transfusion
- If someone takes aspirin then it will destroy part of the function of all the platelets and then won’t start working properly again for another 10 days when the platelets are replenished
- Platelets have a role in primary haemostasis
- Platelets contribute phospholipid, which promotes blood coagulation
Outline the characteristics of lymphocytes
- The lymphoid stem cell gives rise to B cells, T cells and NK cells
- Lymphocytes recirculate to the lymph nodes and other tissues and then back to the blood stream unlike myeloid cells that don’t re-enter the bloodstream once they leave
- The intravascular life span of lymphocytes is very variable
- It is a small cell with more nucleus than cytoplasm. The granules contain cytotoxic proteins
Define anisocytosis and poikilocytosis
Anisocytosis - red cells show more variation in SIZE than is normal
Poikilocytosis - red cells show more variation in SHAPE than is normal. Cells are more oval than round
Define microcytosis and macrocytosis. How would you determine if any of these are present?
Microcytosis – red cells are smaller than normal
Macrocytosis – red cells are larger than normal
You use LYMPHOCYTES as a reference to determine whether the cells are bigger or smaller than normal
Define the terms microcytic, normocytic and macrocytic
- Microcytic – describes red cells that are smaller than normal or an anaemia with small red cells
- Normocytic – describes red cells that are of normal size or an anaemia with normal sized red cells
- Macrocytic – describes red cells that are larger than normal or an anaemia with large red cells
What is hypochromia? What would cells with hypochromia look like and what causes hypochromia?
- Normal red cells have about ONE THIRD of the diameter that is pale
- This means that in hypochromia, the red cells appear much paler in the middle
- Definition of hypochromia: the cells have a larger area of central pallor than normal
- This results from a lower haemoglobin content and concentration and a flatter cell
- Hypochromia and Microcytosis often go together as they are both caused by a reduced synthesis of haemoglobin
- You see a rim of redness around the cell, almost all of it is pale. Such cells can often be seen in patients with thalassaemia where one or more of the globin chains are absent
Define hyperchromia. Why does this occur and what would hyperchromatic cells look like?
- Definition: the cells LACK central pallor
- This can occur because they are thicker than normal or because their shape is abnormal
- Hyperchromia has many causes since many abnormally shaped cells lack the central thinner area
What are the two different types of hyperchromatic cells?
Spherocytes and Irregularly Contracted Cells
Spherocytes are very round and hyperchromatic
Irregularly contracted cells don’t show a complete circle. They are smaller than the cells surrounding them (so contracted)
What are the characteristics of spherocytes and how do they come about?
○ They are approximately spherical in shape. The biconcave shape which would usually be hollow in the middle is lost and the indentation is filled out
○ They have a round regular outline and lack central pallor
○ They result from the loss of cell membrane without the loss of an equivalent amount of cytoplasm
○ This happens because the surface of the red cell membrane is not completely tethered to the cytoskeleton of the cell so bits of the cell membrane are lost
○ This means that the cell is forced into a spherical form
○ You get spherocytes in hereditary spherocytosis
NOTE: not all the red blood cells will be spherical. Some will be normal and some may be halfway in between spherocytes and normal RBCs
What are the characteristics of irregularly contacted cells and what causes them to come about?
○ Irregular in outline and smaller than normal cells
○ They have also lost their central pallor
○ They usually result from oxidant damage to the cell membrane and to the haemoglobin. This results in oxidation of the haemoglobin to methaemoglobin
○ The damage could be due to people injecting oxidant substances or the production of oxidant substances by the body itself (like during infection and sepsis)
○ This helps to narrow down the diagnoses
○ The body has mechanisms for protecting itself from oxygen damage – there is an enzyme within red cells called glucose 6 phosphate dehydrogenase. If people are deficient in this enzyme then they are much more susceptible to oxygen damage. They can develop these irregular contracted cells with much lower concentrations of oxidant drugs or substances than normal people
What is polychromatic and what does it indicate?
- Definition: an increased blue tinge to the cytoplasm of a red cell
- As red cells mature they go from being dark blue to pink
- The blue tinge to the cells in polychromasia indicates that the cells are young
- Reticulocytes are red blood cells that are slightly younger than the proper mature cells. They also appear slightly larger than the other circulating erythtrocytes
What are reticulocytes and how can they be observed in a blood sample?
• Reticulocytes are red blood cells that are slightly younger than the proper mature cells. They appear slightly larger than the other circulating erythtrocytes
• These reticulocytes can be stained with methylene blue
Reticulocytes can be detected using a reticulocyte stain - methylene blue
This method allows you to count the exact number of reticulocytes in the blood – they usually only make up 1-2% of the blood but this may increase in someone with haemolytic anaemia or a haemorrhage
What is poikilocytosis and what are the different cell types?
Literally means irregularly shaped cells
Different types of cells are sickle cells, spherocytes, irregularly contracted cells, target cells, elliptocytes and fragments
What are target cells and in what conditions do they occur?
• Cells with an accumulation of haemoglobin in the middle of the central pallor • They occur in: ○ Obstructive jaundice ○ Liver disease ○ Haemoglobinopathies ○ Hyposplenism
What are eliptocytes and what conditions do they occur in?
• These are elliptical in shape
• They occur in:
Hereditary Elliptocytosis – nothing wrong with body’s production of haemoglobin but the defect is in the red cell membrane so there is an abnormal shape despite normal Hb concentration
Iron Deficiency – defect in the synthesis of haemoglobin due to lack of iron so cells are hypochromatic
What are sickle cells and how do they occur?
- These are sickle shaped. There is loss of water from the cells as they start to sickle
- They result from the polymerisation of haemoglobin S (sickle haemoglobin) when it is present in a high concentration
- The sickle cell gene has to be inherited from both parents and individuals only have HbS (no HbA at all)
What are fragment cells and how do they occur?
- These don’t look like full cells
- They are also called schistocytes
- They are small pieces of red blood cells
- They indicate that a red cell has fragmented
- The fragments do still tend to have the red cell colour and sometimes even the central pallor - it’s just the shape that is different
- This happens either because the cell is defective or a normal cell has been exposed to stresses that have caused it to fragment (e.g. due to turbulent blood flow caused by a faulty artificial heart valve)
What is rouleux and why does it occur?
• These are stacks of red cells
• They resemble a pile of coins
• They result from alterations in the plasma proteins
The plasma protein levels are increased and are pushing the cells together
What are agglutinates and why do they occur?
- These form irregular clumps rather than tidy stacks seen in rouleaux
- They usually result from antibodies on the cell surface
- These antibodies make the red cells stick to each other by binding between the two red cells
What are Howell-Jolly body and what causes this to occur?
- This is a nuclear remnant in a red cell
- Commonest cause: lack of splenic function
- The spleen should remove these tiny remaining bits of nuclear material (pitting). The presence of these bodies therefore tells us the patient has inadequate splenic function
- You usually find a lot of these in the bone marrow
- This is seen in the blood film as a very precise and distinct dot
What is the difference between sign and symptom?
Sign – something that can be seen by the doctor or the patient or can be physically felt
Symptoms – cannot be seen but can be discovered through tests or can be felt internally by the patient
What do normal lymphocytes look like and what does an atypical lymphocyte look like? Why do these occur?
- Lymphocytes are normally small and round with a large nucleus and little cytoplasm
- Sometimes you get atypical lymphocytes that have a large and very visible nucleus with loads of really faint cytoplasm
- When people see a huge nucleus they expect it to be a blast but these cells have a lot of cytoplasm too
- NOTE: these are totally typical of having a viral infection - this is seen in glandular fever (infectious mononucleosis). You can also get them in other viral infections
What is left shift?
Left shift means that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood. The maturation sequence is going in reverse
What does normal neutrophil maturation look like? How would you identify left shift in a blood sample?
- You normally start off with a big cell with a big nucleus and then you get lots of granules appearing
- Then the nucleus gets smaller and smaller and start to segment
- One of the first steps in segmenting is that it becomes a slightly more squashed looking nucleus that has more of a band shape and then it starts to segment
- If someone’s blood film has a lot of these band form neutrophils then you say that there has been a left shift
- Normally, you don’t see many band forms
- If it is more severe you may also see myelocytes and promyelocytes
- Left shift suggest that you are fighting an infection because it shows that the bone marrow is chucking out lots of lymphocytes
What is toxic granulation and why does it occur?
- Toxic granulation is the heavy granulation of neutrophils
- It results from infection, inflammation and tissue necrosis
- This is also a feature of normal pregnancy
What are hypersegmented neutrophils and what causes them?
- This means there is an increase in the average number of neutrophil lobes or segments
- Normal lobe count is 3-4
- It usually results from a lack of vitamin B12 or folic acid
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