1. Physiology of Blood Cells and Haematological Terminology

Question 1

What are all blood cells derived from and where do they originate?

Answer 1

Blood cells of all types originate in the bone marrow

They are ultimately derived from multipotent haematopoietic stem cells

Question 2

What do pluripotent stem cells give rise to?

Answer 2

Lymphoid stem cells
Multipotent myeloid stem cells/precursors
From both of these, red cells, granulocytes, monocytes and platelets are derived

Question 3

What can a multi potent lymphoid-myeloid stem cell differentiate into?

Answer 3

• 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

Question 4

What are the characteristics of haematopoietic stem cells and why are they important?

Answer 4

• 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

Question 5

How are erythrocytes initially produced?

Answer 5

• 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

Question 6

Outline the normal erythrocyte maturation process

Answer 6

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.

Question 7

How does the colour of the erythroblasts change as they mature?

Answer 7

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

Question 8

Why is erythropoietin important and how is it made?

Answer 8

• 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

Question 9

Wher does erythropoietin production take place?

Answer 9

Mainly from juxtatubular interstitial cells in the KIDNEYS

A small amount of erythropoietin is produced in the LIVER by hepatocytes and interstitial cells

Question 10

What is the lifespan of erythrocytes and how are they destroyed?

Answer 10

The red cells are ultimately destroyed by phagocytic cells (macrophages) in the SPLEEN but can also be anywhere else in the body

Question 11

How do white cells come about and what is needed for this?

Answer 11

• 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

Question 12

Outline the granulocyte maturation process

Answer 12

• 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

Question 13

Outline the main characteristics and function of neutrophils

Answer 13

• 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

Question 14

How can a neutrophil get out of the bloodstream?

Answer 14

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

Question 15

Outline the main characteristic of eosinophils

Answer 15

• 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

Question 16

Outline the characteristics of basophils

Answer 16

Have a role in ALLERGIC RESPONSES

In basophils there are often so many dark blue dots that you don’t even see the nucleus

Question 17

Outline the characteristics of monocytes

Answer 17

• 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

Question 18

Outline the characteristics of platelets

Answer 18

• 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

Question 19

Outline the characteristics of lymphocytes

Answer 19

• 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

Question 20

Define anisocytosis and poikilocytosis

Answer 20

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

Question 21

Define microcytosis and macrocytosis. How would you determine if any of these are present?

Answer 21

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

Question 22

Define the terms microcytic, normocytic and macrocytic

Answer 22

• 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

Question 23

What is hypochromia? What would cells with hypochromia look like and what causes hypochromia?

Answer 23

• 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

Question 24

Define hyperchromia. Why does this occur and what would hyperchromatic cells look like?

Answer 24

• 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

Question 25

What are the two different types of hyperchromatic cells?

Answer 25

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)

Question 26

What are the characteristics of spherocytes and how do they come about?

Answer 26

○ 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

Question 27

What are the characteristics of irregularly contacted cells and what causes them to come about?

Answer 27

○ 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

Question 28

What is polychromatic and what does it indicate?

Answer 28

* 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

Question 29

What are reticulocytes and how can they be observed in a blood sample?

Answer 29

• 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

Question 30

What is poikilocytosis and what are the different cell types?

Answer 30

Literally means irregularly shaped cells Different types of cells are sickle cells, spherocytes, irregularly contracted cells, target cells, elliptocytes and fragments

Question 31

What are target cells and in what conditions do they occur?

Answer 31

``` • Cells with an accumulation of haemoglobin in the middle of the central pallor • They occur in: ○ Obstructive jaundice ○ Liver disease ○ Haemoglobinopathies ○ Hyposplenism ```

Question 32

What are eliptocytes and what conditions do they occur in?

Answer 32

• 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

Question 33

What are sickle cells and how do they occur?

Answer 33

* 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)

Question 34

What are fragment cells and how do they occur?

Answer 34

* 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)

Question 35

What is rouleux and why does it occur?

Answer 35

• 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

Question 36

What are agglutinates and why do they occur?

Answer 36

* 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

Question 37

What are Howell-Jolly body and what causes this to occur?

Answer 37

* 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

Question 38

What is the difference between sign and symptom?

Answer 38

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

Question 39

What do normal lymphocytes look like and what does an atypical lymphocyte look like? Why do these occur?

Answer 39

* 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

Question 40

What is left shift?

Answer 40

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

Question 41

What does normal neutrophil maturation look like? How would you identify left shift in a blood sample?

Answer 41

* 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

Question 42

What is toxic granulation and why does it occur?

Answer 42

* Toxic granulation is the heavy granulation of neutrophils * It results from infection, inflammation and tissue necrosis * This is also a feature of normal pregnancy

Question 43

What are hypersegmented neutrophils and what causes them?

Answer 43

* 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

Question 44

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Answer 44

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