Physiology of blood cells and haematological terminology Flashcards
Summarise the origin of the blood cells
Blood cells of all types originate in the bone marrow
They are ultimately derived from multipotent haemopoietic stem cells
The multipotent stem cells gives rise to lymphoid stem cells and myeloid stem cells, from which red cells, granulocytes, monocytes and platelets are derived
all cell types derived from multipotent haematopoietic stem cells in bone marrow - which then form myeloid or lymphoid stem cells
Outline the stem cell hierarchy
Multipotent lymphoid-myeloid stem cell is the ultimate cell- gives rise to myeloid and lymphoid lineages
Blood cell derivatives (RBCs, platelets) are derived from these two lineages
What cells are derived from the multipotent myeloid precursor
Megakaryocytes
Granulocyte-Monocyte
Erythroid
What cells are derived from the multipotent lymphoid precursor?
T cells
B cells
NK cells
Describe the key characteristics of stem cells
Ability to self-renew and produce mature progeny
How is that achieved?
Ability to divide into two cells with different characteristics, one another stem cell and the other a cell capable of differentiating to mature progeny
Self-renewal is important- allows the bone marrow to continue functioning and producing blood cells throughout the entire life span.
Summarise the pathway in the development of erythrocytes
The myeloid stem cell/precursor can give rise to a proerythroblast (earliest recognisable cell in erythrocyte lineage)
This in turn gives rise to erythroblasts and then erythrocytes or red cells
What are some common features of blasts
They have a large nucleus and a small amount of cytoplasm
Will generate the mature cell
i.e erythroblasts will generate erythrocytes.
Outline normal erythroid maturation
Multipotent myeloid stem cell- proerythroblast- Early, intermediate and late erythroblasts (all nucleated) — erythrocytes (enucleated)
On final step of differentiation- cytoplasm squeezed out of endothelium and into sinusoids- which are digested by macrophages
myeloid stem cell > proerythroblast > erythroblast (nucleated) > erythrocyte (have lost the nucleus) - each step in differentiation involves division to produce two cells; nucleus is excluded in final division and ingested by macrophage
What is the term for the production of red blood cells and where does it take place
The process of producing red cells is called erythropoiesis
Normal erythropoiesis requires the presence of erythropoietin
Erythropoietin is synthesized mainly by the kidney, in response to hypoxia
Describe the feedback cycle between the kidney and the bone marrow
Hypoxia and anaemia trigger the kidney to increase erythropoietin synthesis
This leads to increased bone marrow activity
Which in turn leads to a greater production of red blood cells- important in maximising oxygen delivery to the tissues.
How does the colour of red cells change as they mature
When they are immature they are more blue/purple
As they mature they become pinker
Describe the synthesis of erythropoietin (EPO)
§ Normal erythropoiesis requires erythropoietin which is mainly synthesised in the kidneys in response to HYPOXIA.
o 90% of erythropoietin from juxtatubular interstitial cells of the kidneys.
o 10% of erythropoietin from hepatocytes and interstitial cells of the liver
These cells then enter the capillaries to reach the bone marrow via the circulatory system
Outline the key properties of red blood cells
The erythrocyte survives about 120 days in the blood stream
Its main function is oxygen transport
It also transports some carbon dioxide (but most is transported via the plasma)
Ultimately it is destroyed by phagocytic cells of the spleen (and also to a lesser extent by the liver and other cells in the reticulo-endothelial system)
Which property of RBCs allows the potential for blood transfusions
Their long life span- can last a long time when stored in vitro at a low temperature and added with an anti-coagulant
Describe the differentiation of multipotent haematopoietic stem cells into myeloblasts and monoblasts
The multipotent haemopoietic stem cell can also give rise to a myeloblast and a monoblast, which in turn give rise to granulocytes and monocytes
Cytokines such as G-CSF, M-CSF, GM-CSF and various interleukins are needed
Which cytokines are important in the differentiation of myeloblasts to granulocytes and monocytes?
G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; M-CSF, macrophage colony-stimulating factor
Analysed the maturation of these cells in tissue culture and these cytokines happened to stimulated the maturation of these specific cells.
Outline normal granulocyte maturation
Myeloblast ( most primitive recognisable cell)
Promyeloblast (shows evidence of dividing down granulocyte pathway: primary granules, Golgi zone (clear area) and eccentric nucleus- more mature cell in pathway)
Myelocyte (smaller, secondary granules, can tell at this stage which granulocyte is produced (neutrophil, basophil or eosinophil)
Metamyelocyte (differs as it has an indented nucleus)
Band form (just change of shape in nucleus- arranges into band form)
Neutrophil (nucleus segments into lobules- same thing happens in eosinophil and basophil pathway)
2 cells produced until metamyelocyte- from here- any changes are simply just changes in the morphology of the nucleus.
What is a key change to the chromatin upon maturation
The chromatin becomes more condensed with maturation
Initially very diffuse and full of active DNA
Which cell is formed between the late erythrocyte and the mature erythrocyte
A polychromatic erythrocyte (earliest red cell to get out into circulation) - larger than mature cell and has a faint blue tinge (still has ribosomes in cytoplasm- for synthesis of Hb)- keeps going in circulating cell fro a few days after release from bone marrow
20% larger than mature erythrocytes.
How else can we detect the presence of reticulocytes (immature erythrocytes)
Specific stain which reticulocytes takes up
Causes them to form a recticulum (network)- allowing them to be counted
Describe the function of neutrophils
The neutrophil granulocyte survives 7–10 hours in the circulation before migrating to tissues (short life span here too)
Its main function is defence against infection; it phagocytoses and then kills micro-organisms
Can function in the blood to defend against bacteraemias
Essentially, what is pus
A collection of dead neutrophils
Describe the two pools of neutrophils
Circulating- in the middle of the blood vessels
Marginal - adherent to the endothelium of the capillaries
Describe how the neutrophils enter the tissues
Adhesion and margination
Rolling
Diapedesis (actual process of travelling through endothelium)
Migration (chemotaxis) - in tissues towards inflammation- attraction to chemokines.
Phagocytosis
What does the term granulocyte refer to
The 3 lineages (eosinophils, basophils and neutrophils)
Describe the key properties of the eosinophils
A myeloblast can also give rise to eosinophil granulocytes
The eosinophil spends less time in the circulation than does the neutrophil
Its main function is defence against parasitic infection (releases granules which kill parasites)
Red/Orange granules
Describe the key property of the basophils
A myeloblast can also give rise to basophil granulocytes
Basophils have a role in allergic responses
Take up basic stain- why they appear purple
Role in response to various infective stimuli
Summarise the maturation pathway for monocytes
The myeloid stem cell can also give rise to monocyte precursors and thence monocytes
Monocytes spend several days in the circulation
Monoblasts- promonocytes- monocytes
Describe the key properties of monocytes
Monocytes migrate to tissues where they develop into macrophages and other specialized cells that have a phagocytic and scavenging function (called histiocytes or macrophages inside tissue)
Macrophages also store and release iron
They have a kidney bean shaped nucleus (indented nucleus)
They are large
Describe how macrophages can store and release iron
Take up erythroblasts who have ejected their cytoplasm and nucleus into sinusoids
Convert Fe to ferritin and store it as Hemosiderin
Allowing iron to be released when it is needed (i.e during erythropoiesis)
Summarise the maturation pathway of the platelets
The haemopoietic stem cell can also give rise to megakaryocytes and thence platelets
Megakaryocytes large cell- produce platelets by fragmentations of the cytoplasm of the megakaryocytes
Leaving a bare nucleus in the bone marrow to be destroyed.
Describe the key properties of platelets
Platelets survive about 10 days in the circulation
Platelets have a role in primary haemostasis (which block small breaks in blood vessels)
Platelets contribute phospholipid, which promotes blood coagulation (secondary haemostasis)
Describe the key properties of lymphocytes
The lymphoid stem cell gives rise to T cells, B cells and natural killer (NK) cells
Lymphocytes recirculate to lymph nodes and other tissues and then back to the blood stream
Intravascular life span is very variable - due to recirculation
Re-join circulation from lymphatic duct
High nuclear: cytoplasmic ratio
Describe the importance of lymphocyte recirculation
Once they recognise the antigen in the tissue- can recirculate to clear the antigen throughout the body- aiding the body’s defence.
Why is terminology important in medicine
In haematology, specialised language is used to describe blood films and counts
You need to know what the words mean and what the clinical significance might be
Why may a lymphocyte have a granulated nucleus
NKC
OR cytotoxic T lymphocyte
cytotoxic granules to kill pathogen.
Define Ansiocytosis
red cells show more variation in size than is normal
Define Poikilocytosis
red cells show more variation in shape than is normal
Could be due to an inherited haemolytic anaemia
What is meant by microcytosis and macrocytosis
Microcytosis – red cells are smaller than normal
Macrocytosis – red cells are larger than normal
Microcyte – a red cell that is smaller than normal
Macrocyte – a red cell that is larger than normal
how can we determine whether a blood cell is microcytic or macrocytic
RBCs should roughly be equal in diameter to the nucleus of a lymphocyte
We also have automated blood cell counters which measure the size of the RBCs
Describe the different specific types of macrocytes
Macrocytes can be of specific types Round macrocytes Oval macrocytes (significant as common in VB12 or folic acid deficiency) Polychromatic macrocytes (lots of immature cells in circulation- could be responding to haemorrhage or deficient in vitamin administered i.e a previous deficiency but now administered vitamin)
Dependent on shape and staining characteristics upon blood film
What do the terms microcytic, normocytic and macrocytic refer to
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
Describe the normal central pallor of RBCs (hypochromia)
Normal red cells have about a third of the diameter that is pale
This is a result of the disk shape of the red cell; the centre has less haemoglobin and is therefore paler
Describe what is meant by hypochromia
Hypochromia means that the cells have a larger area of central pallor than normal
This results from a lower haemoglobin content and concentration and a flatter cell
Red cells that show hypochromia are described as hypochromic
Hypochromia and microcytosis often go together (often due to Fe deficiency and thus the failure to synthesise Hb)
80-90% of RBC is pale (increased central pallor)
Essentially, what happens in thalassaemia major
Defect in globin genes- can’t synthesise Hb
Will see blobs of Fe in cell- as the Fe is not incorporated with globin
Cells will be hypochromic
What is meant by hyperchromia
Hyperchromia means that cells lack central pallor
This can occur because they are thicker than normal (macrocytes) or because their shape is abnormal
Cells showing hyperchromia can be described as hyperchromatic or hyperchromic
Describe adnormal cell shape as a cause of hyperchromia
Hyperchromia has many causes since many abnormally shaped cells lack the central thinner area
However there are only two important types, spherocytes and irregularly contracted cells
Describe spherocytes
Spherocytes are cells that are approximately spherical in shape
They therefore 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 so the cell is forced to round up and close whatever is left inside the membrane
Describe hereditary spherocytosis
Spherocytes in hereditary spherocytosis – but not all the cells are spherical
Inherited abnormality in RBC membrane- not tethered to the cytoskeleton- so the membrane is lost (BUT the cells start of as disc shaped then become more spherical as the membrane is lost)
Describe irregularly contracted cells
Irregularly contracted cells are irregular in outline but are smaller than normal cells and have lost their central pallor
They usually result from oxidant damage to the cell membrane and to the haemoglobin
Describe some oxidants for Hb
Foreign chemical
Food stuff (fava beans or broad beans)
Strongly oxidant to Hb and RBCs- if RBCs lack the enzyme to metabolise them- can oxidise Hb and cause it to clump- forming irregularly contracted cells
Causing a haemolyitic anaemia which would show these cells on a blood film
What is meant by polychromasia
Polychromasia describes an increased blue tinge to the cytoplasm of a red cell
It indicates that the red cell is young
Cell is often much larger
Normally leave bone marrow with a slight blue tinge
But these cells have been released early in development and so still contain lots of ribosomes, causing the blue to be superimposed
Describe the reticulocyte stain
Another way to detect young cells is to do a reticulocyte stain
This exposes living red cells to new methylene blue, which precipitates as a network or ‘reticulum’
Cells which take up the stain can be counted and expressed as a % of the total cells (needs to look at 100s to get a precise and reliable estimate)
Should only have 1-2% of these cells in the population circulating.
How else can you identify reticulocytes
Detecting polychromasia or increased numbers of reticulocytes gives you similar information (although much harder to see tinges of blue- stain best)
However, identification of reticulocytes is more reliable so they can be counted
What is polychromasia an indication for
early release from bone marrow so many ribosomes - indication for subsequent reticulocyte count / stain
List the different types of Poikilocytes
Spherocytes
Irregularly contracted cells
Sickle cells (crescent shaped with pointy ends)
Target cells (blob of Hb in middle of cell- giving appearance of target)
Elliptocytes (elliptical in shape- a bit fatter- ovalocyte)
Fragments (small bit of RBCs often angular- often called schizocytes)
Describe target cells
Target cells are cells with an accumulation of haemoglobin in the centre of the area of central pallor
They occur in obstructive jaundice, liver disease, haemoglobinopathies and hyposplenism
Also in haemoglobinopathies
Describe elliptocytes
Elliptocytes are elliptical in shape
They occur in hereditary elliptocytosis and in iron deficiency
On a blood film, how can you distinguish between eliptocytes in hereditary elliptocytosis and elliptocytes in iron deficiency
Iron deficiency blood film will also show hypochromic cells (including hypochromic elliptocytes- often called pencil cells)
Also microcytic cells
Describe sickle cells
Sickle cells are sickle or crescent shaped
They result from the polymerisation of haemoglobin S when it is present in a high concentration
Common in conditions of reduced oxygen tension
Describe boat cells
Cells where HbS is polymerised but not to an extent to produce a sickle-shaped cell (but will soon become sickle-shaped)
This gives the appearance of a boat-shaped cell
If found on film- look around for sickle cells
Describe fragments
Fragments or schistocytes are small pieces of red cells
They indicate that a red cell has fragmented
Which two terms describe abnormalities in the relationship between different RBCs
Rouleaux
Agglutinates
Describe Rouleaux
Rouleaux are stacks of red cells
The resemble a pile of coins
They result from alterations in plasma proteins
Explain the different causes of Rouleaux
Normally RBC repel each other and will appear separated on the blood film
However increased in high molecular weight plasma proteins such as Ig during infective and inflammatory states can negate these neutralising forces- causing Rouleaux.
Describe agglutinates
Red cell agglutinates differ from rouleaux in that they are irregular clumps, rather than tidy stacks
They usually result from antibody on the surface of the cells - which cause the RBCs to clump together
What can RBCs sometime have
Inclusions (Howell-Jolly body)
Describe Howell-Jolly bodies
A Howell‒Jolly body is a nuclear remnant in a red cell
The commonest cause is lack of splenic function
Produced in bone marrow but removed by spleen and so should not be seen in circulating blood
Indicates that spleen isn’t functioning (may have atrophied) OR spleen has been removed.
What do the terms leucocytosis and leucopenia refer to
Leucocytosis — too many white cells
Leucopenia — too few white cells
What do the terms neutrophilia and neutropenia refer to
Neutrophilia — too many neutrophils
Neutropenia — too few neutrophils
What do the terms lymphocytosis and lymphopenia refer to
Lymphopenia: not enough lymphocytes
Lymphocytosis — too many lymphocytes
What does the term eosinophilia refer to
too many eosinophils
What do the terms thrombocytosis and thrombocytopenia refer to
Thrombocytosis: too many platelets
Thrombocytopenia: too few
What do the terms erythrocytosis and reticulocytosis refer to
Erythrocytosis: too many erythrocytes
Reticulocytosis: too many reticulocytes
What is the difference between a symptom and a sign
Symptom- what the patient tells you about (often how they feel)
Sign- what you see on examination (i.e pallor)
Describe atypical lymphocytes
An atypical lymphocyte is an abnormal lymphocyte
Often the term is used to describe the abnormal cells present in infectious mononucleosis (‘glandular fever’)
‘Atypical mononuclear cell’ is an alternative term
Often develop in response to infections- but mostly viral infections.
An atypical lymphocyte will have a large nucleus and a large amount of faint cytoplasm
What is meant by left shift
Left shift means that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood
An increase in non-segmented neutrophils
More band forms or promyelocytes e.g
Sign of infection or inflammation (will see heavy granules and vacuoles in band forms which indicate infection)
band cells with no segmentation indicate rapid production during infection
May also see neutrophilia and therefore also leucocytosis.
Describe right shift
Hyper-segmented nuclei in neutrophil
Describe toxic granulation
Toxic granulation is heavy granulation of neutrophils
It results from infection, inflammation and tissue necrosis (but is also a normal feature of pregnancy)
May see heavy granules and vacuoles if infection
Describe hypersegmented neutrophils (right shift)
Neutrophil hypersegmentation means that there is an increase in the average number of neutrophil lobes or segments (should normally see 3/4- but in right shift may see >6)
It usually results from a lack of vitamin B12 or folic acid
How can you look for anaemia on a blood film
How thin the blood spreads depends on its viscosity
If anaemic- low viscosity
Thin film
More spaces between cells
How can sickle cell anaemia lead to the presence of Howell-Jolly bodies
Infarction of spleen- therefore nuclear remanants not removed.
Describe tear drop cells
Dacrocytes
