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Haematology > Physiology of blood cells and haematological terminology > Flashcards

Physiology of blood cells and haematological terminology Flashcards

1
Q

Summarise the origin of the blood cells

A

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

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2
Q

Outline the stem cell hierarchy

A

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

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3
Q

What cells are derived from the multipotent myeloid precursor

A

Megakaryocytes
Granulocyte-Monocyte
Erythroid

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4
Q

What cells are derived from the multipotent lymphoid precursor?

A

T cells
B cells
NK cells

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5
Q

Describe the key characteristics of stem cells

A

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.

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6
Q

Summarise the pathway in the development of erythrocytes

A

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

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7
Q

What are some common features of blasts

A

They have a large nucleus and a small amount of cytoplasm
Will generate the mature cell
i.e erythroblasts will generate erythrocytes.

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8
Q

Outline normal erythroid maturation

A

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

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9
Q

What is the term for the production of red blood cells and where does it take place

A

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

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10
Q

Describe the feedback cycle between the kidney and the bone marrow

A

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.

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11
Q

How does the colour of red cells change as they mature

A

When they are immature they are more blue/purple

As they mature they become pinker

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12
Q

Describe the synthesis of erythropoietin (EPO)

A

§ 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

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13
Q

Outline the key properties of red blood cells

A

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)

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14
Q

Which property of RBCs allows the potential for blood transfusions

A

Their long life span- can last a long time when stored in vitro at a low temperature and added with an anti-coagulant

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15
Q

Describe the differentiation of multipotent haematopoietic stem cells into myeloblasts and monoblasts

A

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

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16
Q

Which cytokines are important in the differentiation of myeloblasts to granulocytes and monocytes?

A

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.

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17
Q

Outline normal granulocyte maturation

A

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.

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18
Q

What is a key change to the chromatin upon maturation

A

The chromatin becomes more condensed with maturation

Initially very diffuse and full of active DNA

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19
Q

Which cell is formed between the late erythrocyte and the mature erythrocyte

A

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.

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20
Q

How else can we detect the presence of reticulocytes (immature erythrocytes)

A

Specific stain which reticulocytes takes up

Causes them to form a recticulum (network)- allowing them to be counted

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21
Q

Describe the function of neutrophils

A

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

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22
Q

Essentially, what is pus

A

A collection of dead neutrophils

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23
Q

Describe the two pools of neutrophils

A

Circulating- in the middle of the blood vessels

Marginal - adherent to the endothelium of the capillaries

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24
Q

Describe how the neutrophils enter the tissues

A

Adhesion and margination
Rolling
Diapedesis (actual process of travelling through endothelium)
Migration (chemotaxis) - in tissues towards inflammation- attraction to chemokines.
Phagocytosis

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25
Q

What does the term granulocyte refer to

A

The 3 lineages (eosinophils, basophils and neutrophils)

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26
Q

Describe the key properties of the eosinophils

A

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

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27
Q

Describe the key property of the basophils

A

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

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28
Q

Summarise the maturation pathway for monocytes

A

The myeloid stem cell can also give rise to monocyte precursors and thence monocytes
Monocytes spend several days in the circulation

Monoblasts- promonocytes- monocytes

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29
Q

Describe the key properties of monocytes

A

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

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30
Q

Describe how macrophages can store and release iron

A

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)

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31
Q

Summarise the maturation pathway of the platelets

A

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.

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32
Q

Describe the key properties of platelets

A

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)

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33
Q

Describe the key properties of lymphocytes

A

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

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34
Q

Describe the importance of lymphocyte recirculation

A

Once they recognise the antigen in the tissue- can recirculate to clear the antigen throughout the body- aiding the body’s defence.

35
Q

Why is terminology important in medicine

A

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

36
Q

Why may a lymphocyte have a granulated nucleus

A

NKC
OR cytotoxic T lymphocyte
cytotoxic granules to kill pathogen.

37
Q

Define Ansiocytosis

A

red cells show more variation in size than is normal

38
Q

Define Poikilocytosis

A

red cells show more variation in shape than is normal

Could be due to an inherited haemolytic anaemia

39
Q

What is meant by microcytosis and macrocytosis

A

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

40
Q

how can we determine whether a blood cell is microcytic or macrocytic

A

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

41
Q

Describe the different specific types of macrocytes

A 
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

42
Q

What do the terms microcytic, normocytic and macrocytic refer to

A

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

43
Q

Describe the normal central pallor of RBCs (hypochromia)

A

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

44
Q

Describe what is meant by hypochromia

A

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)

45
Q

Essentially, what happens in thalassaemia major

A

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

46
Q

What is meant by hyperchromia

A

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

47
Q

Describe adnormal cell shape as a cause of hyperchromia

A

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

48
Q

Describe spherocytes

A

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

49
Q

Describe hereditary spherocytosis

A

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)

50
Q

Describe irregularly contracted cells

A

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

51
Q

Describe some oxidants for Hb

A

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

52
Q

What is meant by polychromasia

A

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

53
Q

Describe the reticulocyte stain

A

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.

54
Q

How else can you identify reticulocytes

A

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

55
Q

What is polychromasia an indication for

A

early release from bone marrow so many ribosomes - indication for subsequent reticulocyte count / stain

56
Q

List the different types of Poikilocytes

A

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)

57
Q

Describe target cells

A

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

58
Q

Describe elliptocytes

A

Elliptocytes are elliptical in shape

They occur in hereditary elliptocytosis and in iron deficiency

59
Q

On a blood film, how can you distinguish between eliptocytes in hereditary elliptocytosis and elliptocytes in iron deficiency

A

Iron deficiency blood film will also show hypochromic cells (including hypochromic elliptocytes- often called pencil cells)
Also microcytic cells

60
Q

Describe sickle cells

A

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

61
Q

Describe boat cells

A

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

62
Q

Describe fragments

A

Fragments or schistocytes are small pieces of red cells

They indicate that a red cell has fragmented

63
Q

Which two terms describe abnormalities in the relationship between different RBCs

A

Rouleaux

Agglutinates

64
Q

Describe Rouleaux

A

Rouleaux are stacks of red cells
The resemble a pile of coins
They result from alterations in plasma proteins

65
Q

Explain the different causes of Rouleaux

A

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.

66
Q

Describe agglutinates

A

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

67
Q

What can RBCs sometime have

A

Inclusions (Howell-Jolly body)

68
Q

Describe Howell-Jolly bodies

A

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.

69
Q

What do the terms leucocytosis and leucopenia refer to

A

Leucocytosis — too many white cells

Leucopenia — too few white cells

70
Q

What do the terms neutrophilia and neutropenia refer to

A

Neutrophilia — too many neutrophils

Neutropenia — too few neutrophils

71
Q

What do the terms lymphocytosis and lymphopenia refer to

A

Lymphopenia: not enough lymphocytes

Lymphocytosis — too many lymphocytes

72
Q

What does the term eosinophilia refer to

A

too many eosinophils

73
Q

What do the terms thrombocytosis and thrombocytopenia refer to

A

Thrombocytosis: too many platelets
Thrombocytopenia: too few

74
Q

What do the terms erythrocytosis and reticulocytosis refer to

A

Erythrocytosis: too many erythrocytes
Reticulocytosis: too many reticulocytes

75
Q

What is the difference between a symptom and a sign

A

Symptom- what the patient tells you about (often how they feel)
Sign- what you see on examination (i.e pallor)

76
Q

Describe atypical lymphocytes

A

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

77
Q

What is meant by left shift

A

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.

78
Q

Describe right shift

A

Hyper-segmented nuclei in neutrophil

79
Q

Describe toxic granulation

A

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

80
Q

Describe hypersegmented neutrophils (right shift)

A

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

81
Q

How can you look for anaemia on a blood film

A

How thin the blood spreads depends on its viscosity
If anaemic- low viscosity
Thin film
More spaces between cells

82
Q

How can sickle cell anaemia lead to the presence of Howell-Jolly bodies

A

Infarction of spleen- therefore nuclear remanants not removed.

83
Q

Describe tear drop cells

A

Dacrocytes

Haematology (11 decks)

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