Week 1 - A - Intro to Haem - Constituents of Blood&Haematopoiesis - RBCs, WBCs, Platelets, Immunophenotyping&Marrow Examination

Question 1

Haematology is the study of blood, the blood-forming organs, and blood diseases What are the particular organs studied in haematology?

Answer 1

Study of bone marrow, liver, spleen and lymphatics

Question 2

Blood is a specialized fluid (technically a tissue) composed of cells suspended in a liquid What is the fluid that blood is suspended in known as?

Answer 2

Blood is suspended in a fluid known as plasma

Question 3

What are broadly, the three types of blood cells?

Answer 3

Red blood cells (erythrocytes) White blood cells (leukocytes) Platelets

Question 4

Red blood cells are the most abundant cell type of the three What are main functions of blood?

Answer 4

They are important for: Fight infection Transport oxygen Prevent bleeding

Question 5

The production of blood cells is termed haemopoiesis (or haematopoiesis) What is the type of cell that blood cells are derived from known as?

Answer 5

Blood is derived from a type of cell known as a Stem cell - these cells are pluripotent and capable of making all the different blood cells

Question 6

What is the site of haematopoiesis during the developing embryo?

Answer 6

Yolk sac then liver then marrow From the 3rd to 7month of gestation - the production of blood also occurs in the spleen

Question 7

Where does blood production take place from birth to maturity? State at which period of gestation the blood production is occurring at?

Answer 7

Blood production by the foetus starts at approximately 5 weeks gestation by the yolk sac This occurs from 5 weeks to 10 weeks The liver also starts producing blood from the 6th week Bone marrow becomes the main source of haemapoeisis at 16 weeks gestation The spleen contributes to haemopeosis from the 3rd to 7th month of gestation

Question 8

During gestation - yolk sac then liver then bone marrow with spleen during this At birth, blood production is most in the bone marrow but also occurs in the liver and spleen when needed Where does blood production take place during adulthood?

Answer 8

From birth to maturity - blood production takes place in the bone marrow The number of active sites in the marrow decrease but the marrow still retains some sites to carry out haematopoesis From adulthood - only really the axial skeleton marrow involved - skull, sternum, ribs, pelvis & proximal ends of femur

Question 9

Summarise the sites of haematopoesis from embryo to adulthood? (embryo, birth, birth to maturation, adulthood)

Answer 9

Embryo - yolk sac then liver then bone marrow Spleen from 3rd to 7th month gestation Birth - bone marrow is the main site of haematopoesis - liver and spleen when needed Birth to maturity - number of active sites decreases but bone still retains its ability for haematopoesis Adulthood - Bone marrow of skull, sternum, ribs, pevlis and proximal end of femur

Question 10

In times of bone marrow stress, which organ may begin producing blood again? (due to its memory for when it produced blood in utero)

Answer 10

This would be the spleen

Question 11

Haematopoietic stem cell generates a wide array of different cell types. Huge numbers are required to maintain the status quo Approximately: * 100 million red cells/minute * 60 million neutrophils/minute * 150 million platelets/minute What two things have to happen to the stem cell to make blood?

Answer 11

The stem cells need to undergo proliferation (increase in number) and differentiation (become specialised) (Development of the features of the specialised end cell population from stem cell )

Question 12

What are the only two stem cells in the haematopoeitc tree? What two features msut stem cells have to be classified as stem cells?

Answer 12

This would be – * long term haematopoietic stem cells and * short term haematopoetic stem cells Stem cells must have the ability of: * Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. * Potency: the capacity to differentiate into specialised cell types.

Question 13

What do short term haematopoeitc stem cells divide to form? (these are known as short term because they have a greater tendency to differentiate whereas the long term can remain quiescent for longer)

Answer 13

ST-HSC form mutlipotent progenitor cells - these have a great ability for potency but cannot self-renew and therefore do not classify as a stem cell

Question 14

It is really the mature cells that come from the original LT-HSC, ST-HSC, MPP cells that are viewed on microscopy in the blood The early cells, such as the progenitor cells are not a distinct and the morphology is not as clear The MPP forms a common lympoid and common myeloid progenitor cell that produce different blood cells What cell do neutrophils stem from?

Answer 14

They come from myeloblasts - these come from the common common myeloid progenitor cells

Question 15

What happens to the size of the cell as it differenitates from myeloblast to neutrophil? (this change in size is true for any cell coming from stem cells)

Answer 15

As the myeloblast continues to differentiate (to promyelocyte, then myleocyte and so on) it decreases in size until it form the neutrophil

Question 16

The daughters of the precursor cells decrease in size as they divide – important to remember these cells are going through mitosis and therefore there is proliferation of cell – ie not 1 neutrophil forms from the myeloblast, instead many neutrophils will form from one myeloblast What are neutrophils also known as and why?

Answer 16

The neutrophils are also known as polymoprhs due to the multilobulated nucleus that is seen - usually has around 2-5 lobes in a neutrophil

Question 17

What is the earliest stage in development of the erthrocyte? By earliest, this refers to when the differentiating cells can only become eryhtrocytes

Answer 17

The earliest stage would be when the erythrocyts is the dividing pronormoblast (proerythroblast)

Question 18

Why does the pronormoblast (proeryhtroblast) have a very large blue cytoplasm surrounding the nucleus? What happens to this blue cytoplasm?

Answer 18

* The pronormoblast has a large blue cytoplasm as this contains lots of RNA which is required to produce the protein for haemaglobin * As more Hb is produced, the blue content slowly turns more red as less RNA exists The colour of the cytoplasm changes from blue at proerthroblast (pronormoblast) and basophillic stages to a pinkish red as a result of the increasing expression of haemoglobin as the cell develops

Question 19

Once the red cell has made all its haemoglobin, no longer have a need for the nucleus (protein already made) and therefore the nucleus disappears IN primitive cells the nucleus is often big – may often seen a nucleolus in the primitive cells When the developing red blood cell is released from the bone marrow, what is it known as? Does it contain a nucleus? What shape is it said to be?

Answer 19

The red blood cell is released from the bone marrow as a reticulocyte The reticulocyte loses some cell volume and the rest of the RNA to become an erythrocyte after a couple of days in circulation The reticulocyte is anucleate and biconcave in shape

Question 20

How long do reticulocytes stay for before maturing to become erythrocytes? (Mature red blood cells) How long are mature red blood cells said to live for?

Answer 20

Newly circulating red blood cells are the reticulocytes - they circulate for 1-2 days before becoming a mature red blood cell - erythrocyte Red cells live for approx. 120 days Which means about 1% of the red blood cells are said to be reticulocytes

Question 21

Neutrophils form from the myeloblast Mature red blood cells form from the proerythroblast What forms from the megakaryoblast?

Answer 21

Platelets will eentually form from the megakaryoblast A megakaryoblast is a precursor cell to a promegakaryocyte, which in turn becomes a megakaryocyte during haematopoiesis. It is the beginning of the thrombocytic series.

Question 22

Megakaryocyte – instead of the cytoplasm dividing, the nucleus divdies form 2 to 4, 4 to 8 etc and the cytoplasm increases with the increasing number of nuclei. A megakaryocyte, “large-nucleus cell”) is a large bone marrow cell with a lobulated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. Once the megakaryocyte continues to expand, what will eventually happen?

Answer 22

Eventually platelets that have formed on the periphery of the megakaocyte (budding) will be released into the bloodstream

Question 23

The functions of blood Fight infection Transport oxygen Prevent bleeding What is the functions of red blood cells (erythrocytes), white blood cells (leukocytes) and platelets?

Answer 23

Red blood cells * Transport oxygen * Buffer CO2 White blood cells * Fight infection Platelets * Stop bleeding

Question 24

What are the different categories of white blood cell?

Answer 24

Granulocytes Monocytes (macrophages) Lymphocytes

Question 25

Granulcoytes contain granules that are easily visible on light microscopy and are names according to their uptake of stains What are the three granulocyes? What colour do they stain? How many lobes is each of their nuclei?

Answer 25

Basophils - baso because they take up basic dyes very well and therefore stain blue/purple - bilobed nucleus Eosinophils - eosin is a red stain and this is the colour which eosinophils stain - bilobed nuclues Neutrophils - these are neutral - have pale red and blue granules - multilobular nucleus

Question 26

Neutrophils are by far the most common granulocyte Structure \* Segmented nucleus (polymorph) \* Neutral staining granules What is the function of the neutrophil?

Answer 26

They have a short life in circulation and transit to tissues to phagocytose foreign invaders but can also release its granules to attract other cells

Question 27

Can see the multilobes of the neutrophil - Increased by body stress – infection, trauma, infarction Describe the structure and colour of eosinophils?

Answer 27

Structure - bi-lobed nucleus - allmost spectacle shaped Colour - bright orange/red Probably more common in regulating the immune system

Question 28

What is the function of the eosinophils?

Answer 28

The function is: Fight parasitic infections Involved in hypersensitivity (igE mediated with eosinophils) Involved in atopy - eg asthma, atopic rhinitis (hayfever)

Question 29

Basophils Structure \* Infrequent in circulation \* Large deep purple granules obscuring nucleus How many lobes does the nucleus tend to have? What do basophils contain?

Answer 29

Basophils is a circulating version of a mast cell It is bilobed under the deep purple granules and contains and releases histamine and heparin form its granules

Question 30

The monocyte has a large single nucleus What do they become once they enter the cells? What is the function of monocytes?

Answer 30

Once monocytes enter the cells they become macrophages The main function of monocytes is phagocytosis, antigen presenting and cytokine production

Question 31

What is the white feature on monocytes and what might they contain?

Answer 31

These are vacuoles These may contain lysozomes - these contain degradative enzymes

Question 32

Lymphocytes are either mature or activated Describe the structure of mature lymphocytes? What is the size of the nucleus compared?

Answer 32

These are small with a condensed nucleus and rim of pale blue cytoplasm The nucleus is compared to the size of a red blood cell

Question 33

Activated (often called atypical) – large with plentiful blue cytoplasm extending round neighbouring red cells on the film, nucleus more ‘open’ structure When are lymphocytes usually activated (atypical)?

Answer 33

atypical lymphocytes are often associated with infectious mononucleosis from Epstein-Barr virus (EBV) infection. Activated lymphocytes is most ly due to EBV (HHV4) but can be in response to infections such as HIV

Question 34

Describe the difference between mature and activated lymphocytes? Lymphocyte functions: \* Function \* Numerous types and function (sub types of B, T, NK)! \* Cognate response to infection \* the brains of the immune system!

Answer 34

Mature lymphocytes These are small and have a condensed nucleus with a rim of pale blue cytoplasm Activated (atypical) lymphocytes These are large and have plentiful blue cytoplasm surrounding round neighbouring red blood cells - the nucleus is more of an open structure

Question 35

The activated lymphocytes are usually T cells – seen in things like glandular fever Where are tcells produced and where do they mature? What is the function of b cells?

Answer 35

T cells are produced in the bone marrow and mature in the thymus B cells function is to respond to antigen presenting by producing large numbers of antibodies

Question 36

These cells (in the red box) are easy to identify in the blood be it on light micrscopy after staining How are more primitive cells identified?

Answer 36

Immunophenotyping is the process used nowadays to recognise primitive precursors \* Immunophenotyping looks at the expression of proteins (antigens) on the surface of cells Bio assays were the old way of identifying primitive precrusors - this involved culture to show lineage of progeny

Question 37

Automated cell counting is the new way of counting cell numbers instead of requiring the biochemist What are common sites for bone marrow aspiration and biopsy?

Answer 37

The posterior iliac crests are sued - near to the posterior superior iliac spines

Question 38

Remember the adult hematopoietic bone marrow is only in the axial skeleton so need to access this skeleton to look at the marrow Why is it that aspirating in the posterior iliac crests is good?

Answer 38

Aspirating here means the needle goes down the plane of the bone to the medulla and also no organs are damaged with a horizontal needle injury

Question 39

What are the white blobs on the image of the bone marrow aspirate? Clue - it is why dogs love chewing on bones

Answer 39

These blobs are fat - bone marrow is basically half fat, half cells

Question 40

What is the difference between a bone marrow aspiration and a core biopsy?

Answer 40

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Question 41

When the bone core biopsy is carried out, what does the solution it is put into cause? Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called a trephine biopsy) and bone marrow aspiration.

Answer 41

The core biopsy is put into a solution to decalcify the bone before sectioning and staining

Question 42

What needle is used to take a sample of a bone marrow biopsy?

Answer 42

Usually a Jamshidi needle is used to take a core biopsy

Question 43

What can be seen on this trephine biopsy?

Answer 43

The pink swirls are trabecular bony fragments - these hold the bone in place The white is fat The other is cellular mass