Introduction to Haematology

Question	Answer
What are the 3 types of blood cell that normal peripheral blood is composed of?	Erythrocytes, leukocytes and thrombocytes.
What proportions of the blood do cells and plasma constitute, respectively?	40% cell, 60% plasma.
What are some effects resulting from the proportion of blood cells to plasma being disrupted?	If the proportion of blood cells increases: the blood can become more viscous and circulation is more difficult, this will result in high blood pressure, and perhaps thrombi. If the proportion of blood cells decreases: anaemia can result, as well as low immunity and low blood pressure.
What is the term for the production of blood cells?	Haematopoiesis.
What are the individual terms for the production of red blood cells, white blood cells, and platelets?	Erythropoiesis, leukopoiesis and thrombopoiesis respectively.
What is the lifespan of an erythrocyte?	~120 days.
If blood cells do not last forever, why do we not always become ill as a result of their loss?	Because a dynamic equilibrium exists between haematopoiesis and apoptosis.
What is the total blood volume of the average 70kg male? Around how many erythrocytes are in this amount?	~5 litres of blood, ~25 x 10^12 in this amount. (~5 x 10^12/L, 4-5 million/uL)
Where does haematopoiesis take place in infants and adults?	In the bone marrow.
Where does haematopoiesis occur in foetuses?	In the yolk sac in the first two months, in the liver and spleen between the 2nd and 7th month, and in the bone marrow between the 5th and 9th month.
In which type of bone marrow does haematopoiesis occur? What is the other type?	The red marrow produces blood cells, and the remainder is inactive, fatty yellow marrow.
Under what circumstances might inactive, fatty yellow marrow be activated for haematopoiesis?	During/after severe blood loss, such as labour or injury.
Haematopoietic stem cells are pluripotent. What does this mean?	This means that haematopoietic stem cells can differentiate into any type of cell and have the ability to replace themselves.
Under the influence of particular cytokines (hormones/growth factors), what two types of cell does the haematopoietic stem cell initially differentiate into?	The common myeloid and common lymphoid progenitor cells.
What three types of cells can the common lymphoid progenitor differentiate into?	The B cell progenitor, the T cell progenitor, and the natural killer cell progenitor.
What three types of cell can the common myeloid progenitor differentiate into?	Erythroid progenitors, megakaryoblast progenitors, and granulocyte-monocyte progenitors.
What types of lymphocyte can a granulocyte-monocyte progenitor differentiate into?	Neutrophils, basophils, eosinophils and monocytes.
What type of cell can a megakaryoblast progenitor differentiate into?	A megakaryoblast which differentiates/matures into a megakaryocyte, which undergoes cytplasmic fragmentation to form platelets.
What are the differentiation steps between the erythroid progenitor and the erythrocyte?	Erythroid progenitor - erythroblast - early normoblast - intermediate normoblast - late normoblast - (nuclei extruded) - erythrocytes.
What are the differentiation steps between the granulocyte progenitor and neutrophils, basophils and eosinophils?	Granulocyte progenitor - myeloblast - promyelocyte - myelocyte - megamyelocyte - basophils, neutrophils and eosinophils.
Is differentiation a bidirectional process?	No. No, it isn't.
What is the term for young erythrocytes?	Reticulocytes, these have just been released into the circulation as the nuclei are removed from the late normoblasts.
Describe the feedback loop that maintains the circulating erythrocyte count within narrow limits.	A decrease in erythrocyte number below the body's lower margin, caused by senescence be it normal or premature, leads to decreased O2 delivery to the tissues. In the kidney, this tissue hypoxia stimulates the production of erythropoietin. Erythropoietin acts on erythrocyte progenitors to speed up their production, and the decrease in/lack of tissue hypoxia completes the feedback loop as erythropoietin production is no longer stimulated.
When erythropoietin acts on erythroid progenitors, what effects does it have?	Shortens cell cycle time, increases maturation, and increases the release rate of erythrocytes from the bone marrow.
In adults, which bones does haematopoiesis occur in?	Vertebrae, ribs, sternum, skull, sacrum and pelvis, and the proximal ends of the femurs.
Does erythropoietin production stop when tissue hypoxia is reduced/stopped?	No, you are always producing erythropoietin, the levels of it simply increases or decreases according the tissue hypoxia resulting from the circulating number of erythrocytes.
How does erythropoietin exert effects on erythrocyte progenitors?	It binds to a receptor on the erythrocyte progenitor which stimulates erythropoiesis.
What type of blood cell is the most numerous in the blood?	Erythrocytes.
Where are erythrocytes sequestered?	The spleen.
What shape and size are erythrocytes?	Erythrocytes are biconcave discoid in shape, and are ~8.4um in diameter. They have a volume (a mean corpuscular volume) of ~88 femtolitres/fL.
What are two significant benefits of the shape of erythrocytes?	Their shape allows them to deform in capillaries so that the cell may fit through the tiny vessels, and it also increases the surface area of the cell for gaseous exchange.
What is the primary function of erythrocytes and what pigment primarily carries this out?	Their primary function is oxygen transport, and this is carried out by haemoglobin, a red pigment present in mature erythrocytes.
Where does the assembly of the haem of haemoglobin occur?	In the mitochondria of erythrocyte precursor cells in red bone marrow.
What is haemoglobin?	A globular protein consisting of four globin chains, each with one iron-containing haem group attached to it. Each haem group can carry a single O2 molecule, and a single erythrocyte contains millions of haemoglobin molecules.
What is the difference in the globin chains between a foetus and an adult?	A foetus' haemoglobin is composed of two alpha and two gamma globin chains, whereas an adult's haemoglobin is composed of two alpha and two beta globin chains. The change is a result of the oxygen affinity not needing to be as high in an adult as in a foetus which receives its blood supply from its mother and so must have a higher affinity for O2 than her erythrocytes in order for O2 to be released from them.
What is the main function of leukocytes?	The immune response to foreign bodies and invading organisms.
How many leukocytes does the average person have?	5x10^9/L of blood.
Which two types of leukocyte are mononuclear cells?	Monocytes and lymphocytes.
Which three types of leukocyte are granulocytes (polymorphonuclear cells)?	Neutrophils, basophils and eosinophils.
List the types of leukocytes in decreasing order of frequency.	Neutrophils, lymphocytes, monocytes, eosinophils, basophils (Naughty Little Monkeys Eat Bananas).
Roughly what percentage of circulating leukocytes do neutrophils make up in adults?	~60%
Describe a feature of the nucleus of a neutrophil.	It is divided into lobes ('polymorphonuclear').
Why is a neutrophil categorised as a granulocyte?	Because its cytoplasm is full of fine granules which stain pink with Romanowsky dyes.
What is a granule?	In cell biology this is a small particle, usually a secretory vesicle. The contents of these are specific to the type of granulocyte and enable their functions.
What is the lifespan of a neutrophil, and what might increase it slightly?	The average lifespan is 6-10 hours, and release of neutrophils into tissues may increase lifespan slightly while it is active.
What is the main function of neutrophils?	Non-specific defence against bacterial and fungal infections. The neutrophils can release their granule contents onto a foreign body and usually break it down.
Roughly what percentage of leukocytes do eosinophils account for?	~1%
Which dyes stain eosinophil granules strongly?	Eosin dyes.
Describe a feature of an eosinophil nucleus.	It is bilobed.
What is the average lifespan of an eosinophil?	~4-5 hours
What size (qualitatively, not quantitatively) are eosinophil granules?	Large.
What are the two main functions of eosinophils?	Defence against parasitic infections and helping to dampen the allergic response.
How do eosinophils function differently with small and large parasites?	Eosinophils engulf small parasites, whereas they empty granules onto larger parasites.
Given their function, name two locations in which eosinophils are particularly frequent.	In the respiratory tract and under the skin.
Why are higher levels of eosinophils found in individuals from developing countries?	Because there is higher exposure to parasites due to poor sanitation and water supplies.
Tissue eosinophils respond to bacterial and fungal infections similarly to which other type of leukocyte?	Neutrophils.
Roughly what percentage of leukocytes do basophils constitute?	<1%, the least numerous leukocyte
The large cytoplasmic granules of basophils stain strongly with what dye?	Methylene blue.
What is the main function of basophils?	Basophils are involved in anaphylactic hypersensitivity and inflammatory reactions.
What small chemical compound do basophils contain in their granules?	Histamine.
Roughly what proportion of leukocytes do monocytes constitute?	~5%
Qualitatively and quantitatively, what size are monocytes?	They are large cells, around 16-22 um in diameter.
Describe a distinct feature of the nuclei of monocytes.	The nuclei of monocytes (which are mononuclear) are kidney shaped and have a distinct cleft in them.
What is the lifespan of an average monocyte?	They circulate for around 10 hours.
Describe the granules of monocytes.	Monocytes have 'a scattering' of granules, a much smaller number than other leukocytes, and these are azurophilic but stain lightly.
Once monocytes exit to the tissues, what do they mature into?	Mature phagocytic tissue macrophages.
List some of the functions of a monocyte.	Monocytes are responsible for the removal and processing of aged erythrocytes and other debris, they play an important role in processing and presenting antigen to T lymphocytes in the acquired immune response, and they also release growth factors to stimulate other leukocytes.
Go through the process of phagocytosis.	Phagocytosis is the process by which a foreign body or aged or unusual cell or organism is engulfed by phagocytic leukocytes, monocytes/macrophages and neutrophils primarily, and processed and exocytosed. First the bacterium (in this instance) becomes attached to the membrane evaginations ('pseudopodia'). Next, the pseudopodia fuse and the bacterium is endocytosed in a phagosome. Inside the phagocytic cell, the phagosome fuses with a lysosome and the lysosomal enzymes and acidic cytoplasm break down the bacterium. Lastly the digestion products, benign and broken down, are exocytosed from the cell as the lysosome fuses with the cell membrane.
Roughly what proportion of leukocytes do lymphocytes constitute?	~33%, they are the second most numerous leukocyte after neutrophils.
What size are leukocytes?	10-12um in diameter.
Describe a distinct feature of the nuclei of lymphocytes.	The nucleus of a lymphocyte is round and appears to almost fill the cell due to them having less cytoplasm than the other leukocytes.
Describe the lifespan of lymphocytes.	The lifespan of lymphocytes is hugely variable depending on the type, and ranges from a few days to a few years.
Receptors on the surface of lymphocytes recognise what part of foreign bodies?	The receptors are complementary to the antigen of a foreign body.
Where do B lymphocytes and T lymphocytes develop, respectively?	B lymphocytes originate and mature in the bone marrow, while T lymphocytes develop in the thymus (an organ in the neck).
What are the relative proportions of B lymphocytes and T lymphocytes of blood lymphocytes?	B lymphocytes constitute between 10-30% of blood lymphocytes, whereas T lymphocytes constitute 40-80% of blood lymphocytes.
What are T lymphocytes responsible for?	Cell mediated immunity.
What are B lymphocytes responsible for?	Producing antibody.
What are the two divisions of B lymphocytes and what do they do?	Plasma cells (which produce specific antibody) and memory cells (which allow for quicker recognition in the future as they possess the specific antibody on their surface).
How do B cells function in the immune response?	A B lymphocyte finds an antigen to match an antibody on its cell surface. It remains attached to this antigen until activated by a T helper cell. Then it divides into plasma and memory cells and the plasma cells produce antibody which 'tag' the foreign bodies expressing the antigen for removal by macrophages or other phagocytic cells.
What is the function of a T helper cell?	T helper cells do not directly remove pathogens but do release cytokines such as interleukins to activate other cells in a cascade.
What do T cytotoxic/killer T cells do?	These directly remove foreign cells such as bacteria and cancerous cells, as well as proteins such as viruses, by lysing them.
What is the function of T regulatory cells?	T regulatory cells act as negative feedback to suppress some immune responses.
What are natural killer cells and roughly what proportion of blood lymphocytes do they constitute?	Natural killer cells are large granular lymphocytes which constitute between 5-35% of blood lymphocytes.
What is the function of natural killer cells and what do they primarily target?	Natural killer cells have a role in innate immunity, they act as non-specific defense against virally infected and cancerous cells by releasing proteins to either perforate the infected/cancerous cell membrane or induce apoptosis.
Roughly how many thrombocytes (platelets) does the average human have?	~250 x 10^9 / L of blood, they are the second most numerous blood cell after erythrocytes.
What size are thrombocytes?	Around 3um in diameter and 1um thick.
Describe a distinct feature of the nucleus of thrombocytes.	Thrombocytes are discoid, anuclear fragments, products of larger cells in the bone marrow.
What is the lifespan of the average thrombocyte?	10-12 days
What is the main function of thrombocytes?	Thrombosis, the arrest of blood loss. They are also involved in the early stages of atherosclerosis.
What proportion of the total blood volume does plasma constitute?	~60%
What is plasma?	Plasma is a major transport system composed of a pale yellow aqueous solution of electrolytes, proteins and small organic molecules such as glucose.
Comment on the composition and balance of plasma electrolytes.	The major extracellular cation in plasma is Na+, but it also contains K=, Ca2+, Fe2+ and Mg2+ in lower concentrations. The major plasma anions are Cl- and HCO3-, but (SO4)2- and (HPO4)2- are also present in lower concentrations. Plasma is always electrically neutral, that is the number of positive and negative electrical charges balances, so it maintains an osmotic balance.
Define normality, in the context of health.	Normality is a comparative phenomenon, that property possessed by the majority of the population (>50%).
Define abnormality, in the context of health.	Abnormality is a minority phenomenon that occurs in <50% of the population, and though it may deviate from the norm, it does not necessarily mean that a person is unwell.
Why can't wellness be used to define normality in health?	Because wellness is relative, and person may feel well despite being subject to considerable abnormality, for example in pre-clinical malignancy.
Why can't healthy be used to define the absence of disease?	Because a person may feel healthy but have an asymptomatic disease.
What are reference ranges and how are they derived and used?	Reference ranges are a range of values derived from a population of 'normals'. They are achieved by defining parameters (e.g. the absence of overt symptoms), then defining the population (e.g. by age, gender or ethnicity), then the value of the parameter is measured in each of the 'normal' individuals (e.g. erythrocyte count, height etc). References ranges are used extensively in medicine in the detection of the presence of disordered states.
List some examples of factors affecting measurements in pathology.	Age (for example, foetuses have higher haemoglobin levels than adults), gender (for example, males have higher haemoglobin levels than women as they tend to be more muscular) and ethnicity (for example, black Africans have a lower neutrophil count than Caucasians).

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