Blood cell physiology Flashcards
Red cells: explain the origin and function of red cells, recall the intravascular life span of red cells, and list the physiological factors that influence the rate of red cell production
Origin of red blood cells
- Blood cells of all types originate in the bone marrow
- They are ultimately derived from pluripotent haematopoietic stem cells
- The pluripotent stem give rise to:
- Lymphoid stem cells
- Multipotent myeloid stem cells/precursors
Red cells, granulocytes, monocytes and platelets are derived from these cells
The multipotent myeloid stem cell/precursor can give rise to the proerythroblast –> This then gives rise to erythroblasts and then erythrocytes/red cells
(The blasts have something in common: they have LARGE nuclei and small amounts of cytoplasm)
- As the red cells differentiate, the color of the cytoplasm goes from dark blue to a more pink colour
- This is because the mature red cell is completely pink
- These precursors are classified based on the morphological appearance of its cytoplasm
- The process of producing red blood cells is called erythropoiesis
- Normal erythropoiesis requires the presence of erythropoietin
- Erythropoietin is synthesized mainly in the kidneys (90% juxtatubular interstitial cells) , in response to hypoxia –> increased bone marrow activity –> increased in red cell production
- Erythropoietin is also partly produced in the liver (10% - hepatocytes or interstitial cells))
Functions of red blood cells
- Erythrocytes have a life-‐span of 120 days
- Main function is oxygen transport
- It also transports some carbon dioxide
- 3.5-5 x 1012 /L
- Contain haemoglobin (Hb)
- Each red cell contains approximately 640 million molecules of Hb
- In the mature red cell there is NO nucleus
- The red cells are ultimately destroyed by phagocytic cells in the SPLEEN
(Because the RBCs don’t have a nucleus and have an extensive cytoskeleton, it is good at wriggling through small holes in the capillaries
Above you see one of the red blood cells trying to squeeze through the wall into the sinus in the spleen
As they get older they become less flexible and less able to squeeze through the wall so they get held up in the spleen and destroyed)
White cells: explain the origin and function of white cells and recall their intravascular life span
Origin of white blood cells
- Multipotent haematopoietic stem cells can also give rise of myeloblasts, which in turn can give rise to granulocytes (neutrophils, baseophiles, eosyniphiles)and monocytes
- For the differentiation you need cytokines: G-‐CSF, M-‐CSF, GM-‐CSF and various interleukins
Appearance
Myeloblasts can look like proerythroblasts -‐ they have a LARGE nucleus and little cytoplasm (these are the hallmarks of a blast)
As this develops you end up with a neutrophil
In the 2D film of a neutrophil you see the segmented nucleus and lots of granules
Outline the function of neutrophils
, including , monocytes, and lymphocytes
- The neutrophil survives 7-‐10 hours in the circulation before migrating into the tissues
- Its main function is defence against infection
- It phagocytoses and kills microorganisms
2 pools of neutrophils within the circulation:
- circulating: flowing in vessels
- marginating:
- adherent to the endothelium
- stick to endothelial cells and they roll along and they exit through by diapedesis
- enter tissues (chemotaxis) controlled by chemokines –> reach infected tissues
Outline the function of 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
- It only has TWO lobes in its nucleus
Outline the structure/function of basophils
- These have a role in ALLERGIC RESPONSES
- In basophils there are often so many dark blue dots that you don’t even see the nucleus
- Role in allergic responses
Outline the structure/function of monocytes
- Myeloid stem cell gives rise to monocyte precursors
- These spend several days in the circulation
- They are large cells with a kidney bean-shaped nucleus (contains very fine granules)
- Monocytes migrate to the tissues where they develop into macrophages and other specialised cell types that have a PHAGOCYTIC function
- Macrophages also store and release IRON
Outline the structure/function 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 (lymph- tissues- bile duct -circulation) and then back to the bloodstream
- The intravascular life span of lymphocytes is very variable
Platelets: recall the intravascular life span of platelets and summarise their origin and function
- Multipotent haematopoietic stem cells can also give rise to megakaryocytes and then to platelets by fragmentation
- Platelets survive about 10 days in the circulation
- Platelets have a role in primary haemostasis
- Platelets contribute phospholipid, which promotes blood coagulation
(If someone takes aspirin then it will destroy part of the function of all the platelets and the won’t start working properly again for another 10 days)
Blood result interpretation: recall and explain common Red blood cell abnormalities in blood counts and films
Abnormalities in red blood cells
- Anisocytosis – red cells show more variation in size than is normal
- Poikilocytosis – red cells show more variation in shape than is normal
- Microcytic (microcytosis)– describes red cells that are smaller than normal (or anaemia with small red cells)
- Macrocytic (macrocytosis)– describes red cells that are larger than normal (or anaemia with large red cells)
Types of macrocytes
- Round macrocytes
- Oval macrocytes
- Polychromatic macrocytes
(Normocytic – describes red cells that are of normal size or anemia with normal-sized red cells) + You use LYMPHOCYTES as a reference to determine whether the cells are bigger or smaller than normal
Normally a red cell is a bit smaller than a lymphocyte
Distinguish between different types of poikilocytosis
Poikilocytes come in a great variety of shapes
- Spherocytes
- Irregularly contracted cells
- Sickle cells
- Target cells
- Elliptocytes
- Fragment
Target Cells
Cells with an accumulation of hemoglobin in the middle of the central pallor
They occur in:
- Obstructive jaundice
- Liver disease
- Haemoglobinopathies
- Hyposplenism
Elliptocytes
- These are elliptical in shape
- They occur in:
- Hereditary Elliptocytosis
- Iron Deficiency
Sickle Cells
These are sickle or cresent shaped
They result from the polymerisation of haemoglobin S when it is present in a high concentration
Fragments
- 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 -‐ its just the shape that is different
Rouleaux
- 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
Agglutinates
- 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
Howell-‐Jolly Body
- 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
- This is seen in the blood film as a very precise and distinct dot
- Platelets overlying red cells have a little bit of fuzziness
Discuss hypochromia, hyperchromia, and polychromasia
Hypochromia
- 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
- Red cells in hypochromia are described as being hypochromic(often goes together with microcytosis)
Appearance:
- You see a rim of redness around the cell, almost all of it is pale
- Iron is visible in the middle of the cell because it can’t be incorporated since there is no haemoglobin
Hyperchromia
Definition: the cells LACK central pallor
This can occur because they are thicker than normal or because their shape is abnormal
Cells are hyperchromatic or hyperchromic
Has many causes since many abnormally shaped cells lack the central thinner area
TWO types of hyperchromatic cells:
1. Spherocytes (στούμπι)
- Spherocytes are very round and hyperchromatic
- Lack of central pallor
- They result from the loss of cell membrane without the loss of an equivalent amount of cytoplasm
- 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
2. Irregularly Contracted Cells
- Irregularly contracted cells don’t show a complete circle
- 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 hemoglobin
- This helps to narrow down the diagnoses
Polychromasia
- 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
- Reticulocytes can be detected using a reticulocyte stain -‐ methylene blue
- Detecting polychromasia or increased numbers of reticulocytes gives you similar information
- However, identification of reticulocytes is more reliable so they can be counted
NOTE: if a patient is anaemic but has reticulocytosis then that shows that the bone marrow is capable of making new cells
Recall and explain common White Blood Cell abnormalities
Leucocytosis ‐ too many white cells
Leucopenia ‐ too few white cells
Neutrophilia ‐ too many neutrophils
NOTE: neutrophilia doesn’t necessarily mean that there are too many because neutrophilia is the normal response to infection
Neutropenia ‐ too few neutrophils
Lymphocytosis ‐ too many lymphocytes
Eosinophilia ‐ too many eosinophils
Thrombocytosis ‐ too many platelets
Thrombocytopenia - too few platelets
Erythrocytosis - lots of red blood cells
Reticulocytosis - lots of reticulocytes
Lymphopenia - decrease in the number of lymphocytes
Atypical Lymphocyte
(not really interested in the size and shape of the white blood cells except for lymphocytes)
- Usually: 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
- 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)
Left shift
- Left shift means that there is an increase in non-segmented neutrophils or that there are neutrophil precursors in the blood
Toxic Granulation
- Toxic granulation is the heavy granulation of neutrophils
- It results from infection, inflammation and tissue necrosis
- This is also a feature of normal pregnancy
Hypersegmented neutrophil
- This means there is an increase in the average number of neutrophil lobes or segments
- It usually results from a lack of vitamin B12 or folic acid
Explain the meaning of the terms ‘reference range and ‘normal range’ and how they are derived
‘Normal’ can be affected by
- Age
- Gender
- Ethnic Origin
- Physiological Status
- Nutritional Status
- Cigarette Smoking
- Alcohol Intake (white cells affected)
How is a normal or reference range determined?
A REFERENCE range is derived from a carefully defined reference population e.g. children 5-‐10 yrs
A NORMAL range is a much vaguer concept -‐ it should represent people that live in the local area and come to the hospital
How is a reference range determined?
- Samples are collected from healthy volunteers with defined characteristics
- They are analyzed by the instruments and techniques that will be used to analyze patient samples
- The data is analyzed by an appropriate technique
- Normal does NOT necessarily mean that it is healthy e.g. the UK average cholesterol is probably quite high
- If the data follows a normal (Gausian) distribution you can determine what is normal by taking the mean and doing 2 standard deviations on each side
- 2 standard deviations on either side will include 95% of the data
Haemoglobin shows a Gausian distribution
White blood cell count does NOT show a Gausian distribution so must be analysed in other ways - Not all results outside the reference range will be abnormal and not all the results within the normal range will be normal
- A health-‐related range may be more meaningful than a 95% range
- There may be some overlap in the results achieved by sick people and healthy people
Interpret the components of a blood count and decide what is normal
Full Blood Count - Abbreviations
WBC – white blood cell count in a given volume of blood (× 109/l)
RBC – red blood cell count in a given volume of blood (× 1012/l)
Hb – haemoglobin concentration (g/l)
Hct – hematocrit (l/l) (% of RBC in blood)
MCV – mean cell volume (fl) (Haematocrit/RBC x10)
good for differentiating between different types of anaemia
MCH - mean cell hemoglobin - amount of haemoglobin in a given volume of blood divided by the number of red cells in the same volume (pg) (Hb/RBCx10)
MCHC– mean cell haemoglobin concentration (Hb/Haematocrit x100) (g/l)
Platelet count – the number of platelets in a given volume of blood (× 109/l)
WBC, RBC and platelet count:
- Initially counted visually, using a microscope and a diluted sample of blood
- Now done by automated machines: They count the number of electrical impulses generated when cells flow between a light source and a sensor or when cells flow through an electric field
Hb
- Initially measured by a spectrometer, by converting haemoglobin to a stable form and measuring light absorption at a specific wave length
- It is now measured by an automated machine but the principle is the same
Hct
- Initially measured by centrifuging a blood sample
MCV
- Initially counted by dividing the total volume of red cells by the number of red cells (PCV/RBC)
- It is now determined indirectly by light scattering or by interruption of an electrical field
- Average red cell size tends to be fairly uniform
- You can’t compare MCV by looking at a blood film unless you have a reference leukocyte
MCH
- MCH is the absolute amount of haemoglobin in an individual red cell
- In microcytic and macrocytic anaemia, the MCH tends to parallel the MCV
- MCHC is the concentration of haemoglobin in the cell
- MCHC is related to the SHAPE of the red cell
- MCHC is measured electronically on the basis of light scattering
- Cells with reduced MCHC can appear less red
- Cells can have normal MCH but low/high MCHC depending on the size of the RBC
