Blood cell physiology Flashcards

(97 cards)

1
Q

Where do blood cells originate?

A

ALL blood cell types originate in the bone marrow.

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2
Q

What stem cells are blood cells derived?

A

Multipotent haemopoietic stem cells.

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3
Q

How do multipotent haemopoietic stem cells differentiate into blood cells?

A

Multipotent stems cells differentiate into LYMPHOID STEM CELLS and MYELOID STEM CELLS. Erythroid = red blood cells.

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4
Q

How do stem cells differentiate and not diminish their own supply?

A

When stem cell divides into two, one stem cell differentiates into mature progeny (meaning offspring); the other divides again and renews supply.

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5
Q

What are the stages of differentiation from a myeloid stem cell to an erythrocyte?

A

□ Myeloid stem cell gives rise to a PROERYTHROBLASTS.

□ Which gives rise to early, intermediate and late ERYTHROBLASTS in the bone marrow. An erythroblast is any cell with RBC potential and a nucleus.

□ Late erythroblast then squeezes its cytoplasm across endothelium, into a sinusoid (type of capillary). This cytoplasm creates a RETICULOCYTE which gives rise to ERYTHROCYTES – nucleus lacking. The nucleus that’s left behind is broken down by a macrophage.

□ The initial erythrocyte in the circulation is called POLYCHROMATIC ERYTHROCYTE and contains ribosomes meaning that it is capable of synthesising haemoglobin.

□ After a few days, the cell shrinks and become MATURE ERYTHROCYTES.

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6
Q

What is the process of producing erythrocytes called?

A

Erythropoiesis.

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7
Q

What hormone is required for erythropoiesis? Stimulus of this hormone? (x2)

A

Erythropoietin. Produced in response to HYPOXIA or ANAEMIA.

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8
Q

Where is erythropoietin produced? (x2)

A

□ 90% - JUXTATUBULAR INTERSTITIAL CELLS of the KIDNEY. (Juxtaglomerular cells are near glomerulus and secrete renin.) □ 10% - HEPATOCYTE and INTERSTITIAL CELLS of the LIVER.

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9
Q

What is the life span of RBCs?

A

120 days. Long time compared to other blood cells.

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10
Q

What are the functions of erythrocytes? (x2)

A

Oxygen and CO2 transport, though most CO2 transport occurs in the plasma.

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11
Q

How are erythrocytes destroyed?

A

By phagocytic cells of the spleen and liver – though mainly spleen.

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12
Q

What are the stages of differentiation from multipotent haemopoietic stem cells to granulocytes and monocytes?

A

Multipotent stem cells give rise to MYELOID STEM CELL which gives rise to MYELOBLASTS and MONOBLASTS, which give rise to granulocytes and monocytes respectively.

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13
Q

What are granulocytes?

A

Category of white blood cells characterized by the presence of granules in their cytoplasm. They include neutrophils, eosinophils, basophils, and mast cells.

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14
Q

What are monocytes?

A

Category of white blood cells, including macrophages and myeloid lineage dendritic cells.

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15
Q

What influences the differentiation of granulocytes and monocytes? (x2) Examples? (x3)

A

□ CYTOKINES and INTEREUKINS. □ Cytokine G-CSF (granulocyte colony-stimulating factor), GM-CSF (granulocyte-macrophage colony-stimulating factor), and M-CSF (macrophage colony-stimulating factor).

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16
Q

What is the life span of neutrophils?

A

7-10 hours in the circulation before migrating to tissues.

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17
Q

What are the is the main function of neutrophils? (x1)

A

Circulate in blood then migrate to tissues where they bind to pathogens, phagocytose them, and kill them. First cells to be recruited to the site of infection.

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18
Q

What are the two types of neutrophil?

A

Circulating and margination neutrophils. Circulating are in the central part of blood vessels, moving with blood; margination neutrophils are adhered to the endothelium of blood vessels, accessing tissues.

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19
Q

How do neutrophils leave blood and enter tissues?

A

Adhesion and margination to endothelium. Here, they roll and squeeze between endothelial cells and into tissue – diapedesis. From here, they migrate to sites of infection by chemotaxis – guided by chemokines.

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20
Q

What is the main function of eosinophils?

A

Phagocytic, release granules, and particularly important in defending against parasitic infection. Help with B cell responses by producing IgA.

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21
Q

What is the main function of basophils? (x2)

A

Have a role in allergic responses and inflammation (produce histamines). Release granules and may act as antigen-presenting cells for ‘type 2’ immunity (refers to antibody mediated immunity).

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22
Q

What is the physiology of monocytes? Functions? (x4)

A

Spend several days in the circulation and then migrate to tissues where they develop into MACROPHAGES and OTHER SPECIALISED CELLS. These cells have four main functions: 1. PHAGOCYTOSIS: Granules containing enzymes fuse with phagosomes, which digest ingested material. 2. MEDIATOR: MACROPHAGE has receptors for microbes, and upon binding and ingesting, release soluble cytokine mediators to recruit further cells. 3. ANTIGEN PRESENTATION: macrophages present fragments of antigen on surface to T-lymphocytes. 4. Macrophages store and release iron (from capacity to consume Hb from erythroblasts in bone marrow).

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23
Q

What do megakaryocytes do?

A

These are large cells of the bone marrow that develop into platelets by fragmentation of the cytoplasm. They leave their nucleus in the bone marrow for macrophages to pick up and destroy.

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24
Q

How long do platelets survive in the circulation?

A

About 10 days.

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25
What are the roles of platelets? (x2)
Have a role in primary haemostasis (formation of platelet plug). When active, they also express a negatively charged phospholipid, which is the binding site of coagulation factors; so platelets also promote blood coagulation (a feature of secondary haemostasis with resultant fibrin deposition and linking).
26
How do lymphocytes circulate around the body?
Recirculate to lymph nodes and other tissues, and then back to the blood stream.
27
What is the function of lymph nodes – how is this exercised?
Nodes filter antigens in the lymph – see if immune system recognises any of those antigens. Afferent lymphatic vessels bring lymph fluid into the node, while efferent leaves the node. Fluid collected is filtered through lymphocytes so can react if antigens are present.
28
What is lymphocyte recirculation?
Primary lymphoid tissues produce naïve lymphocytes that enter the blood and circulate BETWEEN blood and secondary lymphoid tissues until they react or die. Move into lymphoid organs where immune cells may be holding out antigens etc.
29
What are the two types of lymphocyte?
B and T.
30
What are the functions of B-lymphocytes? Maturation?
Involved in humoral immunity – produce antibodies and matured in bone marrow.
31
What are he functions of T-lymphocytes? Maturation?
Attack infected cells and mature in the thymus. Recognise infectious agents and trigger immune respose. Cell-mediated immunity.
32
What do (i) lymphocytes, (ii) neutrophils, (iii) monocytes, (iv) eosinophils and (v) basophils look like?
All cells listed other than lymphocytes are polymorphonuclear granulocytes. (iii) indented nucleus, pale granules; (iv) bi-lobed nucleus, granules are bright pink; (v) granules stain strongly.
33
What is anisocytosis?
Red cells how more variation in size than normal.
34
What is poikilocytosis?
Red cells show more variation in shape than is normal.
35
What is micro- and macrocytosis?
Micro = red cells are smaller than normal; macro = red cells are larger than normal.
36
How can size of red blood cells be assessed without measuring diameter?
Lymphocyte nucleus should have roughly the same diameter as red blood cells.
37
What are the different types of macrocytes? (x3) What are these types based on? (x2) Appearance?
Based on their shape and staining characteristics on blood film. * Round * Oval * Polychromatic.
38
What are polychromatic macrocytes? Disease?
• Immature red blood cells. • DISEASE = Polychromasia. Disorder of abnormally high number of these immature RBCs and seen as an increased blue tinge to the cytoplasm of a red blood cell. The bluer the red blood cell, the more premature it is, and the more ribosomes it still has. • and could be a sign of damage to bone marrow or anaemia.
39
Clinical significance of oval macrocytes?
Can indicate deficiency in vitamin B12 or folic acid.
40
What is hypochromia?
• Normal RBCs have about a third of their diameter looking pale under the microscope – because of their biconcave nature. • This centre looks pale because there is LESS HAEMOGLOBIN. • Hypochromia means that cells have a LARGER AREA of central pallor = LOWER HAEMOGLOBIN CONTENT AND a flatter cell.
41
What RBC disorder is often associated with hypochromia?
Microcytosis because they both usually have same underlying cause e.g. Fe deficiency leading to failed Hb synthesis.
42
What is hyperchromia?
Cells lack central pallor.
43
What is the chromic nature of microcytic, normocytic and macrocytic RBCs?
• MICROCYTIC are usually hypochromic. • NORMOCYTIC are normochromic. • MACROCYTIC are also normochromic, because the mechanism that makes them large doesn’t usually inhibit Hb production.
44
What are the two main types of hyperchromia?
Spherocytes and irregularly contracted cells.
45
What is the cause of each type of hyperchromia? Under the microscope?
* SPHEROCYTES – shape is spherical. They have a round, regular outline. CAUSE: loss of cell membrane without the loss of equivalent amount of cytoplasm, so the cell is forced to round up. * IRREGULARLY CONTRACTED CELLS – are irregular in outline but are smaller than normal cells and have lost their central pallor. CAUSE: from oxidant damage to the cell membrane and to the haemoglobin.
46
What is hereditary spherocytosis?
Hereditary cause of spherocyte hyperchromia. In a blood film, you will only see some spherocytic cells (blue arrows). Others have SMALLER central pallor, so are on their way to becoming spherocytic (red arrows).
47
What is a reticulocyte?
Immature red blood cell without a nucleus, having a granular or reticulated appearance when stained.
48
What is reticulocyte count?
Expose cells to a dye – usually methylene blue. The number of reticulocytes is counted and expressed as a percentage of the number of cells present.
49
What is a reticulocyte count used for?
Detecting polychromasia or reticulocytosis. Although they appear a blue tinge without a stain, it can be harder to identify reticulocytes. This count using a stain is much more accurate.
50
What are the different types of poikilocytosis? (x6)
Sickle cell, target cell, elliptocyte, fragments, spherocytes, irregularly contracted cell.
51
What do sickle cells look like?
Sickle cell shape.
52
What do target cells look like?
Bit of Hb in the middle.
53
What do elliptocytes look like?
Ellipse – oval and elongated.
54
What is the cause of target cell production? (x3)
Occur in obstructive jaundice, liver disease, haemoglobinopathies and hyposplenism.
55
What is the cause of elliptocytes? (x2)
Hereditary elliptocytosis and iron deficiency.
56
What is the physiology of sickle cell?
Result from polymerisation of haemoglobin S when it is present in high concentration.
57
What are schistocytes?
Fragmented part of a red blood cell.
58
What is a rouleaux? Physiology?
Are stacks of red blood cells – likened to a pile of pennies. They result from alterations in plasma proteins: usually, RBCs repel each other.
59
What are agglutinates? Physiology?
Differ from rouleaux in that they are irregular clumps rather than tidy stacks of RBCs. They usually result from antibody on the surface of the cells.
60
What is a Howell-Jolly body?
Is a nucleus remnant in a red blood cell.
61
What is the cause of Howell-Jody body?
Lack of splenic function as spleen normally removes this.
62
What is leucocytosis?
Too many white cells.
63
What is leucopenia?
Too few white cells.
64
What is neutrophilia?
Too many neutrophils.
65
What is neutropenia?
Too few neutrophils.
66
What is lymphocytosis?
Too many lymphocytes.
67
What is eosinophilia?
Too many eosinophils.
68
What is thrombocytosis?
Too many platelets.
69
What is thrombocytopenia?
Not enough platelets.
70
What is erythrocytosis?
Increased numbers of RBCs.
71
What is lymphopenia?
Not enough lymphocytes.
72
What is the difference between symptoms and signs?
Symptoms – what patient tells you about e.g. fatigue; signs – what the doctor notices about the patient e.g. lump, reduced RBC pallor.
73
What are atypical lymphocytes used to describe?
They describe abnormal lymphocytes, but often used to describe abnormal lymphocytes present in infectious mononucleosis (glandular fever).
74
What is left shift?
LEFT SHIFT – meaning that there is an increased number of immature, non-segmented neutrophils from increase in neutrophil precursors in the blood i.e. neutrophils have not reached their final stages of maturation.
75
What is toxic granulation? Causes? (x2 groupings)
Heavy granulation of neutrophils resulting from infection, inflammation and tissue necrosis. This is also a normal feature of pregnancy.
76
What is hyper-segmented neutrophil? Cause?
Increased number of neutrophil lobes. Caused usually by lack of vitamin B12 or folic acid.
77
What is a reference range?
• Derived from a HEALTHY reference POPULATION e.g. healthy males that are aged between 50 and 70. • Defined as the interval between which 95% of values of a reference population fall into, in such a way that 2.5% of the time a value will be less than the lower limit of this interval, and 2.5% of the time it will be larger than the upper limit of this interval, whatever the distribution of these values. • Values are normally distributed.
78
What is a normal range?
This is a much vaguer concept. It is derived in a LABORATORY which has looked at published ranges and created what they deem to believe is ‘normal’. Values within this range is normally distributed. By definition, the range encompasses 95% of the population – so 2.5% of the population fall off each side of the normal range.
79
What is ‘normal’ affected by in haematology? (x9)
• Age • Gender • Ethnic origin • Physiological status • Altitude • Nutritional status • Cigarette smoking • Alcohol intake • Altitude
80
How does altitude affect haemoglobin?
Hypoxia induced stimulation of production of erythropoietin in the kidneys, so Hb concentration increases.
81
How is a reference range determined?
• Samples collected from healthy volunteers with defined characteristics. • They are analysed and samples taken. • The data is analysed using an appropriate statistical technique – data with a normal distribution can be analysed by determining mean and standard deviation, and taking mean +/- standard deviation as 95% range.
82
What is the problem with reference/normal ranges?
* Not all results within the normal range are normal. * Similarly, not all the results outside the reference range are abnormal. * If we use these ranges for diagnostic testing, this can be come problematic – look at photo.
83
What is a full blood count?
Gives details on levels of different cells within your blood.
84
What are the abbreviations in a full blood count and what do they mean, including units? (x9)
• WBC: white blood cell count given in volume of blood (x 10^9/l) • RBC: red blood cell count given in volume of blood (x 10^12/l) • Hb: haemoglobin concentration (g/l). • Hct: haematocrit (l/l). • PCV: packed cell volume (& or l/l) – an older name for the Hct. • MCV: mean cell volume (fl) • MCH: mean cell haemoglobin (pg) • MCHC: mean cell haemoglobin concentration (g/l) • Platelet count: the number of platelets in a given volume of blood (x 10^9/l).
85
How is WBC, RBC and platelet count determined in the lab?
Counted in large automated instruments, by counting electronic impulses generated when cells flow between a light source and a sensor or when cells flow through an electrical field.
86
How is Hb determined in the lab?
Measured in a spectrometer, by converting Hb into a stable form and measuring light absorption at a specific wavelength. Now, this is an automated process. Hb concentration is concentration in the WHOLE blood, and not cell specific i.e. if there are too many RBCs, Hb concentration INCREASES, even though it may be normal in each individual cell.
87
How is PCV or Hct determined a lab?
They are the same – PCV describes manual process; Hct describes the now automated process. Capillary tube of blood (anticoagulated) is centrifuged and different blood components are separated based on density (white cells have smaller density). The proportion of the column occupied by RBCs is measured.
88
How is MCV determined a lab? (x2)
• Initially calculated by dividing total VOLUME of red cells by the NUMBER of red cells in the sample i.e. PCV divided by RBC. • Now determined by light scattering or by interruption of an electrical field.
89
How is MCH determined in a lab?
The amount of haemoglobin in a volume of blood divided by the number of red blood cells in the same volume i.e. Hb divided by RBC.
90
How is MCHC determined in a lab?
The amount of haemoglobin in a volume of blood divided by the proportion of the sample represented by the red blood cells i.e. Hb divided by Hct. Determined nowadays using light scattering.
91
How are MCHC scatterplots interpreted?
Light scattering produces scatter plots. The two vertical lines represents normal RANGES. In first picture, MCHC is low because there are many cells which fall below the lower bound for the range. In the third picture, MCHC is high because there are many cells which are above the higher bound for the range.
92
What is the difference between MCH and MCHC?
• If an RBC is smaller, but has normal Hb concentration inside it, then MCH is reduced, but MCHC is normal – because MCHC determines CONCENTRATION in cell and MCH determines AMOUNT in a single cell. • If an RBC is smaller and got reduced Hb concentration, MCH and MCHC will both be reduced.
93
What is the relationship between MCH and MCV in anaemias?
In microcytic and macrocytic anaemias, the MCH tends to be in correlation with the MCV, because as RBC changes size (and Hb concentration inside them stays the same), the AMOUNT of Hb in each cell will change by the same amount.
94
What happens to MCHC in spherocytic RBCs?
Increases because Hb concentration increases as RBC is enclosed in a smaller amount of cell membrane. MCH however does not change.
95
What happens to MCHC in sickle cells?
Tends to increase because these cells lose fluid, so Hb inside becomes quite dense. MCH however does not change.
96
How does Hb differ across the sexes?
Males have higher Hb.
97
How does Hb, RBC and Hct differ across ages? (x3)
Neonates = highest. Lower in children than in adults.