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1
Q

What is a haematocrit?

A

A measure of the percentage of total blood volume made up by red blood cells. (Increased in polycythaemia.)

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2
Q

What proportion of blood is cells?

A

45% cells, 55% plasma.

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3
Q

Function of red blood cells.

A

Carry oxygen from lungs to tissues, and carbon dioxide from tissues to lungs.

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4
Q

Function of neutrophils.

A

Granular leukocyte. Phagocytosis and killing bacteria with lysozyme. Part of innate immunity and inflammatory response.

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5
Q

Function of eosinophils.

A

Granular leukocyte. Kill parasitic worms (helminths), and combat effects of histamine in allergic reaction by phagocytosing antibody-antigen complex.

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6
Q

Function of basophils.

A

Granular leukocyte. Secrete histamine, heparin, and serotonin to intensify overall inflammatory response.

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7
Q

Function of T lymphocytes.

A

Agranular leukocytes. Attack invading viruses and cancer cells and transplanted tissue cells.

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8
Q

Function of B lymphocytes.

A

Agranular leukocytes. Develop into plasma cells which secrete antibodies.

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9
Q

Function of natural killer cells.

A

Attack infectious microbes and spontaneously arising tumour cells.

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10
Q

Function of platelets.

A

Subcellular fragments from megakaryocytes. Form a platelet plug to prevent blood loss in haemostasis, and secrete chemicals to stimulate vascular spasm and blood clotting.

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11
Q

Where does haematopoeisis occur before birth?

A

Yolk sac, then thymus, liver and spleen.

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12
Q

Where does haematopoiesis occur?

A

Red bone marrow (mostly in axial skeleton but also in pelvic and pectoral girdle, and proximal epiphyses of humerus and femur).

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13
Q

What is red bone marrow?

A

Highly vascularised connective tissue in the microscopic spaces between the trabecular of spongy bone tissue.

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14
Q

Name the two stem cells the pluripotent stem cells in red bone marrow differentiate into.

A

Myeloid stem cell (forms proerythroblasts, megakaryoblasts, mast cells, basophil myeloblasts, eosinophil myeloblasts, myeloblasts, monoblasts), and lymphoid stem cell (forms B lymphoblasts, T lymphoblasts, natural killer lymphoblasts).

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15
Q

Name the haematopoeitic growth factors.

Haematopoiesis is regulated by growth factors produced in stroma.

A

Erythropoietin, EPO (secreted by interstitial fibroblasts in kidney).
Thrombopoietin, TPO - Mpl ligand - also stimulates proliferation of LT-HSCs (secreted by liver).
Cytokines (glycoproteins secreted by red bone marrow cells and leukocytes and macrophages [autocrine and paracrine] that increase proliferation of progenitor cells) e.g interleukins 1 2 3 and 7, colony-stimulating factor (CSF), c-kit ligand (stem cell factor).

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16
Q

Name the blood cells that have similar cells normally found in tissues.

A

Basophils (mast cells in connective tissue).

Monocytes (mature into dendritic cells and macrophages in the tissue).

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17
Q

State the approximate intravascular lifespan of red blood cells, neutrophils and platelets.

A

Red blood cells = 120 days (100-200).
Neutrophils = 1 - 2 days (days in spleen and other tissues).
Platelets = 5 - 9 days.

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18
Q

State the components of blood plasma.

A

Water (solvent, distributes heat).
Plasma proteins (albumins [maintains oncotic pressure for fluid exchange at capillary bed], globulins [immunoglobulins produced by plasma cells], fibrinogen [for blood clotting]).
Electrolytes.
Nutrients (glucose, glycerol, fatty acids, amino acids, vitamins and minerals).
Gases (carbon dioxide, oxygen, nitrogen).
Regulatory molecules (hormones, enzymes, vitamins [cofactors for enzymes]).
Waste products (urea, creatine, creatinine, bilirubin, ammonia [most from protein metabolism]).

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19
Q

What is the name of the glycolipids and glycoproteins (antigens) on the surface of erythrocytes that determine blood type?

A

Agglutinogens.

The antibodies for these are called agglutinins.

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20
Q

Name two major blood groups.

A

ABO and Rh.

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21
Q

In the blood group ABO, what blood type is someone whose RBCs display neither antigen A or antigen B?

A

Type O.

They will have agglutinins for both anti-A and anti-B in their plasma

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22
Q

What is the genetic basis of the ABO blood group?

A

The ABO gene codes for a glycosyltransferase which catalyses the final step in the production of the agglutinogens. There are three polymorphisms, one which codes for antigen-A, one for antigen-B, and one which codes for an inactive glycosyltransferase which results in blood type O.

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23
Q

What are the consequences of an incompatible blood transfusion?

A

The recipient’s antibodies will bind to the antigens on the donor RBCs causing AGGLUTINATION.
Also, the complement proteins in the plasma will make the donor RBC’s plasma membranes leaky so haemoglobin pours out into the plasma (haemolysis). The haemoglobin may damage the kidneys by blocking filtration membranes in the glomeruli.

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24
Q

What is agglutination?

A

Clumping of red blood cells due to an antibody-antigen response in which RBCs become cross-linked to each other.

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25
What are people with type AB blood known as, due to them having neither antibody in their plasma?
Universal recipients.
26
What are people with type O blood known as, due to them having neither antigen on their RBCs?
Universal donors.
27
How many genes may code for the Rh antigen?
Alleles of 3 genes.
28
Does normal blood plasma contain anti-Rh antibodies?
No, but if an Rh- person is exposed to Rh+ blood, their immune system will produce anti-Rh antibodies which will stay in their blood.
29
How does HDN (haemolytic disease of the newborn) develop?
When a Rh- mum has an Rh+ baby for the first time, some of the foetus's Rh+ blood may leak across the placenta at deliver and cause the mum to make anti-Rh antibodies which will stay in her blood. When the mum has a second Rh+ baby, the antibodies will cross the placenta and cause agglutination and haemolysis in the foetus's blood.
30
How is HDN treated?
Inject anti-Rh antibodies into the mum's blood before and after delivery to inactivate the Rh antigens before her immune system gets a chance to make anti-Rh antibodies.
31
What is an antiserum?
Solution containing antibodies.
32
How is blood ABO blood typed?
Add one drop to an antiserum containing only anti-A antibodies and one drop to one containing only anti-B antibodies. If agglutination occurs in the anti-A serum only then the blood is type A. If agglutination occurs in both the blood is type AB. If agglutination occurs in neither then the blood is type O.
33
How is blood Rh blood typed?
Add a drop of blood to an antiserum containing anti-Rh antibodies. Agglutination = Rh+. No agglutination = Rh-.
34
What is a cross-match?
Mix a sample of the donor's and recipient's blood. If no agglutination occurs then the recipient's blood contains not antibodies for the antigens in the donor blood, so blood transfusion is safe.
35
What type of molecule is haem?
Porphyrin containing iron.
36
What metal is present in haem?
Iron, Fe2+.
37
What are the three main causes of oedema?
1) Hypertension causing an increased hydrostatic pressure at the arteriole end of the capillary bed and so and increased rate of fluid moving out of the capillaries. 2) Liver damage causing decreased protein in the blood causing reduced oncotic pressure at the venous end of the capillary bed. 3) Insufficient drainage into lymphatic vessels caused by a blocked lymph node.
38
Give 3 examples of second messengers.
1) Ca2+. 2) cAMP. 3) Inositol triphosphate. 4) Diacylglycerol.
39
What is the cellular effect of a kinase-linked receptor?
Phosphorylation cascade, which can result in changes to cell metabolism, shape, gene expression, and ability to divide.
40
What is the cellular effect of a nuclear receptor?
Receptor-ligand complex acts as a transcription factor in the nucleus, altering gene expression.
41
What do erythrocytes lack?
Nucleus, endoplasmic reticulum, mitochondria.
42
Which blood cells stain red-orange with acidic dyes?
Eosinophils.
43
What do erythrocytes look like?
Biconcave, bright in the middle, small, most numerous cell.
44
What do platelets look like?
Purple fragments.
45
What do neutrophils look like?
Multi-lobed purple nucleus, granular cytoplasm (red granules).
46
What do basophils look like?
Purple granules obscuring multi-lobed nucleus.
47
What do eosinophils look like?
Red granules and a multi-lobed nucleus showing through.
48
What do lymphocytes look like?
Big purple nucleus filling up cytoplasm, smallest leukocyte.
49
What do monocytes look like?
Purple-stained nucleus that looks bean-shaped.
50
Name a common way blood is analysed.
Impedance.
51
Explain how blood is analysed by impedance.
A dilute solution (so one cell passes at a time) of the blood sample is passed through a small aperture across which a current is applied. The cells impede the current (so can be detected) and different cells impede the current differently - according to size and membrane composition. Haemoglobin contains iron which radically changes the surest flow according to the concentration of iron.
52
Which cells secrete perforins, and how do they work?
Cytotoxic (CD8+) T lymphocytes, and Natural Killer cells secrete perforins. Perforins are pore forming proteins that bind to the target cell's membrane and allow diffusion of granzymes (pro-apoptotic proteases) into the cytoplasm.
53
What is the main site of haematopoiesis during foetal life?
Liver (haematopoeitic until just before birth).
54
In early foetal life (definitive haematopoeisis), name the cells (and the embryonic tissue they're derived from) that are produced in the yolk sac and give rise to vascular endothelial cells and haematopoeitic stem cells to form a blood island that develops into a capillary.
Haemangioblasts (derived from mesoderm).
55
Define a haematopoietic stem cell.
Multipotent stem cells, that give rise to all blood cell types.
56
What's the difference between short-term haematoppoietic stem cells (ST-HSCs) and long-term haematopoietic stem cells (LT-HSCs)?
Long-term haematopoietic stem cells are long-lived, divide very rarely (when short-term cells are depleted), and can self-renew. Short-term haematopoietic cells have a shorter lifespan, have only a limited capacity to self-renew, and divide much more frequently to produce committed multipotent progenitor cells.
57
What are committed multipotent progenitor cells?
Stem cells committed to either myeloid or lymphoid lineages, which divide to form more differentiated progenitor cells.
58
What are the large white cells in bone marrow?
Steatocytes - fat cells.
59
Name the cytoskeletal protein in red blood cells that forms a scaffold to maintain the integrity and shape of the RBC membrane.
Spectrin.
60
Name the protein in red blood cells that anchors ion channels to the spectrin scaffold.
Ankyrin.
61
Name the protein in red blood cells which stabilises the interaction of spectrin and actin, so forming the erythrocyte membrane skeleton, and state what a mutation in this protein could lead to.
Band 4.1 protein, deficiency leading to spherocytosis and anaemia.
62
Name the protein making up 25% of the RBC membrane surface, which facilitates the exchange of bicarbonate and chloride ions, so has a key role in the carriage of carbon dioxide (anchored to spectrin by ankyrin).
Band 3 protein (Anion Exchanger 1).
63
What is the volume of plasma in the average person?
2.5 - 3 litres.
64
What is the name of the clear fluid extruded when blood has coagulated?
Serum.
65
Name some key functions of plasma.
Maintain pH balance, transport cells and proteins, distribute heat.
66
Name the machine in the pathology lab used to analyse blood and obtain a Full Blood Count, and name some of the analysis techniques it can use.
Haematological blood analyser. Impedence, spectrometry, flow cytometry, cytochemistry, microscopy, immunoassays (detect concentrations of molecules e.g EPO).
67
Why is it an advantage that haematopoiesis occurs in the bone in an adult?
It is a protected environment.
68
Name the peripheral immune tissues.
Lymph nodes, Peyer's patches, spleen, tonsils = secondary lymphatic tissues (where immune response is mounted). Red bone marrow, thymus = primary lymphatic tissue (where immune cells develop).
69
What is cord blood a very rich source of?
Haemopoeitic stem cells.
70
How do haemangioblasts develop into capillaries?
Haemangioblasts develop from the mesoderm, then aggregate and form blood islands - where the outer cells differentiate into vascular endoderm cells, and the inner cells differentiate into haematopoietic stem cells. Initially in yolk sac, but then primarily in foetal liver.
71
In haematopoiesis, LT-HSCs proliferate the least, and the multipotent stem cells proliferate a lot more. Why is this a good thing?
The LT-HSCs (which are needed to give rise to all blood cells for the whole of your life), and the other HSCs are protected from lots of proliferation, this is good because proliferation always carries the risk of mutation.
72
When a haematopoietic stem cell is stimulated by the growth factors (protein regulators), what are the four possible effects?
Self-renewel, death, expansion, differentiation (following expansion, or maybe directly).
73
What is the difference in the globulin chains between adult and foetal haemoglobin?
Adult = a1, a2, B1, B2. Foetal = two alpha chains, two gamma chains. Foetal haemoglobin has higher affinity for oxygen than maternal.
74
Is haematopoiesis a very rapid process?
Yes.
75
What is an important function of the spleen?
Filtering blood - removal of damaged/old red blood cells by macrophages.
76
What is the difference between the white pulp and red pulp in the spleen?
White pulp is where the immune cells are, red pulp is where the macrophages remove old/damaged red blood cells.
77
What is the usual reason for removal of the spleen?
Surgical trauma. 95% of blood filters through the spleen in 3 minutes, so if it is ruptured then you will bleed to death very fast.
78
What are the antigens that determine blood groups made from?
Sugar residues - so different blood groups have different glycosylation of the RBC.
79
What is a function of the spleen to do with platelets, and what significance cores this have in contraction?
The spleen has a reservoir of platelets. If you injure yourself, splenic contraction occurs and platelets are released into the blood to allow haemostasis.
80
Why do megakaryocytes have multi-lobed nuclei?
They can duplicate their DNA up to 64 times.
81
Name two molecules that are used in haemostasis along with platelets to create aggregates.
Fibrogen, and von Willebrand Factor (vWF).
82
What is the function of platelets?
To force red blood cells to clot by creating aggregates - they also secrete granules containing specific platelet factors, and also produce factors that regulate the immune response.
83
Which are the most common leukocytes in blood and what proportion of the leukocytes do they make up?
Neutrophils - 70%.
84
What is the main function of neutrophils?
To migrate to the site of injury (recruited) and INDUCE INFLAMMATION, phagocytose bacteria, and secrete granules containing toxic compounds.
85
What symptoms do neutrophils cause when they induce inflammation?
Redness, heat, pain, swelling, loss of function.
86
What happens to the dead neutrophils?
Macrophages phagocytose them.
87
Name some conditions that would cause neutrophil leukocytosis (increased neutrophils in the blood).
Pregnancy, malignancy, smoking, iatrogenic (caused by medical treatment/intervention), haemorrhage, inflammatory disease.
88
What does it mean if someone's plethoric?
Red-faced.
89
What is the name of the molecule bound to deoxyhaemoglobin that reduces haemoglobin's affinity for oxygen?
2,3-bisphosphoglycerate.
90
The Bohr effect shifts the oxyhaemoglobin dissociation curve to the right, which effect shifts it to the left?
Haldane effect.
91
Which cell makes up 75% of lymphocytic cells in the blood?
T lymphocyte.
92
What is the difference between HbA and HbF?
HbA is present in adult erythrocytes and consists of 2 alpha and 2 beta chains. HbF is present in foetal erythrocytes and consists of 2 alpha and 2 gamma chains, and so HbF has a higher affinity for oxygen than HbA.
93
What do NK cells do?
Cytotoxic lymphocyte that functions in innate immunity. They release granules containing perforins and granzymes to cause apoptosis in virus infected cells and tumour cells.
94
Name the cells that express immunoglobulin on their surface, divide in response to IL-6, and can present antigen.
B lymphocytes.
95
Which epitopes to B cells recognise, and which epitopes do T cells recognise?
B cells recognise conformational epitopes. | T cells recognise linear epitopes.
96
Which bit of the skeleton is the most important site of red cell production in the adult?
The pelvis. | The long bones become filled with yellow bone marrow instead of red except at the epiphyses.
97
Which cells are produced by the lymphoid lineage?
The three lymphocytes: T lymphocytes, B lymphocytes, Natural Killer cells.
98
Which cells are produced by the myeloid lineage?
Erythrocytes, platelets, basophils, eosinophils, neutrophils, macrophages, mast cells.

Blood (6 decks)

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