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ALS > Block 4 (Josie's Notes) > Flashcards

Block 4 (Josie's Notes) Flashcards

1
Q

What percentage of the blood is formed elements?

A
  • 45%
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1
Q

What percentage of the blood is plasma?

A
  • 55%
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2
Q

What are the formed elements of the blood?

A
  • Erythrocytes (red blood cells)
  • Leukocytes (white blood cells)
  • Platelets
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3
Q

What are erythrocytes?

A
  • Red blood cells
  • Transport oxygen and carbon dioxide
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4
Q

What are leukocytes?

A
  • White blood cells
  • Contribute in different ways to the body’s defence mechanism
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5
Q

What are the five types of leukocytes?

A
  • Neutrophils
  • Basophils
  • Eosinophils
  • Monocytes
  • Lymphocytes (B cells, T cells, NK cells)
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6
Q

What are platelets?

A
  • Release chemicals that promote blood clotting
  • Contain three types of granules - alpha, dense, lambola
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7
Q

What is blood plasma?

A
  • Watery extracellular matrix that contains dissolved substances
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8
Q

What is the production of red blood cells called?

A
  • Erythropoiesis
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9
Q

Describe erythropoiesis?

A
  • Starts in the red bone marrow with a proerythroblast
  • Proerythroblast divides several times, producing cells that begin to synthesise haemoglobin
  • A cell near the end of the development sequence ejects its nucleus and becomes a reticulocyte
  • Loss of nucleus causes the centre of the cell to indent, producing a bioconcave shape
  • RBCs pass from red bone marrow into the bloodstream by squeezing between endothelial cells of blood capillaries
  • Reticulocytes develop into erythrocytes within 1 to 2 days after release from red bone marrow
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10
Q

Describe the structure of red blood cells?

A
  • Bioconcave discs
  • No nucleus
  • Strong flexible plasma membrane - Allows deformation without rupturing
  • Certain glycolipids in the plasma membrane are antigens - Account for the various blood groups (ABO, Rh)
  • Can’t reproduce
  • Can’t carry out extensive metabolic activities
  • Cytosol contains haemoglobin molecules
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11
Q

How are red blood cells highly specialised for their function?

A
  • No nucleus - All internal space available for oxygen transport
  • Lacks mitochondria and generates ATP aerobically - Doesn’t use up oxygen
  • Bioconcave disc - Greater surface area for diffusion
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12
Q

Describe the structure of haemoglobin?

A
  • 2 alpha globin chains
  • 2 beta globin chains
  • 4 haem groups - Each is a porphyrin ring with an iron ion in the centre to bind oxygen
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13
Q

What are the different isoforms of haemoglobin?

A
  • HbA (normal) - 2 alpha chains, 2 beta chains
  • HbA2 - 2 alpha chains, 2 delta chains
  • HbF (foetal) - 2 alpha chains, 2 gamma chains
  • HbS - Improper beta chain folding, sickle cell anaemia
  • HbE - Mutated beta globin, mild microcytic anaemic and enlargement of the spleen
  • HbC - Mutated beta globin, mild haemolytic anaemia
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14
Q

Which leukocytes are granular?

A
  • Basophil
  • Neutrophil
  • Eosinophil
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15
Q

Which leukocytes are agranular?

A
  • Monocyte
  • Lymphocyte
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16
Q

Describe the structure of neutrophils?

A
  • Small, pale lilac granules
  • Granules are neutrophilic (don’t attract wither acidic or basic stain)
  • Nucleus has two to five lobes connected by thin strands of genetic material
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17
Q

What does it mean when neutrophil nuclei have more lobes?

A
  • The cell is older
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18
Q

What is the function of neutrophils?

A
  • Phagocytise bacteria
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19
Q

Describe the structure of eosinophils?

A
  • Large granules
  • Granules are eosinophilic (stained orange-red with acidic dyes)
  • Nucleus usually has two lobes connected by a thin or thick strand of nuclear material
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20
Q

What is the function of eosinophils?

A
  • Kill parasitic worms
  • Complex role in allergy and asthma
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21
Q

Describe the structure of basophils?

A
  • Round, variable sized granules
  • Granules are basophilic (stained blue-purple with basic dyes)
  • Granules commonly obscure nucleus, which has two lobes
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22
Q

What is the function of basophils?

A
  • Release histamine and other mediators of inflammation
  • Contains heparin (anticoagulant)
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23
Q

Describe the structure of lymphocytes?

A
  • Nucleus stains dark and is round or indented
  • Cytoplasm stains blue and forms a rim around the nucleus
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24
Q

What is the function of lymphocytes?

A
  • B cells - Release antibodies and assist activation of T cells
  • T cells - T helper (CD4+) activate and regulate T and B cells, cytotoxic T (CD8+) attack virus infected and tumor cells
  • NK cells - Attack virus infected and tumor cells
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25
Q

Describe the structure of monocytes?

A
  • Nucleus is usually horseshoe shaped
  • Cytoplasm is blue-grey and has a foamy appearance (due to lysosomes)
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26
Q

What are monocytes called when they migrate into tissues?

A
  • Macrophages
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27
Q

What is the function of monocytes?

A
  • Phagocytosis
  • Macrophages in tissue
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28
Q

What are MHC antigens?

A
  • Major histocompatibility complex antigens
  • White blood cells and all other nucleated cells in the body have MHC antigens
  • They are unique for each person
  • Essential for the acquired immune system to recognise foreign molecules
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29
Q

Describe the formation of platelets?

A
  • Under the influence of thrombopoietin, myeloid stem cells develop into megakaryocyte units that develop into megakaryoblasts
  • Megakaryoblasts transform into megakaryocytes that splinter into 2000 to 3000 fragments
  • Each fragment enclosed by a piece of the plasma membrane is a platelet
  • This happens in the red bone marrow, platelets then enter the blood circulation
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30
Q

What are the critical components of platelets?

A
  • Membrane proteins
  • Secretory granules (alpha, lambola, dense)
  • Surface connected open cannalicular system (SCOCS)
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31
Q

What do alpha granules contain?

A
  • Platelet factor 4,
  • vWF
  • Thrombospodian
  • Fibronectin
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32
Q

What do lambola granules contain?

A
  • Hydrolytic enzymes
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33
Q

What do dense granules contain?

A
  • ADP
  • ATP
  • Calcium
  • Serotonin
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34
Q

What do the chemicals in plasma granules do?

A
  • Promote blood clotting
  • Form platelet plug
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35
Q

What is haematopoiesis?

A
  • The process by which the formed elements of the blood develop
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36
Q

Where is the primary site of haematopoiesis in adults?

A
  • Red bone marrow
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37
Q

What are the two types of stem cells that develop from pluripotent stem cells in order to form blood cells?

A
  • Myeloid stem cells - Develop in red bone marrow
  • Lymphoid stem cells - Begin their development in red bone marrow but complete it in lymphatic tissue
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38
Q

Name three haemopoietic growth factors?

A
  • Erythropoietin (EPO)
  • Thrombopoietin (TPO)
  • Cytokines
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39
Q

What is erythropoietin?

A
  • Increases the number of red blood cell precursors
  • Produced primarily by cells in the kidneys
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40
Q

What is thrombopoietin?

A
  • Stimulates the formation of platelets from megakaryocytes
  • Produced by the liver
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41
Q

What are cytokines?

A
  • Stimulate proliferation of progenitor cells in the red bone marrow
  • Activate and regulate activities of cells involved in nonspecific defences (B cells and T cells)
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42
Q

What are the two important families of cytokines that stimulate white blood cell formation?

A
  • Colony-stimulating factors
  • Interleukins
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43
Q

Where are blood cells formed in the foetus?

A
  • Yolk sac from week 4
  • Liver until shortly before birth
  • Spleen until cartilagenous bones vascularise
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44
Q

Where are blood cells formed in infants and adults?

A
  • Marrow of most bones in children
  • Marrow of pelvis, sternum, vertebrae, and cranial bones in adults
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45
Q

What is blood plasma made of?

A
  • Water (91.5%)
  • Protein (7%)
  • Other solutes (1.5%)
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46
Q

Name some proteins found in blood plasma?

A
  • Albumin
  • Globulins
  • Fibrinogen
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47
Q

Where are plasma proteins synthesised?

A
  • By hepatocytes in the liver
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48
Q

What is the ABO blood group based on?

A
  • Two glycolipid antigens - A and B
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49
Q

What is blood group A?

A
  • Only have antigen A
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50
Q

What is blood group B?

A
  • Only have antigen B
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51
Q

What is blood group AB?

A
  • Have both A and B antigens
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52
Q

What is blood group O?

A
  • Have neither A nor B antigens
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53
Q

What are agglutinins?

A
  • Antibodies for the antigens your red blood cells lack
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54
Q

How many alleles does the gene controlling the ABO blood group have?

A
  • 3
  • IA and IB are codominant
  • i is recessive (type O)
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55
Q

Which blood group is the universal donor?

A
  • Group O
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56
Q

Which blood group is the universal acceptor?

A
  • Group AB
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57
Q

What is Rh+?

A
  • People who have Rh antigens on their red blood cells
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58
Q

What is Rh-?

A
  • People who lack Ph antigens
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59
Q

What happens if an Rh- person receives Rh+ blood?

A
  • Immune system starts making anti-Rh antibodies that remain in the blood
  • If second Rh+ transfusion is given later, anti-Rh antibodies will cause agglutination (clumping together) and hemolysis of red blood cells
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60
Q

What is primary lymphoid tissue?

A
  • Sites where lymphocytes differentiate to express antigen receptors
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61
Q

What are the primary lymphoid tissues?

A
  • Thymus (T lymphocytes)
  • Bone marrow (B lymphocytes)
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62
Q

What is secondary lymphoid tissue?

A
  • Sites for turning on the acquired immune response
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63
Q

What are the secondary lymphoid tissues?

A
  • Lymph nodes - Meeting place for cells of the immune system
  • Spleen - Directs immune responses to antigens, important in clearance of old red blood cells
  • MALT - Aggregates of lymphocytes (GALT, NALT)
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64
Q

What is an immunoglobulin (antibody)?

A
  • Combines specifically with the epitope on the antigen that triggered its production
  • Aids in the pathogens destruction
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65
Q

What are the main actions of antibodies?

A
  • Neutralising antigens
  • Immobilising bacteria - Limits spread
  • Agglutinating and precipitating antigen
  • Activating compliment
  • Enhancing phagocytosis
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66
Q

What are the four polypeptide chains in antibodies?

A
  • 2 heavy chains
  • 2 light chains
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67
Q

What holds the light chains and the heavy chains together?

A
  • Disulfide bond
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68
Q

What is the hinge region? (2)

A
  • Two disulfide bonds link the midregions of the two heavy chains
  • The hinge region is flexible
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69
Q

What is the part of the molecule with only the heavy chain called?

A
  • Fragment crystaliser
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70
Q

What is the part of the molecule with the combination of light and heavy chains?

A
  • Fragment antigen binding
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71
Q

What are the five types of antibodies?

A
  • IgG
  • IgA
  • IgM
  • IgD
  • IgE
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72
Q

What is the most abundant antibody?

A
  • IgG
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73
Q

Where are IgG antibodies found?

A
  • Blood, lymph, intestines
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74
Q

What do IgG antibodies do?(3)

A
  • Enhances phagocytosis
  • Neutralises toxins
  • Triggering compliment
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75
Q

Which antibodies can cross the placenta?

A
  • IgG
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76
Q

Where are IgA antibodies found?

A
  • sweat
  • tears
  • mucus
  • saliva
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77
Q

What do IgA antibodies do?

A
  • Provides localised protection of mucous membranes
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78
Q

Where are IgM antibodies found?

A
  • Blood, lymph
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79
Q

What is the first antibody to be secreted after exposure to antigen?

A
  • IgM
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80
Q

What do IgM antibodies do?

A
  • Activated compliment
  • Causes agglutination and lysis of microbes
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81
Q

What type of antibodies are ABO antibodies?

A
  • IgM
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82
Q

Where are IgD antibodies found?

A
  • Mainly on surface of B cells as antigen receptor
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83
Q

What do IgD antibodies do?

A
  • Activation of B cells
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84
Q

Where are IgE antibodies located?

A
  • Located on mast cells and basophils
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85
Q

What do IgE antibodies do?

A
  • Involved in allergic and hypersensitive reactions
  • Protection against worms
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86
Q

Where do B cells originate?

A
  • Red bone marrow
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87
Q

What do B cells form from?

A
  • Common lymphoid progenitor cells (CLPs)
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88
Q

Where does negative selection occur?

A
  • Red bone marrow
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89
Q

What is negative selection of B cells?

A
  • If a cell expresses surface IgM that is specific to multivalent cell surface antigens (MHC) they are eliminated by clonal deletion
  • If a cell binds soluble self-antigens, it loses its ability to express IgM via downregulation (anergy)
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90
Q

What do immature B cells act as?

A
  • Antigen presenting cells
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91
Q

What do immature B cells do? (3)

A
  • Ingest antigens via phagocytosis
  • Process antigens and present them on the cells surface for activation purposes
  • Migrate to lymphatic tissue to present antigen to T cells
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92
Q

What are the two types of mature B cells?

A
  • Plasma cells
  • Memory cells
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93
Q

What is the function of plasma cells?

A
  • Secrete antibodies
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94
Q

What is the function of memory cells?

A
  • Specific to certain antigens
  • Have a long lifespan
  • Activate in the presence of a second infection
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95
Q

Where do T cells form?

A
  • T cells form in the red bone marrow from lymphoid stem cells
  • T cells then migrate to the thymus
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96
Q

How many T cells die through positive and negative selection in the thymus (central tolerance)?

A
  • 98%
97
Q

Describe positive selection of T cells?

A
  • Occurs in the thymus cortex
  • Mediated by thymic epithelial cells - express many surface MHC molecules
  • Any cell that recognises the MHC molecules are saved from apoptosis
  • This ensures T cells that recognises MHCs are made
  • T cells start as CD4+CD8+ double positive (cluster of differentiation)
98
Q

What do T cells become if they recognise MHC1?

A
  • CD8+ cells
99
Q

What do T cells become if they recognise MHC2?

A
  • CD4+ cells
100
Q

Describe negative selection of T cells?

A
  • Occurs in the thymus medulla
  • Removed potential autoimmine cells
  • Mediated by medullary thymic epithelial cells (mTECs) and dendritic cells
  • mTECs display self-antigens and induce apoptosis in any cell that binds to them too
  • strongly
  • This is dependent on the expression of tissue specific antigens, which are regulated by auto immune regulator
101
Q

What causes autoimmune diseases?

A

A defective autoimmune regulatory (AIRE) leads to a lack of negative selection and the creation of cells that can attack the body

102
Q

What are CD4+ cells?

A
  • T helper cells
103
Q

What are the different types of T helper cells?

A
  • TH1 - Protects against intracellular pathogens, induces autoimmunity
  • TREG - Protects against autoimmunity
  • TH2 - Protects against helminths, induces autoimmunity and allergy
104
Q

What are CD8+ cells?

A
  • Cytotoxic T cells
105
Q

What is the difference between MHC1 and MHC2?

A
  • MHC1 presents on all nucleated cells, MHC2 presents on antigen presenting cells
  • MHC1 carries peptides generated in cytosol or ER, MHC2 carries peptides manufactured in endosomal compantments
  • MHC1 presents to CD8+, MHC2 presents to CD4+
  • MHCDescribe MCH1 presentation to CD8+ cells
  • MHC1 is surveillance for viral infection and self change, MHC2 is surveillance for exogenous pathogens
106
Q

Describe MCH1 presentation to CD8+ cells?

A
  • Virus infects cell
  • Viral proteins synthesised in cytoplasm
  • Peptide fragments of viral proteins are bound by MHC1 on rough ER
  • Bound peptides transported to cell surface by MHC1
  • CD8+ cells recognise complex and kills cell
107
Q

Describe MHC2 presentation to CD4+ cells?

A
  • Macrophage, B cell, or dendritic cell engulf bacterium and degrades it producing peptides
  • Bacterial peptides bound by MHC2 in vesicle
  • Bound peptides transported to cell surface by MHC2
  • CD4+ recognise complex and activates respective cells
108
Q

What is costimulation?

A
  • T cell activation required both antigen and costimulating signals
  • No antigen causes no response
  • No costimulation renders T cell unresponsive
  • Both antigen and costimulation leads to T cell activation
109
Q

Give some examples of immunosuppressants?

A
  • Cyclosporin and tacrolimus - Block T cell and B cell receptors (Hightly immunosuppressive)
110
Q

What is Hb?

A
  • The concentration of haemoglobin in the blood
111
Q

What is MCV?

A
  • The mean volume of red blood cells
112
Q

What is RBC?

A
  • The number of red blood cells in the blood
113
Q

What is MCH?

A
  • Mean haemoglobin quantity within the blood cells
114
Q

What is Hct?

A
  • The ratio of the volume of red blood cells to the volume of blood
115
Q

What is WCC?

A
  • The number of white blood cells in the blood
116
Q

What are bands?

A
  • Precursors of neutrophils
  • An increase shows immune system has been activated
117
Q

What is Plt?

A
  • The number of platelets in the blood
118
Q

What are reticulocytes?

A
  • The number of reticulocytes (immature red blood cells) in the blood
  • Used to help determine if the bone marrow is responding adequately
119
Q

What is ESR?

A
  • Erythrocyte sedimentation rate in a period of one hour
120
Q

What is EPO?

A
  • The level of EPO in the blood (hormone secreted by the kidneys that increases red blood cell production)
121
Q

Describe the process of prothrombin time (PT)?

A
  • Measures the time it takes for blood plasma to clot
  • Evaluates the extrinsic pathway of coagulation
  • Tissue factor is added to plasma and clotting time is measured optically
122
Q

What is INR?

A
  • International normalised ratio
123
Q

Why is INR used?

A
  • Takes into account the differences in the batches of tissue factor (ISI)
124
Q

Describe the process of activated partial thromboplastin time (aPTT)?

A
  • Measures intrinsic and common pathways
  • Measures time taken for plasma to clot after calcium and an activator is added
125
Q

What are the functions of platelets?

A
  • Adhere to damaged tissue
  • Store alpha/dense granules
  • Aggregate other platelets
  • Provide a surface for coagulation factors
126
Q

What do alpha granules store?

A
  • Platelets factor 4 - Neutralises heparin, inhibits thrombin
  • vWF - Binds to exposed collagen in wound
  • Fibronectin - Adhesion to other cells
  • Thrombospondin - Promotes platelet-platelet interaction
127
Q

What do dense granules store?

A
  • ADP - Promotes aggregation
  • ATP - Energy and ADP source
  • Serotonin - Increased vasoconstriction, decrease pain
  • Ca2+ - Required for coagulation and platelet functions
128
Q

What are the three mechanisms that reduce blood loss?

A
  • Vascular spasm
  • Platelet plug formation
  • Blood clotting (coagulation)
129
Q

What happens during vascular spasm?

A
  • Smooth muscle in walls of damaged arteries/arterioles contracts immediately
  • Reduces blood loss
  • Caused by damage to smooth muscle, substances released from activated platelets, reflexes initiated by pain receptors
130
Q

What happens during platelet plug formation?

A
  • vWF binds to exposed collagen in wound
  • Platelets adhere to vWF via GP1b receptor - adhesion
  • Due to adhesion platelets become activated
  • ADP causes platelet aggregation, makes other platelets in the area sticky
  • Accumulation and aggregation of large numbers of platelets forms a mass called a platelet plug
  • Plug reinforced with fibrin threads formed during clotting
131
Q

Which molecules activate nearby platelets?

A
  • ADP
  • Thromboxane A2
132
Q

Which molecules promote vasoconstriction?

A
  • Serotonin
  • Thromboxane A2
133
Q

What are the two pathways of the coagulation cascade?

A
  • Extrinsic
  • Intrinsic
  • Both lead to the common pathway
134
Q

Which clotting factors are vitamin K dependent?

A
  • 2, 7, 9, and 10
  • Calcium is required to convert these factors
135
Q

What is the intrinsic pathway of coagulation?

A
  • Contact activation
  • Damaged surface converts factor XII to XIIa
  • XIIa converts XI to XIa
  • XIa converts IX to IXa
  • IXa combines with VIIIa to convert X to Xa (prothrombinase)
136
Q

What is the extrinsic pathway of coagulation?

A
  • Tissue factor exposed in subendothelial tissues due to trauma
  • Tissue factor forms complex with VII to form VIIa
  • VIIa converts X to Xa (prothrombinase)
137
Q

What is the common pathway of coagulation?

A
  • Xa (prothrombinase) coupled with Va converts prothrombin to thrombin
  • Thrombin converts fibrinogen to fibrin
  • Fibrin starts to form a clot by layering over the surface of the wound
  • XIIIa binds with fibrin, cross linking it to stabilise the clot
138
Q

What is factor I also known as?

A
  • Fibrinogen
139
Q

What is factor II also known as?

A
  • Prothrombin
140
Q

What is factor III also known as?

A
  • Tissue factor
141
Q

Which factor is Christmas factor?

A
  • Factor IX (9)
142
Q

Which factor is deficient in Hemophilia?

A
  • Factor VIII (8)
143
Q

What is anaemia?

A
  • Decrease in red blood cells or haemoglobin in the blood
144
Q

What is microcytic anaemia?

A
  • Low MCV (<80fl) due to a failure in heamoglobin synthesis or insufficiency
  • Generally hypochromic
145
Q

Name some of the types of microcytic anaemia?

A
  • Iron deficiency
  • Thalassaemia
  • Anaemia of chronic disease
  • Lead poisoning
146
Q

What is iron deficiency?

A
  • Most common type
  • Has many causes including insufficient dietary intake, blood loss, parasitic infection
147
Q

What is thalassaemia?

A
  • Alpha or beta chain deformity
  • Hereditary haemolytic disease
148
Q

What is anaemia of chronic disease?

A
  • Anaemia found in people with certain long-term medical conditions (e.g. crohns, HIV)
149
Q

What is lead poisoning?

A
  • Depresses haem synthesis and shortens lifespan of red blood cells
150
Q

What is macrocytic anaemia?

A
  • High MCV (>100fl)
151
Q

What is megaloblastic anaemia?

A
  • Due to B12 and/or folate deficiency, low level means cells cannot replicate fast enough so grow too big before they divide
152
Q

What are the types of megaloblastic anaemia?

A
  • Pernicious anaemia
  • Removal of functional portion of stomach
153
Q

What is pernicious anaemia?

A
  • Lack of intrinsic factor so can’t absorb B12
  • Antibodies directed towards intrinsic factor or parietal cells
154
Q

What is removal of the functional portion of stomach called?

A
  • e.g. gastric bypass
  • Reduces B12/folate absorption
155
Q

How can COPD cause macrocytic anaemia?

A
  • Low oxygen concentration causes fast turnover of RBCs
  • New RBCs slightly larger than old ones
156
Q

What is normocytic anaemia?

A
  • MCV normal
  • Overall Hb level decreased
157
Q

Name some types of normocytic anaemia?

A
  • Decreased production of RBCs
  • Increased destruction/loss of RBCs
  • Aplastic anaemia
158
Q

What are types of anaemia that can cause increased destruction/loss of RBCs?

A
  • Haemolysis
  • Hemorrhagic anaemia
159
Q

What is aplastic anaemia?

A
  • Decrease in haemopoietic stem cells due to destruction of bone marrow
  • Mixture of causes from both macro and microcytic anaemia
160
Q

What is autoimmune haemolytic anaemia?

A
  • Antibodies directed against RBCs
161
Q

What is congenital spherocytosis? (2)

A
  • Defective membrane proteins
  • RBCs are spherical, less flexible, and are broken down in the spleen
162
Q

What is hypersplenism?

A
  • Overactivity of the spleen results in destruction of RBCs
163
Q

What is sickle cell anaemia?

A
  • Substitution of glutamic acid to valine
  • Disrupts haemoglobin - HbS
  • Crystalises and causes deformation of cell shape (sickle cell)
164
Q

What is sideroblastic anaemia?

A
  • Sideroblasts produced instead of RBCs
  • Sideroblasts are nucleated erythroblasts with iron granules around nucleus (ridged)
165
Q

What are the types of hereditary anaemias?

A
  • Sickle cell anaemia
  • Thalassemia
  • Congenital pernicious anaemia
  • Congenital spherocytosis
166
Q

What are the symptoms of anaemia?

A
  • Fatigue
  • Lack of energy
  • Breathlessness
  • Feeling faint
  • Pale skin
  • Palpitations
167
Q

Describe the lifecycle of red blood cells?

A
  • Produced in red bone marrow as reticulocytes
  • Reticulocytes released from bone marrow and develop into erythrocytes after a couple days
  • Live around 120 days due to wear and tear of plasma membranes
  • Macrophages in spleen, liver, or red bone marrow phagocytise ruptured and worn out red blood cells
168
Q

What is the control condition for the negative feedback system of erythropoiesis?

A
  • Amount of oxygen delivered to body tissues
169
Q

Describe the negative feedback system of erythropoiesis?

A
  • Hypoxia may occur if there is too little oxygen in the blood
  • Hypoxia stimulates kidneys to release more EPO
  • This speeds up the development of proerythroblasts into reticulocytes in bone marrow
  • More reticulocytes in circulation so increase in RBCs
  • Increased oxygen delivery to tissues
  • When oxygen delivery to kidneys increases back to normal, body returns to homeostasis
170
Q

What is polycythemia?

A
  • Increase in the number of RBCs which thickens the blood
  • Extra blood cells may collect in the spleen causing it to enlarge
  • May also cause bleeding problems and increase the risk of clots
171
Q

Which gene mutation is involved in polycythemia?

A
  • JAK-2 gene mutation
172
Q

What does the JAK-2 gene mutation do?

A
  • Makes haemopoietic stem cells more sensitive to growth factors
173
Q

What is primary polycythemia?

A
  • Myeloproliferative disease
  • Defective bone marrow
  • Often excess WBCs and platelets too
174
Q

What is secondary polycythemia?

A
  • Increased EPO
  • e.g. altitude related, COPD, genetics
175
Q

Give some examples of congenital bleeding disorders?

A
  • Haemophilia A - Factor VIII deficiency
  • Haemophilia B - Factor IX deficiency
  • Von Willebrand’s disease - vWF deficiency
176
Q

What is haemophilia B also known as?

A
  • Christmas disease
177
Q

Give some examples of acquired bleeding disorders?

A
  • Liver disease - Thrombocytopenia (low platelets)
  • Vitamin K deficiency
  • Autoantibodies
  • Renal disease - Platelet dysfunction
178
Q

What is innate immunity?

A
  • Non specific immunity
179
Q

What are the three stages of innate immunity?

A
  • Anatomical barriers
  • Inflammation
  • Complement
180
Q

Give some examples of anatomical barriers?

A
  • Skin - Sweat, physical barrier
  • Eyes - Tears
  • Respiratory airways - Mucociliary escalator
  • Nasopharynx - Mucus, saliva, lysozyme
  • GI tract - Acid, peristalsis, digestive enzymes
181
Q

What are the five symptoms of inflammation?

A
  • Redness
  • Heat
  • Pain
  • Swelling
  • Loss of function
182
Q

Which cells initiate inflammation?

A
  • Cells already present in the tissue (macrophages, mast cells, dendritic cells, neutrophils)
183
Q

What are the three stages of acute inflammation?

A
  • Increased blood flow - Vasodilation
  • Increased permeability of capillaries - Oedema
  • Migration of leukocytes - Guided by chemotaxis and engulf bacteria
184
Q

Describe the function of neutrophils in inflammation?

A
  • Phagocytosis
  • Degranulation - Release hydrogen peroxide granules
  • Release factors that summon other cells
185
Q

Describe the function of macrophages in inflammation?

A
  • Phagocytosis
  • Release histamine (vasodilator)
186
Q

Describe the events of phagocytosis?

A
  • Chemotaxis and adherence of microbe to phagocyte
  • Ingestion of microbe by phagocyte
  • Formation of phagosome (phagocytic vesicle)
  • Fusion of phagosome with lysosome to form a phagolysosome
  • Digestion of ingested microbe by hydrolytic enzymes
  • Formation of residule body containing indigestible material
  • Discharge waste materials
187
Q

Name the three complement pathways?

A

lternative - C3 forms C3b which binds to pathogen
* Classical - Initiated by antibodies (IgG/IgM) binding with antigen, activated C3
* Lectin - Initiated by proteins binding to pathogen

188
Q

Describe the alternative complement pathway?

A
  • C3 splits into C3a and C3b
  • C3b binds to pathogen (opsonisation) and also initiates a series of reactions that bring about cytolysis
  • C5b binds to C6 and C7 which attaches to plasma membrane
  • C8 and C9 form membrane attack complex - Insert into plasma membrane and cause cytolysis
  • C3a and C5a bind to mast cells - Release histamine
  • C5a also attracts phagocytes
189
Q

What is adaptive immunity?

A
  • Foreign soluble antigen is absorbed by antigen presenting cell (MCH2)
  • Antigens present in the lymph are phagocytosed by dendritic cells
  • Dendritic cells present at the site of infection absorb antigens then migrate to the nearest lymph node and stimulate CD4+ cells (T helper)
  • T helper cells release cytokines and other stimulatory signals
  • Signals cause activation of T killer cells, macrophages, and B cells
  • B cells undergo clonal selection to form plasma cells and memory cells
190
Q

Why can’t dendritic cells already be in the lymph activate T cells?

A
  • Don’t have information about the infection site
191
Q

What are plasma B cells?

A
  • Secrete antibodies
192
Q

What are memory B cells?

A
  • Can quickly divide into plasma and memory cells if the same antigen reappears at a future time
193
Q

What is the time frame of immune responses?

A
  • Innate - 0-4 hours
  • Early induced - 4-98 hours
  • Adaptive - >98 hours
194
Q

Which antibodies are involved in the immune response?

A
  • IgG
  • IgM
195
Q

Which type of antibody concentration peaks first?

A
  • IgM
196
Q

Which antibody concentration is greater?

A
  • IgG
197
Q

Does the primary of secondary immune response cause greater antibody production?

A
  • Secondary
  • More IgG produced
198
Q

What is autoimmunity?

A
  • Malfunction in adaptive immune system caused by a loss/failure of self and non-self recognition
  • Immune system attacks its own cells
199
Q

What are autoantibodies?

A
  • Antibodies directed toward the body’s own cells
200
Q

Why are autoantibodies created?

A
  • As a result of an autoimmune disease
  • When combating waste products or cancer
201
Q

Give some examples of organ specific autoimmune diseases?

A
  • Grave’s disease (hyperthyroidism)
  • Hashimoto’s (hypothyroidism)
202
Q

Give some examples of systemic autoimmune diseases?

A
  • Myasthenia Gravis
  • Rheumatoid arthritis
203
Q

What is peripheral tolerance?

A
  • If an autoimmune cell makes its way into the peripheral tissues, there are several ways by which they are prevented from causing harm
204
Q

Give examples of peripheral tolerance?

A
  • Ignorance - Self-reactive T cells are not activated at immunoprivileged sites (brain and testes)
  • Fat-ligand induced apoptosis
  • Anti-inflammatory cytokines (TGF-β and IL-10)
  • Blood-tissue barrier with tight junctions
  • Induced anergy when T and APC interact
205
Q

What is HIV?

A
  • Human immunodeficiency virus
  • Retrovirus that attacks the immune system
206
Q

What is a retrovirus?

A
  • RNA virus which inserts a DNA copy of their genome into the host cell in order to replicate
207
Q

What are the three stages of HIV?

A
  • Acute HIV infection
  • Clinical latency stage
  • AIDS
208
Q

Describe the acute HIV infection stage?

A
  • Flu like symptoms
  • CD4+ levels drop rapidly until viral set point
209
Q

What is the viral set point?

A
  • Relatively stable level of virus
  • CD4+ can increase
210
Q

Describe the clinical latency stage?

A
  • No/very mild symptoms
  • Virus replicates at very low levels
211
Q

What is AIDS?

A
  • Acquired immunodeficiency syndrome
  • Final stage of the HIV infection
  • Low levels of CD4+
  • Vulnerable to opportunistic infections e.g. pneumonia
212
Q

What is hypersensitivity?

A
  • Overly reactive to a substance that is tolerated by most other people
213
Q

What are the four types of hypersensitivity?

A
  • Type 1 - Anaphylactic
  • Type 2 - Cytotoxic
  • Type 3 - Immune-complex
  • Type 4 - Cell mediated
214
Q

Describe the type 1 hypersensitive reaction?

A
  • In response to first exposure to allergen, IgE antibodies bind to surface of mast cells and basophils
  • When same allergen re-enters it attaches to IgE
  • Mast cells and basophils release histamine and other vasoactive chemicals
215
Q

What does the release of histamine and other vasoactive chemicals cause?

A
  • Vasodilation
  • Increased permeability of capillaries
  • Increased smooth muscle contraction in airways
  • Increased mucus secretion
216
Q

What is an anaphylactic shock?

A
  • Symptoms usually accompanied by shock due to vasodilation and fluid loss
  • Treated by adrenaline to dilate airways and strengthen heart beat
217
Q

Describe the type 2 hypersensitive reaction?

A
  • Caused by antibodies (IgG or IgM) directed against antigens on a person’s blood/tissue cells
  • Perceived by immune system as foreign so compliment is activated leading to cell destruction by MAC
  • Damage cells by causing lysis
218
Q

Give examples of type 2 hypersensitive reactions?

A
  • Incompatible blood transfusion
  • Myasthenia gravis
219
Q

Describe the type 3 hypersensitive reaction?

A
  • Involves reaction between soluble antigens with IgG, complement, and neutrophils
  • IgG binds to antigen forming a circulating immune complex
  • They are often deposited in the vessel walls of the joints and kidneys
  • This initiates a local inflammatory reaction by activating compliment
220
Q

Give examples of type 3 hypersensitive reactions?

A
  • Rheumatoid arthritis
  • Serum sickness
221
Q

Describe the type 4 hypersensitive reaction?

A
  • Delayed hypersensitive reaction
  • Helper T cells (CD4+) are activated by APCs
  • When antigen is presented in future, memory T cells will activate macrophages and cause inflammatory response
222
Q

Why are type 4 reactions described as being delayed?

A
  • Appear 12-72 hours after exposure to allergen
223
Q

Give examples of type 4 hypersensitive reactions?

A
  • Poison Ivy
  • Mantoux test
224
Q

Give examples of drugs used for anaemia?

A
  • Hydroxocobalamin - B12
  • Folic acid
  • Ferrous sulphate - Iron
225
Q

What is hydroxocobalamin?

A
  • Natural form of B12
  • Administered by injection as deficiency commonly results from malabsorption
  • Treats megaloblastic anaemia
226
Q

What is folic acid?

A
  • Given orally as tablet
  • Deficiency usually caused by inadequate dietary intake and pregnancy
  • Treats megaloblastic anaemia
227
Q

What is ferrous sulphate?

A
  • Iron tablets
  • Treats iron deficiency anaemia
  • Can cause unwanted effects including nausea, abdominal cramps, diarrhoea
228
Q

Name some treatments for polycythemia?

A
  • Low dosages of aspirin - Suppresses prostaglandin and thromboxane production
  • Venesection - Regular removal of blood
  • JAK-2 inhibitors - Currently being trialled
229
Q

What is warfarin?

A
  • Vitamin K reductase inhibitor
  • Prevents clotting factors 2, 7, 9, and 10 being made
  • Prevents blood clotting
230
Q

What is heparin?

A
  • Binds irreversibly to antithrombin III
  • Inhibits action of factor Xa and thrombin
  • Prevents blood clotting
  • Works faster than warfarin
231
Q

What are tissue plasminogen activator and sterptokinase?

A
  • Activate plasminogen by catalysing its conversion to plasmin
  • Plasmin degrades fibrin clots
  • Prevents blood clotting
232
Q

What are factor concentrates?

A
  • Made from human plasma and contains a mixture of clotting factors
  • Rapid and relatively easy method of improving coagulation stability
233
Q

What is fresh frozen plasma?

A
  • Blood plasma with no blood cells
  • High risk of transmission of infectious diseases compared to other treatments
  • Large volumes must be transfused which can lead to circulatory overload
234
Q

What is cryoprecipitate?

A
  • Plasma containing a high concentration of VIII
  • Effective for joint and muscle bleeds
  • Hard to store and administer
235
Q

Describe the action of glucocorticoids?

A
  • Suppress cell-mediated immunity
  • Inhibits genes that code for interleukins so T cell proliferation is reduced
  • Also suppresses humoral immunity (antibody mediated) due to low IL-2
236
Q

Describe the action of cytostatics?

A
  • Inhibit cell division and growth
  • Generally used alongside cytotoxic drugs
  • Uses include chemotherapy, skin diseases, and infection
237
Q

Describe the action of immunosuppressants?

A
  • Cyclosporin and Tacrolimus - Inhibit calcineurin, prevent transition from G0 to G1 in the cell cycle
  • Sirolimus - Acts on the secondary phase (signal transduction and lymphocyte clonal proliferation) prevents transition from G1 to S
238
Q

What are the risks of long term use?

A
  • Low bone density
  • Cardiovascular risk
  • Cateracts (clouding of lens in eye)
239
Q
A

ALS (10 decks)

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