PBL Topic 2 Case 7 Flashcards

(181 cards)

1
Q

Explain how haemoglobin is involved in the return of CO2 to the lungs

A
  • Contains carbonic anhydrase
  • Allows CO2 to react with H2O
  • To form bicarbonate ions
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2
Q

What does mean corpuscular volume measure?

A
  • Size of red blood cells
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3
Q

What is the normal range of the mean corpuscular volume?

A
  • 80 - 99 femtolitres (fL)
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4
Q

What is the mean diameter, thickness and volume of red blood cells?

A
  • Diameter: 7.8 uM
  • Thickness: 2.5 uM
  • Volume: 90-95 cubic uM
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5
Q

How does the average number of red blood cells differ in males and females?

A
  • Males: 5,200,000

- Females: 4,700,000

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6
Q

What is meant by the term hematocrit?

A
  • Percentage of blood composed of red blood cells
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7
Q

What is the normal value of hematocrit?

A
  • 45 per cent
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8
Q

Where are red blood cells produced in early embryonic life?

A
  • Yolk sac
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9
Q

Where are red blood cells produced during the second trimester?

A
  • Liver
  • Spleen
  • Lymph Nodes
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10
Q

Where are red blood cells produced during the final month of gestation and after birth?

A
  • Bone marrow
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11
Q

In which types of bones does the marrow typically produce red blood cells after birth?

A
  • Membraneous bones

- Including sternum, ribs and vertebrae

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12
Q

What is a pluripotential haematopoietic stem cell?

A
  • Type of cell from which all cells of the circulating blood are derived
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13
Q

What is a committed stem cell?

A
  • Type of cell that differentiates to form other types of cell
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14
Q

What is a CFU-E?

A
  • Colony-Forming-Unit Erythrocyte

- A committed stem cell that produces erythrocytes

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15
Q

What is a CFU-GM?

A
  • Colony-Forming-Unit Granulocyte and Monocyte

- A committed stem cell that produces granulocytes and monocytes

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16
Q

Identify factors that affect the formation of growth and differentiation inducers in erythrocytes

A
  • Exposure to low oxygen in the blood
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17
Q

Identify factors that affect the formation of growth and differentiation inducers in lymphocytes

A
  • Exposure to a pathogen in the blood
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18
Q

What is CFU-M?

A
  • Colony-Forming-Unit Megakaryocyte

- A committed stem cell that produces platelets

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19
Q

What is the role of erythropoietin?

A
  • Stimulates proliferation of erythrocyte progenitor cells

- Stimulates their differentiation in mature erythrocytes

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20
Q

What is the role of thrombopoeitin?

A
  • Stimulating of megakaryocyte production

- Via its c-mpl receptor

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21
Q

Identify the roles of 3 different colony stimulating factors

A
  • GM-CSF: Increases stem cell commitment to granulocyte and monocyte production
  • G-CSF: Increases stem cell commitment to granulocyte production
  • M-CSF: Increases stem cell commitment to monocyte production
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22
Q

Identify the roles of IL-3, IL-5 and IL-11

A
  • IL-3: Growth and reproduction of all types of stem cells
  • IL-5: Growth and differentiation of eosinophils
  • IL-11: Promotes megakaryocyte production
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23
Q

Identify the role of Stem Cell Factor

A
  • Synergises with IL-3 and GM-CSF

- To increase proliferation of many types of stem cells

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24
Q

Identify the six generations of erythrocytes

A
  • Proerythroblast
  • Basophil Erythroblast
  • Polychromatophil Erythroblast
  • Orthochromatic Erythroblast
  • Reticulocyte
  • Erythrocyte
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25
What occurs during the successive stages of red cell differentiation?
- Accumulation of haemoglobin (B) - Nucleus is absorbed (B) - Endoplasmic reticulum is absorbed (B) - Passage from the bone into the capillaries by diapedesis (R)
26
Where is erythropoietin produced?
- Kidneys
27
Explain how erythropoietin stimulates erythropoietic activity?
- Under hypoxic conditions - Binds to Hypoxia Inducible Factor - Which binds to Hypoxia Response Element - Activates gene transcription - Via the combined effects of nuclear factor and co-activator p300 - Increased proportion of committed cells to erythropoiesis - Stimulation and differentiation of CFU-E
28
Explain how under normal conditions HIF is controlled
- The HIF-alpha subunit is hydroxylated - Which promotes interaction with von Hippel-Lindau E3 ubiquitin ligase - Resulting in degradation of HIF
29
What is the lifespan of an erythrocyte?
- 120 days
30
Identify five roles of the cytoplasmic enzymes contained within erythrocytes
- Glucose metabolism - Maintain pliability - Membrane transport - Maintain ferrous iron - Prevents oxidation of proteins
31
What is the role of Kupffer cells?
- Types of macrophages produce by the liver | - Phagocytosis of haemoglobin from worn out red blood cells
32
What is the role of Transferrin?
- Transport of iron from the haemoglobin from worn out red blood cells to the bone marrow - For either production of new red blood cells or storage as ferritin
33
What happens to the porphyrin portion of the haemoglobin of worn out red blood cells?
- Converted into bilirubin my macrophages | - Removed from the body by secretion through the liver into the bile
34
Explain how red blood cells may self-destruct in the spleen
- Squeeze through red pulp into the trabeculae
35
Explain how a molecule of pyrrole is produced in the formation of Haemoglobin
- Succinyl coenzyme A is formed in the Krebs cycle | - It binds with glycine to form Pyrrole
36
Explain how protoporphyrin IX is produced in the formation of Haemoglobin
- Four molecules of pyrrole combine
37
Explain how haem is formed formed protoporphyrin IX
- Protoporphyrin IX reacts with ferrous iron (Fe2+)
38
Explain how a haemoglobin chain is produced from haem
- Haem combines with globulin
39
Which chains make up Haemoglobin A?
- 2 x Alpha Chain | - 2 x Beta Chain
40
How many molecules of oxygen can be transported by a molecule of haemoglobin? Why is this the case?
- Four - There are four haem group - Which contain a single iron atom - That can form a loose bond with oxygen
41
How does the T conformation of haemoglobin differ to the R conformation?
- T: Globin chains are held tight together - R: Oxygen binding sites are more exposed - Therefore R conformation has a higher affinity for oxygen
42
Why is haemoglobin considered an allosteric protein
- Binding of one oxygen molecule increases oxygen affinity of the remaining binding sites - This explains the sigmoid shape of the oxygen dissociation curve
43
What is the effect of binding of hydrogen ions and carbon dioxide to haemoglobin?
- Reduced affinity for oxygen - Bohr Effect - Oxygen dissociation curve shifts right and downwards
44
What is the effect of oxygenation on haemoglobin?
- Reduced affinity for Carbon Dioxide | - Haldane Effect
45
What is the effect of 2,3-BPG on haemoglobin?
- Stabilises T-conformation - Reduced affinity for oxygen - Oxygen dissociation curve shifts right and downwards
46
Explain the role of ferrireductase
- Conversion of ferric iron (Fe3+) to ferrous iron (Fe2+)
47
Explain the role of DMT1 (Divalent Metal Transporter)
- Divalent Metal Transporter | - Transports iron across the luminal surface of the mucosal cells in the small intestine
48
Explain the role of HCP1
- Haem Carrier Protein 1 | - Transports haem across the luminal surface of the mucosal cells in the small intestine
49
Explain the role of FPN-1
- Ferroportin 1 - Transports iron out of mucosal cell - Requires hephaestin
50
Explain the role of Hepcidin
- Regulation of iron absorption - By binding to iron-exporting protein Ferroportin 1 - Causing its degradation - Decreasing iron efflux
51
What is the role of apotransferrin
- Combines with iron to form transferrin | - Which is transported in the plasma
52
Identify two locations where iron is deposited
- Liver | - Bone Marrow
53
Explain how haemoglobin is produced from circulating iron
- Transferrin attaches to surface receptor on erythrocyte - Iron is released and transported to mitochondria - Iron combines with protoporphyrin to form haem
54
Explain how iron is stored from circulating iron
- Transferrin attaches to surface receptor on erythrocyte | - Iron combine with apoferritin to form ferritin
55
How does ferritin differ from hemosiderin
- Ferritin is soluble | - Hemosiderin is insoluble
56
Identify three causes of iron deficiency
- Blood loss, typically from GI tract - Demands of growth and pregnancy - Decreased absorption - Poor intake
57
Identify the four generations of granulocytes
- Myeloblast - Promyelocyte - Myelocyte - Metamyelocyte
58
What are band forms?
- Immediate precursor of mature granulocytes | - With irregular horseshoe shaped nucleus
59
What is the difference between left and right shift?
- Left shift involves mobilisation of metamyelocytes | - Right shift involves further maturation
60
Identify five locations in which lymphocytes and plasma cells are produced
- Bone marrow - Spleen - Thymus - Lymph Glands - Peyer's Patches underneath epithelium in gut wall
61
What is anaemia?
- Reduction in haemoglobin | - Below the reference level for the age and gender of the individual
62
Identify three types of anaemia, how are they classified?
- Microcytic Anaemia - Normocytic Anaemia - Macrocytic Anaemia - Classified based on MCV
63
Identify two mechanisms that occur, resulting in an asymptomatic patient of anaemia
- Enhancement of oxygen carrying capacity of blood | - Rise in 2,3-BPG allowing for oxygen dissociation at the tissues
64
Identify 7 general symptoms of anaemia
- Fatigue - Headache - Faintness - Breathlessness - Angina - Claudication - Palpitations
65
What is claudication?
- Pain in limb - That occurs on exercise - Due to obstruction of an artery
66
Identify 7 signs of anaemia
- Pallor - Tachycardia - Systolic Flow Murmur - Koilonychia (spoon shaped nails) - Jaundice - Bone deformities - Leg ulcers
67
How can exercise be used to assess the effects of anaemia?
- Exercise causes angina and intermittent claudication
68
Identify five evaluation tools when a patient presents with a low haemoglobin count
- Red blood cell indices - White blood cell count - Platelet count - Reticulocyte count (as this indicates marrow activity) - Blood film
69
What is meant by the term dimorphic and when may this be seen on a blood film?
- Two populations of red cells are seen - In patients with double deficiencies - For example iron and folate deficiency in coeliac disease
70
What is meant by the term poikilocytosis?
- Variation in cell shape | - As demonstrated in microcytic anaemia
71
What is mean by the term anisocytosis?
- Variation in cell size | - As demonstrated in microcytic anaemia
72
Identify two methods of obtaining and examining bone marrow
- Aspiration provides a film which can be examined by microscopy - Trephine provides a core of bone which is processed on a histological specimen
73
Identify five components that are assessed when examining bone marrow
- Cellularity - Type of erythropoiesis - Cellularity - Infiltration of marrow e.g. by cancer cells - Iron stores
74
What is the most common cause of microcytic anaemia?
- Iron deficiency - Chronic disease (Crohn's) - Sideroblastic Anaemia - Thalassaemia
75
Identify seven clinical features of microcytic anaemia
- Brittle nails - Koilonychia (spoon-shaped nails) - Brittle hair - Atrophy of the papillae of the tongue - Angular stomatitis - Dysphagia - Glossitis
76
What would a blood count and film show in iron-deficiency anaemia?
- MCV < 80 fL | - Poikilocytosis and Anisocytosis
77
How are serum iron, ferritin, transferrin receptors and iron-binding capacity affected in iron-deficiency anaemia?
- Serum iron is reduced - Serum ferritin is reduced - Transferrin receptors is increased - Total iron-binding capacity is increased
78
How are serum iron, ferritin, transferrin receptors and iron-binding capacity affected in anaemia of chronic disease?
- Serum iron is reduced - Serum ferritin is reduced - Transferrin receptors are normal - Total iron-binding capacity is is reduced
79
Identify two causes of sideroblastic anaemia?
- Inherited as an X-linked disease | - Acquired through myelodysplasia, myeloproliferative disorders or myeloid leukaemia
80
How can Perl's reaction be used to demonstrate sideroblastic anaemia?
- Accumulation of iron in mitochondria | - Due to disordered haem synthesis
81
What is the treatment for iron-deficiency anaemia?
- Fasted ferrous sulphate
82
What is the treatment of sideroblastic anaemia?
- Withdrawal of alcohol and drugs | - Pyridoxine
83
How are serum iron, ferritin, transferrin receptors and iron-binding capacity affected in sideroblastic anaemia?
- Serum iron is raised - Serum ferritin is raised - Transferrin receptors are raised - Total iron-binding capacity is normal
84
Identify two causes of normocytic anaemia
- Endocrine disorders e.g. hypopituitarism, hypothyroidism | - Haematological disorders e.g. aplastic anaemia, haemolytic anaemia
85
What is a megaloblast?
- Erythroblast with delayed nuclear division - Due to defective DNA synthesis - Large immature nuclei
86
Identify two causes of megaloblastic macrocytic anaemia
- Vitamin B12 deficiency or abnormal B12 metabolism | - Folic acid deficiency or abnormal folate metabolism
87
What would a blood count and film show in megaloblastic macrocytic anaemia
- MCV > 96 fL - Megaloblasts with large immature nuclei - Macrocytes with six or seven lobes in the nucleus
88
Outline the pathophysiology of pernicious anaemia
- Replacement of chief cells by mucin-secreting cells - Atrophic gastritis - Reduced HCl secretion (achlorhydria) - Absence of intrinsic factor production - Resulting in B12 malabsorption
89
Identify three autoimmune diseases that are associated with Pernicious anaemia
- Thyroid Disease - Addison's Disease - Vitiligo
90
Identify the clinical features of pernicious anaemia
- Jaundice and pallor caused be breakdown of haemoglobin - Glossitis and angular stomatitis - Neurological changes, including polyneuropathy caused by low levels of B12
91
Why is serum bilirubin reduced in pernicious anaemia?
- Ineffective erythropoiesis
92
Identify the treatment for pernicious anaemia
- Intramuscular hydroxocobalamin OR - Oral B12
93
Identify three unwanted effects of intramuscular hydroxocobalamin
- Iron deficiency - Hypokalaemia - Hyperuricaemia
94
Identify 8 causes of non-megaloblastic macrocytic anaemia
- Pregnancy - Alcohol excess - Liver disease - Reticulocytosis - Hypothyroidism - Aplastic Anaemia - Sideroblastic Anaemia - Hydroxycarbamide - Azathioprine - Cold agglutinins
95
What is aplastic anaemia?
- Pancytopenia with hypocellularity of the bone marrow
96
What is meant by pancytopenia?
- Deficiency of all three cellular components of the blood | - Erythrocytes, leukocytes and platelets
97
What is meant by hypocellularity?
- Reduced number of cells in the bone marrow
98
Outline the pathophysiology of aplastic anaemia
- Reduced number of pluripotential stem cells - Due to immune mechanisms - Such as activated cytotoxic T cells
99
Identify a genetic cause of aplastic anaemia
- Fanconi's anaemia | - Due to mutations of BRCA2
100
Outline four drugs that may cause aplastic anaemia
- Cytotoxic: Busulifan, Doxorubicin (Chemotherapy) | - Non-Cytotoxic: Chloramphenicol, Gold and Carbimazole
101
Outline three clinical features of aplastic anaemia
- Bleeding (blood blisters in mouth) - Infection - Anaemia
102
Why are broad-spectrum antibiotics given in aplastic anaemia?
- To prevent infection
103
Why are transfusions given in aplastic anaemia?
- Pancytopenia
104
When are antithymocyte globulin and cyclosporin prescribed?
- Patients with severe disease over 40 - Younger patients with severe disease with an HLA-identical sibling donor - Patients who do not have severe disease but who are transfusion dependent
105
What is the main cause of haemolytic anaemia?
- Increased destruction of red blood cells
106
What is compensated haemolytic disease?
- Increased red blood cell output from bone marrow - By increasing number of cells committed to erythropoiesis - Compensates destruction of red blood cells
107
Where does most of the destruction of red blood cels take place?
- Extravascular destrcution
108
Outline the pathophysiology of haemolytic anaemia
- Haemoglobin is oxidised to methaemoglobin - Which dissociates into ferrihaem and globulin - Ferrihaem binds to haemopexin, or - Ferrihaem binds to albumin to form methaemalbumin (seen on Schumm's test)
109
Outline the pathogenesis of hereditary spherocytosis
- Autosomal dominant condition | - Affecting roughly 1 in 5000
110
Outline the pathophysiology of hereditary spherocytosis
- Defect in erythrocyte structural protein spectrin - Increased permeability to sodium - Increased active transport of sodium, out of cell - Reduced surface-to-volume ratio - Cell become spherical
111
How do spherocytes differ to erythrocytes?
- Rigid and less deformable - Unable to pass through splenic microcirculation - Shorter lifespan
112
Identify five clinical features of spherocytosis
- Jaundice - Anaemia - Splenomegaly - Leg Ulcers
113
Identify the main course of action with spherocytosis and its associated therapies
- Splenectomy | - Appropriate immunisation and lifelong penicillin prophylaxis
114
Briefly describe foetal haemoglobin
- HbF-aa/YY - 2 x Alpha Chain - 2 x Beta Chain
115
What is BCL IIA and what is its role?
- Zinc finger protein | - Suppresses the Y gene expression of HbF
116
What is Haemoglobin A?
- A2B2 | - Comprises 97% of adult Hb
117
What is Haemoglobin A2?
- A2D2 | - Comprises 2% of adult Hb
118
What is Haemoglobin F?
- A2Y2 - HB of foetus - Increased in B-thalassaemia
119
What is Haemoglobin H?
- B4 - Found in a-thalassaemia - Biologically useless
120
What is Haemoglobin Barts?
- Y4 - Comprises 100% of Hb in homozygous a-thalassaemia - Biologically useless
121
What is Haemoglobin S?
- a2B2s | - Substitution of valine for glutamine in position 5 of B chain
122
What is Haemoglobin C?
- a2B2c | - Substitution of lysine for glutamic acid in position 6 of B chain
123
What is meant by B0 and B+ and what is their cause?
- In homozygous B-thalassaemia - B0 = No B-chain produced - B+ = Reduced B-chain produced - Caused by point mutations
124
Identify three types of Hb that are present in B-thalassaemia
- HbA2 - HbF - Small amounts of HbA
125
Outline the clinical features of Thalassaemia Minor?
- Carrier state | - Asymptomatic
126
Outline the clinical features of Thalassaemia Intermedia?
- Splenomegaly - Leg ulcers - Gallstones
127
Outline the clinical features of Thalassaemia Major (Cooley's Anaemia)
- Bacterial infections - Severe anaemia - Hepatosplenomegaly, giving rise to thalassaemic facies - 'Hair on end' appearance of bony trabeculation
128
What is the main cause of a-Thalassaemia
- Gene deletions | - Duplications
129
What is the four gene deletion?
- Hb Barts (Y4) | - Hydrops fetalis
130
What is the three gene deletion?
- HbH (B4) | - Moderate anaemia and splenomegaly
131
What is the two gene deletion?
- HbA (a2B2) | - Microcytosis with mild anaemia
132
What is the one gene mutation?
- HbA (a2B2) | - Very mild anaemia or no anaemia
133
Outline how the pathogenesis of Sickle Syndromes
- Single base mutation of adenine to thymine | - Substitution of valine for glutamic acid
134
In which country is the sickle gene most common?
- Africa
135
Outline the pathophysiology of sickle cell anaemia
- HbS molecules are rigid and take up sickle appearance - Lose membrane flexibility due to dehydration - Caused by potassium leaving through Gados Channel - Resulting in shortened cell survival - And impaired passage through the microcirculation
136
Identify five factors that precipitate cell sickling
- Infection - Dehydration - Cold - Acidosis - Hypoxia
137
Outline the three clinical syndromes that can occur in Sickle Syndromes
- Homozygous HbSS (most severe) - Combined heterozygosity HbSC (intermediate) - Heterozygous HbAS (least severe)
138
Explain why dactylitis occurs in sickle cell anaemia
- Pain in hands and feet - Due to vaso-occlusion - - Adhesion proteins such as VCAM-1 - Trapping of rigid sickle cells
139
Explain why pulmonary hypertension occurs in sickle cell anaemia
- Haemolysis leads to increased cell-free plasma Hb - Which consumes NO - A vasodilator substance
140
Explain why Acute Chest Syndrome occurs in sickle cell anaemia
- Infections - Fat embolism from necrotic bone marrow - Pulmonary infarction due to sequestration of sickle cells
141
What does a blood count show in sickle cell anaemia?
- Hb range of 60-80 g/L
142
What does a blood film show in sickle cell anaemia?
- Hyposplenism | - Sickling
143
What does a Sickle Cell Solubility Test show in Sickle Cell anaemia?
- Turbid (cloudy) appearance | - Due to precipitation of HbS
144
Outline the management of Sickle Cell anaemia
- Prophylactic penicillin and vaccination - Blood transfusions - Inhaled nitric oxide - Stem cell transplantation
145
Identify three causes of acquired haemolytic anaemias
- Autoantibodies - Drug-induced antibodies - Alloantibodies
146
What are warm agglutinins?
- Autoantibodies that react with red blood cells at 37 degrees - Typically IgG
147
What are cold agglutinins?
- Autoantibodies that react with red blood cells at less than 37 degrees - Typically IgM
148
What are agglutinogens?
- Antigens on the surface of red blood cells | - Either type A or type B
149
What is type O?
- When neither A or B agglutinogens are present
150
What is type A?
- When only type A agglutinogens are present
151
What is type B?
- When only type B agglutinogens are present
152
What is type AB?
- When both type A and B agglutinogens are present
153
What blood type is a person who has the genotype OO?
- Type O
154
What blood type is a person who has the genotype OA or AA?
- Type A
155
What blood type is a person who has the genotype OB or BB?
- Type B
156
What blood type is a person who has the genotype AB?
- Type AB
157
List the genes in order of frequency from most frequent
- O - A - B - AB
158
When do anti-A agglutinins develop?
- When type A agglutinogen is not present
159
When do anti-B agglutinins develop?
- When type B agglutinogens is not present
160
What are agglutinins?
- Gamma globulins produced in the bone marrow and lymph glands - That produce IgM or IgG antibodies
161
Identify two occasions in which agglutinins develop
- Food | - Bacteria
162
What occurs when blood is mismatched?
- Agglutinins bind to agglutinin - 2 with IgG, 10 with IgM - Cells clump together - Phagocytosis results in haemolysis
163
What is the difference between the O-A-B system and the Rh system?
- In the Rh system, spontaneous agglutinins almost never occur - Person must first be exposed to an Rh antigen before agglutinins cause a significant transfusion reaction
164
Identify the six types of Rh factors
- C - D - E - c - d - e
165
What is the relationship between CDE and cde
- A person has either a CDE or a cde
166
Which Rh antigen is most prevalent?
- D
167
What is meant by the term Rh positive?
- A person possessing the D antigen
168
How does the percentage of Rh positive individuals differ in white and black populations?
- 85% of white people are Rh positive | - 95-100% of black people are Rh positive
169
What is meant by alloimmunisation?
- Immune response | - Against foreign RBC antigens
170
Outline the pathophysiology of of an immediate haemolytic transfusion reaction
- Complement activation by the antigen-antibody reaction - Caused by IgM antibodies - Leads to rigors, lumbar pain, hypotension and renal failure
171
Outline the pathophysiology of of a delayed haemolytic transfusion reaction
- Secondary immune response - Caused by IgG antibodies - Anaemia and jaundice - Blood film shows spherocytosis and reticulocytosis
172
Identify three documentation errors that may occur prior to a blood transfusion
- Failure to check identify of donor when taking the sample - Mislabelling blood sample with wrong name - Failure to perform patient identify check before blood is transfused
173
Why may urticarial reactions occur during a blood transfusion?
- Plasma protein incompatibility
174
What is the treatment for a urticarial reaction during a blood transfusion?
- Administration of chlorphenamine | - Slowing or stopping treatment
175
Why may anaphylactic reactions occur during a blood transfusion?
- Anti-IgA in a patient lacking IgA - Is mixed with transfused blood containing IgA -
176
What is the treatment for an anaphylactic reaction during a blood transfusion?
- Adrenaline | - Or chlorphenamine
177
Which viruses are screened and tested for prior to blood transfusion?
- HBV - HCV - HIV-1 - HTLV-1
178
Why are patients asked about recent travel prior to giving blood?
- Exclude risk of West Nile Virus | - Which is the causal agent of meningoencephalitis
179
Identify a microorganism that can proliferate in red cell and platelet concentrates
- Yersinia enterocolitica
180
Identify three measures to avoid bacterial contaminates when taking blood
- Donor arm cleaning - Diversion of initial collection of samples for testing - Bacterial detection system for platelet concentrates
181
Why is each donation test using the TPHA?
- Treponema Palladium Haemagglutination Assay | - Test for syphilis