Red Cell Diseases + Anaemia Flashcards
(323 cards)
1
Q
How long is the average lifespan of a red blood cell?
A
~120 days
2
Q
What is the role of the spleen in red cell homeostasis?
A
Removes fragile old RBCs from circulation
3
Q
What happens to old red blood cells?
A
Phagocytic cells of the liver and spleen engulf old RBCs
4
Q
What are globular Hb proteins broken down to?
A
Amino acids
5
Q
What does iron bind to when haemoglobin is broken down?
A
Transferrin
6
Q
From what cells are proerythroblasts derived from?
A
Myeloid stem cells
7
Q
What cells do proerythroblasts differentiate to?
A
Polychromatic erythroblast
8
Q
What cells are mature erythrocytes differentiated from?
A
Reticulocytes
9
Q
What cells does a polychromatic erythroblast differentiate into?
A
Orthochromatic erythroblast
10
Q
How does a reticulocyte form?
A
Orthochromatic erythroblasts extrude their nucleus leaving only some ribosomal RNA behind
11
Q
What cell stage does Hb first appear in the cytoplasm along the red cell differentiation?
A
Polychromatic erythroblast
12
Q
At what cell stage does the nucleus shrink and the full Hb complement form in the cytoplasm along the red cell differentiation?
A
Orthochromatic erythroblast
13
Q
What is the approximate diameter of a red blood cell?
A
8 micrometres
14
Q
What is the approximate thickness at the edge of a red blood cell?
A
2 micrometres
15
Q
What is the approximate thickness in the centre of a red blood cell?
A
1 micrometre
16
Q
How does the flexible membrane of the red blood cell benefit it?
A
Can deform to allow cells to squeeze in single file through capillaries
17
Q
What is the typical haematocrit in men?
A
40-50%
18
Q
What is the typical haematocrit in women?
A
36-46%
19
Q
What is the packed cell volume composed of?
A
Red blood cells (haematocrit)
“Buffy coat”:
- Platelets
- White blood cells
20
Q
What is the typical RBC count in men?
A
4.5-6.5 x10^12/L
21
Q
What is the typical RBC count in women?
A
3.8-5.8 x10^12/L
22
Q
What ‘pump’ regulates RBC ion balance and cell volume?
A
Energy-dependent Sodium/Potassium ATPases (‘the sodium pump’)
23
Q
What is the only route for ATP synthesis in RBCs and why?
A
Anaerobic glycolysis
Since they have no mitochondria
24
Q
What does NADH gained from glycolysis in RBCs do? Why is this important?
A
Keeps iron in Fe2+ state
Methaemoglobin (HbFe3+) cannot bind oxygen
25
What does the hexose monophosphate shunt in red blood cells do? Why is this important?
Produces NADPH
| Required for maintenance of adequate levels of reduced glutathione
26
When is 2,3-bisphosphoglycerate produced?
When pO2 is reduced
27
What is the purpose of 2,3-bisphosphoglycerate?
Releases O2 from Hb
28
What is the structure of glutathione?
Tripeptide consisting of:
- Glutamate
- Cysteine
- Glycine
29
What does reduced glutathione do?
Combats oxidative stress
30
What is consumed in the conversion of glucose to glucose-6-phosphate?
ATP (to ADP)
31
What enzyme catalyses the conversion of glucose to glucose-6-phosphate?
Hexokinase
32
What enzyme catalyses the conversion of glucose-6-phosphate to fructose-6-phosphate?
Phosphoglucose isomerase
33
What is consumed when fructose-6-phosphate is converted to fructose-1,6-bisphosphonate?
ATP (to ADP)
34
What enzyme catalyses the conversion of fructose-6-phosphate to fructose-1,6-bisphosphonate
Phosphofructokinase
35
What is fructose-1,6-bisphosphonate converted to next in the glycolysis pathway?
Glyceraldehyde-3-phosphate
36
What is glyceraldehyde-3-phosphate converted to next in the glycolysis pathway and what conversion occurs alongside this?
1,3-bisphosphoglycerate
| 2NAD+ -> 2NADH
37
What can 1,3-bisphosphoglycerate be converted to? What does one of these conversions produce?
2,3-bisphosphoglycerate
3-phosphoglycerate:
- Producing 2 ATP
38
What is 3-phosphoglycerate converted to?
Phosphoenolpyruvate
39
What is produced when phosphoenolpyruvate is converted to pyruvate?
2ATP
40
What is produced when pyruvate is converted to lactate?
NAD+
41
What does NAD(P)H oxidase xanthine oxidase do?
Converts O2 to O2.- (oxygen free radical species)
42
What does superoxide dismutase do?
Converts O2.- to H2O2
43
What do catalase and GSH peroxidase do?
Convert H2O2 to H2O
44
What does reduced glutathione do?
Detoxifies H2O2
45
What else can glucose-6-phosphate be converted to (apart from fructose-6-phosphate)? What is produced and what is consumed?
Hexose monophosphates
| NADP+ -> NADPH (Consumes GSSG -> GSH)
46
What are pentose phosphates formed from in glycolysis?
Hexose monophosphates (Produces NADPH)
Fructose-6-phosphate
Glyceraldehyde-3-phosphate
47
What enzyme converts glucose-6-phosphate to hexose monophosphates?
Glucose-6-phosphate dehydrogenase
48
What enzyme, alongside NADPH and H+, converts oxidised glutathione to reduced glutathione?
Glutathione reductase
49
What enzyme catalyses the conversion of reduced glutathione to oxidised glutathione? What conversion occurs alongside this?
Glutathione peroxidase
| H2O2 -> H2O
50
What percentage of CO2 is dissolved in the blood?
10% (proportional to inhaled pCO2)
51
What percentage of CO2 is bound to Hb? What is it called?
30%
| Carbaminohaemoblogin
52
What percentage of CO2 is present in the blood as bicarbonate?
60%
53
What enzyme facilitates CO2 transport in the blood?
Carbonic anhydrase
54
What exchanger facilitates the transport of bicarbonate out of erythrocytes?
Bicarbonate/Chloride:
- Bicarbonate moves out
- Chloride moves in
55
When fully saturated, how much oxygen will 1g of Hb bind?
1.34ml
56
What does haemoglobin synthesis require?
Synthesis of globin chains (4 per Hb)
Synthesis of porphyrin ring (haem group)
Insertion of Fe2+ into haem
57
What is the predominant globin structure of foetal Hb?
alpha2 gamma2
58
What happens to the structure of foetal Hb in late gestation?
Gamma expression falls
| Beta expression rises
59
What is the predominant globin structure of adult Hb?
alpha2 beta2
60
What is the normal adult [Hb} in men?
130-180g/L
61
What is the normal adult [Hb] in women?
115-165g/L
62
What does the co-operative behaviour of oxygen binding to Hb mean?
Binding of a ligand to one site on the molecule affects the binding of a ligand to a different functional site
63
What does the steep, venous phase of the haemoglobin oxygen dissociation curve do?
Favours O2 off-loading to tissues
64
What does the plateau, arterial phase of the haemoglobin oxygen dissociation curve do?
Sustains SaO2 >90% over wide range of inspired pO2
65
Does foetal Hb have a lower or higher affinity for oxygen than adult Hb?
Higher
66
Does foetal Hb have a lower or higher affinity for 2,3-BPG than adult Hb?
Lower
67
[Hb] below what level in adult males is considered anaemia?
<130g/L
68
[Hb] below what level in adult females is considered anaemia?
<120g/L
69
At what wavelength is spectrophotometry carried out to determine [Hb]? What does this measure?
540nm
| Optical density
70
What is Beer's Law?
Optical density of a Hb solution is proportional to Hb
71
How is a Hb solution stabilised?
Cyan-Methaemoglobin
72
When may haematocrit not be a good marker of anaemia?
In rapid blood loss:
- [Hb] and Hct could be = as plasma volume also drops
Haemodilution:
- Same RBC mass but decreased [Hb] and Hct
73
Why do reticulocytes stain purple/deeper red than mature RBCs?
They still have remnants of RNA
74
What are the two pathophysiological classifications of anaemia?
```
Decreased production:
- Hypoproliferation
- Maturation abnormality
Increased loss/Destruction:
- Bleeding
- Haemolysis
```
75
If MCV is low (microcytic), problems with what part of the production of red cells should be considered defective?
Haemoglobinisation
76
If MCV is high (macrocytic), problems with what part of the production of red cells should be considered defective?
Maturation
77
What compound is protoporphyrin made from?
Porphobilinogen
78
Where is protoporphyrin made?
Mitochondria
79
What is haem made from?
Fe2+
| Protoporphyrin
80
Where is haem made?
Cytosol
81
What is Hb made from?
Haem
| Globins
82
Where is Hb made in the cell?
Cytosol
83
Shortage of what components in the production of Hb result in microcytic anaemias?
Globins
| Haem
84
What is deficient in hypochromic microcytic anaemia?
Hb synthesis (cytoplasmic defect)
85
What can cause a haem deficiency?
Lack of iron for erythropoiesis
Problems with porphyrin synthesis
Congenital sideroblastic anaemia
86
What can cause problems with porphyrin synthesis?
Lead poisoning
| Pyridoxine responsive anaemias
87
What is thalassaemia?
Globin deficiency
88
How much iron is absorbed per day?
1mg
89
How much iron exists in the plasma?
~4mg
90
How much iron is stored in parenchymal tissues (eg. liver, other)?
500mg
91
How is iron in parenchymal tissues stored?
Ferritin
92
How much iron is lost from parenchymal tissues per day?
1mg
93
How much iron is present in the erythroid marrow?
150mg
94
How much iron is present in red cell Hb?
2500mg
95
How much iron is in macrophage stores?
500mg
96
How is iron stored in macrophages?
Ferritin
97
What is circulating iron bound to?
Transferrin
98
How can transported iron be assessed?
Serum iron
Transferrin
Transferrin saturation
99
How many binding sites does transferrin have?
Two
100
What donor tissues does transferrin transport iron from?
Macrophages
Intestinal cells
Hepatocytes
101
How is transferrin saturation affected in iron deficiency?
Reduced
102
How is transferrin saturation affected in anaemia of chronic disease?
Reduced
103
How is transferrin saturation affected in genetic hemochromatosis?
Increased
104
How many ferric (Fe3+) ions can ferritin store?
4000
105
Where is most ferritin present?
Intracellularly
106
There is a tiny amount of ferritin present in the serum, what does this reflect?
Intracellular ferritin synthesis in response to iron status
107
What does low ferritin indicate?
Iron deficiency
108
What are relative causes of iron deficiency?
Women of child-bearing age
| Children
109
What is an absolute cause of iron deficiency?
Vegetarian diet
110
What malabsorptive conditions can result in iron deficiency?
Coeliac disease
| Achlorhydia
111
What is the average volume of blood loss from menstruation a month? What is this equivalence in iron mass?
30-40ml/month
| 15-20mg/month
112
What are the consequences of negative iron balance?
1. Exhaustion of iron stores
2. Iron deficient erythropoiesis (Falling RBC MCV)
3. Microcytic anaemia
4. Epithelial changes (skin, koilonychia)
113
What is macrocytosis?
Enlargement of RBCs with normal [Hb]
114
What is macrocytic anaemia?
Increased RBC volume with decreased [Hb] and number of RBCs
115
What units is MCV measured in?
Femtolitres (1 femtolitre = 10^-15L)
116
What is the normal range for MCV?
80-100fL
117
What is a megaloblast?
An abnormally large nucleated red cell precursor with an immature nucleus
118
What are the prominent defects in megaloblastic anaemias?
DNA synthesis
| Nuclear maturation
119
What is relatively preserved in megaloblastic anaemias?
RNA synthesis
| Hb synthesis
120
What happens to developing erythroid cells in the marrow?
Accumulate Hb
Decrease in size
Stop dividing and lose nucleus
121
What regulates the loss of the nucleus in developing erythrocytes?
Hb content
122
Why do megaloblastic anaemias cause increased MCV?
Cytoplasma is mature (and big) enough to divide
Nucleus is still immature:
- Cell thinks it has the right amount of Hb so doesn't divide
123
What are the main deficiencies that result in megaloblastic anaemia?
Vitamin B12 deficiency
| Folate deficiency
124
What drugs can cause megaloblastic anaemia?
Folic acid antagonists (eg. Methotrexate)
Phenytoin
Nitrous oxide
125
What are Vitamin B12 and Folate essential for?
Nuclear maturation:
| - Enable chemical reactions that provide nucleosides for DNA synthesis
126
What does the Methionine cycle produce?
s-adenosyl methionine
127
What is the folate cycle important for?
Nucleoside synthesis
| eg. Uridine to Thymidine conversion
128
What is the function of s-adenosyl methionine?
Methyl donor to DNA, RNA, proteins, lipids and folate intermediates
?Impact on myelin
129
An inherited deficiency of what receptors in the ileum can result in a vitamin B12 deficiency?
Cubin receptors
130
What are dietary folates converted to?
Monoglutamate
131
What is the dietary source of vitamin B12?
Animal meat
132
What are dietary sources of folate?
Leafy veg.
Yeast
(Destroyed by cooking)
133
How long is vitamin B12 stored in the body?
2-4 years
134
How long is folate stored in the body?
4 months
135
Where is vitamin B12 absorbed?
Ileum
136
Where is folate absorbed?
Duodenum
| Jejunum
137
What is the daily requirement of vitamin B12?
1-3 micrograms/day
138
What is the daily requirement of folate?
100 micrograms/day
139
What stomach pathologies can result in a B12 deficiency?
PA
Atrophic gastritis
PPIs/H2 receptor antagonists
Gastrectomy/Bypass
140
How can chronic pancreatitis result in megaloblastic anaemia?
Causes a B12 deficiency
141
How can folate be utilised excessively resulting in its deficiency?
Haemolysis
Exfoliating dermatitis
Pregnancy
Malignancy
142
What drugs can result in a folate deficiency?
Anticonvulsants
143
What symptoms are common to both vitamin B12 and folate deficiency?
```
Weight loss
Diarrhoea
Infertility
Sore tongue
Jaundice
Developmental problems
```
144
What symptoms are caused by vitamin B12 deficiency only? What are they related to?
Myelin:
- Dorsal column abnormalities
- Neuropathy
- Dementia
- Psychiatric manifestations
145
What is the pathology behind pernicious anaemia?
Autoimmunity resulting in the destruction of gastric parietal cells
146
What is pernicious anaemia associated with?
```
Atrophic gastritis
PMHx/FHx of other autoimmune disease:
- Hypothyroidism
- Vitiligo
- Addison's Disease
```
147
How do dendritic cells play a role in pernicious anaemia?
Clear apoptotic parietal cells produced during turnover of gastric mucosa
Activation of CD4+ T-cells:
- Recognise H+/K+ ATPase expressed in parietal cells
148
What features of an FBC would be seen in pernicious anaemia?
Macrocytic anaemia
| Pancytopaenia (in some)
149
What features of a blood film would be seen in pernicious anaemia?
```
Macrovalocytes
Hypersegmented neutrophils (3-5 nuclear segments)
```
150
What autoantibodies might be seen in pernicious anaemia?
```
Anti-gastric parietal cell (GPC):
- Sensitive
- Not specific
Anti-intrinsic factor (IF):
- More specific
- Not sensitive
```
151
What test, that is not routinely used, can be used to diagnose pernicious anaemia?
Schilling's Test
152
What can cause macrocytosis but are not usually causes of macrocytic anaemia?
Alcohol
Liver disease
Hypothyroidism
153
What are other causes of macrocytic anaemia?
Myelodysplasia
Myeloma
Aplastic anaemia
154
How can reticulocytosis result in spurious macrocytosis?
Marrow response increases in:
- Acute blood loss
- Haemolysis
Reticulocytes are bigger so increased MCV
155
What is another cause of spurious macrocytosis?
Cold-agglutinins:
| - Clumps of agglutinated cells registered as 1 'giant cell'
156
How can pernicious anaemia cause mild jaundice?
Intramedullary haemolysis (ineffective erythropoiesis):
- RBCs die prematurely in marrow
- Hb and lactate dehydrogenase are released
- Hb converted bilirubin
157
How soon does plasma have to be frozen to be called fresh frozen plasma?
8 hours
158
How much of a therapeutic dose of platelets is obtained from one blood donation?
1/4
159
How much blood is taken is the typical blood donation?
465ml
160
What is the minimum weight of an individual who can donate blood?
50kg
161
How are RBCs stored?
At 4 degrees celsius
| Shelf life of 35 days
162
What happens in RBCs are removed for more than 30 minutes?
Transfuse within 4 hours
OR
Discard
163
How are platelets stored?
Store at room temp. (22 degrees) with continual agitation (promotes gas exchange)
Shelf life of 7 days (if bacterial monitoring)
164
How soon must platelets be transfused?
Within 1 hour
165
How is fresh frozen plasma stored?
At -30 degrees
For up to 3 years
Thaw prior to transfusion
166
How soon must FFP be transfused once thawed?
4 hours
167
When is FFP used?
To replace coagulation factors:
- Blood loss
- Liver disease (can't make own)
168
What are the structures of naturally occurring ABO-Abs?
Mostly IgM
| Some IgG
169
On what chromosome is our ABO blood group inherited on?
Chromosome 9
170
What do 'A' and 'B' code for?
Specific transferase enzymes:
| - Add a sugar residue to a precursor 'H' substance on RBC membrane
171
What is the recessive ABO gene?
'O' (it's silent)
172
On what chromosome is our Rhesus blood group inherited on?
Chromosome 1
173
What is the blood group denoted by K and k?
Kell
174
What is the blood group denoted by Fya and Fyb?
Duffy
175
What is the blood group denoted by Jka and Jkb?
Kidd
176
What are some possible indications for red cell transfusion?
Low Hb with:
- Reduced exercise capacity
- Congenital medical/surgical problems
- Heart/Lung disease
- "Anaemia" symptoms
177
What is the typical volume of blood in a person?
70ml/kg
178
How can blood volume be maintained before a blood transfusion is prescribed?
Saline
| Albumin gelofusion
179
How long does it take for a full ABO, Rh(D), Ab screen and cross-match?
1 hour
180
How long does it take for a type specific (ABO and Rh(D) and immediate cross-match)?
10-20 minutes
181
What blood can be used immediately in an emergency?
O negative blood
182
What level of urine output should be maintained in acute blood loss?
>30ml/hr
183
What [Hb] should be maintained in acute blood loss?
>100g/L
184
How long does platelet apheresis take?
30-90 minutes
185
How often can a person donate platelets by platelet apheresis?
Every 3 weeks
186
What are the benefits of prescribing a dose of platelets obtained from apheresis compared to a dose pooled from 4 donors?
Reduced risk of infection
| Reduced risk of tissue Ag sensitisation
187
What should the platelet level in thrombocytopaenia be maintained at following:
- General surgery
- Neurosurgery?
```
General = 50x10^9/L
Neurosurgery = 100x10^9/L
```
188
What are the indications for FFP?
Correcting coag. deficiency in liver disease with bleeding
Coagulopathy following massive transfusion
DIC:
- Overwhelming infection
- ABO mismatch
189
In an immediate haemolytic transfusion reaction, what effects do C3a and C5a have?
Anaphylotoxins:
- Increase vascular permeability
- Dilate blood vessels
- Serotonin and Histamine release (fever, chills, hypotension, shock)
190
In an immediate haemolytic transfusion reaction, what effects does the MAC have?
Haemolysis of transfused RBCs
191
What activates the kinin system in an immediate haemolytic transfusion reaction?
Factor XIIa
192
When the kinin system is activated, what happens?
```
Formation of bradykinin:
- Arteriolar dilatation
- Increased vascular permeability
Hypotension:
- Catecholamine release
- Vasoconstriction in kidneys (and other organs)
```
193
When does a delayed haemolytic transfusion reaction occur?
5-10 days post-transfusion
194
What are the lab features of a delayed haemolytic transfusion reaction?
```
Anaemia
Spherocytes
Increased bilirubin and LDH
Positive DAGT +/or red cell allo-Ab
+/- renal failure
```
195
What causes a febrile non-haemolytic transfusion reaction?
Abs against contaminating white cells:
| - Cytokines and vasoactive substances released from white cells during storage
196
How can a febrile non-haemolytic transfusion reaction be investigated?
HLA Abs
| No evidence of RBC incompatibility
197
How can a febrile non-haemolytic transfusion reaction be treated?
Antipyretics
| Leucodepleted blood components
198
How can urticarial blood transfusion reactions be treated?
Slow transfusion
| Antihistamines
199
What patients are at most risk of having circulatory overload during a blood transfusion?
Elderly
| CCF
200
How can circulatory overload be prevented?
Slow transfusion rate
| Diuretics (not good practice)
201
What bacterial infections are related to red cell transfusions?
Pseudomonas
| Yersinia
202
What bacterial infections are related to platelet transfusions?
Staph.
Strep.
Serratia
Salmonella
203
What is the structure of HbA?
2 alpha chains
| 2 beta chains
204
What is the structure of HbA2?
2 alpha chains
| 2 delta chains
205
Where are the alpha-like genes for Hb?
Chromosome 16
206
How many alpha-like genes are on each chromosome?
2 alpha genes per chromosome 16 (4 total)
207
Where are the beta-like genes for Hb?
Chromosome 11
208
How many beta-like genes are on each chromosome?
1 beta gene per chromosome 11 (2 total)
209
When are adult levels of Hb reached?
6-12 months of age
210
What are haemoglobinopathies?
Hereditary conditions affecting globin chain synthesis
211
How are most haemoglobinopathies inherited?
Autosomal recessive
212
What are thalassaemias?
Hereditary disorders of globin chain synthesis
213
What type of anaemia do thalassaemias result in?
Microcytic hypochromic
214
How does alpha thalassaemia result?
Deletion of one or both alpha genes from chromosome 16
215
What is alpha thalassaemia trait?
One or two genes missing
216
What is HbH disease?
Only one functional alpha-gene present on one chromosome 16
217
What is Hb Barts Hydrops Foetalis?
No functional alpha genes on either chromosome 16
218
How can alpha thalassaemia trait be distinguished from iron deficiency?
Ferritin normal
| RBC count raised
219
What does a FBC show in HbH disease?
Anaemia
Very low:
- MCV
- MCH
220
What happens to Hb in HbH disease?
Excess beta chains form tetramers (beta4):
- Called HbH
- Cannot carry oxygen
221
What are HbH bodies?
Red cell inclusions seen in HbH disease with a special stain
222
What causes splenomegaly in HbH disease?
Extramedullary haematopoiesis
223
What causes jaundice in HbH disease?
Haemolysis
| Ineffective erythropoiesis
224
How are severe cases of HbH disease treated?
Splenectomy
| +/- Transfusion
225
What are some long term sequelae of HbH disease?
Growth retardation
Gallstones
Iron overload
226
Where is HbH disease most common?
SE Asia
Middle East
Mediterranean (where (--/alpha alpha) is prevalent)
227
What forms of Hb are the majority at birth in Hb Bart's Hydrops Foetalis Syndrome?
Hb Bart's (gamma4)
| HbH (beta4)
228
What are the clinical features of Hb Bart's Hydrops Foetalis Syndrome?
Severe anaemia (many nucleated RBCS in film)
Cardiac failure and oedema
Growth retardation
Severe hepatosplenomegaly
Skeletal and cardiovascular abnormalities
Most die in utero
229
In beta thalassaemia, only beta chains are affected, what kind of Hb is affected?
HbA only
230
Where are the highest levels of beta thalassaemia carriers?
SE Asia
Cyprus
Sardinia
231
What causes beta thalassaemia trait?
Reduced beta/beta
OR
Absent beta/beta genes
232
How can beta thalassaemia trait present?
Asymptomatic
| No/Mild anaemia and low MCV/MCH
233
What causes beta thalassaemia intermedia?
Reduced beta/reduced beta
OR
Absent beta/reduced beta
234
How does beta thalassaemia intermedia present?
Moderate severity
| Requires occasional transfucion
235
What causes beta thalassaemia major?
Absent beta/absent beta
236
How does beta thalassaemia major present?
Severe, lifelong transfusion dependency
237
What does a film show in beta thalassaemia major?
```
Microcytosis
Hypochromia
Anisopoikilocytosis:
- RBCs of varying sizes and abnormal shapes
Target cells
```
238
When do patients with beta thalassaemia major tend to first present?
6-24 months
239
What does extramedullary haematopoiesis in beta thalassaemia major cause?
Hepatosplenomegaly
Skeletal changes
Organ damage
Cord compression
240
What is the purpose of the regular transfusion programme in managing beta thalassaemia major?
Maintain [Hb] at 95-105g/L
Suppress ineffective erythropoiesis
Inhibit over-absorption of iron
241
What is the main cause of mortality in beta thalassaemia major?
Iron overload from transfusion (>70%)
242
What endocrine dysfunctions occur in iron overload?
Impaired growth and pubertal development
Diabetes
Osteoporosis
243
What cardiac diseases occur in iron overload?
Cardiomyopathy
| Arrhythmias
244
What liver disease occur in iron overload?
Cirrhosis
| Hepatocellular cancer
245
How does Desferrioxamine work?
Iron chelating
246
How is Desferrioxamine administered?
S/C or IV
247
What are the side effects of high dose Desferrioxamine?
Ocular toxicity
| Ototoxicity
248
What is the benefit of Deferiprone?
Better at removing cardiac iron
249
What are the side effects of Deferiprone?
Arthralgia
GI upset
1% risk of agranulocytosis
250
What does a blood film of thalassaemia show?
Hypochromia
Target cells
Anisopoikilocytosis
251
What does high performance liquid chromatography show in beta thalassaemia trait?
Raised HbA2 (diagnostic)
252
What does high performance liquid chromatography show in alpha thalassaemia trait?
It is normal
253
What is the mutation in sickling disorders?
Point mutation in codon 6 of the beta globin gene that substitutes glutamine to valine
254
What is the pathophysiology of sickling disorders?
BetaS produced
Alters Hb structure:
- HbS (alpha2, betaS2)
255
What happens to Hb in sickling disorders?
Polymerised if exposed to low oxygen for prolonged period:
- Distorts cell
- Damages RBC membrane
256
When may a sickle crisis occur in sickle trait?
Severe hypoxia:
- High altitude
- Under anaesthesia
257
How is sickle cell disease inherited?
Autosomal recessive
258
What is a sickle crisis?
Episodes of tissue infarction due to vascular occlusion
259
What are the symptoms of sickle cell disease?
Dactylitis
Bone marrow, lung, spleen, CNS
Pain may be extremely severe
260
What does chronic haemolysis in sickle cell disease result in?
Shortened RBC lifespan
261
What happens to sickled RBCs?
Sequestered in liver and spleen
262
How does hyposplenism result in sickle cell disease?
Repeated splenic infarcts
263
What can precipitate a sickle crisis?
```
Hypoxia
Dehydration
Infection
Cold exposure
Stress/Fatigue
```
264
How is a painful sickle crisis treated?
```
Opiates
Hydration
Rest
Oxygen
Antibiotics if infection
```
265
What indicates a severe sickle crisis?
Chest
| Neurological symptoms
266
How is a severe sickle crisis treated?
Venesect -> Transfuse -> Venesect -> Transfuse:
- Reduces [HbS]
- Increases tissue perfusion
267
What are the long term organ damages in sickle cell anaemia?
```
Pulmonary hypertension
Renal disease
Avascular necrosis
Leg ulcers
Stroke
```
268
How is hyposplenism treated in sickle cell disease?
```
Prophylactic penicillin
Vaccination:
- Pneumococcus
- Meningococcus
- Haemophilus
```
269
What bacteria often cause infections in sickle cell disease?
Encapsulated bacteria
270
What are the other treatments for sickle cell disease?
Folic acid supplementation
| Hydroxycarbamide can reduce severity by inducing HbF production
271
What does HbSC disease increase the risk of?
Thrombosis
272
What stain can identify reticulocytes by staining the rRNA?
New methylene blue
273
What is extravascular haemolysis?
Taken up by reticuloendothelial system (liver, spleen)
274
What is intravascular haemolysis?
RBCs destroyed within circulation
275
What is released in extravascular haemolysis?
Release of protoporphyrin:
- Unconjugated bilirubin causes jaundice and gallstones
- Urobilinogenuria
276
What results in intravascular haemolysis?
Haemogloboinaemia
Methaemoglobinaemia
Haemoglobinuria (Pink urine - black on standing)
Haemosiderinuria
277
What can cause intravascular haemolysis?
```
ABO incompatibility
G6PD deficiency
Severe falciparum malaria (Blackwater fever)
Even rarer:
- Paroxysmal Nocturnal Haemoglobinuria
- Paroxysmal Cold Haemoglobinuria
```
278
On a blood film, how do membrane damaged red cells appear?
Spherocytes
279
On a blood film, what do red cell fragments (schistocytes) indicate?
Mechanical damage
280
What do Heinz bodies on a blood film indicate? What might they be seen in?
Oxidative damage
| G6PD deficiency
281
What immunoglobulins are involved in warm autoimmune haemolysis?
IgG
282
What immunoglobulins are involved in cold autoimmune haemolysis?
IgM
283
What are the causes of warm autoimmune haemolysis?
```
Idiopathic (commonest)
Autoimmune disorders (SLE)
Lymphoproliferative disorders (CLL)
Drugs (penicillins, NSAIDs, quinidine)
URTIs
```
284
What are the causes of cold autoimmune haemolysis?
Idiopathic
Infections (EBV, mycoplasma)
Lymphoproliferative disorders
285
How is autoimmune haemolysis investigated?
Direct Coombs' Test
286
What sort of immunoglobulins are involved in an alloimmune immediate haemolytic reaction? Is it intra- or extravascular?
IgM
| Intravascular
287
What sort of immunoglobulins are involved in an alloimmune delayed haemolytic reaction? Is it intra- or extravascular?
IgG
| Extravascular
288
What is Zieve's Syndrome?
```
Haemolysis due to an acquired membrane defect
Alcoholic liver disease
Hyperlipidaemia
Blood film:
- Anaemia
- Polychromatic macrocytes
- Irregularly contracted cells
```
289
How can Paroxysmal Nocturnal Haemoglobinuria be tested for?
Ham's Acid Haemolysis Test (Tests for RBC fragility)
290
What can a Vitamin E deficiency cause?
An acquired RBC membran defect
291
What are Pappenheimer bodies seen in?
Beta thalassaemia major
292
What can serum ferritin act as? Because of this, when else can it be raised?
Acute phase protein:
- Infection
- Malignancy
293
What iron transporters aid in the absorption of iron?
DMT-1
| Ferroportin
294
What is Hepcidin?
Major negative regulator of iron uptake:
| - Downregulates ferroportin
295
What organ produces Hepcidin and in response to what?
In the liver in response to:
- Iron load
- Inflammation
296
What is the function of DMT-1?
Transports iron into the duodenal enterocyte
297
What is the function of ferroportin?
Facilitates iron export from enterocyte
| Passed on to transferrin
298
What is primary iron overload (primary haemochromatosis)?
Long-term excess iron absorption with parenchymal (rather than macrophage) iron loading
299
What are the clinical features of hereditary haemochromatosis?
```
Weakness/Fatigue
Joint paints
Impotence
Arthritis
Cirrhosis
Diabetes
Cardiomyopathy
```
300
When does hereditary haemochromatosis present?
Middle/Old age when iron overload >5g
301
What are the potential mutations that can result in primary haemochromatosis?
Mutations of HFE gene:
- C282Y
- H63D
- Mainly results in reduced hepcidin synthesis
302
What transferrin saturation might suggest a risk of iron loading?
>50%
303
What serum ferritin levels can indicate iron overloading??
>300 micrograms/L in men
| >200 micrograms/L in pre-menopausal women
304
How is hereditary haemochromatosis treated?
Weekly phlebotomy:
- 450-500ml
- Equivalent to 200-250mg iron
305
What is the initial aim of hereditary haemochromatosis?
Exhaust iron stores:
| - Ferritin <20 mcg/L
306
After initial therapy for hereditary haemochromatosis, what is the purpose of further treatment?
Keep ferritin <50 mcg/L
307
What is the main cause of death in hereditary haemochromatosis?
Hepatoma
308
How is secondary iron overload treated?
Iron chelating agents
309
Below what [Hb] level is anaemia likely in children (6 months to 6 years)?
110g/L
310
Below what [Hb] level is anaemia likely in children (6-14 years)?
120g/L
311
Below what [Hb] level is anaemia likely in adult males?
130g/L
312
Below what [Hb] level is anaemia likely in adult females (non-pregnant)?
120g/L
313
Below what [Hb] level is anaemia likely in adult females (pregnant)?
110g/L
314
What can indicate impaired RBC production?
Anaemia with lesser reticulocyte response
315
What mnemonic can be used to remember the causes of hypochromic microcytic anaemia?
```
T - Thalassaemia
A - Anaemia of chronic disease
I - Iron deficiency
L - Lead poisoning
S - Sideroblastic anaemia
```
316
What hypoproliferative disorders can result in a normochromic normocytic anaemia?
```
Chronic disease:
- Inflammation
- Infection
- Malignancy
Anaemia of renal failure
Hypometabolic states (eg. Hypothyroidism(
Marrow failure:
- Aplasia
- Infiltration
```
317
Where does haematopoiesis occur in the embryo?
Yolk sac then liver
| Spleen from 3rd - 7th month
318
Where does haematopoiesis occur in adults?
Bone marrow of:
- Skull
- Ribs and sternum
- Pelvis
- Proximal ends of femur
319
When does neutrophilia occur physiologically?
Infection
Trauma
Infarction
320
What is the function of eosinophils?
Fight parasitic infections
| Hypersensitivity
321
When can eosinophilia occur?
Asthma
| Atopic rhinitis
322
What is the structure of a mature lymphocyte?
Small
| Condensed nucleus and rim of cytoplasm
323
What is the structure of an activated (/atypical) lymphocyte?
Large
Plentiful blue cytoplasm extending round neighbouring RBCs
Nucleus more 'open'
