[W1] Red Blood Cells + Anaemia Flashcards
1
Q
What is the shape of a red blood cell (RBC)?
A
Biconcave disc
2
Q
What is the mean diameter of an RBC?
A
7μm
3
Q
What is the mean volume of an RBC?
A
78 – 101 fl
4
Q
Do mature RBCs have a nucleus or cytoplasmic organelles?
A
No, mature RBCs lack a nucleus and cytoplasmic organelles.
5
Q
What percentage of an RBC is hemoglobin (Hb)?
A
25% by volume and 33% by weight
6
Q
What is the primary function of red blood cells (RBCs)?
A
To act as the “packaging” for hemoglobin (Hb).
7
Q
How do RBCs contribute to oxygen transport?
A
They carry oxygen (O₂) bound to hemoglobin (Hb).
8
Q
How do RBCs help remove carbon dioxide?
A
They transport carbon dioxide (CO₂) in the blood.
9
Q
What role do RBCs play in acid-base balance?
A
They help maintain plasma pH.
10
Q
How does the biconcave shape of RBCs help their function?
A
It provides pliability for capillary passage and increases surface area for gaseous exchange.
11
Q
Why do mature RBCs lack a nucleus and organelles?
A
To optimize hemoglobin (Hb) content and increase deformability.
12
Q
How far does an RBC travel in its lifespan?
A
Approximately 300 miles.
13
Q
How many times does an RBC circulate through the heart in its lifespan?
A
Around 170,000 circuits.
14
Q
What advantage does RBC deformability provide?
A
It allows RBCs to squeeze through narrow capillaries efficiently.
15
Q
What is the composition of the RBC membrane?
A
40% lipids, 52% protein, 8% carbohydrate.
16
Q
What type of structure does the RBC membrane have?
A
A lipid bilayer.
17
Q
Why are the outer surfaces of the RBC membrane hydrophilic?
A
To make them “water wettable” and interact with plasma.
18
Q
What is the charge of the RBC membrane surface?
A
Negatively charged.
19
Q
Why is the RBC membrane negatively charged?
A
To prevent RBC aggregation (clumping).
20
Q
what are 6 components of the RBC membrane?
A
- band 3 protein
- glycophorin A
- glycophorin C
- ankyrin
- spectrin
- “actin complex”
21
Q
what is the function of the band 3 proteins found in the RBC membrane?
A
Anion transport, esp. chloride and bicarbonate
22
Q
what is the function of the Glycophorin A found in the RBC membrane?
A
Maintenance of negative charge – electrostatic repulsion to prevent aggregation, sugar transport
23
Q
what is the function of the Glycophorin C found in the RBC membrane?
A
regulating cell shape, membrane deformability, and membrane mechanical stability
24
Q
what is the function of the ankyrin found in the RBC membrane?
A
links lipid bilayer to spectrin
25
what is the function of the Spectrin found in the RBC membrane?
Maintenance of biconcave disc. Most abundant cyto-skeletal protein
26
what is the function of the "actin complex" found in the RBC membrane?
links lipid bilayer to spectrin
27
What is the arrangement of some RBC membrane proteins called?
The cytoskeleton.
28
What is the main metabolic pathway in RBCs?
Anaerobic glycolysis.
29
Why does RBC metabolism maintain Haem Fe in the Fe²⁺ state?
To prevent oxidation to Fe³⁺, which forms MetHb, an inoperative oxygen carrier.
30
Why do RBCs produce ATP?
To maintain membrane deformability and regulate ion and water exchange.
31
What metabolic pathway produces NADPH in RBCs?
The pentose phosphate pathway.
32
What is the function of 2,3 DPG (2,3 BPG) in RBCs?
It helps regulate oxygen affinity.
33
What is erythropoiesis?
The process of red blood cell (RBC) production, part of haemopoiesis.
34
Where does erythropoiesis occur in adults?
In the marrow spaces of the sternum, pelvis, and long bones.
35
How many RBCs are destroyed and replaced daily?
Approximately 10¹¹ RBCs per day (nearly 1 million per second).
36
What hormone regulates RBC production?
Erythropoietin (Epo), a cytokine produced in the kidneys.
37
How does erythropoietin (Epo) increase RBC numbers?
It acts on committed erythroid precursors in the bone marrow to increase cell division
38
What triggers Epo production in the kidneys?
Renal hypoxia (low oxygen levels).
39
What happens to RBC nuclei before their release from the marrow?
They are extruded and phagocytosed by macrophages.
40
What organelles remain in immature RBCs (reticulocytes) after release?
Mitochondria and ribosomes, which continue Hb synthesis for 1–2 days.
41
By how much can RBC production be increased if needed?
It can be uprated by 10×.
42
What is the normal RBC count in 1 mm³ of blood?
3.5 – 5.5 × 10⁶ RBCs.
43
what are the 2 types of immature RBCs?
- Nucleated RBCs ("normoblast")
- Reticulocyte
44
what is the lifespan of a RBC?
approx. 120 days
45
What is haemolysis?
A shortening of the RBC lifespan.
- rupturing of RBC
46
What is compensated haemolysis?
Haemolysis that is balanced by increased RBC production, preventing anemia.
47
What does an increased reticulocyte count indicate?
An increased rate of RBC production.
48
What is the normal adult reticulocyte range?
0.5 – 1.5%.
49
What do splenic macrophages do?
They remove granular debris, defective membranes, and destroy senescent RBCs.
50
What is the function of the spleen in RBC filtration?
It acts as a very discriminating filter.
51
What are splenic cords?
Blind sacs in the spleen.
52
What are splenic sinuses?
Blood spaces in the spleen.
53
What separates splenic cords and sinuses?
3μm windows.
54
Where are macrophages located in the spleen?
They line the splenic cords.
55
What hastens destruction of red blood cells by splenic macrophages in the red pulp?
Loss of membrane pliability or antibody coating hastens destruction.
56
How is iron (Fe) recycled in the spleen?
Iron is recycled by splenic macrophages.
57
What particles are removed by splenic macrophages?
Nuclear material (Howell-Jolly bodies), cytoplasmic organelles, siderotic granules (Pappenheimer bodies), and oxidized Hb (methaemoglobin, Heinz bodies).
58
Why are reticulocytes “sticky”?
Reticulocytes are sticky, which slows their passage through the spleen.
59
How is O2 transported from the lungs to respiring tissue?
O2 binds reversibly to a haem group (Fe atom in a porphyrin ring), with the Fe remaining in its reduced form (Fe2+).
60
What is the difference between oxyhaemoglobin and deoxyhaemoglobin?
Oxyhaemoglobin is the oxygenated state (bright red), while deoxyhaemoglobin is the deoxygenated state (dark red).
61
How is CO2 transported in the blood?
About 95% of CO2 is transported via RBCs, with 25% directly bound to Hb, and 70% as bicarbonate (HCO3-) in plasma.
62
What is the role of carbonic anhydrase in CO2 transport?
Carbonic anhydrase catalyses the conversion of CO2 and H2O to carbonic acid (H2CO3), which dissociates to H+ and HCO3-.
63
How does Hb act as a buffer?
Hb binds H+ ions from carbonic acid dissociation, helping to maintain plasma pH and protect against acidosis.
64
What is the normal physiological pH of blood?
The physiological blood pH is between 7.35 and 7.45.
65
what are the equations for oxygenation regarding Hb?
Fe 2+ → Fe 2+ O2
= Hb → OxyHb
66
what are the equations for oxidation regarding Hb?
Fe 2+ → Fe 3+
= Hb → MetHb
67
Hb oxidation is a(n) _____________ change and is .....
Hb oxidation is an irreversible change and is incompatible with oxygen transport.
68
What is the molecular weight and structure of hemoglobin (Hb)?
Hemoglobin is a tetrameric molecule about 68kDa, consisting of 4 globin chains of two types.
69
What is the structure of adult hemoglobin (HbA)?
Adult Hb (HbA) has the structure α2ß2.
70
What is the structure of Hb A2?
Hb A2 has the structure α2δ2.
71
What is the structure of fetal hemoglobin (HbF)?
Fetal Hb (HbF) has the structure α2γ2.
72
What is the role of the globin chains in hemoglobin?
Each globin chain surrounds a haem group (1 Fe atom and a porphyrin ring), so there are 4 haem groups in each Hb molecule.
73
What does O2 affinity refer to in hemoglobin?
O2 affinity refers to the relationship between Hb O2 saturation and partial pressure of O2 (pO2), indicating how much oxygen is bound to Hb at different pO2 levels.
74
Why is a variable affinity required for hemoglobin?
A variable affinity is needed to have high O2 affinity where pO2 is high and low affinity where pO2 is low.
75
what is the Hb: O2 dissociation curve
- a graphical representation of the relationship between the amount of oxygen bound to hemoglobin and the partial pressure of oxygen in the blood.
- The curve is sigmoidal, with a steep slope at low partial pressures of oxygen and a more gradual slope at higher partial pressures.
76
How does the high affinity of fully oxygenated hemoglobin prevent arterial deoxygenation?
The relatively high affinity of fully oxygenated hemoglobin prevents the release of oxygen in the arteries, ensuring arterial oxygenation is maintained.
77
How does the release of the first O2 molecule affect hemoglobin's ability to release the next ones?
After the first O2 is released, the next two O2 molecules are more easily released, improving oxygen delivery to metabolically active tissue.
78
How does the conformational change of hemoglobin affect its O2 affinity?
The conformational change adjusts O2 affinity by varying access to the haem groups, influencing O2 binding and release.
79
How does 2,3-diphosphoglycerate (2,3DPG) affect hemoglobin's oxygen affinity?
2,3DPG binds preferentially to deoxyHb, reducing its oxygen affinity and promoting further deoxygenation, which increases oxygen supply.
80
How does acidosis (blood pH <7.35) influence oxygen affinity?
Acidosis reduces O2 affinity (Bohr effect), which increases O2 supply to tissues.
81
Why does fetal hemoglobin (HbF) have a higher O2 affinity compared to adult hemoglobin (HbA)?
HbF has increased O2 affinity due to less active binding of 2,3DPG by the γ chains, facilitating O2 transfer from maternal HbA to fetal HbF in utero.
82
What is one advantage of synthetic red blood cells over transfused human RBCs regarding storage?
Synthetic RBCs can have better storage temperature control and shelf-life.
83
How does synthetic red blood cells compare to natural blood in terms of effectiveness?
Synthetic RBCs have immediate effectiveness, avoiding the lag seen with natural blood due to 2,3-DPG and nitric oxide depletion during storage.
84
What is a major benefit of synthetic RBCs in terms of disease transmission?
Synthetic RBCs eliminate the risk of disease transmission, unlike transfused human RBCs.
85
What are the advantages of synthetic RBCs regarding donors?
Synthetic RBCs are not dependent on donors, unlike human RBCs.
86
How do synthetic RBCs help avoid cultural or religious issues?
Synthetic RBCs can avoid religious/cultural issues, such as those faced by Jehovah’s Witnesses.
87
Why can't hemoglobin be transfused in solution?
Free globin chains are toxic to the kidneys, scavenge nitric oxide, leading to vasoconstriction and hypertension, and have an unfavorable, fixed O2 affinity with a short half-life (30 minutes).
88
Are Hb-based products currently licensed for clinical use in Europe or the US?
No, Hb-based products are not currently licensed for clinical use in Europe or the US.
89
Is there an alternative to donor blood currently in general use?
No, there is no alternative to donor blood in general use at the moment.
90
What is "re-manufactured" hemoglobin, and give an example?
"Re-manufactured" hemoglobin refers to polymerized globin chains, such as bovine globin in Hemopure (licensed in South Africa in 2001).
91
What is conjugated hemoglobin, and give an example?
Conjugated hemoglobin involves linking Hb to another substance, like polyethylene glycol in Hemospan.
92
What are artificial or bioengineered cells containing hemoglobin?
Artificial/bioengineered cells, like yeasts, E. coli, and liposomes ("neohemocytes"), can contain hemoglobin.
93
What is blood "pharming"?
Blood "pharming" refers to the in vitro differentiation and growth of stem cells into RBCs. The first clinical trial occurred in November 2022 in the UK.
94
what is anaemia?
reduced [Hb] in blood
95
when do symptoms of anaemia occur?
In general appear when [Hb] falls below 90 – 100 g/l
96
what type of anaemia is better tollerated by the body?
slow-onset anaemia
97
what are 7 symptoms of anaemia?
- Shortness of breath
- Weakness
- Pallor
- Lethargy
- Palpitations
- Headaches
- Heart failure and confusion (older patients)
98
what symptoms of anaemia are dependant on type?
- Concave nails
- Jaundice
- Leg ulcers
- Bone deformities
- Recurrent infection and / or bruising if due to e.g. bone marrow failure or leukaemia.
99
what are the 2 parameters that anaemia is usually classified by?
- size of RBCs
- Hb concentration
100
what is the normal range of mean cell volume?
80 - 101 fl
101
what is the normal range of Mean Corpuscular Haemoglobin Concentration (MCHC, Hb ÷ Hct) ?
300 - 350 g/l
102
what is the normal range of Mean Cell Hb (MCH, Hb ÷ RBC)?
27 - 34 pg
103
how does normocytic, normochromic anaemia present?
- are of normal volume (MCV normal)
- Hb is at a normal concentration (MCHC is normal)
- So the RBCs contain a normal amount of Hb (MCH is normal)
- RBC count is reduced
104
how does microcytic, hypochromic anaemia present?
- RBCs are reduced in volume
- have less Hb at a lower concentration than normal
- MCV, MCH and MCHC all reduced
105
what causes normocytic, normochromic anaemia?
acute bleed, marrow failure, haemolysis or renal failure (Epo deficiency)
106
what causes microcytic, hypochromic anaemia?
Fe deficiency, thalassemia, anaemia of chronic disorder
107
how does macrocytic, normochromic anaemia present?
- MCV is increased
- MCHC is normal
- so MCH is increased
108
what causes macrocytic, normochromic anaemia?
B12 or folate deficiency
109
What are the two main types of bleeding that can cause anemia?
Acute and/or chronic bleeding.
110
What deficiencies can lead to anemia?
Deficiencies in iron (Fe), vitamin B12, or folate.
111
What type of anemia is caused by RBC cytoskeletal disorders?
Congenital hemolytic anemia.
112
How can erythropoiesis impairment lead to anemia?
It can be either acquired or inherited, leading to reduced RBC production.
113
What are the two types of acquired hemolytic anemia?
Auto-immune and mechanical.
114
What are RBC enzymopathies, and how do they cause anemia?
They are congenital enzyme deficiencies that lead to hemolytic anemia.
115
What are the two main types of hemoglobinopathies?
i) Structural hemoglobin (Hb) variants.
ii) Globin chain synthesis impairments (thalassemias).
116
What does normocytic, normochromic mean in the context of blood loss?
RBCs are qualitatively normal in size and color, indicating no intrinsic RBC defects.
117
How much acute blood loss can a young, healthy patient tolerate with little or no effect?
500–1000 mL (10–20% of blood volume).
118
What are the effects of losing 1000–1500 mL of blood?
Generally tolerated if the person is lying or sitting.
119
What symptoms may appear with a 1500–2000 mL blood loss?
Variable loss of consciousness, shortness of breath (SOB), and sweating.
120
What are the consequences of losing more than 2000 mL of blood?
Severe shock, possibly irreversible, leading to death.
121
Why might there be no anemia immediately after significant blood loss?
For up to 2–3 days post-bleed, hypovolemia occurs, but anemia may not be present due to plasma loss.
122
When does the reticulocyte response occur after significant blood loss?
In 3–5 days.
123
what causes Microcytic, hypochromic anaemia?
Poor diet, malabsorption or chronic blood loss.
124
What is the main treatment for iron deficiency anemia (IDA)?
Replenishing iron stores through oral or parenteral (injected) iron administration.
125
What is an example of an oral iron supplement for IDA?
Ferrous sulfate tablets.
126
When is parenteral iron administration used instead of oral iron?
When rapid replacement is needed (e.g., late pregnancy) or when oral iron is not tolerated or absorbed.
127
How quickly should hemoglobin (Hb) levels rise with iron treatment?
Hb should increase by about 10 g/L per week.
128
When is blood transfusion considered for IDA?
In severe cases of anemia.
129
What is important to address alongside iron supplementation in IDA treatment?
The underlying cause, such as dietary deficiency, malabsorption, or bleeding.
130
how does a vitamin B12 or folate deficiency effect macrocytes?
make them oval shaped
131
What is bone marrow infiltration, and what can cause it?
Replacement of erythropoietic tissue by tumor (e.g., metastatic prostate or breast cancer, leukemia) or fibrotic tissue (e.g., myelofibrosis).
132
What type of anemia is associated with bone marrow infiltration?
Normocytic, normochromic (NN) anemia.
133
What can cause transient bone marrow failure?
Parvovirus infection or drugs, especially cytotoxic drugs.
134
What type of anemia is seen in transient bone marrow failure?
Normocytic, normochromic (NN) anemia.
135
What condition is usually associated with severe anemia due to bone marrow infiltration or fibrosis?
Extramedullary hematopoiesis (hemopoiesis outside the bone marrow).
136
What are key blood smear findings indicating extramedullary hematopoiesis?
- Tear-drop poikilocytes
- Nucleated red blood cells (NRBCs)
- Immature white blood cells (WBCs)
137
What term describes a blood smear with tear-drop poikilocytes, NRBCs, and immature WBCs?
A leucoerythroblastic picture.
138
What type of leukemia is associated with anemia due to impaired erythropoiesis?
Chronic Granulocytic Leukemia (CGL), also known as Chronic Myelogenous Leukemia (CML).
139
How does Chronic Granulocytic Leukemia (CGL) cause anemia?
It impairs erythropoiesis by disrupting normal bone marrow function.
140
What are two rare inherited causes of impaired erythropoiesis?
Fanconi anemia and Diamond-Blackfan anemia.
141
What is Fanconi anemia?
A rare inherited disorder causing progressive bone marrow failure, leading to death from hemorrhage or infection. It also increases the risk of solid tumors (28% after 40 years) and hematological malignancies (33% after 40 years, especially AML).
142
What is Diamond-Blackfan anemia?
A congenital pure red cell aplasia first reported in 1938, presenting in early infancy with decreased erythroid precursors. Steroids can help, and median survival is about 38 years.
143
What is the only cure for Fanconi anemia and Diamond-Blackfan anemia?
A stem cell or bone marrow transplant from a matched, healthy donor.
144
What does AIHA stand for?
Autoimmune Hemolytic Anemia.
145
What are the 5 main causes of AIHA?
- 50% are idiopathic (unknown cause)
- Lymphoproliferative disorders
- Mycoplasma and Epstein-Barr Virus (EBV) infection
- Drug-induced (e.g., Penicillin)
- Other autoimmune diseases
146
What is microangiopathic hemolysis?
Mechanical fragmentation of red blood cells (RBCs) within the circulation.
147
What are the two main categories of hemoglobinopathies?
Structural variations – Over 800 types, where hemoglobin is produced in normal amounts but has an abnormal structure.
Thalassemia syndromes – Characterized by a variable loss of the ability to produce a specific globin chain.
148
What are Hbopathies?
Structural variations in hemoglobin due to amino acid substitutions in globin chains.
149
How are Hbopathies demonstrated?
By High-Performance Liquid Chromatography (HPLC).
150
Most significant Hbopathy variants affect which chain?
The β chain.
151
HbS (Sickle cell) mutation:
α2β2, 6 Glu → Val.
152
HbD Punjab mutation:
α2β2, 121 Glu → Gln.
153
HbE mutation:
α2β2, 26 Glu → Lys.
154
HbC mutation:
α2β2, 6 Glu → Lys.
155
HbG Philadelphia mutation:
α268Asp → Lys (α-chain).
156
Hb Reading mutation:
α1 or α2, 48 Leu → Pro (α-chain).
157
What is the commonest inherited blood disease in the world?
Sickle Cell disease.
158
What is the average lifespan for individuals with Sickle Cell in sub-Saharan Africa?
Less than 10 years.
159
What is the average lifespan for individuals with Sickle Cell in the UK?
About 60 years.
160
Why is the HbS gene frequency maintained in malarial areas?
Due to the advantage of heterozygotes in resisting malaria.
161
What is a balanced polymorphism?
A situation where heterozygotes are more fit than either homozygote.
162
What is the effect of HbAA in malaria?
Individuals are susceptible to Plasmodium falciparum (malaria).
163
What is the effect of HbSS in Sickle Cell disease?
It causes a life-limiting hematological disorder.
164
What benefit do HbS heterozygotes have?
They have some resistance to Plasmodium falciparum without usually experiencing sickling.
165
What are examples of unstable hemoglobins (Hb)?
Hb Köln and Hb Zurich.
166
How many different unstable hemoglobins have been identified?
Over 100 different unstable Hbs.
167
What is the typical result of unstable hemoglobins?
Hemolytic anemia.
168
What percentage of unstable hemoglobin cases are due to new mutations?
Approximately 30%.
169
What causes abnormal unstable hemoglobins?
1. Abnormality in the heme pocket, causing loose binding of heme and water entry > metHb.
2. Interference in the binding of α & β chains.
3. Interference with α chain structure.
170
What happens when unstable hemoglobins oxidize heme iron?
The heme precipitates and damages the red blood cell membrane.
171
What are the precipitates formed in unstable hemoglobins called?
Heinz bodies.
172
How are Heinz bodies visualized?
By supravital staining, such as methylene blue or brilliant cresyl green.
173
What happens when Heinz bodies are removed by macrophages?
"Bite cells" are formed.
174
What is the result of RBC destruction in unstable hemoglobins?
Hemolytic anemia.
175
What characterizes thalassemia disorders?
Reduced globin chain synthesis (α or β).
176
Where are thalassemias generally prevalent?
In populations that evolved in warm, humid areas where malaria was endemic.
177
Do thalassemias affect all races?
Yes, thalassemias now affect all races.
178
What is the benefit of thalassemias in malaria-endemic areas?
Thalassemias provide varying resistance to malaria.
179
What is impaired in α-thalassemia?
The ability to synthesize α globin chains.
180
What happens due to the excess β chains in α-thalassemia?
The excess β chains form β tetramers, known as Hb H.
181
What forms in the fetus in α-thalassemia?
Excess γ chains, forming Hb Barts.
182
What happens to β tetramers (HbH)?
They aggregate, forming HbH bodies, which can be stained by brilliant cresyl blue.
183
What type of anemia is usually seen in α-thalassemia?
A mild, microcytic hypochromic anemia
184
How many α genes do we normally inherit from each parent?
2 α genes from each parent.
185
What happens in α-thalassemia regarding α genes?
One or more α genes may be deleted.
186
Inheritance of 3 normal α genes:
Almost no effect on hemoglobin production.
187
Inheritance of 2 normal α genes:
α-thalassemia trait, with nearly normal hemoglobin production but mild microcytic, hypochromic anemia.
188
Inheritance of 1 normal α gene:
HbH disease, with microcytic, hypochromic anemia.
189
Inheritance of 0 normal α genes:
Incompatible with life, resulting in a stillborn fetus.
190
What is impaired in β-thalassemia?
The ability to synthesize β globin chains.
191
Where are mutations found in β-thalassemia?
In the HBB gene on chromosome 11.
192
What are the types of mutations in β-thalassemia?
βo mutations (no β chain production) and β+ mutations (some β chain production).
193
What happens due to excess α chains in β-thalassemia?
Excess α chains bind to the RBC membrane, damaging it.
194
What are the consequences of α chain excess in β-thalassemia?
Ineffective erythropoiesis and reduced RBC survival.
195
What happens when β-chains are reduced in β-thalassemia?
There is an increase in the production of γ and δ chains, leading to more HbF (α2γ2) and HbA2 (α2δ2).
196
What is the result of being heterozygous for β-thalassemia?
Mild microcytic, hypochromic anemia, referred to as thalassemia trait (carrier status).
197
What happens in homozygous β-thalassemia?
Severe anemia, usually fatal in infancy or childhood without intervention.
198
What skeletal abnormalities are seen in homozygous β-thalassemia?
Expansion of hematopoietic spaces.
199
What is the treatment for β-thalassemia?
Transfusion-dependent therapy, leading to iron overload, which requires iron chelation therapy. Bone marrow transplant is an extreme option.
200
What is CasgevyTM?
A gene therapy that knocks out the BCL11A gene, which normally stops HbF production at birth, using CRISPR technology.
201
How are the stem cells modified in CasgevyTM therapy?
The patient’s stem cells are harvested, edited to knock out the BCL11A gene, and then re-infused.
202
What is the result of re-infusing the modified stem cells?
The modified stem cells re-colonize the bone marrow and produce HbF-containing RBCs.
203
Why does HbF provide viable RBC function and lifespan in this therapy?
HbF contains γ chains instead of β chains, allowing for functional and viable RBCs.
204
What is the cost of CasgevyTM gene therapy?
US$2 million per patient.
205
Is CasgevyTM approved?
Yes, it is approved by the UK Medicines Regulator.
