Practice Test #2 Flashcards
What kind of therapy is needed for treating anaemia resulting from renal disease or from various other causes
Recombinant erythropoietin
What is the method of administration for Recombiant erythropoietin
Subcutaneously
How often is Recombinant erythropoietin used in treatment
three times weekly or once every 1–2 weeks or every 4 weeks
What is the main indication for Erythropoietin therapy
End-stage renal disease (with or without dialysis)
What is also needed in erythropoietin therapy
oral or intravenous iron
True or False, A high serum erythropoietin level prior to treatment is valuable in predicting an e ective response
False, Low Level
What are some common side effects for recombinant erythropoietin therapy
Side‐effects include a rise in blood pressure, thrombosis and local injection site reactions.
What hormones are necessary for effective erythropoiesis
Androgens and thy- roxine
What metals are needed in successive erythropoietin synthesis
iron and cobalt
What is the dominant haemoglobin in blood after the age of 3–6 months) c
HbA
What are the 4 polypeptide chain in Haemoglobin A
α2 β2, each with its own haem group
What are the clinical uses of erythropoietin
Anaemia of chronic renal disease
Myelodysplastic syndrome
Anaemia associated with malignancy and chemotherapy
Anaemia of chronic diseases, e.g. rheumatoid arthritis
Anaemia of prematurity
Perioperative uses
What is the main site for the protoporphyrin synthesis
Mitochondria
Where is Iron supplied from for erythropoiesis
Circulating transferrin
What synthesis occurs largely in the mitochondria
Haem
What is the key rate‐limiting enzyme in Haem Synthesis
δ‐aminolaevulinic acid (ALA) synthase
What is the coenzyme for Haem synthesis
Pyridoxal phosphate (vitamin B )
The condensation of which two compounds occurs in the biochemical reaction for haem synthesis
condensation of glycine and succinyl coenzyme A
The combination of which two compounds for Haem
Protoporphyrin combines
with iron in the ferrous (Fe2+)
True or False the contact of α1α2 β2β1 stabilises the structure of Haemoglobin
False it is, α2β2, α1β1
When O2 is unloaded β chains are pulled apart permitting the entry of which metabolite
2,3‐diphosphoglycerate (2,3‐DPG)
True or False, The entry of the metabolite in the β chains results in higher affnity of the molecule for O2.
False, lower
What is the P50 (i.e. the partial pressure of O2 at which haemoglobin is half saturated with O2) of normal blood
26.6 mmHg
What occurs with an increased affnity for O2 in a haemoglobin oxygen (O2) dissociation curve
Curve shifts to the left
True or False, The P50 will rise when there is an increase affinity for O2
False, it will fall
What causes the curve to shift to the right in a haemoglobin oxygen (O2) dissociation curve
Decreased affinity for O2
A rise in P50 is as result of
Decreased affinity for O2
In vivo, O2 exchange operates at ____ saturation in arterial blood
95%
in vivo, What is the mean arterial O2 tension
95mmHg
In vivo, O2 exchange operates at ____ in venous blood
70%
In vivo, What is the mean venous O2 tension
40 mmHg
The normal position of the curve depends on which 3 compound in the red cell
2,3‐DPG, H+ ions and CO2
What is the difference between normal Adult Hb and Fetal Hb
Fetal Hb is unable to bind 2,3 DPG
Rare abnormal haemoglobins associated with polycythaemia, will cause the oxygen dissociation curve to shift to which direction
Left
What is the name of the clinical state in which circulating haemoglobin is present with iron in the oxidized (Fe3+) instead of the usual Fe2+ state.
Methaemoglobinaemia
Where does Methaemoglobinaemia arise from
hereditary deficiency of methaemoglobin reductase deficiency or inheritance of a structurally abnormal haemoglobin (Hb M)
What illness is likely to show in patients with Methaemoglobin
Cyanosis
What process does Haemoglobin use to generate ATP
anaerobic glycolytic (Embden–Meyerhof) pathway
What is glucose metabolised to through facilitated transfer in RBC
Lactate
What is generated in the breakdown of Glucose
NADPH, NADP
For every Glucose molecule used, How many ATP molecules are generated
2
The energy generated is used for the maintenance of what in RBC
Shape, flexibility, volume
What is the enzyme methaemoglobin reductase used for
Reduce functionally dead methaemoglobin containing ferric iron, to functionally active, reduced haemoglobin containing ferrous ions
In Embden–Meyerhof pathway, Luebering–Rapoport shunt, or side arm, of this pathway generates what metabolite
2,3‐DPG
What pathway facilitates appx 10% of the glycolysis
Hexose monophosphate (pentose phosphate) shunt
What is linked with NADPH in Hexose monophosphate (pentose phosphate) shunt, to maintain sulphydril SH groups
Glutathione
What is the oxidative pathway for Hexose monophosphate (pentose phosphate) shunt
glucose‐6‐phosphate is converted to 6‐ phosphogluconate and so to ribulose‐5‐phosphate
The deficiency of what substance causes red cells to be extremely susceptible to oxidant stress
glucose‐6‐phosphate dehydrogenase
What process is used to number red cell proteins based on their mobility
Polyacrylamide gel electro- phoresis (PAGE)
What structural proteins make up the membrane skeleton in RBC
α and β spectrin, ankyrin, protein 4.1 and actin
What is described as a reduction in the haemoglobin concen- tration of the blood below normal for age and sex
Anaemia
What is the normal value of haemoglobin in adult males
less than 135g/L in adult males
What is the normal value of haemoglobin in adult females
115 g/L in adult females
From the age of 2 years to puberty, less than how much Hb indicates anaemia is present
less than 110g/L
What are the main causes of Anaemia
iron deficiency (hookworm, schistosomiasis), sickle cell diseases, thalassaemia, malaria and the anaemia of chronic disorders
True or False, Rapidly progressive anaemia causes less symptoms than anaemia of slow onset
False, causes more symptoms
Thee presence or absence of clinical features can be considered under what four major headings.
Speed of Onset, Severity, Age, Haemoglobin O2 dissociation curve
What are the different signs of Anaemia for
a) iron deficiency
b) haemolytic or megaloblastic anaemia
c) sickle cell
d) thalassaemia major
a) Koilonychia (spoon nails) with iron deficiency,
b) jaundice with haemolytic or megaloblastic anaemias,
c) leg ulcers with sickle cell and other haemolytic anaemias, d) bone deformi- ties with thalassaemia major.
What are the three different classifications of anaemia
microcytic, normocytic and macrocytic
True or False, The Mean Corpuscular Volume (MCV) is usually high in newborns but low in infancy
True
True or False, in normal pregnancy there is a decrease in MCV levels
False, there is an increase
Thalassaemia
Anaemia of chronic disease (some cases)
Lead poisoning
Sideroblastic anaemia (some cases) is associated with which classification of Anaemia
Microcytic
After acute blood loss
Renal disease
Mixed deficiencies
Bone marrow failure (e.g. post‐ chemotherapy, infiltration by carcinoma, etc.) is associated with which classification of anaemia
Normocytic, normochromic
Megaloblastic: vitamin B12 or folate deficiency
Non‐megaloblastic: alcohol, liver disease, myelodysplasia, aplastic anaemia, etc. is associated with which type of anaemia
Macrocytic
MCH <27pg
Microcytic, hypochromic
MCV 80-95fL
Normocytic, normochromic
MCV >95fL
Macrocytic
MCH ≥27pg
Normocytic, normochromic
MCV <80fL
Microcytic, hypochromic
The laboratory finding of what two substances aid in distinguishing ‘pure’ anaemia from ‘pancytopenia’ (subnormal levels of red cells, neutrophils and platelets)
Leucocyte and platelet counts
What is the normal Reticulocyte count and percentage
0.5–2.5%, 50–150 × 109/L
True or False, The higher the Reticulocyte count, indicates the more severe of anaemia
True
How long does it take for an erythropoietin response after an acute major haemorrhage
6 hours
How long does it take before the reticulocyte count raises
How long does it take before the the reticulocyte reaches its maximum
2-3 days
6–10 days
If the reticulocyte count is not raised in an anaemic patient, what does it suggest.
impaired marrow function or lack of erythropoietin stimulus
What red cell abnormality is formed from Oxidant damage– e.g. G6PD deficiency, unstable haemoglobin
Basket cell
What is examination is done when the cause of anaemia or other abnormality of the blood cells cannot be diagnosed from the blood count, lm and other blood tests alone
Bone marrow examination
What are the two methods for bone marrow examination done
aspiration or trephine biopsy
In aspiration of bone marrow, what is used to stain the liquid sample
Romanowsky technique
What is usually observed in the liquid aspiration samples
the proportion of the different cell lines assessed
True or false, trephine biopsy specimen is less valuable than aspiration when individual cell detail is to be examined
True
Which bone marrow examination, provides more of a panoramic view of the marrow
trephine biopsy
Which bone marrow examination, shows presence of fibrosis or abnormal infiltrates, with immunohistology
trephine biopsy
Why is Erythropoiesis term ineffective
Because 10%-15% of developing erythoblasts die within the marrow before reaching mature cells
What two substances facilitate the breakdown of Haemoglobin
Unconjugated Bilirubin. lactate dehydrogenase (LDH)
What is the site of Bone Marrow investigation
Posterior iliac rest
What stain is used in Trephine Biopsy
Haematoxylin and eosin; reticulin (silver stain)
How long does it take for the Results to be available in
a) Aspiration
b) Trephine Biopsy
a) 1-2 hours
b) 1-7 days
What does NADH prevent in haemoglobin
oxidation of haemoglobin
What does NADPH prevent in haemoglobin
keeps cell proteins in the membrane and haemoglobin in the reduced state
