Anaemias Flashcards
1
Q
__________ causes a decrease in the oxygen-carrying capacity of the blood.
A
Anaemia
2
Q
Anaemia arises because of _______ haemoglobin, or non-functional haemoglobin.
A
Reduced
3
Q
True or false: anaemia is not a disease itself, but a symptom of an underlying disease process.
A
True
4
Q
List laboratory analytes assessed in anaemia investigation.
A
Haemoglobin, red cell count (RCC), haematocrit (proportion of RBC:total proportion of blood), red cell index (classification of RBC, based on size and [Hb] content; to calculate index, [Hb] measurement, RCC, and haematocrit are required), and reticulocyte (immature RBC) count
5
Q
What are the WHO classification of anaemia guidelines?
A
Non-anaemic
Adult males: >130g/L
Adult females: >120g/L
Grade 1 (Mild anaemia)
Adult males: 110 - 130g/L
Adult females: 110 - 120g/L
Grade 2 (Moderate anaemia)
Both sexes: 80 – 110g/L
Grade 3 (Severe anaemia)
Both sexes: <80g/L
6
Q
____________ of the nails may be observed.
A
Koilonychia
7
Q
True or false: chronic anaemia generally has many symptoms.
A
False
8
Q
Mean cell _________ indicates the average volume of individual erythrocytes, indicating whether they are normocytic, microcytic, or macrocytic.
A
Volume
9
Q
Mean cell haemoglobin (MCH) determines the average weight of [Hb] in individual ____________.
A
Erythrocytes
10
Q
Mean cell ____________ concentration (MCHC) determines the ratio of [Hb] mass to volume in which it is contained; indicates if RBC are normo- or hypochromic.
A
Haemoglobin
11
Q
Red cell distribution width (RDW) is useful in the event of ____________.
A
Anisocytosis
12
Q
A ____________ count should always be performed in suspected cases of anaemia.
A
Reticulocyte
13
Q
What two stains combine to form the Romanowsky stain?
A
Giemsa and Wright stains
14
Q
List three further tests for anaemia.
A
Folate level measurement, iron studies, and liver function tests
15
Q
___________ defects of anaemia are from problems with the haematopoietic stem cells (HSC) and progenitor cells.
A
Proliferation
16
Q
What causes maturation defects?
A
May be as a result of DNA synthesis, which impacts the nucleus, or may also be caused by cytoplasm issues, such as iron deficiency, thalassaemia, and haemoglobinopathy
17
Q
Survival defects arise from ________ or haemorrhage.
A
Haemolysis
18
Q
Normocytic and normochromic cells indicate __________ anaemias, or anaemia of chronic disease.
A
Haemolytic
19
Q
___________ and microchromic cells suggest deficient haemoglobin or defective haem synthesis, such as iron-deficiency anaemia.
A
Microcytic
20
Q
Macrocytic cells indicate anaemias that are due to defective _____ metabolism.
A
DNA
21
Q
Anaemia with __________ reticulocyte count is associated with haemolysis, acute blood loss, and response to treatment.
A
Elevated
22
Q
Diminished reticulocyte counts are associated with bone marrow ____________, due to drugs, toxins, and infection.
A
Suppression
23
Q
True or false: normal reticulocyte counts pertain to nutritional deficiency, chronic disease, and erythropoietin-involving anaemias.
A
True
24
Q
Blood film, iron studies, and HGB electrophoresis are used in the investigation of ______________ anaemia.
A
Microcytic
25
Blood film, serum Vitamin B12 level, serum and RBC folate levels, LFT, s-TSH levels, bone marrow examination, and cytogenetics are used in evaluating ____________ anaemia.
Macrocytic
26
Blood film, s-bilirubin, s-LDH, iron studies, RFT, erythropoietin level, and bone marrow analysis are performed when assessing _____________ anaemia.
Normocytic
27
Iron deficiency is associated with hypochromia and ___________.
Microcytosis
28
Approximately 70% of stored iron is stored as ____________.
Ferritin
29
Stored iron has an apoferritin shell, with __________core.
Hydroxy
30
_____________ is an insoluble protein-iron complex, found in macrophages.
Haemosiderin
31
Name an iron-containing enzyme.
Cytochrome
32
___________-bound iron is iron in transit to erythroblasts and reticulocytes.
Transferrin
33
List three foods that are rich in iron.
Red meat, green vegetables, and cereals
34
Iron absorption occurs in the __________ and upper jejunum
Duodenum
35
Iron absorption ____________ in iron deficiency.
Increases
36
Iron absorption ____________ in iron overload.
Decreases
37
Control of absorption is by the ferritin level of intestinal _________.
Mucosa
38
______ ferritin level causes increased absorption.
Low
39
High ferritin level causes absorption _____________.
Inhibition
40
Iron replacement therapy (very high concentration) employs ____________ ________ across the gut wall.
Passive diffusion
41
List five factors that favour iron absorption.
Ferrous form Fe++
Organic iron
Acids, such as HCl, and Vitamin C
Solubilising agents, like sugars, or amino acids
Iron deficiency
42
List five factors dissuading iron absorption.
Ferric form Fe+++
Inorganic iron
Alkalis, antacids
Precipitating agents: phosphates/phthylates
Iron overload
43
Once iron is absorbed, there is no __________ mechanism for excretion of excess iron from the body, other than blood loss i.e., pregnancy, menstruation, or other bleeding.
Physiological
44
Transferrin is a ______ globulin.
Beta
45
Transferrin is synthesised in the _________.
Liver
46
Transferrin transports iron to specific receptors on _________ erythroblasts.
Marrow
47
What are the stages of iron-deficiency anaemia development?
Iron depletion
Iron-deficient erythropoiesis
Iron-deficiency anaemia
Iron stores, ferritin and haemosiderin become completely depleted before IDA occurs
48
List three causes of iron-deficiency anaemia.
Blood loss, malabsorption, and malnutrition
49
The onset of iron-deficiency anaemia is described as being __________.
Insidious
50
List four features that would be expected on a blood film for iron-deficiency anaemia.
Pencil cells, hypochromic cells, microcytic cells, and poikilocytosis
51
_______________ count is high in great blood loss.
Reticulocyte
52
Reticulocyte count is low in protracted ________ _______.
Blood loss
53
__________ ______ _________ __________ is a measure of the concentration of transferrin.
Total iron binding capacity
54
What are the reference ranges for serum ferritin?
28-220µg/L (males), and 15-180µg/L (females)
55
Abnormal haem synthesis (reduced availability of iron, and reduced porphyrin synthesis), and abnormal globin synthesis (reduced polypeptide chain synthesis, and amino acid substitution) causes ___________ cells.
Microcytic
56
___________ of chronic disease is caused by chronic, inflammatory conditions, such as TB, osteomyelitis, etc., malignant diseases, or non-infections diseases, like Crohn's disease.
Anaemia
57
What is the pathogenesis of anaemia of chronic disease?
Decreased release of iron from iron stores, which is blocked as a consequence of inflammatory cytokines; for example, hepcidin sequesters ions from pathogens.
58
List three complications of sickle cell anaemia.
Stroke, microvascular occlusion, and acute chest syndrome
59
Sickle cell anaemia's blood film features normocytic, normochromic anaemia with marked _______________.
Reticulocytosis
60
State the principle of the sickle cell solubility test.
Decreased solubility of deoxygenated HbS is demonstrated, although this varies between homozygotes vs heterozygote, facilitated by in-vitro lysis of red cells, and impregnation with plasma. Sickle cell anaemia will produce a turbid complex in the test tube; a normal result is a red colour. Homozygous expression will give a very cloudy complex
61
For sickle cell anaemia, _____________ is useful in homozygotes, which have no HbA, and in heterozygotes, with no HbA and HbS.
Electrophoresis
62
Thalassaemia is an inherited blood condition in which there is an imbalance in the globin produced due to gene deletion and _______ _____________.
Point mutation
63
What is the pathogenesis of thalassaemia?
Reduction of or total absence of synthesis of one or more of the globin chains types, leading to ineffective erythropoiesis and a shortened red cell life span
64
True or false: there are both minor and major forms of thalassaemia.
True
65
A normal ratio of _____ production of α- and β-globin chains exists.
1:1
66
Excess ___ chains (α-thalassaemia) can combine to form a molecule with four β chains (HbH).
β
67
In ___-thalassaemia, high oxygen affinity makes for a poor transporter of oxygen.
HbH is unstable and mainly precipitates inside older red cells, which are prematurely destroyed in the spleen, resulting in moderate to severe haemolysis.
α
68
Excess α chains (β-thalassaemia) are unstable and ___________ in cells.
Precipitate
69
The blood film of α-thalassaemia typically shows hypochromia, ________________, and target cells.
Microcytosis
70
α-thalassaemia occurs when there is a deletion of any of the _______ genes.
Globin
71
True or false: carrier status comes from the loss of one α globin gene, and has many symptoms.
False
72
Minor/trait status is the loss of ______ α globin genes (causing mild anaemia).
Two
73
Major/___________ ___ disease is the loss of three α globin genes (causing moderate to severe anaemia).
Haemoglobin H
74
True or false: loss of all four α globin genes means incompatibility with life.
True
75
_____________ ________ _______ stain will demonstrate HbH inclusion bodies.
Brilliant cresyl blue
76
One gene deletion on chromosome is noted as ____.
α+
77
_____ gene deletions on same chromosome is noted α0.
Two
78
__-______________ is a point mutation within or close to the b globin gene complex.
β-thalassaemia
79
β-thalassaemia can be minor/_______________/major, varying in severity.
Intermediate
80
Reduced MCV and MCH
Haemoglobin is not normally below 95g/L
RCC usually normal or slightly increased
Blood film shows microcytic and hypochromic, target cells
Electrophoresis showing Hb A2 (α2δ2) above 3.5% is diagnostic (Normal Hb A2 1.5 - 3.0 %)
For which form of thalassaemia would the above findings be expected?
β-thalassaemia
81
Thalassaemia major is also called __________ anaemia.
Cooley's
82
Cooley's anaemia features greatly-reduced or absent _____ chain synthesis, and increased alpha chain production,
Beta
83
List two clinical features of Cooley's anaemia.
Gross haemolytic anaemia and hepatosplenomegaly
84
List three laboratory findings of Cooley's anaemia.
Microcytosis, hypochromia, and severe anaemia
85
What is the main treatment used in supporting the patient with Cooley's anaemia?
Blood transfusion
86
List a chelating agent, used to prevent haemosiderosis.
Desferrioxamine
87
Macrocytosis is defined as erythrocytes which have MCV of >_____fL, with a normal MCHC.
100
88
List three causes of genuine macrocytosis.
Alcoholism, Vitamin B12 deficiency, and hypothyroidism
89
True or false: hyperglycaemia can erroneously elevate macrocytic cell counts.
True
90
_______________ macrocytic anaemia, such as B12 and folate deficiencies, is characterised by retardation of DNA synthesis.
Megaloblastic
91
B12 is similar to ________.
Haem
92
B12 acts as a ___-__________ in two biochemical reactions, one of which pertains to ATP production.
Co-enzyme
93
B12 consists of four pyrrole rings, linked to a ____________ atom, with a nucleotide at a right angle.
Cobalt
94
List the four molecules attached to B12'S cobalt atom.
Methyl group
Deoxyadenosyl group
Cyano group
Hydroxy group
95
True or false: B12 is a stable vitamin, and little loss occurs in cooking.
True
96
B12 Complexes in 1:1 ratio with ___________ _________.
Intrinsic factor
97
Intrinsic factor is a glycoprotein secreted by _________ cells of stomach.
Parietal
98
B12/IF complex moves to the ileum, and attaches to specific receptors on ____________ ___________ _______.
Ileal mucosal cells
99
Name Vitamin B12's two transport proteins.
Transcobalamin and haptocorrins
100
Haptocorrins are synthesised by _______________.
Granulocytes
101
True or false: congenital absence of haptocorrins leads to no impairment.
True
102
_______________ synthesise folic acid from pteridine, PABA and glutamic acid.
Bacteria
103
True or false: humans are able to synthesise folic acid naturally.
False
104
By what other name is folic acid known?
Pteroylglutamic acid
105
List three dietary forms of folate.
Polyglutamates, dihydrofolate, and tetrahydrofolate
106
Folic acid is involved in the synthesis of ______________ from homocysteine.
Methionine
107
Absorbed folates converted to ___-__-_____________________________ (5-MTHF) and released into portal blood.
N-5-methyltetrahydrofolate
108
List three causes of Vitamin B12 deficiency.
Malnutrition, old age, and pernicious anaemia
109
Outline the pathogenesis of megaloblastic anaemia.
Defective DNA synthesis in rapidly dividing cells occurs. Nuclear maturation is delayed, relative to cytoplasm. Asynchrony means that the nucleus and cytoplasm are not maturing at same rate, with the nucleus at the proerythroblast stage, and cytoplasm at the reticulocyte stage. The megaloblast is the large, nucleated, immature progenitor of the abnormal erythroblast. This results in premature destruction of erythrocytes in marrow (and other cell types) (ineffective haematopoiesis)
110
True or false: onset of megaloblastic anaemia may be insidious.
True
111
In megaloblastic anaemia, MCV is usually increased, white cell count is generally ___________ , and platelet count is often decreased.
Decreased
112
Common features of megaloblastic blood films include oval macrocytes and _______________.
Anisocytosis
113
Increased LD, increased unconjugated bilirubin, increased serum methylmalonic acid (MMA), and increased plasma homocysteine is often observed in __________________ anaemia.
Megaloblastic
114
________________ considers Vitamin B12 and folate (and iron).
Haematinics
115
Pernicious anaemia is due to the loss of _________ ___________ cells, most commonly due to autoimmune attack.
Gastric parietal
116
Outline the principle of the Schilling's test.
Measures the ability of the patient to absorb B12 first without, and then with, a dose of exogenous intrinsic factor. Radiolabelled B12 is ingested, and a 24 hour urine sample is collected. If >7% of the radiolabelled material excreted in the urine, it means absorption is normal. If <7% is excreted, absorption is abnormal. In case of the abnormal result, repeat the test with the addition of an intrinsic factor. If absorption corrects, this favours the deficiency of the endogenous intrinsic factor as seen in pernicious anaemia. If it does not correct, then the possibility is intestinal malabsorption which causes B12 deficiency
117
_______________ haemolysis plays little to no role in RBC destruction.
Intravascular
118
Extravascular haemolysis is removal of red cells by ______________ of liver, spleen and bone marrow.
Macrophages
119
List two inherited forms of haemolytic anaemia.
Hereditary elliptocytosis and hereditary spherocytosis
120
Outline the pathophysiology of glucose 6 phosphate dehydrogenase (G6PD) deficiency.
Deficiency leads to reduction in reduced glutathione levels (major antioxidant), and is usually asymptomatic. Haemolysis occurs in response to oxidant stress (drugs, infections, fava beans). Oxidation (loss of electron) of haem ring produces methaemoglobin (Fe3+), that is unable to carry oxygen. Oxidation of globin chains causes precipitation of chains as Heinz bodies (oxidised, denatured haemoglobin). Acute intravascular haemolysis results. Blood count between crises is normal. Deficiency is detected by enzyme assay, and during a crisis, ‘bite’ cells (after removal of Heinz bodies by spleen) may be observed
121
Pyruvate kinase deficiency leads to reduced _____ levels.
ATP
122
List three other ways by which haemolytic anaemia would develop.
Drugs, infections, and venom
123
List the four mechanisms by which extrinsic acquired haemolytic anaemia developed.
Passively acquired antibody (perhaps from HDNB, or antibody in donor blood given to recipient with corresponding antigen
The presence or development of antibody against transfused donor red blood cells
The action of antibodies formed against drugs (three mechanisms)
The presence of autoantibodies other than due to drugs
124
True or false: warm-type acquired haemolytic anaemia may be idiopathic, or secondary to underlying disease.
True
125
In warm-type acquired haemolytic anaemia, a Coombs' test will be ___________.
Positive
126
List the three forms of cold-type acquired haemolytic anaemia.
Cold haemaggluttin disease, cold autoimmune haemolytic anaemia, and paroxysmal cold haemoglobinuria
127
List the laboratory findings of acquired haemolytic anaemia.
Blood counts are difficult to perform unless the blood is warmed
Mild to moderate normochromic, normocytic anaemia
Polychromasia , spherocytes, rouleaux, sometimes NRBCs
The Coombs test with anti-complement antibody is positive
The titre is usually 1:1000, or greater
128
Outline the pathogenesis of hereditary spherocytosis.
Defects in proteins involved in vertical interactions between membrane skeleton and the lipid bilayer of cell membrane are observed. Parts of the lipid membrane that are not supported by the cytoskeleton are lost. Initially cells are normal shape, become increasingly spherical in the circulation. Ultimately, they are unable to pass through spleen and die prematurely
129
Describe the laboratory findings in cases of spherocytosis.
Anaemia (may be mild, moderate or severe)
Reticulocyte count of 5% - 20%
Microspherocytes in the film
Decreased MCV, increased MCHC
Red cell lifespan of between 6 - 20 days
Increased osmotic fragility
130
True or false: membrane function has no bearing on a cell's osmotic fragility.
False
131
Spherocytes are osmotically ____________ compared to normal RBC.
Fragile
132
State three laboratory findings of increased RBC destruction.
Increased bilirubin, haemoglobinuria, and decreased RBC lifespan
133
Increased reticulocyte count, polychromasia, and bone marrow erythroid hyperplasia are signs of __________ _________________.
Increased erythropoiesis
