Anaemias Flashcards
__________ causes a decrease in the oxygen-carrying capacity of the blood.
Anaemia
Anaemia arises because of _______ haemoglobin, or non-functional haemoglobin.
Reduced
True or false: anaemia is not a disease itself, but a symptom of an underlying disease process.
True
List laboratory analytes assessed in anaemia investigation.
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
What are the WHO classification of anaemia guidelines?
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
____________ of the nails may be observed.
Koilonychia
True or false: chronic anaemia generally has many symptoms.
False
Mean cell _________ indicates the average volume of individual erythrocytes, indicating whether they are normocytic, microcytic, or macrocytic.
Volume
Mean cell haemoglobin (MCH) determines the average weight of [Hb] in individual ____________.
Erythrocytes
Mean cell ____________ concentration (MCHC) determines the ratio of [Hb] mass to volume in which it is contained; indicates if RBC are normo- or hypochromic.
Haemoglobin
Red cell distribution width (RDW) is useful in the event of ____________.
Anisocytosis
A ____________ count should always be performed in suspected cases of anaemia.
Reticulocyte
What two stains combine to form the Romanowsky stain?
Giemsa and Wright stains
List three further tests for anaemia.
Folate level measurement, iron studies, and liver function tests
___________ defects of anaemia are from problems with the haematopoietic stem cells (HSC) and progenitor cells.
Proliferation
What causes maturation defects?
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
Survival defects arise from ________ or haemorrhage.
Haemolysis
Normocytic and normochromic cells indicate __________ anaemias, or anaemia of chronic disease.
Haemolytic
___________ and microchromic cells suggest deficient haemoglobin or defective haem synthesis, such as iron-deficiency anaemia.
Microcytic
Macrocytic cells indicate anaemias that are due to defective _____ metabolism.
DNA
Anaemia with __________ reticulocyte count is associated with haemolysis, acute blood loss, and response to treatment.
Elevated
Diminished reticulocyte counts are associated with bone marrow ____________, due to drugs, toxins, and infection.
Suppression
True or false: normal reticulocyte counts pertain to nutritional deficiency, chronic disease, and erythropoietin-involving anaemias.
True
Blood film, iron studies, and HGB electrophoresis are used in the investigation of ______________ anaemia.
Microcytic
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
Blood film, s-bilirubin, s-LDH, iron studies, RFT, erythropoietin level, and bone marrow analysis are performed when assessing _____________ anaemia.
Normocytic
Iron deficiency is associated with hypochromia and ___________.
Microcytosis
Approximately 70% of stored iron is stored as ____________.
Ferritin
Stored iron has an apoferritin shell, with __________core.
Hydroxy
_____________ is an insoluble protein-iron complex, found in macrophages.
Haemosiderin
Name an iron-containing enzyme.
Cytochrome
___________-bound iron is iron in transit to erythroblasts and reticulocytes.
Transferrin
List three foods that are rich in iron.
Red meat, green vegetables, and cereals
Iron absorption occurs in the __________ and upper jejunum
Duodenum
Iron absorption ____________ in iron deficiency.
Increases
Iron absorption ____________ in iron overload.
Decreases
Control of absorption is by the ferritin level of intestinal _________.
Mucosa
______ ferritin level causes increased absorption.
Low
High ferritin level causes absorption _____________.
Inhibition
Iron replacement therapy (very high concentration) employs ____________ ________ across the gut wall.
Passive diffusion
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
List five factors dissuading iron absorption.
Ferric form Fe+++
Inorganic iron
Alkalis, antacids
Precipitating agents: phosphates/phthylates
Iron overload
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
Transferrin is a ______ globulin.
Beta
Transferrin is synthesised in the _________.
Liver
Transferrin transports iron to specific receptors on _________ erythroblasts.
Marrow
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
List three causes of iron-deficiency anaemia.
Blood loss, malabsorption, and malnutrition
The onset of iron-deficiency anaemia is described as being __________.
Insidious
List four features that would be expected on a blood film for iron-deficiency anaemia.
Pencil cells, hypochromic cells, microcytic cells, and poikilocytosis
_______________ count is high in great blood loss.
Reticulocyte
Reticulocyte count is low in protracted ________ _______.
Blood loss
__________ ______ _________ __________ is a measure of the concentration of transferrin.
Total iron binding capacity
What are the reference ranges for serum ferritin?
28-220µg/L (males), and 15-180µg/L (females)
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
___________ 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
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.
List three complications of sickle cell anaemia.
Stroke, microvascular occlusion, and acute chest syndrome
Sickle cell anaemia’s blood film features normocytic, normochromic anaemia with marked _______________.
Reticulocytosis
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
For sickle cell anaemia, _____________ is useful in homozygotes, which have no HbA, and in heterozygotes, with no HbA and HbS.
Electrophoresis
Thalassaemia is an inherited blood condition in which there is an imbalance in the globin produced due to gene deletion and _______ _____________.
Point mutation
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
True or false: there are both minor and major forms of thalassaemia.
True
A normal ratio of _____ production of α- and β-globin chains exists.
1:1
Excess ___ chains (α-thalassaemia) can combine to form a molecule with four β chains (HbH).
β
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
Excess α chains (β-thalassaemia) are unstable and ___________ in cells.
Precipitate
The blood film of α-thalassaemia typically shows hypochromia, ________________, and target cells.
Microcytosis
α-thalassaemia occurs when there is a deletion of any of the _______ genes.
Globin
True or false: carrier status comes from the loss of one α globin gene, and has many symptoms.
False
Minor/trait status is the loss of ______ α globin genes (causing mild anaemia).
Two
Major/___________ ___ disease is the loss of three α globin genes (causing moderate to severe anaemia).
Haemoglobin H
True or false: loss of all four α globin genes means incompatibility with life.
True
_____________ ________ _______ stain will demonstrate HbH inclusion bodies.
Brilliant cresyl blue
One gene deletion on chromosome is noted as ____.
α+
_____ gene deletions on same chromosome is noted α0.
Two
__-______________ is a point mutation within or close to the b globin gene complex.
β-thalassaemia
β-thalassaemia can be minor/_______________/major, varying in severity.
Intermediate
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
Thalassaemia major is also called __________ anaemia.
Cooley’s
Cooley’s anaemia features greatly-reduced or absent _____ chain synthesis, and increased alpha chain production,
Beta
List two clinical features of Cooley’s anaemia.
Gross haemolytic anaemia and hepatosplenomegaly
List three laboratory findings of Cooley’s anaemia.
Microcytosis, hypochromia, and severe anaemia
What is the main treatment used in supporting the patient with Cooley’s anaemia?
Blood transfusion
List a chelating agent, used to prevent haemosiderosis.
Desferrioxamine
Macrocytosis is defined as erythrocytes which have MCV of >_____fL, with a normal MCHC.
100
List three causes of genuine macrocytosis.
Alcoholism, Vitamin B12 deficiency, and hypothyroidism
True or false: hyperglycaemia can erroneously elevate macrocytic cell counts.
True
_______________ macrocytic anaemia, such as B12 and folate deficiencies, is characterised by retardation of DNA synthesis.
Megaloblastic
B12 is similar to ________.
Haem
B12 acts as a ___-__________ in two biochemical reactions, one of which pertains to ATP production.
Co-enzyme
B12 consists of four pyrrole rings, linked to a ____________ atom, with a nucleotide at a right angle.
Cobalt
List the four molecules attached to B12’S cobalt atom.
Methyl group
Deoxyadenosyl group
Cyano group
Hydroxy group
True or false: B12 is a stable vitamin, and little loss occurs in cooking.
True
B12 Complexes in 1:1 ratio with ___________ _________.
Intrinsic factor
Intrinsic factor is a glycoprotein secreted by _________ cells of stomach.
Parietal
B12/IF complex moves to the ileum, and attaches to specific receptors on ____________ ___________ _______.
Ileal mucosal cells
Name Vitamin B12’s two transport proteins.
Transcobalamin and haptocorrins
Haptocorrins are synthesised by _______________.
Granulocytes
True or false: congenital absence of haptocorrins leads to no impairment.
True
_______________ synthesise folic acid from pteridine, PABA and glutamic acid.
Bacteria
True or false: humans are able to synthesise folic acid naturally.
False
By what other name is folic acid known?
Pteroylglutamic acid
List three dietary forms of folate.
Polyglutamates, dihydrofolate, and tetrahydrofolate
Folic acid is involved in the synthesis of ______________ from homocysteine.
Methionine
Absorbed folates converted to ___-__-_____________________________ (5-MTHF) and released into portal blood.
N-5-methyltetrahydrofolate
List three causes of Vitamin B12 deficiency.
Malnutrition, old age, and pernicious anaemia
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)
True or false: onset of megaloblastic anaemia may be insidious.
True
In megaloblastic anaemia, MCV is usually increased, white cell count is generally ___________ , and platelet count is often decreased.
Decreased
Common features of megaloblastic blood films include oval macrocytes and _______________.
Anisocytosis
Increased LD, increased unconjugated bilirubin, increased serum methylmalonic acid (MMA), and increased plasma homocysteine is often observed in __________________ anaemia.
Megaloblastic
________________ considers Vitamin B12 and folate (and iron).
Haematinics
Pernicious anaemia is due to the loss of _________ ___________ cells, most commonly due to autoimmune attack.
Gastric parietal
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
_______________ haemolysis plays little to no role in RBC destruction.
Intravascular
Extravascular haemolysis is removal of red cells by ______________ of liver, spleen and bone marrow.
Macrophages
List two inherited forms of haemolytic anaemia.
Hereditary elliptocytosis and hereditary spherocytosis
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
Pyruvate kinase deficiency leads to reduced _____ levels.
ATP
List three other ways by which haemolytic anaemia would develop.
Drugs, infections, and venom
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
True or false: warm-type acquired haemolytic anaemia may be idiopathic, or secondary to underlying disease.
True
In warm-type acquired haemolytic anaemia, a Coombs’ test will be ___________.
Positive
List the three forms of cold-type acquired haemolytic anaemia.
Cold haemaggluttin disease, cold autoimmune haemolytic anaemia, and paroxysmal cold haemoglobinuria
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
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
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
True or false: membrane function has no bearing on a cell’s osmotic fragility.
False
Spherocytes are osmotically ____________ compared to normal RBC.
Fragile
State three laboratory findings of increased RBC destruction.
Increased bilirubin, haemoglobinuria, and decreased RBC lifespan
Increased reticulocyte count, polychromasia, and bone marrow erythroid hyperplasia are signs of __________ _________________.
Increased erythropoiesis
