Anaemia Flashcards
define anaemia
Anaemia describes a reduction in red cells and/or their haemoglobin content
What are male and female haemoglobin levels
- Male:
- 12-70 years (140-180)
- >70 years (116-156)
- Female:
- 12-70 years (120-160)
- >70 years (108-143)
What are symptoms of anaemia
- Tiredness/pallor
- Breathlessness
- Swelling of ankles
- Headaches
- Palpitations
- Dizziness
- Chest pain
what are symptoms specific to iron deficiency anaemia
- Pica describes dietary cravings for abnormal things such as dirt and can signify iron deficiency
- Hair loss can indicate iron deficiency anaemia
what are signs of anaemia
- Pale skin
- Conjunctival pallor
- Tachycardia
- Raised respiratory rate
What are signs specific to iron deficiency anaemia
koilonychia, angular chelitis, atrophic glossitis, brittle hair
what is the most common type of anaemia
iron deficiency anaemia
What would be your initial investigations for anaemia
the size of the red cells (mean cell volume, MCV) and amount of haemoglobin (mean cell haemoglobin, MCH).
what are the different types of anaemia according to the size of the red cells (mean cell volume, MCV) and amount of haemoglobin (mean cell haemoglobin, MCH).
- A low MCV (microcytic) and MCH (hypochromic); i.e. microcytic hypochromic anaemia, suggests iron deficiency or thalassaemia
- A normal MCV (normocytic) and MCH (normochromic), i.e. normocytic normochromic anaemia, suggests either acute blood loss or anaemia of chronic disease
- A high MCV (macrocytic anaemia) suggests vitamin B12 or folate deficiency
After discovering that an individual has hypochromic microcytic anaemia what would be your next investigation
ferritin level
After discovering that an individual has normochromic normocytic anaemia what would be your next investigation
reticulocyte count
After discovering that an individual has macrocytic anaemia what would be your next investigation
B12/folate level
A decrease in body concentrations of iron leads to enhanced uptake at the intestine. Dietary iron is ingested as heme/ionised iron in meat and as heme/ionised iron in plant products
heme then ionised
what transporter is responsible for the absoption of heme and ionised iron
heme = apical transporter
ionised = divalent metal transporter 1
once absorbed heme iron is converted into ionised iron which is incorporated into the protein
ferritin
what is the function of ferritin
intracellular iron store
any iron that isnt bound to the epithelial ferritin is transported across the serosal membrane by which transporter
ferroportin
Once in the blood iron binds to the protein _____ which transports iron to various tissues such as the liver, spleen and bone marrow
transferrin
once in the liver iron is stored as
ferritin or hemosiderin
what is the name of the liver protein responsible for regulating iron balance and how does it achieve this
iron loading in the liver causes the production of hepciding which inhibits ferroportin (serosal transport protein that move iron from the epithelial cell to the blood).
when iron levels are low hepcidin is down-regulated thereby increasing iron transfer from the gut
what is a sign of hyperaemia
excess iron = black faeces due to the renewal of the epithelial cells of the GI tract every 5 days so any that is incorporated into ferritin will be shed in faeces
Iron deficiency anaemia is a description not a diagnosis. list some causes for this
- chronic blood loss (e.g. peptic ulcer; carcinoma of stomach, caecum, colon or rectum; menorrhagia)
- diet (children and elderly)
- increased requirements (e.g. in childhood and pregnancy)
- malabsorption (due to gastrectomy, coeliac disease)
- malnutrition
how would you treat someone with iron deficiency anaemia
replacement therapy (Fe) - oral or IV
what are features of intravascular haemolysis
Particular features of intravascular haemolysis are the presence of free haemoglobin in plasma and urine (hemoglobinemia, haemoglobinuria), of methaemalbumin in plasma (oxidised haem bound to albumin) and of haemosiderin in urine (in shed renal tubular cells that have reabsorbed haemoglobin from the tubular contents; the haem is incorporated into haemosiderin).
what are spherocytes and what types of anaemias have this feature
Spherocytes are spherical red blood cells without the normal bi-concave disk space.
Hereditary spherocytosis (RBC membrane defect) and immune haemolytic anaemia
What are the management options for haemolytic anaemia
- Support marrow function
- Folic acid
- Correct cause
- Immune suppression if autoimmune
- Steroids
- Treat trigger e.g. CLL, lymphoma
- Remove site of red cell destruction
- Splenectomy
- Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular
- Immune suppression if autoimmune
- Consider transfusion
What is the name of haemolytic anaemia caused by RBC membrane defects and name some of the commonly affected structural proteins
hereditray spherocytosis and spectrin (alpha and beta), ankyrin, band 3 and protein 4.2
what is the inheritance pattern for hereditary spherocytosis
autosomal dominant
What are the treatment options for those with hereditary spherocytosis
- Folic acid prophylaxis (5mg once weekly for life)
- Splenectomy should be considered if anaemia severe – improves but does not normalise red cell survival
- Transfusion
What is the function of G-6-P dehydrogenase what is the outcome of its deficiency
G6PD produces NADPH, which is vital for the reduction of glutathione. Reduced glutathione protects haemoglobin and red cell membrane from oxidative damage.
Deficiency means there is no protection against oxidative stress hence individuals with this condition experience haemolytic anaemia under these circumstances e.g. ingestion of an oxidant drug (antimalarial/antibiotic/aspirin), broad bean or infection
what is the inheritance pattern of G6P dehydrogenase deficiency
X-linked
what is the inheritance pattern of Pyruvate kinase deficiency
autosomal recessive
What is the results of pyruvate kinase deficiency
accumulation of erythrocyte 2,3-BPG. This reduces the oxygen affinity of haemoglobin and increased oxygen delivery to the tissues.
What causes sickle cell anaemia
Substitution of valine for glutamic acid in position 6 in the beta chain of globin results in a haemoglobin (HbS) that irreversibly becomes crystalline (aggregation and polymerisation) at low oxygen tensions.
what are the consequences of sickle cell anaemia
chronic haemolytic anaemia and microvascular occlusion, causing ischaemic tissue damage.
what is the management of sickle cell disease
- Life long prophylaxis:
- Vaccination
- Penicillin (and malarial) prophylaxis
- Folic acid
- Acute events
- Hydration
- oxygenation
- Prompt treatment of infection
- Analgesia
- Opiates
- NSAIDs
- Blood transfusion
- Complications:
- Alloimmunisation
- Iron overload
- Complications:
- Other:
- Disease modifying dugs
- Hydroxycarbamide
- Bone marrow transplantation
- Gene therapy
- Disease modifying dugs
What is the cause of thalaseemia
in thalassaemia the globin chains are of normal composition, but the rate of production of the globin chains (alpha or beta) is synthesised is reduced or absent
What is the spectrum of thalassaemia
-
Homologous alpha zero thalassaemia (a0/a0)
- No alpha chains
- Hydrodrops fetalis – incompatible with life
-
Beta thalassaemia major (homozygous beta thalassaemia)
- No beta chains
- Severe anaemia
- Present at 3-6 months of age
- Expansion of ineffective bone marrow (gives characteristic ‘hair on end’ Xray appearance - see image
- Bony deformities
- Splenomegaly
- Growth retardation
- Transfusion dependent anaemia
- 4-6 weekly
- Tx results in normal growth and development
- Tx causes iron overloading
- Iron chelation therapy – S/C or oral
- Requires regular monitoring with ferritin and mri scan
- Those with transfusion tx die in the 2nd or 3rd decades of life due to heart/liver/endocrine failure if iron loading untreated but those that adhere to chelation have a near normal life expectancy
- Iron chelation therapy – S/C or oral
- Life expectancy untreated or with irregular transfusions <10 years
- Bone marrow transplant is curative
-
Non-transfusion dependent thalassaemia – ‘intermedia’
- Range of genotypes e.g. HbE/beta thal, HbH disease
-
Thalassaemia minor (common)
- ‘trait’ or carrier state
- Hypochromic microcytic red cell indices
What test confirms immune mediated haemolysis
Positive Coombs test (DAGH)
What conditions correspond to a warm antibody positive Coombs test
- Chronic lymphocytic leukaemia
- Drugs e.g. penicillin
- Autoimmune conditions such as SLE and RA
What conditions correspond to a positive cold antibody coombs test
- Cold haemagglutinin disease (CHAD)
- Infections
- Lymphoma
What causes macrocytic anaemia
Vitamin B12 or folate deficiency
In the stomach Vitamin B12 becomes bound to what glycoprotein produced by parietal cells
intrinsic factor
Vitamin B12 – intrinsic factor complex attaches to specific intrinsic factor receptors in the _______, where vitamin B12 is absorbed,
distal ilium
How long does it take for the body store of Vitamin B12 to become depleted
several years
where does absorption of folate occur
proximal jejunum
how long does it take for the folate stores to become depleted
the stores are modest - it only takes a couple of weeks
What are causes of vitamin B12 deficiency
- Pernicious anaemia
- Gastric/ileal disease
what are causes of folate deficiency
- Malnutrition
- increased requirements (e.g. pregnancy and lactation, haemolytic anaemias, myelofibrosis, malignancy, extensive psoriasis or dermatitis)
- GI pathology causing malabsorption e.g. coeliac disease or crohn’s
What is the cause of pernicious anaemia
Pernicious anaemia is due to an autoimmune process, resulting in atrophy of the chief and parietal glands of the stomach, with consequent failure of acid and intrinsic factor production.
what antibodies are found in pernicious anaemia and which is the most specific to the condition
autoantibody to:
parietal cells
intrinsic factor (specific)
