Anaemia and haematinic deficiencies Flashcards
What is blood made up of?
plasma 55% (91% is water) buffy coat (white cells and platelets + red blood cells - 45%
What is anaemia?
lack of blood - reduction in Hb, red cell count or haematocrit
What are the normal levels of haemoglobin?
males >130 g/L females >120g/L pregnant woman >110 g/L children 6-59 months >110g/L children 5-11 years >115 g/L children 12--14 years >120 g/L
How many new red cells are made per day and what is their life span?
10 to the power of 12 new ones per day
life span: 120 days
form in the bone marrow from myeloid cells - differentiate from blasts which are regulated by erythropoietin
the nucleus of the cell is removed just before leaving the bone marrow
What are the 3 main types of anaemia?
Microcytic (MCV <80fL)
Normocytic (MCV 80-90fL)
Macrocytic (MCV >95 fL)
The size of the red blood cells can help determine the cause
What are the causes of microcytic anaemia?
Thalassaemia and thalassaemia trait (NOT sickle cell)
Iron deficiency (most common cause worldwide)
Anaemia of chronic disease
Sideroblastic anaemia (congenital or acquired)
What are the causes of normocytic anaemia?
Anaemia of chronic disease
Acute blood loss
Mixed haematinic deficiencies
Bone marrow failure (not able to produce enough cells) - aplastic anaemia, drugs e.g chemo
What are the causes of macrocytic anaemia?
Megaloblastic anaemia Myelodysplasia- ware and tare on the bone marrow Haemolytic anaemia liver disease Alcohol Drugs - esp. antiepileptics, hydrocarbamide Hypothyroidism Pregnancy
It is typical with b12 and folate deficiencies
What is MCV?
mean corpuscular volume = average volume of a red blood cell
What are the main causes of acquired anaemia?
unable to make red cells
- deficiencies in b12, folate, iron
- bone marrow pathology - aplastic anaemia, myelodysplasia, myeloma
- displacement of bone marrow - leukaemia, myelofibrosis
- chronic disease- renal failure, chornic inflammatory conditions
destroying red blood cells
- haemolysis
- bleeding
What are the main causes of congenital anaemia?
membrane defect
- hereditary spherocytosis
- hereditary epilptocytosis
haemoglobin defect
- sickle cell anaemia
- thalassemia
enzyme defect
- G6PD deficiency
- pyruvate kinase deficiency
What happens during bleeding?
Rapid loss of whole blood= hypotensive - Hb conc remains the same
Then plasma vol expands to try and maintain BP = dilution of red cells so Hb falls but MCV remains the same (normocytic)
Chronically, iron stores deplete due to making new red cells but Hb and MCV remain relatively normal
However, once iron stores are depleted, you become iron deficient, microcytic hypochromic red cells being made
What are haemotinics?
B12, folate, iron - needed to make healthy red blood cells
What are the signs and symptoms of anaemia?
Signs: pica, koilonychia, pallor, tachycardia, flow murmur, hyperdynamic circulation
Symptoms: restless leg, breathlessness, palpitations, fatigue, tinnitus
Why might someone that’s unwell have low serum iron levels?
iron is stored away to protect it from bacteria because bacteria feed off iron
What are the causes of iron deficiency?
Most common cause of anaemia worlwide
In men and post menopausal women = GI malignancy until proven otherwise
1) poor intake - diet
2) poor absorption- coeliac disease, CD
3) Increased requirement - pregnancy
4) iron loss - bleeding
- GI: cancer, angiodysplasia, ulcers, gastritis, infection
- menorrhagia
- urinary
How do you diagnose iron deficiency?
History and exam: diet, bleeding
FBC and film: microcytic hypochromic anaemia, target cells, pencil cells
Ferritin (measure of iron stores): low in iron deficiency, raised with inflammation
Iron studies: serum iron, transferrin saturation, total iron binding capacity
What is maelena?
bleeding in stool
What does it mean by functional iron deficiency?
Evolutional advantage to keeping iron out of the way of bacteria
Increased iron stores in infection/inflammation
Decreased absorption via hepcidin in enterocyte basolateral membrane
Not available for erythropoiesis
How do you manage iron deficiency?
Find the underlying cause:
- gastroscopy and colonoscopy unless frail or menstruating women
-low threshold for investigating young people with fam history - 2x1st degree relatives or 1 if <40
- unless gastroscopy shows gastric malignancy or coeliac disease, must proceed to lower GI investigation
Treat deficiency
What concentration of oral iron is given and what is unusual about this?
100-200mg elemental iron/day
- normally we absorb about 3mg of iron per day but in iron deficiency pts they can absorb about 10mg a day yet we give them way over that limit therefore it is not surprising they get side effects
Should take for 3 months post normal Hb to relpenish stores
What are some ways to improve adherence and absorption of oral iron supplementation?
start at a low dose
take on an empty stomach
avoid tea because the tanins prevent its absorption t
take with orange juice
What is an alternative to oral iron?
Intravenous iron- venofer, cosmofer, monofer, gerinject
- guaranteed delivery, faster increase in Hb, large dose delivered
Contraindicated in active bacterial infection but otherise very safe
Also more expensive
How do we produce DNA?
Absorb dietary folate in the gut and combine with b12 to produce DNA
What is folate?
it is pteroylglutamic acid = family of compounds - extra carbon groups reduced at different positions
How is folate absorbed and lost?
Proton-coupled transporter in the duodenum
Lost in urine, sweat and skin - excretion in bile
It is tightly bound intracellularly until cell death
Require 100mg/day and body stores 15025mg = 4 months store (not as good a store of folate as B12)
Veg are rich in folate
What are good sources of folate?
liver, spinach, yeast, greens, nuts, fortified foos )bread and cereal)
- certain groups that commonly have low folate levels: alcoholics, elderly, poor, psychiatrically disturbed
What are the causes of folate deficiency?
Low intake
Impaired absorption- coeliac/crohn’s, selective malabsorption, drugs (cholestyramine)
increased requirement - haemolysis, pregnancy, prematurity,inflammation
increased excretion/loss - dialysis, drugs (dihyrdofolate reductase inhibitors)
How can you measure folate levels?
Good assays for blood
Elisa technique
Serum - not that great because all you are really analysing is how much folate they had that morning, it is cincreased in b12 deficiency
red cell - low in b12 deficicnec, this is more fiddeley but provides better results
What are the signs and symptoms of folate /b12deficiency?
Signs: jaundice, glossitis, angular cheilosis, skin hyperpigmentation, pallor, tachycardia, flow murmur,
Symptoms: breathlessness, palpitations, fatigue, tinnitus
Can cause infertility and neural tube defects, pancytopenia (deficiency of all 3 cellular blood parts)
How do you treat folate deficiency?
Replacement - almost always oral
5mg/day
4 months depending on cause
400mcg given prophylactically in pregnancy, 5mg for previous NTD
What is the role of B12 and how is it made? What are the requirements?
DNA synthesis and amking succinyl coA in krebs cycle
Synthesised by micro-organisms
Require 5-30mg per day in average diet
- loss 1-2mg per day
stores 2-3 mg per day (store for about 3-4 years)
How is B12 absorbed?
passive - <1% absorbed in the duodenum and ileum
Active- binds intrinsic factor produced by parietal cels and this protects it, also binds haptocorrins (saliva), cubulin receptor (ileum), transbalamin (circulation), enterohepatic circulation
What are the neurological features of b12 deficiency?
Neurological symptoms: - parasthesiae - muscle weakness - difficulty walking - confusion, slowness signs: - peripheral neuropathy - long tract demyelination - dementia, psychosis
What are the causes for b12 deficiency?
Poor intake - liver, kidney, shellfish, eggs, cheese and milk
Malabsorption- gastric, ileal, drugs (metformin)
Congenital
Nitrous oxide
Apparent deficiency in HRT/pregnancy
Measure: B12 assay which is much better than hva to test bone marrow (can look low in women taking contraceptive pill), schilling test
What is pernicious anaemia?
Associated with other autoimmune disorders
Common in older women
Destruction of intrinsic factor = impaired absorption
Look for 2 different antibodies but intrinsic factor ab is the most important, the other one is parietal cell antibody
What is the treatment for b12 defiency?
oral replacement if no evidence of PA/malabsorption - 1mg cyanocobalamin
1MG HYDROXYCOBALAMIN intamuscularly - 3/week x6 doses then every 3 months
continue indefinitely unless clear reversal of cause
Routine post gastrectomy or ileal resection
What is assessed in a haemolysis screen?
FBC
Blood film-
LDH - measure of cell turnover
Haptoglobin - measure of free haem
Unconjugated bilirubin - breakdown product of Hb
Direct antiglobulin test - only tells you if in the presence of haemolysis whether it is an immune cause
What are the key features of autoimmune haemolytic anaemia (warm)?
IgG
Associated with other autoimmune disease especially ITP
May be precipitated by infection or cancer
Treatment with steroids, splenectomy or rituximab
What are the key features of autoimmune haemolytic anaemia (cold)?
IgM Associated with EBV, mycoplasma pneumonia, lymphoma Does not respond to steroids keep warm transfuse (through a blood warmer) treat underlying infection/lymphoma
What is hereditary spherocytosis?
autosomal dominant membrane disorder
many different proteins-usually spectrin deficiency
different phenotypes but consistent in familiies
symptoms exacerbated by intercurrent illness
Treatment: folic acid, splenectomy, rarely transfusion
What is an example of an enzymopathy and what are the features of it?
G6PD deficiency
- ATP is required for membrane shape change, ion exchange, reduce methaemoglobin to deoxyghaemoglobin
- mature red cells are unable to synthesis protein and have no mitochondria
- ATP from anaerobic glycolysis
X-linked - total deficinecy is incompatible with life
Red cells unable to deal with oxidative stress (neonatal haemolytic anaemia, acute non-spherocytic haemolytic anaemia
Treatment: avoidance of precipitating factors, folic acid, splenectomy
What is acquired non-immune haemolytic anaemia?
mechanical intravascular destruction of red cells
- microangiopathic haemolytic anaemia e.g. thrombotic thrombocytopenic purpura = shearing of red cells as they pass through fibrin strands
- macrovascular e.g. valve haemolysis, march haemolysis
