Lec 22- anaemia Flashcards
What is anaemia
-anaemia is a decrease in the number of red blood cells RBC/ Hb in the blood
Epidemiology
-World-50% pregnant women; 40% of infants
-UK-14% women 55-64; 3% of men 35-64
Symptoms of anaemia
- Tiredness and lethargy
- Inhibition of physical exercise
- Reduced mental performance
- The available blood will be fully oxygenated in the lungs
- May get a compensatory increase in cardiac output
Clinical assessment/ investigation of a patient with suspected anaemia
- Investigations- it is essential to find the underlying cause. There is no place for blind treatment
- Full blood count is an essential screening test
- 1st step look at MCV(mean cap volume) (rem diam 2-2.5)
The full blood count- Why; when; how
Why- full blood counts are commonly requested as part of a general screen in a patient who is unwell to screen for a variety of disorders- anaemia; infection; inflammation; nutritional status; bleeding
- When- as determined by the clinician, there are many illnesses which will affect the full blood count and the result may help to make a diagnosis
- How- A blood sample take from a vein in the arm or finger-prick or heel prick (new borns)
Fe in Hb- structure of Hb
-4 sub units- 2a and 2b
-Fe
Haem
Binds 4 O2 molecules
Production of red blood cells (normal erythropoiesis)
- Pluripotent stem cell –>
- Erythyroid burst forming unit (EPO target) –>
- Erythroid colony forming unit>
- Erythroblast –>
- Reticulocyte –>
- Erythrocyte –>
- MADE IN BONE MARROW
Underlying causes of anaemia
1) RBC loos without RBC destruction (Haemorrhage)
2) Deficient RBC production
3) Increased RBC destruction- haemolytic anaemias
1) RBC loss without RBC distraction
- Haemorrhage- due to trauma; due to disorders- cancer, ulcer, TB, IBS
- Menstrual flow
- Gynaecological disorders (endometriosis; fibroids)
- Pregnancy-especially at gestation
- Parasitism- hookworm
- 100mls blood= 40 days Fe intake, in a western diet
2) Deficient effective RBC production
This is the MAIN ONE
A)Regulation of erythropoiesis
B)Fe deficiency anaemia
C)Sideroblastic anaemia- cannot incorporate Fe into Hb
D)Megaloblastic anaemia: pernicious anaemia(cannot absorb B12); B12 deficiency; folate deficiency
A) regulation of erythropoiesis
- Kidneys monitor blood O2 (hypoxaemia)
- If renal tissue is hypoxic, erythropoietin is produced by renal peritubular interstitial cells
- Athletes- altitude training
Factors necessary for erythropoiesis
- Erythropoietin
- Fe
- B12
- Folic acid
- Ascorbic acid
- Pyridoxine (B6)
- Amino acids
Recombinant Erythropoietin (RhuEPO) is used to treat anaemia in:
- CKD- prior to dialysis (there is always destruction of RBC in dialysis as the blood goes through the dialysis pump)
- AIDS
- Transplants
- Cancer- for patient who have undergone Chemotherapy that destroyed some fo the bone marrow
- Premature children
Haemocrit
- Plasma 55%
- Buffy coat- leukocytes and platelets <1%
- Erythrocytes 45%
- EPO- abused primarily by professional cyclists
- Causes increased blood viscosity; increase BP; increased Heart workload; can lead to HF
B) Fe deficiency anaemia
- Fe deficiency is the most common cause of anaemia
- Results in microcytic hypo chromic anaemia (small RBC)
Normocytic
- Normal RBC’s.They have a zone of central pallor about 1/3 the size of the RBC.
- A few small fuzzy blue platelets are seen
- In the centre of the Field are a band of neutrophil on the left and a segmented neutrophil on the right
Microcytic
- The RBC here are smaller than normal and have an increase zone of pallor
- This is indicative of a hypo chromic (less Hb in each RBC) microcytic (smaller size) anaemia
- The most common cause of this is Fe deficiency
Fe deficiency anaemia- common causes
- Lack of Fe in diet
- Partial gastrectomy due to ulcers (gut removed so can’t absorb)
- Blood loss due to: bleeding peptic ulcers; malignancy
- Malabsorption syndromes: CF; coeliac disease
Fe - absorption’s
- Absorbed from the duodenum (where most drugs are absorbed) and upper jejunum
- Vit C taken with the Fe increases absorption by reducing dietary ferric (Fe3+) to ferrous (Fe2+) Fe
- Caffeine and other xanthines decrease absorption
- Usually 1-2mg dd
- Macrophages when they break down RBC they recycle Fe
Fe therapy
- Lots of Fe
- Normal levels 12g/dL of blood
- Takes 40 days to obtain Fe in 100mls of blood
- Therapy ferrous sulphate 200mg TDS
- Will take 1-2 weeks to raise by 1g/dL
Fe therapy- side effects of oral preparations
-Only absorbed well in the ferrous form
-Ferrous sulfate; ferrous gluconate; ferrous fumarate
Side effects: nausea; gastric discomfort; constipation; cramps; diarrhoea; dark stools
C) sideroblastic anaemia’s
- A group of conditions diagnosed by finding ring sideroblasts in bone marrow
- Both hereditary (rare) and acquired forms
- 30% of alcoholics admitted to hospital having sideroblastic anaemia
- Main defect- reduced activity of enzyme 5-aminolevulinate synthase (ALAS)- involved in haem synthesis
- ALAS= involved in the 1st step of the synthesis of haem- and requires pyridoxal phosphate (Vit B6) (precursor pyridoxine) as co-factor
sideroblastic anaemia
- Erythroblasts have Fe granules surrounding the cell nucleus
- Rings are known as ring sideroblasts
- Fe is concentrated in mitochondria suggesting cell is unable to bind haem and Fe due to deficient enzymes
Causes of acquired sideroblastic anaemia
-Associated with other disorders \+Myeloid Leukaemia \+Myeloma \+Collagen disease -Drugs and toxins \+Alcohol (metabolite +acetaldehyde lowers levels of ALAS and pyridoxal) \+Isoniazid \+Chloramphenicol \+Lead poisoning
Treatment of sideroblastic anaemia
- The main medication-pyridoxine- may take months to see the benefit
- If reversible (drugs and toxins)- remove the offending agents
- Severe cases- blood transfusions- however, there is a problem with Fe overload- so a chelating agent e.g. desferrioxamine is required
D) Megaloblastic (microcytic) anaemia
- Due to lack of folic acid or Vit B12
- Folate (folic acid) interacts with Vit B12: essential for normal blood and nerve function
- Lack of either prevents the formation of DNA so RBC production doesn’t occur or occur abnormally
- Macrocytic cells (large cells) which may have enough Hb, but are not concave and are fewer in number
- Therefore cannot take up or transport O2 normally
- The cells are more easily damaged- also contributing to the anaemia
Macrocytic anaemia
- The hypersegmented neutrophil and also that the RBC are almost as large as the lymphocyte
- Finally, not that there are fewer RBC’s
Pernicious anaemia: Vit B12
- Also called the extrinsic factor
- Must combine with intrinsic factor IF produced by the parietal glands of the stomach
- The combination enables binding to receptor and phagocytosis of the complex by the distal ileum cells
- Lack of Vit B12 is called pernicious anaemia
- It is usually a result of an autoimmune disease, that destroys the parietal cells of the stomach
Vit B12 treatments
- Normal patients= oral
- Pernicious anaemia- B12 can be given via IM or IV
Folic acid therapy
Sources
- Green veg; nuts; cereal; fruit; yeast
- Folate therapeutics- usually in multivitamin preparations; also as folic acid 5mg tablets
Pregnancy
- Pregnant female needs 3.5mg folic acid per day compared with 0.9mg for adult male
- Partially suppled by increase absorption (and pica- craving)
- Also a much greater need for folate for developing foetus
3) Increased RBC destruction (haemolytic anaemias)
Intrinsic abnormalities
-Thalassaemia (deficient a or b protein)
-Sickle cell anaemia
-Glucose-6-phosphate dehydrogenase deficiency
Extrinsic abnormalities
-Infection- malaria
-Drugs- sulfasalazine
Haemolytic anaemia
Thalassaemias
-Autosomal recessive condition
-Many types of mutation in a and b subunit. affects O2 carrying capacity
Sickle cell anaemia
-Inherited condition genetically. Autosomal recessive gene
-Another from Hb s produced. Also makes RBC membranes inflexible, problems in microcirculation
-Symptoms- feel ill, ab pain, jaundice; dark urine
Haemolytic anaemia- treatment
- Increase the RBC production, therefore, folate may help in sickle cell anaemia; EPO is very severe cases
- No effective treatment for thalassaemia, severe sufferers may need blood transfusion from an early age
G6PD- anaemia-
Glucose-6-phosphate dehydrogenase deficiency
- Autosomal recessive hereditary condition
- Affects 400 million people worldwide
- 300 different forms of deficiency- only some cause anaemia
- The most common form found in 15% of Afro-Caribbean origin- anaemia caused when the individual is exposed to a trigger factor
- A more severe form is the Mediterranean variant- patients may have chronic haemolytic anaemia without a trigger
- G6PD- is an enzyme that indirectly involved in the production of reduced glutathione
- Glutathione produced in response to oxidising agents and protects RBC
G6PD- investigation/treatment
Investigation
-clinical history (family) and any findings- may be used to differentially diagnose suspected cases
-Confirmation- by measuring G6PD activity
Treatment
-Avoid trigger factors or food (broad beans) often called favism due to eating fava beans
-No specific drug treatments
-Patients can be given a list of drugs to avoid but since these are POM, it is important the patient informs HPC of their conditions
Malaria
- Plasmodium …
- Parasite infects RBC and replicates
- They then break out and kill that RBC
Anaemia diagnosis
-Important to know which type of anaemia especially for microcytic, since folate treatment will not treat B12 deficiency induced neuropathy
-Blood tests- examine RBC morphology
-Measure blood folate levels
0Use a B12 radio-ligand to test absorptions, test for antibodies to instrinsic factor
Differential diagnosis using MCV
- Macrocytic anaemia- larger than normal cells (MCV=150fl)
- Normocytic (MCV=80-96fl)- cells are normal in volume
- Microcytic anaemia (MCV=50 fl)- cells are smaller than normal
Algorithm for the assessment of anaemia
LOOK AT BB SLIDE
