Session 7 ILO's Introduction to anaemia, B12 & folate metabolism and megaloblastic anaemia Flashcards
Define the term anaemia
A haemoglobin concentration lower
than the normal range.
Normal range will vary with age, sex and ethnicity so the point at which a patient becomes anaemic depends on these parameters
Understand the important causes of microcytic anaemia
Microcytic anaemia (decreased RBC size):
TAILS:
- Thalassaemia
- Anaemia of chronic disease
- Iron deficiency
- Lead poisoning
- Sideroblastic anaemia
Serum Iron studies will help you determine which one of TAILS microcytic anaemia is caused by
- Reduced haem synthesis (iron deficiency, lead poisoning, anaemia of chronic disease, sideroblastic anaemia)
- Reduced global chain synthesis (alpha-thalassaemia or beta-thalassaemia)
Understand the important causes of normocytic anaemia
Normocytic anaemia (normal RBC size):
- Mostly acquired e.g. as a result of disease = anaemia of chronic disease (ACD) or anaemia of inflammation
- Also can be congenital or can be a complication from a particular medication
Causes: primary bone marrow failure (aplastic anaemia), secondary bone marrow failure (e.g. ACD, uraemia, HIV)
Understand the important causes of macrocytic anaemia
Macrocytic anaemia (increased RBC size):
Causes:
- Vit B12 deficiency
- Folate deficiency,
- Myelodysplasia
- Liver disease
- Alcohol toxicity
E.g. in
- Megaloblastic anaemias
- Macronormoblastic anaemias
- ‘Stress’ erythropoiesis
What causes the signs and symptoms of anaemia?
Haemoglobin carries O2. General signs and symptoms therefore related to insufficient delivery of O2 to tissues
Outline the symptoms of anaemia (8)
- Shortness of breath
- Palpitations
- Headaches
- Claudication
- Tachypnoea
- Angina
- Weakness & Lethargy
- Confusion
Outline the signs of anaemia (5)
- Pallor
- Tachycardia
- Systolic flow murmur
- Tachypnoea
- Hypotension
Discuss the specific signs associated with the causes of anaemia
Discuss a key clinical point about anaemia
Anaemia in itself is not a diagnosis but a manifestation of an underlying disease state and it is important to establish the cause of the anaemia
What is a key clinical point about folate.
Outline the common clinical features and important underlying causes of haematinic deficiency (iron, vitamin B12 or folate deficiency)
Iron deficiency
Iron deficiency - most common nutritional disorder worldwide:
Clinical features: sign not a diagnosis, extreme fatigue, weakness, pale skin, fast heartbeat or shortness of breath
- Physiological effects of anaemia….
- Tiredness
- Pallor
- Reduced exercise tolerance (due to reduced oxygen carrying capacity)
- Cardiac – angina, palpitations, development of heart failure
- Increased respiratory rate
- Headache, dizziness, light-headedness
- Pica (unusual cravings for non-nutritive substances e.g. dirt, ice)
- Cold hands and feet
- Epithelial changes
Could be due to: - Insufficient intake/poor absorption
- Physiological reasons e.g. pregnancy * Pathological reasons e.g. bleeding
Underlying causes:
- Insufficient iron in diet
e.g. Vegan & vegetarian diets - Malabsorption of iron
e.g. Vegan & vegetarian diets - Bleeding
e.g. Menstruation, gastric bleeding due to chronic NSAID usage - Increased requirement
e.g. Pregnancy, rapid growth - Anaemia of chronic disease
e.g. Inflammatory bowel disease
Outline the common clinical features and important underlying causes of haematinic deficiency (iron, vitamin B12 or folate deficiency)
Folate deficiency
Folate deficiency
Clinical features:
- Those related to anaemia
- Reduced sense of taste
- Diarrhoea
- Numbness and tingling in feet and hands (paraesthesia)
- Muscle weakness
- Depression
Underlying causes:
* Dietary deficiency (Poor diet)
* Increased requirements:
- Pregnancy
- Increased erythropoiesis e.g. haemolytic anaemia
- Severe skin disease (e.g. psoriasis, exfoliative dermatitis)
* Disease of the duodenum and jejunum (e.g. coeliac disease, Crohn’s disease)
* Drugs which inhibit dihydrofolate reductase (e.g. Methotrexate)
* Alcoholism (poor diet and damage to intestinal cells)
* Urinary loss of folate in liver disease and heart failure
Outline the common clinical features and important underlying causes of haematinic deficiency (iron, vitamin B12 or folate deficiency)
Vitamin B12 Deficiency
Vit B12 deficiency:
Clinical features:
* Those related to anaemia
* Glossitis & mouth ulcers
* Diarrhoea
* Paraesthesia
* Disturbed vision
* Irritability
Underlying causes:
* Dietary deficiency (Vegan diet lacking B12 supplementation)
* Lack of intrinsic factor (Pernicious anaemia)
*Diseases of the ileum (Crohn’s disease, ileal resection, tropical sprue)
*Lack of transcobalamin (congenital defect)
*Chemical inactivation of B12 e.g. frequent use of anaesthetic gas nitrous oxide
*Parasitic infestation (rare tapeworm found in fish can trap B12)
* Some drugs can chelate intrinsic factor (e.g. hypercholesterolaemia drug Cholestyramine)
Describe Pernicious anaemia
- Decreased or absent Intrinsic factor (IF) causes progressive exhaustion of B12 reserves.
- Autoimmune disease
- 2 types of Antibody (Ab) :
- Blocking Ab (more common) blocks binding of B12 to IF.
- Binding Ab prevents receptor mediated endocytosis.
Describe the role and complications associated with haematinic replacement treatment
Iron deficiency
Treatments:
Iron deficiency:
- Dietary advice
- Oral iron supplements (Safest, first-line therapy for most patients but many experience GI side effects and compliance with treatment poor)
- Intramusclar iron injections
- IV iron
- Blood transfusion (Only used if severe anaemia with imminent cardiac compromise)
Response:
* Improvement in symptoms
* 20g/L rise in Hb in 3 weeks
- RISK is that excess iron can be deposited in organs as haemosiderin and iron promotes free radial formation and organ damage
- RISK of transfusion associated haemosiderosis or hereditary haemochromostosis
CHECK SLIDES FOR MORE DETAIL ABOUT RISKS
Describe the role and complications associated with haematinic replacement treatment
Vitamin B12 deficiency
Vit B12 deficiency - caused by pernicious anaemia:
- Intramuscular Hydroxocobalamin (not oral)
- RISK of hypokalaemia at the beginning of treatment due to increased K+ requirement as erythropoiesis increases back to normal rate
Vit B12 deficiency - other causes (not pernicious anaemia):
- Oral Hydroxocobalamin
- Note: blood transfusion in patients with severe B12 deficiency anaemia can cause high output cardiac failure
Describe the role and complications associated with haematinic replacement treatment
Folate deficiency
- Oral folic acid
Complications:
- Serious allergic reaction
- Skin rash that may include itchy, red, swollen, blistered or peeling skin.
- Wheezing.
- Tightness in the chest or throat
- Mouth, face, lips, tongue or throat start swelling.
List the different causes of microcytic anaemia
Give examples of good dietary sources of haem and non-haem
iron
Haem Iron (in ferrous form)
- associated with haemoglobin from animals
i.e. liver kidney, beef steak, beef burger, chicken, duck, pork chop, salmon/tuna
Non Haemoglobin iron (Either Fe2+ or fe3+) needs to all be converted to ferrous form, to be absorbed - ferric iron needs to be reduced to serous iron
fortified cereals, raisins, beans, figs, barley, oats, rice, potatoes
Give an overview of iron absorption, transport, uptake, storage and metabolism
Absorbtion:
- Dietary iron (haem Fe2+ or non-haem Fe2+ and Fe3+) is absorbed by DMT1 (vit C is a co-factor in Fe3+ reduction) into the enterocytes of the small intestine
Transport:
- First, Fe2+ needs to be converted to Fe3+
- Two Fe3+ can bind to transferrin which can transport iron around the body
Storage:
- Iron needs to be stored in the ferric form of Fe3+ bound to ferritin (soluble)
- Haemosiderin are aggregates of clumped ferritin (insoluble) which accumulate in macrophages mainly in liver, spleen and marrow
Uptake into tissues:
- Occurs by receptor mediated endocytosis
- Fe3+ bound with transferrin enters cell by receptor mediated endocytosis
- Fe3+ released by acidic environment in endosome and is reduced to Fe2+
- Fe2+ transported to cytosol via DMT1
- Once in the cytosol, Fe2+ can be stored in ferritin, exported by ferroportin or taken up by mitochondria
Understand how iron deficiency leads to anaemia
Anaemia develops if the supply of iron is inadequate for the requirements of haemoglobin synthesis
Describe how iron deficiency anaemia is diagnosed
Iron deficiency anaemia is diagnosed by:
- Plasma ferritin (gives a definitive diagnosis)
- But, normal or increased plasma ferritin does not exclude iron deficiency!
- CHr (reticulocyte haemoglobin content) can test for functional iron deficiency
Appreciate how iron overload can occur
Iron overload can occur by:
- Transfussion associated haemosiderosis
- Repeated blood transfusions cause gradual accumulation of iron
- Iron chelating agents (e.g. desferrioxamine) can reduce this, but can’t prevent it
- Accumulation of iron in liver, heart and endocrine organs - Hereditory haemochromatosis
- Autosomal recessive disease from mutation in HFE gene
- HFE proteins normally interacts with the transferrin receptor reducing the affinity for iron-bound transferrin
- HFE also promotes hepcidin expression through signalling pathways in the liver
- Too much iron enters the cells and accumulates in end organs
- Treatment with venesection
Describe the causes of Hereditary Haemochromatosis
Causes:
Hereditary haemochromatosis is an autosomal recessive disease characterised by excessive absorption of dietary iron. As there is no system for the excretion of excess iron, iron accumulates in tissues and organs disrupting normal function. The most susceptible organs include liver, adrenal glands, heart, joints, and pancreas. Patients therefore present with cirrhosis, adrenal insufficiency, heart failure arthritis or diabetes.
Describe the treatment of Hereditary Haemochromatosis
Therapeutic phlebotomy to remove excess iron.
Describe how you can evaluate anaemia
