B12 and folate deficiencies Flashcards
What are the roles of vitamin B12 and folate
DNA synthesis
Integrity of the nervous system
DNA synthesis
Homocystine metabolism
Both are needed for production of deoxythymidine
Which cells are affected by a vit B12/folate deficiency
All rapidly dividing cells Bone marrow Epithelial surfaces of mouth and gut Gonads Embryos
What are the clinical features of a vit B12/folate deficiency
Anemia: weak, tired, short of breath (macrocytic and megaloblastic) Jaundice Glossitis and angular cheilosis Weight loss, change of bowel habit Sterility
What are the causes of macrocytic anaemia
Vitamin B12/folate deficiency
Liver disease or alcohol
Hypothyroid
Drugs e.g. azathioprine
Haematological disorders (Myelodysplasia,
aplastic anemia
Reticulocytosis e.g. chronic haemolytic anemia)
What is the difference between macrocytic and megaloblastic anaemia
Macrocytic - average red cell size is above normal range
Megaloblastic - morphological change in red cell precursors in the bone marrow.
Define megaloblastic anaemia
asynchronous maturation of the nucleus and cytoplasm in the erythroid series
Maturing red cells seen in bone marrow
Describe the peripheral blood in megaloblastic anaemia
Anisocytosis
Large red cells
Hypersegmented neutrophils
Giant metamyelocytes
Give a source of folate
Fresh leafy vegetables
Destroyed by overcooking/canning/processing
What causes an increased demands in folate
PHYSIOLOGICAL
Pregnancy
Adolescence
Premature babies
PATHOLOGICAL
Malignancy
Erythoderma
Haemolytic anaemias
How is folate deficiency diagnosed/assessed
History (diet, alcohol, illness)
Examination (skin disease, alcoholic liver disease)
Lab
FBC and film
Folate levels in the blood
What are the consequences of folate deficiency
Megaloblastic, macrocytic anaemia
Neural tube defects in a developing foetus
Increased risk of thrombosis in association with variant enzymes involved in homocysteine metabolism
Give examples of neural tube defects
Spina bifida
Anencephaly
What are very high homocysteine levels associated with
Atherosclerosis
Premature vascular disease
High rate of thrombosis
What are mildly elevated levels of homocysteine associated with
Cardiovascular disease
arterial or venous thrombosis
What are the classic features of high homocysteine
Tingling in fingers (parasthesiae) Family history of auto-immune disease Glossitis (inflamed tongue) Premature grey hair Falls over when eyes closed Romberg's sign (loss of proprioception)
What are the neurological consequences of B12 deficiency
Bilateral peripheral neuropathy
Subacute comined degeneration of the cord (Posterior and pyramidal tracts of the spinal cord)
Optic atrophy
dementia
What will the classic clinical history of a patient with B12 deficiency look like
Paraesthesiae Muscle weakness Difficult walking Visual impairment Psychiatric disturbance Absent reflexes and upping plantar response
What are the causes of B12 deficiency
Poor absorption
Reduced dietary intake (vegans at risk)
Infections/infestations (abnormal bacterial flora, tropical sprue, fish tapeworm)
Describe the normal B12 absorption
In small intestine
1. Slow and inefficient (1%) in the duodenum
2. Combination with intrinsic factor from the stomach parietal cells (99%) to bind to ileal receptors
Storage and excretion when stores are in excess
Which 3 things are essential for B12 absorption
Intact Stomach
Intrinsic factor
Functioning small intestine
What may a reduction in intrinsic factor be caused by
Post gastrectomy
Gastric atrophy
Antibodies to intrinsic factor or parietal cells
Describe pernicious anaemia
Autoimmune condition associated with severe lack of intrinsic factor
Peak age = 60
Family history
Describe the antibodies in pernicious anaemia
Intrinsic factor antibodies (can be found in other conditions)
Parietal cell antibodies
90% of adults, 16% normal females >60yrs
What may cause impaired B12 absorption
Reduction in intrinsic factor
Diseases of the small bowel (terminal ileum)
Which disease of the small bowel can cause impaired B12 absorption
Crohns
Coeliac disease
Surgical resection
Which infections can cause impaired B12 absorption
H. Pylori
Giardia
Fish tapeworm
Bacterial overgrowth
Which drugs are associated with low B12
Metformin
Proton pump inhibitors e.g. omeprazole
Oral contraceptive pill
What are the tests done for patients with low B12
- Antibodies to parietal cells and intrinsic factor
- Anitbodies for coeliac disease
- Breath test for bacterial overgrowth
- Stool for H Pylori
- Test for Giardia
What are the possible reasons for no B12 being found in the urine in the shilling test
B12 is not being absorbed (pernicious anaemia or small bowel disease)
B12 deficiency was not corrected before test
What is the shilling test
Prior to test, replenish the stores (drink radio labelled B12 and measure excretion)
Repeat test with intrinsic factor added
Measure excretion of B12
What should be done if there is a classic case of B12 deficiency but B12 is normal
Measure methylmalonyl acid
Measure homocysteine
Look for anti-intrinsic factor antibodies
What is the treatment for B12 deficiency
IM injections of B12
3x a week for 2 weeks then 3 months
