Lecture 10: Vitamin B12 Deficiency Flashcards
What is another name for vitamin B12?
Cobalamin
Describe B12 function and role in folate activation;
- Folate is trapped in the cells in its inactive form
- B12 steals a methyl group, keeping it and thus becoming active
- Both folate co-enzyme and B12 co-enzyme are now active and available for DNA synthesis
What is the source of Vit B12 in the diet?
Animals
Fortified foods (but needs to be in active form)
Made by bacteria feeding off animal proteins
Who are at risk for Vit B12 deficiency?
Vegan and strict vegetarians
Describe the process of vitamin B12 absorption;
1) HCL, pepsin removes B12 from animal protein
2) Saliva secretes haptocorrin which binds freed B12 to preserve it (in stomach)
3) Pancreatic proteases degrade HC.CBl
4) Gastric parietal cells release IF which allows IF.CBl uptake into brush border of enterocytes in ilium (IF recycled here)
5) 20% binds Holotranscoalbumin (TC.CBl) taken up by all cells for DNA synthesis, high turnover (short half life). 80% binds HC again and is transported through the blood.
MUST BE BOUND IN BLOOD.
What stores B12 and how much is released daily?
- About 1mg daily is secreted in bile (enterohepatic circulation)
- Liver stores of B12.
What happens with B12 deficiency?
- Macrocytic anemia
- large irregular shape
Neuropathy? - Sub acute combined degeneration of the spinal cord, (from build up of SAM?)
Can B12 be supplemented?
- Yes, Vegans
- Malabsorption syndromes i.e pernicious anemia
Usually treated with intra-muscular injections
Would a patient notice a drop off in haemoglobin?
If it occurs over 6 months they would not notice it.
What are reticulocytes and what would a large increase in them suggest?
They are precursors to RBC and a low value would suggest that the bone marrow is not able to respond to the usual stimulus of anemia
Severe trauma would not see an decrease in this (might see heamoglobin drop off)
Are WBC impacted in anemia?
Yes they are observed to be impacted in anemia, such as hypersegmented neutrophils
What are the usual requirements for normal erythropoesis?
- Iron
- Folate
- B12
What can cause low B12?
- Diet
- Failure to absorb
- Requirements to absorb;
- Normal acid secretion
- Normal intrinsic factor*
- Normal pancreatic secretion
- Normal ileal absorptive function*
- = Most important factors
Describe the absorption of B12 again;
- Gastric acid cleaves food bound B12
- B12 needs to bind intrinsic factor to be absorbed in TERMINAL ilium.
- Binding of B12 to intrinsic factor can be interfered with by other proteins. R-proteins released in saliva and stomach to prevent B12 breakdown must be cleaved by pancreatic enzymes before intrinsic factor can bind.
What stomach issues can caused B12 mal-absorption?
- Lack of intrinsic factor i.e pernicious anemia, means that B12 cant be absorbed in terminal ilium
What is pernicious anemia?
Autoimmune disorder where the individual develops auto-antibodies against intrinsic factor and parietal cells.
What small intestine problems can cause B12 deficiency?
- B12 binding IF normally but removal of the terminal ilium, crohns causing inflammation in the terminal ilium presents absorption form taking place.
How can pernicious anemia be diagnosed?
Autoantibodies detected in blood test:
- ab to parietal cells
- ab to intrinsic factor
Evidence of autoimmune gastritis;
- Gastric biopsy evidence
- Low acid output (raised plasma gastrin)
- Evidence of other autoimmune disease i.e thyroids
What is the treatment to pernicious anemia?
- 3-5 years for reserves to run out
- High dose replacement every week for 4-6, then 3 monthly top up.
- Intramuscular
Monitor;
- B12
- Heamoglobin and reticulocyte response
- Resolution of neurological symptoms
If someone has mutliple resections on their small bowel what is some important considerations?
B12 and bile absorption may become impaired;
- Secretory Diarrhoea, high fecal fat b/c bile (impaired fat absorption)
- Low Hb and B12
- Tiredness and short of breath (Anemic)
Where does a partial gastrectomy take place?
Bottom of stomach therefore there is a loss of key cells in antrum and possibly pylorus.
What cells are lost in gastrectomy and what are the consequences?
No G cells = low gastrin
- Reduced acid secretion, difficulty releasing B12 from food
- Reduced pancreatic secretion (Gastrin plays role in pancreatic enzyme secretion)
No pylrous - Bile reflux from small intestine
What does bile reflux from small intestine lead to?
- Bile reflux causes atrophic gastritis (body atrophies)
- Atrophic gastritis leads to loss of parietal cells and IF secretion therefore no B12 absorption
Where is iron absorbed?
Proximal SI
