Lecture 10: Vitamin B12 Deficiency

Question 1

What is another name for vitamin B12?

Answer 1

Cobalamin

Question 2

Describe B12 function and role in folate activation;

Answer 2

• 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

Question 3

What is the source of Vit B12 in the diet?

Answer 3

Animals

Fortified foods (but needs to be in active form)

Made by bacteria feeding off animal proteins

Question 4

Who are at risk for Vit B12 deficiency?

Answer 4

Vegan and strict vegetarians

Question 5

Describe the process of vitamin B12 absorption;

Answer 5

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.

Question 6

What stores B12 and how much is released daily?

Answer 6

• About 1mg daily is secreted in bile (enterohepatic circulation)
• Liver stores of B12.

Question 7

What happens with B12 deficiency?

Answer 7

• Macrocytic anemia
• large irregular shape

Neuropathy? - Sub acute combined degeneration of the spinal cord, (from build up of SAM?)

Question 8

Can B12 be supplemented?

Answer 8

• Yes, Vegans
• Malabsorption syndromes i.e pernicious anemia

Usually treated with intra-muscular injections

Question 9

Would a patient notice a drop off in haemoglobin?

Answer 9

If it occurs over 6 months they would not notice it.

Question 10

What are reticulocytes and what would a large increase in them suggest?

Answer 10

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)

Question 11

Are WBC impacted in anemia?

Answer 11

Yes they are observed to be impacted in anemia, such as hypersegmented neutrophils

Question 12

What are the usual requirements for normal erythropoesis?

Answer 12

• Iron
• Folate
• B12

Question 13

What can cause low B12?

Answer 13

• Diet
• Failure to absorb
• Requirements to absorb;
• Normal acid secretion
• Normal intrinsic factor*
• Normal pancreatic secretion
• Normal ileal absorptive function*
• = Most important factors

Question 14

Describe the absorption of B12 again;

Answer 14

• 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.

Question 15

What stomach issues can caused B12 mal-absorption?

Answer 15

• Lack of intrinsic factor i.e pernicious anemia, means that B12 cant be absorbed in terminal ilium

Question 16

What is pernicious anemia?

Answer 16

Autoimmune disorder where the individual develops auto-antibodies against intrinsic factor and parietal cells.

Question 17

What small intestine problems can cause B12 deficiency?

Answer 17

• B12 binding IF normally but removal of the terminal ilium, crohns causing inflammation in the terminal ilium presents absorption form taking place.

Question 18

How can pernicious anemia be diagnosed?

Answer 18

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

Question 19

What is the treatment to pernicious anemia?

Answer 19

• 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

Question 20

If someone has mutliple resections on their small bowel what is some important considerations?

Answer 20

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)

Question 21

Where does a partial gastrectomy take place?

Answer 21

Bottom of stomach therefore there is a loss of key cells in antrum and possibly pylorus.

Question 22

What cells are lost in gastrectomy and what are the consequences?

Answer 22

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

Question 23

What does bile reflux from small intestine lead to?

Answer 23

• Bile reflux causes atrophic gastritis (body atrophies)

- Atrophic gastritis leads to loss of parietal cells and IF secretion therefore no B12 absorption

Question 24

Where is iron absorbed?

Answer 24

Proximal SI

Question 25

How can coeliac disease lead to low B12?

Answer 25

• Loss of small bowel villi
• Mainly proximal SI but in severe cases its thoughout
• Loss of endocrine cells that secrete secretin and cholecystokinin (involved in pancreatic stimulation)

Question 26

What are some other potential causes of low B12?

Answer 26

Terminal ilium inflam i.e Crohns
Bacterial overgrowth (B12 and B12/IF used by Bacteria)
Chronic pancreatitis
Total gastrectomy
some drugs i.e Omperazole and metformin