B12 absorption and Perncious Anaemia Flashcards
Describe the process of folate activation
In cells, folate is trapped in its INACTIVE form
To activate folate, B12 removes and keeps the methyl group, which activates B12
Both the folate co enzyme and B12 coenzyme are now active and availibale for DNA synthesis
Dietary sources of B12
Animal sources
produced by bacteria
- Animals eat the bacteria from plants/soil etc and they utilise the B12 and then we eat the meat and ingest B12
Who is at risk of B12 def
Vegan and strict vegetarians
Older people (poor diet)
Long term meds (metformin - used in diabetes)
Describe detailed process of B12 abs
Lecture Slide
Eat B12 with animal protein, complexed with protein it enters the stomach
HCl activates pepsin (gut secretes HCL and pepsin because pepsin breaksdown protein and B12 is released)
B12 then binds with an R protein, can come from salvia and gastric juices.
B12+ R protein enters the duodenum and pancreatic enzymes (proteases) cleave B12 from R protein
Intrinisitic factor released in stomach, flows into duodenum and binds with free B12
B12+IF gets into gut enterocyte in terminal ilieum. In the enterocyte the B12 is released from IF, B12 goes across basolateral membrane into the blood and is bound to transcobalamin (B12 becomes coalamin)
20% is transcobalamin goes into tissue cells where it is used in methylation and 80% will go into enteroheaptic recicurlation (taken back to liver and secreted with bile as B12+R into small intestine)
What does B12 def look like
because it is required in the methylation pathway in the production of new cells, the first biomarker for B1 stats is changes in what RBCs look like
Macrocyctic anaemia and Neuropathy (sub-acute combined degeneration of the spinal chord)
How to diff iron def vs b12 on slide
measure the mean cell volume of an RBC To differentiate between B12 anaemia iron deficiency anaemia etc.
CASE:
Symptoms:
Tired, diff concentrating over 6 months, weight loss, diarrhoea, increasing shortness of breathe, pale
Lab:
LOW haemaglobin
MCV HIGH
Reticulocytes LOW
Platlet, WBC NORMAL
Blood smear: hypersegmented neutrophils
EXPLAIN these symptoms and lab results in term of B12 Def
Severe Anaemia: Low blood count
Low reticulocytes: Made to replace the blood you have lost (step before full RBC)
This implies that the BM is unable to respond to the usual stim of anameia SO might not have the substances to make (eg B12)
Requirements for normal RBC production = iron, folate, B12
- Iron and folate were normal and B12 was low so this explains the non specific symptoms
Reasons for low B12?
- Diet
(lacks meat, cheese, fish, eggs) - Failure of abs
- ? Over use of PPI - Requirements for B12 abs
- Normal acid secretion
- Normal IF
- Normal Pancreatic secretion
- Normal ileal abs function
when is B12 def a gastric or small intestine problem?
Stomach:
-Lack of intrinistic factor (eg pernicous anemia) is an autoimmine disorder where the person has AA against IF and parietal cells
- not enough IF to bind to B12 which means B12 cant be abs later on in the small intestine
Small intestine problem
- B12 binds to IF but is not abs in small intestine
-eg surgery to removal terminal ileum, Crohns causing inflam of terminal ileum
How to diagnose pernicious anameia
AA on blood test
- AA to parietal cells or AA to IF (if IF AA are NEG then HIGLY UNLIKELY to be pernicious anaemia)
Evidence of autoimmune gastritis
- Evidence of autoimmune gastrirtis on gastric biopsies
- Evidence of low acid output (raised plasma gastrin)
- Evidence of other AID dieases (e thyroid)
B12 def treatment and monitoring
Need high dose to replace: 1000mcg every week for 4-6 weeks then maintaince of 1000mcg every 3 months
This is parenteral (intramuscualr) because of impaired abs by GI tract
Monitor:
Check B12 levels (every 6-12 months)
Increase in Hb and reticulcyte response
Resolution of neurlogical symptoms
B12 and small bowel
why does it need B12
Needed it for maintaining cell turnover for replication
After 1-2m of replacement therapy, the overall intergrity of the small bowel mucosa improves and the function returns to normal
Effects of terminal ileum removal on B12
terminal ileum abs B12 and therefore the loss of these receptors on terminal ileum causes B12 and Bile salts unable to be abs.
Bile salts are therefore lost through the colon and this has an irritant effect on the colon -secretory diarrhoea
Impaired fat abs due to reduced bile salts
Why is there Low B12 after partial gastrectomy
No antrum, No G Cells (low gastrin)
Low gastrin causes
1. reduced gastric acid secretion (low acid = diff releasing B12 from food)
2. Reduced pancreatic secretion (gastrin plays a role in stimulating pancreatic enzymes)
No Plyorus (bile reflux from small intestine)
- Bile reflux causes atrophic gastritis (degenretion of stomach)
- atrophic gastritis causes loss of parietal cells and loss of IF secretion
Why is there low B12 in celiac disease
Loss of small bowel villi (mainly proximal part -jejnum)
Causing loss of endocrine cells that secrete secretin and CCK
Other causes of low B12
- Terminal ileum inflam (crohns)
- Bacterial overgrowth (bacteria in small intestine use B12 and IF)
- Chronic pancreatitis (pan needed to release proteases)
- Total gastrectomy (weight loss procedures as well)
- Some drugs - metformin
Schilling test
-what is it
-purpose
-process and resutls
-disadvantages
Radioisotope test
Determine if lack of IF
Oral radioactive B12 is given then IM infection of non radioactive B12 is given to saturate B12 binding proteins and to flush out Co-B12.
Urine is collected for 24hr
NORMAL: will excrete >10% of oral dose because all the B12 sites are bound
if <10% then repeat the test
If now normal then Dx is pernicios anameia or gastroceomy
if still abnormal the lesion must be in terminal ileum or bacterial overgrowth.
Drawbacks
- time consuming
-uses radioisotopes
- collection of urine
- results are challenging to intrepret
