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Digestive (Lecture 10): Vitamin B12 Deficiency Flashcards

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6844798064What does low erythrocytes mean?It implies that the bone marrow is unable to respond to usual stimulation of anaemia. Therefore what the BM needs to produce RBC is deficient. Erythropoiesis requires 1) Iron 2) Folate 3) B120
6844801957What is required for Erythropoeisis?Erythropoiesis requires 1) Iron 2) Folate 3) B121
6844808207What is the Structure of vitamin B12?Corrinoid ring (4 pyrrole rings)2
6844811975Describe how B12 works in the methylation cycle.We require B12 to be a co-factor for MS to make Homocysteine into methionine, which then can become SAM. SAM is a universal methyl donor.3
6844813573What works very close with B12?Folate4
6844814982What are the 2 major functions of the B12 vitamin?1) Co-factor for the methyl donation. Methylation cycle is then important for the production of DNA-> cells (e.g. RBC) 2) Release folate trapped in its inactive form.5
6844816489What can B12-deficiency sometimes mask?Folate deficiency.6
6844826067Describe how B12 releases folate1) Folate is methylated, therefore trapped in its inactive form. 2) To activate folate, vitamin B12 removes and keeps the methyl group (that was on the folate) which activates vitamin B12 3) Both the folate coenzyme and the vitamin B12 coenzyme are now active and available for DNA synthesis.7
6844833098Where do we get B12?Animal sources (Vitamin B12 is made by bacteria) e.g. meat e.g. eggs8
6844834777What is the recommended dietary intake for B12?2.4 micrograms (we are good at storing B12)9
6844835128Who are at risk for B12 deficiency?1) Vegans 2) Strict vegetarians10
6844871426What can go wrong for a person to be B12 deficient (in the B12 absorption cycle)1) People who don't secerete enough Haptocorrin. 2) Damage to stomach- don't secrete enough Intrinsic Factor 3) Not enough pancreatic protease.11
6844837029How is the B12 absorbed in the body?1) Eat food containing B12 e.g. meat -Cobalamin is still bound to protein 2) When Cbl-P it gets into our stomach, Cbl is released from the protein by pepsin 3) The Haptocorrin (HC) binds to Cbl which is secreted in gastric parietal cells and in the saliva. -This protects it from the acid secretion of the stomach. 3) HC.Cbl goes into the duodenum, and the pancreatic protease degrades it. 4) Intrinsic factor then binds to Cbl. (released from gastric parietal cells) 5) Needs to travel to the Distal Ileum before it is absorbed. The brush border receptors for IF allow the transport of the IF.Cbl into the enterocyte. At the same time Cbl is released from the IF. --two transport proteins the Cbl can now bind onto--- 6a) 80%- bind to the Hc.Cbl (haptocorrin) - Taken back up by the liver. (recycled in the bile)- enterohepatic circulation 6b) 20% bind to TC.Cbl (transcobalamin) - Go to cells to produce DNA -Incorporated into the methylation cycle.12
6844874794Where does the IF bind to the Cbl?Duodenum13
6844880110What are Enterocytes?Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells found in the small intestine.14
6844891412How do we test for Deficiency of Vit B12?Blood tests (Megaloblastic anaemia) -People with Vit B12 deficiency tend to have enlarged RBC (megaloblastic blood cells) -RBC shape also are slightly irregular. -Also show neuropathy- subacute combined degeneration of the spinal cord. (Folate deficiency also shows megaloblastic blood cells)15
6844894212What is Megaloblastic anaemia?Anaemia due to poor production of DNA due to deficiency of Vit B12.16
6844899317What are similarities and differences between Folate and B12 deficiency?Both show Megaloblastic RBC However, people with B12 deficiency also show neuropathy. -Sub-acute combined degeneration of the spinal cord- from build up of SAM17
6844910709How do we treat people with B12 deficiencies?Vegans: Take supplementations or fortified foods (e.g. soy milk). Malabsorption syndromes (e.g. pernicious anaemia) are treated with intra-muscular injections.18
6844917905What are some symptoms of B12 deficiency? (case 1) -Clinical -Blood test -Blood filmClinical -tiredness -difficulty concentration -weight loss -diarrhoea -shortness of breath on exertion Blood test -Low haemoglobin -Increased mean cell volume -Normal folate and iron. Blood film -Hypersegmented neutrophils (not always present)19
6844921588What does elevated mean cell volume indicate?The size of the RBC is large. (Macrocytosis)20
6844953486What are the requirements to absorb B12?1) Acid to release food-bound cobalamin -gastric acid releases food-bound B12 2) Secretion of intrinsic factors from healthy parietal cells * -IF binding to B12 critical for absorption by specialized receptors in terminal ileum -Binding of B12 to IF can be interfered with by other proteins 3) Normal pancreatic secretion -Pancreatic enzymes help to release B12 for binding with IF- in the small bowel 4) Normal Ileal function * * most important21
6844954045What is another name for Vit B12?Cobalamin.22
6844967529What is a test that isn't used any more to test for B12 deficiency?Schilling's test. -It uses radioactive isotopes -Time consuming -Difficult to interpret results23
6844970883What is the most likely diagnosis for Case 1? (tired, weight loss, macrocytosis of RBC etc.)Pernicious anaemia related to auto-immune gastritis24
6844974118What should we look for, to find the cause of Pernicious anaemia?Auto-immune gastritis. -Antibodies to parietal cells -Antibodies to intrinsic factor -Evidence of other auto-immune disease e.g. thyroid disease. - Evidence of autoimmune gastritis on gastric biopsies - Evidence of low acid output (raised plasma gastrin)25
6844974119What is Pernicious anemia?Pernicious anemia is defined as a type of vitamin B12 deficiency that results from impaired uptake of vitamin B-12 due to the lack of a substance known as intrinsic factor (IF) produced by the stomach lining. Often related to auto-immune gastritis, where the person has -Antibodies to parietal cells -Antibodies to intrinsic factor -Evidence of other auto-immune disease e.g. thyroid disease. - Evidence of autoimmune gastritis on gastric biopsies - Evidence of low acid output (raised plasma gastrin)26
6844984901What is the treatment for pernicious anaemia?If due to diet: -Just 3x oral doses and supplements -No need for maintenance ---------- If due to Malabsorption: -Need high doses to replace - 1000 mcg every week for 4-6 weeks then maintenance of 1000 mcg every 3 months. -These need to be Parenteral (intramuscular) - because of impaired absorption by the GI tract - Monitor response to B12 replacement 1) Check B12 levels 2) Increase in haemoglobin / reticulocyte response 3) Resolution of neurological symptoms27
6844993792Case 2: -Came in with Caecum cancer -Removed overall 85cm of the ileum -Now developed significant diarrhoea and bowel motions occur 5 times a day. -One year later he has extreme tiredness What are we likely to observe after doing a stool test and a blood test?1) Low Hb g/L 2) Low B12 3) High faecal fat content (because, Bile salts are absorbed in the terminal ileum, so lack of bile salt absorption results in lack of fat break down and absorption)28
6844996930How long does it take for our B12 reserve to 'run out'3-5 years29
6845001811What are some consequences of distal ileal resection?Loss of specialized receptors on terminal ileum leads to: - Failure to absorb B12 - Failure to reabsorb bile salts • Bile salts are instead lost through the colon • Irritant effect of bile salts on colon - secretory diarrhoea • Impaired absorption of fat because of reduced bile salts30
6845004154Why might someone have diarrohea due to Ileal resection?Loss of specialized receptors on terminal ileum leads to: - Failure to reabsorb bile salts • Bile salts are instead lost through the colon • Irritant effect of bile salts on colon (secrete fluids and electrolytes) - result in secretory diarrhoea31
6845006824What is Ileal resection?Ileocecal resection is the surgical removal of the cecum along with the most distal portion of the small bowel—specifically, the terminal ileum (TI). This is the most common operation performed for Crohn disease, though other indications also exist32
6845007993What is Crohn's diseaseCrohn's disease is a condition which causes swelling, thickening and inflammation of the digestive system. It is one of a group of diseases called inflammatory bowel disease.33
6845010535What is another name for Iron?Ferritin Fe34
6845012523What are the two types of Partial gastrectomys1) Billroth 1 -Second part of stomach is removed -Proximal part of duodenum is sutured into the stomach 2) Billroth 2 -Part of the small bowel distally is sutured back into the stomach.35
6845018972Case 3: -Tiredness -Mild anaemia -Low Ferritin/iron stores -Low B12 -Low Vit D -Had a partial gastrectomy. Why might these symptoms occur together?-Due to the partial gastrectomy, the patient has no antrum, no G cells, therefore low levels of gastrin. -Low gastrin leads to: 1) Reduced gastric acid secretion (low acid- difficulty to release B12 from food) 2) Reduced pancreatic secretion (gastrin plays a role in stimulating pancreatic enzymes)-Pancreatic enzymes help to release B12 for binding with IF- in the small bowel ------------------------------ -Due to the P gastrectomy, the patient also has no pylorus, therefore is likely to have bile reflux from the small intestine. - Bile reflux can cause atrophic gastritis e.g. body of stomach atrophies -Atrophic gastritis can lead to loss of parietal cells -This therefore leads to loss of Intrinsic factor secretion -IF is essential for the uptake of B12. ----------------------------- Low Vit B12 intake can result in all the other symptoms.36
6845030295Explain why someone might have low B12 in coeliac disease-In Coeliac disease, inflammation results in loss of small bowel villi (mainly jejunal, some loss of ileal) -Loss of Endocrine cells that secrete secretin and cholecystokinin- that eventually stimulate pancreatic secretion -Pancreatic enzymes help to release B12 for binding with IF- in the small bowel37
6845030296What is coeliac diseaseCoeliac disease is a permanent intestinal reaction to dietary gluten. In coeliac disease the cells lining the small bowel (intestine) are damaged and inflamed. This causes flattening villi, which line the inside of the bowel.38

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