Lecture 10 Flashcards Preview

Digestive System Module > Lecture 10 > Flashcards

Flashcards in Lecture 10 Deck (28):
1

Case 1: 45-year-old teacher. Tiredness, difficulty concentrating over 6 months. Weight loss and diarrhoea. Increasing shortness of breath on exertion. Examination was normal. Blood tests:
Haemoglobin 45 g/L (125-170)
Mean cell volume 115 (80-100)
Platelet count 253 (150-400)
White blood cell 5.5 x 10^9 (4 – 11)
Reticulocytes 5 x 10^9 (10-100)
Blood film – hypersegmented neutrophils present

Severe anaemia (due to low Hb)
Explains shortness of breath and tiredness
Low reticulocytes (abnormally abnormal)
Implies that the bone marrow is unable to respond to the usual stimulus of anaemia to increase reticulocytes in circulation . suggests a deficiency/impariemnt in bone marrow to make more RBC
Requirements for normal erythropoeisis are iron, folate, B12
Iron and folate were normal
Serum B12 very low - explains tingling in fingers, concentration problems – also explains raised MCV - macrocytosis

2

Potential explanation for shortness of breath and tiredness

Severe anemia
-symptoms that are commonly associated

3

Potential reason for having low reticulocytes

Implies that bone marrow is unable to respond to the usual stimulus of anaemia
-normally Bone marrow would respond to low RBC count by increasing its production/release of reticulocytes (immature RBC) to increase RBC count in circulation

4

What could be a result of having a very low serum B12?

Explains tingling in fingers + concentration problem
-also explains raised MCV - microcytosis

5

What could be the reasons for patient 1 to have low B12?

Need to understand many aspects of gastrointestinal physiology

Requirements to absorb B12:
1. Normal acid secretion
2. Normal intrinsic factor*
3. Normal pancreatic secretion
4. Normal ileal absorptive function*

* Most important factors

6

Absorption of B12

1. Gastric acid releases food-bound B12
2. B12 needs to bind to intrinsic intrinsic factor for absorption by specialised receptors in terminal ileum
3. Binding of B12 to intrinsic factor can be interfered with by other proteins
-R-binders (secreted in saliva and in stomach) bind to B12 in the stomach
-Pancreatic enzymes then help release B12 from R-binders to allow binding with intrinsic factor in small bowel

7

What could be reasons for having a stomach problem?

Lack of intrinsic factor due to pernicious anaemia
Autoimmune disorder with antibodies against intrinsic factor and parietal cells (making antibodies against own body cells)-cuasing inactive/distruction
Not enough intrinsic factor to bind to B12, which means B12 cannot be absorbed later on in the small intestine

8

What could be the reason for having small intestinal problem?

B12 binds to intrinsic factor normally but is not absorbed in small intestine
e.g. surgery to remove terminal ileum(surgery), e.g. Crohn’s disease causing inflammation in the terminal ileum

9

Shilling test Generally

Radioisotope test
Used to determine if patient has lack of intrinsic factor
Rarely used in clinical practice these days
Historical interest
-time consuming

10

Principles of Shilling Test

1. Oral Radioactive B12 given
2. Then IntraMuscular injection of Non-radioactive B12 is given - to saturate B12 binding proteins and to flush out Co-B12
3. Urine is collected for 24hrs (radioactive compoenent will be in urine)
4. Normal: person would excrete >10% of oral dose
5. If Abnormal:

11

Disadvantages of Shiling Test:

Time consuming
Involves radioisotopes (not popular with younger patients)
Requires collection of urine (24hrs)
Results can be difficult to interpret – the distinction between ileal and gastric disease not clear-cut

12

Evidence of Pernicious anaemia and Autoimmune Gastritis

1. Antibody blood test - most easily accessable and performed
a) Antibodies to intrinsic factor - very specific test- if positive test = 100% have pernicious anaemia. But not a very sensitive test= doesnt show up in all pernicious anaemia patients
b) Antibodies to parietal cells -present in both pernicious anaemai and health patients. Neg test= No p. anaemia. Pos test = healthy or p. anaemia
Evidence of autoimmune gastritis on gastric biopsies (histological evidence. autoimmune gastritis classically associated with p. anaemia. Not needed for diagnosis but if present indicates pernicious anaemia)
Evidence of low acid output (raised plasma gastrin to lower pH)
Evidence of other autoimmune disease (e.g. thyroid disease) Autoimmune diseases tend to occur together

13

Treatment for Pernicious anaemia + autoimmune gastritis

Depleted large reserves have taken 3-5 years to “run-out”
Need high doses to replace – regular 1000 mcg every week for 4-6 weeks then maintenance of 1000 mcg every 3 months
-sometimes dietary, therefore doesnt need long term
-but pernicious anaemia is chronic therefore requires longterm maintainance
Parenteral (intramuscular) - because of impaired absorption by the GI tract (due to lack of intrinsic factor)
Monitor response to B12 replacement
Check B12 levels
Increase in haemoglobin / reticulocyte response
Resolution of neurological symptoms

14

Case 2: 41-year-old male. Presented with tiredness and breathlessness. Found to have iron deficiency anaemia. Diagnosis of carcinoma of the caecum. The cancer was resected. Removal of right side of the colon and 40 cm of distal ileum.

One year later – symptoms of bowel obstruction. Had excision of 20 cm of ileum. Presented 12 years later with symptoms of bowel obstruction again. Found to have narrowing at the anastomosis – further resection – another 25 cm of ileum. He developed significant diarrhoea after the last operation – bowel motions 5 times per day. One year later presented with tiredness. Found to have low Hb of 69 g/L and low B12. Faecal fat was high

15

Effects of Distal Ileal Resection

Loss of specialized receptors on terminal ileum leads to:
Failure to absorb B12 (lost receptors)
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 salts

16

Case 3:

60-year-old presented with tiredness
Mild anaemia
Low iron stores + feratin
Low B12
Low vitamin D
Past history: Bleeding duodenal ulcer at age 25
Operation – partial gastrectomy

17

Partial Gastrectomy

1. Billroth I Distal Gastrectomy
-distal antrum and beginning duodenum removes. 2x ends directly bought together. Common bile duct + pancreatic duct left inside tube
2. Billroth II Distal Gastrectomy
-distal antrum and beginning duodenum removes. Sown shut. "blind loop". Jejunum sown to stomach. PAncreatic juice and bile from bile duct have to flow further to join chyme

18

Reasons for Low B12 after partial Gastrectomy

No antrum, no G cells – low gastrin
Low gastrin leads to:
Reduced gastric acid secretion
Low acid – difficulty releasing B12 from food
Reduced pancreatic secretion
Gastrin plays a role in stimulating pancreatic enzymes - less removal of B12 or Rproteins
No pylorus – bile reflux from small intestine (no sphincter to stop)-
Bile reflux causes atrophic gastritis i.e. body of stomach atrophies (inflammed and degenerates)
Atrophic gastritis – loss of parietal cells – loss of intrinsic factor secretion

19

What are some additional causes of low B12?

Coeliac disease
Terminal ileal disease e.g. Crohn’s
Bacterial overgrowth(esp if had surgery)
B12 and B12/intrinsic factor complex utilised by intestinal bacteria
Chronic pancreatitis
Total gastrectomy – also weight-loss procedures
Some drugs - omeprazole, metformin

20

Structure of Vitamin B12 Cobalamin

Corrinoid ring (4x pyrrole rings)
Cobalt atom in centre
2x froms in body:
1. Methylcobalamin
2. 5-deoxyadenosial cobalamin (involved in Kreb/citric acid cycle)

21

Methylation Cycle

B12's important in the cycle + B12's relationship with Folate(always combined)-work synergistically in methylation pathway
B12 functions mainly as a co-enzyme in the methylation pathway (helps donation of methyl group by attaching itself to the methyl group, allowing conversion of homocytseine to methionine and back) + (release of Folate from 5 methyl THF to Folate

22

Folate

In cells Folate is trapped in inactive form
To activate folate, Vitamin B12 removes and keeps the methyl group, which activates B12
Both the folate co-enzyme and the Vitamin B12 co-enzyme are no active and available for DNA synthesis
-therefore conditions resulting deficiency in EITHER B12 or folate will have very serious impact on body re ability to produce new cells or produce in-effected/disaffected cells (normal healthy cellular growth and metabolism)

23

B12 sources

Dietary sources only
Vitamin B12 is made by bacteria
-get from contamination of food sources (typically eaten of ruminant sources foods)
-rumin ferments the products of plants that cows eat which is high in B12
Natural B12 sources: eggs, meat (high), poultry, shellfish, milk and milk products
B12 added to: fortified grain products e.g. cereals amd bread
RDI for B12= 2.4 micrograms /day
-tiny amounts daily as very good at conserving and storing in liver (several years worth stored)

24

Who are at risk of primary B12 deficiency?

Vegans and strict vegetarians
-little dairy or low animal products
-high rates of B12 deficiency of Woman, and woman of asian and indian woman
-some groups at higher risk of becoming B12 deficient
-higher secondary B12 deficiencies in NZ (not primary seen that much)

25

Vitamin B12 absorption

Number of diseases can impact on our ability to absorb B12 and hence some people are more/less vulnerable to B12 deficiency than others
1. Eat protein rich foods (dairy, meat) containing Cobalamin
2. CBl.P needs to be released from the Protein.
Cbl cannot travel alone through stomach, must be attached to something/another protein
HR is secreted by gastric parietal cells and salivary glands
3. Once in duodenum, Pancreatic proteases (from pancreas) release CBl from R protein
7. Good at both Storing B12 in liver + Recycling B12 in bile. Therefore we only need small amounts on a daily basis

26

Deficiency of Vitamin B12

1. Pernicious/Macrocytic(large cell) Anaemia. seen clinically
Normal blood cells: The normal size, shape(even and concave) and colour of the BC
BC of pernicious anaemia (Megaloblastic)
-Megalobastic blood cells are 1. slightly larger than normal RBC and have 2. Irregular shapes (due to poor DNA production and lack of methylation)
-film is the same as would be seen with someone with a folate deficiency
-different anaemia than iron deficiency: Microcytic anemia (small cell aneamia)
2. Neuropathy: sub-acute combined degeneration of the spinal cord (?from build up of SAM (s-adenosa myethylone seen in methylation cycle) -not seen in folate deficiency

27

B12 Supplementation

Vegans (as dont get it in diet)
(not good sources of B12
have B12 in its active form (pseudo vitB12))
Malabsorption syndromes:
-pernicious anaemia usually treated with intramuscular injections
- because if you cant absorb B12 you need to be able to source it from intramuscular injection

28

Spirulina and seaweed

not good sources of B12
have B12 in its active form (pseudo vit. B12)
-if you cant absorb B12 you need to be able to source it from intramuscular injection