Normal function and Malabsorption

Question 1

What are the 3 regions of the primitive gut tube that gives rise to the organic of the GI tract?

Answer 1

Foregut
- pharynx to proximal of duodenum
- includes the liver, gall bladder and pancreas
Midgut
- distal half of duodenum to proximal 2/3 of transverse colon
Hindgut:
- distal 1/3 of transverse colon to rectum
- includes urogenital sinus

Question 2

The persistence of Vitelline duct results in what condition?

Answer 2

Merkel’s diverticulum

Question 3

What protein is required for the normal formation of enteral ganglia?

Answer 3

RET protein (receptor tyrosine kinase) 
- mutations of this results in Hirschsprung's disease

Question 4

What are parietal cells?

Answer 4

Epithelial cells that secrete hydrochloric acid, found in the gastric glands in funds and cardia of stomach

Question 5

What controls the secretion of HCl?

Answer 5

Cephalic phase

• sight / taste / smell of food triggers this phase
• postganglionic cholinergic fibres of vagus nerve releases acetylcholine / serotonin which then stimulate mast cells to produce histamine
• ~30% total HCl released

Gastric phase

• food ingestion / astral dilation / intragastric protein / pH > 3 stimulate secretion of gastrin from antrum of stomach and results in increased acid production
• ~50-60%

Intestinal phase

• chyme arriving at duodenum results initially increases acid secretion then it inhibits it by stimulating sympathetic neurone and increasing duodenal enteroendocrine cells to release secretin and cholecystokinin
• reduces gastric mobility too

Question 6

What does the gastric chief cells secrete?

Answer 6

Pepsinogen and gastric lipase

Question 7

What does sucrose (disaccharides) get hydrolysed to?

Answer 7

Glucose and fructose

Question 8

What does lactose (disaccharides) get hydrolysed to?

Answer 8

Glucose and galactose

Question 9

What are fat soluble vitamins?

Answer 9

Vitamin A, D, E and K

• dependent on micellar solubilisation (i.e adequate bile production)
• vit A and D require hydrolysis by pancreatic enzymes before absorption

Question 10

What is the most sensitive test for carbohydrate malabsorption?

Answer 10

Breath Hydrogen testing

• released by fermentation of unabsorbed carbohydrate in the colon by intestinal bacterial flora
• most common indication: lactose malabsorption
• also used for sucrose / fructose malabsorption
• screening for intestinal bacterial overgrowth
• useful for measuring intestinal transit time

Question 11

What is the preferred method of assessing protein-losing enteropathy in children?

Answer 11

Alpha-1 antitrypsin clearance

• compare serum level and level from stools (24hr collection)
• clearance value can then be calculated
• • alpha-1 antitrypsin is similar molecular weight to albumin and resistant to digestion in GI tract**

Question 12

What are the chances of first degree relatives having Coeliac’s disease?

Answer 12

10% in 1st degree
30-40% in HLA identical siblings
60-70% concordance in identical twins

Question 13

What is the chance that someone has coeliac’s disease if HLA D2 / D8 are negative?

Answer 13

Very very low!

Only 1% of people of coeliac’s disease will have negative HLA DQ2 or DQ8

Question 14

What is coeliac disease?

Answer 14

Autoimmune (T-cell immune response) disease resulting in enteropathy

• Essential immunological event is blinding of gliadin by HLADQ2 molecule for antigen presentation to TH1 cells
• i.e type IV hypersensitivity

Question 15

What is abetalipoproteinaemia?

Answer 15

Rare, autosomal recessive disorder that results in lack of apolipoprotein B so TAG’s can’t be packaged into chylomicrons –> low VLDL and LDL’s in blood

• results in severe malabsorption from birth
• FTT
• assoc with peripheral neuropathy from Vit E deficiency, intellectual impairment and cerebella ataxia
• atypical retinitis pigmentosa from adolescence

Rickets may be unusual initial px caused by steatorrhoea induced calcium losses and vit D deficiency

Question 16

What is cystinuria?

Answer 16

Relative common, autosomal recessive disease, characterized by high concentrations of the amino acid cysteine in the urine, leading to the formation of cystine stones.

• dx must be excluded in anyone with renal stones
• check urinary cystine

Question 17

What is glucose-galactose malabsorption?

Answer 17

Rare, autosomal recessive disease due to defect in sodium-glucose cotransporter gene (SGLT1) resulting in osmotic diarrhoea from birth and can cause death from dehydration.
Glycosuria often present even though BSL low.
Stools are acidic / positive for reducing substance
Breath hydrogen test positive
Manage by restricting glucose and galactose, fructose is safe

Question 18

What’s the most common cause of malabsorption in children?

Answer 18

Lactase deficiency

Question 19

What is intestinal lymphangiectasia?

Answer 19

Protein losing enteropathy due to dilation of intestinal lymphatic vessels.
Elevated Faecal alpha-1-antitripysin level will be consistent with protein losing enteropathy
Small bowel biopsy is diagnostic

Question 20

What causes intestinal lymphangiectasia?

Answer 20

Primary
- assoc with turners and noonans
Secondary
- Chronic R) heart failure, constrictive pericarditis
- disturbance to lymphatic system from surgery / obstruction from malrotation or retroperitoneal tutor

Question 21

What are the symptoms / signs of intestinal lymphagiectasia?

Answer 21

Steatorrhoea
Low alb and generalised oedema
Recurrent infections due to low IgG and lymphocytopenia (leakage of lymphocytes into gut)
Chylous ascites

Question 22

What is microvillus inclusion disease?

Answer 22

Rare malabsorption disorder that seems to be inherited in an AR pattern.
Most common cause of persistent diarrhoea (intractable watery) that begins in neonatal period.
Pathology includes
- Villous atrophy
- crypt hypoplasia
- microvillus inclusions in enterocytes and coloncytes
Managed to octreotide (somatostatin analogue) to reduce volume of stools
Needs lifelong TPN / intestinal transplant

Question 23

What is tufting enteropathy?

Answer 23

AR disorder resulting in intestinal epithelial dysplasia
- symptomatic with watery diarrhoea
- present in first few weeks (not like microvillus inclusion disease where it is present immediately after birth
Found in middle eastern population - esp island of Gozo in Malta
Needs lifelong TPN / intestinal transplantation

Question 24

What is the energy of fat / protein / carbohydrate?

Answer 24

Fat 10kcal/g
Protein 4kcal/g
CHO 4kcal/g

Question 25

What is absorbed in the duodenum and the proximal jejunum?

Answer 25

Calcium, magnesium, phosphorous, iron and folic acid

Question 26

What is absorbed in the proximal 100-200cm of small bowel?

Answer 26

Carbohydrate, protein, water soluble vitamin

Question 27

What is absorbed throughout small intestines?

Answer 27

Monoglycerides, fatty cards and MCT

Question 28

What is absorbed in the distal ileum?

Answer 28

Vitamin B12 and bile acids

Question 29

What is absorbed in the colon?

Answer 29

Water and electrolytes

Question 30

Why does renal stones occur with malabsorption?

Answer 30

When there is large amounts of unabsorbed fat available, calcium binds to fat instead of oxalate. Increased oxalate is then absorbed and excreted in renal tract

Question 31

How to test for fat absorption?

Answer 31

Fat balance studies (not diagnostic) Done over 3 days and have to measure fat intake also to calculate % with below formula - [fat intake - (faecal fat losses / fat intake] x 100 Useful in monitoring enzyme replacement therapy in CF

Question 32

What investigations are available for exocrine pancreatic function?

Answer 32

Faecal elastase - stable endoprotease unaffected by exogenous pancreatic enzymes - Does lack full differentiation between primary exocrine pancreatic insufficiency vs exocrine pancreatic dysfunction secondary to intestinal villous atrophy (reduced pancreoenzyme / cholecystokinin secretin leading to pancreatic insufficiency) - false positive in acute diarrhoea Serum tyrinsinogen - raised in CF early in life then gradually falls - Levels in shwachman-diamond syndrome is low

Question 33

What will the histology of coeliac disease look like?

Answer 33

Loss of absorptive villi Hyperplasia of crypts Presence of lymphocytes **injury greatest in proximal small bowel**

Question 34

What are the differential diagnoses for intestinal villi atrophy?

Answer 34

``` Small intestinal lymphoma Crohns Eosinophilic gastroenteritis Giardia Tropical sprue Whipple disease ```

Question 35

What is tropical sprue?

Answer 35

Major cause of malabsorption / endemic in South India, Phillipines, Islands in Caribbean Follows outbreak of acute diarrhoea illness and improves with antibiotics Sx: fever / malaise / followed by watery diarrhoea then 1 week later, sx resolves then develops anorexia / chronic absorption O/e: glossitis, stomatitis, cheilosis, night blindness, oedema To prevent occurrence: 6m therapy with oral folic acid and tetracyclines or sulphonamides

Question 36

What is whipple disease?

Answer 36

Chronic systemic infectious disorder secondary to Tropheryma whippelii (gram positive bacterium) which can be cultured from a lymph node in involved tissue Presents with diarrhoea / abdo pain / weight loss / joint pain Associated with malabsorption / lymphadenopathy / skin increased pigment and neurological changes

Question 37

What % of small bowel loss will result in malabsorption?

Answer 37

50% NB: typical length of small bowel - neonate: 200-300cm - adult: 600-800cm

Question 38

What are the causes of malabsorption in short gut syndrome?

Answer 38

``` Reduced surface area Rapid transit Suboptimal bowel function Acide hypersécrétion Bile acid deficiency Bacterial overgrowth - injury intestinal mucousa further ```

Question 39

What are the clinical features of short gut syndrome?

Answer 39

FTT Steatorrhoea Hyponatraemia, hypokalaemia Acidosis with anions gap in absence of elevated serum lactate (bacterial overgrowth can cause malabsorption and metabolic acidosis secondary to bacterial production of D-lactate which can't be metabolised by humans and not measured by lab)

Question 40

What is the prognosis of short gut syndrome?

Answer 40

Can usually come off TPN - >25cm small bowel and intact ileocecal valve - >40cm w/o IC valve (ileocecal valve resection results in greater tendency to bacterial overgrowth and subsequent mucosal damage) Small bowel bacterial overgrowth has been associated with prolonged dependence on TPN

Question 41

What are complications of short gut syndrome?

Answer 41

``` FTT Water / sodium depletion Nutrient deficiencies Renal stones Gallstones Liver disease Late VB12 deficiency D-lactic acidosis ```

Question 42

What are the differences between fat globules and fat crystals?

Answer 42

Fat globules = problem with digestion (problem with pancreatic enzymes or bile salts) Fat crystals = problem with absorption = (mucosal abnormality)

Question 43

What are the differentials for malabsorption?

Answer 43

Can be divided into: - Lumen - Cell related: Reduced integrity of mucosa, Enzyme deficiency, Transport defects, Substrate overload, Immune related, Altered secretory function - Lymphatics - Structural

Question 44

What are luminal causes of malabsorption?

Answer 44

``` Exocrine pancreatic insufficiency - CF - Schwachman-Diamond syndrome - Johansson-Blizzard syndrome - Chronic pancreatitis Bile acid disorder - Chronic cholestasis - Terminal ileum resection - Bacterial overgrowth - Primary bile acid malabsorption ```

Question 45

What are the causes of reduced integrity of mucosa that can lead to malabsorption?

Answer 45

- infection / post-infection - cow's milk intolerance - coeliac disease - IBD - Tufting enteropathy

Question 46

What are causes of enzyme deficiency that can lead to malabsorption?

Answer 46

Lactase deficiency Sucrase-isomaltase deficiency - primary disaccharide deficiency **sucrose is not a reducing sugar so is clingiest negative unless you add HCl Hereditary fructose intolerance - primary monosaccharide issue secondary to deficiency in 1, 6 bisphonate aldolase - early clinical manifestation resembles galactossaemia w jaundice, hepatomegaly, vomiting, lethargy, irritabliliy and convulsions Enterokinase deficiency - Trypsinogen can't turn into trypsin and in turn, can't active other proteases or cleave cocolipase --> collapse - presents really unwell in early infancy with severe diarrhoea and FTT - Treat with pancreatic enzyme replacement

Question 47

What are transport defects that can cause malabsorption?

Answer 47

Glucose-galactose malabsorption - Abnormality in the Na-glucose co-transporter - affects GIT > renal - positive reducing sugars - can result in low BSL / dehydration - treat with fructose based formula ``` Chloride-losing diarrhoea - severe watery diarrhoea - presents with alkalosis, hypochloraemia, hypokalaemia - potentially fatal Sodium diarrhoea - Na/H exchanger defect - met acidosis, hypoNa - associated with polyhydramnios Acrodermatitis enteropathica ``` Amino acid transport defects - Hartnup disease (malabsorption of neutral amino acid including tryptophan which is a precursor for serotonin, melatonin, niacin; symptomatic with photosensitive pellagra-like rash, headaches, cerebellar ataxia, dev. delay, diarrhoea) - Methionine malabsorption (purple, red-brown coloured urine with cabbage odour; symptoms include white hair, near signs, diarrhoea) - Blue-diaper syndrome (malabsorption of tryptophan and results in bluish discolouration in nappy) Abetalipoproteinaemia Microvillus inclusion disease

Question 48

What are immune-related causes for malabsorption?

Answer 48

Autoimmune enteropathy CVI / AIDS / IgA deficiency Eosinophilic gastroenteropathy