Normal function and Malabsorption Flashcards
What are the 3 regions of the primitive gut tube that gives rise to the organic of the GI tract?
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
The persistence of Vitelline duct results in what condition?
Merkel’s diverticulum
What protein is required for the normal formation of enteral ganglia?
RET protein (receptor tyrosine kinase) - mutations of this results in Hirschsprung's disease
What are parietal cells?
Epithelial cells that secrete hydrochloric acid, found in the gastric glands in funds and cardia of stomach
What controls the secretion of HCl?
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
What does the gastric chief cells secrete?
Pepsinogen and gastric lipase
What does sucrose (disaccharides) get hydrolysed to?
Glucose and fructose
What does lactose (disaccharides) get hydrolysed to?
Glucose and galactose
What are fat soluble vitamins?
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
What is the most sensitive test for carbohydrate malabsorption?
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
What is the preferred method of assessing protein-losing enteropathy in children?
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**
What are the chances of first degree relatives having Coeliac’s disease?
10% in 1st degree
30-40% in HLA identical siblings
60-70% concordance in identical twins
What is the chance that someone has coeliac’s disease if HLA D2 / D8 are negative?
Very very low!
Only 1% of people of coeliac’s disease will have negative HLA DQ2 or DQ8
What is coeliac disease?
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
What is abetalipoproteinaemia?
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
What is cystinuria?
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
What is glucose-galactose malabsorption?
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
What’s the most common cause of malabsorption in children?
Lactase deficiency
What is intestinal lymphangiectasia?
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
What causes intestinal lymphangiectasia?
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
What are the symptoms / signs of intestinal lymphagiectasia?
Steatorrhoea
Low alb and generalised oedema
Recurrent infections due to low IgG and lymphocytopenia (leakage of lymphocytes into gut)
Chylous ascites
What is microvillus inclusion disease?
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
What is tufting enteropathy?
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
What is the energy of fat / protein / carbohydrate?
Fat 10kcal/g
Protein 4kcal/g
CHO 4kcal/g
What is absorbed in the duodenum and the proximal jejunum?
Calcium, magnesium, phosphorous, iron and folic acid
What is absorbed in the proximal 100-200cm of small bowel?
Carbohydrate, protein, water soluble vitamin
What is absorbed throughout small intestines?
Monoglycerides, fatty cards and MCT
What is absorbed in the distal ileum?
Vitamin B12 and bile acids
What is absorbed in the colon?
Water and electrolytes
Why does renal stones occur with malabsorption?
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
How to test for fat absorption?
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
What investigations are available for exocrine pancreatic function?
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
What will the histology of coeliac disease look like?
Loss of absorptive villi
Hyperplasia of crypts
Presence of lymphocytes
injury greatest in proximal small bowel
What are the differential diagnoses for intestinal villi atrophy?
Small intestinal lymphoma Crohns Eosinophilic gastroenteritis Giardia Tropical sprue Whipple disease
What is tropical sprue?
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
What is whipple disease?
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
What % of small bowel loss will result in malabsorption?
50%
NB: typical length of small bowel
- neonate: 200-300cm
- adult: 600-800cm
What are the causes of malabsorption in short gut syndrome?
Reduced surface area Rapid transit Suboptimal bowel function Acide hypersécrétion Bile acid deficiency Bacterial overgrowth - injury intestinal mucousa further
What are the clinical features of short gut syndrome?
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)
What is the prognosis of short gut syndrome?
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
What are complications of short gut syndrome?
FTT Water / sodium depletion Nutrient deficiencies Renal stones Gallstones Liver disease Late VB12 deficiency D-lactic acidosis
What are the differences between fat globules and fat crystals?
Fat globules = problem with digestion (problem with pancreatic enzymes or bile salts)
Fat crystals = problem with absorption = (mucosal abnormality)
What are the differentials for malabsorption?
Can be divided into:
- Lumen
- Cell related: Reduced integrity of mucosa, Enzyme deficiency, Transport defects, Substrate overload, Immune related, Altered secretory function
- Lymphatics
- Structural
What are luminal causes of malabsorption?
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
What are the causes of reduced integrity of mucosa that can lead to malabsorption?
- infection / post-infection
- cow’s milk intolerance
- coeliac disease
- IBD
- Tufting enteropathy
What are causes of enzyme deficiency that can lead to malabsorption?
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
What are transport defects that can cause malabsorption?
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
What are immune-related causes for malabsorption?
Autoimmune enteropathy
CVI / AIDS / IgA deficiency
Eosinophilic gastroenteropathy
