Malabsorption Flashcards
What are the disaccharide sugars, lactose, sucrose and maltose broken down into? What are they broken down by?
Their constituent monosaccharides (simple sugars such as glucose)
By the enzymes lactase, sucrase and maltase
Where are lactase, sucrase and maltase located?
In the apical membrane of the enterocytes lining the small intestine
If the necessary enzyme is lacking, what happens to the disaccharides?
They cannot be digested or absorbed so remain in small intestine
What is result of high conc of sugar due to undigested disaccharides?
Creates osmotic force that draws fluid into the small intestine –> causes diarrhoea
What then occurs to the unabsorbed sugar? What is the result of this?
Fermented by bacteria in the large intestine
Produces acidic stools and gas production, leading to bloating and flatulence
What can cause enzyme deficiency?
Primary: Can be congenital
Secondary: Coeliac disease, tropical sprue, infections of intestine, antibiotics (especially neomycin)
What occurs in inherited enzyme deficiency?
Complete loss of ability to absorb sugar, diarrhoea, baby will die of dehydration if untreated
Why is it possible to screen for mutations regarding the Na+/glucose transporter?
The Na+/glucose co-transporter has been cloned (SGLT1)
Every individual studied has missense mutation in gene encoding SGLT1
What is result of missense mutation in gene encoding SGLT1?
Improper trafficking of protein whilst others result in reduced transport ability –> glucose and galactose transport across the small intestinal epithelium is significantly impaired
Why can lactose intolerance increase with age?
The extent of synthesis of the enzyme lactase is reduced with age, and is a normal occurrence among people from Mediterranean area
What are symptoms of lactose intolerance?
Audible bowel sounds (borborygmi), abdominal bloating, flatulence, nausea, urgent need to defecate, abdominal cramps, diarrhoea
How can severe diarrhoea lead to malabsorption?
Rapid transit time –> pass through gut too quickly to allow adequate absorption
Why do blood glucose levels not rise in lactose intolerance test?
Test dose isn’t broken down into glucose
What can a biopsy of the small intestine show?
- No use in diagnosis of lactase deficiency
- Normal villi virtually excludes celiac disease
What can ingestion of large amounts of hexitols (e.g. sorbitol, mannitol), which are used as sugar substitutes, result in?
Cause diarrhoea as result of their slow absorption and stimulation of rapid small-bowel motility
What is the gene responsible for CF? Where is it located?
CFTR - located on chromosome 7
What does CFTR code for?
cAMP-dependent membrane channel protein
What does the cAMP-dependent membrane channel protein transport?
- Predominantly transports chloride ions
- Bicarbonate (HCO3-) can also be transported to some extent
How can CF cause lung damage?
Cause of recurrent bronchopulmonary infection in children and early adult life –> recurrent infections leads to lung damage
How is pancreatic fluid and HCO3- secretion affected in CF?
Markedly reduced in CF –> leads to blockage of ducts with mucus and limited or negligible delivery of pancreatic enzymes to duodenum
What can pancreatic insufficiency due to CF be caused by?
Inadequate digestion –> steatorrhoea, diarrhoea and wasting
What mutation causes 70% of all CF cases?
The delta F508 mutation
What happens during the delta F508 mutation?
Allows protein to be formed but does not get directed to the cell surface, and is destroyed
What do severe/mild alleles in CF cause?
Severe –> an incomplete (or no) CFTR protein
Mild –> often missense mutations
What is meconium ileus?
One of the most common symptoms of CF –> the inability of a baby to pass meconium (the first faeces) because the meconium is too thick and sticky
What is cholera caused by?
Infection with the gram-negative organism Vibrio cholera
What is the ‘evacuation phase’ of cholera?
Profuse watery diarrhoea ‘rice water’ stools (s called because of presence of mucous flecks in the faecal fluid), and sometimes vomiting
What is the ‘collapse phase’ of cholera?
Caused by dehydration, decreased blood volume leading to circulatory collapse which may be fatal
What is the mechanism by which the cholera toxin works?
- Bacteria produce toxin which enters cells of gut lumen and binds to G protein –> activates chloride channel (CFTR)
- Activates adenyl cyclase increasing cAMP production
- Increases Na+, Cl- and HCO3- secretion into lumen
- Osmotic pressure increased –> water and other electrolytes drawn into bowel lumen
- Diarrhoea
What does all water absorption occur by?
Osmosis
What is osmosis dependent on?
The absorption of electrolytes and nutrients to maintain an osmotic balance with the blood (especially Na+ electrochemical gradient)
What is the effect of the cholera toxin on enterocytes?
- Activation of a chloride channel (CFTR)
- Leads to large amounts of Na+, Cl- and HCO3- secretion into lumen
- Osmotic gradient
- Profuse watery diarrhoea
Where are digestive enzymes found?
Saliva, gastric and pancreatic secretions
What are starches broken down into?
a-dextrins and disaccharides
What do brush border enzymes break down?
- a-dextrins and disaccharides are hydrolysed and then absorbed
- Peptides
What do long chain fatty acids require for adequate absorption?
Bile
What can a deficiency in brush border enzymes (e.g. lactase) lead to?
A failure of breakdown of disaccharides (e.g. lactose) into glucose and galactose
Not digested and remain in gut
What do amphipathic bile salts form?
Micelles (creates fat droplets)
What happens when fatty acids and monoglycerides reach the epithelial cells of the villi?
Diffuse into the cells, leaving micelles behind in the chyme
Where are bile salts reabsorbed?
At the terminal ileum (enterohepatic circulation)
What is steatorrhoea and what is it caused by?
Presence of excess fat in the faeces caused by fat malabsorption
What is appearance of stools in steatorrhoea?
Float, difficult to flush, oily appearance, foul smelling
What diseases is steatorrhoea seen in?
Cholestatic liver disease, pancreatitis, coeliac disease
If fat absorption is impaired, what vitamin deficiencies may occur?
Vitamins A, D, E and K as they are fat-soluble
What is the effect of calcium absorption in a vitamin D deficiency?
Calcium absorption greatly reduced
What is osteoporosis? What is it caused by?
Reduced bone density and increased risk of breaks and fractures
Anorexia, smoking, alcoholism, malabsorption, steroid therapy, vitamin D/calcium deficiency
What is osteomalacia?
- Normal amount of bone but mineral content is low (so bone is dense but soft)
- Rickets occurs if this process is during the period of bone growth (occurs after fusion of the epiphyses)
What are the causes of osteomalacia?
Vitamin D deficiency, malabsorption, renal disease
Where is vit A absorbed? What is a deficiency?
Fat-soluble
Absorbed in small intestine
Xerophthalmia
Where is vit B2 absorbed? What is a deficiency?
Absorbed small intestine
Deficiency angular stomatis, cheilitis
Vit B1 (thiamine)
Thiamine
Absorbed small intestine
Deficiency –> Beriberi, Wernickes
Vit B6
Absorbed SI
Deficiency –> polyneuropathy
Vit B12
Absorbed terminal ileum
Deficiency –> anaemia, SCDC
Vit C
Absorbed proximal ileum
Deficiency –> scurvy
Vit D
Absorbed SI/skin
Deficiency –> osteomalacia
Vit E
Absorbed SI
Deficiency –> Bleeding disorders
Vit K
Absorbed SI
Deficiency –> Bleeding disorders
Where are all minerals absorbed?
SI
What does Vit B12 require for absorption?
Intrinsic factor (IF)
B12/IF complex forms in stomach and is absorbed in terminal ileum
What can lead to B12 deficiency?
- Gastric mucosal atrophy (chronic inflammation of gastric mucosa, gastric glandular cells replaced by intestinal-type epithelium, pyloric-type glands, and fibrous tissue)
- Terminal ileal disease
What can vit B12 deficiency lead to?
- Pernicious anaemia –> decrease in RBC
- SCDC (Subacute combined degeneration) –> metabolic disorder of the spinal cord
How can vit B12/folate deficiency lead to macrocytic anaemia (large RBC with less Hb)?
As normal proliferation of cells depends on adequate folate and vit B12
Folate is necessary for efficient thymidilate synthesis and production of DNA.
Where is iron mainly absorbed?
In the duodenum
What can an iron deficiency be caused by?
- Reduced absorption
- Increased loss (bleeding, sloughed mucosal cells)
What is coeliac disease?
- Inflammation of small intestinal mucosa induced by an autoimmune reaction to the ingestion of gluten
- Villous atrophy / intraepithelial lymphocytosis occurs (flat villi)
What is gluten?
Protein with a high content of amino acid glutamine; found in wheat, barley, rye
How can coeliac disease present in infants?
impaired growth, diarrhoea, vomiting, abdominal distension.
How can coeliac disease present in older children?
anaemia, short stature, pubertal delay, rickets, recurrent abdominal pain or behavioural disturbance.
How can coeliac disease present in adult disease?
chronic/recurrent iron deficiency anaemia, diarrhoea, abdominal pain, bloating, isolated nutritional deficiencies, reduced fertility, osteoporosis, osteomalacia, abnormal LFT
What can cause coeliac disease?
- Intestinal inflammation
- Villous atrophy
How can intestinal inflammation lead to coeliac disease?
- Increased intestinal transit (time traveled in gut)
- Decreased macronutrient absorption
- Negative calorie/ protein balance → diarrhoea and weight loss
How can villous atrophy lead to coeliac disease?
- Reduced surface area for absorption
2. ↓absorption of osmotically active substances → diarrhoea
What can an iron/folate deficiency lead to?
Anaemia
What can a calcium deficiency lead to?
Osteoporosis / osteomalacia
What can a fat / vitamins ADEK lead to?
Clotting disorders
How is coeliac disease diagnosed?
- Serological test –> endomysial (EMA) and tissue transglutaminase (tTG) antibodies
If they are negative and the patient is eating gluten then unlikely they have coeliac
If they are positive then:
- Duodenal biopsy via upper GI endoscopy (sample showing villous atropy)
How is coeliac disease managed?
- Gluten Free Diet
- Replace iron, folate, calcium, vit D
- Monitor bone mineral density
What can cause osmotic diarrhoea?
Malabsorption of nutrients
What is parasthesia?
Tingling in hands
What is parasthesia caused by?
Malabsorption of calcium
What is anaemia caused by?
Malabsorption of iron, folate, possibly B12
What is pancreatic insufficiency?
Reduced delivery of pancreatic enzymes to the duodenum
How is CF related to pancreatic insufficiency?
- Reduced HCO3- and pancreatic fluid secretion
- Blockage of ducts due to thicker mucous
How is chronic pancreatitis and pancreatic insufficiency related?
Irreversible glandular destruction and alteration of anatomy / function due to chronic inflammation
What are the symptoms of chronic pancreatitis?
- Epigastric pain, often radiating to the back
- Food/ alcohol may exacerbate the pain
- Weight loss
What are the causes of chronic pancreatitis?
- Alcohol (>70%)
- Familial, congenital (pancreas divisum- single pancreatic duct is not formed, but remains as two distinct dorsal and ventral ducts)
- Autoimmune
- Genetic
What are the effects of exocrine insufficiency related to chronic pancreatitis?
Fat malabsorption:
- Steatorrhoea
- Fat soluble vitamin deficiency
What are the effects of endocrine insufficiency of chronic pancreatitis?
Diabetes seen in 40-60%
How can chronic pancreatitis be diagnosed?
- Faecal elastase-1 (low level of elastase seen as produced by pancreas and passed in stool largely unaltered)
- Plain abdominal X-ray
- Ultrasound/CT
- MRCP vs ERCP
How can chronic pancreatitis be managed?
- Stop alcohol
- Pain control
- Treat diabetes
Pancreatic enzyme supplements – Creon (pancreatin) (Lipase, protease, amylase) - Vitamin supplementation
What is creon?
Breaks down in SI and provides enzymes to facilitate digestion
Will creon affect elastase levels in faeces?
No - don’t make pancreas work but just aid digestion
What is cholestatic liver disease?
Impairment of bile formation / bile flow
- Steatorrhoea/ fat soluble vitamin malabsorption tends to only occur in prolonged cholestasis
How can Primary Sclerosing Cholangitis (PSC) lead to cholestatic liver disease?
- Inflammatory/ fibrotic process affecting intra/extrahepatic bile ducts
- Leads to bile duct strictures (injury), ~80% associated with IBD
How does cholestatic liver disease present?
Pruritus, fatigue, jaundice –> ultimately leads to cirrhosis and liver failure
What is the only proven treatment in cholestatic liver disease?
Liver transplant
What drug induces malabsorption?
Orlistat: inhibits gastric and pancreatic lipase
How can small bowel bacterial overgrowth lead to malabsoption?
- Upper small intestine is almost sterile (lack of bacteria)
- Normally seen with a structural abnormality (eg. Crohn’s stricture)
- Bacteria can deconjugate bile salts as well as metabolise B12 in upper SI
What is pruritus?
An unpleasant sensation of the skin that provokes the urge to scratch (characteristic feature of many skin diseases)
What is cirrhosis?
A condition in which the liver does not function properly due to long-term damage. This damage is characterised by the replacement of normal liver tissue by scar tissue
