Cystic Fibrosis and the Gastrointestinal tract

Question 1

What is the cystic fibrosis transmembrane conductance regulator (CFTR)?

Answer 1

• a membrane protein and chloride channel
• encoded by the CFTR gene
• this is mutated in cystic fibrosis

Question 2

What type of mutation, in terms of how affected genes are is cycstic fibrosis?

Answer 2

• point mutation
• a single nucleotide is affected

Question 3

What is the most common genetic mutation in cycstic fibrosis?

Answer 3

• deltaF508

Question 4

In cystic fibrosis are the mutations in the CFTR that patients have on their 2 different alleles homozygous or heterozygous?

Answer 4

• can be both
• homozygous (2 of the same gene)
• heterozygous (2 different genes) - RARER

Question 5

In cystic fibrosis mutations in the CFTR affect the membrane proteins ability to pump chloride (Cl-). In the body this specifically affects something that is produced by epithelial cells, and therefore affects very specific tissues. What is it that is affected in cystic fibrosis?

Answer 5

• mucous]
• lungs, pancreas, GIT

Question 6

In cystic fibrosis mutations in the CFTR affect the membrane proteins ability to pump chloride (Cl-). In the body this specifically affects mucous that is produced by epithelial cells, and therefore affects very specific tissues. How can this affected the GIT?

Answer 6

• affects bicarbonate and fluid levels in GIT

Question 7

In cystic fibrosis mutations in the CFTR affect the membrane proteins ability to pump chloride (Cl-). In the body this specifically affects mucous that is produced by epithelial cells, and therefore affects very specific tissues. How can this affected the pancreas?

Answer 7

• exocrine and endocrine secretions are sticky
• leads to pabcreatic insufficiency

Question 8

In cystic fibrosis mutations in the CFTR affect the membrane proteins ability to pump chloride (Cl-). In the body this specifically affects mucous that is produced by epithelial cells, and therefore affects very specific tissues. How can this affected failure to develop?

Answer 8

• canalisation, which is tube formation is impaired if mucous is affected
• the intestine in utero (causing neonatal meconium (dark stricky mucous) ileus)
• essentially blocking of GIT

Question 9

Can cystic fibrosis present as acute or chronic only?

Answer 9

• both

Question 10

Does cystic fibrosis present at any specific age?

Answer 10

• any age
• generally diagnosed early though

Question 11

As the GIT and pancreas are affected, what can this lead to?

Answer 11

• malabsotpion of nutrients

Question 12

If a patient presents at A&E with cystic fibrosis and acute abdomianl pain, what could be some other differential diagnosis that are associated with cystic fibrosis?

Answer 12

• pancreatitis (inflammation of pancreas)
• distal intestinal obstructive syndrome (DIOS)
• cholecystitis (gallbladder inflammation)
• gastro-oesophageal reflux disease (GORD)
• Cystic Fibrosis Liver Disease (CFLD)
• colorectal cancer

Question 13

If a patient presents at A&E with cystic fibrosis and acute abdomianl pain, what could be some other differential diagnosis that are NOT associated with cystic fibrosis?

Answer 13

• IBS
• appendicitis
• gastritis
• gastroenteritis

Question 14

How can cystic fibrosis be inherited?

Answer 14

• autosomal recessive (no sex chromosomes)
• patients need a mutated gene from both parents
• if only one gene they are a carrier

Question 15

If a patient presents at A&E with cystic fibrosis and acute abdomianl pain, what could be some of the tests run that could help identify the problem?

Answer 15

• bloods
• chest X-ray
• abdominal CT scan

Question 16

What is distal intestinal obstruction syndrome (DIOS)

Answer 16

• a complication of cystic fibrosis
• bowel becomes partially or completely blocked
• generallty occurs where the small bowel joins the large bowel.

Question 17

Distal intestinal obstruction syndrome (DIOS) is a complete or partial blockage of the GIT that is a complication of cystic fibrosis. What is the main cause of this?

Answer 17

• thick “stool” blocks intestinal tube

Question 18

Distal intestinal obstruction syndrome (DIOS) is a complete or partial blockage of the GIT that is a complication of cystic fibrosis that is caused by thick “stool” blocking the intestinal tube. Why does thick stool form in cystic fibrosis?

Answer 18

• lack of enzymes (exocrine – amylase, lipase, protease)
• dehydration
• narrow of GIT, ileocaecal area particularly affected
• terminal ileum leads to vitamin B12 absorption
• valve dysfunction leads to “dumping” syndrome from ileum to colon
• can present like an appendicitis

Question 19

Distal intestinal obstruction syndrome (DIOS) is a complete or partial blockage of the GIT that is a complication of cystic fibrosis that is caused by thick “stool” blocking the intestinal tube. Another cause of obstruction, but less common is intussusception. What is intussusception?

Answer 19

• part of the intestine slides into an adjacent part of the intestine
• very dangerous

Question 20

How can we treat distal intestinal obstruction syndrome and/or intussusception?

Answer 20

• rehydration
• laxatives
• enzyme (Creon)
• surgery

Question 21

How can cystic fibrosis cause Cholecystitis?

Answer 21

• CFTR is highliy expressed in liver and biliary tree
• can lead to narrowing bilary tree or mini gall bladder
• bile scretions will be thick and sticky

Question 22

Cystic fibrosis can cause Cholecystitis due to the high expression of the CFTR in the liver and biliary tree. This can lead to narrowing of the bilary tree or a mini gall bladder. What can CF due to bile secretions and increase the risk of?

Answer 22

• bile scretions will be thick and sticky
• increased risk of gall stones and blockage of bilary tree

Question 23

Cystic fibrosis can cause Cholecystitis due to the high expression of the CFTR in the liver and biliary tree. This can lead to narrowing of the bilary tree or a mini gall bladder. The bile scretions can be thick and sticky, increasing the risk of gall stones and blockage of bilary tree. What can this then increase the risk of?

Answer 23

• increased risk from bacterial endotoxins

Question 24

Cystic fibrosis can cause Cholecystitis due to the high expression of the CFTR in the liver and biliary tree. This can lead to narrowing of the bilary tree or a mini gall bladder. The bile scretions can be thick and sticky, increasing the risk of gall stones and blockage of bilary tree and increase the risk of bacterial infections. What else can happen to bile once it has been pumped into the GIT?

Answer 24

• lost in stool as cannot be absorbed
• causes fat/bile acid diarrhoea

Question 25

Cystic fibrosis can cause Cholecystitis due to the high expression of the CFTR in the liver and biliary tree. This can lead to narrowing of the bilary tree or a mini gall bladder. The bile scretions can be thick and sticky, increasing the risk of gall stones and blockage of bilary tree and increase the risk of bacterial infections. What can patients with CF present with?

Answer 25

• jaundice due to blocking of bile ducts

Question 26

Gastro-oesophageal reflux disease (GORD) is common in CF, affecting around 35-80%. Although GORD has a number of nasty symptoms, it can also affect the lungs. How can this occur?

Answer 26

• gastric contents may enter the trachea
• increases risk of infections

Question 27

Gastro-oesophageal reflux disease (GORD) is common in CF, affecting around 35-80%. Although GORD has a number of nasty symptoms including dyspepsia (indigestion), reflux, early satiety and regurgitation, it can also affect the lungs. Gastric contents may enter the trachea and can increases risk of infections. Surgery is the the extreme treatment via a nissen fundoplication, but physiotherapy can also help, how is this possible?

Answer 27

• CF patients have a physiological spincter
• body position can affect this and reduce GORD symptoms

Question 28

Gastro-oesophageal reflux disease (GORD) is common in CF, affecting around 35-80%. Although GORD has a number of nasty symptoms including dyspepsia (indigestion), reflux, early satiety and regurgitation, it can also affect the lungs. Gastric contents may enter the trachea and can increases risk of infections. What drug has been increased in the prescription to CF patients?

Answer 28

• proton pump inhibitors

Question 29

Pancreatitis, which is inflammation of the liver is rare but can occur in VF patients. The pancreas can be pancreatic sufficient (PS) and pancreatic insufficient (PI). Which of these causes pancreatitis and why?

Answer 29

• usually caused by PS
• PS means secretions can be secreted
• BUT these secretions are thick and stick and block pancreatic ducts

Question 30

How can pancreatic sufficiency cause pancreatic insufficiency?

Answer 30

• pancrease pumps exocrine secretions which are thick and sticky
• secretions block the ducts
• chronic blockage and inflammation lead to scarring and atrophy of pancreatic tissue

Question 31

If a patient did present with acute pancreatitis, how would thet generally present?

Answer 31

• acute epigastric pain that radiates to the back
• raised amylase (4x normal)
• raised WBC
• steatorrhea
• may develop nfection type 1 diabetes

Question 32

How can cystic fibrosis cause cystic fibrosis associated liver disease (CFLD)?

Answer 32

• bile acids are thick and highly concentrated
• acidification damages the liver
• affects around 30% of patients, more in women than men

Question 33

How can cystic fibrosis lead to colorectal cancer?

Answer 33

• chronic inflammation of the GIT
• secretions and mucous barrier is impaired

Question 34

The risk of colrectal cancer is increased in cystic fibrosis by 5-10%. What symptoms might CF patients present with?

Answer 34

• blood in stool
• weight loss
• anaemia
• change in bowel habit

Question 35

The risk of colrectal cancer is increased in cystic fibrosis by 5-10%. What investigations should be considered in CF patients?

Answer 35

• faecal immune test (qFIT)
• colonoscopy (polyps)
• capsule enterography

Question 36

In patients with CF they may experience GIT symptoms that require surgery. What are the 2 key anaesthetic risks that must be considered prior to surgery?

Answer 36

• lung function status
• medication doses

Question 37

In patients with CF they may experience GIT symptoms may require surgery. What are the most common procedures that are conducted?

Answer 37

• nasal polypectomy
• gastrostomy insertion (nutrition)
• central line insertion (Portacath, Hickman)
• appendicectomy
• rectal prolapse repair

Question 38

In patients with CF they may experience GIT symptoms and may require surgery. In the instance where they need nutritional support what is the most common approach if they cannot take in caloires orally?

Answer 38

• gastrostomy insertion (nutrition) as longer term and more comfortable than a nadogastronomy
• percutaneous endoscopic gastrostomy (PEG) button

Question 39

Why is nutritional support is important in CF patients in terms of calories required?

Answer 39

• increased metabolic load due to CF
• body essentially has to work harder

Question 40

Although nutritional support is important in CF patients in terms of calories required due to the increased metabolic load, why can this cause a problem in CF?

Answer 40

• lack of pancreatic enzymes (CREON given)
• impaired intestinal absorption
• fat cannot be absorbed so fat soluble vitamins (A,D,E,K) are low
• if stomach is affected there is low intrinsic factor and therefore low B12 absorbed in the terminal ileum