Lecture 11 - CF is a Multisystem Disorder

Question 1

Organs affected by CF
1)
2)
3)
4)
5)
6)
7)
8)
9)

Answer 1

1) Lungs
2) GIT
3) Pancreas
4) Liver
5) Sweat ducts
6) Kidneys
7) Skeleton
8) Genito-urinary
9) Skin

Question 2

Median life expectancy of CF patients today

Answer 2

Mid 30s, early 40s

Question 3

CF sweat test method
1)
2)
3)

Answer 3

1) Apply pilocarpine to arm
2) Run small current through arm, this stimulates sweat
3) Collect sweat on filter paper, gauze or a macroduct coil

Question 4

How is sweat stimulated in CF sweat test?

Answer 4

Pilocarpine iontophoresis

Question 5

Normal [Cl-] in blood

Answer 5

105mL/L

Question 6

Two parts of a sweat gland

Answer 6

1) Secretory coil

2) Reabsorptive duct

Question 7

Tonicity of fluid in the secretory coil

Answer 7

Isotonic

Question 8

Tonicity of fluid in the reabsorptive duct

Answer 8

Hypotonic

Question 9

What happens in the secretory coil?

Answer 9

Water, NaCl is pumped into lumen

Question 10

What happens in reabsorptive duct?

Answer 10

CFTR, ENaC reabsorb Cl- and Na+

Question 11

Relationship between ENaC and CFTR in sweat duct

Answer 11

CFTR stimulates ENaC

Question 12

Relationship between ENaC and CFTR in lungs

Answer 12

CFTR inhibits ENaC

Question 13

Hyponatremic

Answer 13

Low Na+ in plasma

Question 14

Condition of low plasma Na+

Answer 14

Hyponatremic

Question 15

Clinical features of high salt sweat
1)
2)
3)
4)
5)
6)
7)

Answer 15

1) hyponatremic/hypochlorenic dehydration
2) Hypokalemic metabolic alkalosis
3) Headache
4) Muscle cramps
5) Nausea, vomiting
6) Poor concentration
7) Fatigue

Question 16

Hypokalemic metabolic alkalosis

Answer 16

Abnormally high plasma bicarbonate

Question 17

Exocrine pancreatic functions

Answer 17

Lipase, amylase, protease

From pancreatic acini

Question 18

Endocrine pancreatic functions

Answer 18

Islets of Langerhans

Insulin, glucagon

Question 19

Mutation types associated with pancreatic insufficiency

Answer 19

I, II, III, VI

Question 20

Prevalence of pancreatic insufficiency in CF

Answer 20

85%

Question 21

What is steatorrhoea?

Answer 21

Fatty, foul-smelling stools from poor fat absorption

Question 22

Name for fatty stools from poor fat absorption

Answer 22

Steatorrhoea

Question 23

Fat-soluble vitamins

Answer 23

A, D, E, K

Question 24

PERT

Answer 24

Pancreatic enzyme replacement therapy

Lipase, amylase, protease

Question 25

What is ‘enteric coated’?

Answer 25

Coating of PERT tablets

Prevents contents being released in stomach. Contents released in intestine

Question 26

Where in the pancreas is CFTR?

Answer 26

Apical membrane of pancreatic ductal epithelial cell

Question 27

Effects on pancreatic duct of malfunctioning CFTR
1)
2)

Answer 27

1) Defective Cl- secretion –> Reduced volume of luminal liquid
2) Defective bicarbonate secretion –> Luminal liquid becomes acidic

Question 28

CF damage to the pancreas
1)
2)
3)
4)

Answer 28

1) Blocked ducts from viscous luminal liquid
2) Increased acidity prematurely activated pancreatic enzymes, which degrade pancreas
3) Progressive fibrosis, fatty infiltration
4) Increased acidity, from lack of CFTR-dependent bicarbonate secretion

Question 29

CFRDM

Answer 29

Cystic fibrosis related diabetes mellitus

Question 30

Effect of cystic fibrosis related diabetes mellitus on insulin secretion

Answer 30

Less insulin is secreted than normal. Not a cessation of insulin secretion

Insulin insensitivity might be present (not completely understood)

Question 31

Age of onset of CFRDM

Answer 31

Very rare under ten years

50% prevalence at 30 years

Question 32

Effect of CFRDM on mortality

Answer 32

6-fold increase with CFRDM

Question 33

CFRDM detection

Answer 33

Very difficult clinically, as symptoms aren’t obvious.

Normally correlates with decline in lung function

Needs to be tested for regularly

Question 34

Complications of CFRDM

Answer 34

Increased risk of microvascular complications (eyes)

Less likely to have stroke, infarction than type I or II diabetics

Question 35

Prevalence of liver disease

Answer 35

25% patients

Question 36

Pathogenesis of CF liver disease
1)
2)
3)
4)

Answer 36

1) CFTR in epithelial cells lining intra-hepatic bile ducts
2) More viscous bile
3) Plugs form in intra-hepatic bile ducts
4) Multifocal cirrhosis

Question 37

When is liver cirrhosis commonly evident in CF?

Answer 37

20 years of age.

If cirrhosis hasn’t developed by then, patient probably won’t have cirrhosis

Question 38

Clinical features of CF liver disease
1)
2)
3)
4)

Answer 38

1) Prolonged neonatal jaundice
2) Cirrhosis and portal hypertension
3) Hepato-splenomegaly
4) Oesophageal varices

Question 39

Danger of oesophageal varices

Answer 39

Can bleed uncontrollably

Question 40

Frequency of hepatocellular failure

Answer 40

2-3%

Question 41

Where in the liver is CFTR found?

Answer 41

Epithelial cells lining intra-hepatic bile ducts

Question 42

Where is CFTR found in the GIT?

Answer 42

Luminal membrane of intestinal epithelial cells

Question 43

Effects of dysfunctional CFTR on GIT

Answer 43

Decreased luminal liquid volume

Question 44

Possible effects of dysfunctional CFTR on GIT
1)
2)
3)
4)

Answer 44

1) Meconium ileus
2) Constipation
3) Distal intestinal obstructive syndrome
4) Gastro-oesophageal reflux

Question 45

Effects of gastro-oesophageal reflux on lung function

Answer 45

Aspiration of stomach acid leads to greater inflammation of lungs

Question 46

What is meconium ileus?

Answer 46

Inspissated intraluminal meconium causing bowel obstruction

Question 47

Prevalence of meconium ileus

Answer 47

10-15% of neonates

Question 48

What does meconium ileus correlate with?

Answer 48

Pancreatic insufficiency

Question 49

Possible cause for CF gastro-oesophageal reflux

Answer 49

CF can interfere with stomach emptying

Question 50

Why is osteoporosis more common with CF?
1)
2)
3)
4)
5)
6)
7)

Answer 50

1) Impaired lung function
2) Delayed puberty
3) Malnutrition
4) Corticosteroid use
5) Hypovitaminosis of A and K
6) CFRDM
7) Physical inactivity

Question 51

Intussusception 
1)
2)
3)
4)

Answer 51

1) Blockage in intestine
2) Peristalsis tries to push blockage out
3) Small bowel can be telescoped into large bowel
4) Can lead to necrosis

Question 52

Distal bowel obstruction syndrome clinical features
1)
2)
3)
4)

Answer 52

1) Partial or complete bowel obstruction
2) Painful cramp, often localising to right ilial fossa
3) Palpable mass in right ilial fossa
4) Abdominal x ray shows dilated small bowel with bubbly iliocaecal mass

Question 53

Common bone disease with CF

Answer 53

Osteoporosis

Question 54

Difference in fracture rates between CF and unaffected people

Answer 54

2 fold increase for adults with CF

Question 55

Prevalence of infertility in males with CF

Answer 55

99%

Question 56

Genito-urinary effects of CF
1)
2)
3)

Answer 56

1) Infertility
2) Urinary incontinence
3) Pubertal delay, growth delay

Question 57

Renal effects of CF

Answer 57

CFTR present in renal tubules, but no pathology has been found

Aminoglycosides are nephrotoxic, so treatment can cause renal problems

Question 58

ENT effects of CF

Answer 58

1) 10 - 30% patients have nasal polyps

2) Aminoglycosides are ototoxic