Lecture 11 - CF is a Multisystem Disorder Flashcards
Organs affected by CF 1) 2) 3) 4) 5) 6) 7) 8) 9)
1) Lungs
2) GIT
3) Pancreas
4) Liver
5) Sweat ducts
6) Kidneys
7) Skeleton
8) Genito-urinary
9) Skin
Median life expectancy of CF patients today
Mid 30s, early 40s
CF sweat test method
1)
2)
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
How is sweat stimulated in CF sweat test?
Pilocarpine iontophoresis
Normal [Cl-] in blood
105mL/L
Two parts of a sweat gland
1) Secretory coil
2) Reabsorptive duct
Tonicity of fluid in the secretory coil
Isotonic
Tonicity of fluid in the reabsorptive duct
Hypotonic
What happens in the secretory coil?
Water, NaCl is pumped into lumen
What happens in reabsorptive duct?
CFTR, ENaC reabsorb Cl- and Na+
Relationship between ENaC and CFTR in sweat duct
CFTR stimulates ENaC
Relationship between ENaC and CFTR in lungs
CFTR inhibits ENaC
Hyponatremic
Low Na+ in plasma
Condition of low plasma Na+
Hyponatremic
Clinical features of high salt sweat 1) 2) 3) 4) 5) 6) 7)
1) hyponatremic/hypochlorenic dehydration
2) Hypokalemic metabolic alkalosis
3) Headache
4) Muscle cramps
5) Nausea, vomiting
6) Poor concentration
7) Fatigue
Hypokalemic metabolic alkalosis
Abnormally high plasma bicarbonate
Exocrine pancreatic functions
Lipase, amylase, protease
From pancreatic acini
Endocrine pancreatic functions
Islets of Langerhans
Insulin, glucagon
Mutation types associated with pancreatic insufficiency
I, II, III, VI
Prevalence of pancreatic insufficiency in CF
85%
What is steatorrhoea?
Fatty, foul-smelling stools from poor fat absorption
Name for fatty stools from poor fat absorption
Steatorrhoea
Fat-soluble vitamins
A, D, E, K
PERT
Pancreatic enzyme replacement therapy
Lipase, amylase, protease
What is ‘enteric coated’?
Coating of PERT tablets
Prevents contents being released in stomach. Contents released in intestine
Where in the pancreas is CFTR?
Apical membrane of pancreatic ductal epithelial cell
Effects on pancreatic duct of malfunctioning CFTR
1)
2)
1) Defective Cl- secretion –> Reduced volume of luminal liquid
2) Defective bicarbonate secretion –> Luminal liquid becomes acidic
CF damage to the pancreas 1) 2) 3) 4)
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
CFRDM
Cystic fibrosis related diabetes mellitus
Effect of cystic fibrosis related diabetes mellitus on insulin secretion
Less insulin is secreted than normal. Not a cessation of insulin secretion
Insulin insensitivity might be present (not completely understood)
Age of onset of CFRDM
Very rare under ten years
50% prevalence at 30 years
Effect of CFRDM on mortality
6-fold increase with CFRDM
CFRDM detection
Very difficult clinically, as symptoms aren’t obvious.
Normally correlates with decline in lung function
Needs to be tested for regularly
Complications of CFRDM
Increased risk of microvascular complications (eyes)
Less likely to have stroke, infarction than type I or II diabetics
Prevalence of liver disease
25% patients
Pathogenesis of CF liver disease 1) 2) 3) 4)
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
When is liver cirrhosis commonly evident in CF?
20 years of age.
If cirrhosis hasn’t developed by then, patient probably won’t have cirrhosis
Clinical features of CF liver disease 1) 2) 3) 4)
1) Prolonged neonatal jaundice
2) Cirrhosis and portal hypertension
3) Hepato-splenomegaly
4) Oesophageal varices
Danger of oesophageal varices
Can bleed uncontrollably
Frequency of hepatocellular failure
2-3%
Where in the liver is CFTR found?
Epithelial cells lining intra-hepatic bile ducts
Where is CFTR found in the GIT?
Luminal membrane of intestinal epithelial cells
Effects of dysfunctional CFTR on GIT
Decreased luminal liquid volume
Possible effects of dysfunctional CFTR on GIT 1) 2) 3) 4)
1) Meconium ileus
2) Constipation
3) Distal intestinal obstructive syndrome
4) Gastro-oesophageal reflux
Effects of gastro-oesophageal reflux on lung function
Aspiration of stomach acid leads to greater inflammation of lungs
What is meconium ileus?
Inspissated intraluminal meconium causing bowel obstruction
Prevalence of meconium ileus
10-15% of neonates
What does meconium ileus correlate with?
Pancreatic insufficiency
Possible cause for CF gastro-oesophageal reflux
CF can interfere with stomach emptying
Why is osteoporosis more common with CF? 1) 2) 3) 4) 5) 6) 7)
1) Impaired lung function
2) Delayed puberty
3) Malnutrition
4) Corticosteroid use
5) Hypovitaminosis of A and K
6) CFRDM
7) Physical inactivity
Intussusception 1) 2) 3) 4)
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
Distal bowel obstruction syndrome clinical features 1) 2) 3) 4)
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
Common bone disease with CF
Osteoporosis
Difference in fracture rates between CF and unaffected people
2 fold increase for adults with CF
Prevalence of infertility in males with CF
99%
Genito-urinary effects of CF
1)
2)
3)
1) Infertility
2) Urinary incontinence
3) Pubertal delay, growth delay
Renal effects of CF
CFTR present in renal tubules, but no pathology has been found
Aminoglycosides are nephrotoxic, so treatment can cause renal problems
ENT effects of CF
1) 10 - 30% patients have nasal polyps
2) Aminoglycosides are ototoxic
