Lecture 11 - CF - Multisystem disorder Flashcards
What are some other systems that are affected in CF?
• Pancreas • GIT • Sweat glands • Reproductive etc.
What is the life expectancy for individuals with CF?
Late 30’s, early 40’s
NB Life expectancy has been increasing over the years
What is the gold standard test for diagnosing CF?
Sweat test
• stimulation of sweat gland with pilocarpine
• sweat collected in coil
• sweat analysed in the lab
→ Sweat chloride level should be lower than 40
Describe the structure and function of the sweat gland
Secretory coil
• isotonic (cf plasma) secretion of ions (Na+, Cl-) into nascent sweat
Reabsorption duct:
• ions (Na+, Cl-) reabsorbed
• sweat now hypotonic
What happens in the sweat ducts of individuals with CF?
Mutation in CFTR → reduced reabsorption of Na+ and Cl-
Thus, sweat is salty
- Normally in the sweat gland, CFTR stimulates ENaC.
- With CFTR mutation → reduced ENaC activity
What are clinical features of high salt sweat?
- hyponatremic / hypochloremic dehydration
- Pseudo-Bartter’s syndrome
- headache, irritability
- muscle cramps
- nausea
- fatigue
- poor concentration
Describe the endocrine and exocrine function of the pancreas
Endocrine:
• insulin and glucagon production
( • Islets of Langerhans)
Exocrine: • protease • lipase • amylase ( • pancreatic acini)
What are the fat soluble vitamins?
A, D, E, K
What pancreas dysfunction is seen in CF?
What are the sequelae of this?
Pancreatic enzyme insufficiency in 85%
• steatorrhoea
• fat malabsorption
• malnutrition (vitamins)
What is the treatment for pancreatic insufficiency?
PERT; e.g. Creon
• lipase
• amylase
• protease
Describe the pathophysiology of pancreatic disease
CFTR on apical membrane of pancreatic duct all epithelial cell
• luminal liquid composition normally regulated by CFTR
• decreased Cl- transport into luminal liquid
→ increased viscosity
→ obstruction of ducts → fibrosis
• Decreased bicarbonate secretion
→ acidic pH of luminal fluid
• premature activation of proenzymes
→ inflammation and destruction of pancreas
Why is CFRDM important?
Associated with higher mortality (6 fold)
What is an important complication of CF pancreas pathology?
Describe the features of this disease
CF related diabetes mellitus (CFRDM) • rare in young patients ( • insulin resistance) • impaired and delayed insulin secretion • microvascular complications
Is liver disease common in CF?
25% of CF patients
Describe the pathogenesis of liver pathology in CF
CFTR found on epithelial cells lining intra-hepatic bile ducts
- increased viscosity of bile
- plugging of intra-hepatic bile ducts
What are clinical features of liver disease in CF?
- prolonged neonatal jaundice
- cirrhosis and portal hypertension
- hepato-splenomegaly
- raised concentrations of liver enzymes
What are the effects of CF on the GIT?
List some complications
CFTR abundant in the epithelial cells in GIT
• decreased Cl- secretion from epithelial cells
→ dehydration of luminal contents
- constipation
- gastro-oesophageal reflux
- meconium ileus
- DIOS (Distal intestinal obstruction syndrome)
Describe the features of meconium ileus
10-15% incidence in CF neonates
- bowel obstruction due to inspissated (thickened, congealed) intraluminal meconium
- associated with pancreatic insufficiency & DIOS
Describe the features of DIOS
- abdominal pain, RIF (similar to appendicitis)
- palpable mass in RIF (right intestinal fossa)
- partial or complete bowel obstruction
- intussusception (one portion of the bowel slips into the next)
- dilated small bowel
- constipation
Describe the features of gastro-oesophageal reflux
What is the cause?
- very common in CF
- exacerbates declining lung function
Cause: multi factorial, but
• due to delayed gastric emptying
What are some more GI complications?
- Rectal prolapse (due to decreased muscle tone & coughing)
- Coeliac disease
- Fibrosing colonopathy
- Malignancy
What are the complications of CF on the bones?
Osteoporosis (low bone mineral density)
• Bone density is related to going through puberty at the normal time, which is disrupted in people w/ CF
• Pubertal hormones have an important role in bone density
What are the genito-urinary complications?
- Pubertal delay (due to decreased body fat mass)
- Male infertility, in utero obstruction of vas deferens
- reduced female fertility (increased viscosity of cervical mucous)
- urinary incontinence (due to increased coughing)
What are renal complications?
- CFTR present in renal tubules
- no clinical effects
- increased renal clearance of antibiotics
What are the complications on ENT?
(Ear, nose & throat)
- nasal polyps
- reduced smell (–> reduced appetite, nutritional effects)
- sinus involvement
- ototoxic drugs used for treatment
Complications of the heart
Cor pulmonale • pulmonary heart disease • high blood pressure in the lungs → increased vascular resistance in right ventricle → failure of right ventricle
What are the complications seen in the skin?
- rashes
* vasculitis
What is Pseudo-Bartter’s syndrome?
Hypokalemic metabolic alkalosis, secondary to chronic salt loss
In which classes of CFTR mutation is pancreatic insufficiency most often seen?
Class I, II, III or VI
Describe the normal direction of ion flow in: • lungs • sweat glands • pancreas • liver • GIT
Lungs: out of epithelial cells
Sweat glands: into cells
Pancreas: out of cells
Liver: out of cells
GIT: out of cells
What is the name of the condition, in which one portion of the bowel slips into the next?
Intussusception
What is RIF?
Right intestinal fossa
What controls the onset of puberty?
Once a certain body fat mass is reached, puberty is triggered (more or less…)
Which rash is often seen as a complication of CF?
Acrodermatitis enteropathica
What part of CFTR controls ENaC function?
TRL portion on C-terminus
Describe general pathogenesis in the various organs
Thick mucous Damage Inflammation Fibrosis → non functional
What causes microvascular complications?
Fibrosis of the vessels
Narrowing of the vessels
What are oesophageal varices?
- Narrowed vessels in liver
- Blood flows backwards to find a better route back to the heart
- Blood moves through oesophageal vein
- Bleeding into the oesophagus
What causes fibrosing colonopathy?
Too many pancreatic tablets
What are some important causes of osteoporosis?
- corticosteroid use
- delayed puberty
- malnutrition, vitamin deficiency
Describe pathology in the vas deferens
- Blockage of vas deferens due to the thickened mucous
- Vas don’t develop
- Babies born without vas
