lecture 11 Flashcards
Clinical features of CF: - sweat gland - pancreas - liver - gastro-intestinal - skeletal - genito-urinary - renal - ENT - Cardiovascular - Skin
1
Q
What systems are affected by CF?
A
- chronic pulmonary disease
- pancreas
- nutrition
- liver
- gut
- electrolyte disturbance
- ENT
- musculoskeletal
- genito-urinary
- renal
90% of morbidity/mortality due to lung problems
2
Q
What has happened as life expectancy of individuals with CF has risen?
A
- median life expectancy is late 30s/early 40s
- new complications emerging in the adult population
3
Q
How is the sweat gland involved in CF?
A
- Salty sweat was one of the first descriptions of CF in literature: “Woe to that child which when kissed on the forehead tastes salty. They are bewitched and soon will die”
- Involvement of the sweat gland in CF first recognised in 1949
- people with CF don’t sweat more than others, it is just that the sweat they produce is really salty
- Sweat test: gold standard for diagnosing CF
- transdermal administration of pilocarpine by iontophoresis (i.e. they put pilocarpine on the skin and put a small electric current through it which stimulates the sweat gland)
- collection and quantitation of sweat onto gauze or filter paper or into a Macroduct coil
- normal value Cl very close to 105mmol/L in this part (isotonic secretion)
- what normally happens is that the sweat moves up the duct of the sweat gland, and as it moves Na and Cl are resorbed from the sweat leaving a hypotonic (dilute solution) to allow cooling evaporation to occur
- CFTR activates ENaC in sweat duct (opposite to lung) so in CF this reuptake doesn’t occur, >60 = CF
4
Q
What are the clinical features associated with high salt sweat?
A
- hyponatremic/hypochloremic dehydration - bad for all the cells in the body
- hypokalemic (potassium) metabolic alkalosis secondary to chronic salt loss: Pseudo-Bartter’s Syndrome
- headache or irritability
- muscle cramps
- nausea and vomiting
- fatigue
- poor concentration
5
Q
What are the two main functions of the pancreas?
A
Exocrine
- pancreatic acini
- lipase
- amylase
- protease
Endocrine
- Islets of langerhans
- insulin
- glucagon
6
Q
How does CF affect the exocrine function of the pancreas? How is it treated?
A
- pancreatic enzyme insufficiency
- 85% of patients
- class I, II, III or VI mutations (IV, V tend to have pancreatic Sufficiency)
- steatorrhoea (fatty, bulky, smelly, floaty stool)
- fat malabsorption
- malnutrition
- low on fat soluble vitamins: A, D, E, K
- PERT (pancreatic enzyme replacement therapy)
- lipase, amylase, protease
- enteric coated: don’t want enzymes to be released in stomach - need to be released in first part of small intestine
7
Q
What is the pathophysiology of pancreatic disease in CF?
A
- CFTR in the apical membrane of the pancreatic ductal epithelial cell
- regulation of chloride secretion: reduced luminal liquid; if you have a reduction in the chloride secretion into the pancreatic duct you have an increase in the thickness and viscosity of the fluid within those ducts therefore obstructing them
- regulation of bicarbonate secretion: acidic pH of luminal liquid
- Viscous pancreatic secretions
- pancreatic duct obstruction
- progressive fibrosis and fatty infiltration
- premature activation of proteolytic enzymes
- inflammation and destruction of pancreas
8
Q
What is the effect of CF on the endocrine function of the pancreas?
A
- Cystic fibrosis related diabetes mellitus (CFRDM)
- increasingly common with increasing age: rare under 10 years, 20% at 18, 50% over 30 years
- impaired and delayed insulin secretion
- insulin resistance
- higher mortality rates (6 fold) in CFRDM
- lung function decline (faster in patients with CFRDM)
- microvascular complications (as opposed to the macrovascular complications seen in non-CFRDM CF patients) (eye disease, renal, peripheral vascular)
- presents differently type I diabetes: often not aware of symptoms
9
Q
How does CF effect the liver ?
A
- 25% of patients have evidence of disease
- pathogenesis:
- CFTR in epithelial cells lining intra-hepatic bile ducts
- increased viscocity of bile
- plugging of intra-hepatic bile ducts
- cirrhosis, initially multi-focal, in minority
- most cirrhosis evident by 20 years of age
- more linked to modifier genes than to class of mutation
10
Q
What are the clinical features of liver disease in CF?
A
- prolonged neonatal jaundice (can occur for many reasons)
- cirrhosis and portal hypertension
- 5/6-8% of patients
- M:F = 3:1
- hepato-splenomegaly (enlargement of spleen and liver)
- raised liver enzymes, common in CF, may be of no significance
- oesophageal varices in 20% (can develop if there is portal hypertension, increase in dilation/thickness –> can bleed, if so very hard to control the bleeding and that can actually lead to the death of the patient)
- hepatocellular failure is uncommon, 2-3%
11
Q
How does CF affect the GIT?
A
- CFTR abundant at luminal membrane of intestinal epithelial cells
- Dehydration of luminal contents
- Meconium ileus
- constipation
- distal intestinal obstruction syndrome
- gastro-oesophageal reflux (can lead to aspiration of gastric contents –> inflammation –> faster decline of lung function)
12
Q
What is meconium ileus?
A
- inspissated intraluminal meconium (stool produced when foetus is in utero) (yucky black tar-y sticky stuff) causing bowel obstruction
- associated with pancreatic insuffienciency
- incidence: 10 - 15% of CF neonates
- Later complications
- Increased DIOS (distal intestinal obstruction syndrome) risk
- Adhesive small bowel obstruction
13
Q
What is DIOS?
A
Distal Intestinal Obstruction Syndrome - abdominal pain; crampy, RIF (right iliac fossa) - Palpable mass in RIF - Partial or complete bowel obstruction - Intussusception: there is a blockage but normal peristalsis keeps pushing food along leading to further blockage and increased pressure: can lead to necrosis etc - AXR: dilated small bowel with bubbly ileocaecal mass - Constipation also common
14
Q
How does CF affect gastro-oesophageal reflux?
A
- very common in CF
- aeitology is multifactorial
- exacerbates lung disease due to aspiration and reflex bronchospasm
- delayed gastric emptying and small bowel transit also common
15
Q
What are some further GI complications related to cystic fibrosis?
A
- rectal prolapse
- pancreatic insufficient
- frequent stools, diminished muscle tone, coughing
- malignancy
- coeliac disease
- fibrosing colonopathy: less so now but was associated with some of the older preparations of PERT especially if dosage was too high
