Lecture 11 - CF - Multisystem disorder Flashcards Preview

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Flashcards in Lecture 11 - CF - Multisystem disorder Deck (41):
1

What are some other systems that are affected in CF?

• Pancreas
• GIT
• Sweat glands
• Reproductive
etc.

2

What is the life expectancy for individuals with CF?

Late 30's, early 40's
NB Life expectancy has been increasing over the years

3

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

4

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

5

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

6

What are clinical features of high salt sweat?

• hyponatremic / hypochloremic dehydration
• Pseudo-Bartter's syndrome
• headache, irritability
• muscle cramps
• nausea
• fatigue
• poor concentration

7

Describe the endocrine and exocrine function of the pancreas

Endocrine:
• insulin and glucagon production
( • Islets of Langerhans)

Exocrine:
• protease
• lipase
• amylase
( • pancreatic acini)

7

What are the fat soluble vitamins?

A, D, E, K

9

What pancreas dysfunction is seen in CF?
What are the sequelae of this?

Pancreatic enzyme insufficiency in 85%
• steatorrhoea
• fat malabsorption
• malnutrition (vitamins)

10

What is the treatment for pancreatic insufficiency?

PERT; e.g. Creon
• lipase
• amylase
• protease

11

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

11

Why is CFRDM important?

Associated with higher mortality (6 fold)

12

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

13

Is liver disease common in CF?

25% of CF patients

15

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

16

What are clinical features of liver disease in CF?

• prolonged neonatal jaundice
• cirrhosis and portal hypertension
• hepato-splenomegaly
• raised concentrations of liver enzymes

17

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)

18

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

19

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

20

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

21

What are some more GI complications?

• Rectal prolapse (due to decreased muscle tone & coughing)
• Coeliac disease
• Fibrosing colonopathy
• Malignancy

22

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

23

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)

24

What are renal complications?

• CFTR present in renal tubules
• no clinical effects
• increased renal clearance of antibiotics

25

What are the complications on ENT?

(Ear, nose & throat)

• nasal polyps
• reduced smell (--> reduced appetite, nutritional effects)
• sinus involvement
• ototoxic drugs used for treatment

26

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

27

What are the complications seen in the skin?

• rashes
• vasculitis

28

What is Pseudo-Bartter's syndrome?

Hypokalemic metabolic alkalosis, secondary to chronic salt loss

29

In which classes of CFTR mutation is pancreatic insufficiency most often seen?

Class I, II, III or VI

30

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

31

What is the name of the condition, in which one portion of the bowel slips into the next?

Intussusception

32

What is RIF?

Right intestinal fossa

33

What controls the onset of puberty?

Once a certain body fat mass is reached, puberty is triggered (more or less...)

34

Which rash is often seen as a complication of CF?

Acrodermatitis enteropathica

35

What part of CFTR controls ENaC function?

TRL portion on C-terminus

36

Describe general pathogenesis in the various organs

Thick mucous
Damage
Inflammation
Fibrosis
→ non functional

37

What causes microvascular complications?

Fibrosis of the vessels
Narrowing of the vessels

38

What are oesophageal varices?

1. Narrowed vessels in liver
2. Blood flows backwards to find a better route back to the heart
3. Blood moves through oesophageal vein
4. Bleeding into the oesophagus

39

What causes fibrosing colonopathy?

Too many pancreatic tablets

40

What are some important causes of osteoporosis?

• corticosteroid use
• delayed puberty
• malnutrition, vitamin deficiency

41

Describe pathology in the vas deferens

1. Blockage of vas deferens due to the thickened mucous
2. Vas don't develop
3. Babies born without vas