Lecture 11 - CF is a Multisystem Disorder Flashcards Preview

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Flashcards in Lecture 11 - CF is a Multisystem Disorder Deck (58):
1

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

2

Median life expectancy of CF patients today

Mid 30s, early 40s

3

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

4

How is sweat stimulated in CF sweat test?

Pilocarpine iontophoresis

5

Normal [Cl-] in blood

105mL/L

6

Two parts of a sweat gland

1) Secretory coil
2) Reabsorptive duct

7

Tonicity of fluid in the secretory coil

Isotonic

8

Tonicity of fluid in the reabsorptive duct

Hypotonic

9

What happens in the secretory coil?

Water, NaCl is pumped into lumen

10

What happens in reabsorptive duct?

CFTR, ENaC reabsorb Cl- and Na+

11

Relationship between ENaC and CFTR in sweat duct

CFTR stimulates ENaC

12

Relationship between ENaC and CFTR in lungs

CFTR inhibits ENaC

13

Hyponatremic

Low Na+ in plasma

14

Condition of low plasma Na+

Hyponatremic

15

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

16

Hypokalemic metabolic alkalosis

Abnormally high plasma bicarbonate

17

Exocrine pancreatic functions

Lipase, amylase, protease

From pancreatic acini

18

Endocrine pancreatic functions

Islets of Langerhans

Insulin, glucagon

19

Mutation types associated with pancreatic insufficiency

I, II, III, VI

20

Prevalence of pancreatic insufficiency in CF

85%

21

What is steatorrhoea?

Fatty, foul-smelling stools from poor fat absorption

22

Name for fatty stools from poor fat absorption

Steatorrhoea

23

Fat-soluble vitamins

A, D, E, K

24

PERT

Pancreatic enzyme replacement therapy
Lipase, amylase, protease

25

What is 'enteric coated'?

Coating of PERT tablets

Prevents contents being released in stomach. Contents released in intestine

26

Where in the pancreas is CFTR?

Apical membrane of pancreatic ductal epithelial cell

27

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

28

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

29

CFRDM

Cystic fibrosis related diabetes mellitus

30

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)

31

Age of onset of CFRDM

Very rare under ten years

50% prevalence at 30 years

32

Effect of CFRDM on mortality

6-fold increase with CFRDM

33

CFRDM detection

Very difficult clinically, as symptoms aren't obvious.

Normally correlates with decline in lung function

Needs to be tested for regularly

34

Complications of CFRDM

Increased risk of microvascular complications (eyes)

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

35

Prevalence of liver disease

25% patients

36

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

37

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

38

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

39

Danger of oesophageal varices

Can bleed uncontrollably

40

Frequency of hepatocellular failure

2-3%

41

Where in the liver is CFTR found?

Epithelial cells lining intra-hepatic bile ducts

42

Where is CFTR found in the GIT?

Luminal membrane of intestinal epithelial cells

43

Effects of dysfunctional CFTR on GIT

Decreased luminal liquid volume

44

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

45

Effects of gastro-oesophageal reflux on lung function

Aspiration of stomach acid leads to greater inflammation of lungs

46

What is meconium ileus?

Inspissated intraluminal meconium causing bowel obstruction

47

Prevalence of meconium ileus

10-15% of neonates

48

What does meconium ileus correlate with?

Pancreatic insufficiency

49

Possible cause for CF gastro-oesophageal reflux

CF can interfere with stomach emptying

50

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

51

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

52

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

53

Common bone disease with CF

Osteoporosis

54

Difference in fracture rates between CF and unaffected people

2 fold increase for adults with CF

55

Prevalence of infertility in males with CF

99%

56

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

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

57

Renal effects of CF

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

Aminoglycosides are nephrotoxic, so treatment can cause renal problems

58

ENT effects of CF

1) 10 - 30% patients have nasal polyps
2) Aminoglycosides are ototoxic