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AC1 (Izzy) > CF > Flashcards

CF Flashcards

1
Q

How has the demographic of CF pts changed overtime?

A

Used to be a disease of only children, now we see adults also being affected.

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2
Q

What is the inheritance pattern of CF?

What is the carrier status in the UK?

A

Autosomal recessive - 2 faulty copies required to present with CF

Carrier rate: 1 in 24 carriers

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3
Q

What is the likelihood of a child being born with CF in the UK?

A

1/24 x 1/24 x 1/4 = 1 in 2500 births in UK

(likelihood of two adult carriers meeting and that child having CF).

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4
Q

How many people are affected with CF worldwide?

A

70, 000

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5
Q

What are the likely offspring of two carriers?

A

1 child affected

2 unaffected carriers

1 unaffected non carrier

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6
Q

What is the protein affected in cf?

Describe this protein

A

CFTR - cystis fibrosis transmembrane conductance regulator (chloride channel)

2 nucelotide binding domains that go through the cell wall and an R domain –> forms a gate with a regulatory domain at the bottom that opens and closes

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7
Q

What class of protein does the CFTR channel belong to?

What does it allow to move into the cell?

A

ATP driven transmembrane conductance regulator

regualtory domain moves

allows negatively charged Cl- ions through the cell wall

Also plays a role in Na+ transport, Cl- moves, Na+ follows

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8
Q

What occurs to the CFTR to cause CF?

what is the overall effect of this?

A

mutation within DNA –> protein w error

CFTR = complex protein; ER normally ensures correct protein folding, packaged into vesicle and is sent to the cell wall

Misfolded protein –> does not get transported to cell wall

Lack of transport to cell wall, no Cl- transported out the cell, dry sticky mucus an epithelial cell membrane

Thick secretions; harbours pathogens

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9
Q

What are the complications of CF?

A

Obstructive lung disease

harbouring of pathogen

infection

inflammation

causes lung damage

leads to respiratory failure

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10
Q

What is the principle of tx in CF?

A

Early intervention

prevention of lung damage

disease modification

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11
Q

How do you diagnose CF?

A
  1. Newborn screening (UK only) –> Heel prick test
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12
Q

What are the conditions screened for in the UK via heel prick test?

A

CF

congenital hypothyroidism

sickle cell disease

phenylketonuria

medium chain acyl coa ….

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13
Q

What are the pro’s/ cons to screening via heel prick test?

A

Pros: early identification and early intervention; prevention of disease progressing, familial support given early

Cons: missed individuals falsely reassured, not preventing disease,

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14
Q

What makes a good screening test?

A

needs to be an important problem

needs to be a good test

needs to be some form of intervention

screening needs to actually help

needs to be able to be implemented

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15
Q

What is screened for in CF?

A

Immunoreactive trypsinogen (produced by pancreas)

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16
Q

How are IRT levels used to categorise CF risk?

A

Low IRT –> changes of CF v low

higher IRT –> look for genetic mutation –> if 2 mutations CF suspected, 1 mutation susepcted carrier, no mutation CF not suspected

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17
Q

What is a second test used to diagnose CF?

A

Chloride sweat test

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18
Q

How does the CF sweat test work?

A

Epithelial cells with CFTR channel also found in sweat duct

CFTR channel brings NaCl back into the cell, in CF the channel cannot do so and NaCl sits on the skin

CF will have elevated concentrations of sweat chloride; normally this is very low.

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19
Q

What is the effect of screening?

A

Child with median age of survival against 1940 –> median survival only 1 yrs

2007 heel prick test came in nationally, see median age of survival move up into 30 yrs

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20
Q

medical definition of disease

medical definition of illness?

A

Disease –> alteration in biological structure or functioning

Illness –> experience defined, the innately human experience of suffering

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21
Q

What are the sx of CF in newborn?

What are the sx of CF in older children?

A

Newborn:

loose fatty stools (due to lack of absorotion of fats, lack of pancreatic enzyme)

repeated chest infection

productive cough

failure to thrive/ slow growth

bowel obstruction (meconium ileus presents in 1/5 babies)

Older child:

chronic sinusitis

nasal polpys

pancreatitis

constipation

recurrent chronic pancreatitis

infertility due to congenital abscence of vas deferens or thick cervical mucus

metabolic bone disease

diabetes

liver disease

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22
Q

What are the different severities of CF mutation?

A

class 1 stops protein being produced at all –> no fucnction

class 2 –> misfolded protein –> does not transport to cell membrane –> no function

class 3 –> gets to cell membrane but problem with regualtory domain, does not allow conductance

class 4 –> conductance problem, Cl- movement is slower .

Class 5 –> turnover mutation; working protein but not enough of it

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23
Q

What is the timeline of CF pathology?

A
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24
Q

Treatment approaches for CF:

Thick sticky mucus

A
  1. Thick sticky secretions –> dilute, shift the secretion
  • hypertonic saline –> osmotic action; hydrates mucus
  • nebuliser used 1/2 a day
  • DNase (dornase alfa or pulmozyme) –> synthetic enzyme that cleaves neutrophil DNA which makes the mucus particularly viscous (after neutrophils apoptose).
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25
Q

Treatment approaches for CF: Obstructive lung disease

A
  • (inhaler to dilate airway used with hyperreactive airways, potentially sensitive to saline solution )
  • physiotherapy –> mechanically shift mucus by airway clearance techniques –> younger children various patting techniques; older children positive expiratory pressure helps clear out secretions
  • positive pressure also delivered by device
26
Q

Treatment appraoches to CF: infection and inflammation

A

Infection –> antibiotics, treated agressively, early and monitor

Antibiotics used to prevent, treat and to eradicate infection

27
Q

Why might AB’s be given even if infection suspected to be viral?

A

W viral infection likely to be a high degree of inflammation within the airways anyway; leads to further airway damage and high likelihood of secondary bacterial infection occurring.

28
Q

What is a bacterial infection of particular importance in CF?

A

Pseudomonas aeruginosa

gram negative; rod shaped

opportunisitic infection

found everywhere

29
Q

What infections are common in CF?

A

H influenza (early infection)

B cepacia,

MRSA

S.aureus

Pseudomona aeruginosa

30
Q

Why is P.aeruginosa infections particularly bad in CF?

A

Secretes exopolysaccarides –> protects the bacteria therefore difficult to tx in its mucoid form

fills up airway with purulent material that is difficult to clear –> leads to resp failure

31
Q

How common are chronic pseudomonas infections in CF patients?

A

Average number of individuals per CF centre around 7% patients affected

32
Q

What occurs if pseudomonas infection detected?

A
  1. Eradicate with antibiotics
  • ciprofloxain and nebulised ??
  • IV courses if particularly unwell; often two IV AB’s
  • monitor and detect if still there
  • some patients become colonised
33
Q

Extra pulmonary care: nutrition

Why do CF patient’s nutrition suffer?

A

Nutrition is a significant multifactorial problem

lack of pancreatic enzymes, malabsorption of fats and carbohydrates lost in stools

recurrent low grade bronchial infection; chronic cough; less tolerance to illness, vomiting more

34
Q

describe pathology of decreased nutrition in CF pts

A
  • malabsorption of fat
  • lack of fat soluble vitamins
  • progressive pulmonary infection
  • CF related diabetes
  • motility of GI tract
  • small bowel bacterial overgrowth
35
Q

What is the energy requirement of CF pts?

A

110 - 200% compared to healthy population

36
Q

What is PERT?

A

Pancreatic enzyme replacement therapy:

(pancreas can be small, necrosed even at birth in CF pt.

This is why IRT increases in those first few weeks, then drops away )

Enzymes replaced: 1) lipase 500-2500 unit per kg), protease, amylase

37
Q

What is the rationale for PERT?

A

Give pancreatic enzymes to make use of the calories individual already has

38
Q

Extra pulmonary care: increase calorie intake?

A

Enteral supplementation:

Supplements

NG Tube

PEG

39
Q

What vitamins may be given to CF pts?

A

Fat solubule vitamins:

Vitamin A, D, E , K (DAKE)

40
Q

What other than supplementation and vitamins is also given in CF pts?

A

Sodium chloride given due to excess loss of NaCl in sweat; given particularly in summer to prevenet hyponatremia.

41
Q

What is DIOS?

What is it due to?

How may it present?

A

Distal intestinal obstruction sundrome

due to decreased motility, thick intestinal mucus.

May present with pain, altered bowel habits, distention, vomiting, mass on the abdomen. Need to distinguish between complete blockage and incomplete blockage.

42
Q

What are the risks of DIOS?

A

Severe genotype

pancreatic insufficiency

inadequate salt intake

dehydration

history of meconium ileus

post organ transplant

43
Q

How is DIOS managed?

A

DIOS managed with osmotic laxatives:

Movicol

gastrogaffin

klean-prep (liters of water to flush out)

Aim: to avoid surgery and clear blockage

44
Q

How may meconium ileus scar

A

Scar over central abdomen

45
Q

How does the weight of CF patients change with age?

A

Overall loss of weight as CF children approach teenage yrs

Due to onset of CF associated diabetes

46
Q

What is the pathogenesis of diabetes in CF patients?

EDIT CARD

A

Direct effect on the pancreas itself

Reduction in the amount of antioxidants within the body –> beta cell loss

steroid treatments and infections pushes blood glucose up

liver disease also raises glucose

defective CFTR –> decreased alpha cell suppression –> Rise in glucagon

47
Q

How can we test for diabetes in CF pts?

A

Given oral glucose load, measure blood sugar with time.

With adequate response, blood sugar increases and is then brought down due to sufficient insulin.

in cf pts blood sugar remains high

48
Q

What is the definitive criteria for diabetes

A

fasting glucose > 7 mmol/l

2 hour post glucose challenge > 11.1 mmol/L

or HbA1C value of > 6.5%

49
Q

definition of impaired glucose tolerance

A
50
Q

definition of impaired fasting glucose

A
51
Q

What is the benefit of continued glucose monitor

A

less chance of missing unnoticed highs with fingerstick tests

52
Q

What is another complication of CF other than diabetes?

What % affected by cirrhosis/ portal HTN/ fatty liver?

A

Cystic fibrosis related liver disease

20-30% with cirrhosis

5-10% with portal hypertension

23-75% with fatty liver

3rd cause of death

53
Q

What is the pathology of liver disease in CF patients?

A

inflammation of hepatocytes causes obstruction of the bile ducts

there may be focal changes at first that then progresses to cirrhosis.

54
Q

What are the risks associated with development of liver disease in CF patients?

A

Time of diagnosis

Male

previous meconium ileus

exocrine insufficiency

55
Q

clinical signs of liver disease on examination?

A

Ascites

clubbing

splenomegaly

hepatomegaly

palmar erythema

dupytrens contracture

jaundice

56
Q

How do we monitor for liver disease in CF pts?

A

Clinical exam

liver enzyme measurement

PT measurement

ultrasound

biopsy

57
Q

What acid is taken in CF pts to help liver function?

A

Ursodeoxycholic acid –> bile acid that improves bile flow

58
Q

What are the small molecule drugs used in CF treatment?

A

CFTR modulators:

Ivacaftor

Lumacaftor

Tezacaftor

( Orkambi is ivacafotr and lumacafor together)

59
Q

How do the small molecule drugs treat CF?

A

Ivacaftor:

Breaks up, enters cell, finds its way to CFTR protein on cell wall, opens the gate of the CFTR channel and holds gate open.

Therefore only works in patients with class 2 mutations –> only 5% of patients with CF

60
Q

What does orkambi do?

A

Orkambi –> Ivacafotor and lumekaftor -> helps alter misfolded protein so it becomes escorted to cell membrane

Used for class 2 mutations (85% of individuals with delta F508 mutation can be treated).

AC1 (Izzy) (48 decks)

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