CYSTIC FIBROSIS

 It is also known as MUCOVISCIDOSIS (because the secretions in body especially the one in relation with the pancreas, are very thick and contribute to various manifestation)

It is also known as EXOCRINOPATHY (because this condition is having the propensity to involve the exocrine gland)

PATHOGENESIS :

1. AUTOSOMAL RECESSIVE
2. Defect chromosome 7
3. It is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance receptor (CFTR) protein. 

In cystic fibrosis - Phenyl alanine present at 508th position is deleted

so, most common mutation if F508 mutation

CFTR protein malfunction leads multiple manifestations

chloride channel is defective, as a result of which chloride/bicarbonate/water transport doesn't take place across it and due to this periciliary dehydration occurs and mucus becomes highly viscid

Important organs involved in this conditions:

1. Lungs
2. GIT
3. Pancreas - results in type 2 diabetic mellitus in future
4. Liver - biliary stasis can cause liver damage

Root cause of this condition :

1. Low water content of periciliary fluid
2. Acidic environmental of periciliary fluid due to defect in bicarbonate release
3. Mucociliary clearance

↓ 

inhaled bacteria

s.aureus , pseudomonas , burkholderia undergoes mucoid transformation , can forms biofilm impervious to antibiotics.

PATHOLOGIC FEATURES :

First involved in LUNGS

BRONCHIOLITIS

(folicular pluging in airway by thick tenacious secretions)

↓

Bronchitis

↓

Bronchiectasis

(large dilated airways filled pus)

↓

ultimately leads to recurrent pneumonia and cause death of person 

(before first year of life in india)

UPPER RESPIRATORY TRACT

Nasal polyps

recurrent  sinusitis

GASTROINTESTINAL TRACT (GIT)

Pancreas : size decreased

Pancreas secretion become thick and viscid

can be replaced by fibro fatty tissue

Amylase decreased , Lipase decreased

Malabsorption syndrome can occur - failure to thrive

LIVER

Patient end up with secondary biliary cirrhosis

obstructive jaundice/ prolongation of physiological jaundice

absence of cystic duct

TREATMENT : ORGAN TRANSPLANTATION is required in these pts

- Esophageal / duodenal glands(brunner's) filled with thick mucus , unable to secrete  their own secretions  and acid from stomach will not be neutralized and leads to duodenal ulcer

GENITO URINARY SYSTEM

IN FEMALES 

Formation of thick cervical mucus plug causes conception issue(Infertility)

Pregnancy can happen or not depends upon on her lungs function status

(shrunken lungs with decreased lungs volume is contraindicate for pregnancy)

TREATMENT : Regular tobramycin nebulization

IN MALES

Sexual function (normal - ejaculation and erection)

• Agenesis of vas deferens and epididymis
• Azoospermia
• Infertility

clinical features:

Chronic cough productive (purulent) :

• foul smelling pus present
• shortness of breath
• cor pulmonale ; right ventricular failure - non cardiogenic edema
• anterioposterior diameter increased
• chest, hyper resonance
• clubbing present
• sudden deterioration 

- Pneumothorax - respiratory deterioration present

- Massive hemoptysis - blood pressure decreased (hypotension)

Nasal stuffiness :

Meconium ileus :

• Abdominal distension and Delayed passes of meconium (normal < 48hrs)

Investigation of choice : GASTROGRAFFIN  ENEMA

Treatment of choice : GASTROGRAFFIN  ENEMA

GIT :

• Osmotic diarrhea due to absence of poor pancreatic secrections
• Steatorrhea
• Failure to thrive/ protein energy malnutrition (PEM)

VITAMIN - E  Decreased - Hemolytic anemia (Acanthocytes formation occur)

VITAMIN - K Decreased - Bleeding

LIVER CIRRHOSIS - ICTERUS

• Ascites / Hypersplenism / CAPUT medusae , Esophageal varices

GENITO URINARY SYSTEM : Infertility (Agenesis of vas deferens)

SWEAT GLAND :

• Sodium and chloride reabsorption both inhibited in cystic fibrosis also called as "SALTY BABY SYNDROME"  which leads to HYPOCHLOREMIC 

•  HYPOKALEMIC , METABOLIC ALKALOSIS is also seen due to increase aldosterone

DIAGNOSIS CRITERIA FOR CYSTIC FIBROSIS

- Presence of typical clinical features

• Respiratory - COPD , Bronchiectasis
• Gastrointestinal - Meconium ileus , Malabsorption (osmotic diarrhea to steatorrhea)
• Genitourinary - Infertility

OR

- A history of cystic fibrosis in a sibling

OR

- A Positive new born screening test

+

- Laboratory evidence for CFTR 

↓

- Dysfunction :

• Two elevated sweat chloride concentrations obtained on separate days >60mEq/L

OR

• Identification of two cystic fibrosis mutations by DNA sequencing

OR

• An abnormal nasal potential difference measurement

WORKUP :

SWEAT CHLORIDE TEST :

Method used here is PILOCARPINE IONTOPHORESIS - > 60 mEq/L x twice

false positive: sweat chloride > 60

- Anorexia nervosa

- Addison disease

- Congenital adrenal hyperplasia

- Nephrogenic diabetic insipidus

false negative :

- Malnutrition

- Edema

If equivocal report comes here that is

Report 1 ➝ 50

Report 2 ➝ 65

A non confirmatory sweat chloride test. then we do the 2nd test

TRANS EPITHELIAL NASAL POTENTIAL TEST :

Done in case of equivocal test chloride report

DNA  testing :

positive of at least 2 mutation

FECAL ELASTASE LEVEL :

To identify malabsorption component of disease

PULMONARY FUNCTION TESTING :

Obstructive manifestation earlier part of disease/

Restrictive lung disease in later part of disease

HbA1C - Secondary diabetic insipidus

CHEST X RAYS / HRCT CHEST :

Shows dilated airway

SPUTUM CULTURE :

Staph aureus , pseudomonas , infections can occur.

TREATMENT :

1. Human recombinant DNA technology

- DNA ase

- DORN ase

- It will decrease viscosity of sputum so antibiotic penetration and cough out of sputum is relatively easy

2. N - Acetyl cysteine followed by beta agonist nebulization

3. Nebulized Hypertonic saline 7% - can draw water in to perciliary mucus

4. Nebulized TOBRAMYCIN / AZTREONAM weekly (reduce chances of colonization)

5. Chest Percussion / Physiotherapy

6. Hand held oscillometric devices (vibrations help to mobilize secretions)

7. If BURKHOLDERIA CEPACIA infection present : antibiotic of choice - MEROPENEM

8. Steroids : ABPA (Aspergillus broncho pulmonary aspergilloma)

because lot of patient might be having upper airway colonization by aspergillus with highlighted feature of CENTRAL BRONCHIECTASIS - serum precipitin antibody against aspergillosis has to be done

9. IVACAFTOR

- 150mg B/D   IVACAFTOR will improve chloride conductance