Biology – Unit 1 Topic 2: Genes and Health

CYSTIC FIBROSIS

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Students will be assessed on their ability to:
1) Explain how the gene mutation in people with cystic fibrosis (CF) impairs the
functioning of the gaseous exchange, digestive and reproductive system

Text book: pp 116 - 121

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Introduction

- Cystic fibrosis is one of the most common life-shortening, childhood-onset inherited

diseases
- It is a genetic disease affecting the exocrine (mucus) glands of the lungs, liver,
pancreas, intestines as well as reproductive system, causing progressive disability
due to multisystem failure
- It affects the body's ability to move salt and water in and out of cells
- This defect causes sticky mucus to be secreted, blocking passageways and
preventing proper function of organs
- It is caused by a mutation in the gene on chromosome 7 for protein called CFTR
(Cystic Fibrosis Transmembrane Regulator)
- There are actually over 300 different mutations known, the most common mutation
is a deletion of three bases, removing one amino acid out of 1480 amino acids in
the protein
- People without CF have two working copies (alleles) of the CFTR gene, only one is
needed to prevent cystic fibrosis
- CF develops when neither allele can produce a functional CFTR protein - it is
considered an autosomal recessive disease

Mechanism of Disease

- CFTR is a chloride ion channel protein found in the cell membrane of epithelial
(lining) tissue cells
- Mutation causes the absence of channel or non-functional channel, so chloride ions
cannot diffuse out of the cell into the fluid in the airways or ducts
- Chloride ions build up inside these cells, which cause sodium ions to enter (as
sodium ion channel is not inhibited by CFTR)
- The increased concentration of both these ions inside the epithelial cells decreases
the water potential
- Water moves into the cells from the mucus lining the airways via osmosis, causes
the mucus to be drier and more sticky than normal
- Sticky mucus block the tubes into which it is secreted, such as the small intestine,
pancreatic duct, bile duct, sperm duct, bronchioles and alveoli
- These blockages lead to the symptoms of CF: breathlessness, lung infections such
as bronchitis and pneumonia, poor digestion and absorption, and infertility
Biology – Unit 1 Topic 2: Genes and Health

Effect of CF on Gas Exchange System

- Goblet cells in the epithelial lining of the airways produce mucus that coats the
tubes
- Any dust or microorganisms that enter the airways will be trapped in the mucus
- Mucus with the trapped dust is moved by wave-like beating of cilia of the epithelial
cells to the back of the mouth to be removed
- In people with CF, the thick and sticky mucus cannot be moved by the cilia, they
often have severe coughing fits in an attempt to get rid of the mucus
- Thick mucus blocks the narrow airways, preventing ventilation of the alveoli
- Smaller surface area available for gas exchange – inadequate oxygen causes
breathlessness, tiredness and lacking in energy
- Low oxygen concentration in the mucus due to slow diffusion of oxygen through it
encourages the growth of harmful bacteria
- White blood cells and antibodies cannot function effectively in the thickened mucus
- This leads to bacterial infection and inflammation of the airway which cause
damage to the lung tissues

Effect of CF on Digestive System

- Pancreas is an organ responsible for providing digestive juices which help break
down food
- The lack of digestive enzymes leads to difficulty absorbing nutrients as food is
partially digested or undigested with their subsequent excretion in the faeces
- Thick mucus forms a barrier between the content of the intestine and the lining as
well as clogging the villi – reduce surface area for absorption
- Malabsorption leads to malnutrition and poor growth and development because of
calorie loss
- Individuals with CF also have difficulties absorbing the fat-soluble vitamins A,D,E
and K
- Thick secretions block duct, digestive enzymes cannot be secreted into the
duodenum and result in irreversible damage to the pancreas – cyst and fibrosed
tissue within the pancrease
- If damage occurs to cells of Islet of Langerhans, secretion of insulin which is
involved in he control of blood glucose may be impaired – diabetes

Effect of CF on Reproductive System

- Men with cystic fibrosis may be sterile due to the absence of vas deferens which
connects the testes to the ejaculatory ducts so sperm cannot leave the testes
- Thick mucus may also block vas deferens causing fewer sperm present in each
ejaculation
- Some women have fertility difficulties due to thickened cervical mucus which
prevents sperm fromreaching the egg
- In severe cases, malnutrition disrupts ovulation and causes amenorrhea
Biology – Unit 1 Topic 2: Genes and Health

Diagnosis

- Cystic fibrosis may be diagnosed by newborn screening, sweat testing or genetic

testing
- The most commonly-used form of testing is the sweat test - people with CF have
increased amounts of sodium and chloride in their sweat
- When sweat passes along the duct of sweat gland, salt is not reabsorbed due to
non-functional CFTR – losing salt in the sweat
- This will lead to imbalance of ions in the body – changes concentration of body fluid,
affects the normal functioning of nervous system and the heart
- Couples who are pregnant or who are planning a pregnancy can themselves be
tested for CFTR gene mutations to determine the likelihood that their child will be
born with cystic fibrosis

Treatment

- Physiotherapy – carried out regularly a few times each day to dislodge mucus from
the lungs
- Antibiotics – to fight infections in the lungs
- Vaccines – flu and pneumonia vaccine to protect them from flu and pneumonia
- DNAse drugs - to loosen the mucus by breaking down DNA released during the
breakdown of white blood cells in the mucus which increases the stickiness of the
mucus
- Steroids – to reduce lungs inflammation
- Bronchodilators – to increase the size of small airways by relaxing the muscles
- Insulin – to regulate blood gulcose concentration if problems of pancrease has led
to diabetes
- Heart-lung transplant – when heart or lungs become severely damaged
- Digestive enzymes – to help food digestion
- Balanced and high energy diet – to increase calories intake
- Intracytoplasmic sperm injection - to provide fertility for men
- In vitro fertilisation – fertility treatment for women
- Gene therapy – attempts to place a normal copy of the CFTR gene into affected
cells so that normal CFTR protein can be produced