Lifestyle Mx of CF: -Aerobic exercise is encouraged to increase sputum clearance (surfing, due to inhalation of salty air is apparently an excellent past-time for sputum clearance) -A high calorie, high salt diet is recommended with increased amounts of unsaturated fats (not saturated!) -Vitamin D can calcium supplements may be taken to minimise the risk of osteoporosis
Medical Mx of CF:
-Oxygen if necessary: this may be required with sever lung disease. Bilevel positive ariway pressure (BiPAP) ventilators are used (essentially the same as CPAP)
Antibiotic treatment for respiratory infections: -In mild cases: intermittent chemotherapy with cefaclor 500mg 3 x day, Flucloxacillin 500mg every 6hrs for staph. aureus infection -If symptoms persist despite physiotherapy suspect pseudomonas aeruginosa(70% of CF patients have this infection): RX with parenteral or aerosol chemotherapy every 3 months, also ceftazidime 2g IV every 8hrs. Rapid development of antiobiotic resistance is a major problem.
Treating pancreatic insuffiency and malnutrition: -Pancreatic enzymes and a low fat diet can improve steatorrhoea (fat loss) and vitamins are given to replace those not able to be absorbed
-Potential treatments to improve the viscosity of secretions (i.e to make them more watery) include blocking Na reabsorption with amiloride, or stimulating chloride secretion with adenosine/uridine triphosphates -Inhalation of recombinant human DNase decreases DNA amounts released from dead inflammatory cells (adds to viscosity of mucous) -Inhaled antibiotics/corticosteroids reduces inflammation and improves overall function -Chest manipulation/tapping/physiotherapy can be used to dislodge sputum, there are now mechanical devices for this such as the intrapulmonary percussive ventilator (IPV) -Inhalation of hypertonic saline also loosens secretions and ipratropium/albuterol (asthma style drugs) can be used for bronchodilation -There is the possibility of gene therapy as well... -Lung/heart transplantation may be necessary in the later stages of the disease -Infertility: an intracytoplasmic sperm injection is available for men, female infertility may require embryo transfer for rerpoduction -Diabetes is common and is treated with insulin injections -A feeding tube or growth hormones may be given for malnutrition
Cystic Fibrosis CF is a recessive genetic disorder involving a gene on chromosome 7. This defective gene causes lack of an ion transport protein, leading to problems with many bodily organs and systems, with a major effect on secretions. Respiratory problems (esp. recurrent infections) are common.
Bronchiectasis Bronchiectasis is destruction and widening of the large airways, usually caused by recurrent inflammation/infection. It can also be congenital. 50% of bronchiectasis cases can be attributed to cystic fibrosis.
A sweat test measures the amount of salt (sodium and chloride) in sweat. It is done to help diagnose cystic fibrosis. Normally, sweat on the skin surface contains very little sodium and chloride. People with cystic fibrosis have 2 to 5 times the normal amount of sodium and chloride in their sweat.
During the sweat test, medication that causes a person to sweat is applied to the skin. The sweat is then collected on a paper or a gauze pad and the amount of salt chemicals in the paper or gauze is measured in a lab.
An initial test may be done as early as 48 hours of age. However, a sweat test done during the first month of life may need to be repeated. Younger babies may not produce enough sweat to give reliable test results. Also, younger babies may have lower sweat chloride levels than older babies and children with cystic fibrosis.
1. Respiratory Effects: • Recurrent bronchopulmonary infection in childhood and it’s the most important cause in early adult life. • Sinusitis • Finger clubbing • Breathlessness • Haemoptysis • Nasal Polyps • Spontaneous Pneumothorax • Respiratory Failure • Cor Pulmonale
2. Gastrointestinal Effects: • Symptomatic Steatorrhea due to pancreatic dysfunction • Meconium Ileus Equivalent Syndrome • Cholesterol gallstones • Cirrhosis • Increased incidence of peptic ulceration and gastrointestinal malignancy
3. Nutritional Effects: • Malnutrition due t0o malabsorption and maldigestion.
4. Others: • Delay in puberty and skeletal maturity • Males are infertile • Females can conceive but develop secondary amenorrhea as the disease progresses. • Arthropathy and diabetes mellitus.
Newborn Screening The newborn screening tests (Guthrie Test) are used to look for early signs of congenital metabolic disorders. Early diagnosis means that treatment can be started quickly. It is a blood test done 48 – 72 hrs after birth. The blood is taken from the baby’s heel and collected onto special absorbent paper. Over 30 different congenital disorders can be detected using the baby’s blood sample. Two common tests are: - Immunoassay test for: o Congenital hypothyroidism Caused by an absent, small or improperly functioning thyroid gland. o Cystic fibrosis - Tandem Mass Spectrometry tests for o Phenyleketonuria (PKU) The baby cannot properly use the protein phenylalanine, which accumulates in the blood, causing brain damage. o Disorders of amino acid and fatty acid metabolism If the marker for cystic fibrosis is slightly increased then two further tests are performed on the blood - Abnormally high levels of the protein immunoreactive trypsin (IRT) from the pancreas - DNA test showing whether the baby carries any copy of the most common cf gene mutation, ΔF508
Reference Westmead Children’s Hospital – Tests to Protect Your Baby http://www.chw.edu.au/prof/services/newborn/tests030194.pdf Genetic Health Services Victoria – Newborn Screening http://www.genetichealthvic.net.au/pages/diagnosis/newbornscreen.html
In Australia: Incidence of Affected: 1 in 2500 Carrier status: 1 in 25 70 babies each year are born with the condition.
According to data collected by the Cystic Fibrosis Foundation, about 30,000 Americans, 3000 Canadians, and 20,000 Europeans have CF. The disease occurs mostly in whites whose ancestors came from northern Europe, although it affects all races and ethnic groups. Accordingly, it is less common in African Americans, Native Americans, and Asian Americans. About 2500 babies are born with CF each year in the United States. Also, about 1 in every 20 Americans is an unaffected carrier of an abnormal CF gene. These 12 million people usually are unaware that they are carriers. The median life expectancy is in the mid-30s, with end-stage lung disease the major cause of death. There is still no cure.
Causes CF is an autosomal recessive disease resulting from a gene mutation which causes deficiencies in the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR)which is a glycoprotein located on chromosome 7.
In 70% of cases the mutation occurs at delta-F508, where no phenylalanine is coded for. 1 in 22 caucasians are (asymptomatic) carriers.
The CFTR is a membrane protein which regulates chloride transport in epithelial cells. Sometimes mutations can result in non-functional CFTR however in the majority of cases the CFTR is not present in the cell membrane at all. Defective CFTR is made in the endoplasmic reticulum and as it travels to the cell membrane, the immune system recognises its error and marks it for destruction.
Pathophysiology of the symptoms:
Lungs The trachea and lungs are lined with motile cilia which beat in a layer of saline at the cell surface to sweep fluids and foreign particles out of the airway (and lungs). The layer of saline in vital because cilia could not beat freely if they were embedded in a layer of thick mucus. The CFTM chloride pump works to pump Cl- into the extracellular fluid, sodium follows by electrical attraction and water by osmosis. In CF there is no saline layer and the mucus is overly thick and sticky. The respiratory tract becomes congested with thick static mucus which leads to the chronic infections and subsequent pulmonary damage and collapse in CF patients.
Salty sweat: Sweat is secreted by mecrocrine glands which are simple tubular glands with a twisted coil which sits in the dermis. There are special secretory cells in the deep end of the gland and endothelial cells line the duct. In normal physiology, when a sweat gland is stimulated, the cells secrete a fluid (similar to plasma however without the protein) which travels from the coiled portion up through a straight duct to the surface. As it travels up most of the Na+ and Cl- is resorbed and the final secreted sweat contains 99% water. In CF patients the CFTR is absent so the Cl-(and therefore Na+) is excreted. Loss of these electrolytes can lead to arrthymias.
The pancreas secrets enzymes for digestion through the pancreatic duct (which then exports them to the intestine). In normal physiology chloride pumping causes water to flow out into the duct and carry the enzymes in a "watery slurry" (plagerized from kumar and clark-there is no better way to describe it!). However in the absentce of the CFTR, Cl- stays in the cells and water therefore stays in the cells. The enzymes are not pushed into the duct and begin to digest the pancreas itself. This causes inflammation and the production of thick mucus plugs the duct.
Infertility At least 97 percent of men with cystic fibrosis are infertile. These men make normal sperm but are missing vas deferens (which connect the testes to the ejaculatory ducts of the penis. Some women have fertility problems due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes amenorrhea (no menstruation)
saladin, anatomy and physiology kumar and clark, clinical medicine www.ygyh.org/cf/cause.htm http://www.healthinsite.gov.au/topics/Cystic_Fibrosis www.cf.org.au
Clubbing is seen as a thickening of the ends of fingers and sometimes toes underneath the nails. A simple test for clubbing is the diamond test. When the dorsal sides of the phalanges are pressed together and the nails make contact, a diamond shaped gap should be seen between the nails. In clubbing, no such gap is observed as the nails become rounded. The causes of clubbing are not fully understood. However, common conditions which are known to be linked with clubbing are as follows: Congenital heart disease (cyanotic type) Tetralogy of Fallot Tricuspid atresia Transposition of the great vessels Total anomalous venous return Truncus arteriosus Cystic fibrosis Bronchiectasis Lung abscess Crohn's disease Celiac disease Cirrhosis Lung cancer Pulmonary fibrosis
Resources: Cole and Epstein, and national institute of health (NIH) website
One study found that spirometry is important for monitoring pulmonary status in children. 6 years vs. 3 years old. FEV(0.5) may be more sensitive than FEV(1).
Spirometry in Early Childhood in Cystic Fibrosis Patients Vilozni et al. Chest.2007; 131: 356-361
Another suggests RVRTC (raised lung volume rapid thoraco–abdominal compression) and MBW (multiple-breath inert gas washout) for infants who are positive for neonatal test
Sooky Lum et al Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests Thorax, Apr 2007; 62: 341 - 347
10 comments:
Lifestyle Mx of CF:
-Aerobic exercise is encouraged to increase sputum clearance (surfing, due to inhalation of salty air is apparently an excellent past-time for sputum clearance)
-A high calorie, high salt diet is recommended with increased amounts of unsaturated fats (not saturated!)
-Vitamin D can calcium supplements may be taken to minimise the risk of osteoporosis
Medical Mx of CF:
-Oxygen if necessary: this may be required with sever lung disease. Bilevel positive ariway pressure (BiPAP) ventilators are used (essentially the same as CPAP)
Antibiotic treatment for respiratory infections:
-In mild cases: intermittent chemotherapy with cefaclor 500mg 3 x day, Flucloxacillin 500mg every 6hrs for staph. aureus infection
-If symptoms persist despite physiotherapy suspect pseudomonas aeruginosa(70% of CF patients have this infection): RX with parenteral or aerosol chemotherapy every 3 months, also ceftazidime 2g IV every 8hrs. Rapid development of antiobiotic resistance is a major problem.
Treating pancreatic insuffiency and malnutrition:
-Pancreatic enzymes and a low fat diet can improve steatorrhoea (fat loss) and vitamins are given to replace those not able to be absorbed
-Potential treatments to improve the viscosity of secretions (i.e to make them more watery) include blocking Na reabsorption with amiloride, or stimulating chloride secretion with adenosine/uridine triphosphates
-Inhalation of recombinant human DNase decreases DNA amounts released from dead inflammatory cells (adds to viscosity of mucous)
-Inhaled antibiotics/corticosteroids reduces inflammation and improves overall function
-Chest manipulation/tapping/physiotherapy can be used to dislodge sputum, there are now mechanical devices for this such as the intrapulmonary percussive ventilator (IPV)
-Inhalation of hypertonic saline also loosens secretions and ipratropium/albuterol (asthma style drugs) can be used for bronchodilation
-There is the possibility of gene therapy as well...
-Lung/heart transplantation may be necessary in the later stages of the disease
-Infertility: an intracytoplasmic sperm injection is available for men, female infertility may require embryo transfer for rerpoduction
-Diabetes is common and is treated with insulin injections
-A feeding tube or growth hormones may be given for malnutrition
Sources: Kumar and Clark, Wikipedia
From Angela
Definitions
Cystic Fibrosis
CF is a recessive genetic disorder involving a gene on chromosome 7. This defective gene causes lack of an ion transport protein, leading to problems with many bodily organs and systems, with a major effect on secretions.
Respiratory problems (esp. recurrent infections) are common.
Bronchiectasis
Bronchiectasis is destruction and widening of the large airways, usually caused by recurrent inflammation/infection. It can also be congenital. 50% of bronchiectasis cases can be attributed to cystic fibrosis.
Sweat test
A sweat test measures the amount of salt (sodium and chloride) in sweat. It is done to help diagnose cystic fibrosis. Normally, sweat on the skin surface contains very little sodium and chloride. People with cystic fibrosis have 2 to 5 times the normal amount of sodium and chloride in their sweat.
During the sweat test, medication that causes a person to sweat is applied to the skin. The sweat is then collected on a paper or a gauze pad and the amount of salt chemicals in the paper or gauze is measured in a lab.
An initial test may be done as early as 48 hours of age. However, a sweat test done during the first month of life may need to be repeated. Younger babies may not produce enough sweat to give reliable test results. Also, younger babies may have lower sweat chloride levels than older babies and children with cystic fibrosis.
http://children.webmd.com/Sweat-Test?page=3
Symptoms of Cystic Fibrosis:
1. Respiratory Effects:
• Recurrent bronchopulmonary infection in childhood and it’s the most important cause in early adult life.
• Sinusitis
• Finger clubbing
• Breathlessness
• Haemoptysis
• Nasal Polyps
• Spontaneous Pneumothorax
• Respiratory Failure
• Cor Pulmonale
2. Gastrointestinal Effects:
• Symptomatic Steatorrhea due to pancreatic dysfunction
• Meconium Ileus Equivalent Syndrome
• Cholesterol gallstones
• Cirrhosis
• Increased incidence of peptic ulceration and gastrointestinal malignancy
3. Nutritional Effects:
• Malnutrition due t0o malabsorption and maldigestion.
4. Others:
• Delay in puberty and skeletal maturity
• Males are infertile
• Females can conceive but develop secondary amenorrhea as the disease progresses.
• Arthropathy and diabetes mellitus.
Reference: Kumar and Clark pg 872
Newborn Screening
The newborn screening tests (Guthrie Test) are used to look for early signs of congenital metabolic disorders. Early diagnosis means that treatment can be started quickly. It is a blood test done 48 – 72 hrs after birth. The blood is taken from the baby’s heel and collected onto special absorbent paper. Over 30 different congenital disorders can be detected using the baby’s blood sample. Two common tests are:
- Immunoassay test for:
o Congenital hypothyroidism
Caused by an absent, small or improperly functioning thyroid gland.
o Cystic fibrosis
- Tandem Mass Spectrometry tests for
o Phenyleketonuria (PKU)
The baby cannot properly use the protein phenylalanine, which accumulates in the blood, causing brain damage.
o Disorders of amino acid and fatty acid metabolism
If the marker for cystic fibrosis is slightly increased then two further tests are performed on the blood
- Abnormally high levels of the protein immunoreactive trypsin (IRT) from the pancreas
- DNA test showing whether the baby carries any copy of the most common cf gene mutation, ΔF508
Reference
Westmead Children’s Hospital – Tests to Protect Your Baby
http://www.chw.edu.au/prof/services/newborn/tests030194.pdf
Genetic Health Services Victoria – Newborn Screening
http://www.genetichealthvic.net.au/pages/diagnosis/newbornscreen.html
Incidence
In Australia:
Incidence of Affected: 1 in 2500
Carrier status: 1 in 25
70 babies each year are born with the condition.
According to data collected by the Cystic Fibrosis Foundation, about 30,000 Americans, 3000 Canadians, and 20,000 Europeans have CF. The disease occurs mostly in whites whose ancestors came from northern Europe, although it affects all races and ethnic groups. Accordingly, it is less common in African Americans, Native Americans, and Asian Americans. About 2500 babies are born with CF each year in the United States. Also, about 1 in every 20 Americans is an unaffected carrier of an abnormal CF gene. These 12 million people usually are unaware that they are carriers. The median life expectancy is in the mid-30s, with end-stage lung disease the major cause of death. There is still no cure.
Causes and pathophysiology of CF:
Causes
CF is an autosomal recessive disease resulting from a gene mutation which causes deficiencies in the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR)which is a glycoprotein located on chromosome 7.
In 70% of cases the mutation occurs at delta-F508, where no phenylalanine is coded for. 1 in 22 caucasians are (asymptomatic) carriers.
The CFTR is a membrane protein which regulates chloride transport in epithelial cells. Sometimes mutations can result in non-functional CFTR
however in the majority of cases the CFTR is not present in the cell
membrane at all. Defective CFTR is made in the endoplasmic reticulum and as it travels to the cell membrane, the immune system recognises its error and marks it for destruction.
Pathophysiology of the symptoms:
Lungs
The trachea and lungs are lined with motile cilia which beat in a layer of saline at the cell surface to sweep fluids and foreign particles out of the airway (and lungs). The layer of saline in vital because cilia could not beat freely if they were embedded in a layer of thick mucus. The CFTM chloride pump works to pump Cl- into the extracellular fluid, sodium follows by electrical attraction and water by osmosis. In CF there is no saline layer and the mucus is overly thick and sticky. The respiratory tract becomes congested with thick static mucus which leads to the chronic infections and subsequent pulmonary damage and collapse in CF patients.
Salty sweat:
Sweat is secreted by mecrocrine glands which are simple tubular glands with a twisted coil which sits in the dermis. There are special secretory cells in the deep end of the gland and endothelial cells line the duct.
In normal physiology, when a sweat gland is stimulated, the cells secrete a fluid (similar to plasma however without the protein) which travels from the coiled portion up through a straight duct to the surface. As it travels up most of the Na+ and Cl- is resorbed and the final secreted sweat contains 99% water. In CF patients the CFTR is absent so the Cl-(and therefore Na+) is excreted. Loss of these electrolytes can lead to arrthymias.
The pancreas secrets enzymes for digestion through the pancreatic duct (which then exports them to the intestine). In normal physiology chloride pumping causes water to flow out into the duct and carry the enzymes in a "watery slurry" (plagerized from kumar and clark-there is no better way to describe it!). However in the absentce of the CFTR, Cl- stays in the cells and water therefore stays in the cells. The enzymes are not pushed into the duct and begin to digest the pancreas itself. This causes inflammation and the production of thick mucus plugs the duct.
Infertility
At least 97 percent of men with
cystic fibrosis are infertile. These men make normal sperm but are
missing vas deferens (which connect the testes to the
ejaculatory ducts of the penis. Some women have fertility problems
due to thickened cervical mucus or malnutrition. In severe cases,
malnutrition disrupts ovulation and causes amenorrhea (no menstruation)
saladin, anatomy and physiology
kumar and clark, clinical medicine
www.ygyh.org/cf/cause.htm
http://www.healthinsite.gov.au/topics/Cystic_Fibrosis
www.cf.org.au
JESS
Causes of Clubbing:
Clubbing is seen as a thickening of the ends of fingers and sometimes toes underneath the nails. A simple test for clubbing is the diamond test. When the dorsal sides of the phalanges are pressed together and the nails make contact, a diamond shaped gap should be seen between the nails. In clubbing, no such gap is observed as the nails become rounded. The causes of clubbing are not fully understood. However, common conditions which are known to be linked with clubbing are as follows:
Congenital heart disease (cyanotic type)
Tetralogy of Fallot
Tricuspid atresia
Transposition of the great vessels
Total anomalous venous return
Truncus arteriosus
Cystic fibrosis
Bronchiectasis
Lung abscess
Crohn's disease
Celiac disease
Cirrhosis
Lung cancer
Pulmonary fibrosis
Resources:
Cole and Epstein, and national institute of health (NIH) website
Lung function testing.
One study found that spirometry is important for monitoring pulmonary status in children. 6 years vs. 3 years old. FEV(0.5) may be more sensitive than FEV(1).
Spirometry in Early Childhood in Cystic Fibrosis Patients
Vilozni et al. Chest.2007; 131: 356-361
Another suggests RVRTC (raised lung volume rapid thoraco–abdominal compression) and MBW (multiple-breath inert gas washout) for infants who are positive for neonatal test
Sooky Lum et al
Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests
Thorax, Apr 2007; 62: 341 - 347
Pat
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