Pulmonary Hypertension

Definition:

Mean pulmonary artery pressure (mPAP) > 25mmHg at rest or > 30mmHg during exercise. Can present with no apparent underlying disease (primary pulmonary hypertension) or in association with other diseases.

Causes:

1. Pre-capillary (in pulmonary arteries and arterioles)

Most severe. Examples: congenital heart disease (left-to-right shunt), pulmonary embolism.

2. Capillary

Examples: pulmonary fibrosis, COPD.

3. Post-capillary

Examples: left ventricular failure, mitral valve disease.

4. Miscellaneous

Examples: drugs, sickle-cell anaemia.

Pathophysiology:

Hypoxic vasoconstriction, decreased surface area of pulmonary vascular bed, increased right ventricular volume/pressure.

Signs and symptoms:

According to cause, signs and symptoms of right ventricular failure (eg. peripheral oedema, shortness of breath).

Investigations:

CXR - enlargement of pulmonary arteries. ECG – right ventricular hypertrophy, right atrial enlargement. Echocardiogram – enlarged right ventricle.

Management:

Treat underlying cause. Primary – warfarin, oxygen and calcium channel blockers.

Prognosis:

Mean survival of 2-3 years from diagnosis. Cause of death often right ventricular failure or sudden death.

Pulmonary Oedema

Definition:

Collection of fluid in lung interstitial space and/or alveolar spaces. Characterised by extreme breathlessness.

Causes:

Heart failure.

Pathophysiology:

Pressure above 20mmHg causes fluid filtration from capillaries into interstitial space. Further accumulation of fluid disrupts intercellular membranes, leading to collection of fluid in alveolar spaces.

Signs and symptoms:

Acutely breathlessness, wheezing, anxiety and profuse sweating. Cough productive of frothy, blood-tinged sputum. Tachypnoeic with peripheral circulatory shutdown. Tachycardia, raised venous pressure and gallop rhythm. Crackles and wheezes are heard throughout the chest.

Investigations:

CXR - diffuse haziness, owing to alveolar fluid and lines of interstitial oedema. Can be unilateral, giving the appearance of a tumour that disappears on treatment.

Management:

Place in sitting position, high-concentration oxygen/ventilation. Intravenous diuretics, morphine, venous dilators, bronchodilators.

Prognosis:

Acute emergency.

Wat is Cystic Fibrosis??? ...

Definition of cystic fibrosis:
Is an inherited atosomal-reccesive disorder of the exocrine glands, causing those glands to produce abnormally thick secretions of mucus, and elevation of sweat electrolytes.

[autosomal reccesive=A genetic condition that appears only in individuals who have received two copies of an autosomal gene, one copy from each parent. The gene is on an autosome, a nonsex chromosome. The parents are carriers who have only one copy of the gene and do not exhibit the trait because the gene is recessive to its normal counterpart gene. If both parents are carriers, there is a 25% chance of a child inheriting both abnormal genes and, consequently, developing the disease.exocrine glands=are glands whose secretions pass into a system of ducts that lead ultimately to the exterior of the body]


The glands most affected are those in the in the pancreas and respiratory system and sweat glands. Cystic fibrosis is usually recognised in infancy or early childhood, chiefly among caucasians. The earliest manifestation is meconium ileus, an obstruction of the small bowel by viscid stool. [viscid stool= glutinous or sticky] .


The most reliable diagnostic tool is the sweat test, which shows elevations of levels of both sodium and chloride. Because there is no known cure, treatment is directed at prevention of respiratory infections, which are the most frequent cause of death.

Life expectancy in cystic fibrosis has improved markedly over the past several decades, and with early diagnosis and treatment most patients can be expected to reach mid adulthood.


References;

http://medical-dictionary.thefreedictionary.com/viscid

http://imagecache.allposters.com/images/pic/CMSPOD/502-28~Lung-with-Cystic-Fibrosis-Posters.jpg

Mosby's dictionary of medicine, nursing and health professions

Pathophysiology of Cystic Fibrosis

Cystic fibrosis is an autosomal recessive disorder in which mutation occurs on the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The gene encodes a protein, CFTR that regulates multiple ion channels, the chloride channel – CFTR, sodium channel – EnaC etc. that involve in mucus secretion and other cellular processes.

Dehydration of mucus layer in cystic fibrosis
In epithelial cells, epithelial sodium channel (ENaC) is normally inhibited by CFTR. However in cystic fibrosis, ENaC activity is markedly increased while chloride secretion into the lumen is reduced. This leads to an increased reabsorption of sodium into the cells. The ion changes increase passive water reabsorption. Thus in cystic fibrosis, the mucus layer coating respiratory and intestinal epithelial cells becomes dehydrated, thick and sticky. In the lungs, the dehydration leads to defective action and the accumulation of hyperconcentrated secretions. This may obstruct the air passages and predispose to recurrent pulmonary infections.

CFTR in transport of bicarbonate ions
In pancreas, a mutated CFTR can have completely or partially preserved chloride transport, but markedly abnormal bicarbonate transport. The absence of bicarbonate ions decreases luminal pH, which leads to a variety of adverse effects.

Increased salt content in sweat
The function of CFTR in the sweat gland ducts is to reabsorb luminal chloride ions and ENaC to reabsorb sodium. Thus, in the sweat ducts, mutated CFTR gene results in a decreased reabsorption of sodium chloride.

complications and prognosis of people with cystic fibrosis

Complications of people with cystic fibrosis

3 different categories of complications:

Respiratory complications

Chronic respiratory infections:

Pneumonia, bronchitis, chronic sinusitis and bronchiectasis — an abnormal dilation of the walls of the bronchial tubes that makes it more difficult to clear your airways. Asthma can result from chronic inflammation of the bronchial lining.

Respiratory infections are common because thick mucus blocks the airways and provides an ideal breeding ground for bacteria. The most common infective agent in people with cystic fibrosis is Pseudomonas aeruginosa. It causes increased inflammation of the respiratory tract.

People with cystic fibrosis may also develop bleeding from the lungs causing them to cough up blood (hemoptysis), respiratory failure or collapsed lung (pneumothorax). Lung disease eventually may cause the lower right chamber (right ventricle) of the heart to fail. Ultimately, complications from lung problems may lead to fatality for people with cystic fibrosis.

Nutritional complications

People with cystic fibrosis are prone to chronic diarrhea and severe nutritional deficiencies. The thick secretions obstruct the ducts in pancreas, preventing enzymes that digest fats and proteins from reaching the intestines. These secretions also prevent the body from absorbing fat-soluble vitamins (A, D, E, K).

In addition, the bile duct, the duct that carries bile from liver and gallbladder to small intestine, may become blocked and inflamed, leading to liver problems, such as cirrhosis.

Reproductive complications

Cystic fibrosis also affects the reproductive system. The thick secretions often block the tube connecting the testis and prostate gland (vas deferens) causing men with cystic fibrosis to be infertile.

Prognosis of people with cystic fibrosis

Over the last three decades, the prognosis has improved dramatically, although there are still no options of cure for the disease. However, it is found that people with exocrine pancreatic sufficiency, male, absence of infective bacteria mentioned, balanced family function and coping as well as compliance with treatment produce a more favourable outcome of the disease compared to those who aren’t.

Screening is possible for parents who are pregnant to test for the presence of the disease in their newborn child. The development of new gene replacement therapy for cystic fibrosis transmembrane conductance regulator gene (CFTR – gene that causes cystic fibrosis to occur if defect) improve the prognosis of people susceptible to developing the disease.

INCIDENCE OF CYSTIC FIBROSIS

Europe (apparently, it’s similar for Australia)• 1 in 2000-3000 new borns are affected
• There are local and regional variations
o E.g. In France, there is a high incidence in Brittany, and a lower incidence in the South
• Mutations are detected in more than 95% of the CFTR genes taken from CF patients
o Most common mutation – F508del.
o 10-15% of mutations – 5 to 10 other mutations, G542X, N1303K, G551D
o Mediterranean countries – G542X and N1303K most common
o Ethnic specific mutations as well –the incidence is related to a specific country/region

Africa
• No accurate prevalence figures for northern African countries bordering the Medieterranean
o Studies that have been done show largely European mutations (F508del., G542X and N1303K), but at different frequencies
o Some unique mutations present
• There is evidence that CF is quite common (analysis of individuals of sub-Saharan origin) and underdiagnosed
• Carrier frequency – 1 in 42  thus, the calculated expected incidence = 1 in 7056

North America
• Incidence: 1 in 3500
• CFTR mutations reflect the geographic origin of the population
o Strong relationship to Europe
• F508del mutation is the most common CF mutation in African Americans  due to ethnic mixture with Caucasians
• African CFTR mutation (3120+1G A) is the second most prevalent allele in African America CF patients
• Canada
o If the region contain people of French of British origin, their rate of incidence reflects the ancestral British and French rate.
o East to west – decrease in the frequency of F508del. – due to increase in ethnic diversity

Latin America
• Incidence ranges from 1 in 3900 to 1 in 8500
• F508del mutation is the most common cause of CF
o Higher frequency in countries with a higher proportion of individuals of Caucasian origin (e.g. Uruguay, Argentina), and vice versa (e.g.Chile)
Middle East
• Incidence ranges from 1 in 2560 to 1 in 15876
o Incidence varies according to ethnic background and the degree of consanguinity
o 65% - Arab origin
• Mutations shared with other regions of the world – F508del., N1303K, W1282X and 3120+1G>A .
o 3120+1G>A - frequent in those of African descent
o F508del – common in Lebanon and Israel
• Rare mutations throughout the Near and Middle East  rarely observed anywhere else
o A mutation may be specific for an ethnic/religious group
• Due to geographic location, indigenous founder mutations and ethnic mixture  ‘melting pot’ of genetic influences

Asia
• Japan – 1 in 100,000 to 1 in 350,000
• India – 1 in 40,000 to 1 in 100,000
o No single mutation has an incidence greater than 15%
o High heterogenous population
• Pakistan – 60% of patients with CF are homozygous for F508del
o Lower in Indian (20%) and Japanese (10%) patients

Source - From WHO

-Rushmi

Treatment - Medical

PCL TASK
Management of Cystic Fibrosis
Medical
• Bronchodilators
• Improved breathing
• Improved Antibiotics
 Better at fighting infections
 Administered intravenously, orally or inhaled – treat mucus-clogged airways
 Nebulised drugs (steroids, bronchodilators, antibiotics)
 Breathing Devices
• OPEP
• Oscillatory Positive Expiratory Pressure
• As the patient breathes through these, airflow vibrations are created that help to break the mucus loose from the airway walls
• The pressure generated in exhalation keeps the airways open
• Enriched diet
 CF affects the digestive system, the body does not absorb enough nutrients
LUNGS
 Drugs work in the following ways –
• Bronchodilator drugs – open the airways by relaxing surrounding muscle. Relieve tightness and shortness of breath
• Antibiotics – treat or control persistent infection
• Steroids – reduce inflammation in the airways
PANCREAS
- Pancreatic enzyme insufficiency is a common symptom of CF
- CF affects the pancreas so enzyme replacement capsules should be taken with meals to replace pancreatic enzymes and enable people with CF to gain more energy from the foods they eat
- pancreatic enzyme replacement therapy – specially coated enzyme beads. Swallowed in capsules. A dietician will advise on the different concentrations of enzymes needed for different foods.
- interestingly, Australia’s climate is not suited to maintaining the potency of coated microspheres – which must be stored below 250C, in a dark and dry environment.
Enzymes available in Australia are:
CREON® - Solvay Pharmaceuticals (available in several strenghts)
COTAZYM® - Organon
PANCREASE - Janssen-Cilag - Discontinued in Australia December 2005
OTHER ORGAN
- If bones are affected by a lack of minerals, they may get osteoporosis
- Bisphosphanates have been shown to be beneficial

http://www.nlm.nih.gov/medlineplus/cysticfibrosis.html#cat3
http://www.yourlunghealth.org/lung_disease/cystic_fibrosis/treatment/index.cfm
http://www.cysticfibrosis.org.au/treatment/medication/

Screening and Varying Levels of Severity in CF

In Australia, screening for CF occurs shortly after birth for every child, tested for alongside many other conditions with the Guthrie heel prick test. The test looks for increased levels of trypsin, a digestive enzyme, which is markedly increased in every newborn. This detects around 95% of cases, and is confirmed with a sweat test.

The severity of CF varies markedly between individuals, and there is mounting evidence that subtle differences in other genes - besides the defective genes known to cause cystic fibrosis - can significantly modify the inherited disease's severity.

The extent to which the different body systems are involved varies greatly between patient. This difference in severity has many implications for both the treatment and prognossis for the patient with CF, and is largely determined by the extent the lungs are affected.

Diagnosis of Cystic Fibrosis - Sarah

Classic cystic fibrosis reflects two loss-of-function mutations in the CFTR gene and is characterized by chronic bacterial infection of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to obstructive azoospermia, and elevated concentrations of chloride in sweat. Patients with nonclassic cystic fibrosis have at least one copy of a mutant gene that confers partial function of the CFTR protein, and such patients usually have no overt signs of maldigestion because some pancreatic exocrine function is preserved. Although a value of 60 mmol per liter or higher on the sweat chloride test is diagnostic of cystic fibrosis, the concentration of sweat chloride is usually somewhat lower in patients with the nonclassic form of the disease (approximately 60 to 90 mmol per liter) than in those with classic cystic fibrosis (approximately 90 to 110 mmol per liter); moreover, the test result is sometimes borderline (40 to 59 mmol per liter) or normal ² Some CFTR mutations that result in residual CFTR function have been linked to disease of one organ, such as late-onset pulmonary disease, congenital bilateral absence of the vas deferens, or idiopathic pancreatitis.

references
http://www.medical-journals.com/real28.php

Peoples tasks

• Other manifestations of cystic fibrosis - Ari
• What is cystic fibrosis? – Jacquie
• Incidence of cystic fibrosis? - Rushmi
• Pathophysiology - Dillys
• Prognosis/complications - Hasif
• Diagnosis – Sarah - me
• Pulmonary oedema/Pulmonary hypertension - Lionel
• Management
o Medicine – Georgia
o Surgical/preventative - Kylie
• Genetic basis of disease - Sam
o Genetic counselling (reproductive) - Ambu
• Degrees of severity of cystic fibrosis/screening - Steph
• Signs and symptoms of CF, reproductive - Nathan
• Support networks for cystic fibrosis - Jemima

Sorry this is so late guys, completely forgot... =(

Pathophysiology

Cystic fibrosis is an autosomal recessive trait caused by mutations at a single gene locus on the long arm of chromosome 7. Cystic fibrosis reflects the loss of function of the CFTR protein. The CFTR protein normally regulates the transport of electrolytes and chloride across epithelial cell membranes.

More than 1,000 mutations of the CFTR gene have been described to date.Phenotypic appearance depends on the type of mutation (ie, class), location of the gene, molecular mechanism, and interaction with other mutations, as well as genetic and environmental influences.

The most common mutation of the CFTR gene is caused by the deletion of phenylalanine at position 508 (DF508, or delta-F508) and occurs with varying frequency in different ethnic groups. Worldwide, this allele is responsible for approximately 66% of all CF chromosomes.

Screening
Of the 1,000 or more infants born yearly with CF, most are diagnosed at a mean age of 3 to 4 years. Of note, nearly 10% of CF cases are diagnosed in individuals older that 18 years. Newborn screening for cystic fibrosis has been instituted in eight states, although national screening plans have not been mandated. In all, 10% of affected infants in the United States are diagnosed at birth either by prenatal diagnosis (3%) or by newborn screening (7%). The currently available genetic screening tools for CF include the Guthrie test, in which measurements of the immunoreactive trypsinogen in dried blood are taken, and measurement of the most common CF mutations, including DF508.

• Screening should be offered to (1) adults with a family history of CF, (2) reproductive partners of individuals with cystic fibrosis, (3) couples in whom one or both individuals are Caucasian (including Ashkenazi Jewish persons) and are planning pregnancy, and
• Screening should be made available to non-Caucasian or Ashkenazi-Jewish individuals or couples.

Issues to keep in mind include the gestational age at which the couple presents for prenatal care, and the feasibility of pregnancy termination. These factors should be included in the CF screening discussion with parents.