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27 Cards in this Set
- Front
- Back
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How is Cystic Fibrosis inherited?
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Autosomal recessive
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What is the primary defect in Cystic Fibrosis?
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Epithelial Chlorida Channel protein
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What gene encodes for it?
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Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene on the long arm of chromosome 7.
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Functioning CFTR ↓ Na+ channels. mutant CFTR doesn't. What is the sole exception to this?
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Human sweat glands.
Mutant CFTR ↓ Na+ with ↓ Na+ into the cell. |
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How many ATP binding domains does it have?
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Two
1) closed channel (Cl-, Na+) 2) regulatory domain (must be phosphorylated) |
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What are the six classes of CFTR gene mutations?
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Class 1: Defective protein synthesis due to defective mRNA
Class 2: Abnormal protein folding, processing & trafficking. Fails to escape ER. Class 3: Defective regulation and channel Class 4: ↓ conductance resulting in ↓ Cl- current Class 5: ↓ CFTR gene ↓ CFTR Class 6: Altered regulation of seperate ion channels. |
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Describe the most common mutation in Cystic Fibrosis?
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Class II: abnormal proteins don't escape ER to Golgi.
Mutation: 3 base pair deletion Coding: phenylalanine Position: ΔF508 |
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What does CFTR activate in the pancreas? What is then kept in the cell?
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cAMP activated Cl- & HCO3 exchange channel.
HCO3, Na+, H2O, activated digestive enzymes |
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What is the main symptom of pancreatic cystic fibrosis?
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Steatorrhoea secondary to fat malabsorption
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What is meconium ileus?
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Inability for a newborn to pass their first stool.
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What is the most important screening test for cystic fibrosis?
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Sweat test
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What are the respiratory symptoms of cystic fibrosis?
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Chronic cough
Nasal obstruction secondary to chronic sinustitis Small airway obstruction secondary to persistent lung infection Bronchiolitis Respiratory failure |
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What are the gastrointestinal symptoms of cystic fibrosis?
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Pancreas - secondary to maldigestion, lack of digestive enzymes or intestinal obstruction
- Fat & protein maldigestion and absorption - Steatorrhoea - Fat soluble vitamin deficiencies - Recurrent pancreatitis secondary to autodigestion - Hyperglycemia requiring insulin Intestine - Meconium ileus - Abdominal distension - Vomiting |
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What are the genito-urinary symptoms of cystic fibrosis?
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Late onset of puberty (male & female)
Azoospermic secondary to vs deferens obliteration (male) |
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How is cystic fibrosis managed?
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Symptomatically
Respiratory - mucus clearance (breathing exercises, chest percussion) - human DNAase to break down DNA released by dead neutrophils - Prophylactic antibiotics vs lung infections - Bronchodilators (vs acute ep) Gastro-intestinal - pancreatic enzyme replacement - fat soluble vitamin supplements - high caloric diet, low in fat & high in protein |
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Where is the mutation causing sickle cell anaemia?
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6th position of β-globin chain
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What is replaced in the sickle cell mutation?
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Glutamic acid (neg) replaced by valine (uncharged)
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What are the clinical features of sickle cell anaemia?
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- Haemolytic anemia - unable to pass spleen and destroyed.
- Sickling crisis - hypovolemic shock secondary to severe anemia, rapid splenomegaly - Vaso-occlusive disease/pain crisis - responsible for morbidity and mortality. Secondary to microcirculation obstruction leading to ischaemic injury to abdomen, bones, joints and soft tissue. - Chronic hyperbilirubinemia - ↑ unconjugated bilirubin secondary to hemolysis. Pre-hepatic jaundice. ↑ chance of gall stone formation. |
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What three tests are performed for sickle cell anemia?
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Electrophoresis - HbS is not as negative due to valine
Allele specific oligoucleotide (ASO) test - gene probe RFLP analysis |
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What is the histological sign of X-linked muscular dystrophy?
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Muscle fiber replacement by fibrofatty tissue
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Where is the mutant gene in X-linked muscular dystrophy?
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p21 region of the X chromosome that encodes for dystrophin.
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What does dystrophin do?
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intracellular protein in myocytes that forms strong mechanical link to actin over z-lines that transfers the force of contraction to CT.
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What are the clinical features of Duchenne Muscular Dystrophy (DMD)?
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Most common, most severe.
Complete absence of dystrophin from deletions and frame shift mutations. - present at birth but presents at 3-5 - delayed walking & clumsiness - weakness beginning in pelvic girdle and moving to shoulder - learning difficulties - death by 30 due to respiratory failure of cardiomyopathy |
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What are the clinical features of Becker Muscular Dystrophy (BMD)?
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Mutated dystrophin
- present between 5-15 or as late as 30-50 - same muscle wasting pattern - death between 40-60 |
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How is X-linked muscular dystrophy diagnosed?
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Clinical features
↑ Creatine Kinase (CK) Characteristic muscle biopsy Immunohistochemical staining |
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How do you treat X-linked muscular dystrophy?
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Glucocorticoids can slow progression by 3 years
Orthopaedic devices or corrective surgery Tacheostomy or ventilatory support |