Cystic Fibrosis Overview and Treatments

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Questions and Answers

Which of the following is NOT a risk factor associated with preterm labor?

Low socioeconomic status

High income status (correct)

Uterine distortion

Maternal smoking

What is the most common microorganism implicated in intra-amniotic infection related to preterm birth?

Ureaplasma urealyticum (correct)

Mycoplasma hominis

Chlamydia

Gardnerella vaginalis

Which of the following describes a histologic correlate of intrauterine infection?

Cervical incompetence

Placenta previa

Uterine fibroids

Chorioamnionitis (correct)

Intrauterine infection is present in approximately what percentage of all preterm births?

25% Signup and view all the answers

Which factor is involved in the deregulation of prostaglandin expression during preterm labor?

Endogenous Toll-like receptors Signup and view all the answers

Which of the following is a recognized complication of prematurity?

Intraventricular hemorrhage Signup and view all the answers

What condition results from compromised structural support of the cervix?

Cervical incompetence Signup and view all the answers

Multiple gestations, such as twin pregnancies, are considered what in relation to preterm labor?

Increased risk factor Signup and view all the answers

Which of the following is a long-term complication associated with preterm birth?

Developmental delay Signup and view all the answers

What is the impact of earlier gestational age at delivery on intra-amniotic infection?

Increased frequency of infection Signup and view all the answers

What condition is indicated by abnormal nasal trans-epithelial potential difference?

Cystic fibrosis Signup and view all the answers

Which type of mutation is associated with a severe clinical picture in cystic fibrosis?

Class I mutations Signup and view all the answers

What is the role of potentiators in cystic fibrosis therapy?

To increase the probability of CFTR channel opening Signup and view all the answers

What results in mild cystic fibrosis symptoms?

One severe and one mild mutation Signup and view all the answers

Which therapy is used to improve the delivery of mutant CFTR to the cell surface?

Correctors Signup and view all the answers

What is a common cause of azoospermia in cystic fibrosis patients?

Structural abnormalities of the vas deferens Signup and view all the answers

What does a mutation of one allele for cystic fibrosis indicate?

The individual is a carrier Signup and view all the answers

Which drug promotes read-through of premature termination codons in mRNA?

Ataluren Signup and view all the answers

What phenotype would result from two mild mutations in cystic fibrosis?

Very mild phenotype Signup and view all the answers

What characterizes cavernous hemangioma?

It is linked to mutations in CCM genes. Signup and view all the answers

What is a distinguishing feature of lymphangiectasis?

It results in abnormal dilations of lymph channels. Signup and view all the answers

What type of tumor is fibromatosis classified as?

A sparsely cellular proliferation. Signup and view all the answers

What typically occurs to capillary hemangiomas as children grow?

They spontaneously regress. Signup and view all the answers

Which of the following statements about congenital-infantile fibrosarcoma is true?

It is indistinguishable from fibrosarcomas in adults. Signup and view all the answers

What is the primary location for most hemangiomas?

Face and scalp Signup and view all the answers

What is a significant genetic modifier involved in the clinical manifestations described?

Transforming Growth Factor B1 Signup and view all the answers

Which environmental modifier is associated with respiratory problems in infancy and childhood?

Pseudomonas aeruginosa infection Signup and view all the answers

What microscopic feature is characteristic of nasal polyps?

Pseudostratified columnar epithelium Signup and view all the answers

Which condition describes the state of enlarged and dilated bronchi in the lungs?

Bronchiectasis Signup and view all the answers

What type of secretion is typically found in the cysts of the pancreas in chronic conditions?

Thick, tenacious secretions Signup and view all the answers

In the context of liver changes, what is typically observed at end-stage conditions?

Cirrhosis Signup and view all the answers

What histological feature is typically seen in the lungs affected by bronchiectasis?

Mixed inflammatory cells Signup and view all the answers

Which of the following is a characteristic of chronic conditions seen in the lungs?

Prominent fibrotic cores Signup and view all the answers

What is the typical appearance of the bile ducts in cases of bile duct obstruction?

Enlarged and filled with thick secretions Signup and view all the answers

What type of inflammatory changes might lead to squamous metaplasia in the lungs?

Chronic irritation and inflammation Signup and view all the answers

What percentage of malignant tumors occurs in infancy and childhood?

2% Signup and view all the answers

What is the leading cause of death in children aged 4 to 14 years after accidents?

Cancer Signup and view all the answers

Which type of tumor is more commonly seen in children?

Benign tumors Signup and view all the answers

What are most common neoplasms of childhood derived from?

Mesenchyme Signup and view all the answers

What is the primary characteristic of heterotopia or choristoma?

Presence of normal cells in abnormal locations Signup and view all the answers

How does a hamartoma differ from heterotopia?

Hamartoma is characterized by excessive overgrowth of native cells. Signup and view all the answers

Which statement is true regarding the significance of hamartomas?

They can rarely be sites of origin for true neoplasms. Signup and view all the answers

What complicates benign tumors in children?

Their rapid increase in size or location Signup and view all the answers

In what context can heterotopia or choristoma be confused with other conditions?

In their clinical presentation Signup and view all the answers

Which of the following is NOT true about benign tumors in children?

They are always malignant. Signup and view all the answers

Study Notes

Cystic Fibrosis

Cystic fibrosis is an autosomal recessive disease.
A single copy of the mutated gene (allele) means someone is a carrier.
Both alleles mutated leads to the disease.
The severity of the mutation on the CFTR gene dictates the severity of the disease.
Two severe mutations result in a severe clinical picture.
One severe and one mild mutation will likely lead to less severe symptoms.
Two mild mutations will likely lead to a very mild phenotype.

Treatments for Cystic Fibrosis

There are different treatment strategies for cystic fibrosis.
Potentiators increase the probability of CFTR channel opening.
Ivacaftor is an example of a potentiator used to increase the probability of Gly551Asp-CFTR channel opening.
Correctors improve the intracellular processing and delivery of mutant CFTR towards the cell surface.
Lumacaftor is an example of a corrector used for Phe508del-CFTR.
Production correctors help to promote the read-through of premature termination codons in mRNA. This leads to more CFTR protein being produced.
Ataluren is an example of a production corrector that can be used for class I mutations.

Causes of Premature Birth

Prematurity is often associated with a range of factors.
One factor in premature birth is a history of preterm delivery.
Other factors include preterm labor, vaginal bleeding during pregnancy, maternal smoking, low socioeconomic status, poor maternal nutrition, and genetic polymorphisms associated with immune regulation and collagen breakdown.

Intrauterine Infection and Preterm Labor

Intrauterine infection is one of the major causes of preterm labor.
It accounts for 25% of all preterm births.
The earlier the gestational age at delivery, the higher the frequency of intra-amniotic infections.
Histologic correlates of infection include chorioamnionitis (inflammation of placental membranes) and funisitis (inflammation of the fetal umbilical cord).
Common organisms associated with preterm labor include Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella vaginalis, Trichomonas, Gonorrhea, and Chlamydia.
The pathophysiology of infection in preterm labor involves Toll-like receptors (TLRs).
TLRs bind to bacterial components, such as bacterial LPS, and activate the immune response.
This leads to a dysregulation in prostaglandin expression, which induces uterine contractions ultimately resulting in preterm labor.

Structural Abnormalities and Preterm Labor

Other factors that can lead to preterm labor include abnormalities of the uterus, cervix and placenta.
Uterine distortion (e.g., fibroids) can contribute to premature labor.
Cervical incompetence, which involves a structurally compromised cervix, can also lead to preterm labor.
Placenta previa and abruptio placentae are serious complications that can also lead to premature birth.
Multiple gestations involving twin pregnancies are also a risk factor for preterm labor.

Hazards Associated with Prematurity

Premature babies are at a higher risk of complications.
These complications include neonatal respiratory distress syndrome (hyaline membrane disease), necrotizing enterocolitis, sepsis, intraventricular and germinal matrix hemorrhage, and long-term developmental delays.

Clinical Manifestations of Cystic Fibrosis

Cystic fibrosis can affect multiple organs in the body.
The most common clinical manifestations include nasal polyps, dilated bronchi, cystic changes in the pancreas, bile duct obstruction, and hepatobiliary issues.

Cystic Fibrosis: Genetic and Environmental Modifiers

The severity of cystic fibrosis is also influenced by both genetic and environmental factors.
Genetic modifiers include polymorphisms in MBL2, TGF-β1, and IFRD1.
Environmental modifiers include infections by Pseudomonas aeruginosa, alginate-producing bacteria, and concurrent viral infections.

Gross and Microscopic Pathology of Cystic Fibrosis

Cystic fibrosis results in distinctive gross and microscopic findings.
There are multiple nasal polyps, soft and edematous, covering respiratory epithelium. The basement membrane is not thickened.
The lungs show enlarged, dilated bronchi extending to the pleural surface. The bronchi are filled with mucopurulent secretions.
In the microscopic view, the lungs show bronchiectasis, which includes ectatic airways, chronic inflammatory cells, fibrosis, ulceration, and squamous metaplasia.
The pancreas exhibits cystic changes, multiple small cysts filled with thick secretions.
The hepatobiliary system shows bile duct obstructions, enlarged dilated bile ducts, and thick secretions.
The end-stage of cystic fibrosis in the liver is cirrhosis.

Tumors and Tumor-like Lesions in Infancy and Childhood

Tumors in children are less common but account for a significant portion of childhood deaths.
Benign tumors are more common in children and may cause serious complications due to their location or rapid increase in size.
Most common neoplasms in children are soft tissue tumors derived from mesenchymal tissues.

Tumor-Like Lesions

There are two main categories of tumor-like lesions: Heterotopia/Choristoma and Hamartoma.
Heterotopia/Choristoma are composed of microscopically normal cells or tissues in abnormal locations.
Hamartoma refers to an excessive focal overgrowth of cells native to the organ in which it occurs. These cellular elements are mature and identical to those found in the remainder of the organ.
Hamartomas typically do not reproduce the normal architecture of the surrounding tissue although they are rarely the sites of origin for true neoplasms.

Benign Tumors in Infancy and Childhood

The most common benign tumor in infancy is a hemangioma, classified as cavernous or capillary.
Hemangiomas are most often located on the skin, especially on the face and scalp, and appear as elevated irregular, red-blue masses.
Port-wine stains are flat, larger lesions that may represent vascular ectasias.
Most hemangiomas enlarge alongside the child's growth but spontaneously regress.
Some hemangiomas are associated with von Hippel-Lindau disease.

Lymphatic Tumors in Infancy and Childhood

Lymphangiomas are composed of cystic or cavernous spaces and can be hamartomatous or neoplastic.
They are often encountered in the neck, axilla, and mediastinum and increase in size after birth due to fluid accumulation and budding.
Lymphangiectasis is characterized by irregular and abnormal dilations of pre-existing lymph channels.
Lymphangiectasis presents as diffuse swelling in the extremities and is not progressive.

Fibrous Tumors in Infancy and Childhood

Fibromatosis is a sparsely cellular proliferation of spindle-shaped cells.
Congenital-infantile fibrosarcomas are richly cellular lesions indistinguishable from those seen in adults.
These lesions have an excellent prognosis and are associated with the chromosomal translocation t(12;15)(p13;q25).
Myofibromas are nodular proliferates of fibroblast and myofibroblast cells.

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Description

This quiz covers the key aspects of cystic fibrosis, including its genetic basis and the impact of different mutations on disease severity. It also explores treatment strategies, highlighting the roles of potentiators and correctors in the management of the condition.