Practice Problems Quiz 3 Flashcards
Asthma is a disorder characterized by a heightened response to the tracheobronchial tree to numerous s1muli. Dyspnea, coughing, respiratory distress, and wheezing resul1ng from mucosal edema, thickening of the basement membrane, hypertrophy of smooth muscle and infiltra1on of immune cells.
Hypercontrac1on of smooth muscle compounds these effects and increases resistance to airflow.
Where in the respiratory system would hypercontrac1on of smooth muscle be most problema1c? Why?
A 35 year old male presented with low grade fever and cough with mucopurulent sputum, with a history of recurrent similar episodes since childhood. A CT scan, bronchiogram and angiogram of the patient are shown. Discuss what is likely to have gone wrong during development and when. Discuss how the primary lung defect impacted formation of the pulmonary arteries and the pulmonary cavities. What other defects might you suspect could exist in this patient? (From: Lung India. 2008 Jan-Mar; 25(1): 28–30.)
Discussion: This patient shows a very rare complete agenesis of the right lung, with absence of the right bronchial tree and the right pulmonary arteries forming a large, unbranched sinus. There has been significant expansion of the left lung across the midline, suggesting the right pulmonary cavity has also expanded abnormally. This defect is likely to have occurred very early in development at the first bifurcation of the respiratory diverticula. While it is remarkable that this patient is relatively healthy and asymptomatic at age 35, I would be concerned about other defects in the formation of the trachea and esophagus. Given how early this defect arose and the expansion of the right lung, I would also be concerned about possible abnormalities in cardio-pulmonary function. Finally, due to the important role of FGF in lung formation, I would want to check for defects in other FGF-dependent developmental processes (ear formation, neural patterning, heart development, limb development).
A 50 year old male presented with a low grade fever and a tender, palpable, midline neck mass (see below). He was diagnosed as having an infected thyroglossal cyst. Discuss how this condition arose in development and what features of this cyst are likely to have allowed it to become become infected.
Discussion: The thyroid duct normally closes during development. Abnormal persistence of space along the trajectory of the thyroid gland’s migratory path results in a midline cyst (a fluid filled cavity). Occasionally, such cysts maintain a connection with the mouth, throat or the outside of the body (i.e. a thyroglossal fistula). In such cases, the abnormal cystic cavity can become infected. Sometimes infections of this sort are associated with malignant or pre-malignant transformations of the thyroid, so cancer screening would be in order.
The branchial arches are common to all vertebrates, and their cranial/caudal identity is controlled in part by expression of Hox-family genes. Hoxa2 is expressed beginning in the second branchial/pharyngeal arch (PA2) and in all more caudal arches (see illustration).
In mice, null mutations in Hoxa2 result in transformation of second branchial arch derivatives to those of the first branchial arch (Cell. 1993 Dec 31;75(7):1317-31). Conversely, in chick, overexpression of Hoxa2 in the first branchial arch transforms first arch derivatives into second arch elements (see: Development 127, 5355-5365 (2000).
A recent study has identified a mutation in Hoxa2 contributing to a familial form of outer-ear malformation and deafness. Photos and scans of affected individuals are shown below. These patients also inner ear bone malformation (ossicles are derived from both first and second arch). We have not yet studied outer ear formation, but based on the absence or greatly reduced size of the external ear meatus, discuss the likely cause of this defect, and speculate on whether this mutation is likely to cause a loss of Hoxa2 function or a misexpression of Hoxa2 in more cranial arches. (taken from: The American Journal
Discussion: In the branchial arches, just as in the nervous system, Hox genes work in a combinatorial manner to specify cranial-caudal position. When Hoxa2 function is lost, the pattern of gene expression in the second branchial arch is similar to the pattern in the first arch, and a cranial transformation occurs. When Hoxa2 is over expressed in the first arch, the pattern of gene expression now mimics the second arch, and a caudal transformation of the first arch occurs.
In the clinical case illustrated, the outer ear meatus and the eardrum are missing. These structures are normally formed from the cleft and closing plate between the first and second branchial archs, suggesting this interface is not formed in these patients. This could be due to either a cranial or a caudal transformation of branchial arch 2. However, it is more likely the mutation causes a loss of function of Hoxa2—eliminating the distinction between the first and second arch. This would create a single, large branchial arch 1, and therefore eliminate the formation of the cleft and closing plate that normally form between arch 1 and arch 2, while still allowing some outer ear formation. Note that the pinna defects in these patients are predominantly associated with caudal elements normally derived from the second arch (e.g. reduced ear lobe)–while the more cranial components of the pinna that are normally derived from the first arch appear relatively normal. This is just speculation, but certainly, any malformations in branchial arch derivatives warrants a close look at other structures derived from the same region.
Which of the following is a local response that helps accommodate an area of dead space ventilation in the lung?
Arterioles constrict.
Breathing rate increases.
Bronchioles constrict.
Gas exchange becomes diffusion-limited.
Bronchioles Constrict
Dead space ventilation is the situation where alveoli are being ventilated, but blood is not circulating in the alveolar capillaries. A response to that situation is the constriction of local bronchioles supplying those alveoli, which will tend to divert air to other areas that are perfused. Arteriolar constriction is a response to a different problem: shunted areas. Breathing rate is controlled by centers in the brainstem, not locally. Gas exchange mechanisms are not something that can be controlled by tissues, but are dictated by physical chemistry and microanatomy.
Which of the following is a local response that helps accommodate an area of shunted ventilation in the lung?
Arterioles constrict.
Breathing rate increases.
Bronchioles constrict.
Gas exchange becomes diffusion-limited.
Arterioles Constrict
A shunt is the situation where alveoli are not being ventilated, but blood is
circulating in the alveolar capillaries. A response to that situation is the constriction of local arterioles supplying those alveoli, which will tend to divert blood to other areas that are being ventilated. The mechanism involves the smooth muscle cells of pulmonary arterioles constricting in response to low oxygen due to lack of ventilation: hypoxic pulmonary vasoconstriction.
This is the opposite response to that which occurs in arterioles outside the lung. Bronchiolar constriction is a response to a different problem: dead space ventilation. Breathing rate is controlled by centers in the brainstem, not locally. Gas exchange mechanisms are not something that can be controlled by tissues, but are dictated by physical chemistry and microanatomy.
An 8-year-old child is seen in clinic because of difficulty in breathing and extended coughing episodes after catching a cold. She has had a history of such episodes and the clinician can hear whistling sounds on the child’s exhalations. A spirometry test is ordered and while FVC is in the normal range, her FEV1/FVC ratio is reported as 0.51; the ratio from a recent test administered when the child was well was 0.74. The most likely pathology present is:
Asthma.
COPD.
Pulmonary fibrosis.
Pulmonary thrombosis.
The child’s symptoms are consistent with asthma. The low FEV1/FVC ratio indicates an obstructive disease, like asthma or COPD. COPD, however, would be highly unusual at this age and if it were present both the FVC and the FEV1/FVC ratio would have been low in the previous test: it is a complex, chronic condition of diminished lung function and structure. Asthma involves episodes of bronchiolar constriction, “attacks,” between periods of normal breathing. The spirometry test protocol would typically include a treatment with a bronchiole dilating drug, which would increase the FEV1/FVC ratio in the case of asthma, but not if the problem is COPD. Fibrosis would result in a reduced FVC, but a normal or even elevated FEV1/FVC ratio. Pulmonary thrombosis could result in difficulty breathing and chest pain and make spirometry difficult, but should not affect the FEV1/FVC ratio.
Neonatal respiratory distress syndrome can occur in babies delivered before 35 weeks gestation, because surfactant synthesis may not yet be adequate. What situation does this syndrome create?
Dead space ventilation
Pneumothorax
Shunt
Shunt
A) Autosomal dominant
x-linked recessive
Autosmal recessive
x-linked dominant
x-linked recessive
Y-linked
Mitochondrial
Autosomal Dominant
