This is a revision reference. It covers the material from the pre-reading and the class, and works through all eleven questions from the session with every option explained.
Pulmonary thromboembolism
Embolus size decides the artery blocked, and cardiopulmonary reserve decides whether the tissue lives.
Most pulmonary emboli come from a deep vein thrombosis in the leg. The clot breaks free, travels through the right heart, and lodges in a pulmonary artery. Occlusion of that artery has two consequences: pressure rises in the pulmonary artery because flow is blocked, and the lung supplied by the artery becomes ischemic and may infarct. How far each one goes depends on the size of the embolus, which dictates the size of the vessel it can occlude, and on the cardiopulmonary status of the patient.
Virchow’s triadVenous stasis, endothelial injury and hypercoagulability. The post-operative orthopedic patient has all three at once, which is why the opening case was a woman ten days after fixation of a tibial fracture.
Mechanism of the hypoxemia
The chest X-ray can be normal while the saturation is 80%, because the problem is distribution of blood and air rather than loss of lung. Three things run at once.
Region
What happens
Result
Ischemic area
No perfusion behind the embolus, so ventilated alveoli receive no blood. Surfactant production falls
Dead space ventilation, then atelectasis of those alveoli
Non-ischemic area
Over-perfused to compensate, so blood flow outstrips ventilation
Low V/Q ratio and intrapulmonary shunting
Heart
Right ventricular failure against the raised resistance, so cardiac output falls and tissues extract more oxygen
The arteriovenous oxygen difference widens
All three paths end in hypoxemia. The shunt is intrapulmonary, not intracardiac, and the airways themselves are open.
Effects by size
An embolus that obstructs more than 60% of the pulmonary vasculature is called massive.
Embolus
Where it lodges
What happens
Morphology in the lung
Large
Main pulmonary artery, a major branch, or astride the bifurcation as a saddle embolus
Abrupt rise in pulmonary artery pressure, diminished cardiac output, right-sided heart failure (acute cor pulmonale), sometimes sudden death
None. Death comes too quickly for the lung to change
Medium
Medium-sized pulmonary arteries
With adequate circulation and bronchial arterial flow the parenchyma stays alive. Ischemic damage to endothelial cells still ruptures capillaries
Alveolar hemorrhage without infarction. Infarction if cardiovascular status is already compromised
Small
Small peripheral pulmonary arteries
The bronchial supply keeps the tissue alive and fibrinolysis clears the clot, so 60 to 80% cause no symptoms at all
Pulmonary vascular sclerosis, with dyspnea that worsens over time
The lung has two arterial supplies. The pulmonary artery brings deoxygenated blood for gas exchange and the bronchial artery brings oxygenated blood from the systemic circulation, so when one is blocked the other can keep the tissue alive. This is why a medium embolus gives bleeding into the alveoli without infarction, and why infarction follows when that second supply is already inadequate.
Saddle embolus across the bifurcation of the pulmonary trunk, occluding both main branches at once. The lung behind it has had no time to show any change.A red infarct: wedge-shaped and peripheral, base on the pleura and apex pointing at the occluded vessel. It is dark because bronchial blood continues to leak into tissue that has already died.
Clinical features
60 to 80% of pulmonary emboli cause no symptoms at all. The emboli are small, the bronchial circulation keeps the parenchyma alive, and endogenous fibrinolysis clears the embolic mass quickly.
When they do present: dyspnea, tachypnea, tachycardia and pleuritic chest pain.
Chronic cor pulmonale. Repeated showers of small emboli raise pulmonary pressure, fail the right heart and end in vascular sclerosis with worsening dyspnea.
Sudden death. A massive embolus, or many small ones at once, obstructs more than 60% of the pulmonary vasculature.
Diagnosis
The work-up starts from a high degree of clinical suspicion, because pulmonary embolism shares its symptoms with several other conditions. The Wells score turns that suspicion into a probability band, and the band decides which test comes next.
Test
Role
CT pulmonary angiography
Gold standard, and the first imaging choice when probability is high. The clot appears as a filling defect inside the opacified vessel
Chest X-ray
Limited utility, usually done to rule out other causes of the symptoms
Doppler ultrasound and D-dimer
Work-up for the deep vein thrombosis behind the embolus. D-dimer is sensitive and not specific, so it rules out when probability is low or moderate
Ventilation-perfusion scan
The alternative when CT pulmonary angiography is contraindicated or unavailable
When CTPA cannot be usedSevere renal impairment or acute kidney injury, because of contrast-induced nephropathy; severe allergy to iodinated contrast; and pregnancy. In each of these a ventilation-perfusion scan or compression ultrasonography is used instead. Question 5 turns on exactly this.
Prophylaxis and treatment
Prophylaxis is critical: anticoagulation, early ambulation after an operation, elastic stockings, intermittent pneumatic compression of the calves, and isometric leg exercises for patients confined to bed. Patients with a massive embolism who are hemodynamically unstable, with shock or acute right heart failure, are candidates for thrombolytic therapy.
What to rememberPressure rises in the artery and the lung it supplies becomes ischemic. Embolus size dictates the artery blocked; cardiopulmonary status decides whether the tissue survives. Most are silent, and recurrent showers end in chronic cor pulmonale.
Pulmonary hypertension
Sustained pressure remodels the wall, and the change differs with the calibre of the vessel.
Pulmonary hypertension is either idiopathic, meaning no other disease explains it, or secondary to a condition elsewhere. The World Health Organization scheme sorts the secondary causes by where the problem starts.
Group
Cause
Example
1
Pulmonary arterial hypertension
Idiopathic, or heritable with a BMPR2 mutation
2
Left heart disease
Heart failure, valvular disease such as mitral stenosis
Chronic thromboembolic pulmonary hypertension after recurrent emboli
5
Unclear or multifactorial mechanisms
Disorders with more than one mechanism
Reading the historyAn opening snap with a mid-diastolic murmur at the apex places the patient in Group 2, because rheumatic mitral stenosis holds pressure back through the left atrium into the pulmonary veins. Long-standing airflow obstruction or fibrosis places them in Group 3, where alveolar hypoxia drives vasoconstriction. Repeated emboli place them in Group 4.
Idiopathic pulmonary hypertension and BMPR2
Bone morphogenetic protein receptor 2 normally inhibits the proliferation of fibroblasts and smooth muscle cells. Inactivating germline mutations in the gene are found in 75% of familial cases and 25% of sporadic cases. Without that signal the endothelium becomes dysfunctional and vascular smooth muscle proliferates, so the wall thickens and the lumen narrows. Only 10 to 20% of people carrying the mutation develop the disease, so modifier genes and environmental triggers must contribute as well.
Vascular changes
The remodeling is not uniform. Each calibre of vessel has its own change, and that is what the biopsy is read for.
Vessel
Change
Main elastic arteries
Atheromas, a change usually limited to the large pulmonary arteries
Medium muscular arteries
Intimal and smooth muscle cell proliferation, thickening the wall
Small arteries and arterioles
Thickening, medial hypertrophy, reduplication of the elastic laminae
Small artery at a branch point
Plexiform lesion: multiple lumina within one small artery where it branches from a larger vessel. A feature of advanced disease
Right ventricle
Hypertrophy, from pumping against the raised resistance
Marked medial hypertrophy in a small pulmonary artery. The muscular wall has thickened and the lumen is narrowed, the response of an arteriole to sustained pressure.A plexiform lesion, characteristic of advanced disease: multiple lumina inside one small artery at a branch point off a larger vessel.
Chronic thromboembolic pulmonary hypertension
Emboli that are neither lysed nor fully organized leave fibrous webs and bands inside the arteries. Resistance rises, and the vessels that remain open carry more flow than they were built for. That shear stress drives medial hypertrophy and intimal proliferation in those vessels, and in advanced disease plexiform lesions form. Catheterization then finds a raised mean pulmonary artery pressure and the echocardiogram shows a hypertrophied right ventricle. This is WHO Group 4, and it is the route from arc 1 to arc 2.
What to rememberBMPR2 restrains fibroblasts and smooth muscle, and losing it thickens the wall. Elastic arteries get atheromas, muscular arteries get intimal proliferation, arterioles get medial hypertrophy. Advanced disease shows plexiform lesions and right ventricular hypertrophy.
Diffuse alveolar hemorrhage syndromes
Three immune-mediated diseases that share one triad, told apart by antibody, kidney and upper airway.
These are primary immune-mediated diseases that present as a triad of hemoptysis, anemia and diffuse pulmonary infiltrates. Three belong to the group: Goodpasture syndrome, Wegener’s granulomatosis (granulomatosis with polyangiitis) and idiopathic pulmonary hemosiderosis.
Goodpasture syndrome
Goodpasture syndrome is an autoimmune disease of the teens and twenties, more common in males. Circulating autoantibodies are directed against the non-collagenous domain of the α3 chain of collagen IV, a protein present both in the glomerular basement membrane and in the alveolar septa, so one antibody destroys two organs. The antibodies initiate inflammatory destruction of those basement membranes, giving the pulmonary-renal syndrome: a proliferative and rapidly progressive glomerulonephritis alongside a hemorrhagic interstitial pneumonitis. Immunofluorescence shows linear deposition of IgG along the glomerular basement membranes in the kidney and along the alveolar septa in the lung.
Morphology
Level
Findings
Gross
Heavy lungs with red-brown consolidation
Microscopic
Intra-alveolar hemorrhage, patchy necrosis of alveolar walls, intra-alveolar hemosiderin
Later stages
Septal thickening with reactive hypertrophy of type II pneumocytes
Alveolar spaces filled with macrophages whose cytoplasm is loaded with golden-brown pigment, on a background of thickened fibrous septa. The pigment is iron recovered from red cells broken down after the bleed.The same field stained for iron. Prussian blue turns the hemosiderin deep blue, confirming that the pigment is iron and that bleeding has continued long enough for it to be stored.
Comparison
Feature
Goodpasture
Granulomatosis with polyangiitis
Idiopathic pulmonary hemosiderosis
Antibody
Anti-GBM, against collagen IV α3
c-ANCA, against proteinase 3
None detectable
Immunofluorescence
Linear IgG and C3 along basement membranes
Pauci-immune, little or no deposition
Negative
Lung histology
Alveolar hemorrhage with hemosiderin-laden macrophages
Alveolar hemorrhage, abundant hemosiderin, interstitial fibrosis with time
Kidney
Rapidly progressive crescentic glomerulonephritis
Focal necrotizing crescentic glomerulonephritis
Not involved
Upper airway
Not involved
Sinusitis, septal perforation, saddle nose deformity
Not involved
Typical age
Teens and twenties, more often male
40 to 60 years, male and female equally
Children, most under 10
What to rememberThe triad is hemoptysis, anemia and diffuse pulmonary infiltrates. Goodpasture is teens and twenties, mostly male, antibody to the α3 chain of collagen IV, linear IgG in lung and kidney. The lungs are heavy and red-brown, with intra-alveolar hemorrhage and hemosiderin, and septal thickening later.
Acquired atelectasis
Alveoli that have closed, and the direction the mediastinum moves tells you which mechanism closed them.
Resorption atelectasis
Resorption atelectasis begins with an obstructed airway. Most often the obstruction is excessive secretions such as mucus plugs, or exudate within the smaller bronchi, which is why it accompanies bronchial asthma, chronic bronchitis, bronchiectasis and the post-operative state. Aspirated foreign bodies and intrabronchial tumors do the same thing. Air trapped beyond the obstruction is gradually resorbed into the blood and the alveoli collapse behind it. Lung volume is now diminished, so the mediastinum shifts toward the atelectatic lung.
Clinical findings
Sign
Reason
Trachea and mediastinum deviated to the affected side
The collapsed lung takes up less room
Diaphragm elevated on the affected side
It rises to fill the space the lung has given up
Absent breath sounds and absent tactile fremitus
No air moves in or out of the collapsed tissue, so nothing transmits sound or vibration
Reduced movement of that side
The collapsed lung does not expand on inspiration
Compression atelectasis
Here the airways are open and the problem is outside the lung. Fluid or air collecting in the pleural space raises the pressure around the lung and squeezes it, so the alveoli close under compression. Because the pleural space now holds more than it should, the mediastinum is pushed toward the opposite side. Dullness to percussion indicates fluid, and a malignant effusion is a common source in a patient with a known cancer.
Fluid in the left pleural space. The lower zone is dense where the fluid lies, and the lung above it has been compressed into a smaller volume.
Contraction atelectasis
Focal or generalized fibrosis of the lung or of the pleura prevents full expansion. Scar tissue does not stretch, so the alveoli never open to their normal volume. This is the one form that cannot be reversed, because the fibrosis is permanent.
Pleural effusion including malignant effusion; air in the pleural space
Pushed away from the affected side
Yes
Contraction
Fibrosis prevents full expansion
Pulmonary or pleural fibrosis
No shift of this kind
No
Course and complications
Collapsed lung is hypoxic and easily infected, because secretions collect there and bacteria are not cleared. Atelectasis should be treated promptly to prevent hypoxemia and superimposed infection.
What to rememberThree types: resorption, compression, contraction. At the bedside the trachea and mediastinum shift, and which way depends on the type; the diaphragm is often elevated on that side; breath sounds and fremitus are absent. Contraction follows fibrosis and is irreversible. Every other form can be reopened.
The eleven questions
Every question from the session, with the reasoning behind each option.
Question 1 of 11Arc 1 · Pulmonary thromboembolism
A 30-year-old man who was admitted a week ago because of a right femur fracture suddenly experienced shortness of breath, tachycardia and chest pain. His pulse is 115/min and respirations are 23/min. Physical examination shows unilateral swelling of the left leg. A chest X-ray shows no abnormalities and oxygen saturation is 85%. CT pulmonary angiography is done.
What is the most likely underlying pathogenesis of the hypoxia in this patient?
AIncorrect
True right-to-left intracardiac shunt. An intracardiac shunt needs a defect between the chambers, such as a patent foramen ovale with reversed flow. The shunt here is inside the lung, where blood passes through alveoli that are no longer properly ventilated. Nothing in the stem points to a cardiac defect.
BIncorrect
Alveolar hypoventilation caused by absolute airway obstruction. The airways are open. There is no wheeze, no stridor, no aspiration, and the chest X-ray is clear. Obstruction reduces total ventilation and raises carbon dioxide; this is a perfusion problem.
CCorrect
Dead space ventilation and intrapulmonary shunting due to regional alveolar collapse. Behind the embolus the alveoli are ventilated but not perfused, which is dead space, and falling surfactant production collapses them. The unobstructed lung is over-perfused to compensate, so its V/Q ratio falls and blood leaves it incompletely oxygenated. Both run at once, which is how the saturation reaches 85% with a normal chest X-ray.
DIncorrect
Reduced right ventricular afterload. Afterload rises, it does not fall. The obstructed vascular bed increases pulmonary vascular resistance, and that is what fails the right ventricle.
EIncorrect
Reduced dead space ventilation. Dead space increases. A ventilated alveolus that has lost its perfusion is the definition of dead space, so this is the opposite of what happens.
Question 2 of 11Arc 1 · Pulmonary thromboembolism
A 60-year-old man has just got off a direct flight from New York to Tokyo. He complains of sudden onset of chest pain and collapses after taking a few steps. He has no past history of ischemic heart disease. He dies instantaneously. Autopsy shows a large thrombus occluding the bifurcation of the pulmonary trunk.
Which of the following additional morphological features in the lung is most likely associated with this patient’s condition?
AIncorrect
White infarct. Pale infarcts occur in solid organs with a single arterial supply, such as the heart, kidney and spleen. The lung is loose and has a dual supply, so its infarcts are red. Nothing here has had time to infarct at all.
BCorrect
Normal lung parenchyma. A saddle embolus at the bifurcation kills by obstructing the circulation, not by killing lung tissue. Death is instantaneous and morphological change takes hours, so there is no time for alterations in the lung. This is the defining feature of the large embolus.
CIncorrect
Liquefactive necrosis. Liquefactive necrosis is the pattern of the brain and of abscesses. It is not a consequence of arterial occlusion in the lung.
DIncorrect
Coagulative necrosis. Coagulative necrosis is the pattern of ischemic infarction in most organs, and it would be the answer had he survived long enough to infarct. He did not.
EIncorrect
Red infarct. The right pattern for the lung, but the wrong timing and the wrong size of embolus. A hemorrhagic infarct needs hours, and it follows a medium embolus in a patient whose reserve is already compromised.
Question 3 of 11Arc 1 · Pulmonary thromboembolism
A 60-year-old man with a 1-year history of congestive heart failure comes to the physician because of sudden onset of chest pain and shortness of breath. His blood pressure is 108/68 mm Hg, pulse is 102/min and respirations are 22/min. The pain is worse with deep breaths. Physical examination shows swelling of the right lower extremity. Cardiac enzymes are not raised and the chest X-ray is unremarkable. CT angiography shows diminished blood flow in a branch of the pulmonary artery, consistent with pulmonary embolism.
Which of the following morphological changes in the lung is most likely associated with this patient’s condition?
AIncorrect
Pale area of coagulative necrosis. A pale infarct requires a single arterial supply and dense tissue. The lung has neither, so blood from the bronchial arteries floods the dead zone and the infarct is red.
BCorrect
Hemorrhage into the infarcted lung parenchyma. The clot sits in a branch artery, so this is a medium embolus, and his year of congestive heart failure is the compromised cardiovascular status that tips alveolar hemorrhage over into infarction. The result is a red infarct: wedge-shaped and peripheral, with its base on the pleura. The pleuritic pain comes from the inflamed pleura over that base.
CIncorrect
No morphological changes. No change belongs to the large embolus that kills before the lung can react. This man is alive and symptomatic, and the clot is in a branch.
DIncorrect
Liquefactive necrosis. Liquefactive necrosis is the pattern of the brain and of abscesses, not of pulmonary arterial occlusion.
EIncorrect
Hemorrhage without infarction. This is what happens when circulation and bronchial arterial flow are adequate: the endothelium is damaged, capillaries rupture and blood enters the alveoli, but the tissue survives. His reserve is not adequate. This option and the correct one are the two halves of the medium-embolus rule, and congestive heart failure is what separates them.
Question 4 of 11Arc 1 · Pulmonary thromboembolism
A 65-year-old woman presents with progressively worsening dyspnea and peripheral edema over the past 6 months, with a history of multiple undocumented episodes of pulmonary embolism. Transthoracic echocardiography reveals right ventricular enlargement and elevated pulmonary artery pressures.
The pathogenesis of her current condition is best explained by which of the following?
AIncorrect
Massive pulmonary embolism affecting more than 60% of the pulmonary circulation. A massive embolus is an acute event presenting with shock or sudden death, not six months of progressive breathlessness. A patient obstructing more than 60% of the pulmonary vasculature does not reach the clinic.
BIncorrect
Chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease does cause cor pulmonale, through the hypoxic vasoconstriction of WHO Group 3. But nothing in the stem suggests airflow obstruction, and she has a documented embolic history that already explains the findings.
CCorrect
Recurrent showers of small emboli leading to chronic cor pulmonale. Repeated small emboli obstruct the bed a little at a time. Pulmonary pressure rises, the arteries undergo vascular sclerosis, and the right ventricle hypertrophies and then fails. That is chronic cor pulmonale, and as a cause of pulmonary hypertension it is WHO Group 4.
DIncorrect
An acute allergic reaction causing bronchoconstriction. Bronchoconstriction is an airway problem. It would be acute and wheezing, and it would not enlarge the right ventricle over six months.
EIncorrect
The presence of a patent foramen ovale allowing for paradoxical emboli. A patent foramen ovale lets a venous embolus cross into the systemic circulation, which causes strokes and systemic infarcts. It does not raise pulmonary artery pressure.
Question 5 of 11Arc 1 · Pulmonary thromboembolism
A 45-year-old woman with a history of chronic kidney disease presents to the emergency department with sudden-onset shortness of breath and sharp, pleuritic chest pain that started about 2 hours ago. She has had pain and swelling in her right leg for a week and has taken oral contraceptive pills for the past 5 years. Temperature is 37°C, heart rate 110/min, blood pressure 118/70 mm Hg, respirations 24/min and oxygen saturation 88% on room air. A chest X-ray demonstrates no acute pulmonary pathology.
Which of the following is the most appropriate next step in her diagnostic work-up?
AIncorrect
High-resolution chest CT scan. High-resolution CT images the interstitium. It does not opacify the pulmonary arteries, so it cannot demonstrate an embolus.
BIncorrect
Transthoracic echocardiogram. Echocardiography can show right ventricular strain and is useful when a patient is too unstable to move, but it does not make the diagnosis. Her blood pressure is maintained.
CCorrect
V/Q scan. Her Wells score is high: clinical signs of deep vein thrombosis, pulmonary embolism the most likely diagnosis, and a heart rate above 100. Imaging is therefore needed and a D-dimer would add nothing. Her chronic kidney disease is the reason the gold standard is not the answer here, because iodinated contrast risks contrast-induced nephropathy. A ventilation-perfusion scan is what replaces CT pulmonary angiography when CTPA is contraindicated.
DIncorrect
CT pulmonary angiography (CTPA). CTPA is the gold standard and would be correct in almost any other stem. The renal history is in this one for a reason: it is the first of the three contraindications.
EIncorrect
Doppler ultrasound of the lower extremities. Doppler is part of the work-up for the deep vein thrombosis behind the embolus, and a positive study supports treatment. A negative one does not exclude a pulmonary embolism, and she already has clinical signs in that leg.
Question 6 of 11Arc 2 · Pulmonary hypertension
A 36-year-old man presents with progressive exertional dyspnea and occasional palpitations. He reports no chest pain, cough or hemoptysis. Family history is notable for his mother dying from heart problems in her 40s. Heart rate is 106/min, blood pressure 115/72 mm Hg, respirations 20/min and oxygen saturation 94%. Examination shows jugular venous distension, a loud P2 and a right-sided S4. Right heart catheterization confirms pulmonary arterial hypertension. Pulmonary function tests are normal and pulmonary angiography shows no evidence of thromboembolism. Biopsy reveals medial hypertrophy and intimal fibrosis of small pulmonary arteries.
Which mechanism best explains the vascular remodeling observed in this patient?
AIncorrect
Recurrent microthrombi obstructing the pulmonary arteries. Pulmonary angiography shows no thromboembolism, and that sentence is in the stem to exclude this option. It would be WHO Group 4.
BCorrect
Loss of BMPR2-mediated inhibition of vascular smooth muscle and fibroblast proliferation. A man in his thirties, a mother who died of heart problems in her forties, normal lung function and no thromboembolism: this is heritable pulmonary arterial hypertension, WHO Group 1. Bone morphogenetic protein receptor 2 normally restrains fibroblasts and smooth muscle cells, and losing that restraint produces exactly the medial hypertrophy and intimal fibrosis the biopsy shows. Inactivating mutations are found in 75% of familial and 25% of sporadic cases.
CIncorrect
Chronic alveolar hypoxia due to interstitial lung disease. The pulmonary function tests are normal, which excludes interstitial lung disease. This mechanism belongs to WHO Group 3.
DIncorrect
Autoimmune-mediated endothelial injury. No autoimmune disease is described, and the biopsy shows proliferation rather than inflammation. Remodeling under pressure is not a vasculitis.
EIncorrect
Hypoxia secondary to chronic obstructive pulmonary disease. Also WHO Group 3, and ruled out by the same normal pulmonary function tests.
Question 7 of 11Arc 2 · Pulmonary hypertension
A 62-year-old woman with a 10-year history of severe rheumatic heart disease presents with progressive dyspnea on exertion. Vital signs are within normal limits. Physical examination shows a loud S1 with an opening snap over the cardiac apex and a mid-diastolic murmur. Echocardiography confirms the mitral valve abnormality and shows elevated pulmonary artery pressures.
Which of the following vascular changes is the most likely consequence of her condition?
AIncorrect
Malignant endothelial proliferation. That describes angiosarcoma. Pulmonary hypertension remodels vessels; it does not transform them.
BCorrect
Medial hypertrophy of small pulmonary arterioles. A stenosed mitral valve obstructs emptying of the left atrium, so pressure is transmitted back through the pulmonary veins into the capillaries and arterioles. This is WHO Group 2, left heart disease. An arteriole meets sustained pressure by thickening its muscular wall, exactly as a ventricle does.
CIncorrect
Diffuse alveolar hemorrhage. Alveolar hemorrhage belongs to the three immune-mediated syndromes. The question asks for a vascular change, and hers is a pressure change with no antibody behind it.
DIncorrect
Granulomatous inflammation of the tunica media. Granulomatous inflammation of the media occurs in large-vessel vasculitis such as giant cell arteritis. There is no inflammation in her vessels.
EIncorrect
Transmural inflammation with fibrinoid necrosis. Transmural inflammation with fibrinoid necrosis is a vasculitis. Remodeling under raised pressure is not inflammatory.
Question 8 of 11Arc 3 · Diffuse alveolar hemorrhage
A 25-year-old man presents with a 2-week history of hemoptysis, shortness of breath and red-colored urine. He denies fever, weight loss or recent infection. Lung auscultation reveals diffuse bilateral crackles. Laboratory studies show hematuria and mild proteinuria, and the chest X-ray demonstrates diffuse ground-glass opacities. Renal biopsy shows crescentic glomerulonephritis, and immunofluorescence demonstrates a linear pattern of IgG and C3 deposition along the glomerular basement membrane.
Which of the following is the most likely pathogenesis of the patient’s lung symptoms?
ACorrect
Autoantibodies against type IV collagen in the alveolar basement membrane. Linear IgG and C3 is the signature of an antibody bound to a fixed tissue antigen: the non-collagenous domain of the α3 chain of collagen IV. That same protein sits in the alveolar septa, so one antibody destroys two organs at once. Hemoptysis with hematuria in a man of 25 is the pulmonary-renal syndrome of Goodpasture.
BIncorrect
Granulomatosis with polyangiitis affecting the small pulmonary vessels. Granulomatosis with polyangiitis gives c-ANCA and pauci-immune staining, with little or no deposition, and it almost always involves the upper airway. He has neither finding.
CIncorrect
Antibody-antigen complex deposition in the pulmonary capillaries. Immune complexes deposit in a granular, lumpy pattern. The stem specifies linear, and that single word is what the question turns on.
DIncorrect
Activation of type I hypersensitivity in the lung parenchyma. Type I hypersensitivity is IgE and mast cells, which give asthma and anaphylaxis. It does not produce hemoptysis with a crescentic glomerulonephritis.
EIncorrect
Direct toxicity from an inhaled substance. An inhaled toxin would not lay down linear IgG along a basement membrane, and it would not involve the kidney.
Question 9 of 11Arc 3 · Diffuse alveolar hemorrhage
A 48-year-old man presents with a 3-month history of chronic sinusitis, productive cough with occasional hemoptysis and intermittent low-grade fever, with 5 kg of unintentional weight loss. Blood pressure is 128/78 mm Hg, heart rate 96/min, respirations 18/min and temperature 37.8°C. Nasal examination shows ulceration of the septum and lung auscultation reveals scattered crackles. Laboratory studies show mild anemia and raised inflammatory markers, and urinalysis reveals microscopic hematuria. Serologic testing is positive for cytoplasmic ANCA (c-ANCA).
Which of the following microscopic findings is most likely seen in the lung tissue?
AIncorrect
Linear IgG deposition along the alveolar basement membrane. Linear IgG is Goodpasture syndrome. Granulomatosis with polyangiitis is pauci-immune: c-ANCA circulates, but little or nothing is deposited in the tissue.
BIncorrect
Caseating granulomas with central necrosis and acid-fast bacilli. Caseating granulomas with acid-fast bacilli are tuberculosis. There is no exposure history, and a positive c-ANCA with septal ulceration points elsewhere.
CIncorrect
Non-caseating granulomas with eosinophilic infiltration. Non-caseating granulomas with eosinophils describe eosinophilic granulomatosis with polyangiitis, which runs with asthma and a high eosinophil count. Neither appears in the stem.
DCorrect
Patchy necrosis of alveolar walls with intra-alveolar hemosiderin. The sinusitis with a perforating septal ulcer, hemoptysis, hematuria and c-ANCA identify granulomatosis with polyangiitis, which is one of the three diffuse alveolar hemorrhage syndromes. The lung therefore shows that group’s morphology: alveolar walls necrose patchily, and iron from bleeding that has been going on for months is stored as hemosiderin inside alveolar macrophages. The necrotizing granulomas and vasculitis that also define this disease are not among the options offered here.
EIncorrect
Diffuse alveolar damage with hyaline membranes. Diffuse alveolar damage with hyaline membranes is acute respiratory distress syndrome. His course has run for three months.
Question 10 of 11Arc 4 · Atelectasis
A 3-year-old boy is brought to the emergency department after accidentally aspirating a toy piece. A chest X-ray shows complete collapse of the right lung behind an obstructed right main bronchus.
Which of the following clinical findings would you most likely observe?
AIncorrect
Deviation of the mediastinum towards the left side. The mediastinum moves toward the collapse, and the collapse is on the right. Leftward is the opposite direction.
BIncorrect
Trachea shifted away from the affected side. Shifted away is the compression pattern, where the pleural space has gained volume. Here volume is lost, so the trachea is pulled toward the obstruction.
CIncorrect
Absent breath sounds and tactile fremitus on the left side. The obstruction is on the right, so it is the right side that is silent and without fremitus. The left lung is ventilating normally.
DCorrect
Diaphragmatic elevation on the right side. The foreign body obstructs the bronchus, trapped air distal to it is resorbed, and the right lung collapses. Everything then moves to fill the space it has given up: the trachea and mediastinum shift to the right, and the right hemidiaphragm rises.
EIncorrect
Increased respiratory effort but normal oxygen saturation. A collapsed lung is still perfused but no longer ventilated, which is a shunt, so the saturation falls. The effort does increase, but the rest of the option is wrong.
Question 11 of 11Arc 4 · Atelectasis
A 65-year-old woman with a history of breast cancer presents with progressive shortness of breath over the past week. She reports mild left-sided chest discomfort but denies fever or cough. She has had a mastectomy and recent chemotherapy. Heart rate is 110/min, blood pressure 130/78 mm Hg, respirations 28/min and oxygen saturation 88% on room air. Chest examination shows markedly decreased breath sounds over the left lower lung field, dullness to percussion and decreased tactile fremitus. The trachea is deviated toward the right.
Which of the following best explains the mechanism of her lung findings?
AIncorrect
Collapse of alveoli distal to an obstructed airway due to resorption of trapped air. Resorption pulls the trachea toward the affected side. Hers has moved away from the left, so the pleural space has gained volume rather than lost it.
BIncorrect
Accumulation of air under pressure in the pleural space, causing lung collapse. A tension pneumothorax also pushes the trachea away, but air in the pleural space is resonant to percussion. Her percussion note is dull, which means fluid.
CCorrect
Increased intrapleural pressure from fluid accumulation compressing the lung parenchyma. A malignant pleural effusion in a woman with treated breast cancer. Fluid raises the pressure around the lung and squeezes the alveoli closed, so breath sounds and fremitus fall and the percussion note is dull, and the added volume pushes the mediastinum to the opposite side. This is compression atelectasis, and it is reversible once the fluid is drained.
DIncorrect
Destruction of alveolar walls due to chronic inflammation, leading to loss of elastic recoil. Destruction of alveolar walls is emphysema. It develops over years, it gives hyperinflation rather than dullness, and it does not deviate the trachea.
EIncorrect
Interstitial edema causing alveolar flooding and decreased lung expansion. Interstitial edema is bilateral and gives crackles with a raised jugular venous pressure. It does not produce unilateral dullness with the trachea pushed across.
Learning objectives
PATH.7044Explain etiology and findings in pulmonary embolism.
PATH.7045Identify the gross and microscopic appearances of pulmonary infarcts and correlate them with clinical features.
PATH.7046Classify pulmonary hypertension into primary and secondary, and identify the main cause of the secondary type.
PATH.7047Distinguish the vascular changes in pulmonary hypertension.
PATH.7048Distinguish the diffuse alveolar hemorrhage syndromes on clinical features, morphology and laboratory investigations: Goodpasture syndrome, idiopathic pulmonary hemosiderosis and Wegener’s granulomatosis.
PATH.7049Distinguish the types of atelectasis (resorption, compression and contraction) on etiopathogenesis, pathology and clinical features.
PATH.7050Differentiate the effects of large, medium and small emboli.
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Pathology images are reproduced from Robbins and Cotran, Pathologic Basis of Disease, and used with permission for classroom teaching at St. George’s University.
