Differential Diagnosis

Given the pt’s history and physical exam list your differential diagnosis including at least 5 possible diagnoses.[1]

Lower respiratory infection (pneumonia)	Fever, sweating and shaking chills, cough (may have sputum), chest pain, dyspnea, fatigue, nausea, vomiting, diarrhea
Pulmonary embolism	Dyspnea, chest pain, cough (may be bloody sputum), leg pain, pedal edema, cyanosis, fever, excessive sweating, irregular heartbeat or tachycardia, dizziness, tachypnea[2] [3]
Left sided heart failure	Cough (frothy or blood-tinged sputum), decreased urine output, dyspnea (paroxysmal nocturnal dyspnea), fatigue, tachycardia, heart palpitations, edema[4]
Lung abscess	Fever, cough (with sputum), chest pain, gingivitis/periodontal disease, dyspnea, positive pleural friction rub, dullness of chest percussion, digital clubbing[5]
Asthma	Coughing, wheezing, dyspnea, chest pain or tightness

What is your top diagnosis?

Pulmonary embolism

Looking at the symptoms before the physical examination and labs, pulmonary embolism stands out since the symptoms include pedal edema, bloody sputum, chest pain, sweating, fever, tachycardia, and dyspnea. The patient travels often for her job and just returned from a long flight, noting swelling in her left leg (exam indicates right leg, and not left leg edema). This swelling, in addition to risk factors such as a past DVT in 2010, use of oral contraceptive with estrogen, indicate a possible DVT. The clot could have traveled into her lungs to cause a pulmonary embolism.[6] The ECG indicates sinus tachycardia, and it indicates “the most common ECG abnormalities in the setting of pulmonary embolism are tachycardia and nonspecific ST-T wave abnormalities.”[7] Left sided heart failure typically presents with an S3 gallop or accentuated P2 hear sound.[

The lab values indicate a high WBC (12.1x10^3/uL, normal: 4.5-11.0 x 103/uL), which may be normal or elevated in patients with pulmonary embolism, and high D-dimer (2000 ng/mL, normal: <500 ng/mL), which is reported as elevated in 86% of pulmonary edema patients. The D-dimer measures fibrin degradation product, a protein fragment found in the blood after a clot has been degraded by fibrinolysis. It is present in pulomary edema pateints when the edema is caused by the breakdown of a clot in the body (Ex: deep vein thrombosis) that travels to the lungs and causes vessel blockage. [8]  Lab values also indicate low serum chloride ion (94 mEq/mL, normal: 101 to 111 mEq/mL), which do not appear to correlate. One value that was within normal range, but should be noted is serum tropnin. “Serum troponin levels can be elevated in up to 50% of patients with a moderate to large pulmonary embolism, presumptively due to acute right ventricular myocardial stretch.”[9] It is not unsurprising to see a chest radiograph with no specific abnormalities in a pulmonary embolism. In the case of a lung abcess or infection, we would anticipate abnormalities, such as a mass or patchy appearance. 

Given your top diagnosis what specific tests do you need to run in order to confirm it?

Pulmonary angiography

V/Q scan

The V/Q Test

What is the ventilation perfusion ratio (V/Q ratio)?

The ratio between the alveolar ventilation (air getting into the alveoli) and cardiac output. This ratio is essential when comparing the ventilation (bringing in O2 and removing CO2 from the alveoli) and the perfusion of these gases in the bloodstream. This ratio can be changed both physiologically and pathologically. One example of a pathological change is when the V/Q ratio is decreased due to too little ventilation in the region, causing hypoxic vasoconstriction. This causes the blood flow to the area to be diverted to other parts of the lung via vasoconstriction, decreasing perfusion and raising the V/Q ratio to a value closer to normal in the hypoxic region. If the opposite occurs and the V/Q ratio increase, the bronchi will constrict to decrease the ventilation value of the alveoli to the area of poor perfusion, returning V/Q.[10]

What is a V/Q scan? How is it performed?

A V/Q scan is the technique utilized to determine the ventilation perfusion ratio of the lungs in a patient. The test has two parts: alveolar ventilation and perfusion to the lungs.

Ventilation: The patient breathes in a radioactive drug, radionuclide, and after a couple minutes a gamma camera is used to image the lungs. Areas that do not receive ventilation will not collect radionuclide are called “cold spots”, and the areas that collect air/radionuclide are called “hot spots”.
Perfusion: Injection of a radioactive drug into the bloodstream. Areas that receive abnormal blood flow will receive pooling of the radioactive material, or lack of.[11]

What is a V/Q defect? Does a regional V/Q mismatch normally exist in the lungs? What does it tell you? What do you expect for this situation?

A V/Q defect is an abnormal V/Q ratio that reflects on a V/Q scan indicative of an abnormal ventilation or perfusion value compared to the other. These differ from a mismatch in that they will be more global or equally represented in both lungs, such as in the COPD V/Q scan in the figure on the right.

A regional V/Q mismatch occurs if ventilation is normal, but perfusion is abnormal in a segment of the lungs that does not reflect equally in both lungs.[12] This is indicative of pulmonary embolism. In the figure below  you will note that the lower portion of the right lung appears to have “disappeared” due to a lack of perfusion compared to the normal lung.[13]  

There are four vertical regions of the lung, “west zones”, that are defined as the relationship between the alveolar pressure (PA), arterial lung pressure (Pa), venous lung pressure (Pv), and pulmonary interstitial pressure (Pi).

Zone 1: PA > Pa > Pv (Not observed in healthy lung because Pa> PA in all parts of the lung. Observed in patients ventilated with positive pressure, causing alveolar collapse- dead space.)

Zone 2: Pa > PA > Pv

Zone 3: Pa > Pv > PA

Zone 4: Pa > Pi > Pv > PA (Seen in the lung base at low lung volumes or pulmonary edema. Pulmonary edema causes Pi to increase due to increased fluid volume in the lung, causing decreased blood flow due to the decrease in the Pa-Pi pressure difference that acts as the driving force.)[14]

How would O2 help this patient and how would it change the V/Q ratio?

Since a portion of the lung blocked by the pulmonary embolism is not being perfused and there is no gas exchange occurring. This alveolar area is considered “dead space”. Giving oxygen will increase the oxygen saturation in the parts of the lung that are still undergoing gas exchange and allow for an oxygen value closer to normal to diffuse into the body. This would not change the V/Q ratio because blood flow nor the volume or air has changed only the content.[15]

What is the interpretation of the scan below? Match this up with the clinical findings.

The V/Q scans of the patient indicate there is a mismatch defect in the perfusion scans. There is a lack of perfusion to the left lung indicated by the “cold spots” in the left lung compared to the right lung. The ventilation scans appear normal. Therefore, this indicates the presence of a pulmonary embolism. Clinically, a pulmonary embolism presents as breathing problems, shortness of breath, chest pain, coughing (often bloody), and can be related to deep vein thrombosis (presents as swelling and pain in the leg). Our patient presents with all of these symptoms.[16]

Given the positive diagnosis and confirmation of your suspicions what additional tests might be indicated in this patient. Why is that important?

As mentioned in the differential, the swelling of the left leg, and additional risk factors (past DVT in 2010, use of oral contraceptive with estrogen) indicate a possible DVT as the source of the embolus. If a potion of this clot had broken off, if could have easily traveled into the lungs where it formed pulmonary embolism. In order to diagnose this, and since we already have a positive indicator (elevated D Dimer), we would order an ultrasound of both legs to detect a potential clot.

What do we do now that we have the diagnosis? What is the mainstay treatment for a PE? Does this actually remove the clot? There are newer treatment modalities available what is the evidence for these? (Hint: Einstein PE trial)

The first concern is to stabilize and oxygenate the patient (supplemental oxygen, ventilation), and then anticoagulation drugs should be given for pulmonary embolism (also applicable to DVT treatment). For an acute pulmonary embolism, patients are given heparin. These treatments do not actually remove the clot and along with anticoagulant drugs, the body will most often break down these clots within a few weeks to months. In chronic cases, a pulmonary thromboendarterectomy may be performed.[17] Since heparin and other common must be closely monitored, a recent study suggests rivaroxaban, an oral factor Xa inhibitor, is as effective as anticoagulant treatment without the stringent laboratory monitoring.[18]

Works Cited

[1] http://www.turner-white.com/memberfile.php?PubCode=hp_jul04_dyspnea.pdf

[2] http://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/basics/symptoms/con-20022849

[3] http://emedicine.medscape.com/article/300901-clinical#b3

[4] http://www.nytimes.com/health/guides/disease/left-sided-heart-failure/overview.html

[5] http://emedicine.medscape.com/article/299425-clinical#b5

[6] http://www.cdc.gov/ncbddd/dvt/travel.html

[7] Gupta A, Frazer CK, Ferguson JM, Kumar AB, Davis SJ, Fallon MJ, et al. Acute pulmonary embolism: diagnosis with MR angiography. Radiology. 1999 Feb. 210(2):353-9

[8] http://www.nejm.org/doi/suppl/10.1056/NEJMcpc049016/suppl_file/nejmcpc049016_tables.htm

[9] Konstantinides S. Clinical practice. Acute pulmonary embolism. N Engl J Med. 2008 Dec 25. 359(26):2804-13.

[10] https://courses.kcumb.edu/physio/adaptations/vq.htm

[11] http://www.hopkinsmedicine.org/healthlibrary/test_procedures/pulmonary/lung_scan_92,P07751/

[12] https://www.uic.edu/classes/phyb/phyb401a/slides/Handout%202%20(LC55-57).pdf

[13] http://caa.medinuclear.com/site/1946caa_/Interpreting_VQ_scans3.pdf

[14] West J, Dollery C, Naimark A (1964). "Distribution of blood flow in isolated lung; relation to vascular and alveolar pressures". J Appl Physiol 19: 713–24. PMID 14195584.

[15] http://www.uptodate.com/contents/overview-of-the-treatment-prognosis-and-follow-up-of-acute-pulmonary-embolism-in-adults

[16] https://www.nhlbi.nih.gov/health/health-topics/topics/pe/signs

[17] http://www.uptodate.com/contents/overview-of-acute-pulmonary-embolism-in-adults#H15

[18] http://www.nejm.org/doi/full/10.1056/NEJMoa1113572