1. Given the pt’s history and physical exam list your differential diagnosis including at least 5 possible diagnoses. (Remember the differential diagnosis should be broad and really just include causes that could account for the relevant symptoms) Essentially what could account for acute onset dyspnea, chest pain, and tachypnea.

The patient presents with symptoms that could point to several different coniditions, which are listed below. Underneath each diagnoses are the symptoms seen in our patient that are also present with each different condition. 

Pulmonary embolism: an embolism within the lungs that interferes with blood flow

• Risk factors include immobility and having a prior DVT
• Symptoms include: dyspnea, tachypnea, hemoptysis, cough, hypoxemia (would require oxygen)
• Deep vein thrombosis
• Risk is immobility for long periods of time (and she travels often involving long plane trips)
• Pain and swelling in her right leg
• She’s had one before

Acute pulmonary edema: excess fluid within the lungs

• Dyspnea
• Orthopnea
• Wheezing
• Chest pain
• Sputum tinged with blood

Pulmonary tuberculosis: a bacterial infection within the lungs

• Night sweats
• Fatigue
• Dyspnea
• Productive cough
• Chest pain
• Hemoptysis

Heart failure: heart working improperly can result in fluid buildup within the lungs

• Dyspnea with exertion
• Orthopnea
• Edema in legs
• Rapid heartbeat
• Sudden shortness of breath

Acute bronchitis: inflammation of bronchial tubes

• Cough
• Sputum may be blood tinged
• Chest pain
• Wheezing

Reaction to atorvastatin: adverse reaction or side effects experienced from medication meant to lower cholesterol

• Cough
• Tachycardia
• Wheezing
• Chest tightness

Pulmonary hypertension: high blood pressure within pulmonary blood vessels

• Cough
• Chest pain
• Dyspnea

Bacterial Pneummonia: infection in the lungs

• Chest pain worsened by breathing
• Blood tinged mucus
• Breathlessness

Asthma Attack: airways narrowing make it difficult to breathe

• Cough
• Wheezing
• Shortness of breath

2. Now given the clinical presentation, physical exam and labs What is your top diagnosis? (Use your differential and think through what data lead you to believe your top diagnosis is correct and go against the others)

My top diagnosis is that the patient has an acute pulmonary embolism. This is characterized by sudden onset of tachypnea, tachycardia, lower extremity edema, dyspnea, chest pain, wheezing, and hemoptysis. Her white blood cell count is slightly elevated which may occur in patients experiencing this. Also, she has a positive D-dimer result. This test is used to detect abnormal blood clots by looking for fibrin-degradation product, which is present in the blood after a clot is degraded. This product is not normally present at high levels within the blood. Raised levels indicate that there is a clot within the blood that has been recently or is currently being broken down. Pulmonary embolism will sometimes produce an abnormal chest X-ray but this isn’t a consistent finding. 

She also has several risk factors for this disease. These include taking oral contraceptives, hyperlipidemia, travelling for over four hours in the last month, and a prior deep vein thrombosis.

I don’t believe she is experiencing a reaction to her medication because the symptoms she’s experiencing are rare side effects for that medication. The patient can not be having an asthma attack because her inhaler would have provided relief by opening her airways. Acute pulmonary edema would result in hypotension, jugular venous distension, and heart murmurs. The patient doesn’t show any of these symptoms. Pulmonary hypertension would cause the patient to faint, and she hasn’t. The patient didn’t have an X-ray that was characteristic of heart failure because there was no enlarged heart or edema seen. I don’t think it is bronchitis because the patient would have been experiencing green or yellow mucus prior to the event that sent her to the emergency department. It isn’t tuberculosis because there’s no crackling sounds when she breathes or dullness to percussion. Her X-ray results are also inconsistent with someone who has tuberculosis or pneumonia. She also isn’t experiencing any arrhythmias which can occur is some of the other diseases listed in the differential diagnosis. A deep vein thrombosis is not associated with respiratory symptoms at first (even though they can cause it). Her symptoms suggest that if she did have a thrombosis that it has already developed into a more serious condition.

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

I would first look at the ischemia modified albumin level because this level changes quickly during ischemic events and would help indicate an embolism. This is 93% sensitive and 75% specific. Then I would have several options. I could use pulmonary angiography to visualize the embolus. By injecting an ionidated compound I could watch to see if it abruptly stopped while filling the arteries of the lungs, indicating a blockage. A CT scan would also allow me to visualize the embolism and is a less invasive procedure. Duplex Ultrasonography can be used to detect a deep vein thrombosis that may have caused the embolism. This uses regular ultrasonography and dopler ultrasonography to create an image and measure flow. The vein containing the thrombus wouldn’t collapse under the pressure of ultrasonography like a normal vein, making it easy to detect. Ventilation-profusion (V/Q) scanning could also be used to look for a pulmonary embolism. It allows us to compare ventilation to the blood profusion using radioactive pharmaceuticals (see 4C for a more extensive explanation). 

4. Results of a VQ Scan are shown below. Before interpreting the results below please elaborate on the following:
 

a.What is the ventilation perfusion ratio (V/Q ratio)? (Include a short discussion on hypoxic vasoconstriction)

It is the ratio of the amount of air between the amount of blood reaching the alveoli (cardiac output). This helps determine the amount of oxygen and carbon dioxide in the alveoli and blood. The body tries to maintain a normal ratio of 4L of ventilation to 5 L of perfusion. When this is disrupted the body will try to bring it back to normal. When perfusion is higher than ventilation (due to decreased ventilation or increased flow) the ratio is lowered and hypoxic vasoconstriction occurs. Blood vessels within the lungs will constrict in response to low oxygen. This diverts blood flow to other lung regions and reduces perfusion to match ventilation. The ratio can also be altered if ventilation becomes higher than perfusion. Then bronchial constriction will occur to compensate. 

b.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? (Include short discussion of west zones)

A V/Q defect is when an abnormal ratio leads to improper blood oxygenation. A V/Q mismatch does normally exist between lung regions when standing, even though the overall the ratio is about 1. The normal ratio is about 0.8 because blood flow rate is slightly greater than ventillation rate. Due to gravity there is more blood flow to the bottom of the lungs compared to the top. The alveoli are more expanded at the lung apex and compress vessels. Near the base higher blood pressures and more compressed alveoli allow more blood flow. Blood flow and ventillation do not change at the same rate. The apex of the lung is described as Zone 1. Ventilation is lower here, but blood flow is even lower. The blood pressure can become so low that the arteries and veins collapse and almost no perfusion occurs. The V/Q ratio is increased. Zone 2 describes the middle region of the lung. In this zone arterial pressure is higher than alveolar pressure, but venous pressure is lower than alveolar pressure. This slightly interferes with flow but it is not as significant as Zone 1. The V/Q ratio is more towards normal here. Zone 3 is at the base of the lungs where blood pressure and ventilation are the highest. Both arterial and venous pressure are higher than alveolar pressure, and flow exceeds ventilation. The V/Q ratio is decreased.

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

This scan uses radioisotopes to measure the air ventilation and blood perfusion in your lungs. You either inhale or inject them while a camera takes images. The radioactive material is inhaled using a nebulizer and you lay down on a table while a gamma camera takes images. The material will flow to ventilated areas of the lungs as you breathe. Next a different type of material is injected into your arm and pictures are taken again to show the perfusion through the lungs. These two images can be compared and can indicate if the patient is suffering from a pulmonary embolism. Defects are classified on whether there is a low, moderate, or high probability that the embolism would be seen if an angiogram was performed. Classification also takes into account which lung segment it’s located in and how much of that segment isn’t normal. 

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

The embolism would lower blood supply to areas of the lung, and the overall V/Q ratio in those areas would be raised. Pulmonary vessels respond to oxygen by dialating. Increasing oxygen would help increase perfusion in these areas. This helps the patient bring more oxygen into their blood and brings the V/Q ratio towards normal.  

e.What is the interpretation of the scan below (Fig 1)? Match this up with the clinical findings.

To understand the images better, please note that "P" stands for posterior, "A" stands for anterior, "L" stands for left, "R" stands for right, and "O" stands for oblique angle. The pictures from the case below (Fig.1) show different views of the lungs during both the ventilation and perfusion stage of the exam. It shows a posterior (post), right anterior oblique (RAO), and left anterior oblique (LAO) view. The 60 indicates the angle is 60 degrees. Ventilation isn’t affected by a vascular problem, so the ventilation images look normal. Now we’re looking for a differences between the perfusion and ventilation images. In a normal healthy individual the images should look almost the same (Fig 2). As you can see in Figure 1 they do not. Normally defects caused by emboli are wedge-shaped and extend out to the lung periphery (Figure 3). The perfusion image of the right lung seems to have a large defect at the inferior portion of the lung, and some smaller defects on the right side and middle of the image. The left lung seems to be most affected by the embolus. There are several large defects and the image appears “moth eaten”. Appearing “moth eaten” is a classic appearance for a pulmonary embolism because the radioactive material isn’t able to reach certain areas because of the embolus (Figure 3). The lungs appear to be greatly affected and this would explain her severe symptoms of chest pain and dyspnea. The large defects in her left lung would explain the wheezing heard in her lower left chest. 

5. Given the positive diagnosis and confirmation of your suspicions what additional tests might be indicated in this patient. Why is that important (Hint: Where did the embolus come from? There was a clinical finding and a major criteria of well’s score that would indicate further testing)

The patient is also experiencing enough symptoms that her Wells score is above six, which indicates a high probability for pulmonary embolism. Table 5 below shows the different criteria and interpretation of a Wells score. The embolus most likely came from the patient’s right leg because that is the one that is swollen. Duplex ultrasonography would allow detection of the embolus. Finding it in addition to the abnormal imaging of the V/Q scan would confirm that she had indeed experienced an acute embolism. 

6. 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)

Now that we have the diagnosis we treat the patient. Anticoagulation drugs such as Heparin are given immediately to prevent new clots from forming. Another anticoagulant such as Warfarin will be prescribed as well. The initial anticoagulants will need to be taken for a few days in order to allow Warfarin to build up in the system. Thrombolytic therapy is utilized to try and break up the thrombus in the lungs. It activates plasminogen and accelerates the break up to unblock the pulmonary vessels. This treatment does have risk of causing major bleeding in the patient and is only used once the diagnosis is confirmed. If the embolus is very large it can be surgically removed. Recently researchers have been trying to improve the treatment for pulmonary embolism and other clotting disorders like stroke. Direct Xa inhibitors, such as Xarelto, have been explored as a possible treatment. It inhibits Factor Xa, an enzyme in the blood coagulation cascade that links the extrinsic and intrinsic coagulation pathways. Blocking this enzyme prevents clots from forming or getting larger. This drug can be taken orally and the patient doesn’t have to take multiple drugs that the standard care requires. Studies have also found that there are less risks of bleeding with this drug. This may be used more often for patients in the future.

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