1. The patient presents with onset dyspnea, a symptom that can be a result of pneumothorax. In pneumothorax, positive pressure is allowed to push against the lungs preventing the lungs ability to expand or inhale thus causing the patients dyspnea. Accounting for the chest pain, the patient could present with a myocardial infarction or pericarditis in which the heart muscle lacks oxygen supply and the pericardial sac is inflamed, respectively. Considering dyspnea and chest pain, the patient could have pneumonia or a bacterial upper respiratory infection which causes the two symptoms. However, all three symptoms could be explained by pulmonary embolism which is a blockage of the pulmonary arteries. 

2. Given all of the information on the patient, the top diagnosis must be pulmonary embolism. Three of the main determinates were the high levels of D-dimer, previous history of deep vein thrombosis (DVT) and her job-occupation. A D-dimer test examines the levels of D-dimer in a patient which are substances released upon the degradation of a blood clot.[3] The high level in the plasma (2000ng/mL where less than 250ng/mL is normal) indicates that there is a degradation of a clot somewhere in the body. The patient’s occupation requires her to travel from Chicago to Tokyo every week, a 13 hour flight, and because she sits down for that amount of time, she has increased risk of DVT. The increased risk of DVT arises from the lack of calf muscle contractions that would normally push blood up to the heart, increasing the risk of blood clots. Her past history of DVT increases the likelihood that the she would have pulmonary embolism.[4]

With regards to the differential diagnoses, pneumonia and pneumothorax can be ruled out as the radiologist stated that the patient has a “Normal chest x-ray with no acute findings”. Myocardial infarction (MI) and pericarditis could also be ruled out mainly because of the normal levels of troponin I. In patients with MI, the levels of troponin I would be elevated which indicates myocardial damage as in MI. [1] In both MI and pericarditis, there would also be an abnormal EKG but the patient’s EKG demonstrates a normal pattern with no MI or pericarditis as explained by the cardiologist.[2] Additionally, normal S1 and S2 sounds with no murmurs, rubs or gallops further confirms that heart function is normal. 

3.With pulmonary embolism as the top diagnosis, the blood flow to the lungs must be traced in order to discover where exactly the clot is creating the obstruction. A pulmonary angiogram would be the best test to demonstrate this information. In this procedure, a catheter would be inserted through the femoral vein and guided through the pulmonary arteries. A contrast dye would then be injected allowing the dye to be perfused throughout the pulmonary arteries. An x-ray would then be taken of the patients chest which would demonstrate the entirety of pulmonary arterial flow and clot that is causing the patients symptoms.[5]

4a. Ventilation Perfusion ratio demonstrates how well an area of the lung is perfused with blood and is ventilated with airflow. With a higher V/Q ratio, there is greater the ventilation and lower perfusion. This is in contrast to a lower the V/Q ratio where there is lower ventilation and greater perfusion.

In hypoxic vasoconstriction, there is an obstruction of air flow (ventilation) to a part of the ventilation pathway. For example, obstructed alveoli would lead to less blood flow (perfusion) to those alveoli versus other well perfused alveoli. This occurs because the lack of oxygen to the alveolus sends a signal to constrict the pulmonary arterioles that would normally visit the obstructed alveolus. The blood follows the path with least resistance and would avoid the obstructed alveolus with a constricted arteriole leading the blood to the ventilated alveolus with normal perfusion (least resistance).[7][9]

Figure 1 – Hypoxic Pulmonary Vasoconstriction [6]

4b. A V/Q defect is essentially a mismatch in which certain lung units receive a high V/Q or a low V/Q ratio. This impairs the ability for the patient to saturate the blood with enough oxygen for proper delivery to the system (hypoxemia). A normal V/Q ratio is 0.8 and anything higher or lower within the lobe would demonstrate an unformal distribution of ventilation or perfusion. [7][9]
Regional V/Q mismatch does normally exist in a normal upright lung. The apex of the lung has a high V/Q ratio of 3.0 (Well ventilated, poorly perfused) whereas the base of the lung has a low V/Q ratio of 0.6 (Poorly ventilated, well perfused). However, the lung will go out to correct this anatomical dead space that is created by the position of the individual (standing, sitting, lying down). This is such that if there were an alveolus with rich ventilation than perfusion, the lungs would respond by constriction the bronchioles and by dilating the arterioles which would decrease ventilation and increase perfusion, respectively. The opposite would also occur if an alveolus with poor ventilation and rich perfusion were present. [7][9][10]

When discussing the west zones or lung zones, the lung possesses three zones that demonstrate unique pressures amongst the alveoli (PA), arteriole (Pa) and venous (PV) systems in the lung. In zone 1 or the apex of the lung, there is no flow because the Pa is not great enough to overcome PA but this zone is not present in a normal lung as Pa is sufficient to perfuse the apex of the lung. In zone 3, Pa exceeds PA and thus allows continuous flow. Zone 2 and its regional flow depend entirely on the difference between Pa and PA with little regard to PV because of how much smaller it is compared to PA.[9][10][11]

This entire discussion can be followed up by an explanation of A-a gradient which is one way to assess the alveolar-capillary integrity and assist in determining the cause of a patients low PaO2. A normal A-a gradient constitutes is less than the (patients age divided by 4) + 4. In the case of our 35 year old patient, the A-a gradient should be less than 12.75. In other words, if PA is 100mmHg then Pa should be above 87.25mmHg. Anything lower than 87.25mmHg in Pa would indicate an issue with the oxygen transfer between the alveolar-capillary unit. [9][10][11]

Figure 2 – Figure 11 from West et al.’s paper. Left. Diagram of the three zones of the lung. Middle. Relationship between pulmonary artery, pulmonary vein and alveolar pressure. Right. Graph of distance towards the apex of the lung versus blood flow

4c. A V/Q scan involves two nuclear scan tests that measures both ventilation and circulation in the entirety of the lungs. In the perfusion scan, radioactive albumin is injected into a vein in the patients arm while they are placed on a movable table under the gamma scanner. The machine scans the lungs, detecting the radioactive albumin as it flows throughout the pulmonary circulation. In the ventilation scan, the patient breaths in radioactive gas with a mask on while they are sitting or lying beneath the scanner. The entire exam would detect any abnormalities in both blood flow (perfusion) and respiration (ventilation).[8]

Figure 3 – Radioactive albumin injected into a vein in the arm and is part of a nuclear scan test to measure the supply of blood in the lungs. 

4d. In this case of our patient with PE, blood flow would be obstructed in a certain region of the lung. This would then increase blood flow to other parts of the lung that are not obstructed. With increased blood flow velocity, there will be less time for these RBC to become saturated with oxygen at these other alveoli leading to low oxygen delivery in the body. However, if the patient is given 100% oxygen then the alveoli would have pure oxygen supply to feed the RBC. This would give the RBC the opportunity to extract more oxygen in the little time they have (due to increased flow) versus if the alveolus had less oxygen supply. [10] The supply of oxygen would return the V/Q ratio back to normal. With the increased perfusion towards other parts of the lung (explained above) and increased ventilation (due to the 100% O2 supply), there would be a change towards the normal. 

4e. These image scan results would confirm the diagnosis of pulmonary embolism (PE). In the ventilation scan, there is a uniform distribution of airflow. This is in contrast to the blood flow scan which does not present uniformly as the ventilation scan meaning there must be some sort of blockage to flow. 

5. An ultrasound test should be done in order to confirm the diagnosis of PE. The exam itself uses high-frequency waves to check for blood clots in the lower extremities (thigh veins). The patient presented with swelling of the right left which resulted from a clot that arose from her long 13 hour weekly trips from Chicago to Tokyo. Pieces of the clot broke off which circulated through the vena cava into the right side of the heart and eventually stuck within the pulmonary arterioles leading to the PE. [12][13]

6. Now that the patient has been diagnosed with PE, treatment can follow which prevents the blood clot from getting any bigger and any new ones forming. Typically, anti-coagulants would be the mainstay treatment which would prevent the formation of future blood clots. The medicine would be taken as a pill (Warfarin), or as an IV-injection (Heparin). Usually, these are both administered at the same time because heparin is fast-acting whereas warfarin takes up to 2-3 days to take effect. With this particular patient, who has DVT, the regiment would need to last for about 3-6 months.

The use of anticoagulants would not remove the current clot in her system. Removing the clot would only be done if the symptoms are life-threatening since the procedures are very invasive (embolectomy).  In terms of future prevention and life-style changes, the patient would need to cease long durations of sitting down and perform some lower leg exercises that would allow blood to flow normally in the lower extremities. [13]

Newer treatment modalities are available that would pose less risk to patients. Rivaroxaban, a factor Xa inhibitor, would decrease the rate of bleeding which was more likely to happen with the mainstay treatment. [14]