Monday, July 25, 2016

Unilateral Pleural Effusion

Unilateral Pleural Effusion

This week past we discussed a case of a man presenting with a 3 week history of worsening dyspnea. On chest x-ray he had a large right-sided pleural effusion.

There were several teaching points for the case:

1.       Differential diagnosis of shortness of breath: We discussed that although there is a long differential diagnosis for shortness of breath, operationally we are thinking about the top 3-4 most likely and serious causes in our heads when seeing a patient. For shortness of breath this could include:
a.       Heart failure
b.      Pneumonia
c.       COPD
d.      Acute coronary syndrome  

In this case, we know there is a large right-sided pleural effusion, so it shapes our differential diagnosis further.

Differential diagnosis of a pleural effusion includes:
Heart Failure
Infection (bacterial parapneumonic, mycobacterial, fungal, viral, parasitic)
Nephrotic syndrome
Liver cirrhosis
Constrictive pericarditis
Collagen vascular disease (RA, SLE, GPA, EGPA)

GI (pancreatitis, esophageal rupture)



Other (post-CABG, post-radiation, uremia, drug-induced, sarcoidosis

As you can see, the differential diagnosis is broken down by transudate and exudate. But how do we tell? We do a diagnostic thoracentesis and analyze the fluid using Light’s criteria.

-          Guidelines suggest all effusions of >1cm in the decubitus view without a known diagnosis should be investigated with a thoracentesis.
-          Guidelines suggest diagnostic thoracentesis does not need to be performed for bilateral effusions in a clinic setting strongly suggestive of a transudate (i.e. heart failure)
-          Guidelines suggest that for the initial diagnostic thoracentesis the following be sent:
o   Cytology, protein, LDH, pH, Gram stain, culture and sensitivity
-          Don’t forget to measure the serum LDH and total protein in order to be able to calculate Light’s Criteria

Light’s Criteria
Pleural fluid total protein/serum total protein
Pleural fluid LDH/serum LDH
Pleural fluid LDH
>2/3 upper limit of normal
Note: any one of the above positive = exudative. Highly sensitive (98%) but specificity 83% (will misidentify some transudative effusions as exudative

Due to Light’s Criteria proneness to misidentify some transudative effusions as exudative (especially if there has been diuresis for heart failure which can concentrate the fluid), one can use Extended Light’s Criteria to help clarify.

Extended Light’s Criteria = total protein gradient
                                             = serum total protein minus pleural fluid total protein
The fluid is transudative if the total protein gradient is > 31 g/L.

In this case the pleural effusion was exudative on diagnostic thoracentesis.

When working up the unilateral pleural effusion further the following diagnostic algorithm can be used:
From the BTS guidelines on page 11 at:

Further reading

Hooper C et al; BTS pleural guidelines group. Investigations of a unilateral pleural effusion in adults: British Thoracic Society Plerual Disease Guideline 2010. Torax. 2010;65 Suppl 2.

McGrath EE, Anderson PB. Diagnosis of pleural effusion: a systematic approach. Am J Crit Care. 2011;20(2):119-27.

Craig, J., Gold, W. L., & Leis, J. A. (2013). A 44-year-old man with a parapneumonic effusion.Canadian Medical Association Journal, 185(3), 232-234.

Friday, July 8, 2016

Acute Liver Injury

Today’s case involved a young man with no medications and no past medical history who presented with a 2 week history of malaise and jaundice on exam. He was found to have abnormal laboratory values including AST and ALT in the 1000s and bilirubin in the 200s.

There were several teaching points for the case:

We discussed the differential diagnosis for jaundice. We discussed that there are two main categories of hyperbilirubinemia (i.e. jaundice):

1. Unconjugated hyperbilirubinemia: caused by hemolysis or impaired hepatic bilirubin uptake and/or conjuation such as from Gilbert syndrome or medications.

2. Conjugated hyperbilirubinemia: the main cause is cholestasis which can be extrahepatic cholestasis (i.e. biliary obstruction from choledocholithiasis, primary sclerosing cholangitis, tumors, or other causes) or intrahepatic cholestasis (i.e. from hepatitis, primary biliary cholangitis, drugs and toxins, sepsis, infiltrative dieases and other causes)

In this case we were faced with a conjugated hyperbilirubinemia in the context of acute liver injury. We discussed the questions that are important on history that are based on the differential diagnosis for acute liver injury. This includes asking about: medications (including over-the-counter medications), toxins (including acetaminophen and alcohol), other ingestions (specifically mushroom poisoning for Amanita mushrooms), risk factors for viral hepatitis (including travel, country of birth, tattoos, blood transfusions, and injection drug-use), family history (including autoimmune hepatitis, genetic diseases such as Wilson disease), or history of severe illness that could result in hypoperfusion and ischemic hepatitis. We also discussed that it would be important to rule out pregnancy and pregnancy-related causes in a female patient. 

The differential diagnosis of marked transaminitis (i.e. AST and ALT in the 1000s) includes:
Top 3:
1.  Acute viral hepatitis
2.  Drug/toxin-induced liver injury (including acetaminophen)
3. Acute ischemic hepatocellular injury (i.e. “shock liver”)
Other causes (less common but possible): autoimmune hepatitis, acute Budd Chiari, HELLP, acute fatty liver of pregnancy, Wilson’s disease. 

We discussed the key points on physical exam which would include looking for signs of chronic liver disease, examining for jaundice (look at the sclera for scleral icterus, look at the frenulum), examination for hepatic encephalopathy with mental status exam and examination for asterixis, and abdominal exam.

We discussed the investigations that would be indicated, including a work up for the cause of acute liver injury based on the differential diagnosis above (viral hepatitis serology, acetaminophen level, tox screen, and abdominal ultrasound with doppler as a reasonable preliminary work up), and the importance of the liver function tests for prognosis. The liver function tests include: platelets, INR, albumin, bilirubin and blood glucose. We talked about how liver function tests (i.e. the laboratory values related to the liver’s function: produce albumin, coagulation factors, produce glucose in states of starvation)  and liver enzymes (AST, ALT, and ALP) are not the same thing and how the terms are often confused.

We discussed the principles of management:
·         - Ensure hemodynamic stability
·         - Nutritional Support
·         - Accuchecks and IV glucose infusion if needed
·         - Acetylcysteine infusion **Especially if acetaminophen poisoning*** (there is limited evidence that acetylcysteine may also benefit patients with non-acetaminophen-related acute liver failure, possibly through its antioxidant and immunologic effects)
·         - Monitor clinically and through laboratory testing for prognostic evaluation
·         - Involve liver transplantation experts early

For further reading:
1.  A review on acute liver failure from NEJM: Bernal W, Wendon J. Acute liver failure. NEJM 2014;370(12):1170-1.
2. A RCT that provides evidence for the use of N-acetylcysteine infusions in early stage non-acetaminophen-related acute liver failure to improve transplant-free survival: Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology 2009;137:856-64