My patient with cirrhosis has a large right sided pleural effusion with only a small amount of ascites. Could this effusion still be related to his cirrhosis?

Yes! Although we often associate pleural effusions in patients with cirrhosis with the presence of large ascites, some patients present with hepatic hydrothorax even in the absence of significant ascites.1-3  

In fact, in a study involving 77 patients with hepatic hydrothorax, 49% had minimal or small and 9% had no detectable ascites!1  Interestingly, nearly three-quarters of patients in this study had right sided pleural effusion with 10% having bilateral and 17% having left sided effusion only. Hepatic hydrothorax without ascites as the first sign of liver cirrhosis has also been reported.2

Although the mechanism(s) behind hepatic hydrothorax is not fully clear, the passage of peritoneal fluid into the pleural cavity through defects in the tendinous portion of the diaphragm assisted by negative intrathoracic pressure during inspiration is commonly favored. 1-3  

Supportive evidence includes a number of studies involving intraperitoneal injection of air, dyes or technetium 99 m-sulfur colloid that have demonstrated the trans-diaphragmatic flow of ascites into the pleural cavity. 1-4  In the absence of ascites, a complete equilibrium between the amount of ascites produced and its flow into and reabsorption by the pleural cavity is assumed.1,2

Bonus Pearl: Did you know that although most patients with hepatic hydrothorax have a transudative pleural effusion according to Light’s criteria, 1 study showed that 18% of patients may meet the Light’s criteria for an exudative effusion? 5,6


  1. Badillo R, Rockey DC. Hepatic hydrothorax: Clinical features, management, and outcomes in 77 patients and review of the literature. Medicine 2014;93:135-142.
  2. Kim JS, Kim CW, Nam HS, et al. Hepatic hydrothorax without ascites as the first sign of liver cirrhosis. Respirology Case Reports 2016;4:16-18.
  3. Rubinstein D, McInnes IE, Dudley FJ. Hepatic hydrothorax in the absence of clinical ascites: diagnosis and management. Gastroenterology 1985;88:188-91.
  4. Holt KA, Oliviera E, Rohatgi PK. Hepatic hydrothorax demonstration by Tc-99 sulfur colloid ascites scan. Clin Nucl Med 1999;24:609. 
  5. Light RW. New treatment for hepatic hydrothorax? Ann Am Thorac Soc 2016;13:773-74.
  6. Bielsa S, Porcel JM, Castellote J, et al. Solving the Light’s criteria misclassification rate of cardiac and hepatic transudates. Respirology 2012;17”721-726.
My patient with cirrhosis has a large right sided pleural effusion with only a small amount of ascites. Could this effusion still be related to his cirrhosis?

My patient with cirrhosis has hypohonia and cogwheel rigidity. Is there a connection between cirrhosis and Parkinson’s disease?

There is a high prevalence of extra-pyramidal or Parkinson-like (PL) clinical findings in patients with cirrhosis. In fact, over 75% of patients with cirrhosis may exhibit PL signs, such as tremor, rigidity, and akinesia, with 88% also showing hyperintensity in the globus pallidus of basal ganglia on T1-weighted brain MRI.1

What’s even more interesting is the similarity between PL clinical and MRI findings among patients with cirrhosis and those with Manganese (Mn) toxicity.2,3 More specifically, similar MRI findings involving the globus pallidus have been reported in Mn-exposed workers, patients with cirrhosis, and those undergoing total parenteral nutrition with excessive Mn replacement. 4 These observations seem more than coincidental as 67% of patients with cirrhosis have been reported to have elevated blood Mn concentrations, with significantly higher levels in patients with previous portacaval anastomoses or transjugular intrahepatic portosystemic shunt (TIPS).1

Mn-induced parkinsonism is distinguishable from classic Parkinson’s disease in several ways, including the absence of Lewy bodies, more frequent dystonia, and less resting tremor.5 Also, remember that Mn-induced PL disease does NOT respond to L-dopa, a drug used to treat early stages of PD. 5 This finding can be explained by the fact that, in contrast to Parkinson’s disease where many of the dopamine-producing cells in the substantia nigra of the brain degenerate resulting in dopamine deficiency, in Mn-induced PL disease the problem is release of dopamine into synapses not its production.5

Bonus Pearl: Did you know that due to its paramagnetic properties, manganese can be effectively seen by MRI!


  1. Spahr L, Butterworth RF, Fontaine S, et al. Increased blood manganese in cirrhotic patients: relationship to pallidal m agnetic resonance signal hyperintensity and neurological symptoms. Hepatology 1996;24:1116-1120.
  2. Hauser RA, Zesiewicz TA, Rosemurgy AS, et al. Manganese intoxication and chronic liver failure. Ann Neurol 1994;36:871-75.
  3. Krieger S, Jaub M, Jansen O, et al. Neuropsychiatric profile and hyperintense globus pallidus on T1-weighted magnetic resonance images in liver cirrhosis. Gastroenterol 1996;111:147-55.
  4. Lucchini R, Albini E, Placidi D, et al. Brain magnetic resonance imaging and manganese exposure. Neurotoxicity 2000;21:769-75.
  5. Kwakye GF, Paoliello MMB, Mukhopadhyay S, et al. Manganese-induced parkinsonism and Parkinson’s disease: Shared and distinguishable features. Int J Environ Res Public Health 2015;12;7519-40.

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My patient with cirrhosis has hypohonia and cogwheel rigidity. Is there a connection between cirrhosis and Parkinson’s disease?

What is the significance of Terry’s nails in my hospitalized patient?

Terry’s nails were first described in 1954 in patients with hepatic cirrhosis (prevalence 82%, majority related to alcohol abuse) (1). Since then, they have been reported in a variety of other conditions, including adult-onset diabetes mellitus (AODM), chronic congestive heart failure, chronic renal failure, pulmonary tuberculosis, and Reiter’s syndrome (2).

A 1984 study found Terry’s nails in 25% of hospitalized patients (3).  In this study, cirrhosis, chronic congestive heart failure, and AODM were significantly associated with Terry’s nails, while pulmonary tuberculosis, rheumatoid arthritis and cancer were not. The presence of Terry’s nails may be particularly concerning in patients 50 y of age or younger as it increases the relative risk of cirrhosis, chronic congestive heart failure or AODM by 5-fold (18-fold for cirrhosis alone) in this age group (3).

Terry’s nails should be distinguished from Lindsay’s nails or “half and half” nails. Although both nail abnormalities are characterized by an opaque white proximal portion, Terry’s nails have a thinner distal pink to brown transverse band no more than 3 mm wide (3) (Fig 1), while the same anomaly is wider and occupies 20%-60% of the nail bed in Lindsay’s nails (Fig 2). Of interest, Lindsay’s nails have been reported in up to 40% of patients with chronic kidney disease (4,5).


1. Terry R. White nails in hepatic cirrhosis. Lancet 1954;266:757-59. 
2. Nia AM, Ederer S, Dahlem K, et al. Terry’s nails: a window to systemic diseases. Am J Med 2011;124:603-604. 
3. Holzberg M, Walker HK. Terry’s nails: revised definitions and new correlations. Lancet 1984;1(8382):896-99. 
4. Pitukweerakul S, Pilla S. Terry’s nails and Lindsay’s nails: Two nail abnormalities in chronic systemic diseases. J Gen Intern Med 31;970. 
5. Gagnon AL, Desai T. Dermatological diseases in patients with chronic kidney disease 2013;2:104-109.

Figure 1. Terry’s nails in a patient with end-stage liver disease

Figure 2. Lindsay’s nails in a patient with chronic kidney disease

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What is the significance of Terry’s nails in my hospitalized patient?

Should I be concerned about the umbilical hernia in my patient with cirrhosis and ascites?

Although umbilical hernia in patients with cirrhosis and ascites is common and often “expected” (a rate of 20% during the course of their disease), it can be associated with significant risk of complications such as incarceration, ascites drainage, peritonitis, and spontaneous rupture or evisceration from necrosis of overlying skin.1,2

A 2007 retrospective study involving patients with cirrhosis and umbilical hernia reported a complication rate of 77% and related mortality of 15% among those managed conservatively (mean period of observation ~ 5 years); MELD score could not predict failure of conservative management (median 22 in complicated vs 24 in uncomplicated).3

Because the risk of death with hernia repair in urgent settings is 7x higher than for elective hernia repair in cirrhotic patients, there has been increasing interest in elective repair in patients with well-compensated cirrhosis.3 Interestingly, the reported surgical complication rates among patients with well-compensated cirrhosis appear similar to those in noncirrhotic patients.3 If the patient is expected to undergo liver transplantation in the near future, elective hernia repair can be postponed and managed concomitantly.

Bonus pearl: Did you know that spontaneous umbilical hernia rupture is also known as “Flood syndrome” (should be easy to remember!), first described by Frank B Flood, a surgical resident back in 1961? 4


  1. Marsman HA, Heisterkamp J, Halm JA, et al. Management in patients with liver cirrhosis and an umbilical hernia. Surgery 2007;142:372-5.
  2. Coelho, JCU, Claus CMP, Campos ACL, et al. Umbilical hernia in patients with liver cirrhosis: a surgical challenge. World J Gastrointest Surg 2016;8:476-82.
  3. Martens P, Laleman W. Umbilical hernia in a patient with cirrhosis. Cleveland Clin J Med 2015;82: 404-5.
  4. Nguyen ET, Tudtud-Hans LA. Flood syndrome: spontaneous umbilical hernia rupture leaking ascitic fluid-a case report. Perm J 2017;21:16-152. 

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Should I be concerned about the umbilical hernia in my patient with cirrhosis and ascites?

Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

When a patient with congestive heart failure (CHF) or end-stage liver disease (ESLD) doesn’t respond as expected to diuretic therapy, measurement of urinary sodium (Na) can be helpful.

In low effective arterial blood volume states (eg, CHF and ESLD) aldosterone secretion is high, resulting in high urine potassium (K) and low urine Na concentrations. However, in the presence of diuretics, urinary Na excretion should rise.

Patients undergoing active diuresis are often restricted to a 2 g (88 mEq) Na intake/day, with ~10 mEq excreted via non-urinary sources (primarily stool), and ~ 78 mEq excreted in the urine to “break even” — that is, to maintain the same weight.

Although historically measured 1, a 24-hour urine Na and K collection is tedious, making spot urine Na/K ratio more attractive as a potential proxy.  Approximately 90% of patients who achieve a urinary Na/K ratio ≥1 will have a urinary Na excretion ≥78 mEq/day — that is to say, they are sensitive to the diuretic and will have a stable or decreasing weight at the current dose. 2,3

Urine Na/K may be interpreted as follows:

  • ≥1 and losing weight suggests effective diuretic dose, adherent to low Na diet
  • ≥1 and rising weight suggests effective diuretic dose, non-adherent to low Na diet
  • <1 and rising weight suggests ineffective diuretic dose

The “ideal” Na/K ratio as relates to responsiveness to diuretics has ranged from 1.0 to 2.5.4 In acutely decompensated heart failure patients on spironolactone, a K-sparing diuretic, Na/K ratio >2 at day 3 of hospitalization may be associated with improved outcome at 180 days. 5

Remember also that if the patient’s clinical syndrome is not correlating well with the ratio, it’s always a good idea to proceed to a 24-hour urine collection.



  1. Runyon B. Refractory Ascites. Semin Liver Dis. Semin Liver Dis. 1993 Nov;13(4):343-51.
  2. Stiehm AJ, Mendler MH, Runyon BA. Detection of diuretic-resistance or diuretic-sensitivity by spot urine Na/K ratios in 729 specimens from cirrhotics with ascites: approximately 90 percent accuracy as compared to 24-hr urine Na excretion (abstract). Hepatology 2002; 36: 222A.
  3. da Silva OM, Thiele GB, Fayad L. et al. Comparative study of spot urine Na/K ratio and 24-hour urine sodium in natriuresis evaluation of cirrhotic patients with ascites. GE J Port Gastroenterol 2014;21:15-20
  4. El-Bokl M, Senousy, B, El-Karmouty K, Mohammed I, Mohammed S, Shabana S, Shelby H. Spot urinary sodium for assessing dietary sodium restriction in cirrhotic ascites. World J Gastroenterol 2009; 15:3631.
  5. Ferreira JP, Girerd N, Medeiros PB, et al. Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect. Clin Res Cardiol 2016;105:489-507.


Contributed by Alyssa Castillo, MD, with valuable input from Sawalla Guseh, MD, both from Mass General Hospital, Boston, MA.

Why isn’t my patient with congestive heart failure or end-stage liver disease losing weight despite being on diuretic therapy? Is the diuretic dose too low, or is the salt intake too high?

What is the connection between cirrhosis and adrenal insufficiency (AI)?

The reported prevalence of AI in patients with liver disease varies widely (30-60%)1. However, there is no consensus on how to define AI in such patients, nor is the methodology for its evaluation standardized. 

A common criticism is the frequent reliance on total, not free, serum cortisol in cirrhosis which may overestimate the prevalence of AI because cortisol is bound to corticosteroid binding globulin and albumin, commonly found at lower concentrations in cirrhosis. However, even when based on measuring free cortisol, AI is found in 12%-29% of clinically stable cirrhotic patients1.

 Secondary AI due to hypothalamic-pituitary dysfunction has been reported in Child-Pugh class A, B, and C patients (42%, 69%, and 80%, respectively)2. The mechanism of AI in cirrhosis is unclear, but low serum cholesterol in cirrhosis leading to lack of substrate for steroidogenesis, and increased levels of circulating endotoxin and pro-inflammatory cytokines impairing the hypothalamic-pituitary-adrenal axis have been postulated1.



  1. Fede G, Spadaro L, Purrello F. Review: adrenal insufficiency in liver disease. J Liver 2014;3:1.
  2. Zietz, B, Lock, G, Plach, B, et al. Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis. Eur J Gastroenterol Hepatology 2003;15:495-501.
What is the connection between cirrhosis and adrenal insufficiency (AI)?

How do I interpret serum ammonia levels in hospitalized patients with altered mental status?

The primary source of ammonia in the blood is the intestine, where bacterial break down of urea leads to ammonia which is converted back to urea by the liver before it is excreted by the kidneys and colon. Besides hepatic dysfunction and inborn errors of metabolism, portosystemic shunts, urinary diversion, parenteral nutrition, multiple myeloma, distal renal tubular acidosis, drugs (e.g. sodium valproate), and convulsive seizures may also be associated with elevated serum ammonia levels (1).

In end-stage liver disease (ESLD), elevated serum ammonia level is neither very sensitive nor specific for the presence or the degree of hepatic encephalopathy (HE). In fact, over 2/3 of patients with ESLD without encephalopathy may have elevated serum ammonia levels (2).

In contrast, in patients with acute liver failure, an elevated serum ammonia level may be of prognostic value, with arterial ammonia levels >200 ug/dL associated with cerebral herniation in such patients (2).

In patients without suspected liver disease, measuring serum ammonia levels as part of a broader workup for mental status changes is reasonable, but just as in patients with ESLD, hyperammonia-related altered mental status should remain a diagnosis of exclusion.



  1. Hawkes ND, Thomas GAO, Jurewicz A, et al. Non-hepatic hyperammonaemia: an important, potentially reversible cause of encephalopathy. Postgrad Med J 2001;77:717-722.  
  2. Elgouhari HM, O’Shea R. What is the utility of measuring the serum ammonia level in patients with altered mental status? Cleveland Clin J Med 2009;76: 252-4.

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How do I interpret serum ammonia levels in hospitalized patients with altered mental status?