What is the significance of Terry’s or Lindsay’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. https://www.ncbi.nlm.nih.gov/pubmed/13153107 
2. Nia AM, Ederer S, Dahlem K, et al. Terry’s nails: a window to systemic diseases. Am J Med 2011;124:603-604. https://www.ncbi.nlm.nih.gov/pubmed/21683827 
3. Holzberg M, Walker HK. Terry’s nails: revised definitions and new correlations. Lancet 1984;1(8382):896-99. https://www.ncbi.nlm.nih.gov/pubmed/6143196 
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.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945547/ 
5. Gagnon AL, Desai T. Dermatological diseases in patients with chronic kidney disease 2013;2:104-109.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891143/

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 or Lindsay’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. https://www.ncbi.nlm.nih.gov/pubmed/17723889
  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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942747/
  3. Martens P, Laleman W. Umbilical hernia in a patient with cirrhosis. Cleveland Clin J Med 2015;82: 404-5. https://www.mdedge.com/ccjm/article/100682/hepatology/umbilical-hernia-patient-cirrhosis
  4. Nguyen ET, Tudtud-Hans LA. Flood syndrome: spontaneous umbilical hernia rupture leaking ascitic fluid-a case report. Perm J 2017;21:16-152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499604/ 

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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. https://www.ncbi.nlm.nih.gov/pubmed/8303315
  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 https://pdfs.semanticscholar.org/4dc3/4d18d202c6fa2b30a1f6563baab80d877921.pdf
  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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721236/
  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. https://www.ncbi.nlm.nih.gov/pubmed/26615605


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?

Does my patient about to undergo immunosuppressive therapy need antiviral prophylaxis even if she tests positive for hepatitis B surface antibody?

The presence of hepatitis B surface antibody (HBsab) in patients who also test positive for core antibody does not necessarily confer full protection against hepatitis B virus (HBV) reactivation during immunosuppression (incidence 4.3%). 1 This is because despite having HBsab and no HB surface antigen,  a small portion of patients continue to have detectable HBV DNA in the serum and are therefore at risk of reactivation during severe immunosuppression. 2

In fact, the American Gastroenterological Association recommends against using anti-HBs status to guide antiviral prophylaxis in anti-HBc-positive patients. 1

Overall, antiviral prophylaxis may reduce the risk of HBV reactivation by 87% (C.I. 70%-94%). Antiviral drugs with a high barrier to resistance (eg, entecavir) are preferred over lamivudine.

Immunosuppressants often requiring HBV prophylaxis include: 1-3

  • B cell-depleting agents (eg, rituximab, ofatumumab)
  • Anthracycline derivatives (eg, doxorubicin, epirubicin)
  • Prednisone (4 weeks or more)
  • Tumor necrosis factor inhibitors (eg, etanercept, adalimumab, certolizumab, infliximab)
  • Other cytokine or integrin inhibitors (eg, abatacept, ustekinumab, natalizumab, vedolizumab)

Traditional immunosuppressive agents such as azathioprine, 6-mercaptopurine and methotrexate are often considered “low-risk” and do not generally require prophylaxis. 1

Fun Fact: Did you know that hepatitis B virus is very old and probably originated in birds when dinosaurs roamed the earth? 4


  1. Reddy KR, Beavers KL, Hammond SP, et al. American Gastroenterological Association Institute Guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology 2015;148:215-19. https://www.ncbi.nlm.nih.gov/pubmed/25447850
  2. Gigi E, Georgiou T, Mougiou D, et al. Hepatitis B reactivation in a patient with rheumatoid arthritis with antibodies to hepatitis B surface antigen treated with rituximab. HIPPOKATRIA 2013;17:91-93. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738290/
  3. Kim EB, Kim DS, Park SJ, et al. Hepatitis B virus reactivation in a surface antigen-negative and antibody-positive patient after rituximab plus CHOP chemotherapy. Cancer Res Treat 2008;40:36-38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699087/
  4. Suh A, Brosius J, Schmitz J, et al. The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B virus. Nature Communications 2013; Article no. 1791. http://www.nature.com/articles/ncomms2798
Does my patient about to undergo immunosuppressive therapy need antiviral prophylaxis even if she tests positive for hepatitis B surface antibody?

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?


There are many causes of low serum haptoglobin besides hemolysis, including1-4:

  • Cirrhosis of the liver
  • Disseminated ovarian carcinomatosis
  • Pulmonary sarcoidosis
  • Elevated estrogen states
  • Repetitive physical exercise
  • Hemodilution
  • Blood transfusions
  • Drugs (eg, oral contraceptives, chlorpromazine, indomethacin, isoniazid, nitrofurantoin, quinidine, and streptomycin)
  • Iron deficiency anemia
  • Megaloblastic anemia (by destruction of megaloblastic RBC precursors in the bone marrow)
  • Congenital causes

Less well-known is that congenital haptoglobin deficiency (“anhaptoglobinemia”) may not be so rare in the general population at a prevalence of 1% among whites and 4% among African-Americans (>30% in blacks of West African origin)3. Measurement of serum hemopexin, another plasma protein that binds heme, may help distinguish between this condition and acquired hypohaptoglobinemia— in the absence of hemolysis, hemopexin levels should remain unchanged3,5.

Final Fun Fact: Did you know that serum haptoglobin is often low during the first 6 months of life?


  1. Shih AWY, McFarane A, Verhovsek M. Haptoglobin testing in hemolysis: measurement and interpretation. Am J Hematol 2014;89: 443-47. https://www.ncbi.nlm.nih.gov/pubmed/24809098
  2. Sritharan V, Bharadwaj VP, Venkatesan K, et al. Dapsone induced hypohaptoglobinemia in lepromatous leprosy patients. Internat J Leprosy 1981;307-310. https://www.ncbi.nlm.nih.gov/pubmed/7198620
  3. Delanghe J, Langlois M, De Buyzere M, et al. Congenital anhaptoglobinemia versus acquired hypohaptoglobinemia. Blood 1998;9: 3524. http://www.bloodjournal.org/content/bloodjournal/91/9/3524.full.pdf
  4. Haptoglobin blood test. https://medlineplus.gov/ency/article/003634.htm. Accessed August 6, 2017.
  5. Smith A, McCulloh RJ. Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders. Front. Physiol 2015;6:187. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485156/pdf/fphys-06-00187.pdf


In collaboration with Kris Olson, MD, MPH, Mass General Hospital, Boston, MA

What could be causing low serum haptoglobin in my patient with no evidence of hemolysis?

Why are patients with cirrhosis and upper gastrointestinal bleed routinely treated with antibiotics?

Cirrhotic patients with upper gastrointestinal bleed (UGIB) are at high risk of bacterial infections: 22% during the first 48 h after admission, 35-66% within 2 weeks of initial bleeding1. Antibiotic prophylaxis has been shown to reduce short term mortality, bacterial infections, early rebleeding and volume of blood transfused1-4.

But what is the exact connection between UGIB and bacterial infections in cirrhosis? One hypothesis is that UGIB sets up the host for bacterial infection via translocation (eg, due to hypovolemia), procedures necessary in the management of bleeding (eg endoscopy, sclerotherapy, IV access), and aspiration pneumonia. More intriguing is the reverse hypothesis—that is the bacterial infection serves as a trigger for UGIB.  Several lines of evidence support this view1,2.

  • Cirrhotic patients admitted for non-UGIB-related conditions may be 4x more likely to develop UGIB during their hospitalization in the presence of bacterial infection on admission4
  • Infections predispose to early variceal rebleeding
  • Infection/endotoxemia increase portal pressure, and impair liver function and coagulation
  • Commonly cited risk factors for variceal bleeding (eg, hepatic venous pressure gradient, liver function, size of varices) do not readily explain why bleeding occurs unpredictably and why despite daily increases in portal pressure (eg, following daily meals and exercises), UGIB is relatively infrequent.



  1. Thalheimer U, Triantos CK, Samonakis DN, et al. Infection, coagulation, and variceal bleeding in cirrhosis. Gut 2005;54:556-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774431
  2. Goulis J. Bacterial infection in the pathogenesis of variceal bleeding. Is there any role for antibiotic prophylaxis in the cirrhotic patient. Ann Gastroenterol 2001;14:205-11. http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=4&ved=0ahUKEwjNh-rhlpLVAhXGdD4KHSurANcQFgg4MAM&url=http%3A%2F%2Fwww.annalsgastro.gr%2Findex.php%2Fannalsgastro%2Farticle%2Fdownload%2F80%2F71&usg=AFQjCNHJfAyYAjuNXpwsWGrVuyuxxgJYKg
  3. Soares-Weiser K, Brezis, Tur-Kaspa R, et al. Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials. Scand J Gastroenterol 2003;38:193-200. http://www.tandfonline.com/doi/abs/10.1080/00365520310000690
  4. Anastasioua J, Williams R. When to use antibiotics in the cirrhotic patient? The evidence base. Ann Gastroenterol. 2013; 26(2): 128–131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959942
  5. Benavides J, Fernandez N, Colombato L, et al. Further evidence linking bacterial infection and upper G.I. bleeding in cirrhosis. Results from a large multicentric prospective survey in Argentina. J Hepatol 2003;38 (suppl 2):A176. http://www.journal-of-hepatology.eu/article/S0168-8278(03)80592-5/abstract


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Why are patients with cirrhosis and upper gastrointestinal bleed routinely treated with antibiotics?

My patient with cirrhosis has been admitted to the hospital several times this year with bacterial infections. How does cirrhosis increase susceptibility to infections?

Bacterial infections are a common cause of morbidity and mortality in patients with cirrhosis, affecting about 30% of such patients either at admission or during their hospitalization, with an attendant risk of mortality that is twice that of individuals without cirrhosis1.

Two major mechanisms may account for the observed immune dysfunction in cirrhosis: 1. Compromise of the immune surveillance function of the liver itself through damage of the reticulo-endothelial system (RES) and reduced synthesis of innate immunity proteins and pattern recognition receptors (PRRs); and 2. Dysfunctions of circulating and intestinal population of immune cells2.

Damage to the RES in cirrhosis leads to portal-system shunting, loss/damage of Kupffer cells (specialized hepatic macrophages) and sinusoidal capillarization, all hindering blood-borne pathogen clearance. Cirrhosis is also associated with a defect in hepatic protein synthesis, including complement components, decreased PRRs and acute phase reactants (eg C-reactive protein), which may in turn lead to the impairment of the innate immunity and bacterial opsonization.

Cirrhosis can also cause reduction in the number and function of neutrophils (eg, decreased phagocytosis and chemotaxis), B, T, and NK lymphocytes, and decreased in bacterial phagocytosis by monocytes. In addition, damage to the gut-associated lymphoid tissue (eg Peyer’s patches and mesenteric lymph nodes) may facilitate bacterial translocation.


  1. Pieri G, Agarwal B, Burroughs AK. C-reactive protein and bacterial infections in cirrhosis. Ann Gastroenterol 2014;27:113-120. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982625/pdf/AnnGastroenterol-27-113.pdf
  2. Albillos A, Lario M, Alvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol 2014;61:1385-1396. http://www.journal-of-hepatology.eu/article/S0168-8278(14)00549-2/pdf


My patient with cirrhosis has been admitted to the hospital several times this year with bacterial infections. How does cirrhosis increase susceptibility to infections?

My patient with cirrhosis and suspected infection has a normal serum C-reactive protein (CRP). Does cirrhosis affect CRP response to infection?

CRP is primarily synthesized by the liver mainly as a response to IL-6 production in inflammatory states1.  Lower CRP production may then be expected in cirrhotic patients with significant infections and several studies support this view2

In a particularly convincing study involving E. coli-infected patients with bacteremia, the median CRP level in cirrhotic patients was about 40% that of non-cirrhotic patients (62 mg/L vs 146 mg/L)3.  In another study involving bacteremic patients with or without liver dysfunction, median CRP level was about 60% that of  patients with preserved liver function (81 mg/L vs 139 mg/L)4

Some investigators have reported a cut-off CRP value of 9.2 mg/L as a possible screening test for bacterial infections in patients with cirrhosis with a sensitivity and specificity of 88% (AUROC 0.93)5.

Collectively, these data suggest that although CRP response may be diminished in patients with advanced liver disease and acute infection, its synthesis is still maintained.

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  1. Pieri G, Agarwal B, Burroughs AK. C-reactive protein and bacterial infection in cirrhosis. Ann Gastroenterol 2014;27:113-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982625/pdf/AnnGastroenterol-27-113.pdf
  2. Ha YE, Kang C-I, Joo E-J, et al. Usefulness of C-reactive protein for evaluating clinical outcomes in cirrhotic patients with bacteremia. Korean J Intern Med 2011;26:195-200. http://pubmedcentralcanada.ca/pmcc/articles/PMC3110852/pdf/kjim-26-195.pdf
  3. Park WB1, Lee KD, Lee CS et al. Production of C-reactive protein in Escherichia coli-infected patients with liver dysfunction due to liver cirrhosis. Diagn Microbiol Infect Dis. 2005 Apr;51(4):227-30. https://www.ncbi.nlm.nih.gov/pubmed/15808312
  4. Mackenzie I, Woodhouse J. C-reactive protein concentrations during bacteraemia: a comparison between patients with and without liver dysfunction. Intensive Care Med 2006;32:1344-51. https://www.ncbi.nlm.nih.gov/pubmed/16799774
  5. Papp M, Vitalis Z, Altorjay I, et al. Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infection. Liver Int 2011;603-11. https://www.ncbi.nlm.nih.gov/pubmed/22145664


My patient with cirrhosis and suspected infection has a normal serum C-reactive protein (CRP). Does cirrhosis affect CRP response to infection?

Can my patient with cirrhosis and hepatocellular carcinoma still qualify for a liver transplant?


Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related deaths1. Liver transplant removes the HCC tumor and addresses the underlying cirrhosis. Unfortunately, the demand for liver transplants exceeds the supply of available livers, making it necessary to select patients with the best recurrent-free survival following transplantation. .

Mazzaferro2 found that patients who had one lesion <5 cm, no more than 3 lesions each <3 cm, and no extrahepatic involvement or vascular invasion had significantly higher rates of recurrent-free survival following liver transplant than patients with tumors exceeding this criteria (92% vs 59% at 4 years, respectively, P = .002). This criteria, also known as the Milan criteria, has been substantiated by numerous studies3 and widely adopted. Other more inclusive criteria has also been proposed, including the UCSF criteria4 (one tumor <6.5 cm, no more than 3 tumors, all <4.5 cm and cumulative size <8cm) which have good survival rates, but have not been adopted due to limited supply of available livers.

Interestingly, patients with HCC not initially meeting the Milan criteria but who receive treatment to meet the criteria have similar post-transplantation recurrence-free survival rates as those who meet the criteria without downstaging4,5.



  1. El–Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007 Jun 30;132(7):2557-76.
  2. Mazzaferro V, Regalia E, Doci R, et al. L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-699.
  3. Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence‐based analysis of 15 years of experience. Liver Transplantation 2011;17(S2): S44-S57.
  4. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: comparison of the proposed UCSF criteria with the Milan criteria and the Pittsburgh modified TNM criteria. Liver transplantation. 2002 Sep 1;8(9):765-74.
  5. Ravaioli M, Grazi GL, Piscaglia F, et al. Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant. 2008;8:2547–2557.
  6. Yao FY, Kerlan RK, Hirose R, et al. Excellent outcome following down-staging of hepatocellular carcinoma prior to liver transplantation: an intention-to-treat analysis. Hepatology. 2008;48:819–827.

Contributed by Marissa Shoji, Medical Student, Harvard Medical School

Can my patient with cirrhosis and hepatocellular carcinoma still qualify for a liver transplant?

My patient with spontaneous bacterial peritonitis (SBP) is requiring IV albumin. Does IV albumin do anything other than expand the plasma volume?

Yes! Besides expanding the circulatory plasma volume by raising the oncotic pressure, albumin appears to have a vasoconstricting effects by binding to endotoxins, nitric oxide (NO), bilirubin and fatty acids1,2.

Splanchnic vasodilatation, a feature of decompensated cirrhosis (eg ascites, bleeding varices, hepatorenal syndrome, and hepatic encephalopathy), is accentuated by superimposed infections through cytokine-mediated release of endothelial vasodilators3.  By binding to potential vasodilators such as bile acids, endotoxins and NO, albumin may also help restore endothelial function and act as a vasoconstrictor.  

In a cool study involving patients with SBP randomized to either albumin or hydroxyethyl starch (HS, a synthetic volume expander), the albumin (not HS) group had a significant increase in mean arterial pressure, right atrial pressure, pulmonary artery pressure,  systolic volume, left ventricular stroke work, and systemic vascular resistance3.

Albumin may also have an immune-modulating activity in patients with cirrhosis or acute liver decompensation by binding to prostaglandin E-2 (PGE-2), generated as a result of inflammatory reaction in the liver and bacterial translocation4.  PGE-2 is a suppressor of macrophage cytokine secretion and bacterial killing.  By binding to PGE-2, albumin can reverse this immunosuppression by reducing the availability of serum PGE-2.


  1. Baraldi O, Valenini C, Donati G, et al. Hepatorenal syndrome: update on diagnosis and treatment 2015;4:511-20. https://www.ncbi.nlm.nih.gov/pubmed/26558188
  2. Angeli P, Volpin R, Piovan D, et al. Acute effects of the oral administration of midodrine, an α-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites. Hepatology 1998;28:937-43. https://www.ncbi.nlm.nih.gov/pubmed/9755229
  3. Fernandez J, Monteagudo J, Bargallo X, et al. A randomized unblended pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis. Hepatology 2005;42:627-634. https://www.ncbi.nlm.nih.gov/pubmed/16108036
  4. Gleeson, MW, Dickson RC. Albumin gains immune boosting credibility. Clin Transl 2015;6:e86;doi:10.1038/ctg.2015.11. http://www.nature.com/ctg/journal/v6/n4/full/ctg201511a.html
My patient with spontaneous bacterial peritonitis (SBP) is requiring IV albumin. Does IV albumin do anything other than expand the plasma volume?