cirrhosis

Why does my patient with alcoholic liver disease have spider angiomas?

FA Manian MD, MPH, , , , Leave a comment

 

Spider angiomas (SAs), collections of small blood vessels radiating from a central, dilated arteriole that form near the surface of the skin, are  found in 10-15% of healthy adults and young children, as well as in a variety of conditions, including pregnancy, women taking oral contraceptive pills (OCPs),  thyrotoxicosis, and chronic liver disease1.  

Although the exact mechanism of the formation SAs has not been fully elucidated, several hypotheses have been offered:

  • Arteriolar vasodilation caused by estrogen excess due to impaired hepatic metabolism in cirrhosis; 2this is supported by the association of SAs also with other high-estrogen states, such as in pregnancy and OCPs.
  • Vasodilatory effects of substance P, a neuropeptide partially inactivated by the liver and elevated in patients with liver disease. 3 
  • Neovascularization promoted by vascular endothelial growth factor and basic fibroblast growth factor released by damaged hepatocytes. 4
  • Alcohol itself may contribute, as SAs are more commonly seen in individuals with alcoholic cirrhosis than in those with non-alcoholic causes of liver disease. 2

For unknown reasons, in adults spider angiomas most commonly occur in areas drained by the superior vena cava, namely the face, arms, neck, and chest.

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References

  1. Khasnis A, Gokula RM. Spider nevus. J Postgrad Med 2002;48:307.         
  2. Li CP, Lee FY, Hwang SJ, et al., Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function. Scand J Gastroenterol 1999;  34: 520-3.https://www.ncbi.nlm.nih.gov/pubmed/10423070
  3. Li CP, Lee FY, Hwang SJ, et al., Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis. Am J Gastroenterol 1999; 94: 502-7.https://www.ncbi.nlm.nih.gov/pubmed/10022654
  4. Li CP, Lee FY, Hwang SJ,  et al., Spider angiomas in patients with liver cirrhosis: role of vascular endothelial growth factor and basic fibroblast growth factor. World J Gastroenterol 2003; 9: 2832-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4612064/ 

Contributed by Camille Mathey-Andrews, Medical Student, Harvard Medical School

 

Why does my patient with alcoholic liver disease have spider angiomas?

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

FA Manian MD, MPH, , , , , , , , , Leave a comment

The 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 patients. 1

 Secondary AI due to hypothalamic-pituitary dysfunction has also 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 postulated. 1

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References

  1. Fede G, Spadaro L, Purrello F. Review: adrenal insufficiency in liver disease. J Liver 2014;3:1. https://www.ncbi.nlm.nih.gov/pubmed/22234976
  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. https://www.ncbi.nlm.nih.gov/pubmed/12702906
What is the connection between cirrhosis and adrenal insufficiency (AI)?

Why doesn’t excessive ingestion of carrots cause yellow discoloration of the sclera?

FA Manian MD, MPH, , , , , , , Leave a comment

Great question! “Carotenoderma” refers to the yellow discoloration of the skin caused by increased serum carotenoids1.  Carotenoids are absorbed by passive diffusion from the gastrointestinal tract which are partially metabolized in the intestinal mucosa and liver to vitamin A, and then transported in the plasma into the intercellular lipids of stratum corneum of the skin which has a high affinity for carotene1,2.

The maximal accumulation of carotenoids occurs in areas with an abundance of sweat glands (eg, the palms, soles, nasolabial folds). In the absence of strateum corneum, the sclera is spared!

Of note, there are many causes of carotenoderma besides excessive ingestion of carrots.  Among foods, increased ingestion of tomatoes, tangerines, red palm oil, and squash may also be responsible1,2. 

Systemic diseases associated with increase in serum carotenoids (possibly related to decreased conversion to vitamin A, hyperlipidemia, or other factors) include hypothyroidism, diabetes mellitus, anorexia nervosa, nephrotic syndrome, and liver disease.

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References 

  1. Horev L, Ramot Y, Klapholz L. Yellow feet in a patient with breast and thyroid carcinoma, due to oral intake of turmeric. Drug Saf-Case Rep 2015;2:4.https://link.springer.com/article/10.1007/s40800-015-0006-4
  2. Maharshak N, Shapiro J, Trau H. Carotenoderma-a review of the literature. Int J Dermatol 2003;42:178-181. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-4362.2003.01657.x/epdf

 

Contributed by Clara Yang, Medical Student, Harvard Medical School

 

Why doesn’t excessive ingestion of carrots cause yellow discoloration of the sclera?

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , Leave a comment

Howell-Jolly bodies (HJBs, Figure) are often indicative of asplenia (either post-splenectomy or congenital absence) or hyposplenism associated with a variety of conditions, including  sickle cell disease, autoimmune disorders, celiac disease, inflammatory bowel disease (particularly ulcerative colitis), HIV, cirrhosis, primary pulmonary hypertension, splenic irradiation, amyloidosis, sarcoidosis, bone marrow transplantation, and high-dose corticosteroid therapy1-4.

Patients with pneumonia and HJBs on peripheral smear may be hyposplenic and at risk of potentially serious infections, predominantly caused by encapsulated bacteria eg, Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis3.  Such patients should be immunized against these organisms, including sequential receipt of both conjugated and polysaccharide pneumococcal vaccines3,5.

HJBs are nuclear remnants in circulating mature red blood cells which are usually pitted by the spleen under normal physiological conditions. 

Final Fun Pearl:  Did you know that  HJBs were named after Henry Howell, an American physiologist who pioneered the use of heparin as an anti-coagulant and Justin Jolly, a French hematologist who was among the first to film mitotic activity in cells?

howelljollymgh

Figure. Howell-Jolly body in an RBC. Photo courtesy of Michael S. Abers, MD

Contributed by Katarzyna Orlewska, Medical Student, Warszawski Uniwersytet Medyczny, Poland

 

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References

  1. Di Sabatino, A, Carsetti R, Corazza G. Post-splenectomy and hyposplenic states. Lancet 2011;378:86–97. https://www.ncbi.nlm.nih.gov/pubmed/21474172
  2. Brousse, V, Buffet P, Rees D. The spleen and sickle cell disease: the sick(led) spleen. Br J Haematol 2014;166: 165–176. https://www.ncbi.nlm.nih.gov/pubmed/24862308
  3. Mathew H, Dittus C, Malek A, Negroiu A. Howell-Jolly bodies on peripheral smear leading to the diagnosis of congenital hyposplenism in a patient with septic shock. Clin Case Rep 2015;3:714-717. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551333
  4. Ryan FP, Smart RC, Holdsworth CD, et al. Hyposplenism in inflammatory bowel disease 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pubmed/624506
  5. Kuchar E, Miśkiewicz K , Karlikowska M. A review of guidance on immunization in persons with defective or deficient splenic function. Br J Haematol 2015; 171:683-94.  http://onlinelibrary.wiley.com/doi/10.1111/bjh.13660/full

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What is the significance of Howell-Jolly bodies in the peripheral smear of my patient with a spleen who presents with pneumonia?

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

FA Manian MD, MPH, , , , , , , , Leave a comment

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.

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References

  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. https://pmj.bmj.com/content/77/913/717.short  
  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.https://www.ncbi.nlm.nih.gov/pubmed/19339641

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

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

Why does my patient with cirrhosis have a normal serum albumin?

FA Manian MD, MPH, Leave a comment

The finding of normal serum albumin in cirrhotic patients is not at all uncommon. In fact, in a meta-analysis involving 8 published articles, the sensitivity of serum albumin (< 3.5 g/dL) in cirrhosis was only 45% (1).

It turns out that in many patients with cirrhosis, the synthetic ability of liver with respect to albumin appears well preserved until more advanced stages of liver dysfunction develop (2).

So don’t exclude cirrhosis just because serum albumin is normal.

 

References

1. Udell JA, Wang CS, Tinmouth J et al. Does this patient with liver disease have cirrhosis? JAMA 2012;307:832-842. https://www.ncbi.nlm.nih.gov/pubmed/22357834

2. Ballmer PE, Washe D. McNurlan M, et al. Albumin synthesis rates in cirrhosis: correlation with Child-Turcotte classification. Hepatology 1993;18:292-297. https://aasldpubs.onlinelibrary.wiley.com/doi/abs/10.1002/hep.1840180211

Why does my patient with cirrhosis have a normal serum albumin?

Why is serum AST levels generally higher than ALT in alcohol-induced liver injury?

FA Manian MD, MPH, , Leave a comment

Alcohol is thought to cause injury to the mitochondria which contains AST but not ALT. In addition, in chronic alcoholics, pyridoxine (vitamin B6) deficiency may reduce the synthesis of ALT more than AST because the former is more B6-dependent (1).  

AST/ALT ratio >1 may be more common in advanced alcohol liver disease (e.g. cirrhosis) than in the setting of high alcohol consumption without severe liver disease (2). 

Also, remember that AST levels greater than 500 U/L and ALT levels greater than 300 U/L are uncommon in alcohol-related liver injury.  In this setting, other causes such as acetaminophen toxicity should be excluded (1).

References

1. Johnston DE. Special considerations in interpreting liver function tests. Am Fam Physician1999;59:2223-30.  https://www.ncbi.nlm.nih.gov/pubmed/10221307  

2. Nyblom H, Berggren U, Balldin J, et al. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking. Alcohol &Alcoholism 2004;39:336-39. https://www.ncbi.nlm.nih.gov/pubmed/15208167

Why is serum AST levels generally higher than ALT in alcohol-induced liver injury?

Is there a connection between cirrhosis and elevated CK or rhabdomyolysis?

FA Manian MD, MPH, , , , , , , Leave a comment

Besides the usual causes of rhabdomyolysis such as trauma, drugs, alcohol, sepsis, etc…, cirrhotic patients may also have what some have called “hepatic myopathy”.  

One study involving 99 patients with cirrhosis and myopathy (all with elevated serum myoglobin) found “infections” as the most common cause (47%),  followed by “idiopathic” (27%) sources as well as ETOH, herbal medicine, and trauma-related causes (<10% each) (1).  Whether this is truly an entity  or just a non-causal association is unclear.

Another study reported that ~60% of rhabdomyolysis cases in cirrhosis had no apparent cause (2), with mortality among patient with cirrhosis and rhabdomyolysis significantly higher than that of controls without cirrhosis (27.5% vs 14.5%).

So perhaps we should lower our threshold for checking serum CK in our patients with cirrhosis and weakness.

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Reference

1. Lee O-J, Yoon J-H, Lee E-J, et al. Acute myopathy associated with liver cirrhosis. World J Gastroenterol 2006;12:2254-2258.  https://www.ncbi.nlm.nih.gov/pubmed/16610032 .

2. Baek JE, Park DJ, Kim HJ, et al. The clinical characteristics of rhabdomyolysis in patients with liver cirrhosis. J Clin Gastroenterol 2007;41:317-21.

 

Is there a connection between cirrhosis and elevated CK or rhabdomyolysis?

What is the connection between cirrhosis and hyperkalemia?

FA Manian MD, MPH1 Comment

Although, many of the familiar causes of hyperkalemia, including K-sparing diuretics, renal dysfunction, and adrenal insufficieny may be present in our cirrhotic patients as well, a poorly-functioning liver itself may be the culprit.

The liver, just as the muscle tissue, plays an important role in K uptake and serves as a buffer against serum K fluctuations. In a really cool experiment involving subjects given oral K supplements under controlled conditions (1), patients with cirrhosis had much greater bump in their serum K levels than normal controls despite similar weight, renal excretion of K and a significant rise in C-peptide levels. 

So even in the absence of usual risk factors, our cirrhotic patients may be more susceptible to hyperkalemia.

1. Decaux G, Soupart A, Cauchie P, et al. Potassium homeostasis in liver cirrhosis. Arch Intern Med 1988;148:547-8.

What is the connection between cirrhosis and hyperkalemia?