The Mad Hatter Syndrome

A Quick Review of Mercury Poisoning

MadlHatterByTenniel

General:

  • Most human exposure results from fish consumption, dental amalgam, or occupational exposure.
  • Approximately 80% of metallic mercury vapor outgassed from amalgams is absorbed through inhalation, compared with about 7 to 10% absorption of ingested metallic mercury, and about 1% absorption of metallic mercury through skin

Important Elemental Forms:

  • Mercury vapor: Most toxic form. Transported to the brain, either dissolved in serum or adherent to red cell membranes.
  • Metallic mercury: Passes easily through the blood brain barrier and through the placenta. Rapidly oxidized, although not so quickly as to prevent considerable uptake by the central nervous system

Toxicity:

  • Poisons cellular function by altering the tertiary and quaternary structure of proteins and by binding with sulfhydryl and selenohydryl groups.
  • The chief target is the brain, but peripheral nerve function, renal function, immune function, endocrine and muscle function, and dermatitis.

Symptoms:

  • Low-level exposures: nonspecific symptoms like weakness, fatigue, anorexia, weight loss, and gastrointestinal disturbance
  • Higher exposure levels:
    • Pneumonitis
    • Mercurial tremor: fine muscle fasciculations punctuated every few minutes by coarse shaking.
    • Erethism: severe behavior and personality changes, emotional excitability, loss of memory, insomnia, depression, fatigue
    • Acute myocardial infarction, carotid atherosclerosis

Diagnosis:

  • Blood and urine levels correlate fairly well to each other, but not to total body burden
  • It has not been possible to set a level for mercury in blood or urine below which mercury related symptoms will not occur.

Treatment: Chelation!

  • DMPS: increases in urinary mercury output; evidence of decreased body burden
  • Safer than British Anti-Lewisite and more potent than DMSA

 

My lips are swollen!

Hereditary Angioedema

  • Recurrent episodes of angioedema due to excessive production of bradykinin as a result of C1 inhibitor deficiency or dysfunction
  • Typically affects skin and mucosal surfaces of upper respiratory and gastrointestinal tracts
  • Laryngeal involvement can be fatal and lead to asphyxiation
  • Pruritus and urticaria are typically absent as mast cells and histamines are thought to play a minimal role
  • Potential triggers that can cause HAE attacks: dental procedures, mild trauma, menstruation, pregnancy, estrogen-containing medications
  • C1 inhibitor is an acute phase reactant and inhibitor of the classical complement and kinin-generating pathways
  • Inheritance pattern is autosomal dominant with variable clinical expression as 10% of patients are asymptomatic
  • 25% of cases are due to de novo mutations with no family history
  • Typically diagnosed by labs in the context of a suggestive clinical and familial history:
    • Low C1 esterase inhibitor antigenic and functional levels
    • Low C4 level
  • If HAE is diagnosed, consider screening other family members
  • Preventative Treatment:
    • Attenuated androgens (ie danazol, stanazol, tibolone) thought to inactivate kinins
    • Transexamic Acid
    • Regular infusions of C1 inhibitor concentrates
  • Treatment for acute attacks:
    • If laryngeal involvement, assess for airway compromise and intubate if necessary to protect airway
    • First line therapies include human derived and recombinant C1 inhibitors, bradykinin receptor antagonists
    • Second line therapy includes fresh frozen plasma and solvent/detergent-treated plasma

Lactulose and Rifaximin…is there anything else I can do for HE?

There are several trials that explore additional options for the treatment of hepatic encephalopathy. Earlier this month, UT Southwestern researchers (including Dr. Amit Singal, Dr. Jennifer Cuthbert, and other former members of our division of Gastroenterology and Hepatology) published the results of The HELP Randomized Clinical Trial, which compared lactulose to polyethylene glycol (AKA miralax, or golytely!) for the treatment of HE. They concluded that “PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.” Check out the article at JAMA Internal Medicine.

PEG-polyethylene-Glycol-clickonTrends

AMA Intern Med. 2014;174(11):1727-1733. doi:10.1001/jamainternmed.2014.4746.

A Current Review of the Diagnostic and Treatment Strategies of Hepatic Encephalopathy

From the International Journal of Hepatology, here is a more extensive review of the pathophysiology, diagnosis, and treatment of HE.

Z. Poh and P. E. J. Chang, “A Current Review of the Diagnostic and Treatment Strategies of Hepatic Encephalopathy,” International Journal of Hepatology, vol. 2012, Article ID 480309, 10 pages, 2012. doi:10.1155/2012/480309

UTSW Internal Medicine

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