Page 1459 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

998 PART 9: Gastrointestinal Disorders

CHAPTER Jaundice, Diarrhea, Heme catabolism
Unconjugated
104 Obstruction, and bilirubin
Pseudoobstruction
Liver
Paul T. Engels
L. N. Tremblay Conjugated
bilirubin ~95% bilirubin
absorbed by
KEY POINTS terminal ileum
https://kat.cr/user/tahir99/
• Jaundice (hyperbilirubinemia) is seen in critically ill patients and Via blood if Enterohepatic
can occur due to prehepatic, intrahepatic, or posthepatic causes. liver dysfunction recycling
or biliary
• Biliary obstruction and acalculous cholecystitis are two common obstruction
surgical problems requiring urgent intervention.
• For acalculous or calculous cholecystitis, cholecystectomy removes
the inflamed and ischemic gallbladder and prevents recurrence
and thus is preferred in those able to tolerate the procedure. A Urobilinogen?
cholecystostomy tube is indicated for nonsurgical candidates.
• Diarrhea commonly occurs in critical illness (up to 60% of those on Fecal
enteral feeds) and may be related to infection, medications, malab- Urinary excretion
sorption, composition of the enteral feeds, or gastrointestinal disease. excretion
• Clostridium difficile should be ruled out as the cause of diarrhea in FIGURE 104-1. Bilirubin metabolism and excretion.
the ICU or any patient with risk factors (particularly antibiotics or
contact) as morbidity and mortality increase with delay in treatment.
1
• Fulminant Clostridium difficile can present as an ileus or with diar- excretion). The majority of bilirubin (70%-80%) is derived from degrada-
rhea in a toxic patient, and is associated with high mortality and tion of hemoglobin from senescent erythrocytes, with a minor component
frequent need for surgical intervention. of this being premature destruction of newly formed erythrocytes. The
• Studies are ongoing to determine the optimal medical and surgi- remaining 20% to 30% is mostly formed from breakdown of hemoproteins,
cal management of Clostridium difficile. Currently for severe cases such as catalase and cytochrome (CYP family) oxidases, in hepatocytes.
enteral vancomycin plus intravenous metronidazole is suggested ± Bilirubin circulates in plasma tightly, but noncovalently, bound to
subtotal colectomy or ileostomy with colon lavage. albumin. To be excreted, bilirubin must be converted to water-soluble
• Bowel obstruction should be ruled out prior to managing as pseu- conjugates by hepatocytes and subsequently secreted in a multistep
process. Bilirubin is taken up across the sinusoidal membrane of hepato-
doobstruction. cytes and conjugated with uridine diphosphate (UDP)-glucuronic acid
• Commonest causes of adult small bowel obstruction are adhesions and by the enzyme bilirubin UDP-glucuronyl transferase (B-UGT). This
hernia, whereas commonest causes of adult large bowel obstruction are converts the hydrophobic bilirubin into a water-soluble form that can
colon cancer, sigmoid volvulus, and stricture from diverticulitis. be excreted into the bile canaliculus. Any conjugated bilirubin in plasma
• Pseudoobstruction (nonmechanical obstruction) is managed by undergoes renal elimination and this pathway may be upregulated in
resuscitation, removing or limiting precipitants, using nasogastric disorders characterized by cholestasis. With prolonged cholestasis,
or rectal tubes to relieve overdistension, and occasional endoscopic a large proportion of conjugated bilirubin in plasma becomes cova-
decompression or use of neostigmine in appropriate patients. lently bound to albumin (referred to as delta bilirubin) which cannot
be excreted into urine. Of note, this delta bilirubin will take longer to
resolve than typical hyperbilirubinemias as its half-life becomes that
JAUNDICE of albumin, which is 14 to 21 days. Approximately 80% of bilirubin in
bile is in the form of diglucuronides, with the rest being in the form of
■ OVERVIEW monoglucuronides and only trace amounts being unconjugated.
Normal serum bilirubin concentration in adults is less than 1.2 mg/dL
Jaundice is characterized by yellow discoloration of the skin, conjunctivae, or <20 µmol/L. Jaundice is generally not evident until serum concentra-
and mucous membranes as a result of widespread tissue deposition of tions exceed 3 mg/dL or 50 µmol/L. In healthy adults, <5% circulates in
the pigmented metabolite bilirubin. It can present as an isolated abnor- its unconjugated form.
mality, or associated with specific hepatic and/or pancreatic dysfunc- Depending on the laboratory method of measurement, bilirubin
tion, or associated with multisystem organ dysfunction. concentration may be reported as total and conjugated, or potentially
In the intensive care setting, jaundice may be an important sign of a as total, direct, and indirect. Indirect bilirubin is not directly equivalent
condition that requires ICU admission, such as acute cholangitis, or a to unconjugated bilirubin and reliance on direct and indirect measure-
new development in an already admitted patient, such as one with septic ments can lead to errors in the diagnosis of isolated disorders of bilirubin
shock. Patient history, laboratory evaluation, appropriate imaging inves- metabolism. Measurement of the total and conjugated fraction is more
tigations, and a thorough understanding of those conditions that place a useful. However, in disorders with prolonged cholestasis such assays
patient at increased risk for the development of hyperbilirubinemia will may underestimate the conjugated bilirubin concentration because they
help narrow the broad differential diagnosis of jaundice and identify do not accurately detect albumin-bound conjugated bilirubin (delta
those conditions that require specific therapy. bilirubin). Even with modern assay techniques, the levels of total and
■ METABOLISM AND MEASUREMENT OF BILIRUBIN conjugated bilirubin are often not able to distinguish hepatic disorders
from biliary obstruction. Nevertheless, when combined with history and
Bilirubin is a hydrophobic and potentially toxic compound that is an end physical examination, jaundice can be characterized as obstructive or
product of heme degradation (Fig. 104-1 depicts bilirubin metabolism and nonobstructive in over 75% of cases.

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