Clinicopathology conferences: Inflammation-induced cholestasis

Abstract

Intrahepatic cholestasis may arise from many sources, and it therefore presents a particular challenge when it develops in the seriously ill patient. A 54-year-old patient with a myeloproliferative disorder is presented, who developed jaundice in the setting of a severe decubital infection, polypharmacology, multiple blood transfusions for anemia, renal insufficiency, parenteral alimentation, and a history of long-standing alcohol abuse, a positive purified protein derivative, and recent biopsy-proven laryngeal squamous cell carcinoma. The thesis is advanced that many insults may cause local and systemic activation of the inflammatory cytokine system, and that these proinflammatory events are potent inducers of intrahepatic cholestasis. CASE HISTORYA 54-year-old male civil engineer was admitted with a 1-month history of headaches, fever, sore throat, sinusitis, myalgias, and general malaise. He had a long history of heavy drinking (up to 0.5 pints of liquor per day) and heavy smoking (Ͼ100 pack years), extending up to the time of his admission. He was known to be purified protein derivativepositive. On admission, he was a well-developed 83-kg white male with hoarseness, a temperature of 100°F, orthostatic hypotension, and 2ϩ pitting edema to his mid-calves. There was no hepatosplenomegaly. A chest roentgenogram showed mild chronic obstructive pulmonary disease with no evidence of active tuberculosis. His hematocrit was 35.7%, and the peripheral white blood cell count was 22,000/mm 3 with 2% myeloblasts. The erythrocyte sedimentation rate was 126 mm/h. His serum glutamate pyruvate transaminase was 25 IU/L (normal, 5-40 IU/L), serum glutamate oxaloacetate transaminase was 13 IU/L (normal, 5-40 IU/L), serum alkaline phosphatase was 95 IU/L (normal, 35-125 IU/L), serum lactate dehydrogenase was 230 IU/L (normal, 20-200 IU/L), serum total bilirubin was 0.5 mg/dL (normal, Ͻ1.0 mg/dL), and serum albumin was 2.3 g/dL (normal, 3.5-5.5 g/dL). Viral serologies were negative for hepatitis A and hepatitis B (this case antedated hepatitis C testing). A bone marrow aspirate and biopsy indicated a myeloproliferative syndrome, but not acute myelogenous leukemia. The liver and spleen were of normal size by liver-spleen scan, but uptake throughout the liver was mottled, suggesting parenchymal disease. Abdominal computed tomography scan was unremarkable.The presenting symptoms persisted following admission. Continued anemia over several weeks necessitated multiple transfusions, up to as many as 4 units of packed red blood cells three times a week. Persistent throat soreness prompted biopsy of a false vocal cord lesion in week 2, which revealed squamous cell carcinoma. Spiking fevers to as high as 104°F presaged the development of a presacral decubitus ulcer in week 6, from which Proteus mirabilis was ultimately cultured. Broad spectrum antibiotic therapy was initiated, but did not prevent the progression of the decubital ulcer to development of sacral osteomyelitis by week 8. Because of progressive weight loss, parenteral hyperalim...

Liver histology in ICU patients dying from sepsis: A clinico-pathological study

“…Cholangitis and/or cholangiolitis were observed in a few patients. Additionally, ductular cholestasis, a sepsis-specific hepatic lesion [11,12] , suggesting increased risk of mortality [16] was identified only in two of our patients dying of sepsis, while canalicular cholestasis was present in one. Damage to bile duct epithelium has been previously observed in the liver of a female patient with E. coli septicemia [13] ; however, it was not detected in any of our patients.…”

“…In jaundiced septic patients, three histological patterns have been described in a limited number of studies [4,9,11] : canalicular cholestasis, usually most severe in zone 3, ductular cholestasis with inflammation and non-bacterial cholangitis associated with the toxic shock syndrome [12] . Intrahepatic cholestasis in septicemia could be attributed to many factors such as circulating endotoxin causing functional disorders in bile secretion, disturbances in bile canalicular contraction and ischemia [14][15][16][17] .…”

Alterations in Tight Junctions Differ Between Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis

“…These cells then secrete various cytokines, including tumor necrosis factor-␣, interferon-␥, interleukin-1, and interleukin-6, which in turn would aggravate bile duct injury in PBC. 29 The 7H6 changes are fairly specific: no changes of immunostaining for 7H6 occur in BEC of PSC, Ex-C, and in rats with bile duct ligation. 24 We also demonstrated that immunostaining for 7H6 was altered in both BEC and hepatocytes in the late stages of PBC (stages III and IV).…”

Leberversagen bei Sepsis und Multiorganversagen

“…Neben dieser sinusoidalen Entzündungs-reaktion kommt es jedoch auch zu einer Entzündung im Portaltrakt. Es kann dadurch einerseits eine Epithelschädi-gung der Gallengänge mit einem Leak, durch das Gallensäuren austreten kann, entstehen; andererseits dürfte dies auch zur Down-Regulation des hepatozellulären Gallensäurentransportes beitragen und damit die Cholestase aggravieren [20,31,32].…”

“…Zusätzlich könnte das Fehlen einer enteralen Ernährung über einen verminderten Stimulus bzw. verminderter Freisetzung von Hormonen zu einer Verminderung des Gallenflusses und damit Verstärkung der Cholestase führen [32]. Im Rahmen der Sepsis dürfte dies aber eine eher untergeordnete Rolle spielen.…”