Differential diagnoses in 83 dogs with icterus

ABSTRACT: Icterus (jaundice) is a yellowish pigmentation resulting from the depositing of bilirubin in tissues due to its high plasmatic concentration. The pathogenesis of icterus includes metabolic changes or obstructed bilirubin excretion and it is classified as pre-hepatic, hepatic and post-hepatic. This study aimed to evaluate and classify different causes of icterus in dogs during post mortem examination. These dogs were examined from 2014 to 2017, using macroscopic and histologic exams as well as ancillary tests. Eighty-three dogs were examined macroscopically and microscopically. They were separated into groups of icterus types: 24 (28.9%) dogs had pre-hepatic icterus, 45 (54.2%) had hepatic, 13 (15.7%) pre-hepatic and hepatic and one (1.2%) had post-hepatic icterus. Many factors were identified as a cause of icterus, including infectious agents (51/83), neoplasms (13/83), hepatic degeneration (11/83), chronic hepatic diseases (6/83), and obstructive causes (1/87). Among the infectious causes, leptospirosis, ehrlichiosis and disorders suggestive of septicemia were diagnosed. Neoplasms associated with icterus were cholangiocarcinoma, hemangiosarcoma and lymphoma. Other causes of icterus included degenerative diseases, such as lipidosis and glycogen degeneration. Hepatic fibrosis (cirrhosis) as a chronic disease and cholelithiasis also produced icterus. PCR was performed to confirm leptospirosis and ehrlichiosis. Samples of total DNA were used to amplify a fragment of a gene from Leptospira interrogans and Ehrlichia canis. In some dogs, co-infection of these agents was detected. The classification and identification of icterus etiologies in dogs is very important due to the number of diseases with this alteration, where ante mortem diagnosis is not always easily performed when some of these conditions are present.

Bilirubin acts as a multipotent guardian of cardiovascular integrity: more than just a radical idea

Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. Individuals with Gilbert’s syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with individuals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid/protein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and individuals who have GS.

Excretion of fetal biliverdin by the rat placenta-maternal liver tandem

Fetal liver immaturity is accompanied by active heme catabolism. Thus fetal biliary pigments must be excreted toward the mother by the placenta. To investigate biliverdin handling by the placenta-maternal liver tandem, biliverdin-IXα was administered to 21-day pregnant rats through the jugular vein or the umbilical artery of an in situ perfused placenta. Jugular administration resulted in the secretion into maternal bile of both bilirubin and biliverdin (3:1). However, when biliverdin was administered to the placenta, most of it was transformed into bilirubin before being transferred to the maternal blood. Injecting Xenopus laevis oocytes with mRNA from rat liver or placenta enhanced their ability to take up biliverdin, which was inhibited by estradiol 17β-d-glucuronide. The expression of three OATP isoforms in this system revealed that they have a varying degrees of ability to transport biliverdin (Oatp1/1a1 > Oatp2/1a4 > Oatp4/1b2). The abundance of their mRNA in rat trophoblast was Oatp1/1a1 >> Oatp4/1b2 > Oatp2/1a4. The expression of biliverdin-IXα reductase in rat placenta was detected by RT-PCR/sequencing and Western blot analysis. The relative abundance of biliverdin-IXα reductase mRNA (determined by real-time quantitative RT-PCR) was fetal liver > placenta > maternal liver. Common bile duct ligation in the last week of pregnancy induced an upregulation of biliverdin-IXα reductase in maternal liver but had no effect on fetal liver and placenta. In conclusion, several members of the OATP family may contribute to the uptake of fetal biliverdin by the rat placenta. Before being transferred to the mother, biliverdin is extensively converted into bilirubin by biliverdin-IXα reductase, whose expression is maintained even though bilirubin excretion into maternal bile is impaired.