Inflammatory markers of oxidative stress (tumor necrosis factor alpha, NADPH oxidase, and glutathione synthetase) were all increased in the proximal resection group compared to sham and distal resection.
Liver fibrosis measured by Sirius red staining and collagen 1A1 expression were present at higher levels in proximal resection mice, with distal resection showing liver protection.
BOB Ped Surg 2023 - Maria Tecos, AAP - Presentation
▶Ep 15 · 0:00
quoteYou're on call and you get consulted on a 14-day ex-31-week male with a distended tender abdomen, skin changes and free air on abdominal X-ray.↗
▶Ep 15 · 0:30
quoteThese fragile patients are the driving force for the investigative efforts of our lab.↗
▶Ep 15 · 1:00
epidemiologicalApproximately 25% of short gut syndrome survivors go on to have intestinal transplantation.↗
▶Ep 15 · 1:00
epidemiologicalShort gut syndrome patients face a 25% mortality within two years.↗
▶Ep 15 · 1:00
epidemiologicalLess than 50% of short gut syndrome survivors ever regain enteral autonomy.↗
▶Ep 15 · 1:30
clinicalTPN is a significant contributor to liver injury in short gut syndrome.↗
▶Ep 15 · 1:30
clinicalIn a murine small bowel resection model without TPN, intestinal loss alone is sufficient to mount oxidative stress that results in liver fibrosis.↗
▶Ep 15 · 2:00
quoteA question then became why and how does this happen?↗
▶Ep 15 · 2:30
quoteThis led us to question if removing the ileum where bile acids are reabsorbed would have a different liver injury phenotype compared to removing the jejunum.↗
▶Ep 15 · 5:00
clinicalIn mice, serum evidence of liver injury was found as early as post-operative week two in proximal resection mice and persisted to post-operative week 10.↗
▶Ep 15 · 5:00
clinicalLiver injury was only found in proximal resection mice, not in distal resection mice.↗
▶Ep 15 · 6:00
clinicalLiver fibrosis measured by Sirius red staining and collagen 1A1 expression were present at higher levels in proximal resection mice, with distal resection showing liver protection.↗
▶Ep 15 · 7:00
clinicalInflammatory markers of oxidative stress (tumor necrosis factor alpha, NADPH oxidase, and glutathione synthetase) were all increased in the proximal resection group compared to sham and distal resection.↗
▶Ep 15 · 7:00
clinicalThe proximal resection group had a compensatory increase in lipocalin 2, an acute phase protein known to increase against oxidative stress.↗
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clinicalDistal resection resulted in decreased taurolithocholic acid (TLCA), the most toxic, insoluble, hydrophobic bile acid.↗
▶Ep 15 · 8:00
clinicalDistal resection resulted in increased tauro-ursodeoxycholic acid (TUDCA), the most soluble hydrophilic bile acid.↗
▶Ep 15 · 8:00
clinicalProximal resection bile acid profile was the exact opposite of distal resection (increased TLCA, decreased TUDCA).↗
▶Ep 15 · 8:00
clinicalRemoval of the ileum decreased the size of the bile acid pools.↗
▶Ep 15 · 9:00
clinicalCYP7A1, the rate limiting step of de novo bile acid synthesis in the liver, was increased in the distal resection group.↗
▶Ep 15 · 10:00
clinicalTUDCA supplementation in proximal resection mice resulted in significantly less oxidative stress.↗
▶Ep 15 · 10:00
clinicalTUDCA acts as an endogenous antioxidant and cellular chaperone.↗
▶Ep 15 · 10:00
clinicalThe compensatory increase in lipocalin 2 previously observed in proximal resection was absent with TUDCA supplementation.↗
▶Ep 15 · 11:00
clinicalTUDCA supplementation rescued the bile acid profile to a healthier milieu in proximal resection mice.↗
▶Ep 15 · 11:00
clinicalLiver fibrosis measured by Sirius red staining was rescued by TUDCA supplementation.↗
▶Ep 15 · 11:30
opinionThe liver injury in proximal small bowel resection is likely the result of direct liver exposure to oxidative stress and toxic bile acids via enterohepatic circulation.↗
▶Ep 15 · 11:30
opinionRemoving the ileum where bile acid absorption occurs shields the liver from inflammation and stimulates healthy new bile acid production.↗
