Effects of liver failure on inter‐organ trafficking of ammonia: implications for the treatment of hepatic encephalopathy
Bibliographic record
Abstract
Abstract Hepatic encephalopathy due to acute or chronic liver failure is invariably associated with hyperammonemia. High ammonia concentrations have deleterious effects on brain function by both direct and indirect mechanisms. There is increasing evidence to suggest that hyperammonemia in liver failure results from altered inter‐organ ammonia trafficking. Under normal conditions the gut produces ammonia from glutamine and urea. During liver failure, the contribution of the gut to hyperammonemia is predominantly the consequence of a diminished hepatic elimination rather than increased intestinal production. Normally, the liver removes ammonia by two distinct pathways, namely urea and glutamine synthesis catalyzed by enzymes that are, respectively, localized in the periportal and perivenous hepatocytes. The skeletal muscle relies solely on glutamine synthesis to remove ammonia. During liver failure, muscle glutamine production increases and the muscle becomes the major route for ammonia detoxification. The kidney is capable of both producing and removing ammonia. Under normal conditions, the kidney produces ammonia from glutamine which is mainly excreted into the renal vein, the remainder being excreted into the urine. However, in liver failure the excretion of the ammonia produced by the kidney is increased. Like skeletal muscle the brain relies solely on glutamine synthesis to remove ammonia. But unlike muscle, glutamine synthetase in the brain operates at nearly maximal capacity in normal conditions, and its activity is reduced during chronic liver failure. A better understanding of the alterations of inter‐organ ammonia trafficking could give rise to combined therapies aimed at reducing ammonia production and increasing ammonia removal by target organs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".