1. Hypoammonemia

Path of ammonia - (associated illnesses)
- Ammonia made by gut enterocytes from glutamine or bacteria that metabolize nitrogen products like ingested protein, urea.
- Travel from portal vein to liver (portosystemic shunt)
- Metabolized in liver to urea (liver failure like Reyes, cirrhosis, inborn urea cycle disorders like citrullinemia or ornithine transcarbalymase deficiency)
- Urea is transported to kidneys and excreted (renal failure, distal renal tubular acidosis)
Other causes of hyperammonemia
- Organic acidemia/aciduria - disorders of amino acid metabolism (ie branched chain amino acids) leading to accumulation of organic acids in the blood and urine. Clinically manifest with high gap anion acidosis, ketoacidosis, pancytopenia (possibly these amino products inhibit hematological cell maturation) and hyperammonemia because coenzyme A derivatives accumulate and inhibit carbamyl phosphate synthase.
- Drugs- salicylates, antiepileptics (Depakote!!, carbamazepine, topamax), transexamic acid, some chemo agents (5-FU, rituximab)
- Pregnancy
2. Acute liver failure:
-Defined as INR >1.5 + any hepatic encephalopathy
-Fulminant: development of encephalopathy within 8 weeks of onset of hepatic sx
-Subfulminant: development after 8 but before 26 weeks.
3. DDx fulminant hepatic failure:
-Viral: Hepatidities, CMV, EBV, VZV, HSV, hemorrhagic fevers (ebola, marburg, lassa), adenovirus
-Drugs: Tylenol, hypersensitivity drug reactions, Isoniazid, weight-loss drugs (oxyelite pro)
-Toxins: Alcohol, Amanita, B.cereus toxin
-Vascular: Budd-Chiari, Ischemia of any cause, HELLP
-Metabolic: Wilsons, Reyes, Eclampsia, acute fatty liver of pregnancy, congenital enzymatic diseases (galactosemia, fructose intolerance, tyrosinemia)
-Miscellaneous: cancer (breast, small cell, lymphoma, myeloma, melanoma), autoimmune hepatitis
4. Transaminases & diagnosing liver disease 
<100: think hemochromatosis, chronic hep B/C, fatty liver
100-300: NASH, alcoholic hepatitis, autoimmune
>1000: toxins, acute hepatitis, autoimmune, ischemia
5. Figuring out timing of liver failure: 
- PT/INR half life of a few days, albumin has a half life of 21 days
- Albumin is low- are they malnourished or are they in liver failure? Look at factors, including factor VIII. It's not made in the liver, if its low you have malnutrition.
- Someone who appears well is more likely to have acute liver failure, someone with stigmata of cirrhosis (palmar erythema, spider veins, ascites)
6. Wilsons disease: 
-1:30,000-1:100,000
-Usually affects people aged 5-35, although can be older or younger; depends on penetrance.
-Children tend to present with more hepatic disease (jaundice, hepatosplenomegaly)
-Adults tend to present with more neuropsych disease (dysarthria, tremors, parkinsoninan sx, dementia)
-98% of people with neurological symptoms will have kayser-fleischer rings, however you need a slit-lamp exam as this is not always seen with a normal exam.
-In a study comparing wilsons disease to other causes of acute liver failure, the following were found to be most predictive of Wilsons: low Hb, low AST/ALT, very high urine copper, low serum ceruloplasmin (however this is an acute phase reactant)
-Labs: Alk phos is not that high-- it can be normal or sub-normal (Alk Phos/Tbili ratio <4), AST/ALT ratio >2
-Coombs-negative hemolytic anemia is also characteristic
-Thrombocytopenia from splenomegaly
7. Treatment for wilsons disease: 
-Fulminant Wilsons (defined as fulminant hepatic failure at first presentation, INR>2, hemolytic anemia or neuropsych symptoms): Transplant. You can try to bridge to transplant with plasma exchange or dialysis. Survival after transplant for wilsons is excellent- - 88% at 1 year, 80% at 5 years, kids do even better than adults.
-Decompensated Wilsons (defined as acute on chronic, no hemolytic anemia or neuropsych sx): may respond to chelation therapy
-Early Wilsons (few symptoms): chelation agents.
8. Chelation agents: 
-Trientine is now used as first-line by most hepatologists; it doesn't work quite as well as D-penicillamine but it has so many fewer side effects that it's preferred
-D-penicilliamine is second line despite its effectiveness because of its significant side effects- nephrotic syndrome & aplastic anemia (requiring regular CBC/BMP) and patients feel really bad
-Dimercaprol (not used anymore)
9. Transfusion strategies for acute upper gastrointestinal bleeding {RCT, NEJM, n=921}
Villanueva C et al, N Engl J Med. 2013 Jan 3;368(1):11-21.
METHODS:
We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis.
RESULTS:
A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy.
CONCLUSIONS:
As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding.
- Potentially due to increased portal pressure through varices with the blood transfusions/volume.
- Octreotide
10. Advice from rounds 
- B-blockers and surgery: if someone is on a b-blocker, they should definitely stay on it. There is some data that optimizing people to a HR of 60s to 70s may lead to better outcomes.
- Lovenox is better than heparin in people with cancer
- Sgarbossa's criteria: identifying ischemia in the context of LBBB.
- Most common cause of INR spikes: chronic CHF (2/2 liver congestion), diarrhea (loss of gut flora), those 2 are much more common than warfarin o/d's
- In bleeding peptic ulcers, people should be on a nexium drip for 72 hours and then BID PO dosing afterwards.