GI Physio Flashcards
How does liver get substances for first pass metabolism and estrogen?
First pass metabolism is when the absorbed substances from the intestines go to liver via portal vein before entering the blood of systemic circulation.
For, substances such as AMMONIA and drugs given orally—> reaches liver via the portal vein–> Movement is Zone 1-2-3—>Metabolized by liver into urea and leaves liver via HEPATIC VEIN in the middle of each liver lobule.
Estrogen reaches liver via HEPATIC ARTERY PROPER—> Moves Zone 1-2-3–> Broken down into metabolites—-> leaves liver via hepatic vein and excreted in urine, feces.
(So remember–> the clinical significance of this is why do spider angiomas, gynecomastia, amennorrhea testicular atrophy occurs in liver failure—> Estrogen is not metabolized by liver and leaves in hepatic vein in its raw form—> Increased blood serum estrogen!)
Why do we see petechiae and purpura and liver failure?
Liver produces 3 hormones: IGF-1, TPO (Thrombopoeitin), Angiotensinogen—->
Decreased TPO production causes thrombocytopenia which leads to petechiae and purpura.
In Wilson’s disease, we see a lack of ceruloplasmin. How does the copper reach liver?
This is a question to tackle the knee jerk response we see to ceruloplasmin.
Ceruloplasmin is produced by liver to carry copper OUT of liver into the circulation. But copper once ingested in food—> comes to liver, via portal vein carried by ALBUMIN.
Learn the liver bilirubin story.
UCB–> Unconjugated bilirubin
CB–> Conjugated Bilirubin
UGT–>UDP-glucuronyl transferase.
- Liver get bilirubin because of proporphyrin degradation after RBCS break down into heme and iron, and iron gets recycled whereas protoporphyrin is degraded into UCB. (Overhere, extravascular hemolysis in spleen and LN can cause—> INCREASED UCB.)
- UCB is supposed to be converted into CB in zone 1 of liver via the enzyme UDP-glucuronyl transferase.
( immature UGT–> Physiological jaundice
Congenital DECREASED LEVELS of UDP–> Gilbert Syndrome–> UCB will only be increased in times of stress, illness, fasting.
Congenital complete LACK OF UDP–> Crigler-Najjar syndrome)
Keep in mind that, if UCB doesn’t get conjugated—> UCB gets spilled into blood, and because it is INSOLUBLE in water—> it stays in blood as UCB-ALBUMIN.
Rise in UCB-ALBUMIN causes jaundiced skin and sclera, deposition in brain to cause kernicterus. And no other symptom.
- Now, the CB formed after UGT glucoronidation, it moves towards the portal triad ( Zone 3-2-1) to be excreted into canalicular bile ducts in portal triads.
( Bile Canalicular defects like Dubin Johnson and Rotor—>cause impaired release of CB into the bile duct—> so CB gets spilled out in blood now.)
Keep in mind that CB is soluble in blood, so it can also go to kidney and be excreted. INCREASED CB IN BLOOD causes production of urobilin which causes—>INCREASED DARKNESS OF URINE.
- Once, CB is stored as Bile in the gallbladder, it’ll go to the intestines upon meal ingestion. In the intestines,, CB gets converted to Stercobilin and urobilin. Urobilin can go back into the portal vein and then liver to become Bilirubin again. (Enterohepatic circulation)
(Obstructive conditions like gallstones, pancreatic carcinoma, liver cancer, liver fluke. OR bililary tract disease like primary sclerosing cholangitis, primary biliary cholangitis——> Don’t allow bile to enter intestines. this causes lack of stercobilin and leads to clay colored stools, and CB spills out in the blood via hepatic vein and causes DARKENING OF URINE.
So dark urine and clay colored stools often mean a problem in the biliary tract. Because the only problem is lack of stercobilin formed in the intestines because CB doesn’t reach from CBD to intestines.
In GB hypomotility, what will be seen in GB?
Biliary sludge (asked in uworld specifically) Biliary sludge is seen in pregnant woman, rapid weight loss, High Spinal Cord injuries, Prolonged use of octeotride/ TPN.
What will be seen on liver biopsy of person with Right axis deviation?
Right axis deviation–> Right ventricular Hypertrophy/ RVF
Other signs of RVF–> JVD, SOB, lower extremity edema.
But remember—> Right ventricular HF affects the liver and causes–> Hepatomegaly, localized RUQ (Because enlarged liver pushes the hepatic capsule and causes pain)—> This is called CONGESTIVE HEPATOPATHY/ NUTMEG liver—-> In histology, congestion/patchy necrosis or hemorrhage is seen around the CENTRAL vein/ Centrilobular necrosis.
In cholesterol gallstones,
what will be the levels of cholesterol, Bile Acids, phosphatidylcholine?
Cholesterol stones are made, when cholesterol is SUPERSATURATED in bile. So: Cholesterol-> INCREASED. Bile acids---> DECREASED phosphatidylcholine- DECREASED.
Hyperammonemia affects the astrocytes in what way?
Hepatic Encephalopathy causing hyperammonemia–> Excess NH3 crossing the blood brain barrier causes excess production of GLUTAMINE (asked in uworld)
Excess production of Glutamine in Astrocyte—> INCREASED intracellular osmolarity so the cell swells up—> swollen up cell doesn’t release glutamine—> No glutamine released means no glutamate produced so no excitatory neurotransmitter.
Why does Gemfibrozil cause gallstone formation?
Fibrates upregulate lipoprotein lipase, resulting in increased oxidation of fatty acids. In addition, fibrates inhibit cholesterol 7α-hydroxylase.
Inhibition of cholesterol 7α-hydroxylase causes DECREASED BILE ACID production—> causes cholesterol supersaturated in bile—> Gallstones.
Repetitive flicking motions of the hands are seen when the patient is asked to outstretch his arms and dorsiflex his wrists. Which of the following is most likely contributing to this patient’s altered mental status?
A) Accumulation of Blood Urea Nitrogen
B) Increased Absorption of nitrogenous substances from gut
c) Decreased GABA receptor stimulation
A) Accumulation of Blood Urea Nitrogen- WRONG. Urea production is impaired in this case, so BUN will be DECREASED.
BUN is increased in Renal failure, in healthy patient GI bleed can also cause increased BUN because their liver is making urea, and has adequate detoxification abilities.
B) Increased Absorption of nitrogenous substances from gut- CORRECT (e.g. GI bleed increases production of NH3 in gut, and this NH3 is absorbed into the bloodstream causing hepatic encephalopathy.)
c) Decreased GABA receptor stimulation–> In hepatic encephalopathy, there’s INCREASED GABA.
Wilson disease?
The problem is in a hepatocyte copper-transporting receptor (P-type cation transporter transmembrane receptor)—> This causes decreased ceruloplasmin and decreased excretion of copper into bile, and spills copper in blood—> copper gets deposited in liver and extrahepatic tissues like cornea ( Goldren brown rings around peripheral cornea, depostis of copper in the descemet membrane of cornea), CNS (Basal gangle atrophy), Fanconi’s anemia (Defective reabsorption in PCT)
Treated with Copper-chelator—> D-pencillamine, triantene–> Make copper-complexes that are very soluble in water and can be excreted via urine easily–> So in uworld, it said they INCREASE URINARY EXCRETION OF COPPER.
Oral zinc—> Decreases intestinal absorption of copper.
Hemochromatosis
Defective iron SENSING and hence, INCREASED intestinal absorption of iron.
>Restrictive cardiomyopathy (R is the name of the disease itself)
> HLA-A3 association (MHC 1)
> Increased Iron, ferritin, tranferrin saturaion.
> Decreased TIBC.
> Presents after the age of 40 (vs wilsons which present BEFORE the age of 40)
>MCP joint hurt—> calcium pyrophosphate deposition
(Positively birefringent crystals–> Yellow perpendicularly, blue parallel)
ALP is increased in?
> Isolated rise in ALP in Paget’s disease ( osteoblasts jump in because of so much osteoclastic activity, and end up making mosaic pattern bone.)
Choledocholithiasis
Multiple Myeloma.
Difference between choledocholithiasis vs Cholecystitis?
Choledocholithiasis—> Stone in CBD (Increased ALP as bile duct is involved)
Cholecystitis–> stone is cystic duct. (ALP will only increase when there’s bile duct involved matlab ascending cholangitis)
Treatment of hepatic encephalopathy and also tell its mechanisms?
- Lactulose (Lactulose is catabolized by gut bacteria into SHORT CHAIN FATTY ACIDS—> lowers PH (more acidic)—> NH3 gets converted into Ammonium ion.
- Rifaximin, Neomycin—> Both are nonabsorbable antibiotics—-> alter GI flora to reduce ammonia production and absorption into blood–> written as decreases intraluminal ammonia production.
(Rifaximin is used for traveller’s diarrhea too—> is a DNA dependant RNA polymerase inhibitor so keep that in mind too)
