Bile, Enterohepatic, and Portal Circulations (Week 2--Beaven) Flashcards Preview

Block 3: GI, Endocrine, Reproductive > Bile, Enterohepatic, and Portal Circulations (Week 2--Beaven) > Flashcards

Flashcards in Bile, Enterohepatic, and Portal Circulations (Week 2--Beaven) Deck (38):
1


What does a portal triad contain?


1) Hepatic arteriole (25% of blood into liver)

2) Portal venule (75% of blood into liver)

3) Bile ductule

(4) Lymphatic vessels)

2


Blood and bile flow between portal triad and central vein


Blood flows from PT to central vein

Bile flows from central vein to PT

3


Zone 1, 2, 3 of the liver


Zone 1: around PT; highest O2, gluconeogenesis; viral hepatitis comes in through PT so starts here

Zone 2: combo between 1 and 3

Zone 3: around central vein; lowest O2, glycolysis, lipogenesis; fatty liver starts around central vein

4


Portal system


Capillary bed then veins then another capillary bed THEN to the heart

1) Hepatic portal system: capillary bed of gut (splanchnic capillaries) to portal vein into capillary/sinusoids of the liver to hepatic vein to inferior vena cava

2) Pituitary gland

5

What is the endothelium of the liver?


Fenestrated endothelium

So albumin can get access to/from hepatocytes

6


How much of the liver can we cut out?


In humans, cut 1/3 and over 2 to 3 months will grow back

Liver will fill the space its in (either grow or shrink)

7


What liver diseases occur in the hepatic artery (pre-sinusoidal)?


Portal vein thrombosis (blood clot; imbalance in clotting factors, or cancer)

Schistosomiasis (rare, parasitic infection that feeds off nutrients)

8


What liver diseases occur in the sinusoids?


Viral hepatitis (B and C are chronic)

Toxins, alcohol

Cholestatic

Fatty liver

Almost all else

9


What liver diseases occur in the hepatic vein (post-sinusoidal)?


Venoocclusive disease (complication of bone marrow transplant)

Budd Chiari (rare)

Inferior vena cava web (rare)

Heart failure (backflow to liver leads to portal HTN)

10


What happens when you get cirrhosis?


Shrunken, scarred liver (cirrhosis) --> increased blood pressure in portal vein (portal hypertension) -->

1) Esophageal and gastric varices (50% people die when this happens)

2) Paraumbilical varices (caput medusae)

3) Rectal (NOT hemorrhoids) and paracolic varices

4) Spleen enlarges (splenomegaly), and chews up/traps platelets too much (low platelet count)

11


What is the apical/canalicular membrane and what goes across this membrane?

2 hepatocytes form a bile canaliculus between them (blood and bile run perpendicularly)

Hepatocytes makes bile salts/acids and secretes them across this membrane

Cl/HCO3 channel to maintain electrical neutrality

Channels for cholesterol, conjugated bile acids, phospholipids (components of BILE!)

Channels for conjugated bilirubin, GSH, drugs/toxins

12


Flow of bile (Enterohepatic Circulation)


Phospholipids, cholesterol, conj bile acids secreted across apical/canalicular membrane into canaliculus --> thru liver through canals of Hering (liver turns bile acids into bile salts) --> bile salts out of liver into R/L then common hepatic duct, etc. where is modified by absorption/secretion --> gall bladder for concentration (5x)/storage --> through cyctic then common bile duct through sphincter of Oddi --> duodenum --> bile salts partially converted back to bile acids by gut bacteria --> bile salts and bile acids reabsorbed in terminal ileum --> portal vein back to liver

Note: bile acids need to bind to albumin in order to be transported in portal circulation

Portal circulation tied to biliary circulation via Enterohepatic Circulation

13


Which vitamins are at risk if you have disruption with terminal ileum and enterohepatic circulation?


Fat soluble vitamins: K, A, D, E

Water soluble: B12 (because absorbed at terminal ileum)

14


How could enterohepatic circulation be interrupted?


Resection (surgical)

Inflammation/edema (infection, IBD (Chron's, Ulcerative Colitis), autoimmune)

Radiation

15


What is bile composed of?


67% bile salts

26% phospholipids (lecithin) and cholesterol

4.5% proteins

0.3% bilirubin

16


Function of bile acids/salts

1) Form micelles

2) Solubilize fatty vitamins A, D, E, K to absorb

3) Absorb heavy metals (Fe2+)

4) Keep intestinal surface clean

5) Promote intestinal motility

6) Mild bacteriostatic effects

7) If too much in colon, induce water secretion and get really bad diarrhea

17


How do we get rid of cholesterol?


Must secrete it in bile, using bile salts

18


Difference between bile acid and bile salt


Bile acid is base structure, the salt is the conjugated form with Na+ (which can fall off or on)

19


How are bile acids made?


Cholesterol to cholic acid by CYP7A1 (7-alpha-hydroxylase) --> primary bile acids cholic acid or chenodeoxycholic acid conjugated to glycine or taurine (by CYP81B) --> bile salts: glycocholic acid, glycochenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid

20


How does our body know how much cholesterol or bile salts to secrete?


We have endogenous sensors for cholesterol (LXR) and bile acids (FXR) that help control how much cholesterol, conjugated bile acid, and phospholipid is secreted into bile canaliculus

21

Cholestasis

Backup of bile in the liver

Ex: Byler's Disease (common in kids)

22


What do you have to do to prevent gallstones?


"Zone 1" where you have high bile acid, high phospholipid and LOW cholesterol

Bile with >10% cholesterol forms cholesterol crystals and gallstones

23


Diseases of conjugation of bilirubin

1) Gilbert's Syndrome: liver doesn't take up unconjugated bilirubin well or MILD decrease in UDP-glucuronyl transferase; high unconjugated bilirubin but usually asymptomatic

2) Crigler-Najjar Syndrome Type 1: ABSENT UDP-glucuronyl transferase activity so fail to conjugate bilirubin; high unconjugated bilirubin; infants get bilirubin deposition in brain called kernicterus and die within a few years (Note: Type 2 is less severe)

3) Dubin-Johnson; Rotor's Syndrome: Cannot transfer/excrete bilirubin into bile canaliculus to get it out of the liver; high conjugated bilirubin because just can't get it out; liver becomes black; benign

24


What determines which direction bile flows in the biliary tree?


Pressure 1: determined by hydrostatic secretion pressure by liver secretion

Pressure 2: determined by gall bladder secretion induced by CCK

Pressure 3: determined by Sphincter of Oddi open or closed

25


Consequences of cholestasis (failure to secrete bile)


Cholelithiasis (gallstones)

Jaundice

Pruritus

Dark urine (bilirubin)

Malabsorption (K, A, D, E)

Steatorrhea

Pain (epigastric, RUQ, right shoulder--referred pain)

Hepatotoxicity (untamed bile acids are highly toxic)

Kernicterus (in neonates)

Get itchy all over body, don't know mechanism!

26

Extrahepatic causes of cholestasis

Mechanical, plumbing problem, blockage of flow

In biliary tree: gallstones, stricture, cyst, diverticulum, cancer, acalculous cholecystisis

In pancreas: pancreatitis, pseudocyst, cancer

27


Intrahepatic causes of cholestasis

In biliary tree: ischemic injury, primary biliary cirrhosis, primary sclerosing cholangitis

Drug-induced: oral contraceptives and androgens, phenothiazines, macrolide antibiotics (erythromycin), TPN

Parenchymal diseases: cirrhosis, cancer, hepatitis, infection/sepsis (hyperbilirubinemia of sepsis), infiltrating disease (amyloidosis, TB, sarcoidosis)

28


How do you measure cholestasis?


Physical exam: Murphy's sign (pain on pressure where liver should be), jaundice, scleral icterus, pruritis, RUQ/epigastric tenderness

Lab: elevations of bilirubin (conjugated), alkaline phosphatase, GGT, 5' nucleotidase

Imaging: ultrasound, abdominal CT, HIDA scanning, ERCP/MRCP

29


What tests are for hepatocellular disease vs. cholestasis?

AST, ALT: markers of hepatocellular disease

Bilirubin, alkaline phosphatase: markers of cholestasis and biliary dysfunction

30


How do you treat cholestasis?

Treat underlying condition

Lower cholesterol (get to Zone 1 so you don't develop gallstone)

Give ursodiol: exogenous bile acids

31


What are true measures of liver function?


Clotting time (PT), platelet count, albumin level

Because liver makes clotting factors, albumin

32


Diseases that cause increased unconjugated bilirubin


Sickle cell anemia (have hemolysis and would also have high reticulocytes)

Hemolytic anemia

Sepsis?

Gilbert's Syndrome

Crigler-Najjar Type 1

 

33


Diseases that cause increased conjugated bilirubin


Cirrhosis (total, conj and unconj increased)

Dubin-Johnson Syndrome

Rotor's Syndrome

34


What two veins feed into the portal vein?


Superior mesenteric vein

Splenic vein

(Inferior mesenteric vein feeds into Splenic vein)

35


What happens when you get portal hypertension?


1) Portocaval anastamoses swell (esophageal varices, caput medusa, rectal varices)

2) Splenomegaly and platelet consumption

36


Markers elevated in hetapocellular damage


AST

ALT

Total bilirubin

37


Markers elevated in cholestatic diseases


Alkaline phosphatase

Total bilirubin

Conjugated bilirubin

38


In portal hypertension, bleeding from which veins would cause varices where?


Azygous vein: esophageal varices

Left gastric--portal: gastric varices

Splenic: splenomegaly (note: not varices)

Superior mesenteric vein--portal: pancreas, duodenum, jejunum, ileum, cecum, appendix, ascending colon, transverse colon

Falciform ligament: caput medusa

Inferior mesenteric vein (specifically superior rectal vein--portal): sigmoid and descending colon