Hepatobiliary: Anatomy/Histology/Biochemistry

Right, left, quadrate (superior) and caudate (inferior) lobe. The right and left lobe is separated by the interlobar fissure which is an invisible line running from the gallbladder to the IVC.

The liver is secured in its anatomic location by the attachment of the hepatic veins to the IVC.

5th intercostal space
midclavicular

Both enter via the hilum.
Portal vein (60-70% of the blood to the liver): formed by the union of the splenic vein (IMV joins splenic) and SMV

Hepatic artery (30-40%): is a branch off the common hepatic artery which arise from the celiac trunk (T12).

Portal hypertension will cause blood within the portal vein to reverse its flow and enter the IVC to return to the heart. The three main sites are:
Esophageal varices: left gastric vein-esophageal vein.
Caput medusa: paraumbilical vein-superficial and inferior epigastric veins.
Hemorrhoids (rectum): superior rectal vein - middle and inferior rectal veins

Fundus (anterior portion), body, neck (posterior).
The cystic artery (a branch of the right hepatic artery) supplies the gallbladder.
Sensory: the greater thoracic splanchnic nerve (T7-T10).
Motor: vagus (CNX).

The common bile duct passes posterior to the pancreas and ends at the hepatopancreatic ampulla (ampulla of Vader), where it joins the pancreatic duct. The sphincter of Oddi controls bile flow into the 2nd portion of the duodenum.

CCK
Somatostatin

The liver is classically divided into hexagonal lobules oriented around a central vein (terminal veins). Portal tracts (artery, vein, bile duct) are arranged at the periphery. The hepatocytes are arranged in plates around the central vein and are separated by vascular sinusoids (blood drains to central vein). Bile canaliculi are channels between hepatocytes that drain towards the portal triad.

A liver acinus is divided into zone 1 (periportal - closest to portal triad), zone 2 (midzonal), and zone 3 (centrilobular -closest to central vein). The centrilobular hepatocytes are most remote from blood supply.

Ito cells are fat-storing cells found in the space of Disse. Sinusoids are lined by fenestrated endothelial cells. The space between these endothelial cells and the hepatocytes make up the space of Disse. Ito (stellate) cells play a role in storage of vit A and they form collagen producing myofibroblasts in inflammation.

Kupffer cells are resident macrophages found in the liver sinusoids. They secrete proinflammatory cytokines:
TNF-a: cause cholestasis.
IL-6: cause synthesis of proteins by hepatocytes.
TFG-b: cause stellate cells to secrete type I collagen.

Cholesterol, bilirubin glucuronide, bile salts (cholic acid and chenodeoxycholic acid conjugated to tuarine or glycine), phospholipids (lecithin), electrolytes, water, IgA.

Splenic macrophages degrade heme to unconjugated bilirubin (UCB). UCB-albumin complex travels to hepatocytes. UCB is conjugated by UDP glucuronyl transferase to form bilirubin-glucuronide (conjugated,CB and is water soluble). CB is converted to urobilinogen (UBG) by bacteria in the intestines. UBG is oxidized to urobilin.

Most important: glycerol (from TGs), lactate (during exercise), and glucogenic amino acids.
Additionally, all the intermediates of glycolysis and the citric acid cycle.

Glycerol is converted by glycerol kinase to glycerol phosphate which is oxidized (by dehydrogenase) to dihydroxyacetone phosphate (DHAP).

Bloob-borne glucose is converted by exercising muscle to lactate. Lactate is taken up by the liver and reconverted to glucose (lactate to pyruvate)

Leucine and lysine, which are both essential amino acids (obtained from diet). Tyrosine, isoleucine, phenylalanine, and tryptophan are ketogenic and glucogenic.

1) Pyruvate (via p. carboxylase, biotin, CO2, ATP) to oxaloacetate. (Note: oxaloacetate is transported across mitochondrial membrane as malate).
2) Oxaloacetate (via PEP carboxykinase, loss of CO2, GTP) to PEP.
3) F-1,6-P (via F-1,6-Pase) to F-6-P.
4) G-6-P (via G-6-Pase) to glucose.

Glucagon binds to adenylate cyclase, increasing cAMP, thus activating protein kinase A. Protein kinase A favors the phosphorylation of PFK-2/FBP complex which activates fructose bisphosphatase (FBP). Insulin favors dephosphorylation of the complex and activated phosphofructokinase (PFK).
Glucagon also inactivates pyruvate kinsae and activates PEP carboxykinase.

F-2,6-BP: activates phosphofructokinase (glycolysis).
Acetyl CoA: activates pyruvate carboxylase (gluconeogenesis).
AMP: inhibits F-1,6-BPase (inhibits gluconeogenesis)
Glucagon: increases gluconeogenesis.

Skeletal muscle: serve as a fuel reserve for the synthesis of ATP during muscle contraction.

Liver: glycogen is used to maintain the blood glucose concentration (early on in fasting).

Glycogen synthase regulates glycogenesis.

Glycogen phosphorylase regulates glycogenolysis.

In liver:
Glycogen synthase: activated by G-6-P
Glycogen phosphorylase: activated by glucagon and epinephrine and inhibited by G-6-P, ATP, glucose
Muscle:
Glycogen synthase: activated by G-6-P
Glycogen phosphorylase: activated by Ca, AMP, epinephrine and inhibited by ATP, G-6-P

A deficiency of glucose 6-phosphatase, which is responsible for releasing free glucose that can be used to maintain blood glucose levels. Sever fasting hypoglycemia, fatty liver, hepatomegaly, renal disease, growth retardation, etc.

Glucose (via hexokinase) to G-1-P.
Fructose 6-P (via phosphofructokinase) to F-1,6,BP.
Phosphoenolpyruvate (via pyruvate kinase) pyruvate.

Ethanol is converted to acetaldehyde by alcohol dehydrogenase. Acetaldehyde is oxidized to acetate by aldehyde dehydrogenase. It is also inhibited by disulfiram.

This drug causes accumulation of acetaldehyde in the blood which results in flushing, tachycardia, hyperventilation, and nausea.

Ethanol metabolism results in a massive increase of NADH. NADH favors the conversion of pyruvate to lactate and oxaloacetate to malate, thus, shunting these intermediates away from gluconeogenesis..

MEOS (microsomal ethanol-oxidizing system) metabolizes EtOH using NADPH and P450. This pathway is inducible which accounts for tolerance build up. Unfortunately, it produces excess oxygen free radicals (very dangerous).

Acetate is the final product of EtOH metabolism. Acetate is used to make fatty acids.