Liver

Hepar

Also known as: hepar, hepatic

The liver is the largest gland and largest internal organ, weighing about 1.5 kg. It has a dual blood supply from the hepatic portal vein and the hepatic artery, and it processes everything absorbed from the gut. It makes bile and plasma proteins, controls fuel metabolism and detoxifies drugs and waste.

Show on body map Liver Lobule Hypothalamic–Pituitary Axis

Overview

Mass≈1.4–1.5 kg (≈2.5% of body weight)

Blood flow≈1.5 L/min (≈25% of cardiac output)

InflowPortal vein ≈75% · hepatic artery ≈25% (≈50:50 of O₂)

Normal portal pressure≈5–10 mmHg

Bile output≈0.6–1 L/day

Couinaud segments8 (I = caudate)

The liver fills the right hypochondrium and epigastrium and extends into the left hypochondrium, protected by the lower ribs. Its smooth diaphragmatic surface is covered by peritoneum except at the bare area, where it touches the diaphragm directly between the layers of the coronary ligament. Its visceral surface faces down and back. It carries an H-shaped arrangement of fissures and the porta hepatis, and it bears impressions of the stomach, duodenum, colon, right kidney and gallbladder.

Anatomical lobes. The falciform ligament in front, and the fissures for the ligamentum teres and ligamentum venosum behind, separate a large right lobe from a smaller left lobe. On the visceral surface the caudate lobe lies between the IVC and the fissure for the ligamentum venosum. The quadrate lobe lies between the gallbladder fossa and the fissure for the ligamentum teres.

Functional anatomy. The Cantlie line runs from the gallbladder fossa to the IVC along the plane of the middle hepatic vein. It divides the liver into functional right and left livers of roughly equal size, each with its own portal pedicle. The Couinaud classification subdivides these into eight segments, each with its own portal venous, hepatic arterial and biliary branch, and drained by hepatic veins that run between segments. Segment I is the caudate lobe. Segments II and III form the left lateral section. Segment IV (IVa/IVb, which includes the quadrate lobe) is the left medial section. Segments V–VIII form the right liver. Because each segment is self-contained, it can be resected on its own.

Dual blood supply. The hepatic portal vein brings about 75% of the inflow. This blood is rich in nutrients and partly deoxygenated, coming from the gut, spleen and pancreas. The hepatic artery proper brings about 25%, all of it well oxygenated. Each contributes roughly half of the liver's oxygen. Total flow is about 1.5 L/min, roughly 25% of resting cardiac output. Blood mixes in the sinusoids, flows to the central veins, and leaves through the right, middle and left hepatic veins into the IVC just below the diaphragm. When portal flow falls, the hepatic arterial buffer response increases arterial inflow to compensate.

Location: Right upper quadrant (right hypochondrium and epigastrium, extending into the left hypochondrium), beneath the diaphragm. It moves with respiration and is protected by ribs 7–11.

Parts & subdivisions

Right, left, caudate and quadrate lobes
The anatomical lobes, defined by surface ligaments and fissures. The caudate and quadrate lobes belong functionally to the left liver (the caudate drains straight into the IVC).
Couinaud segments I–VIII
I caudate; II, III left lateral; IV left medial (IVa superior, IVb inferior, including the quadrate lobe); V, VIII right anterior; VI, VII right posterior. Numbered clockwise from the caudate in the frontal view.
Porta hepatis
Transverse hilum on the visceral surface, between the caudate and quadrate lobes. The portal vein (posterior), the hepatic artery proper branches (middle) and the hepatic ducts (anterior) pass through it, with lymphatics and nerves.
Peritoneal ligaments
Falciform ligament (with the ligamentum teres, the obliterated left umbilical vein, in its free edge); coronary and left and right triangular ligaments; lesser omentum to the stomach and duodenum. The ligamentum venosum is the remnant of the ductus venosus.
Bare area
Triangular area on the posterior diaphragmatic surface with no peritoneum, in direct contact with the diaphragm and IVC.
Liver lobule
The microscopic structural and functional unit.
Hepatic veins
Right, middle and left hepatic veins run in the intersegmental planes and drain into the IVC.

Anatomy

Innervation: Hepatic plexus, carrying sympathetic fibres from the coeliac plexus and parasympathetic fibres from the anterior vagal trunk (hepatic branch). The Glisson capsule is sensitive to stretch. Capsular distension (hepatitis, congestion) causes right upper quadrant pain, and irritation of the diaphragm can refer pain to the right shoulder (phrenic, C3–C5).
Arterial supply: Hepatic artery proper (from the common hepatic artery of the coeliac trunk) divides into right and left hepatic arteries; the cystic artery usually arises from the right. The hepatic portal vein, formed behind the neck of the pancreas by the superior mesenteric and splenic veins, divides into right and left branches. Normal portal pressure is about 5–10 mmHg.
Venous drainage: Right, middle and left hepatic veins, plus small caudate veins, drain directly into the IVC.
Lymphatic drainage: The liver produces a large share (about a third to a half) of thoracic duct lymph. It drains to hepatic nodes at the porta and then to the coeliac nodes. The bare area drains to phrenic and posterior mediastinal nodes.
Relations: Diaphragmatic surface: diaphragm, pleura and lung bases, pericardium. Visceral surface: stomach and lesser omentum, duodenum, hepatic flexure of the colon, right kidney and suprarenal gland, gallbladder, and the IVC in its groove. The hepatorenal pouch (Morison) between the liver and right kidney is the lowest part of the peritoneal cavity in a supine patient.
Histology: Glisson capsule; hexagonal lobules of hepatocyte plates and sinusoids around central veins, with portal triads at the corners. Kupffer cells line the sinusoids, and stellate cells lie in the space of Disse.
Development: The hepatic diverticulum buds from the distal foregut endoderm in week 4 and grows into the septum transversum. Endodermal cords become hepatocytes and the intrahepatic bile ducts. Septum transversum mesoderm gives the connective tissue and capsule. The ventral mesentery becomes the lesser omentum and falciform ligament. The liver is the main fetal blood-forming organ in mid-gestation, and bile formation starts at about week 12.

Function

Carbohydrate metabolism: glycogen storage and breakdown, gluconeogenesis; buffers blood glucose.
Lipid metabolism: β-oxidation, ketogenesis, synthesis of cholesterol and lipoproteins (VLDL, HDL), and bile acid synthesis.
Protein metabolism: synthesises albumin, clotting factors (I, II, V, VII, IX, X, XI), transport and acute-phase proteins; deaminates amino acids; detoxifies ammonia in the urea cycle.
Bile production (about 0.6–1 L/day): fat digestion and excretion of bilirubin, cholesterol, drugs and copper.
Biotransformation: phase I (cytochrome P450) and phase II (conjugation) metabolism of drugs, hormones and toxins; first-pass effect.
Storage: glycogen, vitamins A, D and B12 (several years' supply), iron (ferritin) and copper.
Endocrine roles: 25-hydroxylation of vitamin D, IGF-1, angiotensinogen, thrombopoietin and hepcidin; T4→T3 conversion.
Immune defence: Kupffer cells filter bacteria and endotoxin from portal blood.
Fetal haematopoiesis, which is the main site in mid-gestation.

Clinical significance

Cirrhosis and portal hypertension

Fibrosis and regenerative nodules raise intrahepatic resistance, giving a hepatic venous pressure gradient above 5 mmHg; at 10 mmHg or more it is clinically significant. Varices, ascites, splenomegaly, encephalopathy and hepatocellular carcinoma follow. See the system-level entry on cirrhosis.

Paracetamol (acetaminophen) overdose

Excess paracetamol saturates glucuronidation and sulfation. The surplus is converted by CYP2E1 into the toxic metabolite NAPQI, which depletes glutathione and causes zone 3 (centrilobular) necrosis. Fulminant hepatic failure can develop over 3–5 days. N-acetylcysteine, which replenishes glutathione, is highly effective if given early (guided by the treatment nomogram or local protocol).

Liver injury and regeneration

The liver is the most commonly injured organ in blunt abdominal trauma (with the spleen). Bleeding can be controlled temporarily by the Pringle manoeuvre, which clamps the hepatoduodenal ligament. The liver can regenerate to near its full mass within weeks even after about 70% resection. This makes major hepatectomy and living-donor transplantation possible.

Mnemonics

Portal triad in the hepatoduodenal ligament

"DAVe": the bile Duct lies anterior and to the right, the hepatic Artery anterior and to the left, and the portal Vein posterior to both.

Test yourself

In paracetamol overdose, hepatocyte necrosis is concentrated in which zone of the hepatic acinus?

Zone 1 (periportal)
Zone 2 (intermediate)
Zone 3 (centrilobular)
Equally in all zones

Answer: Zone 3 (centrilobular)

Zone 3 has the most CYP2E1, which makes the toxic metabolite NAPQI, and the least oxygen. It is therefore hit first by paracetamol, ischaemia and venous congestion ("nutmeg liver").

The cystic artery most commonly arises from the:

Left hepatic artery
Gastroduodenal artery
Superior mesenteric artery
Right hepatic artery

Answer: Right hepatic artery

The cystic artery usually arises from the right hepatic artery within the cystohepatic triangle (of Calot), bounded by the cystic duct, the common hepatic duct and the inferior surface of the liver. Variations are frequent, which is why the critical view of safety matters in cholecystectomy.