49 LIVER

# LIVER

The liver is the largest solid organ in the body (≈1.5 kg) and the only one with a dual blood supply. It sits in the right upper quadrant, tucked under the diaphragm, and acts as the metabolic factory, detoxifier and synthetic powerhouse of the body. For MRCS Part A, examiners love the liver because it spans anatomy (Couinaud segments, Pringle's manoeuvre), physiology (clotting, bilirubin), pathology (cirrhosis, HCC) and clinical surgery (trauma, transplantation).

👩‍⚕️ One-line orientation: stable + non-bleeding liver injury = non-operative management in HDU. Unstable = laparotomy + packing. Occupational history is a giveaway in tumour SBAs (PVC → angiosarcoma; shepherd + calcified cyst → hydatid).

Gross anatomy

The liver has four anatomical lobes divided by surface features, but only two functional lobes divided by the line of Cantlie (gallbladder fossa to IVC):

➡ Right lobe — the largest; functionally distinct.

➡ Left lobe — smaller; lies to the left of the falciform.

➡ Caudate lobe — posterior, between IVC and ligamentum venosum. Drains directly into the IVC via its own short veins, which is why it hypertrophies in Budd–Chiari syndrome.

➡ Quadrate lobe — anterior, between gallbladder fossa and ligamentum teres. Functionally part of the left lobe.

Couinaud segments

The functional anatomy divides the liver into 8 segments, each with its own portal pedicle (portal vein branch, hepatic artery branch, bile duct) and hepatic venous drainage. This makes segment-based resection possible.

- Segment I = caudate lobe

- Segments II–IV = left lobe (II, III above the portal plane; IV = quadrate, subdivided IVa/IVb)

- Segments V–VIII = right lobe (V, VIII anterior; VI, VII posterior)

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Ligaments and peritoneal attachments

- Falciform ligament — connects liver to anterior abdominal wall; its free edge contains the ligamentum teres (obliterated left umbilical vein). Recanalisation in portal hypertension produces caput medusae.

- Ligamentum venosum — obliterated ductus venosus (which in the fetus shunted oxygenated blood from umbilical vein → IVC, bypassing the liver).

- Coronary ligaments form the bare area of the liver (in direct contact with the diaphragm, not covered by peritoneum). Subphrenic abscesses collect here.

- Hepatoduodenal ligament — free edge of the lesser omentum; contains the portal triad.

Blood supply

The liver receives 1500 mL/min — about 25% of cardiac output — from two sources:

Vessel	% flow	% oxygen	Notes
Portal vein	75%	50% of O₂ delivery	Formed behind the neck of the pancreas by SMV + splenic vein. Deoxygenated but nutrient-rich.
Hepatic artery (branch of coeliac trunk)	25%	50% of O₂ delivery	Oxygenated.

Both vessels enter at the porta hepatis and ramify down to the sinusoids. Drainage is via three hepatic veins (right, middle, left) into the IVC just below the diaphragm — there is no extrahepatic course of any length, which is why hepatic vein injuries are catastrophic.

Portal triad and Pringle's manoeuvre

Within the hepatoduodenal ligament:

➡ Portal vein (posterior)

➡ Hepatic artery (medial/left, anterior)

➡ Common bile duct (lateral/right, anterior)

Pringle's manoeuvre = compressing the hepatoduodenal ligament between finger and thumb (or with a soft clamp) at the foramen of Winslow (epiploic foramen) to occlude inflow. If bleeding stops, the source is the portal vein or hepatic artery. If bleeding continues, the source is the hepatic veins or IVC — a far more dangerous problem.

👩‍⚕️ Classic SBA: "Bleeding continues despite Pringle's manoeuvre — where is the bleeding from?" Answer: hepatic vein / retrohepatic IVC.

Microscopic structure and function

Hepatocytes are arranged in lobules: hexagonal units with a central vein in the middle and portal tracts at the corners (portal triad). Blood flows from portal tract → sinusoids → central vein → hepatic vein. Bile flows in the opposite direction, from canaliculi → bile ductules → bile duct.

Zonation matters clinically:

- Zone 1 (periportal) — first to receive oxygen, last to die in ischaemia; first hit by viral hepatitis.

- Zone 3 (centrilobular) — most vulnerable to ischaemia and to toxins requiring CYP450 activation (e.g. paracetamol, alcohol).

Functions — the big list

➡ Synthesis: albumin, all clotting factors except VIII (made by endothelium), thrombopoietin, transport proteins (transferrin, caeruloplasmin), acute phase proteins.

➡ Detoxification: first-pass metabolism of drugs and toxins absorbed from the gut; ammonia → urea (urea cycle).

➡ Bile production: ~600 mL/day; emulsifies fat, excretes bilirubin and cholesterol.

➡ Glucose homeostasis: glycogen storage, gluconeogenesis.

➡ Storage: vitamins A, D, B12, K; iron (ferritin); copper.

➡ Immune: Kupffer cells (resident macrophages) filter portal blood.

👩‍⚕️ Why factor VIII is normal (or even raised) in liver failure: it is made by vascular endothelium, not hepatocytes. Useful for distinguishing liver failure from DIC, where factor VIII falls.

Liver function tests — interpreting the pattern

LFTs split into two patterns:

Pattern	Hepatocellular	Cholestatic
Dominant rise	ALT > AST	ALP, GGT
Mechanism	Hepatocyte injury	Bile flow obstruction or canalicular damage
Causes	Viral hepatitis, drugs, ischaemia, NAFLD	Gallstones, strictures, PBC, PSC, malignancy

Markers of synthetic function (the ones that actually matter):

➡ Albumin — falls in chronic liver disease (half-life ~20 days, so reflects chronicity).

➡ PT/INR — rises acutely (factors II, VII, IX, X are vitamin K dependent and short-lived). INR is the most sensitive marker of acute liver failure.

➡ Bilirubin — rises in both hepatocellular and cholestatic disease.

👩‍⚕️ AST:ALT ratio >2 classically suggests alcoholic liver disease (the mnemonic: "A Scotch and Tonic" — AST high in alcohol).

Acute liver failure

Defined as new-onset coagulopathy (INR ≥1.5) + encephalopathy in a patient without pre-existing liver disease, within 26 weeks.

Causes (in UK order of frequency):

1. Paracetamol overdose — antidote N-acetylcysteine (NAC); replenishes glutathione, which conjugates the toxic metabolite NAPQI.

2. Viral hepatitis — A, B, E (E is dangerous in pregnancy).

3. Drugs — idiosyncratic (flucloxacillin, co-amoxiclav, anti-TB drugs).

4. Ischaemic hepatitis — "shock liver" from hypotension.

5. Pregnancy-related (HELLP, AFLP), Budd–Chiari, Wilson's.

King's College criteria identify patients needing transplant referral:

- Paracetamol: pH <7.3, OR all three of (INR >6.5, creatinine >300, grade III/IV encephalopathy).

- Non-paracetamol: INR >6.5 alone, OR any 3 of 5 (age <10 or >40, non-A/non-B/drug, jaundice >7 days before encephalopathy, INR >3.5, bilirubin >300).

Chronic liver disease and cirrhosis

Cirrhosis = end-stage fibrosis with regenerative nodules disrupting architecture. Mechanism: chronic injury → hepatic stellate cell activation → collagen deposition.

Causes (think ABCDEF):

- Alcohol

- B — hepatitis B

- C — hepatitis C

- D — NAFLD/NASH (now the commonest cause in the West) and Drugs

- E — autoimmunE (PBC, PSC, autoimmune hepatitis), and other metabolic: haemochromatosis (HFE gene, iron overload), Wilson's (ATP7B, copper), α1-antitrypsin deficiency

- F — Fatty liver, cryptogenic

Severity scores

Child–Pugh (5 components, scored 1–3 each, total 5–15):

➡ Bilirubin, Albumin, INR, Ascites, Encephalopathy ("BAIE" or "Pour Another Beer").

- Class A (5–6) = compensated; B (7–9); C (10–15) = decompensated, ~50% 1-year mortality.

MELD (used for transplant prioritisation): bilirubin, INR, creatinine, sodium. Objective, no subjective elements.

Portal hypertension

Portal pressure normally <5 mmHg; clinically significant >10 mmHg; varices bleed >12 mmHg.

Classification by site of obstruction:

- Pre-hepatic: portal vein thrombosis.

- Hepatic: further subdivided —

- Pre-sinusoidal: schistosomiasis, PBC (early).

- Sinusoidal: cirrhosis (by far the commonest).

- Post-sinusoidal: veno-occlusive disease.

- Post-hepatic: Budd–Chiari (hepatic vein thrombosis), constrictive pericarditis, right heart failure.

👩‍⚕️ Examiners often ask: "Cirrhosis causes which type of portal hypertension?" Answer: sinusoidal (some sources say "post-sinusoidal" because of nodular compression of central veins — both appear in exam banks; sinusoidal is the safer answer).

Consequences — follow the porto-systemic anastomoses

Blood backs up into sites where portal and systemic systems meet:

➡ Oesophageal varices (left gastric ↔ azygos)

➡ Caput medusae (recanalised umbilical vein in falciform → epigastric veins)

➡ Anorectal varices (superior rectal ↔ middle/inferior rectal) — distinct from haemorrhoids

➡ Splenomegaly → thrombocytopenia via splenic sequestration (up to 90% of platelets pooled; bone marrow shows megakaryocyte hyperplasia)

➡ Ascites — combination of portal hypertension + hypoalbuminaemia + secondary hyperaldosteronism

➡ Hepatic encephalopathy — ammonia bypasses liver via shunts; treated with lactulose (traps NH₃ as NH₄⁺) and rifaximin.

Liver tumours

Benign

- Haemangioma — commonest benign lesion; "lightbulb" on T2 MRI, peripheral nodular enhancement.

- Focal nodular hyperplasia (FNH) — central scar on imaging; female preponderance; not related to OCP.

- Hepatic adenoma — associated with OCP and anabolic steroids; risk of rupture and malignant change.

Malignant — primary

- Hepatocellular carcinoma (HCC) — commonest primary liver cancer worldwide. Risks: cirrhosis (any cause), chronic hepatitis B (can cause HCC without cirrhosis), aflatoxin (Aspergillus on stored grain). Tumour marker: AFP. Surveillance in cirrhotics: USS + AFP every 6 months.

- Cholangiocarcinoma — bile duct origin; risks: PSC, liver flukes (Clonorchis), choledochal cysts. Marker: CA 19-9.

- Angiosarcoma — rare but classic SBA fodder: vinyl chloride (PVC), arsenic, Thorotrast.

Malignant — secondary

Liver metastases are the commonest malignant lesion of the liver (far more common than primaries in the West). Top primaries: colorectal, breast, lung, pancreas, stomach, melanoma. The portal venous drainage of the gut explains the bowel → liver pattern.

Hepatic abscess

	Pyogenic	Amoebic
Organism	E. coli, Klebsiella, Strep milleri; often polymicrobial	Entamoeba histolytica
Source	Biliary tree (most common), portal (appendicitis), haematogenous	Faecal-oral; travel history
Location	Often multiple	Usually solitary, right lobe
Aspirate	Pus	"Anchovy paste" (sterile on culture)
Treatment	Drainage + IV antibiotics	Metronidazole ± luminal agent (paromomycin); drainage rarely needed

Hydatid disease (Echinococcus granulosus) — sheep/dog exposure, eosinophilia, calcified cyst wall. Do NOT aspirate blindly — risk of anaphylaxis from spillage. Treatment: albendazole + careful surgery (PAIR or pericystectomy) with scolicidal agents.

Liver trauma

Second commonest solid organ injured in blunt abdominal trauma (after spleen). Graded I–VI by AAST.

Management algorithm:

➡ Haemodynamically stable (Grade I–III, sometimes IV) → non-operative management in HDU with serial obs, Hb, and CT.

➡ Unstable → laparotomy. Damage-control: perihepatic packing, Pringle's manoeuvre, then transfer to a hepatobiliary centre.

Absolute indications for surgery: haemodynamic instability despite resuscitation, peritonitis, evisceration/impalement, other indication for laparotomy (e.g. bowel injury).

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Test yourself

A retired PVC factory machinist develops a large, irregular liver tumour on CT. Which lesion is most likely?

• ((Angiosarcoma::☑️ Vinyl chloride, arsenic and Thorotrast are the classic risks for hepatic angiosarcoma.))
• ((Hepatocellular carcinoma::Linked to cirrhosis, hepatitis B/C and aflatoxin — not vinyl chloride.))
• ((Haemangioma::Benign vascular lesion; no occupational link.))
• ((Hepatic adenoma::Associated with OCP and anabolic steroids.))
• ((Cholangiocarcinoma::Linked to PSC, liver flukes and choledochal cysts.))

👩‍⚕️ Occupational history = giveaway: PVC, arsenic, Thorotrast → angiosarcoma.

A haemodynamically stable patient undergoes laparotomy and is found to have a Grade III liver laceration that is not bleeding. What is the most appropriate management?

• ((Washout and close with drain monitoring::Unnecessary intervention for a non-bleeding injury.))
• ((Laparotomy and packing::Reserved for active bleeding or instability.))
• ((Refer to hepatobiliary centre::Not required immediately for a stable, non-bleeding injury.))
• ((Transfer to high-dependency for close observation::☑️ Stable, non-bleeding Grade I–III liver injuries are managed non-operatively.))

👩‍⚕️ Stability — not grade — drives the decision to operate.

A child with kwashiorkor develops hepatomegaly. What is deposited in the liver?

• ((Fat::☑️ Lack of protein → no apolipoproteins → fat cannot be exported → fatty liver.))
• ((Glycogen::Accumulates in glycogen storage diseases, not kwashiorkor.))
• ((Iron::Deposited in haemochromatosis.))
• ((Amyloid::Unrelated to protein-energy malnutrition.))

A 45-year-old man with cirrhosis has splenomegaly and persistent thrombocytopenia. Bone marrow shows megakaryocyte hyperplasia. What is the most likely cause?

• ((Splenic sequestration::☑️ Portal hypertension → congestive splenomegaly → up to 90% of platelets pooled in spleen.))
• ((Decreased thrombopoietin::TPO does fall in cirrhosis, but marrow hyperplasia here shows production is intact.))
• ((Bone marrow failure::Contradicted by megakaryocyte hyperplasia.))
• ((Autoimmune destruction (ITP)::Does not explain the splenomegaly pattern.))

👩‍⚕️ Hyperplastic marrow + big spleen = sequestration, not failure of production.

A 50-year-old shepherd presents with weight loss and tender hepatomegaly. MRI shows a well-rounded calcified liver lesion and FBC reveals eosinophilia. What is the most likely diagnosis?

• ((Hydatid disease::☑️ Echinococcus granulosus from sheep/dog exposure; calcified cyst wall + eosinophilia is classical.))
• ((Hepatocellular carcinoma::Does not calcify or cause eosinophilia.))
• ((Pyogenic liver abscess::Rim-enhancing lesion with sepsis, not calcified.))
• ((Simple hepatic cyst::Thin-walled, no eosinophilia, no calcification.))

👩‍⚕️ Never blindly aspirate a suspected hydatid cyst — risk of anaphylaxis from antigen spillage.

A patient with major liver laceration is bleeding intra-operatively. The surgeon performs Pringle's manoeuvre but bleeding continues. Where is the bleeding most likely coming from?

• ((Hepatic veins or retrohepatic IVC::☑️ Pringle's occludes inflow only (portal vein + hepatic artery); persistent bleeding implicates the venous outflow.))
• ((Portal vein::Would be controlled by Pringle's.))
• ((Hepatic artery::Would be controlled by Pringle's.))
• ((Cystic artery::Too small to cause persistent major bleeding and not in the compressed pedicle here.))

👩‍⚕️ Pringle's tests inflow vs outflow — a key intra-operative decision point.

Which structure is the obliterated remnant of the ductus venosus?

• ((Ligamentum venosum::☑️ Fetal shunt from umbilical vein to IVC; closes at birth.))
• ((Ligamentum teres::Obliterated left umbilical vein, runs in the free edge of the falciform.))
• ((Falciform ligament::Peritoneal fold, not a vascular remnant.))
• ((Median umbilical ligament::Remnant of the urachus, not vascular.))

A cirrhotic patient develops haematemesis from oesophageal varices. Which two venous systems are anastomosing?

• ((Left gastric vein and azygos vein::☑️ The classic porto-systemic anastomosis at the lower oesophagus.))
• ((Superior mesenteric and IVC::No direct anastomosis.))
• ((Splenic and renal::Site of spontaneous splenorenal shunt — not where varices form.))
• ((Superior and inferior rectal veins::Site of anorectal varices, not oesophageal.))

👩‍⚕️ Memorise the four porto-systemic sites: oesophageal, umbilical (caput medusae), rectal, retroperitoneal.

A 60-year-old with known cirrhosis is found to have a 3 cm liver lesion on surveillance ultrasound. Which tumour marker is most useful?

• ((Alpha-fetoprotein (AFP)::☑️ Marker for HCC; surveillance is USS + AFP every 6 months in cirrhotics.))
• ((CA 19-9::Cholangiocarcinoma and pancreatic cancer.))
• ((CEA::Colorectal cancer (and useful in colorectal liver mets).))
• ((CA 125::Ovarian cancer.))

Which clotting factor is typically preserved (or elevated) in acute liver failure?

• ((Factor VIII::☑️ Synthesised by vascular endothelium, not hepatocytes.))
• ((Factor II::Hepatocyte-synthesised, vitamin K dependent, falls early.))
• ((Factor VII::Shortest half-life of all factors — falls first; basis of INR rise.))
• ((Factor X::Hepatocyte-synthesised, vitamin K dependent.))

👩‍⚕️ Normal/high factor VIII distinguishes liver failure from DIC (where VIII drops).

Which segment of the liver hypertrophies in Budd–Chiari syndrome?

• ((Caudate lobe (Segment I)::☑️ Drains directly into the IVC via short veins, bypassing the obstructed hepatic veins.))
• ((Segment IV (quadrate)::No independent venous drainage advantage.))
• ((Segment V::Right lobe segment, drains via right hepatic vein.))
• ((Segment VIII::Right lobe segment, drains via middle/right hepatic vein.))

Which is the commonest malignant lesion found in the liver?

• ((Metastases::☑️ Far more common than any primary liver tumour in the West; commonest primaries are colorectal, breast and lung.))
• ((Hepatocellular carcinoma::Commonest primary liver cancer, but overall less common than mets.))
• ((Cholangiocarcinoma::Less common; arises from bile duct epithelium.))
• ((Angiosarcoma::Rare; linked to vinyl chloride.))

Revision summary

➡ Anatomy: 4 anatomical lobes (right, left, caudate, quadrate); 8 Couinaud segments, each with its own portal pedicle. Caudate (I) drains direct to IVC → hypertrophies in Budd–Chiari.

➡ Ligaments: ligamentum teres = obliterated umbilical vein; ligamentum venosum = obliterated ductus venosus.

➡ Blood supply: portal vein 75% (nutrient-rich) + hepatic artery 25% (oxygenated); both deliver ~50% of O₂. Drainage via three hepatic veins → IVC.

➡ Portal triad in hepatoduodenal ligament: PV (post), HA (medial), CBD (lateral). Pringle's at foramen of Winslow occludes inflow only — persistent bleed = hepatic vein/IVC.

➡ Synthesis: albumin, all clotting factors except VIII. INR rises first (factor VII shortest half-life). Factor VIII normal in liver failure, low in DIC.

➡ LFT patterns: hepatocellular = ALT > AST; cholestatic = ALP, GGT. AST:ALT >2 → alcohol.

➡ Acute liver failure: paracetamol (NAC), viral, drugs, ischaemic. King's College criteria for transplant referral.

➡ Cirrhosis causes: alcohol, hep B/C, NAFLD, autoimmune, haemochromatosis, Wilson's, α1-AT. Severity: Child–Pugh (BAIE: Bilirubin, Albumin, INR, ascites, encephalopathy); transplant prioritisation: MELD.

➡ Portal hypertension (sinusoidal in cirrhosis): varices, caput medusae, anorectal varices, splenomegaly + thrombocytopenia (sequestration), ascites, encephalopathy.

➡ HCC: cirrhosis + hep B; AFP marker; surveillance USS + AFP 6-monthly. Liver mets = commonest malignant lesion overall (colorectal, breast, lung).

➡ Abscess: pyogenic (drain + Abx) vs amoebic (anchovy paste, metronidazole). Hydatid — sheep, eosinophilia, calcified wall, never blindly aspirate.

➡ Trauma: stable + non-bleeding Grade I–III = NOM in HDU. Unstable = laparotomy + packing.