Basic Science: Liver Anatomy and Physiology

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Basic ScienceLiver Anatomy and Physiology

• Andrew Wright MD
• 11/14/01

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Embryology

• 4th Week of Development
• Projection from ventral wall of Midgut
• Cranial Bud ? Liver
• Caudal Bud ? Gallbladder, extrahepatic biliary
  tree
• Ventral Pancreas

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Embryology

• Bile ducts develop from hepatocytes, originating
  at hilum
• 7th Week
• Biliary lumen recanalize
• 12th Week
• Liver begins to secrete bile

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Developmental Anomalies

• Agenesis rare
• Left lobe agenesis reported
• Reidels Lobe
• Long tongue of liver extending inferiorly from
  right lobe
• Usually asymptomatic, may be associated with
  colonic or pyloric obstruction
• Heterotopic liver tissue
• Gallbladder, pancreas, adrenals, omphalocele

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Anatomy

• Position
• Between 4th intercostal space and costal margin
• extends across midline

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Anatomy

• Glissens Capsule
• Peritoneal Membrane
• Peritoneum
• Bare patch under diaphragm next to IVC

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Ligaments

• Falciform
• Attaches to anterior abdominal wall from
  diaphragm to umbilicus
• Includes Ligamentum Teres (round ligament) at
  inferior border
• Former Umbilical Vein
• May recanalize in portal hypertension

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Ligaments

• Right and Left Coronary
• Connect diaphragm to liver
• Lateral aspects become Triangular Ligaments

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Ligaments

• Gastrohepatic
• Anterior layer of lesser omentum
• Continuous with Left Triangular Ligament
• Hepatoduodenal
• Anterior border of Foramen of Winslow
• Contains Portal Triad

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Topographic Anatomy

• Right
• Left
• Quadrate
• Caudate

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Lobar Anatomy (American System)

• Right and Left Lobe determined by Cantlies Line
  (portal fissure)
• Gallbladder Fossa to IVC

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Segmental Anatomy (Couinaud System)

• Caudate Lobe
• Segment I
• Left Lobe
• Segments II IV
• Right Lobe
• Segments V-VIII

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Segmental Anatomy (Couinaud System)

• Caudate Lobe
• Segment I
• Left Lobe
• Segments II IV
• Right Lobe
• Segments V-VIII

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Portal Vein

• 75 of hepatic blood flow
• 1-3cm diameter
• 5-8cm length

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Portal Vein

• Laminar Blood flow
• Affects distribution of amebic abscesses and
  tumor metastases

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Portal-Systemic communication

• Submucosal veins of distal esophagus and proximal
  stomach
• Umbilical and periumbilical veins
• Caput Medusae
• Cruveilhier-Baumgarten bruit
• Tributaries of inferior mesenteric arteries
• Superior hemmorhoidals
• Retroperitoneal communication
• Adrenal veins

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Hepatic Artery
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Hepatic Artery

• Cautions
• Only 55-65 of population has normal hepatic
  arterial anatomy
• Aberrant R hepatic artery may be mistaken for
  cystic artery
• Cystic artery may originate from the
  gastroduodenal artery, the left hepatic artery,
  or the common hepatic artery

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Biliary System

• Triangle of Calot
• Cystic Duct, Common Hepatic Duct, and hilum of
  liver

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Biliary Anomalies
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Hepatic Veins

• Short extrahepatic segment
• Right
• Middle
• Usually joins left
• Left
• Direct communication to IVC from Segment I
  (caudate)

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Lymphatics
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Microscopic Anatomy

• Acinus
• Zone I
• Krebs Cycle
• Zone II
• Zone III
• Cytochrome P-450
• 1st to experience hypoxia
• Lymph generated in perisinusoidal Space of Disse

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Hepatocytes

• Numerous mitochondria
• Glycogen-rich
• Many lysosomes, endosomes, and peroxisomes
• Catabolism of endogenous substances and exogenous
  wastes

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Hepatocytes

• Liver microsomal fraction
• Golgi bodies and endoplasmic reticulum
• Glycogenolysis
• Synthesis of cholesterol and bile salts
• Esterification of free fatty acids to
  triglycerides
• Protein synthesis and glucuronidation

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Hepatic Physiology

• Interface between abdominal viscera and systemic
  circulation
• Energy Metabolism
• Detoxification
• Bile Production
• Filtration of pathogens
• Metabolism of vitamins, hormones, drugs, toxins,
  metals, porphyrins

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Energy Metabolism

• Anabolism
• Local
• Glycogen
• Distant
• Fatty Acids, glycerol and lipoproteins
• Catabolism
• Glycogenolysis
• Produce circulating glucose
• Gluconeogenesis and ketogenesis

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Protein Synthesis

• Albumin
• 10gm synthesized daily
• Binds many molecules
• Bilirubin
• Thyroid hormone
• Cortisol
• Testosterone
• Metals
• Drugs

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Protein Synthesis

• ?-Fetoprotein
• Fetal equivalent of albumin
• Other transport/carrier proteins
• Transferrin
• Haptoglobin
• Ferritin
• Ceruloplasmin
• All procoagulant factors except von Willebrand
  factor

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Detoxification

• Phase I
• Cytochrome P-450
• Oxidation, reduction, hydrolysis
• Phase II
• Transferase enzymes
• Conjugation
• Urea Cycle

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Reticuloendothelial System

• Kuppfer Cells
• Antigen Presenting Cells
• Monocyte/Macrophage lineage
• Clearance of particulate matter
• Destroy microorganisms from alimentary tract
• Clear old blood cells and cellular debris
• Remove endotoxin
• Cell-signaling function
• Prostaglandin, interleukins, TNF, other cytokines

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Bile Production

• 500-1000cc per day
• 85 water
• Components
• Bilirubin
• Bile Salts
• Phospholipids
• 95 lecithin
• Cholesterol

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Bilirubin

• Breakdown product of red blood cells
• Low solubility
• Conjugated by glucuronyl transferase
• High water solubility
• Actively secreted

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Bile Salts

• Steroid molecules
• Solubilize lipids
• Unconjugated
• Cholic and chenodeoxycholic acid
• Bacterial Alteration to 2o Bile Salts
• Conjugated with taurine or glycine
• Deoxycholate and lithocholate

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Bile Circulation

• Enterohepatic Circulation
• Bile salts absorbed in illeum and returned to
  liver
• Bile acids recirculate 6-15x/day
• Loss of enterohepatic circulation
• Regional enteritis, ileal resection,
  Zollinger-Ellison syndrome, radiation enteritis,
  and blind loop syndrome
• Results in diarrhea, steatorrhea, and/or B12
  deficiency

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Bile Production

• Neural Control
• Increase by vagal stimulation
• Decreased by splanchnic stimulation
• Decreased hepatic blood flow
• Endocrine Control
• Increased by secretin
• Also CCK, gastrin and cerulean

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Bile Composition

• Micelle Formation
• Maintains cholesterol in solution
• Depends on ratio of cholesterol, bile salts, and
  phospholipids
• Crystal Formation
• Bile supersaturated with cholesterol
• Can be predicted by cholesterol saturation
  (lithogenic) index gt1

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Gallbladder Function

• Absorption
• 90 of Water absorbed in 4 hours
• Enhanced by unconjugated Bile Salts
• Elevated in systemic bacterial infections
• Increased tendency for cholesterol crystal
  formation
• Secretion
• Glycoproteins
• H

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Gallbladder Function

• Motor Function
• Release of bile requires coordination of GB
  contraction and Sphincter of Oddi relaxation
• Spiral valves of Heister
• Control bile output of gallbladder
• Empties 50-70 in 30 minutes
• Refills over 90 minutes
• Mediated by CCK
• Also active during MMC III due to motilin

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Liver Function Tests

• Capacity to transport ions and metabolize drugs
• Injury to hepatocytes
• Biosynthetic pathway
• Detoxification capacity

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Capacity to transport ions and metabolize drugs

• Bilirubin
• Unconjugated
• Overproduction (hemolysis)
• Impaired conjugation (Gilberts)
• Decreased hepatic uptake
• Conjugated
• Parenchymal disease
• Biliary obstruction
• Defective excretion (sepsis, drug toxicity,
  pregnancy)

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Hepatocyte Injury

• Transaminases
• ALT more sensitive and specific than AST
• LDH
• Specificity poor
• Alkaline Phospatase
• From canalicular membrane
• Represents cholestasis

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LFTs

• Biosynthetic pathway
• Prolonged PT
• Decreased albumin
• Transferrin better reflects acute change
• Detoxification capacity
• Ammonia

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Hepatic Pathophysiology

• Congenital disorders
• Inflammatory Disorders
• Cirrhosis
• Neoplasms

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Congenital Disorders

• Cyst
• Simple
• Polycystic
• Surgical management indicated for symptomatic
  cysts
• High recurrence with non-operative management

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Congenital Disorders

• Carolis Disease
• Multiple cystic dilatations of the intrahepatic
  ducts
• Associated with congenital hepatic fibrosis
• Biliary colic and cholangitis common
• Treatment includes drainage and/or resection

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Inflammatory Disorders

• Abscess
• Ameobic
• Most common worldwide
• More common in Southwestern states
• Surgical intervention rarely necessary
• Respond to metronidazole
• Pyogenic
• More fulminant
• Usually require drainage

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Inflammatory Disorders

• Parasitic Infections
• Schistosomiasis
• Liver Fluke
• Bile stasis and inflammation
• Increased choledocholithiasis, cholangitis, and
  cholangiocarcinoma

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Inflammatory Disorders

• Hyatid Disease
• Echinococcus tapeworm
• Multilocular, calcified cyst with scolieal sand
• Avoid percutaneous drainage

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Inflammatory Disorders

• Viral Hepatitis
• A
• Self-limited
• Gastrointestinal symptoms more pronounced
• B
• 10 Chronic
• C
• 50 Chronic
• Toxic Hepatitis

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Cirrhosis

• Final Common Pathway
• Alcohol, hepatitis most common
• Result of regeneration
• Nodular parenchyma with diffuse fibrosis
• Types
• Micronodular (lt3mm)
• Mixed
• Macronodular (gt3mm)

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Cirrhosis

• Hepatocellular Failure
• Portal Hypertension
• Overgrowth of fibrous tissue results in
  functional obstruction of hepatic venules
• Ascitis
• High portal pressure
• Low intravascular colloidal pressure
• Sodium retention
• May require shunting

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Benign Neoplasms

• Bile Duct Hamartomas
• Fibrotic nodule
• May mimic small metastatic disease
• Hemangiomas
• Central Scar
• Spontaneous hemorrhage rare, may be observed
  safely

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Benign Neoplasms

• Adenoma
• Young women, associated with OCPs
• Prone to rupture and hemorrhage
• Malignant change possible
• Focal Nodular Hyperplasia
• Young women, associated with OCPs
• Bleeding uncommon

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Hepatocellular Carcinoma

• Incidence
• 95 of primary liver tumors
• 1.25 million deaths/year
• Incidence has doubled in last 20 years
• 90 of HCC arises in cirrhotic liver
• HBV, HCV, ETOH
• Aflatoxin
• Aspergillus flavus
• Found in wheat, soybeans, corn, rice, oats,
  bread, milk, cheese, and peanuts

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Hepatocellular Carcinoma

• Other risk factors
• Tamoxifen, oral contraceptives, and androgens?
• Wilson's disease, tyrosinemia, glycogen storage
  disease, blood group B, parasites, porphyria,
  organochloride pesticides, hemochromatosis, alpha
  1 -antitrypsin deficiency, and cigarette smoking

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Hepatocellular Carcinoma

• Treatment
• Resection
• Ablation
• Prognosis
• 11-48 5 year survival post-resection
• Higher in Asian series due to earlier detection
• Transplant may offer even or better survival
• Number of tumors, AFP, and tumor size
• Also portal vein involvement, margin, cirrhosis,
  age, and histology

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Hepatocellular Carcinoma

• LFTs most indicative of underlying chronic liver
  disease
• ?-fetoprotein elevated in 50-75
• Fibrolamellar variant
• Non-cirrhotic, younger patients
• More favorable prognosis
• 2/3 in left lobe

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Primary Malignancies

• Other Primary
• Hepatoblastoma
• lt3 years of age
• 50 survival
• Cholangiocarcinoma
• Intra- or extra-hepatic
• 15-20 5 year survival post-resection
• Cystadenocarcinoma
• May arise from adenoma

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Primary Malignancies

• Other Primary
• Sarcoma
• Associated with exposure to Vinyl Chloride or
  Thorotrast
• Poor prognosis

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Secondary Malignancies

• Widespread metastatic disease
• Lung, prostate, colon, breast, pancreas, stomach,
  kidney, and cervix
• 40 of patients dying with a solid tumor develop
  liver metastases

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Secondary Malignancies

• Isolated Site
• Colorectal cancer, carcinoid, gastric
  leiomyosarcoma
• CEA
• Resection may offer cure
• Up to 60 5-year survival
• Prognosis based on size, number of metastases,
  and presence of residual local disease
• Hepatic Arterial Infusion

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Biliary Pathophysiology

• Congenital
• Biliary Atresia
• Theories
• Failure of recanalization of bile ducts
• Inflammatory process
• Treatment
• 60-80 survival with hepatic portoenterostomy
  (Kasai)
• Transplant is definitive therapy
• Choledochal Cysts
• Premalignant due to stasis and inflammation
• Complications include pain, obstruction, stone
  formation, and cholangitis

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Calculus disease

• Incidence 10
• More common in females and elderly
• Pathogenesis
• Cholesterol Saturation
• Nucleation
• Pronucleating factors in bile sludge
• Stone Growth

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Acute Cholecystitis

• 10-20 of Calculus disease
• Pathogenesis
• Obstruction of cystic duct
• Prostaglandins result in fluid secretion into
  gallbladder
• Edema of gallbladder wall
• Perforation or Necrosis
• Perfusion impaired by luminal distension
• Bacterial infection secondary

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Cholangitis

• Charcots triad
• Fever, Pain, Jaundice
• Bacteremia
• Bacterial infection
• Increased biliary pressure (obstruction)
• Reflux of bacteria into hepatic veins

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Motility

• Biliary symptoms without stone disease
• Sphincter of Oddi
• Calcium channel blockers
• Sphincterotomy
• Gallbladder
• Cholecystectomy

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Benign Stricture

• Usually follows injury
• Open Chole 0.1-0.2
• Lap Chole 0.3-0.5
• Learning curve
• Ischemia
• Aggressive dissection of common duct
• Inflammatory reaction
• Bile leak

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Primary Sclerosing Cholangitis

• Cause unknown
• Associated with Ulcerative Colitis
• Fibrous strictures of intra and extra-hepatic
  bile duct
• Treatment
• Biliary reconstruction
• Transplant
• Proctocolectomy in UC not helpful

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Neoplasm

• Gallbladder Cancer
• Usually adenocarcinoma
• Associated with stone disease
• Cholangiocarcinoma
• Most frequently perihilar
• Associated with sclerosing cholangitis,
  ulcerative colitis, choledochal cysts, and liver
  flukes
• Bile stasis, chronic inflammation, and reflux of
  pancreatic secretions are likely factors