Brief Anatomy

 Five surfaces
 Anterior
 Posterior
 Superior
 Inferior
 Right
 Divided into R, L lobes
 Falciform ligament anteriorly, superiorly
 Fissure of ligamentum teres inferiorly
 Fissure for ligamentum venosum posteriorly
 R lobe >> L lobe (5/6th)
 Caudate, quadrate lobes

 Ligamentum teres represents obliterated umbilical vein

 Ligamentum venosum is the fibrous remnant of ductus
venosus
 The most imortant structure of the liver from the
surgical POV is the porta hepatis. It is a deep fissure in
the inferior surface of the liver situated between the
quadrate lobe in front and the caudate process behind
and through which all the neurovascular and biliary
structures, except the hepatic veins, enter and leave the
liver.

 All these structures are enveloped in the perivascular

fibrous capsule - hepatobiliary capsule of Glisson.
Porta Hepatis

 Portal vein, hepatic artery, hepatic plexus of nerves, bile

ducts enter
 Hepatic ducts, lymphatics leave
Functional Anatomy - Segments
 On the basis of
intrahepatic distribution
of hepatic artery, portal
vein, biliary ducts
 8 segments: each own
hepatic artery branch,
biliary tree
 Useful for planning
surgery
Segments 1,2,3,4 make
up the functional left
lobe
Segments 5,6,7,8 make
Segmental Anatomy
 Segment 1: Caudate lobe
 Segments 2-4: L
hepatectomy
 Segments 2-5, 8:
Extended L hepatectomy
(L trisegmentectomy)
 Segments 5-8: R
hepatectomy
 Segments 4-8: Extended
R hepatectomy (R
trisegmentectomy)
Regulation of Hepatic Blood Flow
 Intrinsic Regulation
 Hepatic arterial buffer response (HABR)
 Metabolic control
 Pressure-flow autoregulation
 Extrinsic Regulation
 Neural Control
 Humoral Control
Regulation of Hepatic Blood Flow
 Intrinsic Regulation
 Hepatic arterial buffer response (HABR)
 Most important regulation
 Changes in PV flow causes reciprocal changes in hepatic artery
flow
 When PV decreases, adenosine accumulates: arteriolar resistance
decreases, hepatic arterial flow increases
 Metabolic control
 Pressure-flow autoregulation
 Extrinsic Regulation
 Neural Control
 Humoral Control
Regulation of Hepatic Blood Flow
 Intrinsic Regulation
 Hepatic arterial buffer response (HABR)
 Metabolic control
 Many blood constituents affect hepatic arterial, PV flow
 Decrease in O2 tension, pH of PV blood increases arterial,
venous flow
 Post prandial hyperosmolarity: increase of flow
 Pressure-flow autoregulation
 Extrinsic Regulation
 Neural Control
 Humoral Control
Regulation of Hepatic Blood Flow
 Intrinsic Regulation
 Hepatic arterial buffer response (HABR)
 Metabolic control
 Pressure-flow autoregulation
 Myogenic response of vascular smooth muscles to stretch
 Stretching (eg HTN): compensatory vasoconstriction
 Regulation less important in ‘fasting states’ (as during surgery)

 Extrinsic Regulation
 Neural Control
 Humoral Control
Regulation of Hepatic Blood Flow
 Intrinsic Regulation
 Hepatic arterial buffer response (HABR)
 Metabolic control
 Pressure-flow autoregulation
 Extrinsic Regulation
 Neural Control
 Vagus, phrenic, splanchnic nerves (post ganglionic T6-T11)
 Sympathetic stimulation: translocation from splanchnic to central
circulation (400-500 ml in seconds)
 Vagal stimulation: alters tone of presinusoidal sphincters: net effect
redistribution of intrahepatic blood without changing total flow
 Humoral Control
Regulation of Hepatic Blood Flow
 Intrinsic Regulation
 Hepatic arterial buffer response (HABR)
 Metabolic control
 Pressure-flow autoregulation
 Extrinsic Regulation
 Neural Control
 Humoral Control
 Hepatic artery: α, β2 adrenergic receptors
 Portal vein: only α receptors
 Differing actions of epinephrine, dopamine, angiotensin II,
vasopressin
 Epinephrine has a biphasic response in the hepatic
arteries, first the apha mediated constriction followed
by a beta mediated dilation. However, in the PV, it
only causes constriction. Dopamine has weak
vasoactive effects in the liver. Angiotensin II causes
decrease in flow because of both mesenteric arterial
and portal vein flow causing a significant lowering of
total hepatic blood flow. Vasopressin, on the other
hand, elevates splanchnic arterial resistance, but lowers
portal venous resistance - may have role in treating
portal HTN.
Brief Physiology
 Multiple Functions
1) Synthetic
Bile salts (conjugation of bile acids with
glycine/taurine: salts of Na or K): enterohepatic
circulation
Proteins:
• Albumin
• Coagulation factors I,II,V,VII,IX,X, fibrinolytic
agents, antithrombotic factors
• Transport proteins: ceruloplasmin ,transferrin
• Angiotensinogen, thrombopoietin, IGF-1
Brief Physiology
 Functions cont…
2) Fat Metabolism
• Oxidation of fatty acids
• Synthesis: cholesterol, phospholipids, most lipoproteins
• Synthesis of fat from proteins, CHO
3) CHO Metabolism
• Storage: glycogen
• Conversion: galactose, fructose to glucose
• Gluconeogenesis
• Formation of many chemical compounds from
intermediate products of CHO metabolism
Brief Physiology
 Functions cont…
4) Vitamin Metabolism
 25 hydroxylation of vitamin D3
5) Breakdown of several proteins/amino acids: Urea
formation
6) Site of erythropoiesis (RBC genesis in early life)
7) Inactivation of various hormones (eg aldosterone,
ADH, insulin, T4), detoxification (eg ethanol)
Brief Physiology
 Functions cont…
8) Excretion of bile pigments, cholesterol, some metals
9) Temperature regulation
10) Immune regulation: Kupffer cells (largest RE organ)
11) Stores iron as ferritin and vitamins A, D, B12
12) Drug metabolism:
 Phase I
 Phase II
 Phase III reactions
 Phase I: Oxidation/reduction/hydrolysis reactions by
microsomal oxidases and hemoproteins of the CYP gene
superfamily to convert drugs to more polar compounds by
insertion of polar groups (OH, NH2, SH) or by removing
non-polar groups.
 Phase II: Increases the polarity of drugs/metabolites by
conjugating reactions with hydrophilic molecules such as
glucuronic acid, acetate, making it more hydrophilic for
excretion in bile/urine.
 Phase III: Uses energy-dependent transporters known as AT-
binding cassette (ABC) transport proteins to excrete drugs
into canalicular bile.
Liver Function Tests
Three categories:
 Markers of acute hepatocyte injury and death
SGPT (AST), SGOT (ALT), AP
 Measures of hepatocyte synthesis function
PT, albumin
 Indicators of hepatocyte catabolic activity
Ammonia
Liver Function Tests
 Transaminases
 Intracellular enzymes found in hepatocytes
 Elevated levels in hepatocyte injury
 Infection
 Ischemia
 Toxins like alcohol, CCL4, some mushrooms etc
 Elevations in “hundreds” : mild injury, in “thousands”:
severe injury
 May be normal in end-stage liver failure
 AST: ALT> 4: Wilson’s Disease;
 AST:ALT ratio 2-4 : alcoholic hepatitis;
 >1 may suggest cirrhosis (mild elevation of both),
 <1: viral hepatitis;
 isolated AST increase: extrahepatic cause
 This test may be NORMAL in end stage liver failure because
there may not be any ongoing acute liver injury because there
are no more viable hepatocytes.

 When AST and ALT are elevated, an AST-to-ALT ratio higher

than 4 is characteristic of Wilson's disease, ratios between 2 and
4 are typical of alcoholic liver disease, and a ratio below 1
suggests nonalcoholic steatohepatitis (without cirrhosis). When
elevations of AST and ALT are mild, ratios above 2 are
consistent with alcoholic liver disease or cirrhosis of any
etiology. If the ratio is elevated and ALT is normal, the
elevation in AST is most likely from an extrahepatic source of
AST.
Liver Function Tests
 Prothrombin Time
 Prolonged PT : decreased Vit K dependent coagulation
factor synthesis: 2,7,9, 10
 “Real” measure of liver synthetic function
Liver Function Tests
 Albumin
 Reflects liver synthetic funtion
 Decreased in advanced cirrhosis, severe acute hepatitis
 Caveats: renal losses, plasma expansion, catabolic states
 Less useful in ‘acute’ fulminant liver disease : long T1/2 (3
wks) [ PT more useful]
 Ammonia
 Metabolite of nitrogen containing products
 Metabolised to urea in liver via Krebs cycle
 Very high levels: fulminant liver failure (poor prognosis)
Liver Function Tests
 Alkaline Phosphatase
 A/w biliary obstruction and cholestasis
 Mild-moderate rise: hepatobilary diseases
 AP>4 times: cholestasis
 Gamma-GT
 Stimulated by alcohol
 Raised in pancreatitis, MI, uremia, COPD, RA
 LDH
 Lacks specificity, use decreasing
 Significant elevation in hemolysis
Pathophysiology
 Central Nervous System
 Up to 80% pts develop acute cerebral edema, raised ICP
 Accumulation of NH3 , Mn, changes in endogenous
transmitters like GABA, glutamate implicated
 Recent evidence: blood breakdown products hemin,
protoporphyrin IX contributory (potent activators of
GABA receptors)
Pathophysiology
 Cardiovascular system
 70 % with end-stage liver disease have a hyperdynamic
state (increased CO and low SVR)
 Due to hepatic bypassing of vasoactive substances
 Recent evidence suggests the role of cannabinoids
 Nitric oxide, cGMP have been implicated as messengers
 Cardiomyopathy
 Possibly due to electrolyte /acid-base imbalance or alcohol abuse
 Atherosclerotic heart disease
 Presence of CAD is a/w high mortality, morbidity: SE is a routine
preop test for adult transplant candidates
 Pericardial effusion
Pathophysiology
 Pulmonary System
 Common complications: restrictive lung disease,
intrapulmonary shunts, V/Q abnormalities, pulmonary
HTN
 Hepatopulmonary syndrome (HPS)
 Portopulmonary HTN (PPH)
Pathophysiology
 Pulmonary System
 Hepatopulmonary Syndrome
 “Triad of chronic liver disease, room air hypoxemia and
pulmonary vasodilation in the absence of intrinsic lung disease”
 Diagnositic Criteria
 Chronic liver disease
 PaO 2 <70 mm Hg or A-a gradient >20 mm Hg
 Intrapulmonary vascular dilatations
 Vasodilation : unclear etiology
 Medical management: disappointing
 Usually resolves after transplantation
Pathophysiology
 Pulmonary System
 Porto Pulmonary Hypertension
 “Raised pulmonary arterial pressures in the setting of liver
disease”
 Pathophysiology: unclear
 Diagnostic criteria:
 Portal hypertension
 Mean pulmonary artery pressure (MPAP) >25 mm Hg
 Capillary wedge pressure (PCWP) <15 mm Hg
 Pulmonary vascular resistance (PVR) >240 dynes.s.cm -5
 Lots of medical treatment options: overall outcome poor
 Grading: Mild, Moderate, Severe
Pathophysiology
 Renal System
 Hepatorenal syndrome
 Functional cause of RF
 Dx: Absence of 1o renal disease, proteinuria, hypovolemia or
hemodynamic cause of renal hypoperfusion
 Result of intense renal vasoconstriction
 Renin-angiotensin-aldosterone system stimulated
 Progressive hypertension
 Dilutional hyponatremia (increased ADH)
 Nephrotoxic antibiotics, contrast avoided, use of cyclosporine
delayed
 Type 1, 2
Pathophysiology
 Renal System
 Hepatorenal syndrome types

Type 1 Type 2
In advanced chronic liver disease same
Histologically kidneys are normal same
Amenable to liver transplant same
Rapid and progressive renal failure Fairly gradual reduction
Commonly precipitated by SBP No known triggers
Without treatment: median survival 3-6 months
14 d
 Type 1 HRS is characterized by a progressive
impairment in renal function and a significant
reduction in creatinine clearance within 1–2 weeks of
presentation. Type 2 HRS is characterized by a
reduction in glomerular filtration rate with an elevation
of serum creatinine level, but it is fairly stable and is
associated with a better outcome than that of Type 1
HRS
Pathophysiology
 Gastrointestinal system
 Esophageal varices, portal HTN, ascites common
 Gastric emptying delayed
 Preoperative treatment of ascites (diuretics, paracentesis,
albumin) decreases mortality
 Importance of optimization prior to transplant
Pathophysiology
 Hematologic system
 Anemia
 Chronic disease, malnutrition, bleeding
 Coagulation defects
 Quantitative and qualitative platelet defects, decreased synthesis
of clotting factors, vitamin K deficiency, synthesis of abnormal
clotting factors, hyperfibrinolysis, DIC
 All clotting factors except III, IV, VIII, vWF synthesized in liver
 Thrombocytopenia
 Splenic sequestration, low levels of thrombopoietin, sepsis, DIC
Pathophysiology
 Drug Metabolism – Anesthesia-related
 Opioids
 Morphine: significantly reduced metabolism; reduce dose, increase
interval
 Fentanyl: even though metabolized by liver, less side effects
 Remifentanyl: opioid of choice
 Sedatives/Hypnotics:
 Despite substantial hepatic metabolism, cirrhosis has minimal impact
on the pharmacokinetic profile
 Neuromuscular blockers
 Vecuronium: avoid
 Rocuronium: prolonged duration
 Atracurium, Cisatracurium: drugs of choice
 Opioids: Morphine if used, should be normally repeated in intervals
exceeding 2-3 times the normal duration.
 Sedatives/hypnotics: Even though all sedatives, hypnotics such as
thiopental, propofol, methohexital, ketamine have variable degree of
metabolism in the liver and are thus expected to have a significant
prolongation of their duration of action or toxicity, end-stage liver
cirrhosis doesn’t seem to have a significant impact on their
pharmacologic profile, at least when used for the duration of
anesthesia.
 NMJ blockers: Aatracurium (nonspecific ester hydrolysis) and
cisatracurium (Hofmann elimination), have elimination half-lives and
clinical durations of action similar to those in normal patients.
Laudanosine, a metabolite of both atracurium and cisatracurium, is
eliminated primarily by the liver; and although its concentration may
increase in patients undergoing liver transplantation, clinically relevant
neurotoxicity has not been reported.
Indications: Liver Transplantation
 Irreversible liver disease with life expectancy <12 mths with no
effective medical or surgical alternatives
 CLD with significant interference with the patient's ability to
work or with his/her quality of life
 CLD with predicted mortality exceeding that of transplantation
(85% one-year patient survival and 70% five-year survival)
Indications
Indications for orthotopic liver transplantations
Cirrhotic disease
Virus-related
Alcoholic cirrhosis
Primary biliary cirrhosis
Crytopgenic cirrhosis
Autoimmune hepatitis
Cancers
Hepatocellular carcinoma
Cholangiocarcinoma
Biliary tract carcinoma
Cholestatic disease
Acute hepatic failure
Metabolic diseases: Wilson’s, hemochromatosis
Others: Budd-Chiari, benign liver tumors, previous
failure
Absolute Contraindications
Absolute Contraindication
Severe cardiopulmonary disease
Irreversible cerebral injury
Sepsis/active infection
AIDS
Extrahepatic malignancy
Active alcohol or drug usage
Psychosocial issue
Vascular
Compensated cirrhosis without
complications
Comment
Worsened by immunosuppresants postop
Disease-free interval should be 2-5 yrs
Abstinence of 3-6 months depeding on
center
Poor medical compliance has bad
outcome
Anatomic anomaly or extensive portal
and mesenteric v thrombosis: technical
difficulty
CTP category A (5-6)
Relative Contraindications
Relative Contraindication Comment
Age>65 years Long term survival poorer in elderly
Severe malnutrition Survival decreases if BMI <19
Other organ failure Except renal failure attributed to liver
status
Previous upper abdominal Technically more demanding
surgery
Poor functional status Severe obesity, wasting
Poor medical compliance
HIV seropositivity
Patient Selection
 Decision more based on severity of dysfunction than
underlying etiology
 Priority is based on specific prognostic criteria
(scoring)
 Child Turcotte classification (CTP)
 Model for end-stage liver disease (MELD)
 Pediatric end-stage liver disease (PELD)
Scoring Systems
 CTP
 Developed in 1998, later modified by Pugh
 Divides patients into three categories: A,
B, C <Points >
Variable <1> <2> <3>
Encephalopathy None 1-2 3-4
Class 5-6
Ascites Absent Slight Moderate A
PT (sec prolonged) <4 4-6 >6 Class 7-9
B
Albumin >3 2-3 <2
Class 10-15
Bilirubin <4 4-10 >10 C
 Problems with this scoring included subjective nature
of assessment of encephalopathy and ascites. Also all
patients with bilirubin >10 (irrespective of the
magnitude) were clumped in one category
Scoring Systems
 Model for end-stage liver disease (MELD): 2002
 Based on three lab values
 Bilirubin, Creatinine, INR
 As good as CTP score, more objective
 MELD = 3.78 (Ln bilirubin) + 11.2 (Ln INR) +
9.75(creatinine) + 6.43
 Interpretation (3-mth mortality)
 >40: 71.3 %
 30-39: 52.6 %
 20-29: 19.6 %
 10-19: 6 %
 <9: 1.9%
Scoring Systems
 Pediatric end-stage liver disease (PELD)
 Children <12 years
 5 variables
 albumin, bilirubin, INR, patient’s age, degree of growth failure
 PELD: 4.80 (Ln bilirubin) + 18.57 (Ln INR) - 6.87(Ln
albumin) + 4.36 (IF <1 year old) + 6.67(IF growth
failure)