ANATOMY, PHYSIOLOGY, FUNCTIONS OF LIVER & LIVER FUNCTION TESTS

Dr Imran.

• Largest organ in the body

• Wt – 1500 to 1600gms

• Reddish brown triangular pyramid shaped, in rt. Hypochondrium and most of epigastrium.

Pancreas

Hepatic artery systemic input

Vena cava systemic outflow

Intestine

Portal venous inflow from gut, spleen and pancreas

Unique Position and Blood Supply of the Liver

Cystic arterysole supply to bile duct

liver

pancreas

spleenPortal vein: 80%

Hepatic artery: 20%

Dual Blood Supply of Liver

Liver has dual blood supply: 80% portal vein 20% hepatic artery

Macro Anatomy

For anatomically divided into 2 left and right lobes with right being bigger.

Functionally divided into lobes by the portal vein into 8 lobes.

Each lobe having a portal vein, branch of hepatic artery and a bile canaliculi.

The biliary system rt and lt hepatic ducts which combine to form common hepatic duct drains to the gall bladder by cystic ducts.

Gall 9cm in length, capacity of 50ml, bld supply from cystic artery, branch of hepatic artery.

Sphincter of ODDI is at the duodenal opening.

It is connected to the diaphragm and abdominal walls by five ligaments:

the membranous falciform (also separates the right and left lobes),

coronary, right and left triangular ligaments,

and the fibrous round ligament (which is derived from the embryonic umbilical vein).

Lobes Of The Liver

Anatomically the liver is divided into a Right and a Left lobe by the falciform ligament

The Right lobe also has two minor lobes- The caudate lobe and The quadrate lobe

Blood Supply: The Liver receives around 1500 ml of blood/min

The blood supply of the Liver is derived from The Portal Vein (80%) and The Hepatic Artery (20%)

Terminal branches of the hepatic portal vein and hepatic artery empty together and mix as they enter sinusoids in the liver.

Sinusoids are distensible vascular channels lined with highly fenestrated endothelial cells and bounded circumferentially by hepatocytes.

12

Splanchnic Circulation

The blood leaves the sinusoids via a central vein , which drains in the hepatic vein.

Claude Couinad

A French surgeon & anatomist who made significant contribution in the field of hepatobiliary surgery ,he was the first to describe segmental anatomy of the liver

Functional divisions of Liver

Middle hepatic vein divides the liver into right and left lobes (or right and left hemiliver). This plane runs from the inferior vena cava to the gallbladder fossa (Cantlie's line)

Right hepatic vein divides the right lobe into anterior and posterior segments

Left hepatic vein divides the left lobe into a medial and lateral part.

Histology

Liver lobules – hexagonal structures consisting of hepatocytes At each of the six corners of a lobule is a portal triad

Portal Triads: Branches of two vessels: portal vein, hepatic artery, along with bile drainage ductules all run together to infiltrate all parts of liver.

Zonal Flow of Blood

Zone 1- Rich in Oxygen, mitochondria

• Concerned with Oxidative metabolism and synthesis of glycogen

Zone 2- transition

Zone 3-

• lowest in Oxygen, anaerobic metabolism, • Biotransformation of drugs, chemicals, and toxins• Most sensitive to damage due to ischemia, hypoxia,

congestion

Hepatic Micro Circulatory Cone

Biliary Tract:

Regulation of Hepatic Blood Flow

Intrinsic Regulation

• Hepatic Arterial Buffer Response -HABR• Pressure flow Autoregulation• Metabolic control

Extrinsic Regulation• Neural Control• Humoral Control

Hepatic arterial buffer system With an intact HABR, changes in portal venous flow

cause reciprocal changes in hepatic arterial flow.

Portal venous flow reduced then there is reduction in hepatic artery resistance.

But not vice versa.

The HABR mechanism involves the synthesis and

washout of adenosine from periportal regions.

Various disorders (e.g., endotoxemia, splanchnic hypo perfusion) may decrease or even abolish the HABR and render the liver more vulnerable to hypoxic injury.

Factors increasing hepatic blood flow: feeding, glucagon, hypercapnia, recumbent position, hepatocellular enzyme induction, ac. Hepatitis.

Factors decreasing: Anesthetic agents, surgical trauma, IPPV, PEEP, bet adrenergic blockade, Hypocapnia, Vasopressin.

PRESSURE FLOW AUTO REGULATION- Hepatic pressure auto-regulation keeps constant

blood flow despite wide fluctuation in systemic BP. The mechanism involves myogenic responses of vascular smooth muscle to stretch.

The hepatic artery exhibits pressure-flow auto

regulation in metabolically active liver (postprandial) but not in the fasting state. Thus, hepatic flow autoregulation is not likely to be an important mechanism during anesthesia.

Pressure-flow autoregulation is nonexistent in the portal circulation.Thus, decrease in systemic blood pressure—as often occurs during anesthesia—typically lead to proportional decrease in portal venous flow

Metabolic Control Decrease in oxygen tension or the pH , ↑ Pco2 of

portal venous blood ,typically lead to increase in hepatic arterial flow.

Postprandial hyperosmolarity increases hepatic

arterial and portal venous flow but not in the fasting state.

The underlying metabolic and respiratory status (e.g., hypercapnia, alkalosis, arterial hypoxemia) also modulates the distribution of blood flow within the liver.

NEURAL CONTROL Fibres of the vagus, phrenic and splanchnic

nerves (postganglionic sympathetic fibres from T6 to T11)enter the liver at the hilum

When sympathetic tone decreases, splanchnic reservoir increases whereas sympathetic stimulation,translocates blood volume from the splanchanic reservoir to the central circulation.

Vagal stimulation alters the tone of the presinusoidal sphincters, the net effect is a redistribution of intrahepatic blood flow without changing total hepatic blood flow.

Humoral Control

Gastrin, Glucagon, Secretin, Bile salts, Angiotensin II, Vasopressin, Catecholamines. Cytokines, Interleukins, and other inflammatory mediators have been implicated in the alteration of normal splanchnic and hepatic blood flow.

FACTORS AFFECTING HEPATIC BLOOD FLOW

INCREASE IN HEPATIC BLOOD FLOW

DECREASE IN HEPATIC BLOOD FLOW

Hypercapnia Acute hepatitis Supine posture Food intake Drug: Beta Agonist

Phenobaritone Enzyme inducers

IPPV Hypocapnia Hyhpoxia Cirrhosis alpha Stimulation Beta blocker Halothane, volatile &

anesthetics Vasopressin

NERVE SUPPLY

Liver is supplied by sympathetic nerve fibres ( T6 to T11).

Parasympathetic fibres – Rt & Lt Vagus.

Fibres from Rt Phrenic nerve.

Some autonomic fibres synapse first with Celiac Plexus whereas others reach the liver directly via splanchnic nerves & vagal branches before forming Hepatic Plexus

FUNCTIONS OF LIVER

1. Vascular functions

2. Metabolic functions

3. Bile formation & Excretion

VASCULAR FUNCTION :

Normal Blood flow – 1500ml/min

25 to 30% from Hepatic Artery

70 – 75% from Portal veins.

Hepatic Artery supplies 45 – 50% of liver’s oxygen requirement

Portal veins supplies the remaining 50 – 55%

The total blood flow from this dual supply represents 25 – 30% of cardiac output

1) RESERVOIR FUNCTION

Portal vein pressure only about 7 – 10mmHg but the low resistance of hepatic sinusoids allows rel. large blood flow through portal vein.

Small changes in hepatic venous tone thus can result in large changes in hepatic blood vol., allowing liver to act as a blood resevoir.

Hemorrhage

↓Decrease in hep. Venous tone

↓

Blood shifts from hep. Veins & sinusoids into central venous circulation & augments

circulating blood vol upto 300ml.

2) Blood Cleansing Function Kupffer cells lining sinusoids are part of monocyte –

macrophage system.

Func – phagocytosis, processing Ag, release of various proteins, enzymes, cytokines & other chem. Mediators.

Phagocytic activity is responsible for removing colonic bacteria & endotoxin entering bloodstream from portal circulation.

Cellular debris, viruses, proteins & particulate matter in blood are phagocytosed

METABOLIC FUNCTIONS

1. Carbohydrate Metabolism

2. Protein Metabolism

3. Fat Metabolism

4. Drug Metabolism

5. Other Metabolic functions

1) Carbohydrate Metabolism

The final products of carbohydrate metabolism are glucose, fructose & galactose.

With exception of large amount of fructose that is converted by liver to lactate, hepatic conversion of fructose & galactose into glucose makes glucose metabolism final common pathway for most carbohydrates.

All cells utilize glucose to produce energy in form of ATP via glycolysis or citric acid cycle

Liver can also utilize the phosphogluconate pathway which not only provides energy but also produces an imp. Cofactor in the synthesis of fatty acids.

Most of glucose absorbed from meal is stored as Glycogen in liver.

When glycogen storage is exceeded in liver, glucose is stored as fat.

Only liver and muscle can store significant amount of glycogen.

Liver and kidney are unique in their capacity to form lactate, pyruvate, amino acids & glycerol.

Hepatic gluconeogenesis is vital in the maintainence of a normal blood glucose concentration.

Glucocorticoids, catecholamines, glucagon & thyroid hormone greatly enhance gluconeogenesis – whereas insulin inhibits it.

2) Fat Metabolism

When carbohydrate stores are saturated liver converts the excess ingested carbohydrates into fat.

Fatty acids thus formed can be used immediately and stored in adipose tissue or the liver for later consumption.

Only RBCs and renal medulla can utilize only glucose.

Neurons normally utilize only glucose but after a few days of starvation they can switch to breakdown products of fatty acids that have been made by liver as an energy source.

3) Protein Metabolism

Liver performs an important function in protein metabolism

Steps include-

1. Deamination from amino acids

2. Formation of urea

3. Interconversion between non essential amino acids

4. Formation of plasma proteins

Deamination Necessary for conversion of excess amino acids to

carbohydrates & fats

Enzymatic processed convert amino acids to their respective keto acids & produce ammonia.

Deamination of alanine plays an important role in hepatic gluconeogenesis.

Liver normally deaminates most of amino acids derived from dietary proteins

Branched chain amino acids are primarily metabolised by skeletal muscle.

Formation of Urea

Ammonia formed from deamination is highly toxic to tissue

2 molecules of ammonia + CO2 – Urea

Urea thus formed readily diffuses out of liver and can be excreted by kidneys

Interconversion between non essential amino acids

Hepatic transamination of appropriate keto acid allows formation of non essential amino acids & compensates for any dietary deficiency in these amino acids

Formation of plasma proteins Nearly all plasma proteins with notable exceptions

of Ig are formed by liver.

Quantitatively the most important of these proteins are albumin, α1 – antitrypsin & other proteases/elastases

Proteins produced by liver Albumin – maintains normal plasma oncotic

pressure and is principal binding & transport protein for fatty acids & large no of hormones & drugs.

All coagulation factors which exception of factor VIII & vonWille Brand factor are produced in liver.

Vit K is necessary co factor in synthesis of Prothrombin, factor VII, IX & X

Liver also produces plasma cholinesterase, an enzyme that hydrolyses esters, including Local anesthetics & Sch

Other important proteins produced are

Protease inhibitors (antithrombin III, α1 – antitrypsin)

Transport proteins (Transferrin, Haptoglobin, Ceruloplasmin)

Complement α1 – acid glycoprotein C – reactive Protein Serum Amyloid - A

Xenobiotic Biotransformation

It is divided into

1. Phase I reaction.

2. Phase II reaction.

3. Phase III reaction.

PHASE I REACTION It is oxidative hydrolysis & reduction reactions

It is mainly microsomal oxidases, CYP isozymes super family.

These CYP isozymes are concentrated in the centrilobular zone.

It needs NADPH for its reactions and hence formation of superoxides and reactive free radicals, more chance of injury to these cells, necrosis.

CYP 450 inhibitors

 Grapefruit juice. erythromycin, isoniazid, sulfonamides, ketoconazole

PHASE II REACTION

Conjugation with the endogenous hydrophilic molecules.

It involves several processes such as glucuronidation, sulphation, methylation, acetylation.

Glucuronidation is the common type.

Hepatic microsomal uridine diphosphate glucuronyl transferase mediates the reaction.

PHASE II contd… These are susceptible to enzyme induction.

Heavy smoking, phenytoin admistration seen to increase glucuronidation in humans.

In some drugs the conjugation ends up with a metabolite more potent than the parent drug. Eg: morphine- becomes morpine 6- glucuronide a potent byproduct which is responsible for some of the analgesia produced by morphine.

PHASE III REACTION It is a energy mediated transport/ elimination by

ATP- binding cassette transport proteins.

Facilitates excretion of xenobiotics and endogenous compounds.

These proteins use ATP hydrolysis to drive molecular transport.

These resides on the canalicular surfaces of hepatocytes and enables biliary excretion of cationic compounds, including anticancer drugs.

Factors affecting Drug Biotransformation

• Genetic factors

• Diet

• Environment

• Age

• Enzyme Induction/Inhibition

• Liver disease

• Cardiac disease

Hepatic drug clearance Factors : rate of hepatic blood flow, protein binding,

hepatic intrinsic clearance.

Drug elimination – is volume of blood from which the drug is completely removed per unit of time.

Is equal to the product of hepatic blood flow and the extraction ratio.

Extraction ratio(E): amt of drug removed from the blood during a simple pass through the liver.

Anesthetics significantly alter extraction by reducing hepatic blood flow.

Inhalational agents may influence drug clearance by altering drug-metabolizing ability or intrinsic clearance

Inhalational agents have been shown both in vitro and in vivo to alter drug metabolism at clinically relevant concentrations.

They are competitively inhibiting p-450, and phase II reactions.

Few drugs with high and low hepatic clearance

High hepatic extraction ratio

Low hepatic extraction ratio

Lignocaine Diazepam

Propranolol Thiopentone

Meperidine Theophylline

Verapamil Digitoxin

Phenytoin

Pancuronium

Other Metabolic Functions Liver plays an important role in hormone, vitamin &

mineral metabolism

Normal thyroid function is dependent on hepatic formation of the more active T3 from T4

Liver is also mojor site of degradation for insulin, steroid hormones, glucagon & ADH

Hepatocytes are principal storage sites for Vit A, B12, E, D & K.

Hepatic production of transferrin & Haptoglobin is important because proteins are important in iron hemostasis.

Coagulation

Hepatocytes make most of the pro-coagulants with exceptions of Factors III, IV, VIII.

Liver also makes protein regulators of coagulation & the fibrinolytic pathways.

Such regulators include protein C, S, Z, Plasminogen Activator Inhibitor, &

antithrombin III

Heme metabolism

Main site.

Hemoglobin is heme and globulin, with heme containing ferrous and porphyrin IX.

20% approx, heme synthesised in the liver.

Rate limiting step is synthesis of 5-aminolevulinic acid catalysed by ALA synthetase.

Bilirubin metabolism Source is from the Heme metabolism.

Approx 300mg of bilirubin formed everyday.

80% by the phagosytosis of scenecent RBCs by the RE cells.

The extracted heme is converted to bilirubin, this is the rate limiting step.

This is then bound to albumin and liver processes the molecules into conjugated bilirubin in 2 steps, and then excreted.

Enterohepatic circulation ensures some of these products to return to the liver.

REVIEW OF ANATOMY AND PHYSIOLOGY

FUNCTIONS OF THE LIVER: Carbohydrate metabolism

GlycogenesisGlycogenolysis Gluconeogenesis

Fat metabolism - ketogenesis

Protein metabolism anabolism deamination urea formation

Secretion of bile Detoxification Metabolism of

vitamins A,D,K,E & Clotting factors,

esp prothrombin Storage Blood store

Liver and Anaesthesia

Anesthesia & anaesthetic drugs affects the hepatic function by following mechanisms :

Alteration in the hepatic blood flow n HABR. Metabolic function. Drug metabolism. Billiary function.

Effect of volatile agents on hepatic blood flow : Halothane: Causes hepatic arterial constincton,

microvascular vasoconstriction

Enflurane: Increase in hepatic vascular resistance

Isoflurane: Increase in microvascular blood velocity

Sevoflurane & Desflurane: Preservation of hepatic blood flow & function

EFFECT OF INTRAVENOUS AGENTS ON HEPATIC BLOOD FLOW

KETAMINE: Little effect on hepatic blood flow

PROPOFOL: Significant splanchnic vasodilator increases both hepatic arterial & portal venous blood flow

THIOPENTONE & ETOMIDATE: Hepatic arterial blood flow reduction, reducedf cardiac output

NEUROMUSCULAR BLOCKING DRUGS

Vecuronium, rocuronium, mivacurium:

• Reduced elimination and Prolong duration of action specially with infusion & repeated doses

Atracurium & cisatracrium:

• Nondependant of hepatic metabolism and can be used without modification of doses in end stage liver disease

REGIONAL ANESHESIA & HEPATIC BLOOD FLOW

Reduction in hepatic blood flow in high spinal & epidural anesthesia

Secondary to hypotension

Reversed by vasopressors like dopamine, ephedrine

Halothane Hepatitis It is immunologically mediated, as it induces both

neoantigens & auto antigens. The incidence of fulminant hepatic necrosis terminating in death associated with halothane was found to be 1 per 35,000.

Demographic factors ; It’s a idiosyncratic reaction, susceptible population include Mexican Americans ,Obese women, , Age >50 yrs, , Familial predisposition, Severe hepatic dysfunction while Children are resistant.

Prior exposure to halothane is a important risk factor & multiple exposure increases the chance of hepatitis.

ISOFLURANE- Isoflurane metabolism yields highly reactive intermediates (TF-acetyl chloride; acyl ester) that bind covalently to hepatic proteins. For this isoflurane most likely causes hepatitis.It undergoes minimal biodegradation, preserves microvascular blood flow & oxygen delivery more than halothane or enflurane . 

DESFLURANE- it is similarly biotransformed to trifluoroacyl metabolites, appears even less likely than isoflurane to cause immune injury because only 0.02 to 0.2% of this agent is metabolized (1/1,000th that of halothane). Desflurane metabolites are usually undetectable in plasma, except after prolonged administration.

Desflurane ↓hepatic blood flow ,it markedly reduce oxygen delivery to the liver and small intestine without producing comparable reductions of hepatic oxygen uptake or hepatic and mesenteric metabolism. Therefore, desflurane anesthesia may decrease the oxygen reserve capacity of both the liver and the small intestine.

SEVOFLURANE - It is metabolized more extensively than isoflurane or desflurane,but slightly less than enflurane, and much less than halothane.The metabolism of sevoflurane is rapid (1.5 to 2 times faster than enflurane), and produces detectable plasma concentrations of fluoride and hexafluoroisopropanol (HFIP) within minutes of initiating the anesthesia. The liver conjugates most of the HFIP with glucuronic acid, which is then excreted by the kidney.

NITROUS OXIDE-

it produces a mild increase in sympathetic nervous system tone leads to mild vasoconstriction of the splanchnic vasculature, leading to a decrease in portal blood flow, and mild vasoconstriction of the hepatic arterial system.

N2O is a known inhibitor of the enzyme methionine synthase, which could potentially produce toxic hepatic effects.

Intravenous Anesthetics-

Etomidate and thiopental at larger doses (>750 mg) may cause hepatic dysfunction by ↓ hepatic blood flow, either from ↑ hepatic arterial vascular resistance or from reduced cardiac output and blood pressure.

Ketamine has little impact on hepatic blood flow, even with large doses

Propofol increases Blood Flow in both the hepatic arterial and portal venous circulation, suggesting a significant splanchnic vasodilator effect

OPIOIDS Opioids have little effect on hepatic function, provided they

do not impair hepatic blood flow and oxygen supply. All opioids increase tone of the common bile duct and the sphincter of Oddi, as well as the frequency of phasic contractions, leading to increases in biliary tract pressure and biliary spasm.

Morphine undergoes conjugation with glucoronic acid at hepatic & extra hepatic site (kidney). The significantly reduced metabolism of morphine in patients with advanced cirrhosis leads to a prolonged elimination half-life, markedly increased bioavailability of orally administered morphine, decreased plasma protein binding, and potentially exaggerated sedative and respiratory-depressant effects. The oral dose of the drug should be reduced because of increased bioavailability

Neuromuscular Blocking Drugs

The volume of distribution of muscle relaxants, may increase due to ↓ albumin an increase in γ-globulin or the presence of edema.so the initial dose requirements of these medications are increased in cirrhotic patients and subsequent dose requirements may be ↓, and drug effects prolonged, owing to ↓ in hepatic blood flow and impaired hepatic clearance, and possible concurrent renal dysfunction.

Neuromuscular Blocking Drugs

Vecuronium-it is a steroidal muscle relaxant It undergoes hepatic elimination by acetylation. Decreased clearance, a prolonged elimination half-life, and prolonged neuromuscular blockade in patients with cirrhosis .

Rocuronium- another steroidal muscle relaxant with a faster onset of action than vecuronium, also undergoes hepatic metabolism and elimination. Hepatic dysfunction can increase the volume of distribution of rocuronium, thereby prolonging its elimination half-life and producing a longer clinical recovery profile and return of normal twitch tension.

Neuromuscular Blocking Drugs Atracurium & Cisatracurium • Elimination half-lives and clinical durations of action

are similar in cirrhotic.82%to Bound albumin they undergo clearance by organ-independent elimination i.e. spontaneous non-enzymatic degradation (Hoffmann's elimination).

• 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

EFFECTS OF HEPATIC DYSFUNCTION OF ANESTHETIC DRUGS

Altered protein binding

Altered volume of distribution

Altered drug metabolism due to hepatocyte dysfuction

EFFECTS OF HEPATIC DYSFUNCTION ON ANESTHETIC DRUGS

Opioids: exaggerated sedative & respiratory depressant effect and Half life is almost doubled

Benzodiazepines : Duration of action increased

Thiopentone, Etomidate, Propofol, Ketamine: Repeated doses & prolong infusion causes accumulation of drugs

Increases risk of hepatic encephalopathy

Effect of surgery

Splanchnic traction and exploratory laparotomy can reduce blood flow to the intestines and the liver

Upper abdominal surgery is associated with the greatest reduction in hepatic blood flow

Elevation of liver chemistry tests is more likely to occur after biliary tract procedures than after nonabdominal procedures

TAKE HOME MESSAGES Liver major organ of metabolism Live dysfuction affects pharmacokinetics of

anesthetic drugs Anesthetic drugs affects liver function Neuroaxial blocks: reduction in hepatic blood flow

due to hypotension Intropetative hypotension, hypoxia, hypocapnia,

use of hepatotoxic drugs in perioperative period can cause postoperative hepatic dysfunction

Liver Function Tests No one test reflects overall hepatic

function. Each test generally reflects one aspect of

hepatic function and must be interpreted in conjunction with other tests alone with clinical assessment of patient.

Liver abnormalities can be divided into 1. Obstructive – affect biliary excretion of

substances2. Parenchymal – result in generalised

hepatocellular dysfunction

Serum Bilirubin Normal total bilirubin - <1.5mg/dl Reflects balance between production &

biliary excretion. Jaundice is usually clinically obvious

when total bilirubin exceeds 2mg/dl >50% conj. Hyperbilirubinemia is ass.

with urinary urobilinogen & may reflect hepatocellular dysfunction, intrahep. Cholestasis or extrahepatic biliary obstruction.

>50% unconj. Hyperbilirubinemia may be seen with hemolysis or cong. Or acquired defects in bilirubin conjugation

Serum Aminotransferases These enzymes are released into circulation

as a result of hepatocellular injury or death. AST is present in many tissues – liver, heart,

skeletal, muscle & kidneys. ALT is primarily located in liver & more

specific for hepatic dysfunction Normal – 35 to 45U/L Mild elevation can be seen in cholestasis or

metastatic liver disease. Abs. levels correlate poorly with degree of

hepatic injury in chronic conditions, but are of great importance in acute liver disease. Eg- drug overdose, ischaemic injury and fulminant hepatitis.

Serum Alkaline Phosphatase Is produced by liver, bone, small bowel,

kidneys & placenta. Excreted into bile Normal level – 25 to 85IU/L Most of circulating enzymes are derived

from bone. Biliary Obstruction – more hepatic alkaline

phosphatase is synthesized and released into circulation.

Increased levels indicate intrahepatic cholestasis & biliary obstruction.

Increased levels in pregnancy & Paget’s disease

INTERPRETATIONSGOT/SGPT BILIRUBIN ALKPO4

BILIARY OBS + ++ +++

HEPATITIS +++ + +

ALCOHOL/DRUGS N/+ ++ N

Serum Albumin

Normal level – 3.5 to 5.5g/dl Albumin level may be normal with Acute

Liver Disease Albumin values <2.5g/dl are generally

indicative of CLD, acute stress or severe malnutrition.

Increased losses of albumin in urine is suggestive of Nephrotic syndrome.

Blood Ammonia

Significant increase of blood ammonia levels usually reflect disruption of hepatic urea synthesis.

Normal whole blood ammonia levels are 47 to 65mmol/L

Increase usually reflect severe hepatocellular damage.

Prothrombin Time Normal level is 11 to 14secs. (Measures the

activity of fibrinogen & factors V, VII & X) Relatively short half time of factor VII (4 to

6Hrs)make PT useful in evaluating hepatic synthesis function of pt with ALD or CLD.

Prologation of PT >3 to 4s from control are considered significant.

Only 20 to 30% of normal factor activity is required for normal coagulation, prolongation of PT reflects severe liver disease unless Vit K deficiency is +

Failure of PT to correct following parenteral administration of Vit K implies severe liver disease

Lactate Dehydrogenase Elevated serum LDH levels -

hepatocellular injury, extrahepatic disorders or both.

Extreme increases – massive liver damage – fulm. Viral hepatitis, drug induced failure or hypoxic hepatitis.

Prolonged concurrent elevation – malignant infiltration of liver.

Notable hep disorders – hemolysis, rhabdolysis, tumor necrosis, renal infarction, acute CVA or MI. (severe ecclampsia)

TESTING FOR SP. DISEASES

Targeted testing is used to identify specific hepatic or biliary diseases.

Examples include – 1. Serologic testing to identify viral,

microbial & autoimmune causes.2. Genetic testing to diagnose heritable

metabolic disorders.3. Tumor marker assays to detect hepatic

malignancies

Identifying viral markers – antibodies, antigens and genetic material – is the key for diagnosis of hepatitis from hepatotropic viruses (A, B, C, E) and herpesviruses such as CMV & EBV.

Special tests – serum α1 – AT and phenotype analysis.

Markers for hepatic malignancy – AFP, des – γ – carboxylated prothrombin.

Other tests

CBC- Hb may show anemia esp with the target cells in jaundiced patients due to macrocytosis.

Leucopenia- complicates portal HTN and hypersplenism.

Leucocytosis- in hepatic abscess, alcoholic hepatitis, cholangitis.

Thrombocytopenia- in cirrhosis, due to dec in thrombopoetin in liver, and hypersplenism.

Thank You

Risk Stratification Child-Pugh Score Model of End-Stage Liver Disease

Score(MELD)

Child-Turcotte-Pugh (CTP) score

initially designed to stratify the risk of portacaval shunt surgery in cirrhotic patients

based upon five parameters: serum bilirubin, serum albumin, prothrombin time, ascites and encephalopathy

good predictor of outcome in patients with complications of portal hypertension

Child-Turcotte-Pugh M&M for pts undergoing intra-abd

surgery Incorporates three biochemical(PT,

albumin, bilirubin) Incorporates three clinical

features(Nutrition, +/-ascites, encephalopathy

Cirrhosis: Child-Pugh Score

Points Assigned 1 2 3

Laboratory value

Bilirubin (mg/adL) < 2 2-3 > 3

Albumin (g/dL) > 3.5 2.8-3.5 < 2.8

PT orINR

< 4 s< 1.7

4-6 s1.7-2.2

> 6 s> 2.2

Signs

Ascites None Slight Moderate

Encephalopathy None Stages 1-2 Stages 3-4

Child class A = 5-6 points; Child class B = 7-9 points; Child class C = 10-15 points

Child CG, Turcotte JG. Surgery and portal hypertension. In: The Liver and Portal Hypertension. Child CG, ed.

Philadelphia: Saunders; 1964:50-64. Pugh RNH, et al. Br J Surg. 1973;60:648-652.

MELD SCORE

Created in 1999 to predict 3 month mortality in pts with chronic dz.

Prioritizes those on transplat list

Looks at bilirubin,INR,and serum creatinine

MELD SCORE

>8: predictive of poor

>24: qualifies for transplantation