5Important points in History Duration of JaundiceProgress & previous attacks of jaundiceProdromeFeverAbdominal pain: Biliary/pancreatic/DullPruritis, Colour of urine and stoolDrug ingestionManifestations of fat soluble Vit deficiencyWeight lossVitamin deficiency: A; night blindness. D: bone pain & muscle weakness: E: leg cramps, K: Easy bruisingJaundice: sudden or gradual, first noticed at placeProgressively worsening jaundice- Malignancy, primary biliary cirrihosis, familial cholestasis, primary sclersing cholangitis, advanced end stage liver disease,Intermittent jaundice: choledocholithiasis, ampullary carcinoma ( sloughing of tu mass), biliary ascariasis, relapsing viral hepatitisSudden onset, progressive steadily deepening obstructive jaundice, weight loss – malignancy
6History suggestive of Normal colored urine/cola color in hemolysis Recurrent episodesRecurrent anaemiaNo prodromePainChills, fever, systemic illnessBiliary surgeryUnconjugated hyperbilirubinemia/hemolysisClay stools – complete biliary obstructionweight loss and its significance – 5% is considered significant, loss of appetite and ass with malignancyAbdominal pain: suggests extrahepatic cause of cholestasis:Biliary colic: severe intermittent colicky pain It is a visceral pain, which is steady rather than intermittent, usually in the epigastrium and right upper quadrant, increases over a period of 15 min to 1hour or more, and then slowly resolving within 6 hours.Pancreatic pain: Dull, continuous pain radiating to back, aggravated by food, and relieved by sitting up or leaning forward.Dull, continuous, dragging type of pain in right hypochondrium- stretching of Glisson capsule due to hepatomegaly.Prodromal symptoms at or before onset: Suggestive of viral hepatitis/drug induced hepatitisGradual or sudden, how much weight loss and its significanceGeneralized pruritis, Clay coloured stool and tea coloured urineBile duct stones/cholangitis/obstructive jaundice
7History suggestive of Cholestasis Contact with other jaundiced patient History of injections or blood transfusionsExposure to drugsProdrome of anorexia, nausea, vomitingPruritisClay coloured stoolsVH/Drug induced HepatitisClay stools – complete biliary obstructionweight loss and its significance – 5% is considered significant, loss of appetite and ass with malignancyAbdominal pain: suggests extrahepatic cause of cholestasis:Biliary colic: severe intermittent colicky pain It is a visceral pain, which is steady rather than intermittent, usually in the epigastrium and right upper quadrant, increases over a period of 15 min to 1hour or more, and then slowly resolving within 6 hours.Pancreatic pain: Dull, continuous pain radiating to back, aggravated by food, and relieved by sitting up or leaning forward.Dull, continuous, dragging type of pain in right hypochondrium- stretching of Glisson capsule due to hepatomegaly.Prodromal symptoms at or before onset: Suggestive of viral hepatitis/drug induced hepatitisYellowish: sudden or gradual, first noticed at placeGradual or sudden, how much weight loss and its significanceGeneralized pruritis, Clay coloured stool and tea coloured urineCholestasis
14General Examination Body mass index Vital signs: Pulse Pallor: GI bleeding, HemolysisIcterusPedal oedema: hypoproteinemia/cirrihosisShiny nail & scratch marks (pruritis)XanthomaEcchymosis, Bitot spots (Vitamin deficiency)
15Abdomial Examination Abdominal distension, distended veins, scar HepatomegalySplenomegalyGall bladder or any mass,Free fluid
16Define Jaundice and where all you will look for this? Bilirubin has high affinity to elastin, and scleral tissue is rich in elastin , therefore scleral icterus is a more sensitive sign of hyperbilirubinemia than generalised jaundiceSites: Sclera, undersurface of the tongue, palms, nails, skin
17Excess plasma bilirubin Normal range < 1 mg/dl Yellowish pigmentation of the sclera, skin, mucous membrane & other tissues: JauneExcess plasma bilirubinNormal range < 1 mg/dl(I: mg/dl;D:0.1—0.4mg/ dl, <5% in Conjugated form)Clinically obvious 2-3 mg/dlSites – Sclera, undersurface of the tongue, palms, nails, skin, hard-palateHigh Affinity for Collagenous tissueBilirubin has high affinity to elastin, therefore scleral icterus is a more sensitive sign of hyperbilirubinemia than generalised jaundiceSites: Sclera, undersurface of the tongue, palms, nails, skinD/D – carotemia, treatment with quinacrine, no scleral icterus
19Bilirubin Metabolism Bilirubin production: 250-350mg/day Ret En System Plasma Liver BileHeme oxygenase Biliverdin reductaseHaem BVD UCB UCB UCBAlbumin70% 30% BMG BMGBMG & BDGHb other BDG BDGhaemoproteinsGlomerulus UrineBilirubin production: mg/day
20Portal veinthe conjugated bilirubin is hydrolyzed and converted to urobilinogen by the intestinal pathogens.The urobilinogen is then oxidized to orange-color stercobilin and excreted in the stool. The yellowish color of stool is the color of the sterocobilin. Therefore, the clay color stool means that there is no bilirubin coming from biliary ducts owing to the obstruction of the bile ducts.About 15 ~ 20 % of the urobilinogen is reabsorbed from the intestine into portal veins and finally 90 % of it is returned to the liver and is re-excreted in the bile, this is called entero-hepatic circulation of bilirubin. The remainding 10 % gets into the systemic circulation and finally exreted in the urine through kidney as urobilin.In obs. J the conj bil enters the gen cir. through hepatic vein and is excreted in urine.
21How will you Differentiate the three types of Jaundice Biochemically?
22FeaturesPrehepatic (hemolytic)Intrahepatic HeptocellularPost-hepatic (Obstructive)UCB↑NormalCBAST or ALT↑↑SAPUrine BilirubinAbsentPresentIncreasedUrobilinogen
23FeaturesPrehepatic (hemolytic)Intrahepatic HeptocellularPost-hepatic (Obstructive)Plasma AlbuminNormalDecreasedNormal or decreasedPTIncreasedIncreased but correccted by Vitamin K
27What are the Pathophysiological consequences of Obstructive / Cholestatic Jaundice?
28Consequences of Cholestasis Retention of bile salt in liverDecreased hepatocyte functionDysfunction of Cyto -450Albumin & clotting factors synthesis decreasedDecreased Kuffer cell activityBile constituents in serumJaundice, PruritisCVS depressionNephrotoxicityHypercholesterolemia, atheroma, XanthomaPruritis: Exact pathology is not known:Central mechanism: Increase central opioidoergic tone in patients with cholestasisPeripheral Mechanism: accumulation of numerous substances (bile acids, histamine, serotonin & endogenous opioids) in the systemic circulation subsequent to failure of elimination
29Consequences of Cholestasis Absence of bile in IntestineEscape of endotoxins into portal bloodMalabsorption of fats, Vit A, D, E & KClay colored stoolsPruritis: Exact pathology is not known:Central mechanism: ↑ central opioidoergic tonePeripheral: accumulation of bile acids, histamine, serotonin & endogenous opioidsPruritis: Exact pathology is not known:Central mechanism: Increase central opioidoergic tone in patients with cholestasisPeripheral Mechanism: accumulation of numerous substances (bile acids, histamine, serotonin & endogenous opioids) in the systemic circulation subsequent to failure of elimination
30Anaesthetic Problems associated with Obstructive Jaundice
31Anaesthetic Problems: CVS Impaired myocardial contractilityBradycardiaVasodilatation ↓ ability to mobilise blood from splanchnic vasculature during haemorrhage↓ sensitivity to vasopressors Hypotension & circulatory collapseSmall blood losses poorly toleratedReplace volume losses immediately in perioperative periodbradicardia
32Anaesthetic Problems: Renal system Etiology MultifactorialArterial hypotension-myocardial depressionReduction in intravascular volumeNephrotoxicity - bile salt, endotoxins & Inflammatory mediatorsIncidence 5 -10%, mortality: 32 – 100%Level of hyperbilirubinemia correlates with postoperative decrease in creatinine clearance
33Anaesthetic Problems: Sepsis Associated cholangitis and bactibiliaEscape of endotoxins from intestine portal blood↓ kuffer cell activityPreventionPerioperative antibioticsPreoperative oral bile salts
34Anaesthetic Problems: Coagulopathy • Vit. K malabsorption(Activation II,VII,IX,X ) ↑ PTPre-op. Vit. K 10 mg OD × 3 days• long lasting biliary obstruction Sec. biliary cirrhosis ↓ syn. of coag factors(poor prognosis) transfusion of FFPVit K acts as cofactor in synthesis of coagation factors by gamma- carboxylation of glutamate residues
35Anaesthetic Problems Multiple Vitamin Deficiency - A, D, E, K ( A - night blindness ,D – osteoporosis and ms weakness, E- leg cramps ,K- easy bruising )Haemorrhagic gastritis and stress ulcerImpaired wound healingAltered drug handling due to cholestasisLong standing extrahepatic biliary obstruction > 1yr → biliary cirrhosis → problems of liver dysfunction
37Assessment for liver cell injury S. BilirubinTransaminase SGOT/SGPT – 35 IU/LSGOT -extrahepatic- heart/sk ms/kidney/brain:less specificSGPT - primarily found in liver, more specificAlcoholic hepatitis SGOT/SGPT > 2 (deficiency of pyridoxine-5-PO4 )Alkaline phosphatase – 35 – 100 IU/LExtrahepatic- bone, intestine, liver, placenta5- Nucleotidase - confirms hepatic origin of ALPGamma Glutamyl Transpeptidase – most sensitive indicator of biliary tract diseaseUNCONJ BIL> 80% - UNCONJ HYPERBILIRUBINEMIACONJ BIL > 50% - CONJ HYPERBILIRUBINEMIAIn general SGOT & SGPT levels parallel each otherAST/ SGOT, ALP/SGPT , GAMMA GLUTAMYL TRANSPEPTIDASE
38Aminotransferases Alk PO4 Diag. Likelihood Viral hep Obstr.> X 6 < X % 10%< X 6 > x % 80%Parenchymal diseases ultimately produce an obstructive component & Long standing Obstructive diseases cause cellular dysfunction
39Assessment of Synthetic Ability of Liver • Prothrombin time – factors II, VII, IX & Xshort t ½ hrGood Indicator of liver fn. in both Acute & ChronicLiver disease.D/D - Obst. jaundice parentral vit. K → PT normalisesin 24 – 48 hrs• Serum albumin – t ½ life daysLiver – substantial reserve for alb. syn.Not a good indicator for acute or mild liver damageIndicator of severity of chronic liver disease< 2·5 gm% - severe damageAlbumin - Albumin daily prod. 10—15g/d ( gm%)Function – Plasma oncotic press. ,transport vehicle, Drug binding
40What are the other Preoperative Investigations required ?
41Preoperative Investigations Hb - ↓ in concealed blood loss, haemolysis,TLC, DLC - ↑ infectionPlatelet Count , clotting studies - PT, PTTKUrea, S. Creatinine, ElectrolyteHBV, HCVChest X-ray, ECG, blood gasesSevere acute & chr. Liver disease are chr. By failure to syn urea & fall in its plasma conc. & rise in conc. Of ammonia.
43InvestigationsUSG-Abd: solid mass in distal CBD, dilated CBD, Intrahepatic Biliary distension with distended GB with hepatomegalyDual Phase CT: Mass at lower end of CBD with dilated upper stream Biliary systemEndoscopy US: Mass in uncinate process likely malignant
52Troisier’s sign Enlargement of Left Supraclavicular Lymph Node due to Secondary involvement seen in malignancies ofG.I.T., Breast and Testis.
53Courvoisier’s lawIf the CBD is obst. due to calculus , the GB is usually not distended owing to previous inflammatory fibrosis.In obstr. of the CBD due to growth, the GB becomes distended in order to reduce the press. in the biliary system.
54What are the Surgical Procedures done for Obstructive Jaundice?
55Ca GB: Radical Cholecystectomy with wedge ressection and CBD excision Choledocholithiasis: ERCP removal or CBD exploration/ bilio-enteric anastmosisCholangio Ca: Liver resection and or local excision of the lesion or WhippleBiliary Stricture: Hepatico-jejunostomy/ liver resection
56Periampullary Ca:Whipple’s ProcedureChronic Pancreatits with head Mass: Whipple/ bilio-enteric anastmosis
57Whipple’s Procedure Pancreaticojejunostomy- end to end Hepatico-jejunostomy – end to sideGastrojejunostomy – end to sideFeeding Jejunostomy
58What are the Risk factors for Operative Mortality in these patients?
59Preoperative Risk factors Dixon etal – GUT 1983Hematocrit < 30 %, S. bilirubin > 12mg%Malignant cause of biliary obstructionMortality 60% if above present, 5 % otherwiseBlamey et al 1983 : Brit J of Surg 8 factorsAge >60 , Malignant D, S Bil> 6mg/dl, Hct <30%, TLC>10000, S. alb <3, S creatinine>1.5, SALP >600Multivariate analysis and retrospective study of 373 pts. By Dixon etal – 1983 identified Hematocrit < 30 %S. bilirubin > 11mg%, Malignant cause of biliary obstruction as predictors of periop mortalily. If all these were present – 60%, none – 5%.OTHER Preop predictors of poor surgical outcome include -If all first 3 are present – 60%, none – 5%
60Preoperative Risk factors Bose et al Ind J Surg 1990Age >60, Associated DM, Previous Biliary tract surgery & prolonged surgeryFriedman –Hepatology June1999Azotemia, Hypoalbuminemia & CholangitisMultivariate analysis and retrospective study of 373 pts. By Dixon etal – 1983 identified Hematocrit < 30 %S. bilirubin > 11mg%,Malignant cause of biliary obstruction as predictors of periop mortalily. If all these were present – 60%, none – 5%.OTHER Preop predictors of poor surgical outcome include -If all first 3 are present – 60%, none – 5%
61What are the anaestheic goals in surgery for an Obstructive Jaundice patient ?
62Anaesthetics Goals Maintain Hepatic oxygen supply – demand relationshipRenal function
68Choosing appropriate anaesthetic agent No drug is contraindicated in Cholestatic liver disease per seOther considerationsCoexisting hepatocellular disorderRenal dysfunctionDrugs ↑ cholestasis e.g.; chlorpromazineAnaesthetic agent of choiceNot dependent on hepatic metabolismMaintains hepatic O2 supply – demand relationship
86Describe the structural/ architectural and the functional units of liver.
87Hepatic lobule: Str. Unit The lobule is the structural unit of the liver . It is easy to observe under microscope and roughly hexagonal in shape, with portal triads at the vertices and a central vein in the middle.Portal lobule comprises of adjoining parts of 3 hepatic lobule with center around portal triadHepatic lobule: Str. Unit
88Zone 1-Richer in O2 and nutrients Zone 3-poorer in O2 and nutrientsThe hepatic acinus represents functional unit because it is oriented around the afferent vascular system .the hepatocytes in acinus are divided into zones that correspond to distance from the arterial blood supply .those hepatocytes closest to the arterioles in zone 1 are the best oxygenated, while those farthest from the arterioles in zone 3 have the poorest supply of oxygen.Hepatic Acinus : Func. Unit - divided into zones that correspond to distance from the blood supply
89Zone I – Periportal –↑ mitochondriaOxidative and phase 2 metabolism, glycogen synthetaseZone 3 - Centrilobular↑ SER, cyt-P-450, NADHAnaerobic & phase 1 metabolismMost sensitive to injury from circulatory disturbances and toxic byproducts
91Isolated elevation of S.Bilirubin Unconjugated hyperbilirubinemiaIncreased Bil Production (Hemolysis)Ineffective erythropoiesis, resorption of hematomaDecreased hepatocellular uptake (Rifampicin)Decreased conjugation (Gilbert & Crigler-Najjar)Conjugated hyperbilirubinemiaDubin Johnson Syndrome and Rotar syndrom
100Protein metabolism – synthesis of plasma pr( albumin & α-acid glcoprotein, C-reactive protein, haptaglobin, pseudocholinestrase, deamination of A.A , formation of urea,Glucose Homeostasis - gluconeogenesis, glycogenolysis( glucagon), glycogenesis (Insulin)Fat Metabolism - Synthesis of lipoproteins, cholesterol, triglycerides, oxidation of FA to ketone bodiesReservoir of BloodEndocrine Function: IGF1, Thrombopoitin, Angiotensinogen, Thyroid homeostasis, steroid hormone inactivation( Testesterone, estradiol, glucocorticoid, ald.)Synthesis of all Plasma protein except y globulin & factor VIII including albumin and coagulation factors .
102Functions of the Liver Bilirubin formation & excretion Drug & Hormone MetabolismPhase I & II reactionsHematological function – haematopoiesis in fetus, heme synthesis,Immunological function – largest RE organ, Kupffer cells - phagocytosis of Antigen from GIT.Synthesis of Coagulation factors:I,II,V,VII,IX, X,XI, XII,XIII, prekallikrein,kininogen- Anticoagulants: Antithrombin III, α1antitrypsin, α2 antiplasmin,protein C & S, plasminogen, plasminogen activator inhibitor