liver anatomy and physiology (1).pptbbbx

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1. LIVER ANATOMY AND PHYSIOLOGY Presented by: Dr. NISHA RAJPUT Moderator: Dr. UDAY SIR Total no of slides =45

2. CONTENTS Anatomy Of Liver Lobes Functional division Blood supply Microanatomy Zones Regulation of hepatic blood flow Factors affecting hepatic blood flow Effects of anaesthetic drugs on liver

3. Anatomy of liver Second largest organ in human body. Responsible to maintain homeostasis. interface between GIT and rest of the body Responsible for metabolic ,synthetic ,immunological, and hemodynamic functions SURGICAL ANATOMY Weight in adults =600g-1800g , female= 603g-1767g , males =968g-1860g (which represents 2-2.5%of total body weight) term newborn=150g-170g, (which represents 5%of total body weight ) One of the heaviest organ of the body

4. 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).

5. 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

6. 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.

7. 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 . Hepatic artery arise from celiac trunk in 80% population in the rest it arises from superior mesenteric artery After giving rise to gastroduodenal artery common hepatic artery enters hilum of liver( porta hepatis) It branches into right and left hepatic arteries supplying right and left side of liver respectively The right hepatic artery give rise to cystic artery which supplies the gall bladder The arteries ultimately terminate in hepatic sinusoids (capillaries) the portal vein (although part of venous system, is a primary source of oxygenated blood to liver) Portal vein carries blood from GIT, pancreas and spleen to the liver

8. Microanatomy Classic liver lobule – Hexagonal prism with a central vein in the center and six vertically aligned portal canals. Portal triad comprises of terminal branches of portal vein + hepatic artery + bile ductules . Liver acinus- Functional microvascular unit.

9. 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

10. Microcirculation- Zones of liver Three heterogenous circulatory zones Zone 1 – Periportal (Well oxygenated ) * Hepatocytes in zone 1 contain numerous mitochondria and have the highest concentration of Kreb’s cycle enzymes * Adapted for high oxidative activities such as gluconeogenesis , beta oxidation of fatty acids amino acid catabolism , ureagenesis, cholesterol synthesis and bile acid secretion

11. Zone 2 – Midzone - moderately well oxygenated Zone 3 – Pericentral – Least well oxygenated –Most susceptible to ANOXIC injury. -Reduced NADPH and cytochrome P450 enzymes ( Xenobiotic metabolism) -Zone 3 necrosis accumulation of toxic products of HALOTHANE and acetaminophen. -Glutamine synthetase captures ammonia that eludes from urea cycle and incorporates it into glutamine substrates.

12. Biliary Tract:

13. D) Bile metabolism - Bile salts ionic detergents for absorption, transport and secretion of lipids. - Activate lipases , promote micelle formation - Intestinal uptake of fat soluble vitamins (vit A,D,E,K) and acts as emulsifier for fat absorption from small intestine. - Importance- Absence of bile salts in the intestine reduces vitamin K .This can impair prothrombin time - Vitamin K dependent proteins include factor II , VII, IX and X Protein C and Protein S fail to undergo gamma carboxylation. - Increased risk of perioperative bleeding and patient should be given parenteral vit K therapy. - Impaired fat absorption can cause steatorrhea and deficiency of other fat soluble vitamins( vit A,D,E)

14. Liver facilitates absorption of bilirubin from bloodstream, conjugation and excretion into biliary system Imp : Hyperbilirubinemia can detect occult liver disease. Transfusion of one unit of blood contains 250mg of bilirubin. This bilirubin load of unit of blood increases as age of transfused blood increases. In patients with impaired liver function this can present as post-op jaundice due to increased exogenous bilirubin.

15. E ) Enterohepatic circulation : Drug is conjugated in the liver reaches the gut lumen via bile. Undergoes deconjugation and reabsorption in gut lumen and reaches liver through portal circulation. - Contributes to longer stay of drug in the body - VECURONIUM attains high concentration in bile.

16. F) First pass metabolism : Metabolism of drug during its passage from the site of absorption into systemic circulation Occurs in liver and gut Drugs that undergo High first pass metabolism a) Lidocaine b) Morphine c) Pethidine d) Propranolol e) Glyceral trinitrate - Intermediate metabolism - Pentazocine

17. Physiologic functions of liver A ) Carbohydrate metabolism : Important homeostatic regulator of blood glucose Stores and releases glycogen Site of gluconeogenesis from amino acids, lactate and glycerol. Importance –Hypoglycemia constant threat in patients with hepatic cirrhosis especially those abusing alcohol. Chronic liver disease due to alcohol abuse – alcohol induced interference with gluconeogenesis Accumulation of lactate which is a substrate for glucose synthesis. • Hypoglycemia which may require a preoperative glucose administration or increased intra-op requirement • Lactic acidosis occurs.

18. B) Protein metabolism Krebs Henseleit cycle - Major pathway for removal ammonia and nitrogenous wastes. This pathway captures nitrogen in the form of urea. Liver cell failure: accumulation of ammonia occurs and could be one of the causes of hepatic encephalopathy. Liver derived proteins - A) Albumin : most abundant. Plays an important role in regulation of oncotic pressure. Albumin binds to and transports – free fatty acids unconjugated bilirubin, hormones and xenobiotics Drugs bound to albumin : Barbiturates, benzodiazepenes and warfarin. Hypoalbuminemia: one of the causes of ascitis and increase in unbound fraction of drugs. B) Alpha 1 acid glycoprotein ( Orosomucoid ): This binds to basic drugs like Bupivaicaine , Lidocaine , Steroids Increases in Obstructive jaundice and decreases in Hepatocellular jaundice. C) Pseudocholinesterase: Plays vital role in degradation of succinylcholine, mivacurium and ester type local anaesthetics

19. C ) Lipid Metabolism : major site of fatty acid synthesis Cholesterol and lipoprotein metabolism Beta oxidation of fatty acids to produce Acetyl CoA which acts an epicenter of intermediary metabolism. Hepatocytes cannot utilize ketone bodies for energy extraction due to lack of Ketoacyl CoA transferase Importance :Stress induces ketosis self limited as ketones stimulate insulin release thereby decreasing availability of substrate for hepatic ketogenesis. When the insulin feedback mloop fails to function these patients are at higher risk of developing diabetic ketoacidosis. Dysfunction leads to wide range of abnormalities of cellular function – cell membranes and hormones. Hypercholesterolemia occurs in liver disease- higher risk for CAD.

20. Regulation of Hepatic Blood Flow Intrinsic Regulation Hepatic Arterial Buffer Response -HABR Pressure flow Autoregulation Metabolic control Extrinsic Regulation Neural Control Humoral Control

21. Hepatic arterial buffer system With an intact HABR, changes in portal venous flow cause reciprocal changes in hepatic arterial flow. 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.

22. 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

23. 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.

24. NEURAL CONTROL Fibers of the vagus ,phrenic and splanchnic nerves(postganglionic sympathetic fibers 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 splanchnic 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.

25. 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 .

26. FACTORS AFFECTING HEPATIC BLOOD FLOW INCREASE IN HEPATIC BLOOD FLOW Hypercapnia Acute hepatitis Supine posture Food intake Drug: Beta Agonist Phenobarbitone Enzyme inducers DECREASE IN HEPATIC BLOOD FLOW IPPV Hypocapnia Hypoxia Cirrhosis alpha Stimulation Beta blocker Halothane, volatile & anesthetics Vasopressin

27. 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.

28. Effect of volatile agents on hepatic blood flow Halothane: Causes hepatic arterial constriction, microvascular vasoconstriction Enflurane: Increase in hepatic vascular resistance Isoflurane: Increase in microvascular blood velocity Sevoflurane & Desflurane: Preservation of hepatic blood flow & function

29. 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, reduced cardiac output

30. REGIONAL ANESHESIA & HEPATIC BLOOD FLOW Reduction in hepatic blood flow in high spinal & epidural anesthesia Secondary to hypotension Reversed by vasopressors like dopamine, ephedrine

31. 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 i mportant risk factor & multiple exposure increases the chance of hepatitis.

32. ISOFLURANE. DESFLURANE . 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 . it is similarly bio transformed 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.

33. Desflurane SEVOFLURANE Desflurane ↓hepatic blood flow 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. 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.

34. 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.

35. 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

36. 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

37. NEUROMUSCULAR BLOCKING DRUGS Vecuronium, rocuronium, mivacurium: Reduced elimination and Prolong duration of action specially with infusion & repeated doses Atracurium & cisatracrium : Nondependent of hepatic metabolism and can be used without modification of doses in end stage liver disease

38. 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.

39. 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.

40. 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 although its concentration may increase in patients undergoing liver transplantation, clinically relevant neurotoxicity has not been reported

41. EFFECTS OF HEPATIC DYSFUNCTION OF ANESTHETIC DRUGS Altered protein binding Altered volume of distribution Altered drug metabolism due to hepatocyte dysfuction

42. 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

43. TO SUMMARIZE Liver major organ of metabolism Liver dysfuction affects pharmacokinetics of anesthetic drugs Anesthetic drugs affects liver function Neuraxial blocks: reduction in hepatic blood flow due to hypotension Intraoperative hypotension, hypoxia, hypocapnia, use of hepatotoxic drugs in perioperative period can cause postoperative hepatic dysfunction

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