Liver Physiology
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Liver Physiology

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Questions and Answers

What is the primary function of bile in the body? Select 3

  • To synthesize proteins
  • Absorption of dietary fats and fat soluble vitamins (DAKE) (correct)
  • Production of cholesterol (correct)
  • To facilitate excretion of toxins, absorption of dietary fats (correct)

    • Which vitamin is necessary for the synthesis of clotting factors II, VII, IX, and X?

  • Vitamin K (correct)
  • Vitamin B12
  • Vitamin A
  • Vitamin D

    • Which zone of the liver acinus is most susceptible to ischemic injury due to its distance from the hepatic artery?

  • Zone 1 - Periportal
  • All zones are equally susceptible
  • Zone 3 - Centrilobular (correct)
  • Zone 2 - Midzone

    • What is the major end-product of hemoglobin degradation?

    <p>Bilirubin</p> Signup and view all the answers

    Which factor has the shortest half-life among the clotting factors synthesized by the liver?

    <p>Factor VII</p> Signup and view all the answers

    How does excess iron get stored in the liver?

    <p>As ferritin</p> Signup and view all the answers

    Kupffer cells primarily function in which way within the liver?

    <p>Phagocytize bacteria from the circulation</p> Signup and view all the answers

    Where does bile flow after exiting the liver lobules?

    <p>Common bile duct</p> Signup and view all the answers

    What is the primary reason for increased cardiac output in cirrhotic patients?

    <p>Low systemic vascular resistance</p> Signup and view all the answers

    How does Hepatorenal Syndrome (prerenal disease) primarily manifest? Select 3

    <p>Sodium and water retention</p> Signup and view all the answers

    What defines severe portal hypertension in terms of hepatic venous pressure gradient (HVPG)?

    <p>HVPG &gt; 10-12 mmHg</p> Signup and view all the answers

    What is a characteristic feature of cirrhotic cardiomyopathy? Select all that apply

    <p>Low blood pressure</p> Signup and view all the answers

    What is the primary treatment for varices resulting from portal hypertension? (select 2)

    <p>Endoscopic ligation</p> Signup and view all the answers

    What impact does chronic cholestatic disease have on hepatocytes?

    <p>Causes hepatocyte destruction - due to impaired bile flow increasing biliary pressure and backflow into liver</p> Signup and view all the answers

    Why is it important to slowly correct hyponatremia in patients with hepatic encephalopathy?

    <p>To prevent seizures and brain injury</p> Signup and view all the answers

    What is the primary function of the Sphincter of Oddi?

    <p>Regulates the flow of bile and pancreatic juices into the small intestine</p> Signup and view all the answers

    Which of the following tests primarily reflects hepatic synthetic function? Select all that apply

    <p>Plasma cholinesterase</p> Signup and view all the answers

    What indicates a potential alcoholic liver disease when evaluating AST and ALT levels?

    <p>A ratio of AST = 2ALT</p> Signup and view all the answers

    Which enzyme is considered the most specific marker of liver injury?

    <p>ALT</p> Signup and view all the answers

    What condition is most commonly associated with extreme elevations of LDH? select 2

    <p>Ischemia</p> Signup and view all the answers

    Which of the following statements about alkaline phosphatase is correct? select 2

    <p>Can indicate intrahepatic or extrahepatic biliary obstruction</p> Signup and view all the answers

    What does an elevation in serum bilirubin levels primarily indicate?

    <p>Excretory function of the liver</p> Signup and view all the answers

    Which of the following is true regarding the performance of liver function tests (LFTs)?

    <p>Reflect hepatocellular injury more than overall liver function</p> Signup and view all the answers

    What causes the hepatic artery buffer response (HABR) to occur?

    <p>Decreased portal vein blood flow leading to low pH and increased release of adenosine resulting in vasodilation of hepatic artery</p> Signup and view all the answers

    Which component makes up 80% of the liver mass and is responsible for various metabolic processes?

    <p>Hepatocytes</p> Signup and view all the answers

    What is the average pressure in the portal vein?

    <p>8-10 mmHg</p> Signup and view all the answers

    Which type of liver cell is primarily involved in regulating hepatic vascular tone and permeability in the lobule?

    <p>Liver sinusoidal endothelial cells</p> Signup and view all the answers

    What effect does sympathetic nervous system stimulation have on hepatic blood flow?

    <p>Decreases hepatic blood flow</p> Signup and view all the answers

    Which process involves converting lactate, glycerol, and amino acids into glucose in the liver?

    <p>Gluconeogenesis</p> Signup and view all the answers

    How does the liver contribute to tolerating hemodynamic changes during hemorrhage?

    <p>Storing and autotransfusing blood</p> Signup and view all the answers

    What is the most common cause of elevated liver enzymes in adults?

    <p>Nonalcoholic Fatty Liver Disease (NAFLD)</p> Signup and view all the answers

    Which treatment is recommended for Nonalcoholic Fatty Liver Disease (NAFLD)?

    <p>Weight loss or bariatric surgery</p> Signup and view all the answers

    What should be indicated by elevated alkaline phosphatase and elevated transaminases in a patient?

    <p>Biliary disease requiring workup</p> Signup and view all the answers

    Which of the following complications may lead to increased Vd of drugs in patients with liver disease?

    <p>Reduced protein binding due to low albumin</p> Signup and view all the answers

    What is a consideration regarding the use of midazolam in patients with liver disease?

    <p>Its clearance may be reduced, prolonging its half-life.</p> Signup and view all the answers

    Which of the following can increase the risk of aspiration and rapid desaturation during general anesthesia induction?

    <p>Presence of jaundice</p> Signup and view all the answers

    Which anesthetic agent is often considered the best choice due to its short duration in patients with liver disease?

    <p>Fentanyl</p> Signup and view all the answers

    Which of the following is NOT a function of hepatocytes?

    <p>Filtration of blood</p> Signup and view all the answers

    What is the major end-product of hemoglobin degradation that is excreted by the liver?

    <p>Bilirubin</p> Signup and view all the answers

    What structure divides the left and right lobes of the liver?

    <p>Falciform ligament</p> Signup and view all the answers

    Which component of the liver is responsible for storing Vitamin A and the regulation of sinusoidal circulation?

    <p>Hepatic stellate cells</p> Signup and view all the answers

    Which of the following is NOT part of the liver's synthetic function? select 2

    <p>Synthesis of gamma globulin</p> Signup and view all the answers

    The hepatic artery buffer response (HABR) compensates for decreased portal vein blood flow through which mediator?

    <p>Adenosine</p> Signup and view all the answers

    What is the primary cause of portal hypertension in cirrhosis?

    <p>Increased resistance to blood flow due to fibrosis</p> Signup and view all the answers

    In the context of anesthetic implications for liver disease, which approach is recommended to reduce the risk of CNS depression?

    <p>Reducing doses of CNS depressants, hepatically cleared drugs, and lengthening intervals between doses</p> Signup and view all the answers

    Which of the following is a characteristic of hepatopulmonary syndrome?

    <p>Triad of liver dysfunction, unexplained hypoxemia, and pulmonary hypertension</p> Signup and view all the answers

    The presence of spider angiomas in a patient with liver disease is often associated with which complication?

    <p>Portal hypertension and varices</p> Signup and view all the answers

    Which type of hepatitis is most likely to develop into a chronic infection?

    <p>Type C</p> Signup and view all the answers

    How does the liver handle ammonia produced as a byproduct of protein metabolism?

    <p>It converts ammonia to urea for excretion.</p> Signup and view all the answers

    What role does albumin play in maintaining blood chemistry and volume?

    <p>Maintaining intravascular fluid volume and binding to various medications</p> Signup and view all the answers

    Which vessel supplies the majority of blood flow (75%) and 50% of the oxygen to the liver?

    <p>Portal vein</p> Signup and view all the answers

    Which vessel carries nutrient-rich, oxygen poor blood from the gastrointestinal tract to the liver?

    <p>Portal vein</p> Signup and view all the answers

    Which vessel has the lowest pressure in the major hepatic vessels and drains blood from the liver to the inferior vena cava?

    <p>Hepatic vein</p> Signup and view all the answers

    What is the approximate average pressure in the hepatic artery?

    <p>90 mmHg</p> Signup and view all the answers

    The hepatic artery arises from which major vessel?

    <p>Aorta via the celiac artery</p> Signup and view all the answers

    Which vessel supplies 25% of the flow but 50% of the oxygenated blood to the liver?

    <p>Hepatic artery</p> Signup and view all the answers

    What percentage of cardiac output does the liver receive?

    <p>25%</p> Signup and view all the answers

    What factors determine hepatic blood flow?

    <p>Hepatic perfusion pressure and splanchnic vascular resistance</p> Signup and view all the answers

    Which of the following factors decrease hepatic blood flow? (Select all that apply)

    <p>SNS stimulation</p> Signup and view all the answers

    How does SNS stimulation result in decreased hepatic blood flow?

    <p>It increases splanchnic vascular resistance.</p> Signup and view all the answers

    What can impede the hepatic artery buffer response (HABR)? select 2

    <p>Volatile anesthetics</p> Signup and view all the answers

    Match the description with its appropriate definition:

    <p>Glycogenesis = Converting glucose to glycogen Glycogenolysis = Breakdown of glycogen for glucose Lipogenesis = Converting excess glucose into fat Gluconeogenesis = Converting non-carbohydrates to glucose</p> Signup and view all the answers

    Ammonia level does not correlate with severity of encephalopathy due to its high potency/toxicity.

    <p>True</p> Signup and view all the answers

    What is the predominant plasma protein in human blood?

    <p>Albumin</p> Signup and view all the answers

    If a patient has signs of liver dysfunction with a normal albumin level, what type of problem is this indicative of?

    <p>Acute liver injury due to half life of albumin ~23 days</p> Signup and view all the answers

    What are the key functions of the liver? (Select all that apply)

    <p>Filtration and storage of blood</p> Signup and view all the answers

    Which of the following plasma proteins are produced by the liver? (Select all that apply)

    <p>Albumin</p> Signup and view all the answers

    What are Phase 1 reactions in drug metabolism?

    <p>Oxidation, reduction, and hydrolysis to convert lipophilic drugs to more polar molecules</p> Signup and view all the answers

    What type of reactions involve cytochrome P450 enzymes?

    <p>Phase 1 reactions</p> Signup and view all the answers

    What is the purpose of the phase 2 conjugation reactions?

    <p>To conjugate drugs to make them more water soluble for excretion</p> Signup and view all the answers

    What is the first pass effect?

    <p>The initial metabolism of a drug as it passes through the liver after being absorbed</p> Signup and view all the answers

    What is a characteristic of a high hepatic clearance drug?

    <p>It is dependent on hepatic blood flow for clearance</p> Signup and view all the answers

    Which type of drug clearance is independent of hepatic blood flow?

    <p>Low clearance drugs</p> Signup and view all the answers

    What percentage of the body's lymph does the liver generate?

    <p>50%</p> Signup and view all the answers

    Which of the following hormones does the liver synthesize? (Select one)

    <p>All of the above</p> Signup and view all the answers

    What type of cell produces bile in the liver?

    <p>Hepatocyte</p> Signup and view all the answers

    Match the steps in the pathway for bile production and excretion:

    <p>1 = bile synthesized by hepatocytes 2 = bile canaliculi 3 = bile ducts 4 = common hepatic duct 5 = common hepatic duct fuses with cystic duct 6 = bile stored in gallbladder 7 = bile excreted via common bile duct through sphincter of Oddi and ampulla of Vater</p> Signup and view all the answers

    Match the steps of hemoglobin (Hgb) catabolism:

    <p>1 = Red blood cells (RBCs) are phagocytized to heme and globin 2 = Heme gets converted to unconjugated bilirubin 3 = Unconjugated bilirubin is transported to the liver where it becomes conjugated (water-soluble) 4 = Conjugated bilirubin is excreted in the bile duct and transported to the duodenum for excretion in feces and urine</p> Signup and view all the answers

    DAKE = fat-soluble vitamins

    <p>True</p> Signup and view all the answers

    Which of the following nutrients are stored in the liver? (Select all that apply)

    <p>Vitamin A</p> Signup and view all the answers

    What organ is the site for the clearance of activated clotting factors?

    <p>Liver</p> Signup and view all the answers

    Which clotting factor is elevated in the setting of liver disease as a compensatory mechanism?

    <p>Factor VIII - produced outside of the liver</p> Signup and view all the answers

    What is the anatomical and functional unit of the liver called?

    <p>Liver lobule</p> Signup and view all the answers

    What does each liver lobule consist of?

    <p>Portal triad, plate of hepatocytes, and central vein</p> Signup and view all the answers

    What are the components of the portal triad?

    <p>All of the above</p> Signup and view all the answers

    What is the acinus?

    <p>A structural unit of the liver that describes blood flow and metabolic activity in terms of zones</p> Signup and view all the answers

    What activities occur in zone 3 of the liver? (Select all that apply)

    <p>Glycolysis</p> Signup and view all the answers

    What is the Ampulla of Vater?

    <p>The anatomical joining point of the bile and pancreatic ducts</p> Signup and view all the answers

    Why do abnormal liver function tests (LFTs) occur late in liver disease?

    <p>The liver has a significant reserve capacity that masks initial dysfunction.</p> Signup and view all the answers

    Which of the following tests are used to assess hepatic excretory function and clearance?

    <p>Direct bilirubin test</p> Signup and view all the answers

    Which test can be used to assess cholestatic or obstructive conditions?

    <p>Alkaline phosphatase</p> Signup and view all the answers

    Which of the following tests can be used to assess hepatic cellular integrity?

    <p>AST</p> Signup and view all the answers

    What test is commonly used to assess hepatic detoxification function?

    <p>Blood ammonia level</p> Signup and view all the answers

    Which of the following statements about aminotransferases is correct?

    <p>Aminotransferases are involved in gluconeogenesis, specifically ALT and AST.</p> Signup and view all the answers

    Which tissues can AST (aspartate aminotransferase) be found in?

    <p>Liver and non-hepatic tissues</p> Signup and view all the answers

    Which of the following are non-specific markers of hepatocellular injury due to their location in extrahepatic tissues? (Select all that apply)

    <p>AST</p> Signup and view all the answers

    What is the most common cause of acute liver failure?

    <p>Tylenol overdose</p> Signup and view all the answers

    What are non-hepatic causes of increased bilirubin? (Select all that apply)

    <p>Hemolysis</p> Signup and view all the answers

    An increase in which lab values indicate obstructive liver or cholestatic disease? select 2

    <p>Alkaline phosphatase (AP)</p> Signup and view all the answers

    What does prothrombin time measure?

    <p>The activity of fibrinogen, prothrombin, and factors V, VII, and X</p> Signup and view all the answers

    What test is noted for its sensitivity to liver injury due to its short half-life?

    <p>Glutathione-S-Transferase (GST)</p> Signup and view all the answers

    Study Notes

    Liver Gross Anatomy

    • Divided into 4 lobes: left, right, quadrate, caudate
    • Left and right lobes are divided by the falciform ligament
    • Liver is the second largest organ in the body, the skin is first
    • Enclosed within Glisson's capsule

    Couinard Classification

    • Division of the liver into 8 independent functional units
    • Used for surgical classification
    • Each unit has its own vascular supply

    Hepatic Blood Flow

    • Receives 25% of cardiac output from the hepatic artery and portal vein

    Hepatic Artery

    • Supplies less of the total blood supply to the liver (20%) than the portal vein, but better oxygenated blood
    • Average pressure is 90 mmHg
    • Comes off of the celiac artery

    Portal Vein

    • Blood draining from the gastrointestinal tract that is rich in nutrients and bacteria
    • Average pressure is 8-10 mmHg
    • Supplies most of the blood to the liver (75%), but less oxygenated

    Hepatic Vein

    • Pressure is 4 mmHg
    • Not a steep gradient between portal vein and hepatic vein
    • Total hepatic blood flow = portal vein + hepatic artery
    • Hepatic artery supplies about 50% of total O2 and portal vein has 50% of total O2 to the liver

    Hepatic Blood Flow Determination

    • 800 to 1200 ml of blood flow per minute
    • Hepatic blood flow is determined by hepatic perfusion pressure (HPP) and splanchnic vascular resistance
      • HPP = hepatic perfusion pressure = mean arterial pressure minus hepatic vein pressure or portal vein pressure minus hepatic vein pressure
      • Splanchnic vessels are innervated by the sympathetic nervous system
    • Sympathetic nervous system stimulation increases splanchnic vascular resistance resulting in decreased hepatic blood flow
    • Hepatic blood flow is reduced by pain, hypoxia, catecholamines, volatile anesthetics, regional anesthesia, surgical site, positive pressure ventilation, excess fluid administration

    Hepatic Artery Buffer Response (HABR)

    • Hepatic artery tone adjusts to changes in portal blood flow up to a 100% increase
    • Response is mediated by adenosine
      • Decreased portal vein blood flow leads to low pH, low O2, or hypercapnia → increased adenosine → hepatic artery vasodilates
      • Portal vein does not compensate for changes in hepatic artery supply
    • Volatile anesthetics and cirrhosis interfere with this response

    Hepatocyte

    • Make up 80% of liver mass
    • Store glycogen, vitamin B12, and iron
    • Participate in lipid turnover and transport
    • Synthesize plasma proteins (albumin, prothrombin, fibrinogen)
    • Metabolize and detoxify fat
    • Turnover of steroid hormones
    • Regulate cholesterol
    • Secrete bile

    Myeloid Cells

    • Kupffer cells play a critical role in detoxification and act as phagocytic macrophages
      • Located in portal and lobular liver sinusoids
    • Dendritic cells promote tolerance to phagocytized particles
    • Hepatic myeloid-derived suppressor cells suppress the immune response in the liver

    Hepatic Stellate Cells

    • Reside in the space of Disse
    • Store vitamin A and regulate sinusoidal circulation
    • Can proliferate in liver injury leading to hepatic inflammation and fibrosis

    Liver Sinusoidal Endothelial Cells

    • Permeable barrier that helps regulate hepatic vascular tone
    • Separates blood cells from hepatocytes/hepatic stellate cells

    Functions of the Liver

    • Filtration and storage of blood
      • Moderates hypotensive response to hemorrhage and hypovolemia
      • Liver is expandable and can store up to 1 L of blood – liver has ability to autotransfuse blood
      • Forms about 50% of body's lymph

    Metabolism of Carbohydrates

    • Glycogenesis = converting glucose to glycogen
    • Glycogenolysis = breakdown of glycogen for glucose
    • Lipogenesis = converting excess glucose into fat
    • Gluconeogenesis = converting lactate, glycerol, and amino acids to glucose; also converting galactose and fructose to glucose = creating glucose from non-carbohydrate sources

    Protein Metabolism in the Liver

    • Deamination of amino acids/proteins to form carbs or fat. Ammonia is a byproduct of this reaction.

    Elimination of Foreign And Chemical Toxins

    • Kupffer cells act as macrophages and filter so that <1% of bacteria from gut gets through the circulation.
    • Liver also generates 50% of body's lymph.

    Hgb Breakdown

    • Bilirubin is the major end-product of hemoglobin degradation that gets excreted by the liver
    • Heme gets converted to bilirubin
      • Bilirubin excreted into bile duct

    Formation of Bile

    • Bile is produced by hepatocytes.
    • Bile facilitates excretion of toxins and absorption of dietary fats.
    • Bile used to excrete endogenous compounds and exogenous compounds.
    • Bile flows from liver lobules → common bile duct → duodenum through the ampulla of Vater.

    Storage of Vitamins And Iron

    • Fat soluble vitamins = A, D, E, and K
    • Vitamin A (10-month supply)
      • Vitamin B12 (> 1 year supply)
      • Vitamin D (3-month supply)
    • Vitamin K necessary for synthesis of Factors II, VII, IX and X
    • Iron
      • Excess iron binds with apoferritin and is stored in the liver as ferritin.

    Formation of Clotting Factors

    • Except factors III, IV, and VIII that are all produced outside of the liver.
    • Hepatocytes contain apoferritin (which combines reversibly with iron)
    • Liver is the site for synthesis of all procoagulant and anticoagulant factors
    • Factor VIII elevated in the setting of liver disease
    • Liver is also the site for clearance of activated factors
    • Factor 7 has the shortest half-life
    • Evaluate factor 7 via PT blood test

    Each Liver Lobule is an Anatomic and Functional Unit of the Liver

    • Consists of a portal triad, plate of hepatocytes, and a central vein
      • Portal triad = branch of hepatic artery, branch of portal vein, and bile ducts
      • Acinus = functional unit of the liver
        • Zone 1 - Periportal
          • Well-oxygenated hepatocytes
          • Very nutrient-rich
          • Responsible for oxidative activities
        • Zone 2 - Midzone
        • Zone 3
          • Hepatocytes furthest from blood supply
          • Penetrating vessels
          • Most susceptible to ischemic injury because they are the furthest from blood supply
          • Responsible for glycolysis, lipogenesis, detoxification, and biotransformation of drugs occur

    Bile Synthesis, Function and Drainage

    • Facilitates excretion of toxins & absorption of dietary fats.
    • Also used to excrete endogenous compounds (bile acids, bilirubin, phospholipids, cholesterol, steroid hormones) and exogenous compounds (drugs, toxins)
    • Bile flows from liver lobules → common bile duct → sphincter of Oddi → ampulla of Vater to the duodenum.
    • Sphincter of Oddi is a muscular valve that controls flow of bile and pancreatic juices into the small intestine via the ampulla of Vater.

    Blood Flow in/around Liver Lobules

    • Space of Disse lies between sinusoidal capillaries and hepatocytes.

    Liver Function Tests

    • Do not measure specific liver function.
    • Abnormalities are late in hepatic disease due to the segmental nature of the liver that provides redundancy.
    • Reflect hepatocellular injury, more than liver function.
    • LFTs can help define pathophysiology with clinical assessment.
    • Hepatic synthetic function:
      • Serum albumin, PT, INR, serum cholesterol, plasma pseudocholinesterase
      • Hepatic protein synthesis: serum albumin, prothrombin time, INR
    • Hepatic excretory function/clearance: direct bilirubin
    • Cholestatic or infiltrative conditions: alkaline phosphatase
    • Hepatic cellular integrity: AST, ALT, LDH, GST
    • Hepatic detoxification function: ammonia

    Aminotransferases

    • ALT primarily found in the liver and the most specific marker of liver injury.
    • AST found in the liver and non-hepatic tissue
    • ALT and AST can be normal in end-stage liver disease because there are no cells left to be injured.
    • Mild elevations occur with any hepatocyte injury.
    • Large elevations are indicative of hepatic necrosis, fulminant viral hepatitis, drug-induced liver injury, shock liver.
    • Ratio of AST/ALT = 2 indicates alcoholic liver disease

    LDH = Lactate Dehydrogenase

    • Non-specific marker of hepatic injury.
    • Extreme elevations seen with ischemia or drug-induced hepatotoxicity (e.g.Tylenol OD)
    • Tylenol OD is the most common cause of acute liver failure.
    • Extrahepatic disorders can increase LDH (e.g.hemolysis, rhabdo, tumor necrosis, renal infarction, MI)

    GST = Gluthathione-S-Transferase

    • Sensitive for liver injury and short half life.

    Alkaline Phosphatase (AP):

    • Mild elevations may be normal
    • Non-specific (found in extra-hepatic tissues)
    • Values 2-4x normal seen in cholestatic disease
    • Can indicate intrahepatic or extrahepatic biliary obstruction

    Serum Bilirubin

    • Indicates excretory function of the liver.

    Portal HTN

    • Increased resistance to blood flow thru the liver leads to portal hypertension (+5 mmHg)
    • Considered severe if hepatic venous pressure gradient (HVPG) >10-12 mm Hg

    Hemostasis

    • Disrupted balance between bleeding and clotting

    Cirrhotic Cardiomyopathy

    • Hyperdynamic circulation characterized by high cardiac output, low blood pressure, and low systemic vascular resistance.
    • Increased overall fluid volume with decreased circulating volume
    • Prolonged QT

    Hepatorenal Syndrome (HRS)

    • Prerenal disease characterized by sodium and water retention
    • Increased prostaglandin levels to help maintain renal perfusion
    • Increased sensitivity to nephrotoxic drugs e.g.aminoglycosides, ACEIs, ARBs

    Hepatopulmonary Syndrome

    • Triad of liver dysfunction, unexplained hypoxemia, intrapulmonary vascular dilation

    Postpulmonary HTN

    • Pulmonary HTN in a Patient With Portal HTN

    Hepatic Hydrothorax

    • Ascites fluid passes from peritoneal cavity to the pleural space

    Hepatic Encephalopathy

    • Result of accumulated neurotoxins directly affecting the brain (e.g.ammonia and others)
    • Symptoms = altered mental status, hyper-reflexiveness, nystagmus, decerebrate posturing.
    • Mortality is related to infection.
    • Treatment = paracentesis and slow correction of hyponatremia.

    Varices

    • End result of portal HTN
    • Treat with beta-blockers to decrease portal pressure and endoscopic ligation.

    Chronic Cholestatic Disease

    • Impaired bile flow increases biliary pressure and backflow into the liver resulting in hepatocyte destruction.
    • If bacteria in bile -> ascending cholangitis, hepatic abscess, sepsis, and acute kidney injury can occur
    • Deficiencies in Vitamin K-dependent clotting factors (II, VII, IX, X)
    • Hypercoagulability
    • Extrahepatic causes = obstruction
    • Labs = Elevated serum AP and GT; may have elevated bilirubin
    • Treatment = endoscopic retrograde pancreatography (ERCP)

    Hepatocellular Carcinoma

    • Most common primary liver malignancy and 3rd most common cause of death globally.
    • Treatment = surgical resection, liver transplant, ablation, chemoembolization

    Nonalcoholic Fatty Liver Disease (NAFLD)

    • Ranges in severity from steatosis (fat deposits on the liver) to hepatocellular necrosis (NASH/steatohepatitis)
    • Associated with metabolic syndrome
    • Most common cause of elevated liver enzymes in adults
    • Treatment = weight loss or bariatric surgery

    Anesthetic Implications

    • Signs to look for during preop assessment = jaundice, bleeding abnormalities, spider angiomas
    • Spider angiomas are associated with varices and hepatopulmonary syndrome.
    • Avoid routine screening LFTs. Test if indicated by physical exam/history.
    • Preop LFTs:
      • Elevated ALT and AST in asymptomatic patient? Proceed if <2x normal and normal alk phos, bilirubin, INR.
      • Transaminases > 2x normal □ Workup prior to elective surgery (US, CT, liver biopsy).
      • Both transaminases and INR abnormal □ Workup prior to elective surgery (US, CT, liver biopsy).
      • Elevated alk phos and elevated transaminases □ Suspect biliary disease and workup indicated.

    Altered Pharmacokinetics

    • Altered protein binding – low albumin so reduced protein to bind resulting in more free drug.
    • Altered Volume of distribution with ascites and increased total body weight.
    • Reduced metabolism.
    • Potentiation of anticoagulants due to decreased production of clotting factors.
    • Smaller doses of meds at longer intervals.

    Induction of GA

    • Increased aspiration risk, rapid desaturation and hypoxemia.
    • Increased susceptibility to CNS depressants.

    Precedex

    • Liver metabolism primarily.
    • Decreased clearance and prolonged half-life

    Midazolam

    • Reduced clearance prolongs elimination half-life.
    • Avoid precedex and midazolam/any drugs that are primarily cleared hepatically.

    Goal platelet >50k

    • Opioids - fentanyl is best choice due to its short duration, remifentanil can be used as well but caution for hyperalgesia.
    • All volatiles decrease cardiac output which can ultimately decrease hepatic blood flow.

    Hepatocyte Functions

    • Hepatocytes are responsible for various functions, including synthesis of plasma proteins, storage of Vitamin B12, and secretion of bile.
    • They are NOT responsible for blood filtration, which is primarily performed by the kidneys.

    Hemoglobin Breakdown

    • Bilirubin is the major end-product of hemoglobin degradation excreted by the liver.

    Prolonged Prothrombin Time (PT)

    • A prolonged PT indicates a dysfunction in protein synthesis within the liver.

    Liver Anatomy

    • The Falciform ligament divides the left and right lobes of the liver.

    Vitamin A Storage

    • Hepatic stellate cells are responsible for storing Vitamin A within the liver.

    Liver Synthetic Functions

    • The liver synthesizes clotting factors II, VII, IX, and X, as well as plasma proteins like albumin.
    • Gamma globulin synthesis is NOT a function of the liver; B lymphocytes are responsible for this.

    Hepatic Artery Buffer Response (HABR)

    • HABR compensates for decreased portal vein blood flow by releasing adenosine.

    Liver Excretory Function Assessment

    • Direct (conjugated) bilirubin is used to assess liver excretory function.

    Portal Hypertension in Cirrhosis

    • Increased resistance to blood flow due to fibrosis is the primary cause of portal hypertension in cirrhosis.

    Anesthetic Implications for Liver Disease

    • Reducing the doses of CNS depressants and lengthening intervals between doses is recommended for patients with liver disease to minimize the risk of CNS depression.

    Hepatopulmonary Syndrome

    • Hepatopulmonary syndrome is characterized by a triad of liver dysfunction, unexplained hypoxemia, and pulmonary hypertension.
    • It is not limited to acute liver disease and can occur in patients with chronic liver disease as well.

    Spider Angiomas and Liver Disease

    • Spider angiomas are often associated with portal hypertension and varices in patients with liver disease.

    Chronic Hepatitis Infections

    • Hepatitis C (Type C) is the most likely type of hepatitis to develop into a chronic infection.

    Elevated Prothrombin Time and INR in Liver Disease

    • An elevated prothrombin time and prolonged INR in patients with liver disease indicate poor protein synthesis and clotting factor production.

    Ammonia Metabolism in the Liver

    • The liver converts ammonia to urea for excretion.

    Albumin's Role in Blood Chemistry and Volume

    • Albumin plays a significant role in maintaining intravascular fluid volume and binding to various medications.

    Liver Blood Flow Vessels

    • Portal Vein
      • Supplies the majority of blood flow to the liver.
      • Carries nutrient-rich blood from the gastrointestinal tract.
      • Blood is less oxygenated.
    • Hepatic Artery
      • Provides oxygen-rich blood to the liver.
      • Arises from the aorta via the celiac artery.
    • Hepatic Vein
      • Drains blood from the liver and delivers it to the inferior vena cava.
      • Has the lowest blood pressure amongst these vessels.

    Blood Flow Percentages

    • The hepatic artery contributes about 50% of the liver's oxygen supply.
    • The portal vein carries about 75% of the total blood flow to the liver.

    Hepatic Artery Pressure

    • The approximate average pressure in the hepatic artery is 90 mmHg.

    Bile's Role

    • Primary function: Emulsifies fats in the small intestine, aiding digestion and absorption

    Vitamin K Synthesis

    • Necessary for: Clotting factors II, VII, IX, and X synthesis

    Liver Acinus Zones

    • Zone 3: Most susceptible to ischemic injury due to distance from hepatic artery

    Hemoglobin Degradation

    • Major end-product: Bilirubin

    Clotting Factor Half-Life

    • Shortest half-life: Factor VII

    Liver Iron Storage

    • Excess iron: Stored as ferritin

    Kupffer Cells

    • Primary function: Phagocytosis within the liver

    Bile Flow

    • Exits liver lobules: Enters bile ducts

    Cardiac Output in Cirrhosis

    • Increased due to: Hyperdynamic circulation, splanchnic vasodilation & reduced systemic vascular resistance

    Hepatorenal Syndrome (prerenal disease) Manifestations

    • Low urine output: Due to decreased glomerular filtration rate
    • Increased BUN: Reflects impaired renal function
    • Elevates creatinine: Indicates kidney failure

    Severe Portal Hypertension

    • Defined by HVPG: Greater than or equal to 12 mmHg

    Cirrhotic Cardiomyopathy Features

    • Dilated cardiomyopathy: Weakens heart muscle
    • Diastolic dysfunction: Impairs heart's ability to relax and fill
    • Reduced contractility: Weakens the heart's pumping power

    Portal Hypertension Varices Treatment

    • Endoscopic variceal ligation: Banding to stop bleeding
    • Beta-blockers: Reduce portal pressure

    Chronic Cholestatic Disease Impact

    • Hepatocyte damage: Due to bile accumulation and injury

    Hyponatremia Correction in Hepatic Encephalopathy

    • Slow correction: Prevents rapid shifts in brain water, preventing cerebral edema

    Sphincter of Oddi Function

    • Controls bile flow: From common bile duct into duodenum

    Liver Synthetic Function Tests

    • Reflects function: Prothrombin time (PT) and INR
    • Reflects function: Albumin levels

    AST and ALT Levels in Alcoholic Liver Disease

    • Potential indication: AST levels 2-3 times higher than ALT levels

    Liver Injury Markers

    • Most specific: Alanine aminotransferase (ALT)

    LDH Elevation Causes

    • Liver damage: Due to cell death and release of LDH
    • Muscle injury: Due to muscle damage releasing LDH

    Alkaline Phosphatase Correct Statements

    • Elevated in: Cholestasis and bone disease
    • Not specific: Can be raised by various conditions

    Elevated Bilirubin Levels

    • Indication: Liver dysfunction or blockage of bile flow

    Liver Function Tests (LFTs) Performance

    • Can't diagnose: Specific liver diseases, only suggest problems

    Hepatic Artery Buffer Response (HABR)

    • Caused by: Increased portal pressure, triggers hepatic artery dilation

    Liver's Major Component

    • 80% of mass: Hepatocytes

    Portal Vein Pressure

    • Average: 5-10 mmHg

    Liver Cell Regulating Vascular Tone

    • Primarily involved: Ito cells

    Sympathetic Nervous System Stimulation on Hepatic Blood Flow

    • Effect: Decreases blood flow

    Gluconeogenesis

    • Conversion of: Lactate, glycerol, and amino acids into glucose by the liver

    Liver Hemorrhage Tolerance

    • Contribution: Vasoconstriction and increased glucose production

    Elevated Liver Enzymes Cause

    • Most common in adults: Non-alcoholic fatty liver disease (NAFLD)

    NAFLD Treatment

    • Recommended: Lifestyle modifications (diet and exercise)

    Elevated Alkaline Phosphatase and Transaminases

    • Indication: Cholestasis, possible biliary tract disease

    Increased Vd of Drugs in Liver Disease

    • Complications: Decreased albumin binding, increased free drug

    Midazolam in Liver Disease

    • Consideration: Requires dose adjustment due to prolonged duration

    Aspiration Risk in Anesthesia Induction

    • Increase: Reduced gastric emptying and delayed gastric emptying

    Best Anesthetic Agent for Liver Disease

    • Often preferred: Propofol due to short duration and fast elimination

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    Description

    Explore the intricacies of liver anatomy, including the division into lobes and classification systems like Couinard. Learn about the hepatic artery, portal vein, and their roles in supplying blood to the liver. This quiz is essential for understanding liver function and surgical classifications.

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