Flashcards in Hepatic Pathophysiology Deck (241):
What is the largest organ in the body?
What is the functional unit of the liver?
The lobule about 50,000-100,000 in the liver
What cells are known as the macrophages of the liver?
What are the capillaries of the liver?
What is the function of the space of disse?
Collects lymphatics fluid
From a radial view of a lobule, how might the provider determine the difference between the portal vein and hepatic artery?
The wall of the artery is thicker due to smooth muscle that is able to constrict the vessel
Where does blood come from to the hepatic artery?
Aorta and celiac circulation
Where does blood come from to the portal vein?
Brings blood from the intestines
Where does the bile drain to?
Where does the liver receive O2 flow from?
Hepatic artery and portal vein (50:50 split)
What is the SaO2 of the portal vein?
How much of the CO goes the liver?
1500mL or 25-30% of CO
What percentage of blood flow to the liver is from the portal vein?
1100mL or 75%
What percentage of blood flow to the liver is from the hepatic artery?
400mL or 25%
What is the average pressure in the hepatic vein leaving the liver and entering the IVC?
What is the average portal vein pressure entering the liver?
Why is it said that the hepatic sinusoids are a low pressure system?
Small pressure difference 9-0mmHg demonstrates that resistance to flow in the hepatic sinusoid is very low
About how long does it take for blood to traverse from the portal vein to the central vein?
What is hepatic arterial blood flow dependent on?
Metabolic demand (auto regulation)
What is hepatic portal vein blood flow dependent on?
Blood flow from the GI tract and the spleen
How will blood flow to the liver differ when change in one source occurs?
A change in blood flow from one source will produce a reciprocal (but somewhat limited) compensatory change in the blood flow from the other source
Decrease in hepatic arterial blood flow produces an increase in portal venous blood flow
What pathology greatly increases the resistance to blood flow in the liver?
Cirrhosis, destruction of liver parenchymal cells results in replacement wit fibrous tissue that contracts around the blood vessels
What is the most common cause of cirrhosis?
Alcoholism (viral hepatitis, obstruction/infection in bile duct and ingestion of poisons)
What is the most common cause of cirrhosis from poisoning?
Carbon tetrachloride, dry cleaning industry
What is the newest cause of cirrhosis that is on the rise?
Non alcoholic fatty liver disease found in the morbidly obese
What are the stages of alcohol induced liver damage?
Fatty liver --> liver fibrosis --> cirrhosis
What causes a fatty liver?
Fat deposition causes liver enlargement
What causes liver fibrosis?
Scar tissue forms, recovery is possible but scar tissue remains
What causes cirrhosis?
Growth of connective tissue destroys liver cells and the damage is irreversible
What type of receptors are located on the hepatic artery?
Alpha1 --> produce vasoconstriction and
Beta2 --> produce vasodilation
Dopamine1 --> produce vadosilation
Cholinergic --> vasodilation
What type of receptors are located on the portal vein?
Alpha1 --> produce vasoconstriction
Dopamine1 --> produce vasodilation
How does the SNS affect hepatic blood flow?
Sympathetic activation results in hepatic artery and mesenteric vessel vasoconstriction and decreased hepatic blood flow
What are the vascular function of the liver?
Functions as a blood reservoir
Hepatic macrophages serve as blood cleansing function
Liver has very high lymph flow
What is the normal amount of blood volume in the hepatic veins and sinusoids?
How much blood can potentially be stored in the hepatic veins and sinusoid as a result of back pressure from the RA?
0.5-1L of blood
How much blood can be shifted to central circulation from the liver when low pressure results such as during hemorrhage?
As much as 300mL
Why does blood entering the portal vein contain so much bacteria?
Because it comes from the intestinal capillaries
What bacteria is most commonly found in the blood of the portal vein?
Bacilli, however extremely rare to grow if you take a systemic sample of blood
What type of cells clean the blood entering the liver from the portal vein?
Kupffer cells that line the hepatic venous sinusoids, it takes about 0.01 second
What other function does the Kupffer cells do besides phagocytosis?
Release various enzymes, cytokines and other chemical mediators as part of an immune function
What system are Kupffer cells apart of?
Monocyte-Macrophage system (reticuloendothelial system)
Why does the liver have very high lymph flow?
Pores in the sinusoids are very permeable and allow easy passage of fluid and protein into the space of Disse
About how much of the lymph comes from the liver?
About 1/2 of all lymph in the bay comes from the liver
What can occur to the lymph fluid if high hepatic vascular pressure is present?
Causes fluid transudation into the abdominal cavity from portal sinusoids and the liver (ascites)
What hepatic vascular pressures result in excessive amounts of lymph fluid?
3-7mmHg increase above normal in hepatic venous pressure
What hepatic vascular pressure can increase lymph flow to 20x normal?
10-15mmHg increase in hepatic venous pressure, produces sweating from the liver surface with large amounts of free fluid entering the abdominal cavity
What causes ascites?
Blockage of the portal vein produces high pressure in the GI tract with transudation of fluid through the gut into the abdominal cavity
What are the final products of carbohydrate metabolism?
Glucose, Fructose and Galactose
What is the final common pathway of most carbohydrate metabolism?
Hepatic conversion of fructose and galactose to glucose
What are liver functions associated with carbohydrate metabolism?
Conversion of galactose and fructose to glucose
Storage of large amounts of glycogen
Formation of many chemical compounds from intermediate products of CHO metabolism
What are glucose, fructose and galactose?
Simple sugars, all have the same chemical formula but their structural formulas are different
What is most of the glucose stored as?
What is the glucose buffer function?
Storage of glycogen allows the liver to remove excess glucose from the blood, store it and return it to the blood when BG concentration decreases
How does a diseased liver affect glycogen storage?
Glucose concentration can rise 2-3 times as much in a person with poor liver function compared to a person with normal liver function
What occurs when glucose storage capacity is exceeded?
The excess glucose is converted to fat
What are the only two things in the body that are able to store significant amounts of glycogen?
The liver and the muscle
What hormone enhances glycogen storage?
What factors enhance glycogen breakdown?
Epinephrine and Glucagon (gucogenolysis)
When are glycogen stores depleted when fasting?
What process is required when glycogen stores are depleted?
Gluconeogenesis, the generation of glucose from non-carbohydrate carbon substrates
What two organs are able to convert amino acids, glycerol, pyruvate and lactate to glucose?
The liver and kidneys
What agents increase gluconeogenesis?
Glucocorticoids, catecholamines, glucagon and thyroid hormone
What agent decreases gluconeogenesis?
What cells are only able to use glucose for energy?
RBCs and renal medulla
What other source of energy can neurons use?
Ketone bodies produced in the liver by the breakdown of fatty acids following a few days of starvation
What are specific liver functions associated with fat metabolism?
Oxidation of fatty acids to supply energy for other body functions
Synthesis of large amounts of cholesterol, phospholipids and lipoproteins
Synthesis of fat from CHO and proteins
What is the purpose of oxidation of fatty acids?
To derive energy from Fat
How does oxidation of fatty acids produce usable energy?
They must split into glycerol and FAs
The FAs are then split by beta oxidation into 2-carbon acetyl radicals that form Acetyl Co A
Acetyl Co A enters the citric acid cycle
Where in the body does beta oxidation occur?
In all body cells but occurs especially rapidly in the hepatic cells
What happens to the Acetyl Co A that isn't used by the liver?
Converted to acetoacetic acid, highly soluble and leaves the hepatocytes enters the blood and is absorbed by other tissues
What do the tissues do with the acetoacetic acid once absorbed?
Reconvert it back into Acetyl Co-A which enters the citric acid cycle
What is an additional function of Acetyl Co A in the liver?
Synthesize cholesterol and phospholipids
What is majority of the cholesterol in the liver synthesized into?
80% Converted to bile salts and secreted into the bile
Where does the remaining 20% of cholesterol in the liver go?
Packaged in lipoproteins and carried by the blood to all tissue cells in the body
What other component is synthesized in the liver and transported predominately as lipoproteins?
What are the functions of cholesterol and phospholipids in the body?
What role does the liver play in fat metabolism?
Almost all synthesis of fat from CHO and proteins occurs in the liver
Without what function in the liver will death occur within a few days?
What are four specific liver functions associated with protein metabolism?
Deamination of proteins
Formation of urea for removal of ammonia from the body
Formation of plasma proteins
Synthesis of amino acids and synthesis of other compounds from amino acids
Why is deamination of proteins required?
Deamination of the amino acids in proteins is required before they can be used for energy or before they can be converted to CHO or fats
What is the byproduct of deamination?
Deamination of what amino acids plays a major role in gluconeogenesis?
Where are branched chain AAs metabolized?
Metabolized by the skeletal muscle
What removed ammonia from the body fluids?
Formation of urea
What causes ammonia to form in the body?
Deamination process and bacteria in the gut with subsequent absorption into the blood
What can occur if the liver does not form urea?
Ammonia concentrations will rapidly rise and result in hepatic coma and death
What is a portal caval shunt and how does it affect ammonia levels in the blood?
Surgical procedure shunts blood from portal to arterial circulation, skips liver and increases amount of ammonia in blood --> encephalopathy
What are the only plasma proteins that are not formed by the hepatocytes?
At what rate can the liver make plasma proteins?
How does plasma depletion affect the liver?
Causes rapid mitosis of hepatocytes and liver growth
What are the most important quantitative plasma proteins?
Albumin (plasma oncotic pressure and binding for transport proteins)
What are the most important qualitative plasma proteins?
What is the difference between essential and non essential amino acids?
Essential have to be taken in dietary while non essential can be synthesized in the liver by interconversion of one AA to another
How are non essential AA formed?
Same chemical composition as the AA to be formed except at the keto oxygen
Amino radical is transferred from an available AA to the veto acid to take the place of the keto oxygen
What are the end products of drug metabolism?
Inactivated or are made more water soluble and can be excreted in urine or bile
What is included in the phase I reaction of biotransformation?
P450 enzymes and mixed function oxidases:
What substances are known to induce the CYP450 system?
What can result from enzyme induction of the CYP450 system?
Tolerance of the drugs
How can cross tolerance occur from enzyme induction?
Tolerance to other drugs metabolized by the same enzymes
A decrease in metabolic clearance is usually due to what?
Reduced hepatic blood flow not hepatocyte dysfunction
What occurs during a phase II reaction in biotransformation?
Involve conjugation of a substance with a water soluble metabolite (glucuronide, sulfate, taurine and glycine)
How are conjugate substances excreted?
In the urine or bile
How is iron stored in the liver?
As ferritin (iron storage and buffer system
What substance binds to excess iron in body fluids?
Apoferritin ( + iron = ferritin)
What carries iron in the blood?
What coagulation factors are not produced by the liver?
Factor VIII and Von willebrand's factor
What factors require vitamin K for synthesis?
II, VII, IX, X
What endocrine hormones is the liver the primary site for degradation?
Steroid hormones (cortisol, aldosterone and estrogen)
What do hepatocytes secrete into the bile canaliculi?
Bile salts, cholesterol, phospholipids and conjugated bilirubin
What makes up the common bile duct?
Hepatic duct and the Cystic duct (gallbladder)
What controls the flow of bile from the common bile duct?
Sphincter of Oddi
What organ serves as a reservoir for bile?
How does the gallbladder concentrate biliary fluid?
Through active transport of Na and passive water reabsorption
What hormone is released by the intestinal mucosa in response to fat and protein that causes the contraction of the gallbladder, relaxes the sphincter of Oddi and ejects bile into the small intestine?
What is the major end product of Hgb degradation?
What component of Hgb is converted to free bilirubin?
4 pyrrole nuclei of the ring are converted to biliverdin which is rapidly converted to free bilirubin and released from the macrophages
Where does the breakdown of the hemoglobin molecule occur?
Inside the macrophage
What does free bilirubin immediately bind to once released from the macrophage?
Albumin (free bilirubin)
What are other names used to describe free bilirubin?
Unconjugated bilirubin or indirect bilirubin
What occurs when bilirubin is released by albumin and absorbed by hepatocytes?
Bilirubin is conjugated:
Once conjugates, what happens to bilirubin?
It is then excreted from the hepatocytes by an active transport process into the bye canaliculi and then into the intestines
What substance does intestinal bacterial convert conjugated bilirubin into?
Urobilinogen which is reabsorbed back into the blood
What are the two paths urobilnogen take once reabsorbed back into the blood?
Some excreted in the urine
Majority is reexcreted by the liver back into the intestines and eliminated in the feces
What term is used to describe an excess of bilirubin in the ECF?
Jaundice (large quantities of unconjugated or conjugated)
What are the two most common causes of jaundice?
Increased destruction of RBCs and Obstruction of the bile ducts or damage to the hepatocytes preventing usual amounts of bilirubin from being excreted in the GI tract
Where is the most common place for obstructive jaundice to occur?
In the common bile ducts
How does hemolytic jaundice occur?
RBCs are hemolyzed rapidly and the hepatocytes simply cannot excrete the bilirubin as rapidly as it is formed (function of the liver is NOT impaired)
What type of bilirubin is elevated in hemolytic jaundice?
The plasma concentration of unconjugated bilirubin rises above normal limits
What are the most common obstructions of the common bile duct?
Gallstones and Malignancy
What is the problem in obstructive jaundice?
The rate of bilirubin formation is normal but the bilirubin cannot pass from the liver into the intestines
How does conjugated bilirubin enter the blood in obstructive jaundice?
Probably by rupture of the bile canaliculi and direct emptying of ice into the lymph system
What form of bilirubin is elevated in obstructive jaundice?
What occurs when there is a total obstruction of bile flow?
No bilirubin can reach the intestines to be covered to urobilinogen therefore none is reabsorbed in the blood and excreted by the kidneys
What do transaminase measurements tell us about the liver?
Reflect hepatocellular integrity as opposed to liver function
What tests measure liver synthetic function?
What is a normal total bilirubin level?
Less than 1.5mg/dL
What total bilirubin level is considered jaundice?
Total bilirubin is greater than 3mg/dL
What conditions can be inferred from predominately conjugated hyperbilirubinemia with an increased urobilinogen
Extra hepatic biliary obstruction
What form of bilirubin is toxic to cells?
What enzymes are released in the circulation asa result of hepatocellular injury?
What are the two commonly measure serum aminotransferases?
AST and ALT
What additional tissues is AST released from?
What are normal AST and ALT levels?
What are mild elevation of AST and ALT associated with?
Cholestasis or metastatic disease
What form of liver disease are absolute AST and ALT levels of value?
Acute liver disease, poorly correlated in chronic disease
Where is alk phase produced?
Liver, Bone, Small bowel, Kidneys and Placenta and excreted into the bile
What is the normal level of serum alk phos activity?
How is alk phos affected by biliary obstruction?
More alk phos is synthesized and released into the circulation
What is the most sensitive indicator of hepatobiliary disease?
gamma glutamyl transpeptidase
What can be concluded from an elevated alk phos?
Elevations up to two times normal are associated with hepatocullular injury or hepatic metals
Higher elevations are indicative of inttrahepatic cholestasis or biliary obstruction
What are normal serum albumin concentrations?
Why might albumin levels be normal in acute liver disease?
Albumin has a long half life, may initially be normal
What can be inferred from an albumin level less than 2.5?
Chronic liver disease
How is albumin typically lost?
In the urine (nephrotic syndrome)
In the GI tract (enteropathy with protein loss)
What is a normal blood ammonia level?
What does an elevated ammonia level often indicate?
Disruption of hepatic urea synthesis
What is a normal PT?
What coagulation factors activity is being measured by a PT?
What can a prolonged PT tell us about liver disease?
Reflects severe liver disease because only 20-30% of normal factor activity is necessary for formal coagulation (unless vitamin K deficiency)
How long does it take the PT to respond to administration of vitamin K?
Up to 24hrs
What factors cause a decrease in hepatic blood flow from anesthesia?
Type of ventilation
How do anesthetics impact portal blood flow?
All volatile agents decrease portal blood flow, halothane the most and isoflurane the least
How is portal blood flow decreased with anesthesia?
By decreasing BP and CO
SNS stimulation causes vasoconstriction of the arterial and venous splanchnic vasculature
How does mechanical ventilation impact hepatic blood flow?
Controlled PPV with high mean airway pressures decreases venous return and CO compromising hepatic blood flow
PEEP accentuates these effects
How do surgical procedures on or near the liver reduce hepatic blood flow by up to 60%?
Local vascular reflexes
Direct compression of vessels of hepatic circulation
What is the order in which opioids cause spasm of the sphincter of oddi?
What drugs can relieve sphincter of oddi spasm?
Naloxone and Glucagon
What is the most common cause of post operative jaundice?
Over production of bilirubin due to reabsorption of a large hematoma or RBC breakdown following transfusion
Why is it common to see mild post op liver dysfunction in health patients?
Decrease hepatic blood flow
What is generally the cause of post op elevations of liver function tests?
The procedure itself or underlying liver disease
What anesthetic agents has hepatitis NOT been associated with?
Sevoflurane and Desflurane
What is thought to be the possible mechanism for Halothane hepatitis?
Formation of hepatotoxic metabolites or Immune hypersensitivity
What are risk factors for Halothane hepatitis?
Repeat exposure (especially within 28 days)
What is usually the cause of acute hepatitis?
Exposure to a hepatotoxin
What factors determine the clinical manifestations of acute hepatitis?
Severity of the inflammatory reaction and Amount of cellular necrosis
What are the most common viruses that cause hepatitis?
Hepatitis A, B, C
How is hepatitis A transmitted?
How is hepatitis B and C transmitted?
Percutaneously and by contact with body fluid
What are additional viruses that are known to cause hepatitis?
Hepatitis D, E
What hepatitis virus does not cause an infection by itself?
Hepatitis D it occurs as a co-infection with acute hepatitis B
Why is hepatitis C so difficult to diagnosis?
Antibodies are not present for a long period
What symptoms are usually present within the first two weeks of hepatitis infection?
Prodromal illness with fatigue, malaise, low grade fever, nausea and vomiting
How long does it take for complete recovery from a hepatitis infection?
Usually takes 4 months, however patients can have a chronic active hepatitis (asymptomatic infectious carriers0
What factors determine extent of drug induced hepatitis?
Dose dependent toxicity of drug or a metabolite
Idiosyncratic drug reaction
What is the most common cause of drug induced hepatitis?
What don't transaminase levels tell you about hepatitis?
Does not correlate well with the degree of cellular necrosis
Which liver enzyme is usually greater in acute hepatitis?
ALT > AST
Which liver enzyme is greater in alcoholic hepatitis?
AST > ALT
What test is the best indicator of synthetic function of the liver with hepatitis?
What drugs can be given to a patient with hepatitis if withdrawal is a concern?
Benzodiazepines and Thiamine
What should be assessed in patients with hepatitis in need of emergent surgery?
Determination of the cause and degree of hepatic impairment
Record drug exposures
Presence of N/V
Correction of dehydration and electrolyte abnormalities
What are the goals of intraoperative management in patients with hepatitis?
Preserve existing hepatic function
Avoid factors that may be detrimental to the liver
Why are inhaled agents preferred over IV anesthetic agents in patients with hepatitis?
Dependence on liver metabolism and elimination
What is the volatile agent of choice in patients with hepatitis?
Isoflurane due to the least effect on hepatic blood flow
What is considered chronic hepatitis?
Persistent hepatic inflammation for longer than 6 months as evidenced by elevated serum aminotransferases
What are the three classifications of chronic hepatitis?
Can only be determined by liver biopsy
Chronic persistent hepatitis
Chronic lobular hepatitis
Chronic active hepatitis (B or C)
What are characteristics of chronic persistent hepatitis?
Chronic inflammation of the portal tracts with preservation of the normal cellular architecture (usually does not progress to cirrhosis)
What are characteristics of chronic lobular hepatitis?
Foci of inflammation and cellular necrosis in the lobules (usually doe not progress to cirrhosis)
What are characteristics of chronic active hepatitis?
Chronic hepatic inflammation with destruction of cellular architecture (associated with development of cirrhosis)
How does cirrhosis occur?
Hepatocyte necrosis followed by fibrosis and nodular regeneration
What are the three major complications associated with cirrhosis?
Variceal hemorrhage from portal hypertension
Intractable fluid retention in the form of ascites
Hepatic encephalopathy in the form of coma
How does chronic portal HT affect the vasculature?
Leads to development of extensive venous collateral channels
What is a good indicator of portal HTN preoperatively?
Dilated abdominal wall veins
What tool can be used preoperatively to predict mortality in patients with cirrhosis?
Child Pugh Classification system
What are the components of the Child Pugh Classification system?
Total serum bilirubin
PT (added INR)
What three hematologic pathologies are associated with cirrhosis?
What causes thrombocytopenia in patients with cirrhosis?
Splenomegaly due to portal HTN
Decreased hepatic synthesis of clotting factors
What should be given to patients with cirrhosis pre op to replace clotting factors?
Cryo and FFP
What cardiac changes are seen in patients with cirrhosis?
Hyper dynamic circulation (CO increased and generalized peripheral vasodilation)
What factors contribute to cirrhosis cardiomyopathy?
Arteriovenous shunts and Decreased blood viscosity
What is thought to cause hypoxemia in patients with cirrhosis patients?
Right to left shunts from increased anomalous AV communication
What Acid/Base disturbance is usually present in patients with cirrhosis?
Metabolic alkalosis from hyperventilation
What is thought to cause ascites in patients with cirrhosis?
Seepage of protein rich lymph fluid from the surface of the liver
Avid renal sodium retention
How does portal HTN cause ascites?
Increased hydrostatic pressure favors fluid transudation across the intestine into the peritoneum
How does ascites affect the kidneys?
Decreased renal perfusion
Altered infrarenal hemodynamics
Enhanced proximal and distal tubule Na reabsorption
Impairment of free water clearance
Why is hyponatremia and hypokalemia common in patients with ascites?
K loss secondary to hyperaldosteronism
What can trigger hepatorenal syndrome in patients with cirrhosis?
What are the primary symptoms of hepatorenal syndrome?
Progressive oliguria, Avid sodium retention, Azotemia, intractable ascites with a very high mortality rate
What is the treatment for hepatorenal syndrome?
Supportive in nature and often unsuccessful unless liver transplant is performed
When are loop diuretics indicated in patients with ascites?
Only after best rest sodium restriction and spironolactone therapy have failed
What should be used to replace intravascular deficits in patients with cirrhosis?
What factors determine the extent of metabolic encephalopathy?
Amount of hepatocellular damage and the degree of shunting of portal blood directly into the systemic circulation
What anesthetic agents should be avoided in patients with encephalopathy?
What factors are known to precipitate hepatic encephalopathy?
Increased dietary protein uptake
Hypokalemic alkalosis from vomiting
Worsening liver function
How is dosing changes in highly ionized drugs in patients with cirrhosis?
Require greater than normal loading dose
How is the elimination of NMBA altered in patients with cirrhosis?
Hepatic elimination of NMBAs is decreased therefore lower than normal maintenance dose
What is the most commonly used combination of anesthetic agents in patients with cirrhosis?
Propofol induction wit isoflurane
When is regional anesthesia appropriate in patients with cirrhosis?
Without thrombocytopenia or coagulopathy but must take caution in avoiding HoTN
What type of blood flow is a cirrhotic liver dependent on?
Hepatic arterial blood flow due to reduced portal blood flow
What complication is associated with significant transfusion in patients with cirrhosis?
Citrate toxicity (citrate is normally metabolized by the liver)
Why is IV calcium usually indicated with transfusions in patients with cirrhosis?
Reverse the negative inotropic effects of decreased ionized Ca
What is the most common cause of cholestasis?
Extra hepatic obstruction of the biliary tract (gallstones, strictures and tumor)
How do treatments vary in intrahepatic versus extra hepatic disease?
Extra hepatic obstruction --> surgery
Intrahepatic cholestasis --> medical
What percentage of the liver is able to be resected?
Why does hypoglycemia often develop after a large liver resection?
Taking away glycogen stores
What are the two components of the Child Pugh scoring system?
Clinical features and Laboratory features
What are the clinical features in the Child Pugh scoring system?
Degree of malnutrition
Control of Ascites
History of encephalopathy
What are the laboratory assessments in the Child Pugh scoring system?
What is considered a class A Child Pugh score and its mortality rate?
The six parameters are normal or near normal
Mortality rate 10%
What is considered a class B Child Pugh score and its mortality rate?
Moderate abnormal to fairly well controlled
Mortality rate 30%