hepatic pathophysiology and disease Flashcards
what are basic characteristics of the liver?
- largest internal organ
- weights about 1400-1800 g
- located right side under ribcage
- ability to regenerate
- over 500 vital functions
- involved in many digestive, vascular, and metabolic activities
what is the basic functional unit of the liver?
hepatic lobules compromised of hepatocytes
what vessels supply blood to the liver?
- portal vein (75%)
- hepatic artery (25% w/ 2/3 of O2 supply)
what percentage of CO does the liver receive?
25-30%
what is unique about the hepatic portal vein?
not a true vein b/c it conducts blood to capillary beds in the liver and not directly to the heart
what is hepatic perfusion pressure (HPP)?
the combination of hepatic arterial pressure and portal venous pressure vs. hepatic venous pressure (CVP)
(HAP + HPV) - CVP
what causes decreased hepatic blood flow?
- increased CVP
- circulating catecholamines
- hypoxia
- hypercarbia (vasoconstriction)
what type of receptors are found in the hepatic artery?
both alpha and beta
what receptors are found in the portal vein?
only alpha receptors
*most effected by alpha vasoconstriction, impacting liver BF
how does the liver usu. compensate for portal blood flow decrease? what blunts this response?
- hepatic artery BF increases to compensate
- halothane blunts this response
- isoflurane does NOT*
how does regional and general anesthesia affect hepatic blood supply?
both reduce hepatic blood supply to varying degrees (regional 30%)
- halothane, enflurane: decreased HPBF; may decrease or may not change HABF
- isoflurane, desflurane: decreased HPBF, increased HABF
what does the liver filter and how?
- filters blood from the GI tract
- Kupffer’s cells
what is the amount of circulatory reservoir held by the liver to be put back into circulation when needed?
350 ml
what are primary functions of the liver?
- bile production
- protein synthesis (albumin, coagulation factors)
- glycogen storage
- protein metabolism
- insulin clearance
- lactate conversion into glucose
- drug metabolism and transformation
what are other functions of the liver?
- filtering
- circulatory reservoir
- creation of bile pigments, synthesis and secretion of bile
- synthesis of cholesterol
- detoxification
- deposition and exchange of vit. (A, B, D), and iron, copper, zinc ions
- regulation/balance b/w coagulant and anticoagulant system; formation of heparin
- destruction of some microorganisms, bacterial ,and other toxins
- deposition of plasma in the blood; regulation of a total amt. of blood
- hemopoiesis in the fetus
what are the four primary causes of liver damage?
- inflammation: immune response
- fibrosis: scar tissue
- cirrhosis: liver cells destroyed & replaced w/ scar tissue
- hepatocellular carcinoma: liver cancer
describe albumin
- plasma protein
- 3.0-3.5 gm/dL
- provides majority of oncotic pressure of the plasma
- 1/2 life 14-20 days
- chief site where drugs are protein bound
- unbound portion of drugs is the portion that interacts w/ receptor sites
what happens when albumin drops below 2.5 gm/dL?
results of drugs (esp. highly protein bound) is exaggerated
what are the main morphological types of damage of the liver?
- hepatitis
- cirrhosis
- cancer
what acute and chronic diseases of the liver contribute to pathophysiology?
- infectious diseases: viruses, bacteria, spirochetes, pathogenic fungi, elementary, helminthes
- toxic substances: hepatotoxins (alcohol, drugs i.e. oncology and bone marrow suppression)
what are rare causes of hepatic dysfunction
- hyperdynamic circulation: AV malformations, hypoviscosity d/t anemia, increased intravascular volme
- hypoxemia: r-l intrapulmonary shunt, V/Q mismatch, ascites (restrictive), decreased FRC, hyperventilation w/ resp. alkalosis
what clinical manifestations are seen with hepatic dysfunction?
- arrhythmias
- increased intra abdominal pressure w/ decreased gastric emptying (ascites)
- poor thermoregulation
- immunocompromised
- anemia
- coagulopathy
- electrolyte abnormalities
- acute renal failure
what enzymes are produced in the liver?
pseudocholinesterase and plasma esterases
*severe liver disease may cause prolonged action of succinylcholine, esmolol, and ester local anesthetics
how does hepatic extraction ratio affect drug clearance?
- drug clearance dependent on hepatic extraction ratio of the drug
- higher extraction ratio depends more on liver blood flow for clearance (propranolol, lidocaine (300%), morphine, meperidine)
- lower extraction ratio depends more on protein binding and the liver’s enzymatic activity
how does decreased BF affect hepatic extraction ratio?
- affects high extraction ratio drugs
- causing to last longer
how does decreased protein (albumin) levels or protein binding issues affect hepatic extraction ratio?
- affects low extraction ration drugs
- cause to last longer
what happens with enzyme induction?
increased tolerance to some drugs from overproduction of enzymes like CP450
what are some causes of enzyme induction?
- smoking
- ethanol
- benzodiazepines
- ketamine
- barbiturates
- phenytoin
what are common drugs that show an increased tolerance d/t enzyme induction?
- sedatives
- opioids
- induction agents
- muscle relaxants
- robinul
what may cause enzyme inhibition?
- cimetidine
* causes an increase in drug’s effect
what is the difference b/w hepatitis and cirrhosis?
- hepatitis: liver inflammation; infection
- cirrhosis: intensified diffuse growth of new connective liver tissue (stroma) on the background of dystrophic and necrotic hepatocytes (parenchyma) damage (thicker and tighter; things cant pass through; filtering is an issue)
describe carbohydrate metabolism disorder
- slowing down of glycogen synthesis may happen when hepatocytes are affected (glycogen synthesis and splitting are main regulatory processes to help liver keep glucose homeostasis, esp. its blood level)
- leads to simultaneous limitation of glucuronic acid formation, which is indispensable in detoxification of many poisons (industrial toxins) and final metabolites and unconjugated bilirubin
describe fat metabolism disorder
- liver regulates nutrient balance
- if no balance in food ingredients, liver takes the surplus substances and stores them until the necessary product appears to construct macromolecules and to expel them into the blood
- w/ pathology, liver stores mainly fats since fat is easier to store and wont be able to supply nutrients it usu. stores
- called fatty liver infiltration
describe albumin metabolism disorder
- hypoproteinemia: blood level decrease of albumins, which are synthesized by hepatocytes; leads to hypooncia and edema results
- hemorrhagic syndrome: decreased synthesis of blood coagulation factors (except VIII) (abnormal PT, PTTs)
- increase in BUN: decreased urea synthesis and ammonia accumulation; seen when 80% of parenchyma are affected
- increase of enzymes level in blood (aminotransperases)
describe copper metabolism disorder
Wilson’s Disease
- rare and treatable disorder of copper metabolism
- abnormal accumulation of copper in the hepatocytes
- affect the basal ganglia (balance and motor), eyes, kidneys
- ceruloplasm carries the copper, but in Wilson’s it is low, so copper cannot be carried to be metabolized
- give a drug that binds copper to be removed
what is hepatocerebral coma?
- syndrome d/t liver insufficiency
- characterized by significant impact on CNS
- loss of consciousness
- loss of reflexes
- cramps
- blood flow and breathing disorders
what are the four most frequent hepatocerebral coma reasons?
- viral hepatitis
- toxic liver dystrophy
- cirrhosis
- portal hypertension
the accumulation of what four toxic neurotropic substances are the main mechanism of CNS damage in hepatocerebral coma?
- ammonia
- decaying products
- low molecular fatty acids
- pyroracemic acid derivatives
describe jaundice
- symptom
- yellowish discoloration of the skin and sclera seen as a result of excess bilirubin in the blood (more than 1.2 mg/dL)
what is bilirubin?
product of RBC breakdown
what are the three main types of jaundice?
- hemolytic jaundice (excessive breakdown of RBCs)
- intrahepatic jaundice (cirrhosis, infection, inflammation)
- extrahepatic obstructive jaundice (gallstones obstructing common duct)
describe cholelithiasis effects
- obstructive jaundice d/t obstruction to outflow of bile
- bile pigment metabolism issues: accumulation of pigments and stones formed in gallbladder; elevated bilirubin, liver enzymes altered, may see steatorrhea
- pts. in an acute gallbladder episode will look like liver failure, except it is treatable
describe cholemic syndrome
- appears w/ obstructive and parenchimatous jaundices
- bile acids enter blood causing symptoms
what are the main four symptoms of cholemic syndrome?
- bradycardia
- hypotension
- excitability
- skin itch (rash)
why may hypoglycemia be seen with hepatic pathology?
d/t glugoneogenesis or glycolosis problems
what clinical triad characterizes hepatopulmonary syndrome?
- portal HTN
- hypoxemia
- pulmonary vascular dilatations
- when liver malfunctions, the 30% of CO coming to it backs up to the lungs (pulm. edema) and then eventually the heart (CHF)
what is portopulmonary HTN (POPH)?
pulmonary HTN syndrome w/ vascular obstruction and increased resistance to pulmonary arterial flow
*liver not able to function properly d/t blocked BF and increased pressures
what is hepatorenal syndrome?
form of pre-renal acute kidney injury that occurs in decompensated cirrhosis
- if liver cant filter blood, toxins reach kidneys
- late symptoms of cirrhosis
what is used to assess mortality risk with cirrhosis?
Child Pugh Classification: score based on
-bilirubin
-albumin
-prothrombin time (PT)
-ascites
-encephalopathy
1-2.5 low, 2.5-3.5 mod., 3.5-5 significant risk
what other measures predict mortality w/ liver cirrhosis?
- ascites
- increased serum creatinine
- pre-op GI bleed
- high ASA physical status
- previous abd. surgery
what represents actual liver function?
- albumin
- prothrombin time (PT)
- pseudocholinesterase concentrations
- if these abnormal, even if LFT normal, treat as liver failure
what is the most sensitive indicator of hepatocellular dysfunction?
INR
*could be result of meds; does not mean chronic damage
what is the diagnostic criteria for portopulmonary HTN (POPH)?
- mean pulmonary artery pressure (mPAP) greater than 25 mmHg at rest and
- pulmonary vascular resistance (PVR) of more than 240 dynes/s/cm-5
- better measure is transpulmonary gradient greater than 12 mmHg (mPAP-PAOP) as this reflects the obstruction to flow (PVR)
- w/ any ICU pt., check for previous caths or measurements
what may cirrhotic pts. w/ end stage liver disease also suffer from?
cirrhotic cardiomyopathy
*portal HTN backs up to lungs, then heart
what are AIs with hepatic encephalopathy?
- more sensitive to benzos d/t increase in number of cerebral GABA receptors
- even small doses can cause apnea (0.5 mg versed)
- w/ liver problems, do pre-op in an area where resuscitation equipment available
what are AIs w/ hyperdynamic circulation?
- CO increased a lot
- SVR decreased
- increased MVO2
- sensitive to catecholamines
- circulation is increased, not liver function, so don’t need more meds d/t increased CO
what are hepatic considerations with sedatives?
- use cautiously
- exaggerated response including apnea
- *highly protein bound and protein is low
what are hepatic considerations w/ aspiration?
- decreased gastric motility
- ascites (full stomach like)
- aspiration prophylaxis
what needs to be avoided with hepatic disease?
- hypoxia
- hypotension
- decreased CO
- *all of which are caused by anesthesia drugs
what are hepatic considerations with regional anesthesia?
- effective if no coagulopathy
- better at maintaining hepatic blood flow than GA if hypotension can be avoided
- platelet function needs to be greater than 100,000
what are hepatic considerations w/ volatile agents?
- all decrease the mean arterial pressure and portal blood flow (vasodilation)
- isoflurane maintains hepatic blood flow best (VOLATILE AGENT OF CHOICE)
- limit N2O: sympathomimetic effects causes hepatic vasoconstriction
what are hepatic considerations with IV anesthetics?
- modest impact on hepatic blood flow
- no meaningful adverse impact on post op liver function if the MAP is adequately maintained
- give small amounts to see how tolerated
- *give time to work
how does ketamine affect hepatic blood flow?
little impact
how does propofol affect hepatic blood flow?
increases total hepatic blood flow in both hepatic arterial and portal venous circulation, suggesting a significant vasodilator effect; but decreases systemic BP 20%
how does etomidate and thiopental affect hepatic blood flow?
-decrease hepatic blood flow either from increased hepatic arterial vascular resistance or from reduced CO and/or BP
what NMB should be used with hepatic dysfunction?
- atracurium (most) and cisatracurium
- Hofmann elimination (atracurium) and ester hydrolysis (cisatracurium)
- have clinical duration of actions similar to those in normal patients
- metabolites metabolized renally and hepatically
what muscle relaxants should you take caution w/ in hepatic disease?
- succinylcholine: may be prolonged r/t decreased enzyme production (don’t give)
- vecuronium, rocuronium: prolonged effect
- *drugs of choice: atracurium and cisatracurium
what should be considered w/ opioids and hepatic dysfunction?
- morphine: most closely associated w/ sphincter of Oddi spasm (give dilaudid or Demerol)
- fentanyl, sufentanil, alfentanil are ok to use
- hepatic metabolism: prolonged effects and side effects
- remifentanil: nonspecific plasma esterase metabolism (wears off quickly, must provide other pain management before stopping)
- give slowly and small doses to see reaction
with any drug when giving to a liver diseased pt. remember?
start low and go slow!
