Hepatic Pathophysiology Flashcards
Acute Hepatitis
Liver inflammation d/t viral infection, drug reaction, exposure to hepatotoxin (i.e. alcohol or carbon tetrachloride)
Acute Fulminant Hepatic Failure
Presents as rapid, massive necrosis of liver parenchyma & ↓liver size
Acute Viral Hepatitis
A oral-fecal route
B & C transmitted primarily percutaneously & via bodily fluid contact
Other viruses D, E, Epstein-Barr, Herpes Simplex, Cytomegalovirus, & Coxsackievirsus
Prodromal illness 1-2wks w/ fatigue, malaise, low-grade fever, N/V
Period may or may not be follow by jaundice - typically lasts 2-12wks
Complete recovery aeb normal serum transaminases usually takes 4mos
Clinical courses complicated & prolonged w/ Hepatitis B/C viruses
Hepatitis A
Least severe
Most patients recover in week to months
Transmission via fecal contamination
Common in 3rd world countries d/t improper sanitation
Hepatitis B
HBsAg (surface antigen)
Often anicteric - does not present w/ jaundice
→ fulminant hepatic necrosis or chronic hepatitis
HBsAg disappears w/ recovery but disease able to be diagnosed through Hepatitis B antibody presence
Transmission via sexual contact or blood
Hepatitis C
Antibodies not present for long period
Difficult to diagnosis - exclusion primarily
Subclinical non-icteric infection common
Rarely produces fulminant hepatic failure
Significant number those who are chronically infected will develop cirrhosis or liver cancer
20% percent develop cirrhosis (major cause hepatocellular carcinoma)
Produces asymptomatic carriers
No effective vaccine currently available
Transmission via blood
Hepatitis E
Similar to Hepatitis A
3rd world countries
Transmission via fecal contamination
Chronic Viral Hepatitis
Chronic active viral hepatitis = acute hepatitis byproduct
3-10% after B virus infection
At least 50% after C virus infection
Chronic Viral Hepatitis
Chronic active viral hepatitis = acute hepatitis byproduct
3-10% after B virus infection
At least 50% after C virus infection
Asymptomatic infectious carriers
- 3-30% patients w/ Hepatitis B (persistent HBsAg present in blood)
- 5-1% patient w/ Hepatitis C remain infectious (correlates w/ amount Hepatitis C viral RNA in blood)
Avoid contact w/ blood & secretions
Immunization highly effective against Hepatitis B infection
No Hepatitis C vaccine available & prior infection does not = immunity upon re-exposure
Post-exposure prophylaxis w/ hyperimmune globulin effect for Hepatitis B not C
Drug-Induced Acute Hepatitis
Clinical course resembles viral hepatitis
Difficult diagnosis
Most common cause = alcohol-induced
Other causes: Tylenol, salicylates, carbon tetrachloride, volatile anesthetics, Phenytoin, sulfonamides, Rifampin, Indomethacin, Isoniazid, Amiodarone, etc.
Acute Hepatitis
Preop Considerations
Postpone elective surgery
↑periop morbidity & mortality
Further hepatic dysfunction & failure risk
- Encephalopathy
- Coagulopathy
- Hepatorenal syndrome
Labs: BUN, creatinine, bilirubin, electrolytes, glucose, transaminase, alk phos, albumin, PT/INR, plt count
- Hep B HBsAg
- ETOH blood alcohol level
Hypokalemia & metabolic acidosis d/t vomiting
Hypomagnesemia in chronic alcoholics → predisposes to dysrhythmias
Correct dehydration & electrolyte abnormalities
Hypoalbuminemia usually not present except in protracted cases w/ severe malnutrition or chronic hepatitis
N/V → RSI
ALT > AST
ACUTE hepatitis
AST > ALT
Alcoholic hepatitis
Synthetic Liver Function
PT = best indicator
Prolongation >3-4sec (INR <1.5) following vitamin K (correct coagulopathy onset 24hr) admin indicates severe liver dysfunction
Acute Hepatitis
Intraop Considerations
GOAL = preserve existing hepatic function
Individualized drug selection & dosages
Acute viral hepatitis → CNS sensitivity to aesthetics
Alcoholic patients (unless acute intoxication) display cross-tolerance to IV & volatile anesthetic agents, require CV monitoring d/t additive depressant effects & possible alcoholic cardiomyopathy
↓anesthetic agents
Inhalational agents are generally preferable to IV agents d/t dependence on liver metabolism & elimination
Standard induction doses IV agents generally used d/t action terminated by redistribution vs. metabolism or excretion
Volatile Agent
Isoflurane - least effect on hepatic blood flow
Avoid ↓hepatic blood flow
- Hypotension, excessive SNS stimulation, ↑mean airway pressure during controlled ventilation
Chronic Hepatitis
Persistent hepatic inflammation >6mos aeb ↑serum aminotransferases
Classification based on 3 distinct syndromes (determined by liver biopsy)
- Chronic persistent hepatitis
- Chronic lobular hepatitis
- Chronic active hepatitis
Chronic Persistent Hepatitis
Present w/ acute Hepatitis (B or C) that has protracted course but eventually resolves
Characterized by chronic portal tract inflammation w/ normal cellular architecture preservation (minimal cell death)
Usually does not progress to cirrhosis (typically resolves)
Chronic Lobular Hepatitis
Present w/ acute hepatitis that resolves but followed by recurrent exacerbations
Characterized by inflammation foci & cellular necrosis in the lobules
Usually does not progress to cirrhosis
Chronic Active Hepatitis
Occurs most commonly after acute Hepatitis B or C episode
Characterized by chronic hepatic inflammation w/ cellular architecture destruction → global
Evidence of cirrhosis present initially or eventually develops
Chronic Hepatitis
Lab Values
Mild elevation serum aminotransferases & generally correlate poorly w/ disease severity
Chronic Hepatitis Treatment
Antiviral medications
Hep B - antiviral + immune modulator drugs (interferon)
Hep C - antiviral cure >95% patients
Chronic Hepatitis
Anesthetic Management
Chronic persistent or chronic lobular hepatitis treat similar to acute hepatitis patients
Assume all chronic active hepatitis have cirrhosis & treat accordingly
Cirrhosis General Considerations
Progressive disease that eventually results in hepatic failure
Result = hepatocyte necrosis followed by fibrosis & nodular regeneration
Destruction
→ portal vein obstruction → portal HTN
→ normal synthetic & metabolic function impairment → multisystem disease
Jaundice & ascites
Spider angiomas, palmar erythema, gynecomastia, & splenomegaly
Cirrhosis CAUSES
Alcohol abuse
Non-alcoholic fatty liver disease
Chronic active hepatitis (B & C)
Chronic biliary inflammation or obstruction
Cirrhosis Complications
Variceal hemorrhage d/t portal HTN
Intractable fluid retention → ascites
Hepatic encephalopathy or coma
Childs-Turcotte-Pugh Score
Surgical risk r/t hepatic impairment degree
Total bilirubin Serum albumin INR Ascites Hepatic encephalopathy
Points 5-6 = Class A
100% 1 year → 85% 2 year survival
7-9 = Class B 80% → 60%
10-15 = Class C 45% → 35%
Cirrhosis Hematological
Portal hypertension S/S → gastroesophageal, hemorrhoidal, periumbilical, retroperitoneal varices, & dilated abdominal wall veins
Variceal bleeding treatment - IVF, blood products, vasopressin, propranolol, balloon tamponade, endoscopic sclerosis or varices ligation
Anemia, thrombocytopenia, coagulopathy, leukopenia
Excessive blood transfusions → encephalopathy
Correct coagulopathy before surgery
Replace clotting factors w/ blood products (i.e. FFP & cryoprecipitate)
Platelet count <100,000 → transfusion
Cirrhosis Cardiovascular
Hyperdynamic circulatory state
↑CO & generalized peripheral vasodilation
AV shunts R → L develop in systemic & pulmonary circulation
Cirrhotic cardiomyopathy d/t AV shunts & ↓blood viscosity → ↑CO
Alcoholic cardiomyopathy → CHF
Cirrhosis Respiratory
Hyperventilation common & results in 1° respiratory alkalosis
Hypoxemia frequent d/t R → L shunt
- ↑anomalous AV communication
- V/Q mismatch
- 40% CO involved
↓lung volumes (particularly FRC) d/t ascites fluid elevates the diaphragm → atelectasis
CXR & ABG
Paracentesis to treat massive ascites w/ pulmonary compromise
Cirrhosis Renal & Fluid Balance
Ascites, edema, electrolyte abnormalities, hepatorenal syndrome
Portal HTN ↑hydrostatic pressure fluid transudation across the intestine into the peritoneum
Hypoalbuminemia ↓plasma oncotic pressure → fluid transudation
Protein-rich lymph fluid 2° distortion & obstruction lymphatic channels
Renal Na+ & H2O retention d/t hepatorenal syndrome
↓renal perfusion, altered intrarenal hemodynamics, enhanced proximal & distal tubule Na+ reabsorption, impairment free water clearance
Dilutional hyponatremia
Hypokalemia - excessive K+ loss 2° hyperaldosteronism or diuretics
Judicious preop fluid management
- Ascites & edema diuresis over several days
- Loop diuretics only after bed rest, Na+ restriction, & Spironolactone therapy failed
Preserve renal function
Correct intravascular fluid deficits w/ colloid infusion
Hepatorenal Syndrome
Functional deficit in patients w/ cirrhosis
Causes: GI bleeding, aggressive diuresis, sepsis, major surgery
S/S: Na+ retention, progressive oliguria, azotemia, intractable ascites
High mortality rate
Treatment = supportive & often unsuccessful unless liver transplant performed
Cirrhosis CNS
Hepatic encephalopathy - mental status alterations, asterixis, hyperreflexia, EEG changes, ↑ICP
Treat encephalopathy preop
*Avoid sedatives
Metabolic encephalopathy r/t hepatocellular damage & degree portal blood shunting directly into systemic circulation → accumulation toxins originating from GI tract (ammonia, methionine metabolites, short chain fatty acids, phenols)
Hepatic Encephalopathy
Precipitating Factors
1° GI bleeding ↑dietary protein intake ↑ammonia Hypokalemic alkalosis d/t vomiting or diuresis Infections Worsening liver function
Drug Response
CNS sensitivity Vd Protein binding Metabolism Elimination
Titrate, titrate, titrate
NMBs
↑Vd highly ionized NMBs
↑loading dose
↓hepatic elimination
↓maintenance dose
Cirrhosis
Intraop Anesthetic Considerations
Cirrhotic liver dependent on hepatic arterial blood flow d/t reduced portal blood flow
Avoid anesthetic agents that potentially ↓hepatic arterial blood flow
Regional anesthesia w/o thrombocytopenia or coagulopathy avoid hypotension
Propofol or Thiopental induction w/ Isoflurane
Choice NMB = Cisatracurium
Opioid supplementation ↓volatile agent requirement but prolonged elimination 1/2 time → prolonged respiratory depression
RSI induction w/ cricoid pressure
CV unstable patient or w/ active bleeding → awake intubation
Cirrhosis Monitoring
5-lead EKG ABGs to evaluate acid-base status R → L shunts A-line to monitor rapid BP changes (excessive bleeding, fluid shifts, surgical manipulations) CVP or PAP UOP Large bore IVs
Cirrhosis Fluid Replacement
Na+ restriction preop
Intraabdominal procedures associated w/ excessive bleeding (venous engorgement d/t portal HTN, adhesions from previous surgery, coagulopathy) & fluid shifts (ascites evacuation & prolonged surgical procedures)
Anemia + coagulopathy → blood transfusion preop
Significant transfusions → citrate toxicity
Citrate
Hepatic metabolism
Cirrhosis impairs citrate metabolism
Citrate bind to serum Ca2+ & leads to hypocalcemia
IV Ca2+ often necessary to reverse the negative inotropic effects r/t ↓iCal
Hepatobiliary Disease
Cholestasis - impaired bile outflow
Most common cause = biliary tract extrahepatic obstruction
Also caused by intrahepatic obstruction
↑conjugated bilirubin >50%
↑alkaline phosphatase
OR cholecystectomy d/t cholecystitis
Treatment - NG suction, IVF, antibiotics, opioid analgesics
High bilirubin levels associated w/ renal failure
Long-term extrahepatic biliary obstruction associated w/ 2° biliary cirrhosis & portal HTN
Extrahepatic Obstruction
Obstruction d/t gallstones, stricture, or tumor w/in common bile duct
Treatment - surgical (remove blockage)
Intrahepatic Obstruction
Bile flow suppression or stoppage at hepatocyte or bile canaliculus level
Most commonly results from viral hepatitis or idiosyncratic drug reaction
Treatment - medical (inflammation)
Gallstone Disease
Cholelithiasis
Present w/ biliary colic 2° to cystic duct obstruction
Gallstones obstruct pancreatic duct → acute pancreatitis
Cholangtitis
Concomitant chills or high fever suggest an ascending bacterial infection of the biliary system
Vitamin K
Vitamin K deficiency d/t extrahepatic biliary obstruction
Full response requires 24 hours
PT unable to correct prior to surgery after vitamin K admin FFP
Hepatobiliary Disease
Intraop Considerations
Opioids → problematic w/ intraop cholangiogram d/t induce Sphincter of Oddi spasm → false +
Treatment = Naloxone or Glucagon
Biliary tract obstruction expect prolong DOA in drugs dependent on biliary excretion (i.e. Propofol or Ketamine)
Agents dependent on renal excretion are preferable
Monitor UOP
Maintain periop diuresis
Hepatic Surgery
Common surgeries - laceration repairs, abscess drainage, tumor resection
80-85% liver able to be resected
Complications - blood loss
Cirrhosis complicates anesthetic management & ↑periop mortality
Multiple large bore IVs, fluid/blood warmers, rapid infusion devices, A-line, CVP, avoid hypotension
Admin antifibrinolytics ↓blood loss (i.e. Aprotinin, Aminocaproic acid, Tranexamic acid)
Hypoglycemia following liver resections
Abscess drainage complicated by peritoneal contamination
Postop Complications
Bleeding
Sepsis
Hepatic dysfunction
Mechanical ventilation postop after extensive resection
HEPATITIS
Hepatitis (liver inflammation) d/t virus/toxin/fatty liver disease →
Acute (fulminant liver failure) d/t Hep B/D or Acetaminophen → 80-90% hepatocyte function loss → encephalopathy/coagulopathy → 1° cause death cerebral edema d/t ↑NH3 in brain & accumulation glutamate & neuronal swelling
Chronic liver disease d/t alcohol/Hep C/non-alcoholic fatty liver disease → hepatocellular death or cirrhosis
Hepatocellular death ↓synthesis/clearance/metabolic derangement → encephalopathy/coagulopathy
Cirrhosis → risk hepatocellular cancer or portal HTN
Portal HTN → ascites/varices/death d/t varices bleeding
Preop Clinical Assessment
Cirrhosis 6-80% mortality - Lap chole 1-6% - TURP 7% - Umbilical herniorrhaphy 13% - Non-lap biliary 20% - Abdominal trauma 47% - Peptic ulcer 54% - Emergency abdominal 57% - Emergency cardiac 80% Chronic hepatitis 0% Hep C lap chole 0% Acute hepatitis ex lap 100% Obstructive jaundice abdominal surgery 5-60%
