Liver Flashcards
How might liver dysfuntion typically present?
What are some labs that are essential to determine the cause and severity?
- typically presents as flu-like symptoms followed by jaundice
- Labs
- bilirubin
- aminotransferases (ALT, AST)
- alkaline phosphatase
- INR
- albumin
- serologic and genetic testing
What is bilirubin?
What is its “pathway?”
- Bilirubin is the pruduct of broken down hemoglobin and myoglobin
- Unconjugated bilirubin is formed in the periphery, it is transported to the liver bound to albumin
- In the liver it is conjugated, making it water soluble so it can be excreted
What increases unconjugated bilirubin?
What increases conjugated bilirubin?
- Unconjugated
- increased bilirubin production
- decreased hepatic uptake
- decreased conjugation
- Conjugated
- decreased canalicular transport of bilirubin
- acute/chronic hepatocellular dysfunction
- obstruction of bile ducts
What is the difference between AST and ALT?
What can the ratio of AST to ALT tell us?
- AST represents Liver AND extrahepatic tissues
- ALT is highly specific to the liver
- Ratio of AST:ALT
- 2:1 is seen in patients with Alcoholic liver disease (ALD)
- <1 is seen in patients with non-alcoholic steatohepatitis (NASH)
What can an elevated alkaline phosphatase tell us?
- Increases in serum Alk phos levels lack specificity because it is found in cell membranes throughout entire body
- In Cholestatic disorders, increased levels may indicate that bile salts are damaging hepatocyte membranes
What can the INR tell us regarding liver disease?
- INR is a good test of the liver’s ability to synthesize things
- if clotting time is prolonged, the liver may not be making adequate clotting factors
- INR depends a lot on factor VII, which is produced in the liver and relies on Vit K
- other vitamin K clotting factors are II, IX, X, proteins C and S
- INR is part of MELD score because it is a reliable independent risk factor for mortality
What is another scoring tool used to determine mortality with ESLD?
Child-Pugh score
How is albumin used to assess liver function?
What else can cause decreased albumin levels?
- Albumin is the most abundant plasma protein and is synthesized exclusively by hepatocytes
- decreased albumin levels also seen in:
- protein malnutrition
- protein-losing disease (nephrotic syndrome)
- severe reduction in synthetic capacity of liver
What lab differences would you see between prehepatic, intrahepatic, and posthepatic dysfunction? (chart)
Bili
AST/ALT
Alk phos
causes of changes
What are the different types of liver disease?
- Biliary disease (acute cholecystitis)
- acute hepatitis
- chronic hepatitis
- cirrhosis
- acute liver failure
- porphyria
What are the functions of the liver?
- Glucose homeostasis
- coagulation
- metabolism of:
- drug/toxin
- heme
- cholesterol/lipid
- protein
- production of thrombopoietin
- **impaired liver function affects nearly every organ system in the body
What is cholecystitis?
Who is at greatest risk?
symptoms
How is it treated?
- gallbladder or biliary tract stone
- Fat, fair, female, forty, fertile
- symptoms:
- N/V
- fever
- abdominal pain
- RUQ tenderness radiating to back
- dark urine
- scleral icterus
- Surgery when condition has stabled
- laparoscopic–>5% convert to open
- ERCP (endoscopic retrograde cholangiopancreatography)
What are some considerations for all laparoscopic procedures?
- insufflation will increase intraabdominal pressure
- risk for inadequate ventilation- decrease TV, increase RR
- decreased venous return leading to decreased CO and increased MAP and SVR
- bradycardia due to peritoneal stretching
- Risk for vascular injury and acute blood loss
- CO2 embolism
General considerations for Liver patients
- Consider volume and electrolyte replacement before procedure
- Consider how pt will be positioned
- trendelenburg- increases venous return and CO
- reverse trendelenberg- aids surgical access and may improve ventilation but decreases venous return and CO
- support HR and BP
- Ventilation-watch PIP and MV
- adjust accordingling: decrease TV, increase RR
- NG/OG tube
- avoid N2O
- careful use of opioids- risk of sphincter of oddi spasm
How do inhaled agents affect blood flow to the liver?
- Halothane: vasoconstriction of hepatic arterial bed, decreased O2 delivery to liver
- also a concern for halothane hepatitis
- NO Halothane, isoflurane, or sevoflurane
- Isoflurane- increased flow velocity in hepatic sinusoids
- Sevoflurane- equal or superior to Isoflurane in maintaining Hepatic artery blood flow (HABF)
What is the Hepatic artery buffer response (HABR)?
- Autoregulatory
- matches a drop in portal bloodflow (PBF) with an increase in hepatic artery blood flow (HABF)
What are the different types of hepatitis?
acute vs chronic?
- Inflammation of the liver parenchyma
- viral
- autoimmune
- drug induced
- Acute- usually self limiting
- most often viral
- can be caused by drugs/toxins
- Chronic- hepatic inflammation >6 months
- cirrhosis, hepatocellular carcinoma or liver failure
- Symptoms can range from minimal (malaise/jaundice) to severe with multiple organ compromise
What is autoimmune hepatitis?
How is it diagnosed?
How is it cured?
Treatment goals?
- cellular immune response against self-antigens in the liver
- diagnosis is confirmed with clinical findings, lab testing, and histologic evaluation
- no curative intervention
- Goal is to induce remission with corticosteroids and immunosuppressive drugs or liver transplantation
What are some drugs that induce hepatitis?
What is APAP? How does it cause problems?
- Drugs that can induce hepatitis: (NOT a complete list)
- analgesics
- anticonvulsants
- antibiotics
- antihypertensives
- APAP is acetaminophen
- uses up all the glutathione stores leading to inability to conjugate substances (free radicals??)
- Administer N-acetylcysteine within 8 hours (it provides cystein to make more glutathione)
- Drug induced hepatitis resembles viral hepatitis so prompt diagnosis is important
- remove offending agent
What is Halothane Hepatitis?
- An immune mediated hepatitis caused by all inhaled agents except sevoflurane
- Trifluoroacetyl halide metabolites covalently bond with microsomal proteins on hepatocytes, changing them from “self” to “non-self”
- IgG antibody mediated
- Halothane is the most common culprit d/t high degree of liver metabolism
- Sensitized ppl may show cross-reactivity with other volatile anesthetics (except sevo)
- use TIVA or Sevo
What is cirrhosis?
What are some signs and symptoms?
- Chronic, progressive parenchymal damage leads to scarring and nodular formation
- Signs/symptoms
- fatigue/malaise
- jaundice
- anorexia, weakness, N/V
- spider angiomata
- hypoalbuminemia
- ascites/hepatomegaly
- coagulation disorders
- endocrine disorders
- hepatic encephalopathy
- gastoresophageal varices
- hyperdynamic circulation
- hepatorenal syndrome
What labs would you expect to see elevated in a pt with cirrhosis?
decreased?
- elevated:
- bilirubin
- aminotransferase (AST/ALT)
- alk phos
- INR
- decreased
- serum albumin
- platelets
- blood sugar
What is the Child-Pugh score?
- People with severe liver disease have a decreased ability to respond to stress
- Child-Pugh score is used to predict surgical mortality with cirrhosis based on extent of liver damage and type of surgery
- total bili, serum albumin, INR, ascites, and hepatic encephalopathy
- Class A- 10% mortality rate with intrabdominal surg
- Class B- 30% mortality
- Class C- 80% mortality
- Class A&B ok for surgery if optimized, Class C avoid or delay elective surgery
How can the liver pt be optimized prior to surgery?
- improve diet with protein and caloric intake
- blood glucsoe control pre/intra/post op
- aldosterone antagonist
- cirrhosis is associated with increased aldosterone secretion
- electrolyte and fluid status
What should you consider if your patient has hepatic encephalopathy?
Ascites?
- encephalopathy
- RSI!
- Use sedatives and induction agents judiciously (or not at all)
- Ascites
- RSI
- mechanical ventilation
- pulmonary artery pressures
- fluid status
What should you consider if your patient has esophageal varices?
- NO esophageal temp probe or NG/OG
- If bleeding, RSI
- octreotide 50 mcg/hr or vasopressin 20 units over 5 minutes
How can you prepare for the coagulopathy common in liver patients?
- type and cross
- vitamin K non-emergently
- FFP, cryo, platelets
- the only factors NOT produced in the liver are factors III, IV, and XII
- PRBCs
- impaired ability to handle citrate loads
- monitor ionized Ca
- may need to administer Ca– especially if they are not responding to pressors
How could liver disease affect pharmacokinetics of some drugs?
- low albumin will cause decreased protein binding and increased volume distribution
- decreased clearance
- Ex. larger initial dose of NDMR to compromise for the increased VD bt decreased subsequent dosing due to decreased clearance
- use caution with drugs dependend on liver for clearance
What muscle relaxants are good choices?
- Cisatracurium
- atracurium
- mivacurium
What is importing regarding hepatic blood flow and anesthetics?
- Need to maintain liver blood flow
- Hepatic artery is 25% of blood flow and 50% of O2 delivery
- Portal vein is 75% of blood flow and 50% O2 delivery
- IV anesthetics maintain hepatic blood flow if arterial pressure is maintained
- All inhalational agents maintain hepatic blood flow except halothane
- avoid SNS stimulation
What are some post-op concerns for patients with cirrhosis?
- Post-op morbidity is increased
- liver dysfunction/failure (#1 problem)
- pneumonia
- bleeding
- sepsis
- poor wound healing
- DTs
- electrolyte disturbances
- renal failure
- frequent aspiration
What is the difference in anesthetic needs between acute and chronic ETOH use?
- Chronic ETOH causes enzyme induction = increased anesthetic needs
- Acute ETOH decreases anesthetic needs due to additive effects
- RSI
What are the symptoms of alcohol withdrawal syndrome?
- increased SNS/catecholamine release
- agitation
- tachycardia
- delirium tremors- 48-72 hours post ETOH; this is a medical emergency
- hallucinations
- diaphoresis
- cardiac dysrhythmias
- hemodynamic instability
- grand mal seizures and hypoglycemia
How is alcohol withdrawal syndrome treated?
- benzos
- beta blockers (propranolol or esmolol)
- airway protection
- correct fluid/electrolyte and metabolic disturbances
- DTs mortality rate is 10% d/t hemodynamic instability, cardiac dysrhythmias and seizures
What is porphyria?
- A metabolic disorder that results from deficiency of specific enzyme in the heme synthetic pathway
- results in overproduction of porphyrins
- accumulation of intermediate forms of porphyrin at the site of blocked enzyme
What are porphyrins essential for?
How is heme production regulated?
- oxygen transport and storage
- Heme is the most important porphyrin
- heme is bound to proteins to form hemoproteins (including hemoglobin and CYP450 isoenzymes)
- Heme production is regulated by aminolevulinic acid (ALA) synthase, which is in mitochondria
- formation of ALA is controlled by endogenous concentrations of Heme in a feedback loop
- ** In porphyria, an increase in heme requirements results in accumulation of pathway intermediates
What can induce ALA synthetase?
What will that cause in a pt with porphyria?
- Any metabolism that relies on CYP450 will induce ALA synthetase
- this will result in increased intermediates in a pt with porphyria
What is the most serious porphyria?
- Acute intermittent porphyria
- affects central and peripheral nervous system
- systemic HTN and renal dysfunction
- this is life threatening!
- affects central and peripheral nervous system
What are some porphyria triggers?
- Enzyme inducing drugs
- allyl group on barbiturates
- steroid structure
- avoid pentathol, thiamylal, methohexital, etomidate
- hormonal fluctuations
- menstruation/menopause/ pregnancy
- fasting (pre-op)
- dehydration
- stress
- infection
What are signs and symptoms of porphyria?
- Severe abdominal pain, N/V, due to autonomic neuropathy
- ANS instability
- electrolyte imbalances (Na, K, Mg)
- skeletal muscle weakness- respiratory failure
- cardiovascular instability resulting in hypertension and tachycardia (hypotension less likely)
- seizures
How is porphyria treated?
- remove triggering agents
- hydration
- carbohydrates
- treat pain, N/V
- BB for HTN and tachycardia
- benzos for sz
- fluid and electrolyte balance
- 10% glucose saline infusion
- Hematin 3-4 mg/kg IV
- Somatostatin
- plasmapharesis
Anesthetic management of porphyria
- Pre-op prep: identify and avoid triggers
- assess skeletal and CN function
- assess cardiac- HTN, tachycardia
- minimize multiple drug exposure
- fluid/electrolyte management
- anticipate post-op ventilation
- minimize stress of pre-op fasting: glucose-saline infusion
- preop meds:
- anxiolytics, aspiration porphylaxis
What drug inhibits ALA synthetase activity and decreases heme consumption?
Cimetidine
GA in a pt with porphyria:
- Use short acting agents
- moniors!
- induction with propofol or ketamine
- maintenance with N2O, IA, opioids or NDMR
- cardiopulmonary bypass is a stressor
Is regional contraindicated in a pt with porphyria?
- Same contraindications and risks as other pts
- Avoid regional in acute exacerbation of porphyria
What are the unsafe drugs for patients with porphyria?
- barbs
- etomidate
- sulfa antibiotics
- ETOH
- diazepam
- Nifedipine
- ketorolac
- phenacetin
