Hepatic Artery

25% of blood supply

50% Oxygen supply

mean aortic pressure 

comes right off aorta and goes directly to liver

Portal Vein

75% of blood supply

50% of Oxygen supply

6-10mmHg

What are the tributaries of the Portal Vein?

T/F Portal HTN causes all of these tributaries to back up/become engorged.

Inferior Mesenteric Vein

Superior Mesenteric Vein

Splenic Vein (supplied by pancreatic veins)

Gastric Vein

Esophageal Vein

True; this causes things like esophageal varices

Supply adequate oxygen and substrate for the livers intrinsic needs

To allow the liver to serve its purposes for the rest of the body (supplies blood to be "cleaned")

Intrinsic Regulation controls _______ in the liver itself and includes 2 mechanisms; List them:

Extrinsic regulation of liver blood flow is controlled by 2 mechanisms:

Intrinsic regulation controls regional microvasculature in the liver itself

 hepatic buffer system

 metabolic regulation

neural (mostly SNS)

humoral (epi, glucagon etc)

Is there any intrinsic regulation of portal venous flow?

Hepatic buffer mechanism

Increases _______ flow in response to decreased _______ flow.

Maximum response is ___% increase in ____ flow in response to ___% decrease in ___ flow.

Hepatic buffer response may be diminished or abolished with ______ hypoperfusion or _____.

Metabolic Regulation

Decrease portal blood ___ & ___ content or increased ____ cause & increase in ______ flow.

This type of regulation is most active in the _______ state, much less so in the ____ state.

Metabolic Regulation

Decrease portal blood pH & O2 content or increased PCO2 cause & increase in hepatic artery flow.

This type of regulation is most active in the postprandial state, much less so in the fasted state.

Hepatic Buffer Response

______ is secreted all of the time in the sinusoids and as portal flow decreases then less of this substance is washed out of the liver and thus ________ and this increases blood flow to liver.

In the Postprandial state

Less active in the fasted state

Extrinsic Regulation - Neural

What is Portal Venous pressure dependent on?

Dependent on the diff in pressures across the:

Splanchnic arteriolar tone

Portal venules

Post-sinusoidal tone

Hepatic Veins

Extrinsic Regulation - Neural

There are _______ receptors in the splanchnic and hepatic arteries etc; but only ______ receptors exist in the portal vein.

So the effect of neural stimulation of the portal vessels causes:(3)

Extrinsic Regulation - Neural

There are alpha and beta2 receptors in the splanchnic and hepatic arteries etc; but only alpha receptors exist in the portal vein.

Increases vascular tone

Reduced blood flow

Reduced blood volume

Epiniphrine

Norepinephrine

Glucagon

Angiotensin II

Vasopressin

T/F Dopamine also has a large effect in the liver.

False it is insignificant here

Glucagon produces ________ arteriolar dilation. 

It accomplishes this effect by....

Glucagon produces long-lasting arteriolar dilation.

antagonizing arterial constriction from other responses

Marked constriction of arterial & portal vasculature

Reduced mesenteric outflow

Reduced total hepatic blood flow

Intense vasoconstriction of splanchnic arterial vessels while decreasing portal venous resistance

Marked decrease in Portal Vein blood flow

Esophageal Variceal bleeding

More common tx is Octreotide/sandostatin

(inhibits glucagon's vasodilation effect)

Hepatic vascular resistance increases

Hepatic blood volume decreases

Blood glucose increases

(increased gluconeogenesis, increased glycogenolysis)

Blood glucose decreases

(increases glycogen synthesis, increases glucoses uptake)

Hepatic Blood Flow

Hepatic Blood Volume

You're in luck!

80% of hepatic blood volume (400-500ml) can be transferred to central circulation within seconds!!!

III - tissue thromboplastin

IV - Ca++

VIII:vWF

II

VII

IX

X

What are modultors of fibrinolysis and clotting produced by the liver? (3)

The liver is therefore important not only in production of clotting factors, but in modulating their consumption by producing fibrinolysis factors.

Antithrombin III

Protein C and S

Fibrinolytic Factors (TPA and urokinase)

T/F all liver derived coagulation factors have short T1/2 lives?

Which coagulation factor has the shortest half life and what is its 1/2 life?

True

Factor VII

T1/2 of 4 hours

The liver synthesizes and secretes 3 endocrine substances:

It biotransforms:

It also inactivates 5 substances:

Synthesis and secretion of:

IGF - 1

Angiotensinogen

Thrombopoietin

Biotransformation of:

conversion of T4 to T3

Inactivation of:
Corticosteroids

Aldosterone

Estrogen, androgens

Insulin

Anti-diuretic hormone

Bilirubin is the end product of _________?

____% is derived from Hgb breakdown.

Heme degradation

75% derived from hemoglobin breakdown

What are the steps of bilirubin excretion? (5)

___% of conjugated bilirubin is absorbed in intestine & returns to liver via ______, where it is sent back through bile to small intestine.

1. Bilirubin binds to albumin & is transported to liver
2. In liver, Albumin is removed from unconjugated bilirubin
3. Then bilirubin is conjugated primarily with glucuronic acid
4. Conjugated bilirubin is excreted into bile
5. Passes into intestine, where it is converted to urobiliongen and excreted

10% of conjugated bilirubin is absorbed in intestine & returns to liver via portal vein, where it is sent back through bile to small intestine.

The Portal Vein

(makes sense b/c this receives blood from gut)

Insulin mediated hepatic extraction of glucose from the portal vein

Excess glucose converted to glycogen

How much glucose can the liver store?

How long could this supply the body with glucose in the fasted state?

What breaks down glycogen?

Glucose is converted to glycogen...Liver can store about 75 gms of glycogen

24hrs

glucagon

Initially glucagon mediated glycogen breakdown

Then muscle & fat catabolism & gluconeogenesis

Portosystemic shunting

(glucose is not taken into the liver to be stored because of portal system congestion and instead it goes straight back into the systemic circulation via a shunt per lecture)

What causes hypoglycemia in advanced liver disease? (3)

What other liver condition may cause hypoglycemia?

Impaired glycogen storage

Impaired glycogenolysis

Impaired gluconeogenesis

Lg hepatocelllular CA d/t glucose uptake by tumor

Carbs

Protein

Lipids

Esterfies FFA to form

Triglycerides

Cholesterol

Phospholipids

False only Non-essential amino acids

Essential a.a. must come from your diet

Glucose production (gluconeogenesis)

Lipid metabolism (lipoproteins)

Further deaminated to keto-acids, glutamine, or ammonia

urea

kidneys

Increasing serum ammonia levels

and

hepatic encephalopathy

Its an important transport mechanism

Binds many anesthetic drugs

20 days

(thus not a good marker to determine liver function)

16hrs = exogenous albumin

In the liver

Which was an easy guess since this is a liver lec

Psuedocholinesterase is required for the degradation of what three anesthetic drugs?

Succinylcholine

Mivacurium

Ester local anesthetics

The impairment of Kupffer cell function is often a precursor to ______ and _______.

Particularly following _______ ischemia or severe ______ pathology.

Effect apparent volume of distribution of drugs

Act to decrease free drug concentrations

Hepatic Biotransformation is metabolism of drug by hepatocytes into _____, _________ substances for excretion in _____ or _____.

Phase 1 reactions render drugs more polar for excretion via what 3 mechanism?

What enzymes facilitated these rxns?

 Oxidation

Reduction

N-dealkylation

Most involve cytochrome P450 enzymes

What occurs during phase II reactions?

What enzymes are required?

Water solubility of the compound is enhanced

Requires transferase enzymes

The fraction of drug metabolized or extracted during a single pass through the liver

What is the basis of classification of drugs as having low to high hepatic extraction ratios?

What is clearance determined by with a high hepatic extraction ratio drug?

 the drug's Intrinsic Clearance; is it high or low

Hepatic Blood Flow

(as BF increases the rate of clearance increases linearly...low hepatic extraction ratio drugs are not affected much by liver BF per graph in handout)

Clearance relatively independent of hepatic BF

Clearance much more effected by increased free fraction/fraction unbound to proteins

(i.e. hypoalbuminemia)

(they have a linear relationship with free fraction; more free fraction = increase effect of drug and more extraction by the liver per graph and lec.)

Reduced hepatic blood flow prolongs the T1/2 and increases the effects of which drugs?

Give an example of anesthetic that decreases liver blood flow and thus may prolong extraction and metabolism of some drugs.

Those with High Hepatic Extraction Ratios

*linear relationship*

IAs

Increased drug effect (more free drug)

More rapid clearance of low HER drugs

*linear relationship*

Portosystemic shunting allows orally administred drugs to partially bypass the liver.

What is the result?

What is the bottom line with administering drugs with liver dysfunction?

Increased systemic effect

Prolonged duration of action

titrate carefully

List examples of

Low hepatic extraction ratio drugs (3)

Intermediate (2)

High (9)

Low hepatic extraction ratio drugs (3)

Alfentanyl

Diazepam

Thiopental

Intermediate (2)

Midazolam

Vecuronium

High (9)

Bupivacaine

Lidocaine

Etomidate

Propofol

Ketamine

Labetalol

Fentanyl

Morphine

Sufentanyl

They can identify a category of dysfunction

Hepatocellular

Hepatobiliary

Hepatic synthesis

What are tests that will indicate hepatocellular damage?

Transaminases

AST (SGOT)

ALT (SGPT)

AST is located...?

ALT is located...?

Many tissues

*less specific

Heart

Muscle

Kidney

Brain

Primarily in liver

Fatty liver

Nonalcoholic steatohepatitis

Drug toxicity

Chronic viral hepatitis

Acute Hepatitis

Exacerbation of chronic hepatitis

Drug or toxin-induced hepatocellular necrosis

Severe viral hepatitis

Ischemic hepatitis secondary to shock

Nope

Decreasing levels may indicate recovery from injury or few surviving hepatocytes left

Note: These enzymes increase in circulation with damage to the hepatocytes b/c they leak out of the damaged cells

Heaptocelluar necrosis

But has very low specificity for liver disease and is not particularly useful

What is GST?

Where is GST found?

Glutathione S-Transferase - a phase II enzyme

Many tissues, but isoenzyme B specific to liver

Where is GST found in the highest concentration?

What is significant about this area?

In Centrolobular (zone 3) hepatocytes

These are most susceptible hypatocytes to ischemic injury and toxic drug metabolites

Many organs

Primarily liver & bone in healthy people

Obstruction to bile flow

May be elevated during normal pregnancy

What is the most sensitive test for biliary tract disease?

BUT what makes it un-useful?

GGT (Gamma glutamyl transpeptidase)

un-useful b/c found in so many tissues it lacks specificity

Severity of jaundice

*we look at conjugated and unconjugated levels*

1-4mg/dl

Excessive production (and then hemolysis)

Defective conjugation

>5mg/dl

Liver disease

Conjugated Bilirubin elevation indicate? (2)

Conjugated bilirubin levels of ___ or greater can cause ____ damage & compound situation.

impaired hepatic excretion

extrahepatic obstruction (ie bile duct)

 liver is conjugated as it should but it cant get it out

>35mg/dl

Renal failure 

Review table on slide 37

How is hepatic synthetic function (livers ability to synthesize) measured?

Serum Albumin

PT/INR

Decreasing serum albumin levels in the absence of some other cause implies ____________?

Other non-liver cause are:

Worsening of chronic liver disease

burns

nephrotic syndrome

poor nutrition

fluid retention

etc

T/F Albumin is only a long term measurement of function b/c half life is 20 days.

True

What are useful markers in acute hepatocellular injury?

May not see a change in above markers with mild or even moderate liver injury b/c?

PT/INR

(d/t short 4 hr 1/2 life of Factor VII)

b/c the body has excess factors floating around and it takes awhile to deplete them per Anderson

What screening test is ultrasound used for?

Hepatic disease

Cholelithiasis (gallstones)

Biliary Tract disease

Cholelithiasis

Biliary tract obstruction

CT

but $$$$$

Endoscopic Retrograde CholangioPancreatography

Endoscopic guidance of a catheter through the ampulla of Vater (sphincter of Oddi) to inject contrast into the pancreatic duct & common bile duct (both which empty from sphincter of Oddi into sm intestine)

Technique of choice when choledocholithiasis (stone in common bile duct) is suspected b/c a sphincterotomy can be done at the same time & the stone can be removed.

Tx sphincter of Oddi spasms with ____ per lec.

What is the only way to know the specific nature of hepatic damage?

glucagon

Liver Biopsy

Hep C

Liver transplant

Platlets less than 60,000

PT more than 3 secs greater than control

What biopsy technique is safer when the coags are out of whack?

T/F Liver biopsies can also be done open?

Transjugular

True

10-15%

Severe alcoholic liver disease!

Acute viral hepatitis reported in the US

HAV?

HBV?

HCV?

HDV and HEV?

HAV - 20%

HBV - 50%

HCV - 30%

 HDV and HEV - seen more in 3rd world countries along with HAV

What is the most common blood-borne infection in the U.S?

This accounts for ___% of chronic liver disease?

 Chronic liver disease will develop in __% of Hep B positive pts & __% of Hep C positive pts.

HCV

This accounts for 40% of chronic liver disease

 Chronic liver disease will develop in 1-5% of Hep B positive pts & 75% of Hep C positive pts.

Acetaminophen

Carbon tetrachloride

Amanita Phalloides (mushroom)

NSAIDS

Volatile Anesthetics

Antibiotics

Antihypertensives

Anticonvulsants

Halothane

1/35000 - Kind of alot

*Note only 1/3000 were nonfatal

What is the biggest risk factor for Hepatitis associated with Halothane?

List 4 other risk factors:

Prior exposure to Halothane (10x more frequent in those with multiple exposures)

female

obesity

Hispanic

Adulthood

(most over 50, children resistant)

Fever

Chills

Anorexia

Nausea

Myalgias

Rash

Jaundice 3-6 days later

Overt Jaundice

Age over 40

Obesity

Affects only a very small percentage of those exposed

Incidence & severity unrelated to dose

What are the clues to the mechanism of halothane hepatitis?

What do we think is the mechanism?

Idiosyncratic

Prior exposure common

Delayed onset

Antibody production

Eosinophilia

Circulating immune complexes

Antibodies that bind to antigens from halothane treated rabbits 

Occupational exposure (Pediatric anesthesiologists have higher serum autoantibodies than controls. Levels are higher w female pedi anesthetists.)

Allergic or immunologic

T/F there are currently no reports of halothane hepatitis from occupational exposure.

The risk for IAs induced hepatitis is related to the degree of _______ and production of ________ ________.

List the IAs in order from most to least metabolized with metabolite:

True

metabolism

&

production of fluoroacetyl metabolites

H>E>I>D>S (0 fluoroacetyl metabolites for S)

Volatile Anesthetics and Hepatic Blood Flow

Volatile Anesthetics and Hepatic Blood Flow

Which IAs has a marked reduction (30%) in hepatic blood flow?

This IAs may also decrease _____ and ______ ______ reserves.

Desflurane

This IAs may also decrease splanchnic and hepatic oxygen reserves

Volatile Anesthetics and Hepatic Blood Flow

Which IAs is best for preserving blood flow and O2 to the liver?

List 2 other benefits of this IA for the liver:

When is this IA NOT best? Then which one is?

Sevo best preserves blood flow and oxygen delivery to liver

1.Hepatic arterial buffer system remains intact
2.Less reactive metabolic products

At very high MAC level (2.0MAC)

Iso is better at these high levels *per graph slide 53-54

N2O increases SNS tone so may slightly reduce hepatic arterial and portal venous flow

also

N2O inhibits methionine synthetase potentially producing toxic effects in the liver

Ketamine produces a dose-dependent increase in markers of hepatic injury.

What is the mechanism?

Sympathomimetic vs direct hepatotoxicity

Altered hepatic metabolism

When might Thiopental cause some hepatic dysfunction?

Other induction agents appear to be _____?

At doses greater than 750mg

Other induction agents appear to be safe

Opiods produce no significant effect on liver if...?

But watch out for..?

Hepatic blood flow and oxygenation remain normal

But look out for that Spincter of Oddi Spasm

(equal risk with all narcotics and can be treated with glucagon)

Sepsis and Inflammation

(hypovolemia & splanichnic hypoperfusion/ lg bacterial toxin load/ impairment of of hepatic arterial buffer response)

Hypoxia and Ischemia

(Liver is extremely sensitive to hypoxic insult; remember 25% of CO goes to liver normally and w/o that ischemic hepatitis can result)

Sympathetic nervous system stimulation

Release of vasopressin (ADH)

Activation of renin-angioensin-aldosterone sys.

Bad

Low flow, non-pulsatile perfusion

Catacholamine usage

Good

Hypothermia

Hepatic arterial buffer response helps maintain blood flow

Chronic Hepatitis implies hepatic inflammation &   _______ for greater than _____ months.

Classified based on: (3)

Hepatic inflammation and necrosis for >6 months

Classified based on:

Cause (based on serologic testing)

Grade (degree of necrosis & inflammation)

Stage (degree of fibrosis)

___% of acute HCV progresses to chronic HCV

1.8 million of US population has HCV and it is the most common indicator for __________.

85% of acute HCV progresses to chronic HCV

Most common indication for liver transplantation

*also cirrhosis per Anderson

What is the most common cause of chronic liver disease in U.S.?

Up to ___% of americans have NAFLD.

Fatty liver disease (non alcohol)

Up to 24% of Americans have NAFLD

What are the risk factors for NAFLD? (2)

Are these pts symptomatic?

Do they develop cirrhosis?

Obesity (70%)

DM II (75%)

Most asymptomatic

Some develop cirrhosis (<5% per Anderson)

Fatty liver (steatosis)

Alcoholic hepatitis

Cirrhosis

(Alcohol) fatty liver disease may develop even after only...?

AFLD is typically ____ and _____.

 brief period of heavy alcohol intake

 typically benign and resolves.

Alcoholic hepatitis is a precursor of ______.

It has up to a ____ fold increase in aminotransferase.

____ is typically higher than ____.

Alcoholic hepatitis is a precursor of cirrhosis

up to 10-fold increase in aminotransferases (ie GST)

AST typically higher than ALT (>2 ratio)

Abstinence

Bedrest

Adequate nutrition

2-3x increase

What are the most frequent etiologies of Cirrhosis?(2)

Cirrhosis is the ___ leading cause of death in US and affects ______ppl

Hep C

Alcohol

12th

3 million

Anorexia

Weakness

N/V

Absominal pain

Jaundice

Encephalopathy

Spider Nevi

Hepatosplenomegaly

Ascites

Hyperdynamic circulation

Decreased PVR

Normal to increased stroke volume

Normal filling pressures

Mildly increased heart rate

Low to normal arterial blood pressure

Total blood volume increased

↑vascular resistance to portal BF (from liver) + ↑portal venous inflow from dilated splanchnic arterioles

↓

↑portal venous pressure & subsequent development of portosystemic collaterals & shunting

↓

Majority of portal venous blood bypassing the liver

How is hepatic oxygenation maintained with Cirrhosis and Portal HTN?

 (remember 75% of liver BF normally comes from portal vein & 50% of oxygen)

Esophageal varices

(back up in esophageal vein)

Hepatic encephalopathy 

Altered drug metabolism

(many drugs bypass liver via shunts)

Susceptibility of bacterial infection

(liver not cleaning normally, & most GI absorption going systemic before going to liver) 

Ascites

Splenomegaly

How many gastroesophageal varices will bleed?

___% that are fatal?

T/F most will not rebleed if controlled with medications.

1/3

30% are fatal

False, most will rebleed

What is the management of Gastroesophageal Varices? (5)

What is the effectiveness rate with Octreotide and Endoscopic band ligation?

Fluid resuscitation/blood replacement

Airway protection

Octreotide (synthetic somatostatin - blocks glucagon effects) 

Endoscopic band ligation or sclerotherapy

TIPS

80% and 90%

Interstitial and airway edema

Mechanical effects of ascites

Pleural effusions

Hepatopulmonary Syndrome

(dyspnea & hypoxia with liver disease; worse when upright)

Chronic liver disease

Increased alveolar-arterial oxygen gradient

Intrapulmonary Vascular Dilations

What is the most common major complication in cirrhosis?

50% of pts with cirrhosis develop ascites within ____ yrs

Ascites

50% develop ascites within 10 years

Na+ and H2O

hypoalbuminemia

Na restriction & gentle diuresis

(if you diuresis too fast may cause RAS activation and subsequent renal issues; plus these pts don't tolerate losses in BV very well d/t lack of liver reservoir fx)

Paracentesis

Peritoneal-venous shut

TIPS

Transplant

Cefotaxime (3rd generation cephalosporin)

Long term antibiotic prophylaxis

Spontaneous Bacterial Peritonitis

1/3 of cases develop ____ failure?

Spontaneous Bacterial Peritonitis

Mortality? With and without renal dysfunction?

54% with renal dysfunction

9% without renal dysfunction

↓Na excretion

↓Free water excretion

(above 2 = ascites)

↓Renal perfusion & GFR

(hepatorenal syndrome)

Intense renal vasoconstriction

Low GFR = hypoperfusion

Preserved renal tubular function

Normal renal histology

(no injury to kidney tissue at first it is just a perfusion issue per lec)

Prostacyclin, nitric oxide, glucagon

↓

Splanchnic arterial vasodilation

↓

Reduced effective blood volume (d/t pooling)

also d/t acities fluid shifts

↓

Activation of renin-angiotensin-aldosterone system and sympathetic stimulation

↓

Intense renal vasoconstriction

1. The livers role as a blood reservoir is impaired so even modest blood loss can produce severe hypotension and lead to acute injury

2. Obstructive Jaundice & elevated levels of conjugated bilirubin contribute to renal toxicity

*so diuresis gently and stay on top of fluid needs!

Disorders of clotting factors & vit k

(decreased synthesis)

Thrombocytopenia

(backed up in spleen and incr destruction)

No, No that's not true

Spontaneous bleeding is uncommon

What is the biggest cause of thrombocytopenia with Cirrhosis?

List 4 other contributing factors:

Portal hypertension-induced splenomegaly with seqestration of up to 90% of circulating platletes in spleen

1. Increased destruction by immune mechanisms

2. Low-grade DIC

3. Sepsis

4. Bone marrow suppression by ehtanol, folate deficiency

Glycogen depletion (d/t poor nutritional state) & interference with gluconeogenesis (by ETOH)

Impaired conversion of lactic acid to lactate and then to glucose

above = acidosis and hypoglycemia

Gonadal dysfunction

Feminization, gynecomastia, shrinkage of testes and prostate

Oligomenorrhea

Amenorrhea

"men become women and women become men per Dr. Anderson"

Reversible, metabolic encephalopathy

Ranging from minimal personality changes or sleep disturbances to confusion, lethargy, coma

30-60% of cirrhotics

Large dietary protein load

GI Bleed

Constipation

Diuretics

Azotemia

(dec renal perfusion = incr. nitrogen waste products ie BUN and urea)

Surgery & anesthesia

Increased availability of agonist ligands of GABA receptors, so called natural benzodiazipines (Improvement in mental status with flumazenil)

Disruption of blood-brain barrier

Neurotoxic compounds

Impaired cerebral energy metabolism

Prevention

Lactulose

Neomycin

Zinc

Liver Transplant

Not broken down in the intestine

Produces mvmt of ammonia from blood to bowel

Cathartic (cleansing/purging)

Primary Hepatocellular Carcinoma

2.4/100,000 in U.S.

When does primary hepatocellular carcionoma occur?

Usually follows cirrhosis

Worldwide - large majority follow viral hepatitis

U.S. - 30-40% after viral hepatitis

Liver transplant

Few patients have a surgically resectable tumor at the time of presentation

When does pregnancy-related liver disease present?

What is it called?

What syndrome is commonly seen with it?

3rd trimester or immediately post-partum

Actue Fatty Liver of Pregnancy

HELLP

Characteristics of Acute Fatty Liver of Pregnancy

Severe?

Recovery?

Tx?

Rarely severe

Most recover fully

Treatment: Expedite delivery

(without delivery pt will go into acute liver failure and die without transplant per Stolting)

What is HELLP?

When may this be seen?

What is tx?

Hemolysis

Elevated Liver Enzymes

Low Platelets

Liver disease of Pregnancy

(caused by ischemic hepatocellular necrosis that will continue until baby is delivered)

Expedite delivery

Nause/Malaise

↓

Rapid onset of jaundice

↓

Altered mental status

List exam findings that would make you suspicious of hepatic disease (9)

1. Icterus (jaundiced sclera)
2. jaundice
3. ascites
4. spider angiomata
5. petechiae
6. asterixis (push hand back and if it flutters = liver issues)
7. gynecomastia
8. splenomegaly
9. palpable enlarged liver

What should we do if we have abnormal labs in the absence of history or physical exam findings?

(previously healthy non-liver diseased pt)

Delay surgery to avoid catching someone in the early, undiagnosed stages of liver disease

Not always practical

T/F Acute hepatic disease, regardless of the etiology, increases perioperative morbidity and mortality

True

acute hepatic disease

Per chart on slide 90

When do you investigate and elevated AST/ALT?

If greater than 2X normal what should you do?

If second test still >2X norm then if ALT>AST consider _____ and if AST>ALT consider ______.

T/F a formal evaluation with these pts will be required before surgery can proceed?

When it is greater than 2X normal 

(if less than 2X then proceed with surgery)

Repeat test

ALT>AST (ratio <1) = viral hepatitis

AST>ALT (ratio >2) = ETOH/drug abuse

True

Per chart on slide 90

If pt with elevated AST/ALT and abnormal INR then consider ______ dysfunction and ____ surgery.

If Alkaline phosphatase elevated >2X norm with abnormal ____ & ____ then = ________ disease and formal workup needed.

If AP up <2X and normal GGT and Bilirubin then you can ________?

hepatobiliary dysfuction

delay (needs workup)

GGT

bilirubin

biliary disease

proceed with surgery

If a pt has 7-8 of these risk factors they have a ____% risk for complications. 

1. Child-Pugh factors
2. Ascites
3. Cirrhosis (other than primary biliary)
4. Serum creatinine
5. COPD
6. Preop infection
7. Preop upper GI bleed
8. Higher ASA physical status
9. Intraop hypotension
10. Higher surgical severity score

100%

Periopertiave Risk Assessment

List components of Child (1964)

Child-Pugh (1972) (this is the current tool used)

Serum Albumin

Serum Bilirubin

Ascites

Encephalopathy

Nutritional status

Serum Albumin

Serum Bilirubin

Ascites

Encephalopathy

PT

Extent of liver disease

Age

Coexisting disease

Type, location, duration of surgery

There is increased cerebral uptake of benzodiazipines

Consider decreased doses

Careful titration

H2 blocker

Metoclopramide

Sodium bicitrate

No it is a low HER drug

Elimination T1/2 unchanged in cirrhosis

Propofol is a high HER drug so is its elimination changed with cirrhosis?

Duration?

Elimination profile unchanged from control

May see slight increase in recovery time/duration following infusion (not significant per Ron)

Etomidate

Clearance

Elimination

Duration/Recovery

Clearance unchanged in cirrhosis

Increased Vd may result in prolonged elimination of T1/2

and

unpredictable recovery

Ketamine

high HER

prolly not the best d/t SNS stimulation but "do what you need to do"

"dont give to a tiger"

Increased free fraction

Decreased clearance

(clearance would be increased with increase in free fraction of drug but, d/t liver disease & its effect on the CYP450 system, the overall clearance is decreased--remember low HER drugs are much more dependant on CYP450 syst)

Fentanyl

Volume of distribution

Elimination T1/2

No change in volume of distribution

Increased Elimination T1/2 d/t decreased clearance

Sufentanyl

No significant pharmacokinetic change from control

May have slightly prolonged effect following multiple doses

Dexmedetomidine (precedex)

Clearance

Elimination T1/2

Significantly decreased clearance

prolonged half-lives

Avoid direct drug-related toxicity

Maintain adequate hepatic perfusion and oxygenation 

How are we going to avoid drug-related toxicty and maintain adequate hepatic perfusion and oxygenation?????!!!!!!!

Most important is simply....b/c blood reservoir is gone.

Maintain adequate:

Cardiac output

Blood volume

Perfusion pressure

Oxygenation

Prompt replacement of fluid & blood

Decreased plasma cholinesterase

but likely not an issue

Hofman elimination

Essentially independent of hepatic & renal disease

Other NDPMR and hepatic disease...?

Dose?

Length of blockade?

Clearance?

Increase Vd so increased inital dose?

(Ron says yes, then can titrate subsequent doses with info gained with 1st dose & PNS)

Anticipate prolonged blockade

(recall all aminosteroidals are metabolized in liver/kidneys)

Markedly decreased clearance

Titrate to effect

Overall there is an increased concentration of _______ substances such as _______ with liver disease, resutling in markedly reduced response to ___________.

So what should you do to treat hypotension?

May need increased doses of catecholamines

or

give a non-adrenergic vasoconstrictor like vasopressin

The severity of liver dysfunction and effect on other organ systems

Coexisting disease

Anticipated extent of surgery

May encounter coagulopathy and excessive bleeding

Will not tolerate hypovolemia well

Least invasive

Allows titration of drugs

Adequate fluid loading

Absence of coagulopathy

Should we use colloids or crystalloids?

If use GETA then you should ______ induction unless emergency and then RSI is route.

No documented difference

titrate

When is monitoring of filling pressures appropriate?

Remember liver disease including_________ results in decreased ability to move blood to the central circulation.

In severe disease or more extensive surgery

 biliary obstruction

What do large increases in serum transaminases post op reflect?

Postop liver dysfunction is ____ but rarely _____ in a previously healthy pt?

Extensive hepatocellular necrosis

Postop liver dysfunction is common but rarely severe previously healthy pt.

Fulminant Hepatic Failure = A term used to describe acute liver failure in a previously healthy pt with the following criteria:

Encephalopathy within 2 weeks of developement of juandice

or

Encephalopathy within 8 weeks of initial manifestation of hepatic disease.

D/C any suspect medication

Investigate potential sources of infection

Consider extrahepatic biliary obstruction

Lab studies to quantify

new onset of hepatic dysfunction

surgery should be delayed

full workup should be done