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ANESTHESIA AND THE LIVER
ANESTHESIA AND THE LIVER
239
Nursing
Graduate
06/26/2011

Additional Nursing Flashcards

 


 

Cards

Term
Hepatic Blood Supply is ___% of cardiac output.
Definition
Hepatic Blood Supply is 25% of cardiac output.
Term
Where does the hepatic blood/oxygen supply come from?
Definition

Hepatic Artery

25% of blood supply

50% Oxygen supply

Portal Vein

75% of blood supply

50% of Oxygen supply

 

 

 

Term
At what pressures do the hepatic artery and portal vein supply the liver with blood?
Definition

Hepatic artery - at mean aortic pressure

Portal vein - at 6-10mmHg

Term

What are the tributaries of the Portal Vein?

 

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

Definition

Inferior Mesenteric Vein

Superior Mesenteric Vein

Splenic Vein (supplied by pancreatic veins)

Gastric Vein

Esophageal Vein

 

True; this causes things like esophageal varices

 

Term
Regulation of hepatic blood flow is designed to do two things:
Definition

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")

Term

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

 

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

Definition

Intrinsic regulation controls regional microvasculature in the liver itself

 

 hepatic buffer system

 metabolic regulation

 

neural (mostly SNS)

humoral (epi, glucagon etc)

Term

Is there any intrinsic regulation of portal venous flow?

 

 

Definition
No none; all intrinsic regulation mechanisms occur with hepatic artery flow
Term

What does the body do if there is a decrease in blood flow to the liver from portal vein (75% of normal bld supply)?

What is max response?

What is this mechanism called?


 

Definition

Increases hepatic artery flow in response to decreased portal vein flow.

 

Maximum response is 100% increase in hepatic artery flow in response to 50% decrease in portal vein flow.

 

Hepatic Buffering system

Term

Metabolic Regulation of liver blood flow

 

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.

Definition

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.

 

Term

Hepatic Buffer Response


What 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 hepatic arterioles dilate and this increases blood flow to liver.

Definition

Adenosine 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 hepatic arterioles dilate and this increases blood flow to liver.

Term
When is metabolic regulation most active?
Definition

In the Postprandial state

Less active in the fasted state

Term

Extrinsic Regulation - Neural


What is Portal Venous pressure dependent on?

Definition

Dependent on the diff in pressures across the:

Splanchnic arteriolar tone

Portal venules

Post-sinusoidal tone (Hepatic Veins)

[image]

Term
Hepatic arterial beds contain which adrenergic receptors?
Definition
alpha & beta receptors
Term
Portal venous beds contain which adrenergic receptors?
Definition
Alpha receptors
Term

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

 

 

 

 

 

Definition

False it is insignificant here

 

Term

What does glucagon do to the vasculature of the liver?

 It accomplishes this effect by?

Definition

Glucagon produces long-lasting arteriolar dilation.

 Antagonizing arterial constriction from other responses

Term
So...if a liver is walking down the street and Angiotensin II jumps out from the bushes...what will happen?
Definition

Marked constriction of arterial & portal vasculature

 Reduced mesenteric outflow

Reduced total hepatic blood flow

Term
What is the effect of Vasopressin on portal vein blood flow?
Definition

Intense vasoconstriction of splanchnic arterial vessels while decreasing portal venous resistance,

= Marked decrease in Portal Vein blood flow

Term

Esophageal Variceal bleeding can be treated by high doses of __________ to reduce portal hypertension & bleeding?

What is the more common treatment for esophageal varicies?

Definition

Vasopressin

 

More common tx is Octreotide/sandostatin

(inhibits glucagon's vasodilation effect)

 

 

 

 

 

 

Term
Which ANS system predominates in the liver?
Definition
Sympathetics predominate over Parasympathetics
Term
What is the effect of Hepatic SNS stimulation? (3)
Definition

Hepatic vascular resistance increases

Hepatic blood volume decreases

Blood glucose increases

(increased gluconeogenesis, increased glycogenolysis)

Term
What is the effect of hepatic parasympathetic innervation? 
Definition

Blood glucose decreases

(increases glycogen synthesis, increases glucoses uptake)

Term
How much of the total blood volume does the liver hold?
Definition
10-15% of the total blood volume
Term
How much blood is provided to the body by the  autotransfusion mechanism of the liver, how does this occur?
Definition
80% of hepatic blood volume (400-500ml) can be transferred to central circulation within seconds, this occurs d/t intense SNS stimulation
Term
How do anesthetic agents predispose patients to circulatory decompensation?
Definition
They suppress the SNS and attenuate the response of transferring hepatic blood volume to central circulation.
Term

Impaired vasoconstrictive responses due to severe liver disease also exacerbates hypotension from hypovolemia. T/F

Definition
True
Term
The liver synthesizes all coagulation factors except? Where are these 3 factors produced?
Definition

III - tissue thromboplastin (vascular wall)

IV - Ca++ (diet)

VIII:vWF (vascular endothelial cells)

Term
What are the vitamin K dependent factors produced by the liver (6)?
Definition

II - prothrombin

VII -Proconvertin

IX - Christmas factor

X - Stuart-Prower factor

Protien C

Protien S

Term
The synthesis of ______ in the liver modulates platelet production?
Definition
thrombopoietin
Term

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

 

Definition

Antithrombin III

Protein C and S

Fibrinolytic Factors (TPA and urokinase)

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

Term

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?

Definition

True 

Factor VII (Proconvertin)

T1/2 of 4 hours

Term
What may be a useful monitor/test of acute liver failure?
Definition
PT
Term
If you've been on Coumadin and I give you Vit K to reverse its effect and your PT/INR doesn't normalize; this may indicate __________________?
Definition
This may indicate underlying hepatic dysfunction
Term

The liver synthesizes and secretes 3 endocrine substances: 

It biotransforms: 

It also inactivates 5 substances:

Definition

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

Term

Bilirubin is the end product of _________?

 What % is derived from Hgb breakdown.

Definition

Heme degradation

75% derived from hemoglobin breakdown

Term

KNOW 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.

Definition
  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.

Term
Dietary carbohydrate arrives in liver via what vessel?
Definition

The Portal Vein

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

Term
What are the postprandial metabolic functions of the liver? 
Definition
Insulin mediated hepatic extraction of glucose from the portal vein ----- Excess glucose converted to glycogen
Term

How much glucose can the liver store? How long could this supply the body with glucose in the fasted state? 

 

Definition

Glucose is converted to glycogen ----- the Liver can store about 75 gms of glycogen ---- 24hrs 

 

Term
What are the fasting hepatic metabolic functions?
Definition

Initially glucagon mediated glycogen breakdown

 

Then muscle & fat catabolism & gluconeogenesis

Term
In chronic liver disease, what is hyperglycemia primarily due to?
Definition

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)

Term

What causes the hypoglycemia that is more common then hyperglycemia in advanced liver disease? (3)

 

What other liver condition may cause hypoglycemia?

Definition

Impaired glycogen storage

Impaired glycogenolysis

Impaired gluconeogenesis

 

Lg hepatocelllular CA d/t glucose uptake by tumor

Term
The liver makes fatty acids from excess?
Definition

Carbs

Protein

Lipids

Term
Then what does the liver do with the fatty acids?
Definition

Esterfies FFA to form

Triglycerides

Cholesterol

Phospholipids

Term
How are fatty acids transported to adipocytes in other parts of the body?
Definition
Packaged into lipoproteins for transport
Term
T/F the liver is capable of synthesizing the essential amino acids?
Definition
False only non-essential amino acids ----- Essential a.a. must come from your diet
Term
Proteins are degraded into amino acids in the hepatic _________.
Definition
Proteins are degraded into amino acids in the hepatic lysosomes.
Term
After proteins are broken down, what are the amino acids used for? (3)
Definition

Glucose production (gluconeogenesis)

 

Lipid metabolism (lipoproteins)

 

Further deaminated to keto-acids, glutamine, or ammonia

Term
The byproduct of amino acid or protien breakdown by the liver is ammonia. Ammonia is converted to ___ in the liver and then is excreted by the _____.
Definition

urea 

kidneys

Term
With liver dysfunction what does the failure of ammonia degradation in the liver lead to?
Definition
Increasing serum ammonia levels and hepatic encephalopathy
Term
How much of the protien produced by the liver is albumin?
Definition
10%
Term
Albumin makes up ___% of the plasma protiens
Definition
60%
Term
T/F The primary determinant of colloid oncotic pressure is Albumin?
Definition
TRUE
Term
Whats the half life of endogenous Albumin? Exogenous?
Definition

20 days (thus not a good marker to determine acute liver function)

16hrs = exogenous albumin

 

 

Term
Where is Psuedocholinesterase made?
Definition

In the liver

 

 

Term

Psuedocholinesterase is required for the degradation of what four drugs used in anesthesia?

Is it okay to use Suc with liver disease?

Definition

Succinylcholine

Mivacurium

Ester local anesthetics

Esmolol

YES - just may last a bit longer, but shouldnt be a big deal

Term
What are Kupffer cells? How much of the liver is made up of Kupffer cells?
Definition

Tissue macrophages which filter toxins, bacteria, debris from GI tract (an immune tissue)

10% of hepatic mass

Term

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

 

Definition

The impairment of Kupffer cell function is often a precursor to Sepsis and Multi-organ failure. Particularly following splanchnic ischemia or severe GI pathology

Term
Protiens made by the liver do what to the volume of distribution of a drug?
Definition
Decrease the volume of distribution of drugs --- decrease free drug concentrations
Term
The sum of all processes used by liver to eliminate a drug from the body is?
Definition
hepatic clearance
Term

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

 

Definition

Hepatic Biotransformation is metabolism of drug by hepatocytes into inactive, water-soluable (polar) substances for excretion in urine or bile.

 
Term
What do Phase 1 reactions in the liver do to drugs? What enzymes facilitate these reactions?
Definition

render drugs more polar for excretion by...

 Oxidation

Reduction

N-dealkylation

 Most involve cytochrome P450 enzymes

Term

What occurs during phase II reactions?

 What enzymes are required?

Definition

Water solubility of the compound is enhanced

 Requires transferase enzymes

Term
What is Intrinsic Clearance?
Definition

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

 

 

Term

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?

Definition

 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)

Term
What is clearance determined by with a low hepatic extraction ratio drug?
Definition

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.)

Term

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.

Definition

Those with High Hepatic Extraction Ratios

 *linear relationship* 

IAs

Term
What is the result of hypoalbuminemia regarding drug action?
Definition

Increased drug effect (more free drug)

More rapid clearance of low HER drugs 

*linear relationship*

Term
The volume of distribution of some drugs will be increased by _______________ and _______.
Definition
The volume of distribution of some drugs will be increased by hypoalbuminemia and ascites.
Term

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?

Definition

Increased systemic effect

Prolonged duration of action

 

titrate carefully

Term

List examples of


Low hepatic extraction ratio drugs (3)

 

Intermediate (2)

 

High (9)

Definition

Low hepatic extraction ratio drugs (3)

Alfentanyl

Diazepam

Thiopental

 

Intermediate (2)

Midazolam

Vecuronium

 

High (9)

Bupivacaine

Lidocaine

Etomidate

Propofol

Ketamine

Labetalol

Fentanyl

Morphine

Sufentanyl

Term

Liver func. tests don't give a dx of a specific hepatic disease...so what are they even good for?

 

What are the 3 categories of dysfunction?

 

Definition

They can identify a category of dysfunction

  1. Hepatocellular
  2. Hepatobiliary
  3. Hepatic synthesis

 

Term

What are tests that will indicate hepatocellular damage?

 

 

Definition

Transaminases

AST (SGOT)

ALT (SGPT)

 

Term

AST is located...? 

ALT is located...?

Definition

AST is in many tissues

*less specific

Heart

Muscle

Kidney

Brain

ALT is primarily in liver

Term
What is indicated by mild elevations (<3 fold) in AST/ALT?
Definition

Fatty liver

Nonalcoholic steatohepatitis

Drug toxicity

Chronic viral hepatitis

Term
What is indicated by larger increases (3-22x) in AST/ALT?
Definition

Acute Hepatitis

Exacerbation of chronic hepatitis

Term
What is indicated by the largest increases in AST/ALT?
Definition

Drug or toxin-induced hepatocellular necrosis

Severe viral hepatitis

Ischemic hepatitis secondary to shock

Term
Are AST and ALT levels good prognostic indicators of hepatocellular damage? why?
Definition

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

Term
AST/ALT ratio of ___  is typical in alcoholic liver disease
Definition

AST/ALT ratio >2 is typical in alcoholic liver disease

Term
AST/ALT ratio of __ is more common with viral hepatitis?
Definition

AST/ALT Ratio <1 is more common with viral hepatitis

Term
When might we see high levels of LDH with liver disease? Is LDH a good indicator of liver function/disease?
Definition
Heaptocelluar necrosis -- But has very low specificity for liver disease and is not particularly useful
Term

What is GST?

 Where is GST found?

Definition

Glutathione S-Transferase - a phase II enzyme

 

Many tissues, but isoenzyme B specific to liver

Term
GST is a useful marker of progression or resolution of liver injury d/t its _________?
Definition
GST is a useful marker of progression or resolution of liver injury d/t its short T1/2 of 90 minutes
Term

Where is GST found in the highest concentration? 

What is significant about this area?

Definition

In Centrolobular (zone 3) hepatocytes 

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

Term
Where is alkaline phophatase found?
Definition
Many organs -- Primarily liver & bone in healthy people
Term
An elevation of Alkaline Phosphatase disproportianate to AST and ALT levels is indicative of what?
Definition

Obstruction to bile flow

May be elevated during normal pregnancy

Term
What the freakin heck is 5'-Nucleotidase (5'NT)?
Definition
An alkaline phosphatase specific to liver disease, so used to assess whether an elevated AP is of hepatic origin.
Term

What is the most sensitive test for biliary tract disease?

 BUT what makes it un-useful?

Definition

GGT (Gamma glutamyl transpeptidase)

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

Term
The GGT has been largely replaced by ____.
Definition
The GGT has been argely replaced by 5'NT, d/t its better specificity to hepatobiliary issues.
Term
What do Bilirubin levels assess?
Definition

Severity of jaundice

 *we look at conjugated and unconjugated levels*

Term
High unconjugated bilirubin levels (what level mg/dl) indicates what, highest levels (mg/dl) indicate?
Definition

1-4mg/dl  

Excessive production (hemolysis) or Defective conjugation

>5mg/dl

Liver disease

Term

Conjugated Bilirubin elevation indicate? (2)

 

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

Definition

impaired hepatic excretion

extrahepatic obstruction (ie bile duct)

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

>35mg/dl

 

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

Serum Albumin

PT/INR

Term
Decreasing serum albumin levels in the absence of some other cause implies _______? Other non-liver cause are?
Definition

Worsening of chronic liver disease 

burns

nephrotic syndrome

poor nutrition

fluid retention

 

Term

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

 

 

Definition

True

 

 

Term

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?

Definition

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

Term

What screening test is ultrasound used for?

 

Definition

Hepatic disease

Cholelithiasis (gallstones)

Biliary Tract disease

Term
What is the best technique for diagnosis of Biliary tract obstruction and Cholelithiasis?
Definition
Ultrasound
Term
What provides a better anatomic definition than ultrasound?
Definition

CT

but $$$$$

Term
What is ERCP and why is it used?
Definition

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.

Term

What type of bilirubin would be elevated with a common bile duct obstruction?

Tx sphincter of Oddi spasms with ____ per lec.

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

Definition

Conjugated (liver is still doing its job, the bilirubin is just not getting into GI tract for elimination d/t obstruction)

Glucagon

Liver Biopsy

Term
What is the other name for the sphincter of Odi? What ducts make up common bile duct? Which other duct empties into common bile duct at sphincter of Odi?
Definition

ampulla of Vater

common hepatic duct and cystic duct

pancreatic duct


Term
Picture of common bile duct
Definition

[image]

Term

 

 

When are percutaneous liver biopsies contraindicated?

 

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

 T/F Liver biopsies can also be done open?

Definition

Platlets less than 60,000

PT more than 3 secs greater than control

Transjugular 

True

Term
How many Americans have some form of hepatobiliary disease?
Definition

 

10% (25 million)

Term
How many americans have Hep B/C?
Definition
5 million!!!
Term
Up to ___% of those with Hepatitis C may go on to Cirrhosis.
Definition
50%
Term
_____% of those who consume large amounts of alcohol will develop Severe alcoholic liver disease?
Definition

10-15%

 

Term

Acute viral hepatitis reported in the US

HAV?

HBV?

HCV?

HDV and HEV?

 

Definition

HAV - 20%

HBV - 50%

HCV - 30% 

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

 

Term

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.

Definition

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.

Term
What are predictable, dose-dependent causes of drug induced hepatitis? (3)
Definition

Acetaminophen

Carbon tetrachloride (dry cleaner)

Amanita Phalloides (mushroom)

Term
What are unpredictable, non dose-dependent causes of drug induced hepatitis?(5)
Definition

NSAIDS

Volatile Anesthetics

Antibiotics

Antihypertensives

Anticonvulsants

Term
What was the IAs most commonly associated w/ occurrence of fulminant heaptitis leading to death? What was ratio?
Definition

Halothane 

1/35000 - Kind of alot 

*Note only 1/3000 were nonfatal

Term

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

 

List 4 other risk factors:

Definition

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

 

female

obesity

Hispanic

Adulthood

(most over 50, children resistant)

Term
When was Halothane induced hepatitis seen in children?
Definition
only following multiple exposures
Term
What are the classic symptoms of Halothane Hepatitis...what occurs ____ days later?
Definition

Fever

Chills

Anorexia

Nausea

Myalgias

Rash

Jaundice 3-6 days later

Term
What are the predictors of a poor prognosis with Halothane Hepatitis? (3)
Definition

Overt Jaundice

Age over 40

Obesity

Term
Whats wierd about halothane hepatitis?
Definition

Affects only a very small percentage of those exposed

Incidence & severity unrelated to dose

Term

What are the clues to the mechanism of halothane hepatitis? 

What do we think is the mechanism?

Definition

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

 

Term

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

 Why is there a risk for hepatitis with IAs exposure?

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

Definition

True 

metabolism & production of fluoroacetyl metabolites 

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

Term

Volatile Anesthetics and Hepatic Blood Flow

Which IAs has the most cardiovascular & respiratory depression and the greatest reduction in hepatic arterial flow?

 

Definition
Halothane
Term

Volatile Anesthetics and Hepatic Blood Flow

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

Definition
Desflurane  -- This IAs may also decrease splanchnic and hepatic oxygen reserves
Term

Volatile Anesthetics and Hepatic Blood Flow

 Hepatic blood flow and oxygenation are well preserved with which IAs?

Definition
Isoflurane and Sevo
Term

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

 

List 2 other benefits of this IA for the liver:

 

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

Definition

Sevo best preserves blood flow & oxygen delivery to liver

 

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

 

At very high MAC level (2.0MAC)

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

Term
No convincing evidence that N2O causes hepatic toxicity in the absence of a precarious O2 supply-demand ratio in the liver...But!!!!
Definition
N2O increases SNS tone so may slightly reduce hepatic arterial & portal venous flow also N2O inhibits methionine synthetase potentially producing toxic effects in the liver
Term
Why does it suck to be a dentist?
Definition
60,000 dentists & dental assistants found a 1.7 fold increase in liver disease (possibly d/t N2O use)
Term
Ketamine produces a dose-dependent increase in markers of hepatic injury. What is the mechanism?
Definition

Sympathomimetic vs direct hepatotoxicity

Altered hepatic metabolism

Term

When might Thiopental cause some hepatic dysfunction?

T/F Other induction agents appear to be safe?

Definition

At doses greater than 750mg

True

Term

Opiods produce no significant effect on liver T/F?

 What is a SE of opioids that could cause liver issues?

How do you treat this SE?

Definition

True as long as blood flow & oxygenation remain normal

  Spincter of Oddi Spasm

(equal risk with all narcotics)

 glucagon, nitroglycerin, narcan

Term
What are some non-pharmacologic causes of hepatitis? 
Definition

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)

Term
How might surgical stress in general effect hepatic perfusion? (3)
Definition

Sympathetic nervous system stimulation

Release of vasopressin (ADH)

Activation of renin-angioensin-aldosterone sys.

all equal less liver blood flow

Term
What is the effect of a laparotomy on hepatic perfusion?
Definition
Produces marked vasoconstriction, reducing splanchnic and hepatic blood flow
Term
What is the effect of a laparoscopy on hepatic perfusion?
Definition
Decreased surgical stress response but... Pneumoperitoneum decreases splanchnic & hepatic flow
Term
List 2 bad and 2 good effects of CABG on hepatic perfusion?
Definition

Bad

Low flow, non-pulsatile perfusion

Catacholamine usage 

Good

Hypothermia

Hepatic arterial buffer response helps maintain blood flow

Term

Chronic Hepatitis implies hepatic inflammation & ______ for greater than _____ months. Classified based on: (3)

Definition

Hepatic inflammation and necrosis for >6 months

Classified based on:

Cause (based on serologic testing)

Grade (degree of necrosis & inflammation)

Stage (degree of fibrosis)

Term

What % of acute HCV progresses to chronic HCV

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

Definition

85% of acute HCV progresses to chronic HCV

 Most common indication for liver transplantation

*also cirrhosis per Anderson

Term
What is the most common cause of chronic liver disease in U.S.? Up to ___% of americans have this disease?
Definition

Fatty liver disease (non alcohol)

 Up to 24% of Americans have NAFLD

Term
What defines NAFLD?
Definition
Fat accumulation in liver >5% by weight
Term

What are the risk factors for NAFLD? (2)

 Are these pts symptomatic?

Do they develop cirrhosis?

Definition

Obesity (70%)

DM II (75%)

 Most asymptomatic

Some develop cirrhosis (<5% per Anderson)

Term
What are the three types of Alcoholic liver disease?
Definition

Fatty liver (steatosis)

Alcoholic hepatitis

Cirrhosis

Term
T/F (Alcohol) fatty liver disease may develop even after only a brief period of heavy alcohol intake. AFLD is typically long lasting and chronic.
Definition
False - it may develop after just a brief period of heavy drinking, but it is benign and resolves usually.
Term

Alcoholic hepatitis is a precursor of ______. 

It has up to a ____ fold increase in aminotransferase. 

Describe the AST/ALT ratio with Alcoholic hepatitis.

Definition

Alcoholic hepatitis is a precursor of cirrhosis


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

 

AST typically higher than ALT (>2 ratio)

Term
What is the treatment for alcoholic hepatitis?
Definition

Abstinence

Bedrest

Adequate nutrition

Term
Perioperative morbidity in alcohol abusers increases ___X?
Definition

2-3x increase

 

 

Term

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

 

Definition

Hep C

Alcoholic Hepatitis

  Cirrhosis is the 12th leading cause of death in US and affects 3 million people

Term
What are the symptoms of Cirrhosis? (4)
Definition

Anorexia

Weakness

N/V

Abdominal pain

Term
What are the signs of Cirrhosis? (5)
Definition

Jaundice

Encephalopathy

Spider Nevi

Hepatosplenomegaly

Ascites

JES HA 

Term
T/F Cirrhosis only affects the liver.
Definition
False, It affects nearly every organ system in the body.
Term
What are the cardiovasuclar effects of Cirrhosis?
Definition

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

Term
What is a cause of cirrhosis that can result in cardiomyopathy?
Definition
Alcoholic liver disease 
Term
*What is the hallmark of end-stage cirrhosis?
Definition
Portal Hypertension
Term
*Describe the steps that lead to portal HTN
Definition

↑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

Term

How is hepatic oxygenation and BF maintained with Cirrhosis & Portal HTN?

 

Definition

Hepatic arterial buffer response 

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

Term
What are the consequences of portosystemic shunting? (6)
Definition

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

Term
Gastroesophageal Varices are present in how many cirrhotic patients?
Definition
50%
Term

How many gastroesophageal varices will bleed? 

___% that are fatal? 

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

Definition

1/3

30% are fatal 

False, most will rebleed

Term

What is the management of Gastroesophageal Varices? (5)

 

 

Definition

Fluid resuscitation/blood replacement

Airway protection

Octreotide (synthetic somatostatin - blocks glucagon's vasodilatory effects) 

Endoscopic band ligation or sclerotherapy

TIPS

 

 

Term
 What are the factors involved in pulmonary dysfunction due to cirrhosis?
Definition

Interstitial and airway edema

(dec albumin production = increased edema)

Mechanical effects of ascites

(dec FRC)

Pleural effusions

Hepatopulmonary Syndrome

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

Term
What is the triad of Hepatopulmonary Syndrome?
Definition

1. Chronic liver disease 

2. Intrapulmonary Vascular Dilations

      Vascular dilations result in arteriovenous communications & hypoxia

3. Increased alveolar-arterial oxygen gradient

      d/t pulm edema from vascular congestion

Term

What is the most common major complication in cirrhosis?

 

 

Definition
Ascites - 50% develop ascites within 10 years
Term
50% of cirrhotics with ascites die within ___ yrs
Definition
3 years
Term
The pathogenesis of ascites is poorly understood but involves ____ and ____ retention and ______.
Definition

Na+ and H2O

hypoalbuminemia

Term
What is the management of ascites? (5)
Definition

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

Term
What brings on spontaneous bacterial peritonitis?
Definition
Develops secondary to translocation of bacteria from the intestines (incr. permeability in walls) to lymph nodes and subsequent bacteremia 
Term
What is the tx for spontaneous bacterial peritonitis?
Definition

Cefotaxime (3rd generation cephalosporin)

Long term antibiotic prophylaxis

Term

Spontaneous Bacterial Peritonitis


1/3 of cases develop what other organ dysfunction?

Definition
Renal
Term

Spontaneous Bacterial Peritonitis

 

Mortality? With and without renal dysfunction?

Definition

54% with renal dysfunction

9% without renal dysfunction

Term
What is hepatorenal syndrome?
Definition

↓Renal perfusion & GFR seen with cirrhosis


 

Term
Characteristics of Hepatorenal Syndrome (4)
Definition

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)

Term

Describe the pathophysiology of hepatorenal syndrome

(5 steps)

Definition

Decreased portal vein blood flow to liver 

Prostacyclin, nitric oxide, glucagon, adenosine

Splanchnic arterial vasodilation (metabolic/buffer system)

Reduced effective blood volume

(d/t pooling in portal system -- also d/t acities fluid shifts)

Activation of renin-angiotensin-aldosterone system and sympathetic stimulation

Intense renal vasoconstriction

Term
What are two situations in cirrhosis that can cause acute renal failure & acute tubular necrosis?
Definition

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

 

2. Obstructive Jaundice & elevated levels of conjugated bilirubin contribute to renal toxicity (>35mg/dl).

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

Term
What is the occurance of thrombocytopenia w/ liver dx?
Definition
50% - liver normally makes thrombopoietin which stimulates platelet production
Term

What are the 2 major coagultion disorders with cirrhosis?

What is the specific cause of each?

Definition

Disorders of clotting factors & vit k (decreased synthesis)

 Thrombocytopenia (backed up in spleen and incr destruction)

Term
What is the biggest cause of thrombocytopenia with Cirrhosis? List 4 other contributing factors:
Definition

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

Term
What contributes to hypoglycemia and acidosis w/ cirrhosis? (2)
Definition

1. Glycogen depletion (d/t poor nutritional state) &

    interference with gluconeogenesis (by ETOH)

2. Impaired conversion of lactic acid to lactate & then to

   glucose


Term
What is a terrible thing that happens to men w/ cirrhosis?
Definition
Gonadal dysfunction - Feminization, gynecomastia, shrinkage of testes and prostate
Term
How do endocrine disorders associated with cirrhosis affect women?
Definition

Oligomenorrhea

Amenorrhea 

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

Term
Describe hepatic encephalopathy.
Definition

Reversible, metabolic encephalopathy

 

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

 

30-60% of cirrhotics

Term
What are precipitators of Hepatic Encephalopathy?
Definition

Large dietary protein load = inc ammonia

GI Bleed

Constipation

Diuretics

Azotemia

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

Surgery & anesthesia

Term
What is the most important factor in causing HE?
Definition
Increased ammonia
Term
What are the possible mechanisms of the global depression seen in hepatic encephalopathy? (4)
Definition

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

Term
What is the treatment for HE?
Definition

Prevention

Lactulose

Neomycin

Zinc

Liver Transplant

Term
How does lactulose treat HE?
Definition

Not broken down in the intestine

Produces mvmt of ammonia from blood to bowel

Cathartic (cleansing/purging)

Term
How does Neomycin treat HE?
Definition
Reduces urease-producing bacteria in gut
Term
How does zinc treat HE?
Definition
Two enzymes needed for converstion of ammonia to urea are zinc dependent
Term
What is the 3rd most frequent cause of death from CA?
Definition

Primary Hepatocellular Carcinoma

2.4/100,000 in U.S.

Term

When does primary hepatocellular carcionoma occur?

 

 

Definition

Usually follows cirrhosis

Worldwide - large majority follow viral hepatitis

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

Term
What is the treatment for primary hepatocellular carcinoma?
Definition

Liver transplant 

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

Term

When does pregnancy-related liver disease present? 

What is this type of liver disease called?

What syndrome is commonly seen with it?

Definition

3rd trimester or immediately post-partum

 Actue Fatty Liver of Pregnancy

 HELLP

Term

Characteristics of Acute Fatty Liver of Pregnancy

Severe?

Recovery?

Tx?

Definition

Rarely severe

Most recover fully

Treatment: Expedite delivery

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

Term

What is HELLP?

 When may this be seen?

 What is tx?

Definition

Hemolysis

Elevated Liver Enzymes

Low Platelets 

Liver disease of Pregnancy

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

Expedite delivery

Term
What in our pre-op history will indicate acute liver failure?
Definition

Nause/Malaise

Rapid onset of jaundice

Altered mental status

 

 

Term

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

 

 

Definition
  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
Term
If there is no history or physical exam suggestive of liver disease should we draw labs looking for it?
Definition
Nope
Term
T/F If hepatic disease is known or suspected you should draw labs to quantify degree of dysfunction
Definition
True
Term

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

 (previously healthy non-liver diseased pt)

Definition
Delay surgery to avoid catching someone in the early, undiagnosed stages of liver disease - Not always practical
Term

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

 

Elective surgery should be postponed if the patient is known to have _____ hepatic disease.

Definition

True by 2-3X

 

acute hepatic disease

Term

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?

Definition

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


Term

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

Biliary disease is indicated with what abnormal labs?

When is it ok to proceed with surgery?

Definition

hepatobiliary dysfuction

delay (needs workup) 

If Alkaline phosphatase elevated >2X norm with abnormal GGT and bilirubin 

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

Term

What risk factors are taken into account when assessing the severity of hepatic disease? 

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

Definition
  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%

Term
List components of Child-Pugh (1972) Periopertiave Risk Assessment Tool:
Definition

Serum Albumin

Serum Bilirubin

Ascites

Encephalopathy

PT/INR

Term
Preoperative concerns include...
Definition

Extent of liver disease

Age

Coexisting disease

Type, location, duration of surgery

Term
Which surgeries are associated with the highest risk of death with liver disease?
Definition
GI and Emergency surgeries
Term
How might our benzos need to be adjusted?
Definition

There is increased cerebral uptake of benzodiazipines

Consider decreased doses

Careful titration

Term
What are the components of the Meld Score? What is this score used for?
Definition

Creatinine

bilirubin

INR

prioritization of liver transplants

meld score = 0.957 x log (creatinine mg/dl) + 0.378 x log (bilirubin mg/dl) + 1.12 x log (INR) + 0.643

Term
Will the duration/elimination be prolonged with use of Thiopental with liver disease?
Definition

No it is a low HER drug

Elimination T1/2 unchanged in cirrhosis

Term

Will the duration/elimination be prolonged with use of Propofol with liver disease?

 

 

Definition

Elimination profile unchanged from control 

May see slight increase in recovery time/duration following infusion b/c it is a HHER drug (not significant per Ron)

Term

Etomidate - high or low HER?

Clearance

Elimination

Duration/Recovery

Definition

High HER

Clearance unchanged in cirrhosis 

Increased Vd may result in prolonged elimination of T1/2 and unpredictable recovery

Term

Ketamine


Definition

high HER

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

 

Term
Morphine and Demerol clearance and elimination with liver dx?
Definition
1.5-2 fold decrease in clearance and increase in elimination T1/2
Term
Alfentanyl free fraction and clearance with liver disease?
Definition

Increased free fraction (less albumin) 

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)

Term

Fentanyl

 Volume of distribution

Elimination T1/2

Definition

No change in volume of distribution

Increased Elimination T1/2 d/t decreased clearance

Term

Sufentanyl



Definition

No significant pharmacokinetic change from control

May have slightly prolonged effect following multiple doses

Term
Remifentanyl - clearance in liver disease
Definition
Clearance unaltered in severe liver disease
Term

Dexmedetomidine (precedex) with liver disease

Clearance

Elimination T1/2

Definition

Significantly decreased clearance

prolonged half-lives

Term
What is Rons Bottom Line on Induction Agents?
Definition
Decreases in plasma proteins may result in a increase of free drug and more significant responses to a "standard" dose of these drugs.
Term
What are the goals for the maintenance of anesthesia?
Definition

Avoid direct drug-related toxicity

Maintain adequate hepatic perfusion and oxygenation 

Term

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.

Definition

Maintain adequate:

Cardiac output

Blood volume

Perfusion pressure

Oxygenation 

Prompt replacement of fluid & blood

Term
Succs in hepatic disease...prolonged?
Definition

Decreased plasma cholinesterase

but likely not an issue

Term
Mivacurium in hepatic disease - prolonged?
Definition
Decreased plasma cholinesterase will prolong action
Term
Atracurium/Cisatracurium with hepatic disease...?
Definition

Hofman elimination 

Essentially independent of hepatic & renal disease

Term

Other NDPMR and hepatic disease...?

 Dose?

Length of blockade?

Clearance?

 

Definition

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

Term

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

 

So what should you do to treat hypotension?

Definition

Overall there is an increased concentration of vasodilatory substances such as glucagon with liver disease, resutling in markedly reduced response to catecholamines

May need increased doses of catecholamines

or

give a non-adrenergic vasoconstrictor like vasopressin

Term
Why is a large bore IV access a must in anything but the most peripheral cases?
Definition

May encounter coagulopathy and excessive bleeding

Will not tolerate hypovolemia well

Term
A regional is typically well tolerated as long as 2 conditions are met:
Definition

Adequate fluid loading

Absence of coagulopathy

Term
 Remember liver disease including _________ results in decreased ability to move blood to the central circulation (autotransfusion)
Definition
biliary obstruction
Term
We may see jaundice postop following ______________ in the absence of liver insult
Definition

We may see jaundice postop following reabsorption of surgical hematoma in the absence of liver insult

Term

What do large increases in serum transaminases post op reflect? 

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

Definition

Extensive hepatocellular necrosis 

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

Term

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

 
Definition

Encephalopathy within 2 weeks of developement of juandice

or

Encephalopathy within 8 weeks of initial manifestation of hepatic disease.

Term
Remember per the study on ASA1 pts on slide 111 that preop elevation of LFT may indicated _______ and surgery should be ______ and ______ done.
Definition

new onset of hepatic dysfunction

surgery should be delayed

full workup should be done

Term
What is Icterus
Definition
jaundice sclera
Term
What is spider angiomata
Definition
a form of telangiectasis characterized by a central elevated red dot the size of a pinhead from which small blood vessels radiate. Spider angiomas are often associated with elevated estrogen levels, such as occur in pregnancy or when the liver is diseased and unable to detoxify estrogens. Also called spider nevus
Term
What is asterixis
Definition
Push hand back and if it flutters = liver issues
Term

Child-Pugh Score 

Class A, B, C, how many points and % surgical mortality?

Definition

Class A = 5-6 pts = 10% surgical mortality

Class B = 7-9 points = 30% surgical mortality

Class C = 10-15 points = 82% surgical mortality

Term
What is the normal AST and ALT levels
Definition

AST = 10-40 units/L

ALT = 7-56 units/L

Term
Describe bilirubin levels, aminotransferase levels, Alkaline phosphatase levels, and causes of prehepatic dysfunction.
Definition

- unconjugated bilirubin levels will be elevated

- AST/ALT levels will be normal

- AP levels will be normal

- Causes: hemolysis, hematoma resorbtion, bilirubin overdose in blood transfusion

Term

Describe bilirubin levels, aminotransferase levels, Alkaline phosphatase levels, and causes of intrahepatic dysfunction.

Definition

- increased conjugated fraction

- increased AST/ALT, GST

- normal or slightly increased AP

- Causes: viruses, drugs, cirrhosis, sepsis, hypoxemia

Term

Describe bilirubin levels, aminotransferase levels, Alkaline phosphatase levels, and causes of posthepatic dysfunction.

Definition

- conjugated bilirubin is increased

- AST/ALT, GST are normal 

- markely increased AP

- Cause: biliary tract stones or sepsis

Term
What is the portal triad?
Definition
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