Liver Flashcards
1
Q
What are some functions of the liver?
A
- 2-2.5% of TBW – largest organ/gland in body
- Adults: 600-1800g average wt (smaller in women)
- 5% neonates (150-170g)
- Adults: 600-1800g average wt (smaller in women)
Multiple life sustaining functions
- Filtration and storage of blood
* Serves as a blood reservoir.
* Kupfer cells within the liver sinusoids avidly remove bacteria and other substances from the portal blood.
- Filtration and storage of blood
- Metabolism of carbohydrates, proteins, fats, hormones, foreign chemicals
* Critical energy metabolism
- Metabolism of carbohydrates, proteins, fats, hormones, foreign chemicals
- Formation of bile
* Critical for emulsification of fats
* Increase surface area for absorption
- Formation of bile
- Storage of vitamins and iron
* Ex: Vit K → formation of coag factors
- Storage of vitamins and iron
- Formation of coagulation factors
* Failure of these fx contributes to intraop/postop hypoperfusion, tissue ischemia and activation of systemic inflammatory response – progression to MODS.
- Formation of coagulation factors
- Alters, excretes and modifies numerous gut derived substances.
- Most vascular organ in the body ~30% CO
2
Q
What is the difference in liver anatomy when looking at it via the surface anatomy vs physiologic anatomy?
A
Surface anatomy - four distinct topographical lobes: (in picture)
- right
- left
- falciform ligament in between R & L
- caudate
- quadrate
- The surface anatomic description doesn’t correspond to the branches of the liver’s vascular supply and therefore is of limited clinical significance.
- hexagonal unit on cross section
- central vein at center of hexagonal cross section
- drains hepatic vein–> IVC
- portal canal contains: connective tissue, lymphatics, nerves and portal triad (portal vein, hepatic artery, bile duct)
Physiologic anatomy → 8 functionally independent segments (AKA Couinaud system)
- Each segment has its own vascular flow and biliary drainage
- The physiologic segmental division of the liver and is based on divisions of the portal vein, hepatic artery, and biliary ducts.
- This anatomic arrangement facilitates limited segmental resection of the liver w/ relatively bloodless surgical dissection along the planes between the segments and thereby prevents major disruption of hepatobiliary function.
- Couinaud anatomy simplifies efforts to preserve healthy tissue and extirpate diseased regions, and has resulted in improved clinical outcomes for patients undergoing hepatic surgery for neoplasms or trauma-induced injuries
- In this model, the liver forms around vertical axis (portal canal) with
- hepatic arteriole,
- portal venule,
- bile ductule,
- lymph vessels,
- nerves
- Blood flows vertical to portal triads directed toward central veins
- as these vessels terminate, it forms the zones of the liver (Zone ,1, 2, 3)
- terminal vein is at periphery of acinus
3
Q
Describe the various zones of the liver in the acinus lobule concept.
A
- Acinus
- functional microvascular unit of the liver
- Forms around a vertical axis (the portal canal
- Consists:
- hepatic arteriole
- a portal venule
- a bile ductule
- lymph vessels
- nerves
- Blood flow vertical to the portal triads and directed radially toward the central veins.
- Center of Acinus = terminal vascular supply
- As terminate → form ZONES
- Zone 1: Most O2 rich blood (center)- periportal zone, gets first dibs on O2
- Zone 2: further away
- Zone 3: receives BF after 2 other regions
- New data suggests the “liver architecture more closely resembles the classic lobule more than it does the acinus.”
- Blood enters the center of the acinus and flows centrifugally to the hepatic venules. Bile flows in the opposite direction. The simple liver acinus lies between two or more terminal hepatic venules.
- The difference between lobule and acinus is that the terminal vein is at the center of the lobule and the terminal vein is at the periphery of the acinus.
- The conceptual advantage of the acinus concept is that the blood supply and biliary drainage of a portion of parenchyma reside in the same portal tract, whereas multiple portal vein branches and arteries supply each classic lobule
- Hepatocytes 75-80% liver volume
-
Zone 1 (periportal zone) – HIGHLY METABOLICALLY ACTIVE
- Cells are closest to the portal axis
- receive blood that is rich in O2 and nutrients
- Major site of:
- oxidative metabolism
- aerobic metabolism
- highest Kreb cycle enzymes/highest number mitochondria (gluconeogenesis, b-oxidation fatty acids, amino acid catabolism, bile acid secretion)
- conversion ammonia to urea*
- oxidative metabolism
- Major site of:
- **Most prone to hepatic reperfusion injury*
-
Zone 2 (midzonal region)
- arbitrary intermediary transition zone
- “anatomic reserve”- overlap with zone 1
-
Zone 3 (pericentral) cells at margin of acinus
- receive blood that has exchanged gases and metabolites with cells in zones 1 & 2
- → least resistant to metabolic and anoxic damage (most sensitive)
- Lowest O2 saturation
-
Major site of:
- CYP450
- anaerobic metabolism– high quantity of ER– (glycolysis and lipogenesis)
- general detox and biotransformation drugs, chemicals, toxins) These cells exquisitely susceptible to injury from systemic hypo-perfusion and hypoxemia – zone 3 cell necrosis is characteristic of acetaminophen/halothane toxicity
- **most prone to ischemic damage**
- receive blood that has exchanged gases and metabolites with cells in zones 1 & 2
4
Q
What is the innervation of the liver?
A
- Stimulation of SNS fibers post-ganglionic T3-T11
-
increases hepatic vascular resistance (decreased blood volume) → release blood into central circulation (referred to earlier as liver storing blood)
- autotransfuion of up to 80% hepatic blood (400-500 mL) if needed in SNS stimulation
- increases glycogenolysis and gluconeogenesis (increased BG)
- (catabolic/mobilization of energy mode)
-
increases hepatic vascular resistance (decreased blood volume) → release blood into central circulation (referred to earlier as liver storing blood)
- Stimulation of PSNS (vagus nerve)
- increases glucose uptake and glycogen synthesis
- (anabolic storage mode)
- increases glucose uptake and glycogen synthesis
- Branches of the splanchnic nerves (postganglionic sympathetic fibers from T6-11), vagus nerve, and phrenic nerve enter the liver w/ the major blood vessels and bile ducts. These nerve fibers form an intercommunicating plexus, w/ synapses on the terminal arterioles and venules.
- Sympathetic innervation of the hepatic and splanchnic vasculature plays a major role in regulating the volume of whole blood stored in, and expelled from, the hepatic reservoir. Studies in canine model = sympathoadrenal stimulation (e.g., hypercarbia, pain, hypoxia) can abruptly decrease hepatic blood flow and splanchnic vascular capacitance. Within seconds, splanchnic nerve stimulation can autotransfuse up to 80% of the hepatic blood (400–500 mL) into the central circulation. Other studies = vagal stimulation alters the tone of presinusoidal sphincters and influences blood flow distribution within the liver rather than total hepatic blood flow.
5
Q
What are some characteristics of the hepatic vascular system?
A
- 25-30% of CO = 1350ml/min
- Portal Vein = 1050 ml/min
- BF: 70-75%
- Oxygenation: 50%
- Blood drained from GI tract into here
- formed by confluence of splenic and superior mesenteric veins and receives blood from GI tract, spleen, pancreas and gallbladder
- portal vein has numerous tributaries of little importance until portal HTN present, and then these connections form large portosystemic shunts which allow venous blood flow to bypass liver and produce pathologies (ie esophageal varices)
- Blood drained from GI tract into here
- Hepatic Artery= 300 ml/min
- BF: 25%
- Hepatic artery arises from the celiac trunk in 80% of the population, the rest the superior mesenteric artery
- Oxygenation: 50%
- Branch off celiac artery (Also supplies rest of GI tract)
- 100% oxygenation going through even though less BF
- BF: 25%
- Portal vein pressure = 9mmHg
- Hepatic vein leading to vena cava = 0mmHg
- Normal Physiology:
- HIGH flow
- LOW resistance/pressure
- Normal Physiology:
6
Q
What regulates hepatic blood flow?
A
- Hepatic arterioles have a myogenic response to stretching keeps local blood flow constant, despite changes in BP
- Increase in transmural pressure (BP) → vasoconstriction (preventing elevations of local BF)
- Decrease in transmural pressure (Bp)→ vasodilation (preserving perfusion during systemic hypotension)
- don’t see this same regulation in portal vein!!
-
Considerations:
- Auto regulation of hepatic artery is present in metabolically active liver (postprandial hyperosmolarity)
- usually absent in fasted state → most OR patients are NPO
- VA dose-dependently decrease response
- Pressure-flow auto regulation does not exist in the portal circulation
-
Drop in BP → directly influence hepatic BF
- Liver sensitive to hypoTN episodes
- Although the liver receives 25% of CO, regional blood flow within the organ is such that certain areas are highly prone to ischemia. Intrinsic (regional microvascular) and extrinsic (neural and hormonal). Also decreases in ph or O2 and inc in CO2 of the portal blood promote increases in hepatic artery flow
- Auto regulation of hepatic artery is present in metabolically active liver (postprandial hyperosmolarity)
-
Hepatic arterial buffer response
- change in portal venous flow causes a reciprocal change in heaptic arterial blood flow
- as protal blood flow decreases, adenosine builds up, transfers to hepatic arterial wall causing a DILATION, which increases hepatic arterial blood flow
- as portal venous flow increases, this washes out the adenosine in the periportal regional and causes arteriolar resistance to rise, lowering hepatic arterial blood flow back to normal
-
Extrinsic influences
- tone of pre-portal splanchnic organs regulate portal vein flow
- decrease in pH or increase PaCO2 (acidosis) causes hepatic arterial flow to increase
- postprandial hyperosmolarity
- increases both hepatic arterila and portal venous flow
7
Q
What are the humoral influences on portal circulation in the hepatic arteries vs portal veins and what are the effects of common vasopressors and inotropes on hepatic blood flow?
A
-
Hepatic arterial bed
- α1 -, α2 -, and β2 -adrenergic receptors
-
Portal vein
- only α-receptors
Vasopressin
-
intensely constricts splanchnic arterial bed- distributes BF out and into central system
- Ex: tx varices → dec BF going to liver and therefore decreasing the blood flow bypassing liver and going to varices
- Lowers portal venous resistance
- effective treatment for portal hypertension/esophageal varices*
Epinephrine
- Epinephrine (all equal efficacy in receptors)
- Arterial side: initial vasoconstriction (α-receptor), followed by vasodilation (β-receptor)
- More balanced effect of epi on arterial beds vs vein because vein only has alpha receptor (missing Beta-2 dilation)
- Portal Vein: only vasoconstriction (α-receptor)
- Drop in portal vein flow
DOpamine
- vasoactive effects weak compared w/ epi and norepi
Glucagon
- dose-dependent relaxation of hepatic arterial smooth muscle
- antagonizes vasoconstrictor responses of the hepatic artery to various physiologic stimuli-including increases in SNS tone (vasodilation)
- ex: liver dx → liver not metabolizing glucagon → excessive levels of glucagon → wide spread dilation)–> causes hyperdynamic circulation seen in liver failure
ANG II
- severely constricts hepatic arterial & portal venous beds, & markedly ↓ both mesenteric & portal venous flow
- blood flow to liver may plummet
8
Q
Describe how the liver is considered a blood reservoir?
A
- Expandable organ
- Hepatic arteries, veins and capillaries contain 450 ml blood = 10-15% TBV
- a large, expandable venous organ capable of acting as a valuable blood reservoir in times of excess blood volume and capable of supplying extra blood in times of diminished blood volume.
- ~20% of blood is in arteries, 10% is in capillaries, and 70% is in veins
- Hepatic arteries, veins and capillaries contain 450 ml blood = 10-15% TBV
- Translocation of blood:
- With increased right heart failure/ increased right atrial pressure liver
- → accommodate an extra liter of blood (pushes blood back to liver)
- Intense SNS stimulation (pain, hypoxia, hypercarbia) can abruptly decrease hepatic blood flow and volume
-
80% of flow (400-500ml) can be expelled in a matter of seconds (ex: for hemorrhage)
- Autonomic innervation of the liver coupled w/ the neurohumoral input from the systemic circulation allows for rapid precise control of the reservoir volume.
-
80% of flow (400-500ml) can be expelled in a matter of seconds (ex: for hemorrhage)
- Anesthetics & liver disease impair this response and severe liver dx pts have impaired vasoconstriction as well incapacitating the splanchnic reservoir – prevent redirection of blood flow to heart and brain
- The normal liver moderates the hypotensive response to acute blood loss and hypovolemia
- With increased right heart failure/ increased right atrial pressure liver
9
Q
Why is the liver considered an endocrine ordgan?
A
- Insulin growth factor – 1- somatomedin
- mediates actions of hormones from other endocrine glands (bone growth in children)
- . Insulin-like growth factor promotes systemic growth, especially bone growth in children.
- Angiotensinogen - precursor of angiotensin II/ all angiotensin proteins, fluid and electrolyte balance
- regulates SBP (systemic tone)
- Regulates water and Na
- Thrombopoietin –
- regulates plt production by stimulating bone marrow precursor cells to differentiate into plt-generating megakaryocytes.
- Hepcidin
- responsible for iron homeostasis and regulates intestinal iron absorption, plasma iron concentrations, and tissue iron distribution by inducing degradation of the hepcidin receptor, ferroportin
- Conversion thyroxine (T4) to tri-iodothyronine (T3)
- T4 (inactive) to T3 (active)
- Inactivation of corticosteroids, ADH, aldosterone, estrogen, androgens, insulin,
- The interaction of altered hormone levels and diminished hepatic synthesis of hormone binding globulins w/ altered metabolism and receptor regulation leads to significant endocrine abnormalities in pts w/ liver disease.
- Nearly half the insulin produced by the pancreas never reaches the systemic circulation bc it’s degraded during a single passage through the liver.
- In addition to hormone synthesis, the liver participates in endocrine function by inactivating many hormones, including thyroxine, aldosterone, antidiuretic hormone, estrogens, androgens, and insulin.
10
Q
What are the coagulation factors formed in the liver?
A
- All coagulation factors formed in liver
- Except:
- vWF
- VIII
- VIII is made in both the liver and endothelial cells – often patients have enough even in severe liver disease
- III (tissue thromboplastin)
- IV (calcium)
- Except:
- Vitamin K dependent: need bile salts to get vit K!
- Prothrombin/Factor II
- Factor VII
- Factor IX
- Factor X
- Proteins C and S (anticoagulants)
- Thrombopoietin → plts
- Stimulate plt production!
- Synthesizes Anticoagulant factors
- antithrombin III, plasminogen activator inhibitor, Proteins C, S, Z, and fibrinolytic factors
- liver dx: see coagulation issues
- antithrombin III, plasminogen activator inhibitor, Proteins C, S, Z, and fibrinolytic factors
- Clearance of activated coagulation factors including fibrinolysins, TPAs (clearance essential for control of fibrinolytic states)
11
Q
What is liver’s role in the formation of erythrocytes production and breakdown? (very unlikely to be a question?)
A
- Liver responsible ~ 20% of heme production
- Used to produce cytochrome P450 enzymes
-
Deficiency in porphobilinogen deaminase (an enzyme in the biosynthetic heme pathway and CYP450 enzymes) → acute intermittent porphyria
- Consequences: NO BARBITUATES (or etomidate!)
- The liver is the primary erythropoietic organ of the fetus between the 9th and 24th week of gestation. It continues to be a major site of hematopoiesis until an infant is about 2 months of age. In healthy adults, the liver is responsible for about 20% of heme production; bone marrow makes the rest
- Metabolism of hgb produces bilirubin
- Hepatocytes responsible for conjugating bilirubin and releasing it into the bile to be eliminated via alimentary tract
Secretion of bile:
- Secretes 500 ml/day from common bile duct to duodenum
- Contains conjugated bile salts, cholesterol, phospholipids, conjugated bilirubins, electrolytes
- Bile acids
- help alkalinize & emulsify large fat particles
- → increase surface area for digestion/aiding absorption
- excretion of several waste products from blood
- ex: xenobiotics, bilirubin, calcium, & cholesterol
- Excretes Compounds >300-500 Daltons = too large for the kidney
- help alkalinize & emulsify large fat particles
- Considerations:
- Opioids interfere w/ biliary flow→ increasing pressure in common bile duct or inducing spasm in sphincter of Oddi
- Mimics angina in awake pt
- Tx: Antagonize action w/ → (dilate bile duct)
- VA’s
- naloxone, nitroglycerin, atropine
- glucagon *
- Opioids interfere w/ biliary flow→ increasing pressure in common bile duct or inducing spasm in sphincter of Oddi
12
Q
What is the liver’s role in excreting drugs, hormones and other substances?
A
- Detoxify or excrete into bile
- Ex: sulfonamides, penicillin, ampicillin, calcium, & erythromycin
- Termination of anesthetic effects via transformation by liver
- Predictable termination of the pharmacologic effects of many anesthetic agents depends on the liver for metabolic biotransformation into inactive products that can be eliminated
- Metabolize Endocrine gland hormones
- chemically alter and excreted by liver
- ex: thyroxine, (steroid hormones) estrogen, cortisol & aldosterone
- chemically alter and excreted by liver
13
Q
Impact of advanced liver disease on drug pharmacokinetics? (from ppt notes)
A
- Significant liver disease – portosystemic shunts allow orally administered drugs to bypass the first pass clearance + decreased liver blood flow= prolonged terminal half-life and increased systemic effects of high extraction drugs.
-
Hypoalbuminia increased free fraction – increased systemic effects, also increases elimination of those with low hepatic extraction ratios.
- If ascites is present may have an increased Vd.
- Doses should be decreased 50%
- It is often difficult in liver disease to predict the pharmacokinetics and pharmacodynamics of drugs.
- Often, cirrhotic patients with co-existing disease are better served receiving a hepatically cleared agent at reduced doses (careful titration) if it provides superior efficacy and side effects than less hepatically cleared agents.
14
Q
Whatis liver’s role in the cyp450 system?
A
- Liver has more than 20 different CYP enzymes
- Lots of genetic differences in people
- Up to four fold variation
- Lots of genetic differences in people
- Many of these isozymes contribute to:
- oxidation of drugs
- environmental toxins
- steroid hormones
- lipids
- bile acids
- Hepatocytes of zone 3 have the highest content of CYP proteins
- Zone 3: most sensitive to ischemic damage
- Also site of biotransformation → if toxic metabolites produced → impacts zone 3 cells
- Ex: acetaminophen → produce toxic metabolites (zone 3 most vulnerable)
- Also site of biotransformation → if toxic metabolites produced → impacts zone 3 cells
- Zone 3: most sensitive to ischemic damage
- Advanced cirrhosis lowers both total CYP and hepatic perfusion and results in significantly reduced clearances of many substances.
CYP Inducers:
- Phenobarbital, phenytoin-> induce several different cyp proteins
- Smoke from cigarettes, cannabis–> induces CYP 1A2
- Alcohol–> induces CYP2EI, CYP3A4
- Induces of CYP not only affect own metabolism, but affect drug metabolism and biologic action of many other substances
15
Q
Refresh on cyp inducers (in notes)
A
- Phenobarbital, phenytoin-> induce several different cyp proteins
- Smoke from cigarettes, cannabis–> induces CYP 1A2
- Alcohol–> induces CYP2EI, CYP3A4
- Induces of CYP not only affect own metabolism, but affect drug metabolism and biologic action of many other substances
- CYP induces activate nuclear orphan receptor transcriptional regulators and can participate in hepatic adaptation to chronic drug admin
- Genetic and environmental influneces are most important variable affecting drug metabolism
16
Q
What is intrinsic clearance of the liver?
A
- Reflects fraction of delivered drug load that is metabolized or extracted during a single pass through liver
-
High clearance – hepatic clearance approaches rates at which they transverse the liver
- Hepatic metabolism/clearance DEPENDS on hepatic BF
- Ex: decrease hepatic BF → highest impact on drugs listed below
- Ex: (see Box 22-1 Miller 8
- Lidocaine
- Diphenhydramine
- metoprolol
- Hepatic metabolism/clearance DEPENDS on hepatic BF
-
High clearance – hepatic clearance approaches rates at which they transverse the liver
-
Low clearance - hepatic clearances are relatively independent of hepatic blood flow
-
Aka: capacity dependent elimination
- Ex: anything changing free fraction of drug effects rate of clearing drug (low albumin [] )
-
Ex:
- Diazepam
- Acetaminophen
- warfarin
-
Aka: capacity dependent elimination
17
Q
What are some lab tests that show hepatocellular damage?
A
-
ALT (Serum alanine aminotransfersase)- SELECTIVE
- Only present in the liver (more selective for LIVER damage)
- Found primarily in zone 1 hepatocytes (area of oxidative metabolism)
- Only present in the liver (more selective for LIVER damage)
-
AST (Serum aspartate aminotransfersase)
- Present in a wide variety of tissues (liver, heart, skeletal muscle, brain, heart)
- Found primarily in zone 1 hepatocytes
- No prognosis can be done with levels of AST/ALT
- Found primarily in zone 1 hepatocytes
- Present in a wide variety of tissues (liver, heart, skeletal muscle, brain, heart)
-
LDH (lactate dehydrogenase)
- Nonspecific
-
GST
- Isoenzyme B found exclusively in liver
-
Specifically ZONE 3
- Worry about ischemic damage/toxic metabolite damage
-
Specifically ZONE 3
- *Highly sensitive
- Half-life (60-90 min)- short
- Track injury evolution
- Found in all acinar hepatocyte zones
- Isoenzyme B found exclusively in liver
18
Q
What are lab tests that assess hepatic synthetic function?
A
-
Albumin
- 1/2 life = 20 days
- Acute ischemic event → albumin levels wont reflect that
- Better tracking long-term/chronic fx
- Protein synthesis = function
- Low levels → fx impairment
- Poor specificity
- Ex: fluid overload, pregnancy → dilutional effect
- 1/2 life = 20 days
-
PT/INR
- CF ½ lives: 4 hrs - 4 days
- Factor VII- 4 hrs
- Fibrinogen- 4 days
- *helpful tracking severe deficits in hepatic fx
- Issue: Excess CF produced normally → if seeing drop in PT/INR, pt pretty sick (ESLD)
- CF ½ lives: 4 hrs - 4 days
- Caffeine clearance
- measure metabolites in saliva
- Idocyanine green
- extracted and metabolized exclusively by the liver
- administer and measure elimination kinetics (plasma disappearance rate/measured transcutaneously)
- Reflects both hepatic fx and hepatic BF
- extracted and metabolized exclusively by the liver
19
Q
What lab tests assess bile flow status?
A
-
Alkaline phosphatase (AP) isoenzymes
- 2-4X increase → suggests cholestatic disease
- Levels vary w/:
- gender, age, blood type
- increased in CHF, pregnancy, smokers, growth spurts, sepsis, hepatitis, etc.
- general screen
-
5’-nucleotidase (5’NT)
- Helps differentiate between intrahepatic vs extrahepatic issue
-
Gamma glutamyl transferase (GGT)
- Nonspecific
-
Serum bilirubin
- HELPFUL → Reflects hepatic excretion capability
- Conjugated levels
- High levels: →
- Mechanical outflow obstruction (→ jaundice)
- High levels: →
- Unconjugated levels:
- High levels → indicates difficulty w/ liver conjugating (2)
- High Hgb metabolism (Ex: hematoma or several blood tx → lots of bilirubin to conjugate)
- High levels → indicates difficulty w/ liver conjugating (2)
- Conjugated levels
- HELPFUL → Reflects hepatic excretion capability
20
Q
What are the common causes of viral hepatitis?
A
- Five types – similar clinical laboratory features
- Hepatitis- inflammation of liver
- Varied presentation among individual patients: asymptomatic VS influenza-like symptoms VS jaundice and acute hepatic failure
- Hepatitis A
- Transmission: Fecal/oral route- contamination of food
- Lasts ~21 days → fully recover
- Transmission: Fecal/oral route- contamination of food
- Hepatitis B (50% US cases)
- Transmission: Blood/sexual intercourse
- Asymptomatic
- Hepatitis C (30% US cases)
- Transmission: Blood/sexual intercourse
- …. 50-85% progress to chronic disease with 5-25% risk of developing cirrhosis – leading cause of transplant. New medications are decreasing viral load and “curing” patients.
- Hepatitis D (20% US cases)
- Transmission: Blood/sexual intercourse
- RNA strand requiring co-infection w/ Hep B
- Hepatitis E (rare)
- Fecal/oral – similar to A
- Foundin asia, Africa, central america
- Miscellaneous Causes – CMV, Epstein Barr, Herpes
21
Q
Describe the pathophysiology of halothane hepatitis including the classic presentation and risk factors?
A
-
All VA (except Sevo) metabolized by Cytochrome P450 2EI→
- oxidizes each anesthetic to yield highly reactive intermediates → covalently bind (acetylation) to hepatocytes (variety of hepatocellular macromolecules)
- Immune system recognizes the intermediary and hepatocyte as FOREIGN protein → ATTACKS
- Altered hepatic proteins trigger an immunologic response → causes massive hepatic necrosis
- oxidizes each anesthetic to yield highly reactive intermediates → covalently bind (acetylation) to hepatocytes (variety of hepatocellular macromolecules)
-
VA metabolism refresher (they would probably want to hear this?)
- Halothane 46% metabolized
- Enflurane 2.5-8.5% metabolized
- Sevoflurane 2-5% metabolized
- Not metabolized into intermediate (0% risk halothane hepatitis)
- Isoflurane 0.2-2% metabolized
- Desflurane 0.02% metabolized
- Halothane gone → less and less risk of developing response
-
Classic presentation of VA associated hepatitis:
- fever, anorexia, nausea, chills, myalgias, rash,
- arthralgia (joint pain)
- eosinophilia
- jaundice (3-6 days later)
- overt jaundice indicates severe disease and may indicate mortality rate of 40%
-
2 types-
- can be mild with small elevation AST/ALT
- Second type is fulminant form known as halothane hepatitis. elevated AST/ALT/bili/AP/massive necrosis
- Risk factors:
-
PRIOR EXPOSURE!
- multiple brief procedures within brief duration of time
- age >40 years old
- obesity, female gender
- Mexican ethnicity (chromosomal vulnerability)
- enzyme induction (ex: pt on barbs/phenytonin)
-
PRIOR EXPOSURE!
22
Q
What is the effect of our anesthetic gases on hepatic blood flow?
A
VA
- Hepatic BF and oxygenation decrease w/ VA
- (Halothane > Enflurane > Desflurane > Isoflurane > Sevoflurane) → sevo reduces BF the LEAST
- Portal BF reduced but hepatic arterial flow is maintained w/ des/iso/sevo
- Decreased CO and stress response → catecholamine-induced vasoconstriction
-
Catecholamines preferentially vasoconstrict splanchnic circulation (normally feeds portal vein) → no BF to portal vein
- Catecholamines improve BP but don’t help portal vein
-
Catecholamines preferentially vasoconstrict splanchnic circulation (normally feeds portal vein) → no BF to portal vein
- Metabolic demands do decrease improving the supply-demand balance a bit
N2O
- Increase SNS activity
- Consequences:
- mild vasoconstriction of splanchnic vasculature → decreased portal flow
- increase flow through hepatic arterial system
- Consequences:
- Inhibition of methionine synthase activity
- prolonged exposure → B12 deficiency
- No concrete evidence it causes hepatic toxicity if O2 supply/demand normal
- Dental providers 7 fold risk for liver dx
32
Q
Pathophys for cirrhosis-induced portal HTN?
A
. Cirrhosis and portal HTN induce circulatory changes that decrease the effective blood volume.
→ activates volume receptors and stimulates neurohumoral and intrarenal reflexes to decrease renal blood flow and to increase renal retention of sodium
- vicious cycle, all leads to retaining more and more fluid, ascites getting worse, and risk of variceal bleeding increasing
Schematic of pathways for cirrhosis-induced portal hypertension:
- the forward and backward theories.
- Cirrhosis and portal hypertension induce circulatory changes that decrease the effective blood volume.
- This activates volume receptors and stimulates neurohumoral and intrarenal reflexes to decrease renal blood flow and
- increase renal retention of sodium.
PVBF, portal venous blood flow; HABF, hepatic arterial blood flow; THBF, total hepatic blood flow; A-V, arteriovenous; PG’s, prostaglandins; ADH, antidiuretic hormone; ANF, atrial natriuretic factor; PAF, platelet activating factor.
49
Q
What are TIPS procedures?
A
Transjugular Intrahepatic Portal-Systemic Shunt Procedure
- percutaneously created intrahepatic connection of portal and systemic circulations
- Uses: ESLD to decrease portal pressure and attenuate complications related to portal hypertension
- Hook up PV to HV
- (Uses ex: variceal bleeding or refractory ascites)
- Improve QOL (not long term)–> minimizes need for paracentesis frequently
- Hook up PV to HV
- Diversion of PBF into the hepatic vein is achieved by placement of an expandable intraparenchymal tract
- Uses: ESLD to decrease portal pressure and attenuate complications related to portal hypertension
Pic:
Miller Figure 73-7 (TIPS) procedure.
A stent (or stents) passed through the IJ vein over a wire into the hepatic vein (A); dilated esophageal varices (EV) are apparent. The wire and stent or stents are then advanced into the portal vein (B), after which blood can pass through the portal vein into the hepatic vein and bypass and decompress dilated esophageal veins (C).
