Hepatic

What is the mortality rate associated with ETOH during sx?

50%

The hepatic portal vein is formed from the splenic and ___________ ______________ veins. A.) inferior mesenteric B.) superior mesenteric C.) distal pancreatic D.) proximal mesenteric

B) Superior Mesenteric & A) Inferior mesenteric

Which 3 types of hepatitis are transmitted via percutaneous mucosa?

B/C/D

Which 3 types of hepatitis comes from blood/blood-derived boy fluid source?

B/C/D

Describe hepatic blood flow

Blood goes from the aorta to the hepatic artery to the liver. Blood from the celiac artery (stomach, spleen, pancreas), superior mesenteric artery (pancreas, small intestines, colon) and inferior mesenteric artery (colon) also proceed to the liver, thru the liver sinusoids starting in zone 1 (closest to terminal vessels, most blood flow, most resistant to hypoxia) and moving medially within the lobule to Zone III (least resistant to hypoxia, hepatotoxins, other agents and most drug metabolism happens here).

***What blood factors are synthesized in the liver?

I, II, V, VII, IX, X so All except: factors III (tissue thromboplastin), IV (calcium), and *VIII (von Willebrand factor)

What is the #1 risk factor for Hep c?

IVDU (61%)

How can the liver autotransfuse the body?

If pt is having low blood volume, liver stores a large amt of blood and will autotransfuse via stores of blood in the liver

The _________________ communicate with the Space of Disse and 1/3 to 1/2 of lymph is produced here

Lymphatic channel

Stones of biliary tract are most often in ____________ and are ____________ gallstones

Stones of biliary tract are most often in FEMALES (20%) and are radiolucent-hydrophobic CHOLESTEROL molecules (90%) - 10% are radiopaque-calcium bilirubinate

procedure to bypass liver, problems associated?

TIPPS - bypass liver = toxins aren't filtered out, bacteremia is BIG risk now

**What is needed for the liver to synthesize prothrombin (Factor II) and factors VII, IX, and X?

Vitamin K -Vitamin K needs fat absorption to be absorbed (prob if biliary disease bc have decreased Vit K) - may respond to intravenous Vit K

**What hepatic disease is associated with accumulation of copper as a result of defective biliary excretion?

Wilson's Disease - age 15 - have neuro/hepatic dysfxn TX: Penicillamin, chelating drug that binds copper and promotes urinary excretion

How much can the hepatic artery compensate if portal vein flow is impeded?

With increased portal vein resistance, hepatic artery can compensate up to 100% to maintain hepatic oxygen delivery = Hepatic Arterial Buffer System *Barash pg 1295

What are the 3 zones of the liver? and what do they do?

Zone 1: - close to terminal vessels (gets blood first) - FIRST to regenerate - LAST to develop necrosis (bc getting that oxygen rich blood) - carbohydrate metabolism here Zone 2: - less oxygen and nutrient content than zone 1 Zone 3: - MOST susceptible to hypoxia, hepatotoxins, other agents - drug metabolism here **Bile flow is COUNTER-current to blood flow

What is the Space of Disse?

between sinusoidal capillaries and hepatocytes

How long will immunity with Hep A vaccine last for children and for adults?

children: 14-20 years adults: 25 years

gall bladder obstruction may interfere with what?

clearance of some muscle relaxants - esp ROC with lap chole think: - increased intra-abd pressure (from the insufflation and reverse T) - reverse T - insufflation of CO2 (and subsequent desufflation)

Why use RSI for induction?

delayed gastric emptying

What divides the left and right loves of the liver?

falciform ligament

*Why do hepatic failure pts have increased risk of sepsis?

liver produces complement proteins that kill invaders. liver disease = not producing complement proteins to kill bacteria --> risk of sepsis

What is normal Portal pressure and what is portal HTN?

nml: 5-10 mmHg HTN: >20

What happens if the portal system is not functioning?

portal system is vital to get things to liver to be metabolized. atrophy of intestine --> translocation of bacteria --> liver not functioning well --> bacteremia throughout the body

What is the treatment for Hep A?

post exposure IgG - hep A vaccine (even post exposure)

For hepC what labs do you monitor?

pt will continue to have antibodies to hep C, but that doesn't matter - watch ALT (transaminases)

How will ascites effect gas exchange?

respiratory problem d/t ascites pushing up and restricting air exchange Labs - resp alkalosis - hyperventilating, run TEG - check INR/PT, H/H, platelets, BUN/Crt

**What are some respiratory effects from cirrhosis?

- *hyperventilation with respiratory ALKALOSIS - hypoxemia d/t R to L shunt up to 40% of CO -*INCREASED diaphragm w/decreased lung volumes and DECREASED FRC - *Restrictive Ventilation defect --> pleural effusions (elephant sitting on chest)

How much does the Hepatic Artery supply blood to liver?

- 25% of total FLOW - 45-50 % of oxygen requirement (saturated with 98% oxygen) - maintains nutrition of connective tissue and walls of bile ducts

How much does the Portal Vein supply blood to liver?

- 75% of total FLOW - supplies 50-55% of oxygen requirement (saturated with 85% oxygen) .....first supplies oxygen to pancreas, stomach, spleen, THEN portal vein, then liver

How do we eliminate gallstones?

- Chenodiol or ursodoxycholic acid - dissolves cholesterol stones - Methylterbutyl ether infused through transhepatic catheter to dissolve stones -Lithotripsy in select cases - cholecystectomy, CBD exploration

Pt with ascites doesn't have good gastric emptying, what premed may be helpful?

- H2 histamine blocker (ranitidine), metoclopramide (reglan), Na+ citrate

**Describe bilirubin metabolism leads to what?

- Hepatocytes produce roughly 500 mL of bile daily. - Between meals, high pressure in the sphincter of Oddi diverts bile to gallbladder for storage - The gallbladder holds 35 to 50 mL of bile in concentrated form - presence of fat in the duodenum causes release of the hormone cholecystokinin from duodenal mucosa --> reaches the gallbladder via circulation and stimulates gallbladder contraction - Bile contains bile salts, bilirubin, and cholesterol. - Bile salts act as a detergent, solubilizing fat into micelles, which are absorbed - Bile salts return to the liver via the portal vein, completing the enterohepatic circulation - **Prob with liver dysfxn: Bile salts are needed for fat absorption, and cholestasis can result in steatorrhea (fatty, bulky stool) and vitamin K deficiency = **bleeding risk

**What labs will be INCREASED with POST-HEPATIC dysfunction?

- Increased Alk phos, conjugated -normal trasaminase (AST/ALT) Gall*stones (cholelithiasis), cholecystitis (also sepsis and cancer, placenta)—**biliary system involvement - complication with ERCP = pancreatitis - think gallbladder issues = increased alkphos (post-hepatic prob)

**What labs are INCREASED with INTRA-HEPATIC dysfunction?

- Increased transaminase (SGOT/SPGT or AST/ALT) Increases conjugated bilirubin d/t direct damage to liver -Hep C and liver involvement (viruses, drugs, sepsis, hypoxemia, CHF, cirrhosis), acetaminophen OD (d/t metabolite)

**What labs are Increased with PRE-HEPATIC dysfunction?

- Increased unconjugated bilirubin (indirect) w/ HEMATOMA metabolism, GI bleeding (increased bili absorbed)

What are the tx for hep c?

- Interferon -Ribavirin -Sofosbuvir (Sovaldi) - Simeprevir (Olysio)

Which induction agent is the safest to use with a pt with liver diseases because they have SMALL hepatic extraction ratio (NOT dependent on blood flow)?

- Sodium Thiopental (STP) - Roc (however increased vol of distribution and onset is prolonged) - Phenytoin

If pt has elevated PT/PTT, what would you do?

- Vitamin K 10mg 3x/day for a few days - BUT it needs at least 24 hours for effect - immediate: FFP, platelets (1 pack = 10,000)

What is the AST/ALT ratio difference for alcoholic liver disease vs viral hepatitis?

- alcoholic liver disease, in which the ratio = >2 - viral hepatitis ratio <1

Where are the bile canaliculi?

- between hepatocytes within each plate and JOIN to FORM bile ducts

**What does it mean if a drug has low hepatic extraction ratio and what drugs have this

- blood flow doesn't matter, drug will still be metabolized (independent of changes in liver blood flow) 1) sodium thiopental 2) Roc 3) phenytoin

Renal and fluid imbalance issues d/t cirrhosis?

- decreased renal perfusion (hepatorenal syndrome) - Electrolyte disturbances: hyponatremia, hypokalemia

CNS changes with cirrhosis?

- encephalopathy - increased ICP d/t toxins affecting BBB - toxins: ammonia, short chain fatty acids--> effect BBB

**Is albumin a good indicator in ACUTE and CHRONIC liver disease?

- good indicator in CHRONIC bc *1/2 life is 14-21 days, will see decrease with Chronic - NOT good indicator in acute - provides 70% of oncotic pressure: albumin keeps volume in the blood. issues with ascites and edema bc less albumin in chronic hepatic disease so less to hold volume in blood and volume leaks interstitially - 10-15gm produced/day - normal level 3.5-5 gm/dl

Why would you choose to NOT use propofol infusion on a pt with liver disease? but propofol for induction may be ok

- has LARGE hepatic extraction ratio = metabolism of propofol is DEPENDENT on blood flow --> will have prolonged effect of propofol d/t not being metabolized as normal

**Why does ascites form?

- increased portal venous pressure (increased hydrostatic pressure) - decreased albumin - decreased ADH metabolism (= increased ADH holding in fluid) -> increased vol of distribution

What is the pathogenesis of Hep B?

- incubation period 6 weeks from exposure-avg 90 days - **90% of infants develop chronic, asymptomatic infection (only 2-6% of adults develop chronic infx). if over age 5 at exposure = less likely to be chronic carrier. adults have jaundice - Death from chronic infx 15-25% d/t cirrhosis or hepatic cancer (predisposed to liver cancer, *older you are with hep B = more likely to die) Hep B = think liver cancer - think 90% of kids are asymptomatic and will have chronic infx

What can happen to adults on 2nd exposure to Halothane?

- liver metabolizes 20% of agent - 20% of adults will have mild hepatitis on 2nd exposure - may be ok for kids tho

What is the pulmonary problem with Alpha 1 antitrypsin globulin deficiency?

- lungs become TOO compliant (too stretchy) - genetic d/o - progressive hepatic cirrhosis w/abnormal protein in liver cells

Would you give furosemide to hepatic disease pt?

- maybe AFTER albumin administration - pt is usually dry - *give albumin

**What is high hepatic extraction ratio and examples of drugs?

- metabolism of drugs is dependent on blood flow to liver. poor liver BF = drugs won't be metabolized as quickly - don't use these with pt with liver disease 1) Lidocaine 2) Bupivacaine 3) Ketamine 4) Metoprolol Induction meds: 1) Propofol 2) Etomidate 3) ketamine 4) Methohexital

s/sx of acute cholecystitis?

-Obstruction of cystic duct by gallstones - can lead to necrotic gall bladder bc neck of gallbladder is where blood supply is - eat something fatty --> gall bladder contracts --> stone is in cystic duct and wears on lining = pain - ABRUPT onset severe MID EPIGSATRIC pain extending to RIGHT UPPER ABDOMEN - Murphy sign: accentuated pain with inspiration Tx: NG, fluid replacement, pain relief Emergency sx needed if free air/perforation (lining worn through)

What lab tests tell us about liver cellular injury?**

-aspartate aminotransferase (AST) - alanine aminotransferase(ALT) - increased with hepatic disease *ALT is local to liver = better determinant of liver injury -AST is also found in heart, skeletal muscle, kidney, and brain

What are some manifestations of hepatic dysfunction ETOH cirrhosis?

1) **malnourishment, wt loss 2) loss of skeletal muscle mass on face, neck, shoulders, arms 3) ascites - increased hydrostatic pressure (pushing fluid out) and decreased oncotic pressure 4) **hepatomegaly, splenomegaly - blood products sequestered in spleen = thrombocytopenia 5) palmar erythemia, spider angiomas, subQ bleeding, esophageal varicies 6) elevated ALT, AST, PT, decreased albumin

What is the effect of 3 mediators on hepatic blood flow?

1) glucagon = dilates hepatic artery --> increased BF (glucagon is NOT metabolized with liver diease = may see profound dilation) 2) Angiotensin = constricts --> decreased hepatic blood flow 3) Vasopressin = constricts splanchnic BF --> decreased portal vein flow but DILATES INTRAhepatic portal vessels

**Gluconeogenesis is enhanced by what?

1) glucocorticoids 2) Catecholamines 3) Glucagon 4) thyroid hormone - if liver is failing = can't do gluconeogenesis --> NO glycogen stores = can't convert to glucose if have low blood sugar PLUS - decreased metabolism of insulin = PROFOUND hypoglycemia *concerned with conversion of nonglucose molecules to glucose, ex. amino acids --> glucose

The liver manufactures 2 very important things:??

1) synthesis of plasma proteins - needed for drug binding 2) clotting factors - need Vitamin K to synthesize prothrombin (Factor II) and factors VII, IX, and X

**Why are liver failure pts bleeding?

1) thrombocytopenia 2) impaired platelet function (have adequate # but functionality is decreased) *3) decreased synthesis of clotting factors/short-half life 4) portal HTN 5) formation of abnormal clotting factors 6) decreased CLEARANCE of anti-coagulation substance (so they just keep anti-clotting) 7) increased fibrinolysis (bc anticoag substances re not clearing --> DIC picture) *lack of absorption of Vit K d/t lack of bile salt

What 3 factors does hepatic elimination depend on?

1. Hepatic blood flow 2. Protein binding 3. Intrinsic ability of the liver

What 2 types of hepatitis do NOT acquire chronic infection?

A and E

Which 2 types of hepatitis are transmitted via fecal-oral?

A and E

**What hormones, minerals, vitamins are synthesized and stored in liver?

A, D, E, B12, T3, T4 - liver produces deidonase. if liver disease = not as much T3 d/t not converting T4 to T3 d/t lack of deidonase.

Which 3 types of hepatitis to we have immunization for?

A/B/D

What is the washout effect?

As portal vein HTN increases --> flow is decreased --> adenosine is released --> to increase hepatic artery blood flow

What does the sphincter of Oddi do?

Contract: bile is blocked from entering the duodenum Relax: allows bile to enter the duodenum

How much blood supply to liver?

Dual supply: 1500 ml/min blood flow (25% of cardiac output) - high blood flow d/t low vascular resistance from portal vein Hepatic Artery: 25% Portal Vein: 75% (more O2 from vein bc more flow from vein)

Which type of hepatitis can be prevented with safe drinking water?

E

**Which type of hepatic dysfunction is more common in females? males?

Females = Primary Biliary Cirrhosis Males = Hemochromatosis

What is the thin connective tissue capsule that covers the liver?

Glission's capsule

What are the circulatory effects from cirrhosis?

HYPERdynamic state - icnreased CO - decrased vascular resistance (Vasodilation d/t glucagon and nitric oxide) - increased circulating blood volume - ETOH can cause cardiomyopathy - sensitive to chgs in cardiac filling

*What liver disorder is caused by LARGE amoutns of iron being deposited in hepatocytes causing scaring, cirrhosis, and portal HTN?

Hemachromatosis - autosomal recessive - more common in males TX: get it before complete failure, periodic phlebotomies, give things to bind with iron (deferoxamine)

what is a big difference between characteristics of Hep A vs Hep B?

Hep A = single strand RNA, fecal-oral transmission Hep B = DNA virus, blood-mucosa transmission

Which type of viral hepatitis: - DNA virus, survives 7 days outside body - transmitted via sex with infected partner, IVDU, birth from infected mother

Hep B

Which viral hepatitis often has a coinfection with Hep B?

Hep D - no vaccination

**Which antigen needs to be produced to cure Hep B, and have no chronic infection?

Hep-B surface antibodies (anti-HBs) - KEY to determine if chronic vs recovery - anti-HBs produces around day 32 (after 4.5 wks) -Anti-HBc (core antigen) is the only marker during window period

Which type of viral hepatitis is: - *SINGLE STRAND RNA virus - transmission via fecal-oral route - infectious 2 weeks BEFORE s/sx (jaundice/liver enzymes) - infectious 1 week after s/sx - NO Chronic shedding = will not have it again

Hepatitis A

Which type of viral hepatitis: - single strand RNA virus - transmitted via blood/IVDU/vertical transmission, occupational exposure/ sex - 80% asymptomatic - Chronic infection: DM 3x more likely, glomerulonephritis, pophyria (abnml heme prod), non-hodgkins lymphoma

Hepatitis C serology: antiHCV - 7 weeks after exposure Tx: Ribavirin & interferon therapy. Sofosbuvir, Simprevir.

**This is a restrictive lung disease (pleural effusion) causing vasodilation in the vasculature when glucagon and NO cannot diffuse, and hypoxic pulmonary vasoconstriction is lost causing shunting (O2 sat decreases)

Hepatopulmonary syndrome

**What liver disease is a pre-renal state w/ decreased blood flow to kidneys

Hepatorenal Syndrome - follows GI bleed (BUN increases w/GI bleed as blood is metabolized), aggressive diuresis, sepsis, or major surgery. *kidneys shut down d/t lack of blood flow -manifest: oliguria, NA retention, azotemia (high levels of nitrogen), ascites, increased morality Goal - preserve renal fxn periop -ie liver txp pt not doing well

Where is the highest concentration of hep B virus in body fluids?

High: blood, serum, wound exudates (lives 7 days outside the body) Mod: semen, vag fluid, saliva Low/not detectable: urine, feces, sweat, tears, breast milk

Which clotting factors are in intrinsic pathway vs extrinsic pathway and which does heparin/coumadin effect?

Intrinsic pathway - affected by heparin - measures: I, II, V, VIII, IX, X, XI, XII Extrinsic pathway - affected by coumadin - measures: I, II, V, VII, X

**If anti-HBs is missing, what happens with HEp B infection?

It becomes a chronic infection instead of recovery

**Should liver failure people have succ?

NO! - they have decreased pseudocholinesterase activity = won't break down succ = prolonged paralysis and possibly prolonged intubation (unexpected ICU) :( - only a problem in Chronic disease not acute bc half life is 8-16 hrs - also affects metabolism of local anesthetics (esters), amides might be ok but CYP450 system - use cisatricurium (Hoffman elimination)

What controls blood supply?

Neural, myogenic, metabolic controls - changes in pH/O2 content (more acidotic) = increase blood flow

Does Hep E have a chronic and acute state?

No - only acute

**How can liver dysfunction affect blood sugar?

Normally, if blood sugar rises --> insulin secreted --> blood sugar is lowered --> if BG gets below a set point then glucagon causes the liver to convert stored glycogen into glucose (glycogenolysis) to raise blood sugar - increased glycogen stores promote increased insulin and insulin is not broken down d/t impaired liver = HYPOGLYCEMIA!!

* What liver disorder is an autoimmune, inflammatory destruction of intrahepatic small bile ducts?

Primary Biliary Cirrhosis - females more likely (90%) - TX: transplant

How do Kupffer cells help prevent bacteremia?

Reticuloendothelial cells (Kupffer cells) line the venous sinusoids. These macrophages PHAGOCYTIZE bacteria that enter the sinusoids from the intestines. Less than 1% of bacteria that enter the liver pass through the systemic circulation. Barash pg 1295

What organelle is involved in drug metabolism and more likely in zone 3 hepatocytes?

Smooth endoplasmic reticulum

What forms the common bile duct? Into what structure does it empty?

The hepatic duct (from liver) and the cystic duct (from gallbladder) form the common bile duct. It meets with the pancreatic duct and empties into the duodenum of the small intestine under the control of the Sphincter of Oddi.

Where to portosystemic venous collaterals develop and what is their function?

function: collaterols develop to go around the portal system and void liver. problem = toxins, bacteria, carbs, proteins, will now NOT be process via the liver --> bacteremia, ascites, etc 4 areas: 1) gastroesophageal 2) hemorrhoidal 3) periumbilical 4) retroperitoneal

Bilirubin is toxic for many enzymes and occurs with very high concentrations. How can the toxicity be moderated?

give albumin - excess bilirubin can cause neurotoxicity - associated with bilirubin-mediated changes in ATPase and inhibition of protein synthesis and cell growth

SNS associated with ___________ PNS associated with _____________

glucagon (celiac plexus) insulin (vagus)

Can glycogen be used systemically?

glycogen from liver can be used systemically -glycogen from muscle can only be used locally in muscle

**What are the 2 types of drug biotransformation?

hepatic biotransformation - end products are either inactivated or more water soluble for bile or urine elimination 2 types: 1) enzymatic: oxidation, reduction, deamination, sulfoxidation, dealkylation, methylation - fentanyl, morphine inactivated by phase 1 2) conjugation: binding of things to be eliminated quickly

What is the highest risk factor for acute hep B?

heterosexual contact (41%)

What lies between the cellular plates of arterioles and venules in the liver?

sinusoids

**What is an indicator of damage to hepatocytes? (intrarenal)

transaminases (AST/ALT) (aka LFTs) - spill into circulation in response to hypoxemia, drugs, viruses - 3x normal in post-op period = acute hepatocellular damage

What does HBeAg represent?

viral replication

Why avoid hypocarbia?

will aggravate encephalopathy that likely already exists