Hpathic Physiology, Pathophysiology and Anestetic Considerations

Question 1

The hepatic artery arises from the … in 80% of the population. In the reminder, it arises from the …

Answer 1

Celiac trunk

Superior mesenteric artery

Question 2

Hepatic stellate cells (HSCs) make up 8% to 10% of all resident liver cells. These specialized cells reside in the … between liver sinusoidal endothelial cells (LSECs) and the hepatocytes. In the normal liver, HSCs are believed to…
In the setting of liver injury, these cells become activated in response to … generated by hepatocytes, LSECs, as well as leukocytes and Kupffer cells.
The stellate cells proliferate and differentiate into … participating in …

Answer 2

Space of Disse

be in a quiescent state

cytokines and chemokines

myofibroblasts

hepatic inflammation and fibrosis

Question 3

Phase I enzymes consist of … that convert lipophilic drug molecules to hydrophilic molecules primarily through …
Non-… enzymes include monoamine oxidases, alcohol dehydrogenases, and aldo-keto reductase.

Answer 3

the cytochrome P450 family of enzymes

oxidation, reduction, or hydrolysis

CYP450

Question 4

The phase II pathway consists of the … of the products of the phase I pathway with hydrophilic endogenous moieties to make them more water-soluble. Polar molecules may undergo Phase II metabolism without having undergone Phase I metabolism. The most common Phase II reaction is …

Answer 4

conjugation

glucuronidation

Question 5

The phase III pathway involves the … by molecular transporters that are transmembrane proteins which facilitate the movement of large or ionized molecules across cell membranes.

Answer 5

excretion of compounds into the sinusoids or canalicular bile

Question 6

The liver is the site of synthesis for … % of the circulating proteins including hormones, coagulant factors, cytokines, and chemokines. As such it plays a significant role in the functioning of the body. Albumin is the predominant protein produced by the liver, accounting for over 50% of total plasma protein. It functions to transport lipids and hormones and maintain blood volume. The liver plays a central role in protein degradation. Amino acids are catabolized through one of two reactions:…
Both reactions lead to the production of …, which the liver converts to … through the …

Answer 6

80% to 90%

deamination or transamination

ammonia

urea

urea cycle

Question 7

Following the ingestion of food, fatty acids in the duodenum stimulate the release of … which causes the gallbladder to contract and the sphincter of Oddi to relax leading to the release of bile into the duodenum

Answer 7

cholecystokinin (CCK)

Question 8

The vast majority (95%) of the bile acids released into the duodenum are reabsorbed in the … and returned to the liver to be reused. This pathway for recycling bile acids is known as the …

Answer 8

terminal ileum

enterohepatic circulation (EHC)

Question 9

The liver plays a significant role in the coagulation system. It synthesizes all coagulation factors except … It also synthesizes proteins that regulate coagulation and fibrinolysis such as …

Answer 9

factors III (thromboplastin), IV (calcium), and VIII (von Willebrand factor [vWF])

protein S, protein C, plasminogen activator inhibitor, and antithrombin III

Question 10

A number of factors require vitamin K to become active. Coagulation factors …, as well as … undergo posttranslational modification with vitamin K to become active. Briefly, glutamic acid in the amino terminus of these proteins is converted to gamma-carboxyglutamic acid. These gamma-carboxylated procoagulants can then bind calcium ions and form bridges to phospholipid surfaces that are essential for the formation of activation complexes. Warfarin acts by inhibition of …

Answer 10

II, VII, IX, X

protein C and protein S

gamma-carboxylation

Question 11

…% of heme synthesis takes place in the bone marrow with the resultant heme used to produce hemoglobin. Most of the remainder of the heme is produced in the liver and used primarily to synthesize…Whereas the rate of heme synthesis in the bone marrow is a function of the availability of …, the rate of synthesis in the liver is a function of the available free heme pool in the body

Answer 11

80 to 90%

cytochrome P450 enzymes

iron

Question 12

Heme is synthesized through an eight-step enzymatic cascade known as the… Synthesis begins with glycine and succinyl CoA and proceeds through porphyrinogen intermediaries. A deficiency in any of the enzymes involved in heme synthesis leads to the development of …

Answer 12

Shemin pathway

porphyria

Question 13

The most common porphyria is … with an estimated incidence of 5 to 10 per 100,000. It is caused by a deficiency in …, which catalyzes the conversion of … to hydroxymethylbilane

Answer 13

acute intermittent porphyria

porphobilinogen deaminase

porphobilinogen

Question 14

Patients with acute intermittent porphyria typically have adequate levels of the enzyme for heme homeostasis; however, in response to endogenous or exogenous triggers that induce the Shemin pathway, the capacity of the system is exceeded and they accumulate precursors leading to symptoms. Common triggers include …

Clinical symptoms of an attack include …
Hyponatremia occurs in 40% of attacks. Change in urine color to dark red (especially on …) is a common finding.

Treatment consists of discontinuing the triggering agent, administering pain medication, carbohydrates, and …

Answer 14

erythromycin, trimethoprim, rifampicin, phenytoin, and barbiturates

severe, poorly localized abdominal pain (in >90% of cases), nausea, vomiting, agitation, and confusion

exposure to light

hematin

Question 15

Bilirubin is a product of heme catabolism. The primary source is … that are phagocytosed by macrophages in the spleen, liver, and bone marrow. The released heme is metabolized by heme oxygenase into bilirubin, yielding … in the process. Unconjugated bilirubin is water insoluble and thus tightly bound to albumin in the circulation. Hepatocytes convert bilirubin into a water-soluble form by conjugating it to … via the enzyme… Conjugated bilirubin is then transported across bile canaliculi and excreted in the bile. In the colon, bilirubin is deconjugated, metabolized by bacteria, and converted into … and it is either reabsorbed through the enterohepatic circulation or excreted in the urine and stool, giving urine and stool their characteristic colors

Answer 15

senescent erythrocytes

carbon monoxide and iron

glucuronic acid

glucuronyl transferase

urobilinogen

Question 16

The liver can participate in endocrine functions through hormone synthesis or hormone degradation. Hepatocytes synthesize hormones or prohormones such as …

In addition to hormone synthesis, the liver participates in endocrine function by inactivating many hormones, including …

Answer 16

hepcidin, insulin-like growth factor, and angiotensinogen

thyroxine, aldosterone, antidiuretic hormone, estrogens, androgens, and insulin

Question 17

Most causes of hepatic injury are associated with higher ALT than AST levels. However, … are classically associated with an AST-ALT ratio greater than 1; in some cases, a ratio of 4 has
been documented.

Answer 17

Wilson disease and alcoholic liver disease

Question 18

The ALT to AP ratio
helps differentiate hepatocellular injury (ALT:AP …) from cholestatic disease (ALT:AP …) from a mixed picture

Answer 18

> 5

< 2

Question 19

Is a benign condition with genetically low levels of the hepatic enzyme glucuronyl transferase, associated with mild or intermittent elevation in unconjugated bilirubin

Answer 19

Gilbert syndrome

Question 20

Coagulation factors
have shorter half-lives than albumin, ranging from 4 hours
for … to 4 days for …

Answer 20

factor VII

fibrinogen

Question 21

Intrahepatic cholestasis can have several etiologies ncluding immune-mediated,
infectious, drug-induced, paraneoplastic, and ischemic.
The first step in the evaluation is the measurement of … to rule out …

Answer 21

antimitochondrial antibody titers

primary biliary cholangitis (PBC).

Question 22

is an autoimmune disease that is characterized by the destruction of intrahepatic cholangiocytes and the presence of AMAs.

Treatment consists of ursodeoxycholic acid (UDCA) administration. UDCA, a bile acid, is thought to act by modifying the bile acid pool and reducing inflammation.

In patients who have a suboptimal response to UDCA, administration of obeticholic acid, a farnesoid-X receptor agonist, has been shown to reduce the serum levels of AP. Fibrates and corticosteroids have also shown benefit when combined with UDCA in patients who are unresponsive to UDCA alone

Answer 22

Primary biliary cholangitis

Question 23

Is a rare cholestatic, immune-mediated disease that occurs most frequently in men aged 30 to 40 years old. It is characterized by inflammation and fibrosis of the bile ducts. The majority of these patients have ulcerative colitis as wel.

The disease is progressive, with biliary fibrosis
leading to cirrhosis and ultimately end-stage liver disease (ESLD). Liver transplantation is the only effective therapy

Answer 23

Primary sclerosing cholangites

Question 24

Hepatic effects of volatile anesthesia

Answer 24

The hepatic effects of volatile anesthetics result primarily from alterations in liver perfusion.
Volatile anesthetics reduce mean arterial pressure (MAP) and cardiac output, leading to a reduction in portal blood flow in a dose-dependent manner. The hepatic arterial buffer response is preserved with isoflurane, sevoflurane, and desflurane leading to preservation of THBF (total hepatic blood flow), but not with halothane

Question 25

In general, intravenous anesthetics such as … do not adversely affect the liver. Furthermore, the pharmacokinetic properties of these agents are unchanged in patients with cirrhosis.
Cirrhotic patients may be more sensitive to their central nervous system depressant effects

Answer 25

propofol, thiopental, etomidate, and methohexital

Question 26

Does hepatic insufficiency affect midazolan and dexmedetomidine?

Answer 26

Midazolam elimination is impaired in liver dysfunction leading to prolongation of sedative effects.

Dexmedetomidine elimination is reduced in patients with hepatic impairment, necessitating
dose reduction

Question 27

Does hepatic insufficiency affect NMBA?

Answer 27

Reduced levels of pseudocholinesterase in patients with hepatic dysfunction may prolong the effects of succinylcholine and mivacurium.

Aminosteroid neuromuscular blocking agents (vecuronium, rocuronium, pancuronium) have a larger volume of distribution in cirrhotic patients. They have a slower rate of onset and a longer duration of action, necessitating judicious dosing and close train-of-four monitoring

Question 28

The Child-Turcotte-Pugh (CTP) score is calculated based on the values of five variables: …

The score is then used to classify the patient into one of three groups: Class A (score of …), Class B (score of …), and Class C (score …)

Answer 28

degree of HE, degree of ascites, INR, serum albumin, and total bilirubin

5-6

7-9

> 10

Question 29

Apart from the severity of cirrhosis and the specific surgical procedure, risk factors associated with increased postoperative morbidity and mortality in cirrhotic patients include …

Answer 29

emergency surgery, American Society of Anesthesiologists (ASA) physical status classification, the presence of renal
insufficiency, male gender, and advanced age

Question 30

Right hepatectomy involves resection of segments …

Left hepatectomy involves resection of segments …

Right lobectomy, also described as an extended
right hepatectomy or right trisegmentectomy, involves resection of segments …

An extended left hepatectomy (left trisegmentectomy) is the resection of segments …

Answer 30

V-VIII

II-IV

IV-VIII with or without segment

II-V and VIII

Question 31

Selective portal vein embolization (PVE) is typically indicated for patients with an anticipated future liver remnant (FLR) less than …% in the absence of cirrhosis, and less than
…% in the presence of cirrhosis

Answer 31

20%

40%

Question 32

Intraoperative blood loss during liver resection is associated with an increased risk of morbidity and mortality.
Several preoperative factors have been associated with an increased risk of transfusion. These include …

Answer 32

• preoperative anemia,
• the need for an extrahepatic procedure,
• the need for caval exposure,
• major hepatectomy (>3 segments),
• tumor size,
• thrombocytopenia,
• cirrhosis,
• and a repeat operation

Question 32

Hepatic vascular occlusion techniques may be used by surgeons to limit blood loss by limiting blood flow to the liver.

The most commonly used vascular occlusion technique is occlusion of the hepatic artery and portal vein by clamping the hepatoduodenal ligament.
This technique is called …

Answer 32

Pringle maneuver or total hepatic inflow occlusion

Question 33

Drawnback of Pringle maneuver

Answer 33

Potential for hepatic ischemia and reperfusion injury

• To mitigate this effect, surgeons typically make use of intermittent clamping with 15- to 20-minute intervals of clamping interspersed with 5- to 10-minute intervals of unclamping for a total ischemic time of less than 120 minutes

Question 34

The application of sevoflurane for 30 minutes of preconditioning prior to the Pringle maneuver has been shown in one single-center randomized, controlled trial to significantly reduce postoperative transaminitis
and complications in cases with greater than 30 minutes of continuous inflow occlusion. In a subsequent threearmed randomized controlled trial, the same group reported reductions in postoperative transaminitis and complications when sevoflurane was administered after the Pringle maneuver (“post-conditioning”) or with the use of intermittent clamping

T or F

Answer 34

T

Question 35

A number of techniques have been described for reducing CVP during hepatic resection. The most commonly reported approach is the use of …

Answer 35

intraoperative fluid restriction with rates of 1 mL/kg/h

• Vasopressors are used as needed to maintain SBP over 90 mm Hg and urine output more than 25 mL/h

Question 36

Two multicenter, randomized, placebo-controlled trials have examined the efficacy of prophylactic recombinant Factor VIIa (rFVIIa) administration to reduce transfusion patients undergoing hepatic resection.
The studies found a mild benefit of prophylactic rFVIIa with respect to mortality, red blood cell transfusions, or adverse events.

T or F

Answer 36

F

The studies found no benefit of prophylactic rFVIIa with respect to mortality, red blood cell transfusions, or adverse events.

Question 37

A single randomized, controlled trial in 214 patients undergoing primarily minor hepatic resections (82% of cases) found that the administration of tranexamic acid (TXA) resulted
in same rate of transfusions and same blood loss when compared to placebo. In the study group, 500 mg of TXA was administered intravenously prior to incision followed by 250 mg every 6 hours for 3 days

T or F

Answer 37

F

A single randomized, controlled trial in 214 patients undergoing primarily minor hepatic resections (82% of cases) found that the administration of tranexamic acid (TXA) resulted
in fewer transfusions and less blood loss compared to placebo. In the study group, 500 mg of TXA was administered intravenously prior to incision followed by 250 mg every 6 hours for 3 days

Question 38

Hemodynamic effects of Prongle maneuver

Answer 38

The Pringle maneuver, both during open
and laparoscopic hepatic resections, leads to an increase in MAP and systemic vascular resistance and a decrease in cardiac output