Week 5 - Hepatobiliary Flashcards
(34 cards)
Hepatic Blood Flow
25% Arterial 75% Venous
O2 is 50/50
25% of resting CO
Portal Vein in Afferent, Hepatic vein is Efferent
How does severe liver damage affect pharmacokinetics
Absorption
- Reduce oral, lipophilic impaired
Distribution
- Decreased protein binding due to decreased albumin levels in severe
- Increase TBW increase Vd for water soluble
- Decreased
Metabolism
- Decreased CYP450. Extends drugs half life and accumulation
Elimination
Accumulation with impaired biliary excretion
- Gets worse if renal function also has issues
What do phase 1/2 reactions do in order to metabolize drugs
Phase 1 - Reduction, Oxidation, Hydrolysis (only non CYP related fx)
Phase 2 - Conjugation (Commonly glucuronidation)
- Acetylation important for Amides, Hydralazine
Goal - Make more ionized/water soluble
What is the overall goal of phase 1 & phase 2 reactions for metabolism
Goal - Make more ionized/water soluble
What is the principle enzyme of Phase 1 Reactions
CYP 450
Therefore enzyme deficiency or over abundance can alter drug metabolism
How is the liver a synthesis organ
- makes most proteins (except IGG)
- Synthesizes most coagulation factors except III, IV, VIII, wVF
- Synthesizes proteins that regulate coagulation & fibrinolysis: protein S, C, plasminogen, anti-thrombin III
- Also synthesizes hormones: hepcidin, insulin-growth like factor, angiotensinogen
What labs are indicative of synthetic dysfunction of the liver? Which is the quickest
PT is fastest sign of synthetic dysfunction
Albumin levels will take longer (T1/2 = 21 days)
Why do patients with liver disease become coagulopathic?
The liver makes most of the coagulation factors (except for 3,4,8,vWF)
Changes to PK/PD
Less albumin, Higher Vd
What lab values will be elevated with a biliary obstruction
Alkaline Phosphatase**
Conjugated bilirubin
Y-Glutamyl Transpeptidase (GGT)
5”-Nucleotidease
ALT/AST/PT elevations are a late sign
Miller: elevations of ALP, GGT w or w/o elevations in bilirubin
What is the abnormal lab value associated with Hepatorenal syndrome
elevated serum creatinine
Per Miller’s:
* creatinine greater than or equal to 0.3 mg/dL from baseline w/i 48 hrs or ^ 50% increase in creatinine over last seven days
Hepatorenal syndrome definition/cause
Renal Failure due to chronic liver/advanced hepatic failure/portal hypertension
- Can be due to GI hemorrhage, sepsis, surgery, or too much diuresis
Impairs renal function
Abnormalities of arterial circulation
Vasoactives
Hepatorenal syndrome s/s and treatment
Progressive ascites
Azotemia
Oliguria
Long term - Multisystem organ failure
Tx - Transplant is the only fix
- Temporarily improve renal bloodflow (renal vasodilation, splanchnic vasoconstriction)
Why does cirrhosis have such a high mortality
Decompensated cirrhosis = Avg 2 year survival
With ascites/variceal hemorrhage/hepatic encepalopathy, survival goes from 80% to 30%
Nonsurgical tx for hemorrhage from esophageal varices
Pharm
- Ocreotide: reduce congestion by inhbiting splanchnic vasodilation
- Vasopressin: Splanchnic vasoconstriction
- Ceftriaxone: ABX prophy
-Nonspecific beta blockers: propanolol, timolol
Nonpharm
- Blakemore or variant (balloon tamponade)
- Ligation
What lab value would be elevated with Cholecystitis
Like obstructive
Alkaline Phosphotase
y-Glutamyl Transferase (GGT)
Conjugated Bilirubin
Hepatic blood flow receives how much cardiac output?
25-30% or 1500 ML/min
Sequalae of Portal HTN
Hemodynamics
- Hyperdynamic, Low BP/SVR state
Splenomegaly
Varices
Hemoohoids
Hepatorenal/pulmonary syndrome
Portopulmonary HTN
Which NMB are considered safe to use in the case of Hepatobiliary disease?
Cisatracurium (Nimbex)
- Undergoes Hoffman elimination (non-liver dependent)
Considerations for paralytic in patients with Cholangiocarcinoma
*Roc ok if sugammadex is available (changes to renal clearance)
*Do NOT like neostigmine for this
*Cis/atra better
*Sux has risk of hyperkalemia & increased gastric pressure
Strategies for hepatic resection
- Potential for high blood loss case (Cell Saver, ANH)
- Can be done laparascopically for small lesions in peripheral segments
- Temp vascular occlusion (Pringle technique)
** Hemihepatic or Total inflow occlusion - Maintain a low CVP (<5), stroke volume variation
Monitoring needed for hepatic resection
- Adequate venous access obtained
- arterial line
- CVC, CVP
- potential for stroke volume variation
Pain management for hepatic resection
thoracic epidural (TEA) highly effective means of pain control
Describe blood flow to the liver (from aorta & from mesentery)
Aorta –> Celiac Trunk –> 3 Branches: Common Hepatic Artery –> Proper hepatic artery
Superior mesenteric vein –> Splenic Vein – merge–> portal vein
