Hepatic Physiology

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Hepatic Blood Flow
Metabolic Functions
Drug Metabolism

HEPATIC BLOOD FLOW
-hepatic blood flow ~ 1500 ml/min provided by both the hepatic artery and portal vein

Hepatic artery
-hepatic artery supplies 25 – 30% of total hepatic blood supply: ~ 375 - 450 ml/min
-hepatic artery supplies 45 –50% of hepatic oxygen demand / metabolic requirements
-hepatic artery pressure correlates with arterial pressure
-hepatic artery oxygen saturation generally 100% Sa02
-hepatic artery flow generally dependent on metabolic oxygen demand / autoregulation

Receptors within hepatic artery include:
α1 adrenergic receptors: stimulation results in vasoconstriction
β2 adrenergic receptors: stimulation results in vasodilation
D1 dopaminergic receptors: stimulation results in vasodilation
Cholinergic receptors: stimulation results in vasodilation

Sympathetic stimulation upon hepatic artery results in:
-vasoconstriction of hepatic artery
-resultant decreased hepatic blood flow

Portal vein
-portal vein supplies 70 – 75% of total hepatic blood supply : ~ 1050 - 1125 ml/min
-portal vein supplies 50 – 55% of hepatic oxygen demand / metabolic requirements
-portal vein pressure correlates with venous pressure, generally x < 10mmHg
-portal vein oxygen saturation generally approximately 85% Sa02
-portal vein flow generally dependent on blood flow to both GI tract and spleen

Receptors within the portal vein include:
α1 adrenergic receptors: stimulation results in vasoconstriction
D1 dopaminergic receptors: stimulation results in vasodilation

Sympathetic stimulation upon mesenteric artery results in:
-vasoconstriction of mesenteric artery
-resultant decrease in hepatic blood flow

METABOLISM

CARBOHYDRATE METABOLISM
-carbohydrates are metabolized primarily into glucose, galactose and fructose
-glycolysis: process of utilizing glucose to produce ATP: 1 glucose produces 2 ATP
-TCA cycle: process of utilizing pyruvate (from glucose) to produce ATP: 1 glucose produces 38 ATP
-when plasma glucose is abundant (ex. postprandial): may be stored as glycogen within liver and muscle
-when glycogen storage exceeds its capacity extra glusose then becomes stored as fat within adipose tissue
-hepatic glycogen storage capacity ≈ 70 grams
-average daily glucose consumption ≈ 150 grams
-gluconeogenesis helps maintain normal blood glucose levels via de novo synthesis of glucose

Glycogen synthesis enhanced with:
-insulin

Glycogen synthesis inhibited with:
-epinephrine
-glucagon

Gluconeogenesis enhanced with:
-glucocorticoids
-catecholamines
-glucagon
-thyroxine

Gluconeogenesis inhibited with:
-insulin

FAT METABOLISM
-fatty acids are metabolized into acetyl-CoA
-acetyl-CoA is oxidized using the TCA cycle to produce ATP

PROTEIN METABOLISM
-deamination of amino acids
-formation of urea
-bidirectional conversion of amino acids ←→ protein
-production of plasma proteins
-production of all clotting factors (except factor VIII)
-production of vitamin K dependent factors (X,IX,VII,II)
-production of plasmacholinesterase
-production of pseudocholinesterase
-protease inhibitors (ex. antithrombin III, α2 antiplasmin, α1 antitrypsin)
-transport proteins (ex. transferin, haptoglobin, ceruloplasmin)
-complement proteins
-glycoproteins (α1 acidic glycoprotein)
-C-reactive protein
-serum amyloid proteins

DRUG METABOLISM

Phase I reactions: attempt to inactivate the molecule
ex. cytochrome P450 enzyme complex involved with:
-oxidation
-reduction
-deamination
-sulfoxidation
-dealkylation
-methylation

Factors which may stimulate cytochrome p450 enzymes includes:
-increases tolerance of drugs dependent on p450 due to increased metabolism and removal
-ethanol
-barbiturates
-ketamine
-benzodiazipine (ex. diazepam)

Factors which may inhibit cytochrome p450 enzymes includes:
-increases sensitivity of the drugs dependent on p450 therefore caution must be given to prevent overdose
-cimetidine
-chloramphenicol

Phase II reactions: attempt to make the compound more water soluable via conjugation
-therefore more readily excreted via urine

Conjugation may occur with the following compounds:
-glucuronide
-sulfate
-taurine
-glycline

Drugs dependent on Hepatic Blood Flow may be due to:
-increased rate of hepatic extraction
ex. lidocaine
-morphine
-verapamil
-labetolol
-propranolol