Transcript Hepatic Physiology

Hepatic Physiology
Tariq Alzahrani
Demonstrator
College of Medicine
King Saud University
Objectives
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It is an important topic?
Hepatic Anatomy
Hepatic Physiology
Effect of anaesthesia
Effect of surgery
• The largest organ in the body is the liver
• Involved with almost all of the biochemical pathways
that allow growth, fight disease, supply nutrients,
provide energy, and aid reproduction
• Dual blood supply: portal-venous (75%) and
hepatic-arterial (25%).
• Surgery and anesthesia impact hepatic function
primarily due to their impact on hepatic blood flow
and not primarily as a result of the medications or
anesthetic technique utilized
• Approximately 1 of every 700 patients admitted for
elective surgery has abnormal liver chemistry test
results (Conn, 1991).
• Up to 10% of patients with end-stage liver disease
may have surgery during the last 2 years of their
lives (Jackson, 1968).
Liver location
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Inferior to diaphragm
Mainly right side
Protected by rib cage
Large – 1.4 kg
Superior to stomach
Right upper quadrant
Liver gross anatomy
• Falciform ligament
– Attached to diaphragm
and anterior abdominal wall
– Round ligament
remnant of umbilical vein
Liver gross anatomy
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Hepatic portal vein
Hepatic artery
hepatic veins
Common hepatic duct
Gall bladder
Liver microscopic anatomy
• Liver lobule
– Structural &
functional unit
– Hexagonal solid
– Cords of hepatocytes
around central vein
– Components
Liver microscopic anatomy
• Portal triads at periphery
– Branch of hepatic artery
– Branch of hepatic portal vein
– Bile duct
Liver microscopic anatomy
• Hepatic sinusoids between liver cords
Liver microscopic anatomy
• Kupffer cells –
liver macrophages
along sinusoids
• Hepatocytes
• Bile canaliculi –
between hepatocytes,
leads to bile duct
Hepatocytes
• synthesize and secretes
several plasma proteins
– Albumin
– Globulins
– Fibrinogen
• produces bile salts,
detoxifies poisons
• Peroxisomes detoxify
alcohol
• Storage of glycogen
Blood flow in liver
• Hepatic artery branch
– Oxygenated blood to lobule
• Portal vein branch
– Deoxygenated blood with
substances from intestine
• Blood flows through
sinusoids
– Kupffer cells phagocytize
bacteria, foreign material,
old rbc’s
• Plasma seeps out and
bathes hepatocytes
• According to the its blood supply, liver is divided into
8 segments.
• Sympathetic
: T6-11 (Celiac plexus),
• Parasympathetic: RT &LT vagi,RT phrenic.
• Gall bladder : right vagus.
Hepatic Physiology
• Only major organ in the body that receives a dual
afferent blood supply
• 2 vessels supplying (hepatic artery and portal vein)
– Portal vein = 75% of HBF (55% of 02)
– Hepatic artery = 25% of HBF (45% of 02)
– Total hepatic blood flow = 25% of CO
• Portal venous pressure is normally 7-10mmHg
Liver Functions
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Protein synthesis
Glucose homeostasis
Lipid and lipoprotein synthesis
Vitamin storage
Clotting factor synthesis
Bile acid synthesis
Drug metabolism
Physiology ~ carbohydrate
metabolism
• Main role ~ storage of glycogen. Normally, about
75 grams of glycogen is found in the liver
• Depleted by 24-48 hours of starvation
• Poor nutrition or pre-existing liver disease may
lower glycogen stores ~ prone to hypoglycemia
Carbohydrate
Gut
Digestive
enzymes
Pancreas
Blood
Glucose
Insulin
hepatic glucose
production
and storage of
glycogen
Regulation of
lipolysis
Adipose
tissue
Muscle
Liver
Insulin-stimulated glucose uptake
• The Liver is the only organ which contain glucose-6phosphatase,so:
- It is the only organ,which can liberate glucose from
glycogen into the circulation.
- Other organs, e.g. muscle, can also store glycogen
but are only able to utilize it locally.
Physiology ~ fat & protein
metabolism
• Beta oxidation of fatty acids and the formation of
lipoproteins.
• Synthesis of plasma proteins ~ All proteins,
except immunoglobulins , antihemophiliac factor (8)
& v W f.
• Normally, 10-15 grams of albumin are produced
daily (3.5-5.5 g/dl)
• Clotting factors V, VII,
IX, X, prothrombin and
fibrinogen are all dependent
on the liver for synthesis ~
many of the factors require
only 20-30% of normal
levels to stop bleeding,
significant impairment of
liver function must occur
before problems begin.
• Important facts:
 Plasma half-lives of clotting
factors are measured in
hours. Therefore, acute liver
dysfunction can lead to
coagulopathies.
 Both severe parenchymal
disease and biliary disease
may lead to coagulopathy the former due to impaired
synthesis and the second by
decreased vitamin K
absorption due to the
absence of bile salts
secondary to biliary
obstruction.
Physiology ~ drug metablism
Divided into 2 phase:
1. Phase I metabolism
 Oxidation
 Reduction
2. Phase II metabolism
 Conjugation
Factor affecting drug metabolism:
 microsomal enzyme system
 route of administration
 liver blood flow
 competitive inhibition
Hepatic Excretion
• Some drug molecules are not metabolized before
excretion
– May see decreased metabolites or accumulation
of metabolites if excretion impaired
• To be eliminated, the drug must cross sinusoidal
membrane and return to blood as it flows toward
central vein, or be transported into bile
• Factors affecting HE:
– Blood flow
– Protein binding
– Hepatic intrinsic clearance (ability of hepatocytes
to remove drug from liver when blood flow,
protein binding, and translocation to the site of
metabolism or elimination are not rate-limiting)
Hepatic Clearance
• Volume of blood from which drug is removed
completely per unit time
• Hepatic clearance is not equal to systemic
clearance
Bioavailability
• Fraction of the absorbed dose that reaches the
systemic circulatio
Volume of Distribution
• Vd= D % C
• May or may not be affected by liver disease,
depending on extravascular distribution and tissue
binding
Effect of anaesthesia
• Most inhalation agents decrease hepatic blood flow
• Fatal hepatic necrosis resulting from halothane is
rare (1 case in 35,000), but severe liver dysfunction
may occur in 1 case in 6000
• Isoflurane is a safer choice because the effect on
hepatic blood flow and oxygenation is much less
than that of halothane. In fact, isoflurane increases
hepatic arterial blood flow.
• Nitrous oxide is not hepatotoxic
• Hypotension resulting in "shock liver injury" is
possible
• Delayed clearance of drugs such as midazolam,
fentanyl, and morphine
• Hypercarbia causes decreased portal blood flow
and must be avoided
Effect of surgery
• Splanchnic traction and exploratory laparotomy can
reduce blood flow to the intestines and the liver
• Upper abdominal surgery is associated with the
greatest reduction in hepatic blood flow
• Elevation of liver chemistry tests is more likely to
occur after biliary tract procedures than after
nonabdominal procedures