22. Liver Physiology Flashcards
Describe the anatomy of the liver
weight
lobes
small unit
Portal triad
What drains
Whats functional unit
• Adult liver weighs approximately 1800–2000 g.
• Divided into right and
left hemi-liver plus caudate lobe.
• Histological unit of the liver
is the lobule (see Fig. 22.1).
Lobules are hexagonal in shape
and have several portal triads
located at their periphery.
• Portal triad is composed of
hepatic artery,
portal vein and
bile duct.
• The central vein (branch of hepatic vein)
is present in the centre of the lobule,
surrounded by hepatocytes.
• Sinusoids traverse the lobule,
draining blood from
the peripheral portal
triads to the central vein.
• Sinusoids also contain Kupffer cells,
part of the reticuloendothelial system.
• Hepatocytes produce bile,
which is excreted into the
hepatic ducts of the
portal triad via the bile canaliculi.
• Functional unit of the liver is the acinus (see Fig. 22.2), a diamond-shaped area of the liver supplied by a terminal branch of the portal vein and of the hepatic artery and drained by a terminal branch of the bile duct.
What are hepatic zones?
The liver acinus is divided into zones 1–3.
The portal triad is composed
of the hepatic artery,
portal vein and
bile duct.
It is the portal triad that forms
the centre of the acinus and,
as such, forms zone 1.
Blood becomes progressively poorer in oxygen and nutrients from zone 1 to zone 3 (i.e. zone 3 represents the microcirculatory periphery).
Zone 1 –
Hepatocytes close to the portal triad.
Surrounding blood is rich in
oxygen and nutrients.
Mitochondria-rich cells are present,
which are suited to oxidative metabolism
and glycogen synthesis.
Zone 3 – Hepatocytes at the periphery of the acinus, which receive blood that has already undergone exchange of gases and metabolites with cells in zones 1 and 2.
Zone 3 is rich in smooth endoplasmic reticulum
and cytochrome P450,
making this the key region
for drug and toxin biotransformation.
It is also this zone that is most at risk of
cellular damage during circulatory disturbances.
Describe the blood supply to the liver.
• The liver is an extremely vascular organ,
receiving a blood supply of
100 mL/kg/min
(approximately 1800 mL/min).
• It has a dual blood supply, receiving approximately 70% of its blood flow from the portal vein and 30% from the hepatic artery.
• The portal vein is formed by the union of the splenic vein and superior mesenteric vein and thus carries blood from the gastrointestinal tract to the liver.
• The hepatic artery is a branch of the coeliac artery.
• Hepatic portal vein blood only has an oxygen saturation of approximately 70%, and so it only provides around 40% of the liver’s oxygen requirements.
• The hepatic artery provides
approximately 60% of the liver’s
oxygen requirements.
• Normal hepatic oxygen extraction is
less than 50%.
However, this can increase in
response to increased oxygen demand.
What factors affect blood flow to the liver?
• Blood flow through the hepatic artery
is autoregulated
(maintenance of constant flow
despite changes in mean arterial pressure)
down to a mean arterial pressure of
approximately 60 mmHg.
Below this, flow is pressure dependent.
• In contrast, blood flow through the
portal vein is passive and
dependent upon splanchnic blood flow.
• Therefore, only the arterial component
of hepatic blood flow is
controllable.
• The hepatic arterial blood flow is under
intrinsic and extrinsic control.
Intrinsic control of hepatic arterial blood flow:
• Myogenic response:
as the mean arterial pressure rises,
the hepatic artery constricts to maintain
a constant blood flow and vice versa.
• Hepatic arterial buffer response (arterio-venous reciprocity): as hepatic portal venous flow changes, the hepatic artery vasoconstricts or vasodilates reciprocally in order to maintain overall constant hepatic blood flow.
Extrinsic control of hepatic blood flow:
• Sympathetic nervous system:
stimulation results in hepatic arterial
vasoconstriction.
• Drugs:
volatiles and noradrenaline
reduce hepatic blood flow.
• General anaesthesia and spinal anaesthesia:
both reduce hepatic blood flow.
• Surgical handling of the liver:
reduces hepatic blood flow.
Classify and discuss the functions of the liver.
Think of a patient with hepatic failure,
who may exhibit the
following symptoms or signs
because of loss of hepatic function:
jaundice, encephalopathy, coagulopathy, ascites, raised intracranial pressure, hypoglycaemia, renal dysfunction, loss of vascular tone and immunosuppression.
- Biotransformation:
2.
Synthetic function:
3
Synthetic function:
4.
Digestive functions:
5.
Storage functions:
6.
Capacitance function
7.
Immunological function:
Biotransformation:
Biotransformation:
the liver plays a key role in the biotransformation of drugs, chemicals and toxins via the cytochrome P450 electron transport chain.
• Phase 1 reactions (Hydrolysis/Oxidation/Reduction):
These provide a
reactive group for subsequent
phase 2 reactions.
They generally reduce
the activity of a drug but
may sometimes produce a
toxic or active intermediate.
If the product is water-soluble following phase 1 reactions, it will not require further phase 2 reactions, but will be renally excreted.
• Phase 2 reactions
(Glucuronidation/
Acetylation/
Sulphonation/
Methylation):
These involve conjugation of
phase 1 products to increase
water solubility allowing
renal or biliary excretion of the compound.
• Factors determining hepatic clearance: 5
1 Proportion of unbound drug in the plasma
(cf. highly protein-bound drugs)
2 Rate of drug presentation to the liver (i.e. flow limited) – important for drugs with high first-pass metabolism, e.g. morphine and lignocaine
3 Rate of enzymatic breakdown (i.e. capacity-limited) – important for drugs with low first-pass metabolism, e.g. diazepam and warfarin
4 May be increased or decreased by
hepatic enzyme inducers or
inhibitors respectively
5 Hepatic function, e.g. affected by disease processes such as cirrhosis
Synthetic function:
Synthesis of albumin, immunoglobulins, clotting factors (all except factor VIII), haptoglobin, C-reactive protein and anti-thrombin III.
Metabolic functions:
• Carbohydrates –
the liver maintains blood glucose
concentrations via glycogenesis,
gluconeogenesis and glycogenolysis
• Proteins – synthesises, transaminates or deaminates proteins. Converts
ammonia into the less toxic urea.
• Lipids – synthesises cholesterol and triglycerides.
• Ketone bodies –
produces acetoacetate and β-hydroxybutyrate.
• Vitamins – activates vitamin D.
Digestive functions:
The liver produces bile.
Bile is primarily used for the emulsification
of dietary lipids to allow their absorption.
In addition, bile is
required for the absorption of
fat-soluble vitamins A, D, E and K.
Storage functions:
- The liver stores approximately 100 g glycogen.
- Vitamins A, D, E, K.
- Copper.
- Iron (as ferritin).
Capacitance function
Capacitance function:
at any one time the liver can hold as much
as 15% of the circulating volume
and therefore can act as a large blood reservoir.
Approximately half of this blood
can be returned to the circulation during
periods of sympathetic stimulation.
Immunological function:
Kupffer cells form part of the reticuloendothelial
system and have the function of removal of old erythrocytes, bacteria and
other antigens via phagocytosis.
Give examples of some liver function tests.
Alanine and aspartate aminotransferases (ALT and AST)
• Released into the blood following
hepatocelluar damage.
• Serum level does not correlate
with extent of liver injury.
• ALT more liver-specific than AST.
Indicators of biliary tract disease
• Elevated conjugated bilirubin.
• Elevated alkaline phosphatase (ALP)
and gamma-glutamyl transferase
(GGT).
Indicators of hepatic synthetic function
• All clotting factors are synthesised
by the liver except factor VIII.
• Prothrombin time (PT) indirectly
determines the amount of available
clotting factors and is therefore
used to assess synthetic function.
• Serum albumin is difficult to
interpret in the setting of critical illness
because of renal and gastrointestinal losses;
however, it will be reduced
in chronic liver disease.
