Liver Function

• Anatomy • Function and

– Gross Anatomy Alterations during
– Microscopic Anatomy Disease

• Biochemical • Function Tests

Functions
ANATOMY
 Gross Anatomy
• A large organ ( approx.
1.2-1.5 kg in weight)

• A complex organ
responsible for
performing vital tasks
that impact all body
systems.
 Gross Anatomy
• Located beneath and
attached to the
diaphragm

• Protected by the lower Insert Liver Picture

rib cage In Human Body

• Held in place by
ligamentous
attachments.
 Gross Anatomy
• Divided equally into 2 lobes (Left and Right) by a
falciform ligament.

• The right lobe is approximately six times larger than

the left lobe which is functionally insignificant

• blood is delivered to the liver via hepatic portal vein

(drains from the intestine /enterohepatic circulation)
and hepatic artery (drains from the general
circulation).
 Blood and Bile Flow
Blood Flow

Deoxygenated
Venules Central vein Vena cava
blood

Hepatic Portal
sinusoids hepatic vein
Vein
 Blood and Bile Flow
Bile Flow

Bile produced in
bile ductules gall bladder gall bladder
hepatocytes

secreted into
common duct bile duct
canaliculi
• Approximately 1,500 ml of blood passes through the
liver per minute.

• The liver is drained by a collecting system of veins

that empties into hepatic veins and ultimately into
the inferior vena cava.

• Excretory system of the liver begins at the bile

canaliculi which are small spaces between the
hepatocytes that form intrahepatic ducts.
• Excretory system of the liver begins at the bile
canaliculi which are small spaces between the
hepatocytes that form intrahepatic ducts.

• The intrahepatic duct, where the excretory products

of the cell can drain, join to form the right and left
hepatic duct which drain the secretions from the
liver.
• The right and left hepatic ducts merge to form the
common hepatic duct which eventually joined with
the cystic duct of the gall bladder to form the
common bile duct.

• Combined digestive excretions are then expelled to

the duodenum.
Excretory System of the Liver
 Microscopic Anatomy
Liver

• Is divided into microscopic functional unit called

lobules. They are responsible for all metabolic and
excretory functions.

• Each lobule is roughly a six-sided structure with a

centrally located vein (central vein) with portal triads
at each corner.
Portal Triad
• contains a hepatic artery, a portal vein and a bile
duct surrounded by connective tissue.

The liver contains two major cell types:

• Hepatocytes
• Kupffer cells
Hepatocytes

• Makes up approx. 80% of the volume of the organ;

are large cells that radiate outward from the central;
form plates separated each other by large capillary
spaces called sinusoids.

• Responsible for the regenerative properties of the

liver.
Phagocytic Kupffer

• Are macrophages and act as a active phagocytes

capable of engulfing bacteria, debris, toxins, and
other substances flowing through the sinusoids.

• These cells also line the sinusoids. Since the

sinusoids are filled with blood, each hepatocyte has a
direct contact to the blood.
 Components of Liver lobules
Central vein
• Drains blood from the
sinusoids to the hepatic vein
that will carry to general
circulation.
Sinusoids
• Spaces between hepatic
plates
Hepatic plates
• Lined with 1-2 layers of
hepatocytes
Bile canaliculi
• Spaces within hepatic plates
Bile ducts
• Carries bile and drain it to
the hepatic bringing it to the
gall bladder and the
duodenum.
Liver lobule
 Biochemical Functions
• The liver has more than
500 functions, including:

– Storage of Nutrients
– Breakdown of
erythrocytes
– Bile Secretion
– Synthesis of plasma
Proteins
– Synthesis of cholesterol
 Storage of Nutrients
• Hepatocytes absorb and
store excess nutrients in
the blood
– Glucose (glycogen)
– Iron
– Retinol (Vitamin A)
– Calciferol (Vitamin D)

• Nutrients released when

levels are too low
Breakdown of Erythrocytes
• RBC’s have a life span of
120 days.

• RBC’s weaken and

rupture, releasing
hemoglobin into the
blood plasma.

• Hemoglobin is absorbed
by phagocytosis by
Kupffer cells in the liver.
An electron micrograph of a Kupffer cell from the
liver. The Golgi apparatus (marked with arrows) is
well developed. The dark granules associated with
the Golgi saccules are lysosomes. At the cell surface,
identify the filopodial processes
• Hemoglobin is split into

• Heme groups

– Iron is removed from heme leaving a substance called

bilirubin (bile pigment).
» Iron is carried to bone marrow where it is used
to new hemoglobin for RBC’s
» Bilirubin becomes a component of bile

• Globins
− Hydrolyzed to amino acids and returned to the blood
 Bile Secretion
• Bile Contents
– HCO3- (Bicarbonate)
– Bile salts
– Bile pigment
– Cholesterol

• Stored in gall bladder

– Concentrated
– acidified

• Discharged into small

intestine via bile duct
 Synthesis of Plasma Proteins
• Produced by RER of Hepatocytes

• 3 main types
– Albumin
– Globulin
– Fibrinogen
 BILIRUBIN METABOLISM AND MEASUREMENT

• Each day, a healthy adult produces approximately

4 mg/kg of bilirubin (i.e., almost 0.5 mmol in a 70-kg
person).

• Most bilirubin (70% to 80%) is derived from

degradation of hemoglobin from senescent
erythrocytes, and a minor component arises from
premature destruction of newly formed erythrocytes
in the bone marrow or circulation
 Metabolism
• Heme from hemoglobin and other hemoproteins is
converted to biliverdin and then to bilirubin (Br),
predominantly in reticuloendothelial cells in the bone
marrow and spleen.

• Bilirubin is released into plasma (in its unconjugated

form), where it is tightly but reversibly bound to albumin
(Alb).

• Bilirubin is then taken up at the sinusoidal membrane of

hepatocytes, possibly via a member of the organic anion
transporter (OATP) family.
• Bilirubin is conjugated, via the activity of bilirubin UDP-
glucuronyl transferase (B-UGT), to form bilirubin
diglucuronide (BrG).

• Biliary secretion of BrG occurs at the canalicular

membrane by the multispecific organic anion transporter
MRP2.
• Under physiological conditions, the vast majority of
BrG is eliminated in bile caniculi.

• Once in the hepatic duct, it combines with the

secretions from the gallbladder through the cystic
duct and is expelled to the intestines through the
common bile duct.
• Intestinal bacteria work on conjugated bilirubin to
produce mesobilirubin, which is reduced to form
mesobilirubinogen then urobilinogen.

• The majority of the remaining 20% of urobilinogen will

be absorbed by extrahepatic circulation to be recycled
through the liver and re-excreted.

• The urobilinogen is oxided to urobilin(stercobilin) which

gives stool its brown color.
• The remaining of urobilinogen will enter systematic
circulation and will be flitered by the kidney and excreted
in the urine.

• Thus, under normal conditions, at least 95% of bilirubin

in plasma is present in the unconjugated form.
 Measurement
• The normal bilirubin concentration in the serum of
adults is lower than 1 to 1.5 mg/dL.

• In general, jaundice is not evident until the serum

bilirubin concentration exceeds 2 mg/dL.

• In healthy persons, most bilirubin circulates in its

unconjugated form; less than 5% of circulating
bilirubin is present in conjugated form.
• In cholestatic conditions, the proportion of
unconjugated bilirubin may increase as a
consequence of upregulated MRP3 expression.

• The importance of accurate measurement of

bilirubin is underscored by its incorporation as a
critical variable in scoring systems such as the Model
for End-stage Liver Disease (MELD), which provide
estimates of survival in various acute and chronic
liver disorders
 Synthesis of Cholesterol
• Produced by hepatocytes
• Some used for bile production
• Some trasnsported for use in the rest
of the body
– Synthesis and repair of cell
membranes or stored in the liver.
– Precursor by testis, ovaries or the
adrenal gland to make steroid
hormones.
• progestins
• glucocortoids
• androgens
• estrogens
• mineralocortoids
– It is also a precursor to vitamin D.
Liver Function Alterations During Disease

1. Jaundice

• Pre-hepatic Jaundice
• Post-hepatic Jaundice
• Hepatic Jaundice

2. Cirrhosis
3. Reye Syndrome
4. Alcohol and Drug-related Disorders
1. Jaundice – “icterus”

• yellowish pigmentation of the skin, mucous

membrane and sclera of the eyes.
• due to accumulation of abnormal amounts of
either free or conjugated bilirubin or both.
• 0.5-1.0 mg/dL- normal con’c of bilirubin in the
blood.

*** Jaundice cecomes clinically evident at 2ml/dL

• Jaundice due to high levels of free bilirubin in
the blood is caused by an excessively high rate
of red blood cell destruction.

 This is the cause of jaundice in newborns

who suffer from Erythroblastosis faetalis
(Hemolytic Disease of the Newborn).
• Physiological jaundice of the newborn is due to
high levels of free bilirubin in otherwise healthy
neonates.

 This type of jaundice may be caused by

rapid fall in blood hemoglobin con’c. that
normally occurs at birth.
• In pre-mature infants, it is caused by inadequate
amounts of hepatic enzymes that are needed to
conjugate and thus excrete it in the bile.

Treatment:
Phototherapy – newborn with
jaundice
• Phototherapy

→ the newborn are place

under blue light in 400-500
nm wavelength range.

→ light is absorbed by
bilirubin in the cutaneous
vessel and it results in the
conversion of bilirubin to a
more polar isomer.
• ▪ Polar isomer

→ it is soluble in the plasma without having to be

conjugated with glucuronic acid.

→ the more soluble photoisomer of bilirubin can be

excreted in the bile or urine.
Classes of Jaundice
Pre-hepatic Jaundice
→ known as hemolytic
or retention jaundice

→ due to excessive
destruction of red
blood cells.
Post-hepatic Jaundice
→ known as
regurgitive,obtructive
or cholestatic jaundice

→ due to obstruction
in the biliary form
→ due to obstruction
of the extra-hepatic
biliary tree