hepatology and anatomical function of liver.ppt

lecture on hepatology explain functional and anatomical featurs of liver

1. The liver
Dr jabbar jasim

2. one of the heaviest organs in the body, it of1.2-1.5 kg. It divided into
left and right lobes by the falciform ligament, but useful functional
division is into the right and left hemi livers, based on the hepatic
blood supply.
The right and left hemi livers are further divided into a total of eight
segments in accordance with subdivisions of the hepatic and portal veins.
liver segment is made up of multiple smaller units known as lobules,
comprised of a central vein (terminal hepatic veins ) , radiating sinusoids
separated from each other by single liver cell (hepatocyte) plates, and
peripheral portal tracts.
The functional unit of the liver is the hepatic acinus.
The Blood flows into the hepatic acinus via a single branch of the portal vein
and hepatic artery situated centrally in the portal tracts, blood flows
outwards along the hepatic sinusoids into one of several tributaries of the
hepatic vein at the periphery of the acinus.( from zone 1 to 3)
 Bile flows in the opposite direction from the periphery of the acinus through
channels termed cholangioles, which converge in interlobular bile ducts in
the portal tracts( from zone 3 to 1)

4. Hepatic function
1.Carbohydrate, amino acid and lipid metabolism .
2.Clotting factors :- coagulation factors (II, VII, IX and X) are post-
translationally modified by vitamin K-dependent enzymes.
3.Storage of vitamins and minerals :- Vitamins A, D and B12 are
stored by the liver in large amounts, while others, such as vitamin K
and folate, are stored in smaller amounts and disappear rapidly if
dietary intake is reduced.
4.Immune regulation :- Kupffer cells derived from blood monocytes ,
the liver macrophages and natural killer (NK) cells , as well as B and T
cells of the adaptive immune response (They remove aged and
damaged red blood cells, bacteria, viruses, antigen-antibody
complexes and endotoxin. In addition, they are able to produce a
wide variety of inflammatory mediators that can act locally or may
be released into the systemic circulation)
5.Bilirubin metabolism and bile

5. Bilirubin is the degradation product of the heme moiety of
hemoproteins, a class of proteins involved in the transport
or metabolism of oxygen .
Between 70 and 90% of bilirubin is derived from the
hemoglobin of erythrocytes that are sequestered and
destroyed by mononuclear phagocytic cells of the
reticuloendothelial system, principally in the spleen, liver,
and bone marrow.
The remainder results primarily from the turnover of
nonhemoglobin hemoproteins such as myoglobin, the P-
450 cytochromes, catalase, and peroxidase, principally in
the liver.
 A minor fraction reflects ineffective erythropoiesis, which
is the premature destruction of newly formed erythrocytes
within the bone marrow.
The source of heme moiety

6. B
ilirubin metabolism and bile

Between 425 and 510 mmol (250-300 mg) of unconjugated bilirubin
is produced from the catabolism of haem every day.
Bilirubin in the blood is normally almost all unconjugated and,
because it is not water-soluble, is bound to albumin and does not
pass into the urine.
Unconjugated bilirubin is taken up by hepatocytes at the
sinusoidal membrane, where it is conjugated in the endoplasmic
reticulum by UDP-glucuronyl transferase, producing bilirubin
mono- and diglucuronide.
Impaired conjugation by this enzyme is a cause of inherited
hyperbilirubinaemias .
 These bilirubin conjugates are water-soluble and are exported
into the bile canaliculus by specific carriers on the hepatocyte
membrane.
The conjugated bilirubin is excreted in the bile and passes into the
bowel lumen.

7. Congegated biliruin in bowel
colonic bacteria
stercobilinogen
oxidised to stercobilin
excreted in the stool, contributing to its
brown colour
A small amount of stercobilinogen (4 mg/day)
is absorbed from the bowel
passes through the liver and is excreted in
the urine
known as urobilinogen following
further oxidisation, urobilin
The liver secretes 1-2 L of bile daily .
Bile contains bile acids (formed from cholesterol),
phospholipids, bilirubin and cholesterol.

9. J
aundice
is yellowish discoloration of skin ,sclera& mucous membrane dueto increase serum
bilirubin more than 3mg/dl (50 μmol/L )
•The causes of jaundice might be prehepatic, hepatic or post hepatic.
Pre-hepatic jaundice
This is caused either by haemolysis or by congenital
hyperbilirubinaemia, and is characterised by an isolated raised
indirect bilirubin level.
In haemolysis, destruction of red blood cells or their precursors in
the marrow causes increased indirect bilirubin production.
Jaundice due to haemolysis is usually mild because a healthy liver
can excrete a bilirubin load six times greater than normal before
unconjugated bilirubin accumulates in the plasma. This does not
apply to the newborn, who have a reduced capacity to metabolise
bilirubin.
The most common form of non-haemolytic hyperbilirubinaemia is
Gilbert's syndrome, an inherited disorder of bilirubin metabolism.

10. Hepatocelular jaundice
Results from an inability of the liver to transport bilirubin across
the hepatocyte into the bile, occurring as a consequence of
parenchymal liver disease.
Mechanisms of elevated bilirubin
1.Bilirubin transport across the hepatocytes may be
impaired at any point between uptake of unconjugated
bilirubin into the cells and transport of conjugated
bilirubin into the canaliculi.
2.In addition, swelling of cells and edema resulting from
the disease itself may cause obstruction of the biliary
canaliculi.
The type of bilirubin elevated in hepatocellular jaundice??
 Both unconjugated and conjugated bilirubin in the blood
increase.

11. 
Hepatocelular damage
•Jaundice due to parenchymal liver disease is associated
with increases in transaminases (AST, ALT), but increases
in other LFTs, including cholestatic enzymes (GGT, ALP)
may occur, and suggest specific aetiologies.
•Acute jaundice in the presence of AST > 1000 U/L is highly
suggestive of
1.an infectious cause (e.g. hepatitis A, B),
2.drugs (e.g. paracetamol) or
3.hepatic ischaemia.

12. PBC primary biliary cirrohosis
PSC primary sclerosing cholangitis
NAFL non alcoholic liver disease

13. Obstructive (cholestatic) jaundice
Obstructive mean dilated biliary system.
Cholestatic mean no dilitation of biliary system.
Mechanisms of elevated bilirubin
1.Failure of hepatocytes to initiate bile flow.(no dilitation of
biliary system)
2.Obstruction of bile flow in the bile ducts or portal tracts.
3.Obstruction of bile flow in the extrahepatic bile ducts
between the
porta hepatis and the papilla of Vater.(mean dilated biliary
system).
In the absence of treatment, cholestatic jaundice tends to become
progressively more severe because conjugated bilirubin is unable
to enter the bile canaliculi and passes back into the blood, and also
because there is a failure of clearance of unconjugated bilirubin
arriving at the liver cells.

14. •Patient with prolong obstructive or cholestatic
jaundice will have greenish appearance because
of conversion of bilirubin to biliverdin.

15. Hepatic jaundice
which either due to hepatocellular damage or
intrahepatic cholestasis
Intrahepatic cholestasis
1)Primary biliary cirrhosis
2)Primary sclerosing cholangitis
3)Alcohol
4)Drugs
5)Cystic fibrosis
6)Severe bacterial infections
7)Hepatic infiltrations (lymphoma, granuloma, amyloid,
metastases)
8)Pregnancy.
9)Inherited cholestatic liver disease, e.g. benign recurrent
intrahepatic cholestasis
10)Chronic right heart failure

16. Extrahepatic
Carcinoma
 Ampullary
 Pancreatic
 Bile duct (cholangiocarcinoma)
 Liver metastases

Choledocholithiasis
Parasitic infection
Traumatic biliary strictures
Chronic pancreatitis
Post hepatic ( obstructive )

17. Clinical features in cholestatic jaundice
THOSE DUE TO CHOLESTASIS ITSELF, THOSE DUE TO SECONDARY INFECTION
(CHOLANGITIS) AND THOSE OF THE UNDERLYING CONDITION.

Early features
•Jaundice, Dark urine Pale stools .
•Pruritus (may be a dominant feature, and can be accompanied by skin
excoriations).
Late features
• Malabsorption (vitamins A, D, E and K).
•Weight loss.
•Steatorrhoea.
•Osteomalacia
•Bleeding tendency.
•Xanthelasma and xanthomas .
Cholangitis
• Fever& Rigor
•Pain (if gallstones are present) .

18. Courvoisier's Law
Gallbladder is palpable in jaundiced patient, suggests that
jaundice is due to a malignant biliary obstruction (e.g.
pancreatic cancer) and it is unlikely to be caused by biliary
obstruction due to gallstones, probably because a chronically
inflamed stone-containing gallbladder cannot readily dilate.
•Cholangitis is characterised by 'Charcot's triad' of
1.jaundice,
2.right upper quadrant pain and
3. fever.
•Cholestatic jaundice is characterised by a relatively greater
elevation of ALP and GGT than the aminotransferases.

19. U
ltrasound evaluation is
in
dicated in all cases to
d
etermine whether there is
evi
dence of mechanical
obstruction an
d dilatation of
the biliary tree .

20. Clinical features suggesting an underlying cause of cholestatic jaundice*
Clinical feature Jaundice Causes
Static or increasing
Carcinoma
 
Primary biliary cirrhosis
 
Primary sclerosing cholangitis
Fluctuating
Choledocholithiasis
 
Stricture
 
Pancreatitis
 
Choledochal cyst
 
Primary sclerosing cholangitis
Abdominal pain
Choledocholithiasis
 
Pancreatitis
 
Choledochal cyst

21. Cholangitis
Stone
 
Stricture
 
Choledochal cyst
Abdominal scar
Stone
 
Stricture
Irregular hepatomegaly
Hepatic carcinoma
Palpable gallbladder
Carcinoma below cystic duct (usually
pancreas)
Abdominal mass
Carcinoma
 
Pancreatitis (cyst)
 
Choledochal cyst
Occult blood in stools
Ampullary tumour