Liver pdf - حسن سالم

LEC 1:

ا.م.د.ﺣﺴﻦ اﻟﺠﻤﻴﻠﻲ

Liver and biliary tract disease

Introduction:

Liver cells

Hepatocytes comprise 80% of liver cells.

The remaining 20% are the endothelial

cells lining the sinusoids ,epithelial cells

lining the intrahepatic bile ducts, cells of

the immune system (including

macrophages (Kupffer

cells)

Hepatic function

1-Carbohydrate, amino acid and lipid metabolism

•Amino acids from dietary proteins are used for synthesis of

plasma proteins, including albumin.The liver produces 8–14 g

of albumin per day..

• Following a meal, more than half of the glucose absorbed is

taken up by the liver and stored as glycogen --preventing

hyperglycaemia. During fasting, glycogen is broken down to

release glucose (gluconeogenesis), thereby preventing

hypoglycaemia

• The liver plays a central role in lipid metabolism, producing

VLDL and further metabolising LDL &HDL .Dysregulation of

lipid metabolism is thought to have a critical role in the

pathogenesis of NAFLD.

2-Clotting factors

The liver produces key proteins that are
involved in the coagulation cascade. Reduced
clotting factor synthesis is an important and
easily accessible biomarker of liver function
in the setting of liver injury.

Prothrombin time

(PT or INR) is therefore one

of the most important clinical tools available
for the assessment of hepatocyte function.

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.
The liver is also able to metabolise vitamins to more
active compounds, e.g. 7-dehydrocholesterol to

25(OH) vitamin D.

Vitamin K is a fat-soluble vitamin

and so the inability

to absorb fat soluble vitamins, as occurs in biliary
obstruction, results in a coagulopathy.
The liver stores minerals such as

iron, in ferritin and

haemosiderin, and copper,

which is excreted in bile.

4 Immune regulation

Approximately 9% of the normal liver is

composed of immune cells .

Kupffer

cells

derived from blood monocytes, the

liver macrophages and natural killer

(

)cells, as well as ‘classical’ B and T

cells

They remove aged and damaged red

blood cells, bacteria, viruses, antigen–

antibody complexes and endotoxin

5-billrubin and bile metabolism:

Bile contains bile acids ,phospholipids ,

bilirubin and cholesterol

Investigations

1- Bilirubin and albumin

The degree of elevation of bilirubin can reﬂect the degree of

liver damage. A raised bilirubin often occurs earlier in the

natural history of biliary disease (e.g. primary biliary

cirrhosis) than in disease of the liver parenchyma (e.g.

cirrhosis) where the hepatocytes are primarily

involved.

Serum albumin levels are often low in patients with liver

disease.. Since the plasma half-life of albumin is about 2

weeks, albumin levels may be normal in acute liver failure

but are almost always reduced in chronic liver failure.

2-Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) :

are located in the cytoplasm of the hepatocyte;
Although both transaminase enzymes are widely
distributed, expression of ALT outside the liver is
relatively low and this enzyme is therefore
considered more speciﬁc for hepatocellular damage.
Large increases of aminotransferase activity favour
hepatocellular damage, and this pattern of LFT
abnormality is known as ‘hepatiti

c’

3-Alkaline phosphatase and gamma-glutamyl transferase

(

ALP)

is widely distributed in the body, but the main sites of

production are the

liver, gastrointestinal tract, bone, placenta and

kidney

, levels rise with intrahepatic and extrahepatic biliary obstruction

and in inﬁltrative liver disease.

(

GGT

) is a microsomal enzyme found in many cells and tissues of the

body. The highest concentrations are located in the liver

-The pattern of a modest increase in aminotransferase activity and

large increases in ALP and GGT activity favours biliary obstruction and

is commonly described as ‘cholestatic’ or ‘obstructive’ .

Isolated elevation of the serum GGT is relatively common, and may

occur during ingestion of microsomal enzyme-inducing drugs,

including alcohol ,but also in NAFLD.

4-Other biochemical tests
•

Hyponatraemia

occurs in severe liver disease

due to increased production of ADH
•

Serum urea

may be reduced in hepatic failure,

whereas levels of urea may be increased
following
GI haemorrhage.
• Signiﬁcantly elevated

ferritin

suggests

haemochromatosis. Modest elevations can be
seen in inﬂammatory disease and alcohol
excess.

5-Haematological tests

•

A normochromic normocytic anaemia

-gastrointestinal

haemorrhage,

chronic blood loss is characterised by a hypochromic

microcytic anaemia secondary to iron deﬁciency.

-(macrocytosis) is associated with alcohol misuse,

•

Leucopenia

may complicate portal hypertension and

hypersplenism, whereas leucocytosis may occur with

cholangitis, alcoholic hepatitis and hepatic abscesses.

. •

Thrombocytopenia

--due to reduced platelet production,

hypersplenism. Thrombopoietin, required for platelet

production, is produced in the liver and levels fall with

worsening liver function. A low platelet count is often an

indicator of chronic liver disease,

Thrombocytosis

is unusual in patients with liver disease but

may occur in those with active GI haemorrhage and, rarely, in

hepatocellular carcinoma

6-Coagulation tests

vitamin K-dependent coagulation factors
(1972)in the blood are short (5–72 hours) and
so
changes in

the prothrombin time

occur

relatively quickly following liver damage. An
increased PT is evidence of severe liver
damage in chronic liver disease.
Vitamin K does not reverse this deﬁciency if it
is due to liver disease, but will correct the PT
if the cause is vitamin K deﬁciency, as may
occur with biliary obstruction due to non-
absorption of fat-soluble vitamins.

7-Immunological tests
- Elevation in overall serum
immunoglobulin levels can also be

suggestive of autoimmunity

(immunoglobulin (Ig)G and IgM).
-Elevated serum IgA can be seen,
often in more advanced
alcoholic liver disease and NAFLD

8 Ultrasound

a ‘ﬁrst-line’ test to identify gallstones, biliary
obstruction or thrombosis in the hepatic
vasculature.
Focal lesions, such as tumours, may not be
detected if they are below 2 cm in diameter
and have echogenic characteristics similar to
normal liver tissue.

. Doppler ultrasound allows blood ﬂow in the
hepatic artery, portal vein and hepatic veins to
be investigated

Endoscopic ultrasound provides high-
resolution images of the pancreas, biliarytree
and liver

(CT)

detects smaller focal lesions in

the liver, especially when combined
with contrast injection .

(MRI

) can also be used to localise

and conﬁrm the aetiology of focal
liver lesions, particularly primary and
secondary tumours

10-Cholangiography

(MRCP)& ERCP

, or the

percutaneous
approach (percutaneous
transhepatic cholangiography,

PTC

). The latter does not allow

the ampulla of Vater or
pancreatic duct to be visualised

11-liver biopsy

can conﬁrm the severity of liver

damage and provide aetiological information.
It is performed percutaneously with a Trucut or

Menghini

needle, usually through an intercostal space

under local anaesthesia, Percutaneous liver biopsy is
a relatively safe procedure.
mortality of about 0.01%. The main complications
are abdominal and/or shoulder pain, bleeding and
biliary peritonitis.
liver disorders can be broadly classiﬁed histologically
into fatty liver (steatosis), hepatitis (inﬂammation,
‘grade’) and cirrhosis (ﬁbrosis, ‘stage’).