The liver

The liver
Outlines!
1-What is the liver?
2-funcation of the liver
3-jaundice
4-metabolism bilirubin
5-a-biochemical assement to liver
function
6-b-non biochemical assement to liver
function
7-Liver disease
The liver: The largest solid organ in the body,
situated in the upper part of the abdomen on the
right side.
The liver has two blood supply sources: the hepatic
artery (a branch of the celiac artery) delivers oxygenated
blood along with cholesterol and other substances (such
as hormones) necessary for processing food, while the
portal vein collects venous blood from the entire
intestinal region and supplies this nutrient-rich blood to
the liver for processing and metabolizing. This blood
then flows through a network of tiny channels in the liver;
nutrients are metabolized, while toxins are processed for
expulsion....

Functions of liver
a.Excretory function: bile pigments, bile salts
and cholesterol are excreted in bile into
intestine.
b.Metabolic function: liver actively participates
in carbohydrate, lipid, protein, mineral and
vitamin metabolisms.
c.Hematological function: liver is also
produces clotting factors like factor V, VII.
Fibrinogen involved in blood coagulation is
also synthesized in liver. It synthesize plasma
proteins and destruction of erythrocytes.
④ Storage functions: glycogen, vitamins A, D and
B12,and trace element iron are stored in liver.
⑤ Protective functions and detoxification:
Ammonia is detoxified to urea. kupffer cells of
liver perform phagocytosis to eliminate foreign
compounds. Liver is responsible for the
metabolism of xenobiotic.
JAUNDICE
What is jaundice?
Jaundice is not a disease but
rather a sign that can occur in
many different diseases. Jaundice
is the yellowish staining of the skin
and sclerae (the whites of the
eyes) that is caused by high levels
in blood of the chemical bilirubin.
The color of the skin and sclerae
vary depending on the level of
bilirubin. When the bilirubin level is
mildly elevated, they are yellowish.
When the bilirubin level is high,
they tend to be brown.
Broad Differential Diagnosis
↑production ↓transport or
↓conjugation
Impaired
excretion
Biliary
obstruction
↑Unconjugate ↑Unconjugate ↑Conjugated ↑Conjugated
Hemolysis Gilbert’s Rotor’s CH/CBD stone
Transfusions Crigler-Najarr DubinJohnson Stricture
Txfusion rxn Neonatal Cancer Cancer
Sepsis Cirrhosis Cirrhosis Chronic
pancreatitis
Burns Hepatitis Hepatitis PSC
Hgb-opathies Drug inhibition Amyloidosis
Pregnancy
Metabolism Bilirubin
Bilirubin is a product of heme catabolism. Red cell hemoglobin
accounts for approximately 85% of all bilirubin. In newborns, the
normal hemoglobin level is 15-18 mg/dl so the physiologic rate of
RBC destruction is proportionately high. Excessive bruising from
birth trauma or abnormal blood collections such as in a
cephalohematoma may further add to the rate of RBC destruction
and bilirubin formation.
Heme is catabolized to unconjugated bilirubin in the
reticuloendothelial system. Unconjugated bilirubin is bound to
albumin in the plasma and transported bound to albumin to the liver
and is conjugated with glucuronic acid in the hepatocytes; the
conjugation is catalyzed by glucuronyl transferase. Conjugated
bilirubin is secreted into the bile and enters the duodenum. In the
small bowel, some of the bilirubin is hydrolyzed to yield
unconjugated bilirubin and glucuronic acid. Most unconjugated
bilirubin is excreted in the stool, but some is reabsorbed and
returned to the liver for re-conjugation (enterohepatic circulation(.
The level of glucoroynl transferase is low in the newborn and any
increase in the rate of bilirubin formation can overwhelm the
Liver function tests
( LFTs )
What is Purpose of LFTs?
LFTs alone do not give the physician full information,
but used in combination with a careful history, physical
examination (particularly ultrasound and CT
Scanning(, can contribute to making an accurate
diagnosis of the specific liver disorder.
Different tests will show abnormalities in response to
liver inflammation
liver injury due to drugs, alcohol, toxins, viruses
Liver malfunction due to blockage of the flow of bile
Liver cancers
LFTs are divided into
 true tests of liver function,
such as serum albumin, bilirubin, and
protime,
 tests that are indicators of liver injury or
biliary tract disease.
Classification of liver functions test
Classified based on the major functions of liver:
a.Excretion: Measurement of bile pigments, bile salts.
bSerum enzymes: Transaminase (ALT, AST(, alkaline
phosphate(ALP(, 5’-nucleotidase, LDH isoenzyme.
c.Synthetic function: Prothrombin time, serum
albumin.
d.Metabolic capacity: Galactose tolerance and
antipyrine clearance
e.Detoxification:
Sample Indices Normal Hemolytic
Jaundice
Hepatic
Jaundice
Obstructive
Jaundice
Serum Total Bil >1mg/dl <1mg/dl <1mg/dl <1mg/dl
Direct Bil 0~0.8mg/dl ↑ ↑↑
Indirect Bil >1mg/dl ↑↑
Urine Color normal deeper deep deep
Bilirubin — — ++ ++
Urobilinogen A little ↑ uncertain ↓
Urobilin A little ↑ uncertain ↓
Stool Color normal deeper lighter or
normal
Argilous
(complete
obstruction(
Liver Disease
Live diseases is general term of any
damage that reduces function liver
Different types of liver
disorders include hepatitis,
cirrhosis, liver tumours, and
liver abscess (collection of
pus(.
1-ACUTE VIRAL HEPATITIS
Causes:
 Hepatitis A and B (commonest(.
. Hepatitis C, D and E viruses
(serologic tests available(.
 Other viruses e.g. EBV, CMV
Clinical Features:
Preicteric phase:
flu-like illness, nausea, vomiting, diarrhoea,
abdominal pain.
Icteric phase
o 2/3 of cases never develop jaundice
("anicteric or subclinical hepatitis"(.
Icteric phase
Jaundice
dark urine (bilirubin and
urobilinogen(.
 if severe intrahepatic
cholestasis develops: pruritus,
pale stools and
steatorrhoea.
 Recovery phase:
 prolonged lassitude,
depression.
2-CHRONIC HEPATITIS /
CHRONIC LIVER DISEASE
Chronic hepatitis is defined as hepatic
inflammation due to
any cause, persisting for more than 6 months.
Causes
.Viral, toxic or autoimmune hepatitis
Alcohol
.
Cirrhosis:widespread disruption of normal liver structure by fibrosis and the
formation of regenerative nodules that is caused by any of various chronic
progressive conditions affecting the liver (as long-term alcohol abuse or hepatitis(
CAUSES OF CIRRHOSIS:
Alcohol
Viral B/C
Cryptogenic
Primary Biliary Cirrhosis
Hemochromatosis
Wilsons
Alpha 1 antitrypsin deficiency
Autoimmune
Sclerosing Cholangitis
Liver failure
Severe acute liver injury with impaired
synthetic function and encephalopathy in a
person with a normal liver or well-
compensated liver disease.
What in the history gives us clues to the
cause?
Travel: hepatitis virus?
Over the counter drugs: acetaminophen?
Natural remedies: drug or toxin?
Childbearing age: fatty liver of pregnancy?
Non-specific Management
Hypoglycemia
Encephalopathy
Infections
Hemorrhage
Coagulopathy
Hypotension(hypovolemia, vascular resistance↓(
Respiratory failure
Renal failure
Pancreatitis
ALCOHOLIC LIVER DISEASE
Is common cause of liver disease
Biochemical features include
 raised GGT because of induction as well as cholestasis
(since
GGT levels decline with abstention, GGT is used to monitor
alcohol intake(;
 mild disease - few additional biochemical indicators are
present.
 severe disease- transaminases are elevated, especially
AST
(therefore the ALT/AST ratio is less than 1(
in cirrhosis
increased immunoglobulins esp. IgA producing
"betagamma bridging" on serum electrophoresis
NON-ALCOHOLIC
STEATOHEPATITIS (NASH(
form of chronic hepatitis which is similar histologically to
hepatitis, but which occurs in non-alcoholic patients
alcoholic
risk factors associated with the condition include
 obesity (present in the majority of patients(.
 NIDDM (present in the majority of patients(.
 jejenal-ileal bypass.
 small bowel resection and small bowel bacterial
contamination.
 drugs such as amiodarone, calcium channel blockers
and others.
1 sur 24

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The liver

  • 2. Outlines! 1-What is the liver? 2-funcation of the liver 3-jaundice 4-metabolism bilirubin 5-a-biochemical assement to liver function 6-b-non biochemical assement to liver function 7-Liver disease
  • 3. The liver: The largest solid organ in the body, situated in the upper part of the abdomen on the right side. The liver has two blood supply sources: the hepatic artery (a branch of the celiac artery) delivers oxygenated blood along with cholesterol and other substances (such as hormones) necessary for processing food, while the portal vein collects venous blood from the entire intestinal region and supplies this nutrient-rich blood to the liver for processing and metabolizing. This blood then flows through a network of tiny channels in the liver; nutrients are metabolized, while toxins are processed for expulsion.... 
  • 4. Functions of liver a.Excretory function: bile pigments, bile salts and cholesterol are excreted in bile into intestine. b.Metabolic function: liver actively participates in carbohydrate, lipid, protein, mineral and vitamin metabolisms. c.Hematological function: liver is also produces clotting factors like factor V, VII. Fibrinogen involved in blood coagulation is also synthesized in liver. It synthesize plasma proteins and destruction of erythrocytes.
  • 5. ④ Storage functions: glycogen, vitamins A, D and B12,and trace element iron are stored in liver. ⑤ Protective functions and detoxification: Ammonia is detoxified to urea. kupffer cells of liver perform phagocytosis to eliminate foreign compounds. Liver is responsible for the metabolism of xenobiotic.
  • 6. JAUNDICE What is jaundice? Jaundice is not a disease but rather a sign that can occur in many different diseases. Jaundice is the yellowish staining of the skin and sclerae (the whites of the eyes) that is caused by high levels in blood of the chemical bilirubin. The color of the skin and sclerae vary depending on the level of bilirubin. When the bilirubin level is mildly elevated, they are yellowish. When the bilirubin level is high, they tend to be brown.
  • 7. Broad Differential Diagnosis ↑production ↓transport or ↓conjugation Impaired excretion Biliary obstruction ↑Unconjugate ↑Unconjugate ↑Conjugated ↑Conjugated Hemolysis Gilbert’s Rotor’s CH/CBD stone Transfusions Crigler-Najarr DubinJohnson Stricture Txfusion rxn Neonatal Cancer Cancer Sepsis Cirrhosis Cirrhosis Chronic pancreatitis Burns Hepatitis Hepatitis PSC Hgb-opathies Drug inhibition Amyloidosis Pregnancy
  • 8. Metabolism Bilirubin Bilirubin is a product of heme catabolism. Red cell hemoglobin accounts for approximately 85% of all bilirubin. In newborns, the normal hemoglobin level is 15-18 mg/dl so the physiologic rate of RBC destruction is proportionately high. Excessive bruising from birth trauma or abnormal blood collections such as in a cephalohematoma may further add to the rate of RBC destruction and bilirubin formation. Heme is catabolized to unconjugated bilirubin in the reticuloendothelial system. Unconjugated bilirubin is bound to albumin in the plasma and transported bound to albumin to the liver and is conjugated with glucuronic acid in the hepatocytes; the conjugation is catalyzed by glucuronyl transferase. Conjugated bilirubin is secreted into the bile and enters the duodenum. In the small bowel, some of the bilirubin is hydrolyzed to yield unconjugated bilirubin and glucuronic acid. Most unconjugated bilirubin is excreted in the stool, but some is reabsorbed and returned to the liver for re-conjugation (enterohepatic circulation(. The level of glucoroynl transferase is low in the newborn and any increase in the rate of bilirubin formation can overwhelm the
  • 10. What is Purpose of LFTs? LFTs alone do not give the physician full information, but used in combination with a careful history, physical examination (particularly ultrasound and CT Scanning(, can contribute to making an accurate diagnosis of the specific liver disorder. Different tests will show abnormalities in response to liver inflammation liver injury due to drugs, alcohol, toxins, viruses Liver malfunction due to blockage of the flow of bile Liver cancers
  • 11. LFTs are divided into  true tests of liver function, such as serum albumin, bilirubin, and protime,  tests that are indicators of liver injury or biliary tract disease.
  • 12. Classification of liver functions test Classified based on the major functions of liver: a.Excretion: Measurement of bile pigments, bile salts. bSerum enzymes: Transaminase (ALT, AST(, alkaline phosphate(ALP(, 5’-nucleotidase, LDH isoenzyme. c.Synthetic function: Prothrombin time, serum albumin. d.Metabolic capacity: Galactose tolerance and antipyrine clearance e.Detoxification:
  • 13. Sample Indices Normal Hemolytic Jaundice Hepatic Jaundice Obstructive Jaundice Serum Total Bil >1mg/dl <1mg/dl <1mg/dl <1mg/dl Direct Bil 0~0.8mg/dl ↑ ↑↑ Indirect Bil >1mg/dl ↑↑ Urine Color normal deeper deep deep Bilirubin — — ++ ++ Urobilinogen A little ↑ uncertain ↓ Urobilin A little ↑ uncertain ↓ Stool Color normal deeper lighter or normal Argilous (complete obstruction(
  • 15. Live diseases is general term of any damage that reduces function liver Different types of liver disorders include hepatitis, cirrhosis, liver tumours, and liver abscess (collection of pus(.
  • 16. 1-ACUTE VIRAL HEPATITIS Causes:  Hepatitis A and B (commonest(. . Hepatitis C, D and E viruses (serologic tests available(.  Other viruses e.g. EBV, CMV
  • 17. Clinical Features: Preicteric phase: flu-like illness, nausea, vomiting, diarrhoea, abdominal pain. Icteric phase o 2/3 of cases never develop jaundice ("anicteric or subclinical hepatitis"(.
  • 18. Icteric phase Jaundice dark urine (bilirubin and urobilinogen(.  if severe intrahepatic cholestasis develops: pruritus, pale stools and steatorrhoea.  Recovery phase:  prolonged lassitude, depression.
  • 19. 2-CHRONIC HEPATITIS / CHRONIC LIVER DISEASE Chronic hepatitis is defined as hepatic inflammation due to any cause, persisting for more than 6 months. Causes .Viral, toxic or autoimmune hepatitis Alcohol .
  • 20. Cirrhosis:widespread disruption of normal liver structure by fibrosis and the formation of regenerative nodules that is caused by any of various chronic progressive conditions affecting the liver (as long-term alcohol abuse or hepatitis( CAUSES OF CIRRHOSIS: Alcohol Viral B/C Cryptogenic Primary Biliary Cirrhosis Hemochromatosis Wilsons Alpha 1 antitrypsin deficiency Autoimmune Sclerosing Cholangitis
  • 21. Liver failure Severe acute liver injury with impaired synthetic function and encephalopathy in a person with a normal liver or well- compensated liver disease. What in the history gives us clues to the cause? Travel: hepatitis virus? Over the counter drugs: acetaminophen? Natural remedies: drug or toxin? Childbearing age: fatty liver of pregnancy?
  • 23. ALCOHOLIC LIVER DISEASE Is common cause of liver disease Biochemical features include  raised GGT because of induction as well as cholestasis (since GGT levels decline with abstention, GGT is used to monitor alcohol intake(;  mild disease - few additional biochemical indicators are present.  severe disease- transaminases are elevated, especially AST (therefore the ALT/AST ratio is less than 1( in cirrhosis increased immunoglobulins esp. IgA producing "betagamma bridging" on serum electrophoresis
  • 24. NON-ALCOHOLIC STEATOHEPATITIS (NASH( form of chronic hepatitis which is similar histologically to hepatitis, but which occurs in non-alcoholic patients alcoholic risk factors associated with the condition include  obesity (present in the majority of patients(.  NIDDM (present in the majority of patients(.  jejenal-ileal bypass.  small bowel resection and small bowel bacterial contamination.  drugs such as amiodarone, calcium channel blockers and others.