Outlines!

1-What is the liver?2-funcation of the liver

3-jaundice4-metabolism bilirubin

5 -a-biochemical assement to liver function6-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 liver①Excretory function: bile pigments, bile salts

and cholesterol are excreted in bile into intestine.

②Metabolic function: liver actively participates in carbohydrate, lipid, protein, mineral and vitamin metabolisms.

③Hematological 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

↓conjugationImpaired excretion

Biliary obstruction

↑Unconjugate ↑Unconjugate ↑Conjugated ↑Conjugated

HemolysisGilbert’sRotor’sCH/CBD stone

TransfusionsCrigler-NajarrDubinJohnsonStricture

Txfusion rxnNeonatalCancerCancer

SepsisCirrhosisCirrhosisChronic pancreatitis

BurnsHepatitisHepatitisPSC

Hgb-opathiesDrug inhibitionAmyloidosis

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 capacity to conjugate.

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 inflammationliver 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 :

①Excretion: Measurement of bile pigments, bile salts.

②Serum enzymes: Transaminase (ALT, AST), alkaline

phosphate(ALP), 5’-nucleotidase, LDH isoenzyme.

③Synthetic function: Prothrombin time, serum

albumin.

④Metabolic capacity: Galactose tolerance and

antipyrine clearance

⑤Detoxification:

SampleIndicesNormal Hemolytic Jaundice

Hepatic Jaundice

Obstructive Jaundice

SerumTotal Bil ＜1mg/dl ＞1mg/dl ＞1mg/dl ＞1mg/dl

Direct Bil0～0.8mg/dl ↑ ↑↑

Indirect Bil＜1mg/dl ↑↑

UrineColornormal deeper deep deep

Bilirubin — — ＋＋ ＋＋

Urobilinogen A little ↑ uncertain ↓

UrobilinA little↑uncertain↓

StoolColornormal 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 andsteatorrhoea. Recovery phase:

prolonged lassitude, depression.

2 -CHRONIC HEPATITIS / CHRONIC LIVER DISEASEChronic 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/CCryptogenic

Primary Biliary CirrhosisHemochromatosis

WilsonsAlpha 1 antitrypsin deficiency

AutoimmuneSclerosing Cholangitis

Liver failureSevere 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

HypoglycemiaEncephalopathyInfectionsHemorrhageCoagulopathyHypotension(hypovolemia, vascular resistance ↓)Respiratory failureRenal failurePancreatitis

ALCOHOLIC LIVER DISEASEIs 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.