THE JAUNDICED PATIENT

BY

DR.SEFEEN SAIF ATTYA

SOHAG TEACHING HOSPITAL

JAUNDICE

Jaundice is a syndrome ,the hallmark of which is yellowish discoloration of body tissues produced by an excess of circulating bilirubin (conjugated or unconjugated)

Normal serum bilirubin is ranging from 0.1-1 mg % and jaundice is detected clinically in the sclera of the eye when the level rises above 2.5 mg%

It is most evident in tissues which have a high elastic tissue content (skin –sclera of the eye – blood vessels)

BILIRUBIN METABOLISM Bilirubin is formed from haem (a compound of iron and

protoporphyrin) , Haem comes from breakdown of mature red cells in the reticuloendothelial system

This unconjugated bilirubin which is water insoluble is toxic and transported attached to plasma proteins to the liver cells

In the hepatic cells it is conjugated into water soluble bilirubin (conjugated bilirubin)

Conjugated bilirubin is excreted into the bile canaliculi Disturbance of the flow of bile led to stagnation and retention of conjugated bilirubin (cholestasis)which may occur in the intrahepatic bile ducts (intrahepatic cholestasis)or in the extrahepatic bile ducts (extrahepatic cholestasis)

Mechanisms of jaundice(1)Excess bilirubin production

(2)impaired uptake and transport of bilirubin by the hepatocytes (3)failure of conjugation

(4)Impaired secretion of conjugated bilirubin into the bile canaliculi (5)Impaired bile flow subsequent to secretion by the hepatocyte

Thus there are 3 categories of jaundice Haemolytic jaundice)1(Hepatocellular jaundice)2-4(

( Obstruvtive jaundice)5

Classification of JaundiceDefect in bilirubin metabolismPredominant hyperbilirubinemiaExamples

Increased productionUnconjugatedCongenital hemoglobinopathies, hemolysis, multiple transfusions, sepsis, burns

Impaired hepatocyte uptakeUnconjugatedGilbert’s disease, drug induced

Reduced conjugationUnconjugatedNeonatal jaundice, Crigler–Najjar syndrome

Impaired transport and excretionConjugatedHepatitis, cirrhosis, Dubin–Johnson syndrome, Rotor syndrome

Biliary obstructionConjugatedCholedocholithiasis, benign strictures, chronic pancreatitis, sclerosing

cholangitis, periampullary cancer, cholangiocarcinoma

The term cholestatic jaundice may be intrahepatic (hepatic disease impairing transport of conjugated bilirubin from the hepatocyte to bile canaliculi and intrahepatic

ducts)

or Extrahepatic (from large bile duct obstruction )

The later is referred to as surgical jaundice

JAUNDICE DUE TO INCREASED BILIRUBIN LOAD

(HAEMOLYTIC JAUNDICE-UNCONJUGATED HYPERBILIRUBINAEMIA)

Hereditary spherocytosisSickle cell anaemia Thalassaemia acquired haemolytic anaemiaIncompatible blood transfusion Severe sepsisdrugs

DISTURBED BILIRUBIN UPTAKE & CONJUGATION

Grigler –najjar familial non-haemolytic jaundice

Familial neonatal hyperbilirubinaemiaGilbert’s familial non haemolytic

hyperbilirubinaemiaViral hepatitis Hepato-toxinscirrhosis

DISTURBED BILIRUBIN EXCRETION (CHOLESTASIS)

A- intrahepatic cholestasis CirrhosisVira hepatitisDrugs(chlorpromasine- oral contraceptives)Dubin-johnson familial conjugated

hyperbilirubinaemiaPrimary biliary cirrhosis(chronic non-

suppurative destructive cholangitis)

B-EXTRAHEPATIC CHOLESTASIS 1- INSIDE DUCT

Ductal stonesF.B.(broken T-tube)Parasites (hydated liver fluke, round worm)Titanium clips internalization

2-IN DUCT WALLCongenetal atresia traumatic stricture Sclerosing cholangitis

Bile duct tumours 3 -OUTSIDE WALL

Cancer head pancreas cacer ampulla of vaterPacreatitis

Porta hepatis metastasis

INVESTIGATION OF THE JAUNDICED PATIENT

Parenchymal(hepatocytes)

ALT AST

canalicular(biliary)ALP, 5'NT, GGT

synythetic Function and metabolism

INR, bilirubin, albumin

A- LABOLATORY TESTS

B- Imaging studiesNON-INVASIVE METHODS

1 -ULTRASOUND Ultrasonography is both sensitive and specific in

detecting gallbladder stones and dilatation of bile ducts. Ultrasound usually misses stones in the common duct.

When ultrasound shows dilated bile ducts, THC will nearly always be technically successful.

ultrasound image demonstrate the normal gallbladder The thin wall of the gallbladder is seen as a white ring surrounding bile, which appears as a black fluid. The wall thickness should be less than 3 mm in adults .

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2-SPIRAL C.T. Spiral C.T. with I.V. contrast enhancement is

essential in all patients with suspected tumours I.V. superparamagnetic ferric oxide (endorem)

which yields even greater definition This shows liver tumours as white areas (no

kupffer cells) against a black background (contrast in kupffer cells)

CT image demonstrates a large gallstone in the gallbladder

3-RADIONUCLIDE SCAN (HIDA SCAN) Technetium 99m-labeled derivatives of

iminodiacetic acid (IDA) are excreted in high concentration in bile and produce excellent gamma camera images.

Following intravenous injection of the radionuclide, imaging of the bile ducts and gallbladder normally appears within 15–30 minutes.

4 -Magnetic Resonance Imaging Available since the mid-1990s, MRI provides

anatomic details of the liver, gallbladder, and pancreas similar to those obtained from CT.

Using MRI with newer techniques and contrast materials, accurate anatomic images can be obtained of the bile ducts and the pancreatic duct.

It has a sensitivity and specificity of 95 and 89%, respectively, at detecting choledocholithiasis.

5 -MAGNITIC RESONANCE CHOLANGIOPANCREATOGRAPHY (MRCP)

Is completely non-invasive and does not require injection of contrast

It is a specialized type of MRI that uses radio waves and magnets to obtain pictures of the bile ducts

INVASIVE METHODS 1 -PERCUTANEOUS TRANSHEPATIC

CHOLANGIOGRAPHY PTC is performed by passing a fine needle through

the the hepatic parenchyma and into the lumen of a bile duct. Water-soluble contrast material is injected, and x-ray films are taken.

The technical success is related to the degree of dilatation of the intrahepatic bile ducts. THC is especially valuable in demonstrating the biliary anatomy in patients with lesions of the proximal bile duct, or when ERCP has been unsuccessful.

These two radiographs demonstrate the skinny needle used to puncture the bile duct during PTC .

THC should not be done in patients with cholangitis until the infection has been controlled with antibiotics.

Virtually all patients should be premedicated with antibiotics regardless of whether they have cholangitis or not

septic shock has been produced by sudden inoculation of organisms from bile into the systemic circulation

2 -ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP) ERCP involves cannulating the sphincter of

Oddi under direct vision through a side-viewing duodenoscope.

Usually, it is possible to opacify the pancreatic as well as the bile ducts.

It is usually the preferred method of examining the biliary tree in patients with presumed choledocholithiasis or obstructing lesions in the periampullary region.

The endoscope transmits dynamic images of the lumen of the gut allowing the physician to carefully examine the

lining. During the procedure air is blown into the digestive tract to expand mucosal folds making examination thorough

The ERCP is usually performed in the radiology department under fluoroscopic guidance. The patient is sedated, and the endoscope inserted through the mouth into the duodenum. The physician looks for the major duodenal papilla to insert the guide catheter to perform the retrograde

study of the biliary tree

This picture shows the catheter from the endoscope within the papilla. This allows the physician to perform a

retrograde filling of the biliary tree.

This picture shows the major duodenal papilla before the endoscope is inserted .

3-Endoscopic ultrasonography (EUS) With the considerable advances in transducer

technology and related image-processing software ,EUS has been shown to be extremely useful for the diagnosis and staging of bile duct and proximal pancreatic pathology

A more recent development is intraductal ultrasonography (IDUS) where a fine transducer probe is introduced in the bile or pancreatic duct at ERCP

4-Laparoscopy with laparoscopic contact US

This provides the most senitive and reliable assessment ,staging of hepatic ,biliary and pancreatic cancers

C- LIVER BIOPSY Should not be done until a bleeding tendency

has been excluded The procedure is hazardous in the presence

of ascites Hydatid disease of the liver must be excluded

as accidental puncture can spread the disease throughout the peritonial cavity or give rise to anaphylactic shock

SURGICAL JAUNDICESURGICAL JAUNDICE

1-Gallstones and ductal calculi

2 -Pancreatic disease

3 -biliary malignancy

4-hepatic malignancy

5 -benign bile duct strictures

1-GALLSTONES & DUCTAL CALCULI

Gallstones are very common worldwide ,the prevalence is 18% with a female preponderance (2-1)

The currentaly accepted classification recognizes 3 main types of gallstonesA-cholesterol stones: essentially metabolic stones that form in the gall bladder B-black pigment stones : form in the gall bladder and consist of bilirubin pigments with a varrying amount of cholesterolC- brown pigment stones :form in the bile ducts (primary ductal stones) ,they are amorphous soft stones that consist of calcium bilirubinate and palmitate bound in a matrix of organic material

DUCTAL CALCULI

Ductal calculi can result from migration of gallstones through a patent cystic duct (secondary ductal calculi –black pigment calculi) or formed de novo in the ducts (primary ductal calculi-brown pigment stones)

Ductal calculi may form around foreign bodies within the lumen of the common bile duct ,a common example of this nowadays is caused by the internalization of titanium metal clips used to secure the medial end of the cystic duct stump during laparoscopic cholecystectomy ,the patient present several months after an uneventful L.C.with jaundice and /or cholangitis

ERCP demonstrates stones in the common bile duct on the left radiograph, and cystic duct on the right radiograph

CLINICAL TERMS TO DESCRIBE DUCTAL CALCULI

UNSUSPECTED STONESAre those discovered accidentally when routine intraoperative cholangiography is performed ,these stones are usually small and floating and the C.B.D. is of normal caliber

MISSED STONESAre stones missed after intervention (surgical or endoscopic) that fails to achieve complete ductal clerance

Ductal calculi that diagnosed within 2 years of the intervention are described as missed stones

RECURRENT STONES

Present at least 2 years after the first intervention

These tend to be primary ductal stones (brown pigment stones)and are almost always

associated with dilatation of the C.B.D .

MANAGEMENT

1 -GALLSTONES AND DUCTAL CALCULI

Cholecystectomy is only indicated for symptomatic gallstones and their copmlications (acute cholecystitis,acute pacreatitis ,jaundice due to ductal calculi)

There is now firm evidence from several prospecive randomized trials that “early” cholecystectomy for acute cholecystitis (operation within the same hospital admission )is superior to “delayed” cholecystectomy (2-3 month after resolution of the attack )provided the patient is fit for surgery and anaesthesia

operative cholangiogram. The catheter is inserted into the cystic duct and contrast media injected as radiographs are taken. The entire distal biliary tree is demonstrated without stone or dilation of the ducts. This confirms that stones are limited to the gallbladder, which was removed

The benefits of early cholecystectomy include Reduced overall morbidity Reduced hospital stay Prevention of further attacks that may occur in

patients managed by yhe delayed cholecystectomy policy

Unfit patients should be treated conservatively in the first instance with the expectation that acute cholecystitis will resolve in 80% of cases

If this conservative treatment fails or in cases with empyema of the G.B. an ulrasound laparoscopically guided cholecystostomy or microcholecystostomy (under u/s guidance ) will tide the patient over the critical illness

The current treatment for patients with concomitant ductal stones is preoperative endoscopic stone extraction followed by cholecystectomy preferably during the same hospital admission

Single stage L.C. and ductal stone clerance either by the transcystic route (stones <6mm )or by laparoscopic supraduodenal direct C.B.D. exploration (large stones) is prefered in some centres instead of the two-stage approach

A large cholesterol stone (white arrow) is released from a wire basket into the duodenum

sphincterectomy (blue arrow) was performed to allow a stone to be removed and release

stagnated bile into the duodenum

This image demonstrates the completion of the ERCP. A stent has been placed in the common bile duct (white arrow). After a stone was removed

T-tube cholangiogram. The tube inserted into the common bile duct. As you can see the tube is long extending to the outside of the body .

22--PANCREATIC DISEASEPANCREATIC DISEASE

Periampullary cancers are usually resectable and are treated by pancreatoduodenectomy if the patient is fit for major surgery

By contrast most proximal pancreatic adenocarcimomas are not resectable and are managed palliatively (biliary bypass) with stenting (by interventional endoscopy or interventional radiology )

In patients with jaundice thought to be due to chronic pancreatitis the options are between a formal pancreatoduodenectomy or subtotal resection of the head leaving a rim of pancreas in the duodenal curve and releasing the transpancreatic duct (Beger’s procedure)

Amodification of Beger’s procedure involves transection of the bile duct just above the pancreas with reimplantation into the duodenum , Both operations preserve the duodenum

If there is doubt concerning the diagnosis the appropriate procedure is a formal pancreatoduodenectomy

3 -BILIARY TRACT MALIGNANCIES

A-CARCINOMA OF THE GALLBLADDER is the most common malignancy of the

biliary tract and accounts for 3-4 % of all gastrointestinal malignancies

It is a disease of old age and carries a poor prognosis

Gall stones are present in 75-90% of cases

B-BILE DUCT CANCERS (cholangiocarcinomas)1-intrahepatic:from major hepatic ducts

2-proximal:from right and left hepatic ducts ,hilar confluence and proximal CHD

3-middle :from distal CHD ,cystic duct and its confluence with the CHD

4-distal: included with periampullary tumoursRadiologically they give rise to a stricture with proximal dilatation

TREATMENT OF BILIARY MALIGNANCY

cacinoma of the gall bladder is a miserable disease that is always incurable when diagnosed clinically

Palliation of the jaundice and itching due to involvement of the C.H.D. is achieved by

endoscopic or radiological stenting In the rare instance when the disease is

resectable and the patient is fit resection is indicated

If the tumour invades the hepatic parenchyma a right hepatectomy with resection of the C.B.D.and nodal clearance is performed

In selected cases if the lesion is confined to the G.B. the liver resection is limited to the gall

bladder bed

Middle and distal bile duct tumours are resected with removal of the pancreas and duodenum

Proximal tumours (hilar) may be resected if the patient’s condition is good . The resection extendes beyond the bifurcation and must always include the caudate lobe

Non-resectable or inoperable bile duct tumours can be either stented or bypassed surgically

Expandable metalic wall stents give better palliation than plastic stents

There is some debate as to whether surgical palliation should include a gastroenterostomy in addition to biliary bypass

4 -HEPATIC MALIGNANCY

hepatic malignancy can be primary (H.C.C.)

or secondary from a primary in another site The presence of jaundice in association

with liver tumours indicate extensive involvement of the liver parenchyma with the patient being incurable and unlikely to benefit from any form of treatment

HEPATOCELLULAR CARCINOMA may arise on a morphologically normal liver or

complicate established cirrhosis The aetiology is varied but the vast majority is the

result of HBV or HCV Some cases are associated with oral

cotraceptives and androgenic steroids Ingestion of food contaminated with aflatoxins

produced by fungus Aspergillus flavus has been incriminated in some cases

Symptoms include pain in the right hypochondrium ,hepatic enlargement and ascites

In some cases the tumour gives rise to systemic manifestations including polycythemia, carcinoid syndrome ,hypoglycaemia and hypercalcaemia

Raised alpha-fetoprotein is present in 60-70% of cases

HEPATIC METASTASIS 90% of hepatic tumours are metaststic from

primary in the gastrointestinal tract ,pancreas,lungs and breast

The most common are secondary hepatic deposits from colorectal cancer

Morphologically on laparoscopic inspection secomdary hepatic tumours may be

1- discretely nodular : (single or muliple)2-miliary: widespread small seedling deposits

TREATMENT OF HEPATIC TUMOURS

Hepatocellular carcinoma Only patients who are not jaundiced ,have no

evidence of disease elsewhere (including hepatic nodes) and are fit with good liver functions are suitable for hepatic resection

Hepatectomy is not usually possible in patients who develop the disease on a backgroud of cirrhosis ,treatment is by in situ ablation or embolization

Secondary tumours usually from colorectal cancer are a much

more common problem There is a definite place for surgical resection

if the disease is confined to one side and there are no more than 3 deposits

The most imortant factor infuencing outcome after surgical resection is a tumour free margin of at least 1.5 cm

Systemic chemotherapy with high dose 5FU with folinic acid induces disease regression in 30% of cases

There is no evidence that regional hepatic

intra-arterial chemotherapy is any more effective than systenic chemotherapy

Only discretely nodular disease is potentially curable by surgical resection

Only 5% of patients with hepatic metastasis are suitable for this treatment

Palliation can be obtained by systemic chemotherapy and by insitu ablation techniques provided that the extent of hepatic involvement is <25%

IN SITU ABLATION

In situ ablation either laparoscopic or image –guided can be achieved by:

1-alcoholinization (small lesions <2 cm)

2-cryosurgery with high eficiency liquid nitrogen

3-radiofrequency thermal ablation

4-interstitial laser hyperthermia

The advantage of in situ ablation is that it can be repeated if new lesions or recurrence at the treated sites detected on follow up

The early results of a combination of in situ ablation with systemic chemotherapy look very promising

5 -BENIGN BILE DUCT STRICTURES

1-Iatrogenic bile duct injury during cholecystectomy

2-the constriction and compression of the intrapancreatic segment of the CBD by the pseudotumour of chronic pancreatitis

3-parasitic infestation of the biliary tract

4-multiple strictures of sclerosing cholangitis

ERCP Radiograph shows a stricture of the common bile duct.

SCLEROSING CHOLANGITIS

Is arare chronic disease characterized by fibrous thickening of the intrahepatic or extrahepatic bile ducts often associated with multiple strictures

CAUSES

PRIMARY SCLEROSING CHOLANGITIS: the exact cause of which remains unknown ,probably an autoimmune disease

SECONDARY TO :ductal stones,congenital lesions or operative trauma

PRESENTATION the disease is 2-3 times more common in men

than in women Symptoms include malaise ,jaundice,abdominal

pain ,anorexia,weight loss ,fever,pruritisAbout one third of cases are associated with

chronic inflammatory bowel disease (U.C. or C.D.)

Hepatitis virus does not cause primary sclerosing cholangitis

DIAGNOSIS The diagnosis of primary sclerosing cholangitis is based on

clinical suspicion confirmed by cholangiographic demonstration of multiple strictures separated by segments of ducts of normal or increased diameter (beaded apperance)

Liver biopsy confirm the diagnosisDIFFRENTIAL DIAGNOSIS. The clinical and histologic patterns of S.C. overlap those of

primary biliary cirrhosis ,however the latter disease typically affects middle aged women with keratoconjunctivitis sicca,hyperpigmentation and high titres of A.M.A.

Cholangiography allows diffrentiation as primary biliary cirrhosis never involves extrahepatic ducts

TREATMENT(controversial) If a major stricture involves extrahepatic duct (bypass

procedure) Other cases have been treated successfully by T.tube

drainage of the C.B.D. and by stenting of strictures High dose steroids can be effective in relieving the fibrous

strictures The oral adminstration of ursodiol shows promise ,it

reduces serum bilirubin , decreases clinical jaundice ,decreases serum transaminase levels and improve symptoms

Liver transplantation is the only effective treatment of end stage liver disease

PROGNOSIS Some patients die from liver failure within

months of diagnosis Others may live relatively symptom free for

many years 10% of patients with sclerosing cholangitis

will develop bile duct carcinoma

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