Você está na página 1de 6

Obstructive Jaundice Jaundice Yellowish staining of skin, sclera, mucous membranes Deposition of bilirubin (yellow orange bile pigment)

Bilirubin > 2mg/dl (34.2 umol/L) Causes of Jaundice Pre-hepatic Hepatic Post-hepatic (obstructive) Anatomy Ventral bud (hepatic diverticulum) y Liver y Gallbladder y Biliary tree Most caudal part of foregut (early in 4th week) Divides into 2 parts Cranial Part (Pars Hepatica) Caudal Part (Pars Cystica) Primordium of liver Form gallbladder, stalk Become cystic duct

Common Bile Duct Supraduodenal Retroduodenal Intrapancreatic

Bilirubin Metabolism Pre-Hepatic Bilirubin (formed in macrophages of RES) Substrate Haemoglobin Heme group Biliverdin Bilirubin (insoluble)

Bilirubin (insoluble) + Albumin Circulates in Blood Uptake by Liver Pre-hepatic jaundice y Bilirubin not taken up by liver y Produced in excess, unconjugated bilirubin y Deposited in extra-hepatic tissues Hepatic Bilirubin (taken up into hepatocytes) Bound to intracellular proteins Bilirubin + UDP glucuronic acid Bilirubin diglucuronide Bilirubin monoglucuronide UDP

Bile Formation, Composition Produced by Liver (500 1000 ml/day) Production stimulated by y Vagus y Food particles in duodenum, secretin Composed of y Water y Electrolytes y Bile salts y Bile pigments y Protein y Lipids Cholesterol 1 bile salts Conjugation + Na Bile salts Small intestine Absorbed in terminal ileum (80%) Deconjugated (2 bile acids) Absorbed in colon 95% of bile acid pools is reabsorbed (enterohepatic circulation)

Bilirubin (water soluble) Excreted into Bile (bile canaliculus by carrier-mediated transport) Hepatic jaundice y Disorder of bilirubin uptake y Disorder of bilirubin conjugation Post-Hepatic Glucuronide-conjugated bilirubin in bile Degraded to urobilinogen Pathways Urobilinogen y Reabsorbed by gut Returned to liver y Converted to urobilin y Reabsorbed into plasma (excretion by kidneys) Conjugated Bilirubin y Bacterial enzymes in gut (bile pigment stercobilinogen) (stool colour) y Stercobilinogen Reabsorbed into plasma (recycling to liver) Excretion by kidney Oxidized to stercobilin Partially reabsorbed into plasma

Obstructive jaundice y Failure of bilirubin to reach gut y Pigment within stool

RBC break down after 120d Unconjugated bilirubin transported to liver (bound to albumin) Bilirubin conjugated with glucuronyl transferase Conjugated bilirubin excreted in small bowel (acted on by bacteria) Urobilinogen absorbed into blood Excreted by kidneys Remainder excreted as stercobilin in faeces (after enterohepatic circulation) Functions of Bile Intestinal digestion, absorption of lipids Elimination of environmental y Toxins y Carcinogens y Drugs y Metabolites (xenobiotics) Primary route of excretion of variety of endogenous, metabolic products y Cholesterol y Bilirubin y Hormone

Pathophysiology of Obstructive Jaundice (Post-Hepatic) Absence of bile constituents in intestines y Bilirubin y Bile salts y Lipids Cause spillage into systemic circulation Pale stool (less bilirubin reaches intestine) Absence of bile salts Malabsorption Steatorrhea Deficiencies of fat-soluble vitamins (A, D, K) Vitamin K deficiency ( prothrombin levels) Long standing cholestasis Concomitant Vitamin D, Ca2+ malabsorption Osteoporosis, osteomalacia Jaundice Medical causes Not detectable clinically under bilirubin > 35 mmol/L Painless progressive jaundice is malignancy Investigations y FBC y LFT y Clotting y Urinary urobilinogen y Depend on underlying cause Bilirubin Retention Produce mixed hyperbilirubinemia Conjugated bilirubin (tea-coloured urine) Pruritus ( circulating bile salts) Hyperlipidaemia y Cholesterol, phospholipid retention y Liver synthesis Plasma esterification of cholesterol Common Causes Choledocholithiasis Cholangiocarcinoma Ampullary cancers Cancer of Pancreas Biliary strictures Clinical Features History Fever, chills, RUQ pain (cholangitis) Hepatitis risk factors Exposure to toxic substances Inherited disorders (liver disease, haemolytic conditions) History of blood transfusion Obstructive Jaundice (Hallmark) Jaundice Dark urine Pale stools Generalized pruritus Causes Cholangitis/ Choledocholithiasis History of fever Biliary colic Intermittent jaundice Peri Ampullary Cancer Deep jaundice y Greenish hue y Fluctuate in intensity

Investigations Biochemistry (Hematological) y Conjugated bilirubin > 35 mmol/L y ALP/ GGG >> AST / ALT y Albumin y PTT y Cholesterol Urinalysis Haemolysis Obstruction Hepatocellular Conjugated bilirubin Normal Normal Urobilirubin Nil Normal Imaging y Abdominal X-ray y Ultrasonography y CT y Endoscopic Retrograde CholangioPancreaticography (ERCP) y Endoscopic Ultrasonography y MRI y Magnetic Resonance CholangioPancreatography (MRCP)

Pancreatic Cancer Weight Abdominal mass Pain radiating to back Progressively deepening jaundice Extrahepatic Malignancy Couvoissier s Sign Palpably enlarged gall bladder Jaundice

Physical Examination Signs of end stage liver disease (cirrhosis) y Ascites y Splenomegaly y Spider angiomata y Gynecomastia Jaundice tongue, conjunctiva, skin (>1.5mg/dL) Hyperpigmentation (hemochromatosis) Kayser-Fleischer ring (Wilson s disease) Xanthomas (1 biliary cirrhosis)

Stones Choledocholithiasis Common bile duct stones (primary, secondary) Clinical manifestation y Silent y Present with o Biliary colic o Cholangitis o Gallstone pancreatitis o Obstructive jaundice Diagnosis y US y MRC y ERCP

Malignant Pancreatic Cancer Etiology Smokers Fat, Protein, Caffeine, Alcohol diets Genetic Pathophysiology Arise from epithelial cells of pancreatic ducts Tumour in late stage spread throughout pancreas Can be result of metastasis disease from y Lung y Breast y Thyroid y Kidney y Skin Rapid growing with spread to surrounding tissue Head of pancreas (most common site) Thromboplastic factors y Necrotic pancreatic tumours y Results in thrombophlebitis Clinical Management (Prevent spread of tumour) Chemotherapy, radiation Pain control Total resection Head of pancreas removal Whipple procedure Nutritional support TPN, tube feeding Fluid, electrolyte replacement Glucose monitoring Cholangiocarcinoma Slow growing malignancy Biliary tract Infiltrate locally, metastasize late Extra-hepatic (90%) 60-70 y/o, M=F ( Incidence Japan, Israel, Native Americans) Etiology Pathology Ulcerative colitis Adenocarcinoma Sclerosing cholangitis Types Choledochal cysts y Papillary Hepatolithiasis y Nodular Liver flukes y Sclerosing Papillomatosis of bile ducts Best prognosis papillary distal tumours Thorotrast exposure Typhoid carrier Adult polycystic kidney disease

Cancer of Common Bile Duct (CBD) Bifurcation Periampullary Carcinoma Pathology Adenocarcinoma Arises from 4 different tissues of origin y Head of pancreas y Distal bile duct y Ampulla of Vater y Periampullary duodenum Treatment

Standard Whipple pancreaticoduodenectomy

Non-Malignant Primary Biliary Cirrhosis (PBC) Slowly progressive autoimmune liver disease Female (90%), 40 y/o peak Portal inflammation, autoimmune destruction of intrahepatic bile ducts Leads to y Cirrhosis y Liver failure Have antimitochondrial antibody (90-95%) Causes Genetic factors (common in 1st degree relatives) Molecular mimicry (to certain bacteria, viruses) Environmental chemical exposure Clinical Features Physical Examination Asymptomatic (50%) Normal Fatigue Spiders, skin excoriations Pruritus Xanthelasmas Hepatomegaly Hyperlipidaemia Jaundice Hypothyroidism Osteopenia Autoimmune diseases Portal hypertension Liver failure HCC Diagnosis +ve AMA Abnormal LFT Compatible biopsy Pathological Stages (4) Destruction of bile ducts (in portal tracts) Inflammation (beyond portal tracts) Fibrous septa (link portal triads) Cirrhosis Primary Sclerosing Cholangitis (PSC) Chronic inflammatory cholestatic disease Progressive destruction of bile ducts May progress to cirrhosis Autoantibodies ANCA ANA SMA Natural History 20-30 y/o diagnosed M:F = 3:1 Inflammatory bowel disease (80% have)(eg. Ulcerative colitis) Etiology, Pathogenesis Familial HLA associations B8, DR3, DRw52a, DR2, DR4 Polymorphism of TNF gene Immune factors Clinical Manifestations Asymptomatic Pruritis Jaundice Pain Fatigue Cirrhosis Portal hypertension PSC Associated with IBD Ulcerative colitis (85%) Crohns Indeterminate colitis

Cholangiocarcinoma Risk of HCC

Bowel Cancer More proximal More advanced More fatal

Treatment Ursodeoxycholic acid (UDCA) y Bilirubin, ALP, AST, ALT, Cholesterol, IgM y Delays fibrosis, varices Colchicine Methotrexate Budesoide Liver transplantation

Diagnosis MRCP, ERCP (multifocal strictures, dilatation) Clinical, Biochemical, Histological Liver biopsy (onion skin fibrosis) Laboratory LFTs (cholestatic pattern ALP 3-5X ULN) y AST/ ALT y Bilirubin (advanced disease, dominant stricture, cholangio ca, stones, cholangitis) Management Ursodeoxycholic acid (UDCA) Steroids Endoscopic treatment (balloon dilatation, stenting) Liver transplant

Complications Stenosis of Sphincter of Oddi Inflammation, fibrosis, muscular hypertrophy Episodic biliary pain Abnormal LFT Dilated common bile duct (difficult to cannulate, delayed emptying of contrast) Causes (Bile duct strictures) Operative injury Fibrosis (due to chronic pancreatitis) Common bile duct stones Acute cholangitis Biliary obstruction (due to cholecystolithiasis) (Mirizzi s syndrome) Sclerosing cholangitis Cholangiohepatitis Strictures of a biliary-enteric anastomosis Bile Duct Strictures Recurrent cholangitis, 2 biliary cirrhosis, portal hypertension Present with cholangitis, jaundice US, CT, MRC, PTC, ERCP Treatment y Endoscopic dilatation y Stent placement y Roux-en-Y choledochojejunostomy y Hepaticojejunostomy y Choledochoduodenostomy Cholangitis Ascending bacterial infection Associated with partial, complete obstruction of bile ducts Infection Escherichia coli Klebsiella pneumoniae Streptococcus faecalis Bacteroides fragilis Clinical Manifestations RUQ pain Fever Jaundice Hypotension Altered mental status Additional History Pruritus Acholic stools PMH for gallstones CBD stones Recent ERCP Cholangiogram Treatment Medical Antibiotics y Ampicillin + Gentamicin y Carbapenems y Levofloxacin Surgical Endoscopic biliary drainage PE Tachycardia Hepatomegaly (mild)