Jaundice and Ascites

Group#7:
Amor, Merryl Grace
Buela, Crislee Dave
Castilla, Maria Alizza
Desengano, Catherine
JAUNDICE
Filio, Jerry Generoso
Francisco, Jezaliel Kaye
Hubilla, Jan Bembot
Lao, Jan Mirabel

JAUNDICE BILIRUBIN METABOLISM

➢ (also called icterus) refers to the yellow pigmentation of skin

which is caused by elevation in serum bilirubin level

➢ Sclerae icterus is evident at a serum bilirubin level of

>51µmol/L

➢ Occurs when elevated serum carotene levels buy without the

pigmentation of the sclerae
➢ It is the major breakdown product of hemoglobin that released
from senescent erythrocytes.
➢ Bounded to albumin and transported into the liver as it is
conjugated to a water-soluble form (glucuronide) by
glucuronosyltransferase and excreted into the bile and
converted to urobilinogen in the colon.
 ETIOLOGY
➢ Urobilinogen is mostly excreted in the stool; a small portion is
reabsorbed and excreted by the kidney.
Hyperbilirubinemia occurs as a result of
(1) overproduction;
➢ Bilirubin can be filtered by the kidney only in its conjugated
form (measured as the “direct” fraction); thus, increased direct (2) impaired uptake, conjugation, or excretion of bilirubin;
serum bilirubin level is associated with bilirubinuria. Increased (3) regurgitation of unconjugated or conjugated bilirubin
bilirubin production and excretion (even without from damaged hepatocytes or bile ducts
hyperbilirubinemia, as in hemolysis) produce elevated urinary
urobilinogen levels.

EVALUATION GILBERT SYNDROME

➢The initial steps in evaluating jaundice are to determine
➢ Impaired conjugation of bilirubin due to reduced bilirubin UDP
whether
glucuronosyltransferase activity. Results in mild
(1) hyperbilirubinemia is conjugated or
unconjugated hyperbilirubinemia, almost always
unconjugated, and
(2) other biochemical liver tests are abnormal.
➢ Disorder is lifelong and most often detected in young adults
➢Essential clinical examination includes patient history
with vague nonspecific complaints.
➢physical examination
➢blood liver tests, and complete blood count.
➢ Affected are 3%-5% of the population as it is a genetic pattern
however often difficult to establish
 Causes of Isolated Hyperbilirubinemia
Blood Tests of I. Indirect hyperbilirubinemia

Liver Function
A. Hemolytic disorders
B. Ineffective erythropoiesis
C. Increased bilirubin production
1. Massive blood transfusion
2. Resorption of hematoma
D. Drugs
1. Rifampin
2. Probenecif
3. Ribavirin
4. Protease inhibitors (Atazanavir, Indinavir)
E. Inherited conditions
1. Crigler-Najjar types I and II
2. Gilbert’s syndrome

Causes of Isolated Hyperbilirubinemia

Algorithm
II. Direct hyperbilirubinemia (inherited conditions)
A. Dubin-Johnson syndrome for
B. Rotor syndrome
PT with
Jaundice
 • BILIRUBIN
Provides indication of hepatic uptake, metabolic (conjugation) and excretory
functions; conjugated fraction (direct) distinguished from unconjugated by
chemical assay.

• *AMINOTRANSFERASES (TRANSAMINASES)
Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase
(ALT; SGPT); sensitive indicators of liver cell injury; greatest elevations seen
in hepato- cellular necrosis (e.g., viral hepatitis, toxic or ischemic liver injury,
acute hepatic vein obstruction), occasionally with sudden, complete biliary
obstruction (e.g., from gallsto ALT more specific measure of liver injury,
because AST also found.

➢ Algorithm for evaluation of abnormal liver tests. a,AT, a, antitrypsin; AlkP,

alkaline phosphatase; ALT, alanine aminotransferase; AMA,
antimitochondrial antibody; ERCP, endoscopic retrograde
cholangiopancreatogram; GGT, yglutamyl transpeptidase; HAV, hepatitis A
virus; HBc, hepatitis B core; HBSAG, hepatitis B surface antigen; HCV,
hepatitis C virus; MRCP, magnetic resonance cholangiopancreatography; p-
ANCA, perinuclear antineutrophil cytoplasmic antibody; SMA, smooth-muscle
antibody.
➢ In striated muscle and other organs; ethanol-induced liver injury usually
produces modest increases with more prominent elevation of AST than ALT.
ALKALINE PHOSPHATASE
Sensitive indicator of cholestasis, biliary obstruction (enzyme increases more
quickly than serum bilirubin), and liver infiltration; mild elevations in other forms of
liver disease; limited specificity because of wide tissue distribution; elevations also
seen in normal childhood, pregnancy, and bone diseases; tissue- specific
isoenzymes can be distinguished by fractionation or by differences in heat stability
(liver enzyme activity stable under conditions that destroy bone enzyme activity).
5'-NUCLEOTIDASE (5'-NT)
Pattern of elevation in hepatobiliary disease similar to alkaline phosphatase; has
greater specificity for liver disorders; used to determine whether liver is source.
 HEPATOCELLULAR CONDITIONS THAT MAY PRODUCE JAUNDICE
• Viral hepatitis
– Hepatitis A, B, C, D, and E
– Epstein-Barr virus
– Cytomegalovirus
– Herpes simplex
Common Patient Presentations – Alcoholic hepatitis
• Drug toxicity
– Predictable
• dose dependent, (e.g., acetaminophen)
– Unpredictable
• idiosyncratic, (e.g., isoniazid)

HEPATOCELLULAR CONDITIONS THAT MAY PRODUCE JAUNDICE CHOLESTATIC CONDITIONS THAT MAY PRODUCE JAUNDICE
• Environmental toxins • Intrahepatic
– Vinyl chloride – Viral hepatitis
– Jamaica bush tea • 1. Fibrosing cholestatic hepatitis—hepatitis B and C
• pyrrolizidine alkaloids • 2. Hepatitis A, Epstein-Barr virus infection, cytomegalovirus infection
– Kava Kava – Alcoholic hepatitis
– Wild mushrooms – Drug toxicity
• Amanita phalloides or A. verna • 1. Pure cholestasis—anabolic and contraceptive steroids
• 2. Cholestatic hepatitis—chlorpromazine, erythromycin estolate
• Wilson’s disease
• 3. Chronic cholestasis—chlorpromazine and prochlorperazine
• Autoimmune hepatitis
CHOLESTATIC CONDITIONS THAT MAY PRODUCE JAUNDICE CHOLESTATIC CONDITIONS THAT MAY PRODUCE JAUNDICE
• Primary biliary cirrhosis
• Cholestasis of pregnancy
• Primary sclerosing cholangitis
• Total parenteral nutrition
• Vanishing bile duct syndrome
• Nonhepatobiliary sepsis
– 1. Chronic rejection of liver transplants
– 2. Sarcoidosis • Benign postoperative cholestasis
– 3. Drugs • Paraneoplastic syndrome
• Congestive hepatopathy and ischemic hepatitis • Veno-occlusive disease
• Inherited conditions • Graft-versus-host disease
– 1. Progressive familial intrahepatic cholestasis
– 2. Benign recurrent cholestasis

CHOLESTATIC CONDITIONS THAT MAY PRODUCE JAUNDICE CHOLESTATIC CONDITIONS THAT MAY PRODUCE JAUNDICE

• Infiltrative disease • II. Extrahepatic

– 1. TB – Malignant
– 2. Lymphoma • 1. Cholangiocarcinoma
– 3. Amyloidosis • 2. Pancreatic cancer
• 3. Gallbladder cancer
• Infections • 4. Ampullary cancer
– 1. Malaria • 5. Malignant involvement of the porta hepatis lymph nodes
– 2. Leptospirosis
CHOLESTATIC CONDITIONS THAT MAY PRODUCE JAUNDICE γ-GLUTAMYL TRANSPEPTIDASE (GGT)
• GT functions in the body as a transport molecule,
• Benign helping to move other molecules around the body. It
– 1. Choledocholithiasis plays a significant role in helping the liver metabolize
– 2. Postoperative biliary strictures drugs and other toxins.
– 3. Primary sclerosing cholangitis • GGT is concentrated in the liver, but it’s also present
– 4. Chronic pancreatitis in the gallbladder, spleen, pancreas, and kidneys.
– 5. AIDS cholangiopathy GGT blood levels are usually high when the liver is
– 6. Mirizzi’s syndrome damaged.
– 7. Parasitic disease (ascariasis)

COAGULATION FACTORS
• Measure of clotting factor activity; prolongation results from
clotting factor deficiency or inactivity; all clotting factors except
factor VIII are synthesized in the liver, and deficiency can occur
rapidly from widespread liver disease as in hepatitis, toxic
injury, or cirrhosis; single best acute measure of hepatic
synthetic function; helpful in diagnosis and prognosis of acute
liver disease. Clotting factors II, VII, IX, X function only in the
presence of the fat-soluble vitamin K; PT prolongation from fat
malabsorption distinguished from hepatic disease by rapid and
complete response to vitamin K replacement.
ALBUMIN
Decreased serum levels result from decreased hepatic synthesis (chronic liver disease or
prolonged malnutrition) or excessive losses in urine or stool; insensitive indicator of acute
hepatic dysfunction, because serum half-life is 2–3 weeks; in pts with chronic liver disease,
degree of hypoalbuminemia correlates with severity of liver dysfunction.

GLOBULIN
Mild polyclonal hyperglobulinemia often seen in chronic liver diseases; marked elevation HEPATOBILIARY IMAGING
frequently seen in autoimmune chronic active hepatitis.
PROCEDURES
AMMONIA
Elevated blood levels result from deficiency of hepatic detoxification pathways and portal-
systemic shunting, as in fulminant hepatitis, hepatotoxin exposure, and severe portal
hypertension (e.g., from cirrhosis); elevation of blood ammonia does not correlate well with
hepatic function or the presence or degree of acute encephalopathy.

ULTRASONOGRAPHY (US) CT
• Rapid, non invasive examination of abdominal structures
• No radiation exposure • Useful in detecting, differentiating, and directing percutaneous
• Low cost needle biopsy of abdominal masses, cysts, and
• Equipment portable lymphadenopathy.
• Valuable for detecting biliary duct dilation and gallbladder stones (>95%) • Imaging enhanced by intestinal or intravenous contrast dye and
• Most sensitive means of detecting ascites unaffected by intestinal gas.
• Useful in detecting percutaneous needle biopsies of suspicious lesions
• More sensitive for choledocholithiasis
• DOPPLER US - useful to determine patency and flow in portal, hepatic
veins and portal-systemic shunts • Useful to determine diffuse hepatic diseases (e.g. fatty
• Endoscopic US - sensitive for determining the depth of tumor invasion infiltration, iron overload)
through bowel wall.
 MRI
• Most sensitive detection of hepatic masses and cysts.
• Allows easy differentiation of hemangiomas from other hepatic
tumor.
• Most accurate noninvasive means of assessing hepatic and
portal vein patency, vascular invasion by tumor.
• Useful for monitoring Iron, copper deposition in liver (e.g. in
hemochromatosis, Wilson’s Disease).
• Magnetic Resonance Cholangiopancreatography) MRCP -
useful for visualizing the head of the pancreas and pancreatic
and biliary ducts.
CHOLANGIOGRAPHY
• Most sensitive means of detecting biliary duct calculi, biliary
tumors, sclerosing cholangitis, choledochal cysts, fistulas, and
bile duct leaks.
• Maybe performed via endoscopic (transampullary) or
percutaneous (transhepatic) route.
• Allows sampling of bile and ductal epithelium for cystologic
analysis and culture.
• Allows placement of biliary drainage catheter and stricture
dilation.
RADIONUCLIDE SCANNING
• HIDA and related scans - useful for assessing biliary patency
and excluding acute cholecystitis in situations where US is
not diagnostic.
• CT, MRI and Colloid scans - detects liver tumor and
metastasis.
• CT and combination of Colloidal liver and lung scans -
detects right subphrenic (suprahepatic) abscesses.
ANGIOGRAPHY
• Most accurate means of determining portal pressures
and assessing patency and direction of flow in portal
and hepatic veins.
• Highly sensitive for detecting small vascular lesions and
hepatic tumors.
• Gold Standard for differentiating hemangiomas for solid
tumors.
• Most accurate means of studying vascular anatomy in
presentation for complicated hepatobiliary surgery and
determining resectability of hepatobiliary and pancreatic
tumors.
 PERCUTANEOUS LIVER BIOPSY
• Most accurate in disorders causing diffuse changes throughout
the liver.
• Subject to sampling error in focal infiltrative disorders such as

ASCITES
metastasis.
• Should not be the initial procedure in the diagnosis of
cholestasis.
• Contraindication to Percutaneous liver biopsy - include
significant ascites and prolonged international normalized ratio
(INR).
• In such setting, the biopsy can be formed via transjugular
approach.

ASCITES Physical Examination

• Accumulation of fluid within the • Bulging flanks, fluid wave, shifting dullness, “puddle sign” (dullness over
peritoneal cavity. Or it is the abnormal dependent abdomen with pt on hands and knees).
build-up of fluid in the abdomen
• Weight gain and dyspnea due to fluid accumulation and increase
• Small amounts may be asymptomatic abdominal pressure
• Increasing amounts cause abdominal • May be associated with penile or scrotal edema, umbilical or inguinal
distention and discomfort, herniation, pleural effusion.
• anorexia, nausea, early satiety,
heartburn, flank pain, and respiratory
distress.
 Physical Examination EVALUATION
Evaluation should include rectal and
pelvic examination, assessment of liver
and spleen. Palmar erythema and • Diagnostic paracentesis
spider angiomata seen in cirrhosis. (50–100 mL) essential. (
Periumbilical nodule (Sister Mary
fluid removal)
Joseph’s nodule) or supraclavicular
node (Virchow’s node) suggests an
abdominal malignancy.

• Ultrasonography/CT
- Very sensitive; able to distinguish
fluid from
cystic masses.

Routine evaluation includes : Differential Diagnosis

• gross inspection, protein, albumin, glucose, cell count • It is most often caused by:
and differential, Gram’s and acid-fast stains, culture, • Liver cirrhosis – 75%
cytology; also check amylase, LDH, triglycerides, culture • Malignancy 10%
for tuberculosis (TB).
• Heart failure ( cardiac ascites) 3%
• Pancreatitis 1%
• Tuberculosis 2%
 Serum-Ascites Albumin Gradient (SAAG)

• Diseases of peritoneum: Infections (bacterial, tuberculous,

fungal, parasitic), neoplasms, connective tissue disease, • It is the difference in albumin concentrations between
miscellaneous (Whipple’s disease, familial Mediterranean fever, serum and ascites as a reflection of imbalances in
endometriosis, starch peritonitis, etc.). hydrostatic pressures and can be used to differentiate
between potential causes of ascites
• Diseases not involving peritoneum: Cirrhosis, CHF, Budd-Chiari
syndrome, hepatic venoocclusive disease, hypoalbuminemia
(nephrotic syndrome, protein losing enteropathy, malnutrition),
miscellaneous (myxedema, ovarian diseases, pancreatic
disease, chylous ascites).

CIRRHOTIC ASCITES
Pathogenesis
Contributing factors:
-portal hypertension
-hypoalbuminemia
- hepatic lymph
- renal sodium retention—secondary to
hyperaldosteronism, (increased renin-angiotensin
production).
 Cirrhotic Ascites
1. Dietary salt restriction is advised (<2 g Na/d).
2. For moderate ascites, diuretics usually necessary; spironolactone 100–
200 mg/d PO (can be increased to 400 mg/d if low-sodium diet is
confirmed and fluid not mobilized); furosemide 40–80 mg/d PO or IV may
be added if necessary (greater risk of hepatorenal syndrome [HRS],
encephalopathy),can increase to maximum of 120–160 mg/d until effect
achieved or complication occurs.
3. Monitor weight, urinary Na and K, serum electrolytes, and creatinine.
• If ascites is still present with the above measures, this is defined
as refractory ascites.
COMPLICATIONS
• Spontaneous Bacterial Peritonitis
– Suspect in cirrhotic pt with ascites and fever, abdominal
pain, worsening ascites, ileus, hypotension, worsening
jaundice, or encephalopathy; low ascitic protein
concentration is predisposing factor.
Treatment modalities include:
a. Pharmacologic therapy: add midodrine or clonidine to diuretic
therapy
b. Repeated large-volume paracentesis (5 L) with IV infusions of
albumin (6–8 g/L ascites removed)
c. Consider transjugular intrahepatic portosystemic shunt (TIPS).
While TIPS manages the ascites, it has not been found to improve
survival and is often associated with encephalopathy potential
causes of ascites
Diagnosis
➢ ascitic fluid PMN cell count >250/µL
➢ confirmed by positive culture (usually Escherichia coli and other
gut bacteria; however, gram-positive bacteria including
Streptococcus viridans, Staphylococcus aureus, and
Enterococcus spp. also can be found)
Initial Treatment
➢ Cefotaxime 2 g IV q8h. Risk is increased in pts with variceal
bleeding, and prophylaxis against spontaneous bacterial
peritonitis is recommended when a pt presents with upper GI
bleeding.
 Hepatorenal Syndrome (HRS)
• Functional renal failure without renal pathology; occurs in 10% of pts with
advanced cirrhosis or acute liver failure

Two types:
• type 1 HRS—decrease in renal function within 1–2 weeks of
presentation;
• type 2 HRS—associated with a rise in serum creatinine but is associated
with a better outcome. Often seen in pts with refractory ascites.

Treatment: midodrine along with octreotide and IV albumin.

For either type 1 or 2 HRS, prognosis is poor in the absence of liver

transplantation.