Management of Icterus Viewed From the Clinical And

8/2/2019 Management of Icterus Viewed From the Clinical And

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RUZANAZ SYAFIRA

030.07.334

FK USAKTI

MANAGEMENT OF

ICTERUS VIEWED FROMTHE CLINICAL AND

LABORATORIC ASPECTOF DIFFERENTETIOLOGIES


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ANATOMY OF THE LIVER

The liver consists of two mainlobes, both of which are made upof thousands of lobules.

These lobules are connected tosmall ducts that connect withlarger ducts to ultimately form thehepatic duct.

The hepatic duct transports thebile produced by the liver cells to

the gallbladder and duodenum (thefirst part of the small intestine).


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PHYSIOLOGY OF LIVERSome of the more well-known functions include thefollowing:

Production of bile, which helps carry away waste andbreak down fats in the small intestine during

digestion.Production of certain proteins for blood plasma.

Production of cholesterol and special proteins to helpcarry fats through the body.

Conversion of excess glucose into glycogen forstorage. (This glycogen can later be converted backto glucose for energy.)


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PHYSIOLOGY OF LIVER

Regulation of blood levels of amino acids, which formthe building blocks of proteins.

Processing of hemoglobin for use of its iron content.(The liver stores iron.)

Conversion of poisonous ammonia to urea. (Urea isone of the end products of protein metabolism thatis excreted in the urine.)

Clearing the blood of drugs and other poisonous

substances.Regulating blood clotting.

Resisting infections by producing immune factorsand removing bacteria from the blood stream.


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BILIRUBIN METABOLISM


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Liver biochemistry


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ENZYMES THAT DETECT HEPATOCELLULARNECROSIS AMINOTRANSFERASES

The aminotransferases (formerly transaminases) are the mostfrequently utilized and specific indicators of hepatocellular necrosis.

ALT is primarily localized to the liver but the AST is present in a widevariety of tissues like the heart, skeletal muscle, kidney, brain andliver.

Whereas the AST is present in both the mitochondria and cytosol ofhepatocytes.


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MILD, MODERATE AND SEVERE ELEVATIONS OFAMINOTRANSFERASES1. Severe ( > 20 times, 1000 U/L) :

The AST and ALT levels are increased to some extent in almost all liver diseases.The highest elevations occur in severe viral hepatitis, drug or toxin inducedhepatic necrosis and circulatory shock.

Although enzyme levels may reflect the extent of hepatocellular necrosis theydo not correlate with eventual outcome. In fact declining AST and ALT mayindicate either recovery of poor prognosis in fulminant hepatic failure.

2. Moderate (3-20 times):

The AST and ALT are moderately elevated in acute hepatitis, neonatal hepatitis,chronic hepatitis, autoimmune hepatitis, drug induced hepatitis, alcoholichepatitis and acute biliary tract obstructions.

The ALT is usually more frequently increased as compared to AST except in

chronic liver disease. In uncomplicated acute viral hepatitis, the very high initial levels approach normal

levels within 5 weeks of onset of illness and normal levels are obtained

in 8 weeks in 75% of cases.

For reasons, which are not, understood AST levels appear

disproportionately low in patients with Wilson disease.


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3. Mild (1-3 times) :

These elevations are usually seen in sepsis induced neonatalhepatitis, extrahepatic biliary atresia (EHBA), fatty liver, cirrhosis,

non alcoholic steatohepatitis(NASH), drug toxicity, myositis,duchenne muscular dystrophy and even after vigorous exercise.

One third to one half of healthy individuals with an isolatedelevation of ALT on repeated testing have been found to be normal


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ALKALINE PHOSPHATASE

Alkaline phosphatases are present in nearly all tissues. In liver, alkaline phosphatase is found histochemically in the

microvilli of bile canaliculi and on the sinusoidal surface ofhepatocytes.

Alkaline phosphatase from the liver, bone and kidney are thoughtto be from the same gene but that from intestine and placenta arederived from different genes.

Highest levels of alkaline phosphatase occur in

cholestatic disorders. Elevations occur as a result of both

intrahepatic and extrahepatic obstruction to bile flow and the degree

of elevation does not help to distinguish between the two.


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The mechanism by which alkaline phosphatase

reaches the circulation is uncertain; leakage from the bile

canaliculi into hepatic sinusoids may result from leaky

tight junctions and the other hypothesis is that the

damaged liver fails to excrete alkaline phosphatase made

in bone, intestine and liver.

In acute viral hepatitis, alkaline phosphatase is usuallyeither normal or moderately increased. Hepatitis A may

present a cholestatic picture with marked and prolonged

itching and elevation of alkaline phosphatase.

Tumours may secrete alkaline phosphatase into plasma


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GAMMA GLUTAMYL TRANSPEPTIDASE

g Glutamyl transpeptidase(GGT) is a membrane bound glycoproteinwhich catalyses

the transfer of g glutamyl group to other peptides, amino acids andwater.

Large amounts are found in the kidneys, pancreas, liver, intestineand prostate.

Men have higher values

The normal range is 0-30IU/L 1,5

In acute viral hepatitis the levels of g glutamyl

transpeptidase may reach its peak in the second or third

wk of illness and in some patients they remain elevated

for 6 weeks.


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In liver disease g glutamyl transpeptidase activity

correlates well with alkaline phosphatase levels but rarely

the g glutamyl transpeptidase levels may be normal inintra hepatic cholestasis like in some familial intrahepatic Cholestasis.

Other conditions causing elevated levels of g glutamyl

transpeptidase include uncomplicated diabetes mellitus,

acute pancreatitis and myocardial infarction. Drugs like phenobarbital, phenytoin, paracetamol, tricyclic

antidepressants may increase the levels of g glutamyltranspeptidase.

Non-hepatic causes of increased levels of the enzyme includeanorexia nervosa, Gullian barre syndrome, hyperthyroidism, obesityand dystrophica myotonica.


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SERUM PROTEINS

The liver is the major source of most the serum proteins. Theparenchymal cells are responsible for synthesis of albumin,fibrinogen and other coagulation factors and most of the a and bglobulins.

Albumin : Albumin is quantitatively the most important protein in

plasma synthesized by the liver and is a useful indicator of hepaticfunction. Because the half life of albumin in serum is as long as 20days, the serum albumin level is not a reliable indicator of hepaticprotein synthesis in acute liver disease. Albumin synthesis isaffected not only in liver disease but also by nutritional status,hormonal balance and osmotic pressure. Liver is the only site ofsynthesis of albumin.

The serum levels are typically depressed in patients with cirrhosisand ascites. In patients with or without ascites, the serum albumin

level correlates with prognosis.


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Normal serum values range from 3.5g/dl to 4.5 g/dl. The averageadult has approximately 300 to 500 g of albumin. The serum levelsat any time reflect its rate of synthesis, degradation and volume of

distribution. Corticosteroids and thyroid hormone stimulate

albumin .

The serum albumin levels tend to be normal in diseases like acute

viral hepatitis, drug related hepatotoxicity and obstructive jaundice. Albumin levels below 3g/dl in hepatitis should raise the suspicion of

chronic liver disease like cirrhosis which usually reflects

decreased albumin synthesis.

In ascites there may be normal synthesis but the levels may appearreduced because of increased volume of distribution.

Hypoalbuminemia is not specific for liver disease and

may occur in protein malnutrition, nephrotic syndrome

and chronic protein losing enteropathies.


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SERUM CERULOPLASMIN

Normal plasma levels are 0.2-0.4g/L. It is synthesized in the liver andis an acute phase protein.

The plasma concentration rise in infections, rheumatoid arthiritis,pregnancy, non Wilson liver disease and obstructive jaundice.

This is an important diagnostic marker in Wilson

disease, in which the plasma level is usually low.

Low levels may also be seen in neonates, Menkes disease,

kwashiorkor, marasmus, protein losing enteropathy,

copper deficiency and aceruloplasminemia.


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ICTERUS

DEFINITION Icterus is the accumulation of bilirubin or its conjugates in body

tissues produces, which is characterized by high plasma bilirubinlevels and deposition of yellow bilirubin pigments in skin, sclerae,mucous membranes, and other less visible tissues.

Normal serum values of total bilirubin typically are 0.2-1 mg/dL (3.4-17.1 mol/L.

Mild icterus is seen first at the sclera with bilirubin levels ofbetween 2-2,5mg/dL.

If the icterus is clearly visible,than the estimated level of bilirubinhas maybe reached 7mg/dL.


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PATHOPHYSIOLOGY OF ICTERUS

Pre hepatic

Hepatic

Non hepatic


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ICTERUS PRE HEPATIC

Pre-hepatic

hepatic

post-hepatic

Haemolysis bile duct

haem breakdown Hepatocyte

Unconjugated

Bilirubin conjugation

Liver uptake conjugated

bilirubin


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ICTERUS HEPATICPre-hepatic hepatic post-hepatic

blood bile duct

haem Hepatocyte damage

Unconjugated

bilirubin conjugation

Liver uptake conjugated

bilirubin


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ICTERUS POST HEPATICPre-hepatic hepatic post-hepatic

blood bile duct

haem Hepatocyte

Unconjugated

Bilirubin conjugation

Liver uptakeobstruction

conjugated bilirubin


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CLINICAL MANIFESTATION


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CLINICAL MANIFESTATIONS

Jaundice is a sign of an underlying disease process. Common signsand symptoms seen in individuals with jaundice include:

yellow discoloration of the skin, mucous membranes, and thewhites of the eyes,

light-colored stools,

dark-colored urine, and

Itching of the skin.


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HISTORY POSSIBILE CAUSE

Potential toxins (eg, drugs),environmental chemicals (eg, solvents), orwild mushrooms

toxic hepatitis

Risk factors:TransfusionIntravenous (IV) drug useMultiple sexual partnersExposure to a person who is infected

viral hepatitis

Colicky abdominal pain or fever. gallstone disease

Weight loss malignancy or chronic infection

Recent anesthesia with the use ofhalothane

halothane hepatitis

intense pruritus cholestatic disease resulting from biliaryobstruction or intrahepatic cholestasis

A family history of jaundice inborn errors of bilirubin metabolism

Severe right heart failure or tricuspid

insufficiency with hepatomegaly

hepatic congestion


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Physical

brownish discoloration of the urine

scleral icterus reflects the unconjugated fraction of bilirubinthat binds tissues much more avidly.

Palpation of the abdomen may reveal the following:

A mass (eg, a distended gallbladder, abdominal tumors)

Tenderness over the liver (eg, as in cases of hepatitis or hepatic distention

resulting from congestion or infiltrative disease)

Tenderness over the gallbladder fossa (as occurs in cases of biliary diseaseor infection)

In cases of biliary obstruction or stasis, stool may be acholic

and light gray. Unexplained darkening of the skin, diabetes, or heart failure

suggests hemochromatosis.

Kaiser-Fleisher rings or a low serum ceruloplasmin

concentration suggests Wilson disease.


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LABORATORY INVESTIGATIONSFunction test Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice

Total bilirubin Normal / Increased IncreasedConjugated bilirubin Normal Increased Increased

Unconjugated bilirubin Normal / Increased Increased NormalUrobilinogen Normal / Increased Increased Decreased / Negative

Urine Color Normal Dark (urobilinogen + conjugatedbilirubin) Dark (conjugated bilirubin)

Stool Color Normal PaleAlkaline phosphatase levels

NormalIncreased

Alanine transferase and Aspartate

transferase levels Increased

Conjugated Bilirubin in Urine Not Present Present


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MANAGEMENT

Pre-hepatic jaundice In treating pre-hepatic jaundice, the objective is to prevent the

rapid breakdown of red blood cells that's causing the level ofbilirubin to build up in the blood.

In cases of infections, such as malaria, the use of medication to

treat the underlying infection is usually recommended.

For genetic blood disorders, such as sickle cell anaemiaor thalassemia, blood transfusions may be required to replace thered blood cells.

Gilbert's syndrome doesn't usually require treatment because thejaundice associated with the condition isn't particularly serious anddoesn't pose a serious threat to health.


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Hepatic jaundice

In cases of intra-hepatic jaundice, there's little that can be done torepair any liver damage, although the liver can often repair itself

over time. Therefore, the aim of treatment is to prevent any furtherliver damage occurring.

For liver damage that's caused by infection, such as viral hepatitisor glandular fever, anti-viral medications may be used to helpprevent further damage.

If the damage is due to exposure to harmful substances, such asalcohol or chemicals, avoiding any further exposure to thesubstance is recommended.

In severe cases of liver disease, a liver transplant is another possible

option. However, only a small number of people are suitablecandidates for a transplant and the availability of donated livers islimited


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Post-hepatic jaundice

In most cases of post-hepatic jaundice, surgery is recommended tounblock the bile duct system.

During surgery, it may also be necessary to remove:

the gallbladder

a section of the bile duct system

a section of the pancreas to prevent further blockages occurring


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MANAGEMENT OF VIRAL HEPATITIS

Treatment for acute of HAV infectionTreatment for acute hepatitis caused by HAV is supportive innature, because no antiviral therapy is available. Hospitalization isneeded for patients whose nausea and vomiting places them at riskfor dehydration. Patients with acute liver failure require close

monitoring to ensure they do not develop fulminant hepatic failure. Treatment for chronic HBV infection

At this time, the key goal of antiviral treatment of HBV is the inhibition ofviral replication. This is marked by the loss of HBeAg (in patients withHBeAg-positive chronic hepatitis B) and by the suppression of HBV DNAlevels. Secondary aims are to reduce symptoms, if any, and prevent ordelay the progression of chronic hepatitis to cirrhosis or HCC.

Treatment for acute HCV infection

Acute hepatitis C is detected infrequently. When it is identified, early

therapy with interferon should be considered.


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MANAGEMENT FOR DRUG INDUCED HEPATITIS Monitoring hepatic enzyme levels is appropriate and necessary with a

number of agents, especially with those that lead to overt injury

ALT values that are within the reference range at baseline and rise 2 - to 3-fold should lead to enhanced vigilance in terms of more frequentmonitoring.

ALT values 4-5 times higher than the reference range should lead toprompt discontinuation of the drug.

No specific treatment is indicated for drug-induced hepatic disease.Treatment is largely supportive and based on symptomatology.

The first step is to discontinue the suspected drug.

Specific therapy against drug-induced liver injury is limited to the use of N-acetylcysteine in the early phases of acetaminophen toxicity. L-carnitineis potentially valuable in cases of valproate toxicity.

Cholestyramine may be used for alleviation of pruritus.

Ursodeoxycholic acid may be used.


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CASE


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PATIENT IDENTITY

Name : Mr. RAge : 20 years old

Sex : Male

Marital Status : Single

Religion : Islam

Race : Javanese

Occupation : Student

Address : Pulomadura 2 RT003/011, Aren Jaya,Bekasi Timur

Date of admittance: 24 February 2012


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HISTORY

Chief complaint: skin and eyes turning yellowsince 1 day before admitted

Other complaints: nausea, vomiting, anorexia,

heartburn, tea-colored urine, pale-coloredfeces


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History of Present illness

Patient came to RSUD Kota Bekasi with the chief complaint ofhis skin and eyes turning yellow since yesterday. Four daysbefore that, the patient started to have a fever, high at nightbut low in the morning and evening. His fever is accompaniedwith chills and malaise.

Two days before, he had gone to the PUSKESMAS to gettreatment for his fever. The doctor at the PUSKESMASdiagnosed him with typhoid fever and prescribedchloramphenicol, ranitidine and paracetamol.

A day before he started noticing his skin and eyes becomingyellow and also nausea, vomiting, anorexia, heartburn, hisurine turning tea-colored and feces turning pale. By this time,he has no fever. All this complaints are still present by the

time he is admitted to RSUD Kota Bekasi.


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Past medical history

The patient has no history of having the same illnessbefore. At the age of 4 months old, the patient hadreceive medication for tuberculosis for 6 months. Thepatient also had a history f typhoid fever at the age

of 10.He is allergic to antibiotics sulfa and cefotaxime.

There is no known history of asthma,DM,

hypertension or heart disease


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Family history

There is no history of the same disease inhis family,neither do DM, hypertension orheart disease. The patients mother has a

history of asthma


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Social history

The patient said that two of his friends had thesame illness.

The patient exercises 1 time per week, doesnt

smoke nor drinks alcohol. He never controlswhat he consumed. The patient never went torural areas outside of the city.


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PHYSICAL EXAMINATION

Vital signs:Blood pressure : 110/70 mmHg

Pulse :90x/minute

Temperature : 36,5 CRespiratory rate : 12x/minute


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Head : normocephali, normal hair distribution,hair color black

Eyes : anemic conjungtiva -/-, icteric sclera +/+,Ears : normotia,secrete -/-, blood -/-

Nose : no septal deviation, hipermic -/-, secrete

-/-, blood -/-Mouth : good oral hygiene, no coated tongue

Pharynx : not hyperemic, tonsil T2-T2

Neck : lymph nodes and tyroid not enlarged


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Thorax :

Inspection : symmetrical movement of chest

wall, ictus cordis cannot be seen

Palpation : symmetrical vocal fremitus, ictuscordis at ICS 4

Percussion : sonor on both hemithorax, rightheart border at ICS 5 right midclavicularis line,left heart border at 1cm medial of left

midclavicularis lineAuscultation : vesicular breath sounds, rochi -/-,wheezing -/-, regular S1 and S2 heart sounds,

no murmur, no gallop


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Abdomen :

Inspection : flat, supple

Palpation : tenderness at epigastrium,hepatomegaly of left liver lobe about 2cmbelow Xyphoid process, no splenomegaly

Percussion : tympani at all four abdomenquadrant

Auscultation : peristaltic sound at 3x per

minute


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Extremity :No edema, warm on palpation

Skin color: icteric


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INVESTIGATIONSo Chest x ray: normal


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LABORATORY FINDINGS Complete Blood count :

ESR: 4 Leucocyte 6,9 Haemoglobin : 16,7 Hematocryte : 49,3 Thrombocyte :232 Total protein : 6,74 Albumin : 4,92 (increase) Globulin : 1,82 Ureum: 13 (decrease)

Creatinine : 0,88 Blood glucose :105 Natrium : 139 Kalium : 3,9 Chloride : 104


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Liver function test :

Ast : 769 (increase)

Alt : 1603 (increase)

Alkali phosphate: 171(normal)

Total bilirubin:4,72(increase)

Direct bilirubin: 3,86(increase)Indirect bilirubin : 0,86 (increase)

Widal test:

s.typhi O:1/40s.typhi H: 1/80

C l t i


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Complete urine:

Dark yellow color

Clear

Molecular weight 1025

Albumin +1 Glucose

Ketone

Urobilinogen 1

Bilirubin +1

Trace blood- Leucocyte esterase

Nitrite

Erythrocyte 0-2

Leukocyte 0-5

Cylinder Squamous epithel +

Crystal

Bacteria +1

Others -


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Hepatitis virus serology :hbsAg : nonreactive

anti HAV : reactive


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RESUME Patient Mr R, 20 years old,came to RSUD Kota Bekasi with the chief complaint of

his skin and eyes turning yellow since yesterday. Four days before that, the

patient started to have a fever, high at night but low in the morning and evening.His fever is accompanied with chills and malaise. Two days before, he had gone tothe PUSKESMAS to get treatment for his fever. The doctor at the PUSKESMASdiagnosed him with typhoid fever and prescribed chloramphenicol, ranitidine andparacetamol.A day before he started noticing his skin and eyes becoming yellowand also nausea, vomiting, anorexia, heartburn, his urine turning tea-colored and

feces turning pale. By this time, he has no fever. All this complaints are stillpresent by the time he is admitted to RSUD Kota Bekasi. From the patients socialhistory, two of his friends had the same illness.

From physical examination, it is found that the patient had icteric sclera+/+, icteric skin, tenderness on epigastrium region and hepatomegaly of the left

lobe about 2 cm below the xyphoid process. The complete blood count shows increase in albumin, decrease in ureum.

The liver function test, show an increase in AST(769) , ALT(1603), totalbilirubin(4,72), Direct(3,86) and indirect bilirubin(0,86). Widal test show anegative result. The complete urine test shows dark yellow colored urine,albuminuria, and bilirubinuria. The hepatitis virus serology test show a reactive

antiHAV.


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FINDINGS1. Icterus

S : skin and eyes turning yellow, history of fever,chills,malaise, anorexia,tea-colored urine and pale colored feces.

O : -icteric sclera +/+, icteric skin, tenderness on epigastrium region andhepatomegaly of the left lobe about 2 cm below the xyphoid process.

- The liver function test, show an increase in AST(769) , ALT(1603), totalbilirubin(4,72), Direct(3,86) and indirect bilirubin(0,86). Widal test

show a negative result. The complete urine test shows dark yellowcolored urine, albuminuria, and bilirubinuria. The hepatitis virusserology test show a reactive antiHAV.

A: Icterus et causa acute viral hepatitis A

P: -high intake of calori

-bed rest- trifusion500(fructose,glucose,xylitol): d5%, 2:1 / 8 hours

-immunos (immunomodulator) 1x1 tablet

-Hp pro(liver protector) 3x3 tablet


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2. Dyspepsia

S: nausea, vomiting, heartburnO: tenderness on epigastrium region

A: dyspepsia

P: -vomita syrup 3xIC-prosogan(lansoprazole) 1x1 ampoule


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PROGNOSIS

Ad vitam : dubia ad bonamAd fungsionam: dubia ad bonam

Ad sanationam: dubia ad malam


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CONCLUSIONIcterus can be caused by several types of etiologies

depending on which step of bilirubin metabolism is effected; prehepatic, hepatic and post hepatic.

Which type of icterus can be determined by careful analysis ofclinical and laboratory measurements. The management of icterus

depend on which type the patient has and the underlying cause oficterus.

The prognosis also depends on the underlying cause. Someconditions are easily managed and carry an excellent prognosis,while others may become chronic and require lifelong physician

supervision. Unfortunately, some conditions causing jaundice may befatal despite medical or surgical intervention.


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THANK YOU

Management of Icterus Viewed From the Clinical And

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