PHYSICAL DIAGNOSIS

ALTERATIONS IN GI FUNCTION: PART 2

Maria Krishja T. Dela Torre, MD
01/05/2021
Lecture #3.3

OUTLINE • XBilirubin comes from the catabolism of the RBCs and also when
I. Jaundice you have ineffective RBC production which is usually seen in the
a. Bilirubin Metabolism bone marrow. And also in tissue heme or heme proteins that are
b. Etiology present in the liver.
II. Evaluation of Jaundice • XThese sources will produce the heme and eventually, the heme
a. Measurement of Serum Bilirubin
be converted into biliverdin. Then through biliverdin reductase,
b. Algorithm
this will be further converted to bilirubin.
III. Liver Function Test
a. Evaluation of Liver Function • XAll of these happen in the reticuloendothelial system.
b. Different Liver Function Tests • XThe best example of your RE system is your macrophage.
c. Imaging Test Hindi lang sya part ng innate immune system, it also helps
d. Summary produce the bile.
REFERENCES • XOnce in the circulation, bilirubin binds to your serum albumin. It
• Harrison’s 20 edition
th
is then transprted from your serum to your liver. It is taken up by
• Dr. Dela Torre’s PPT your liver. Through the help of glucoronosyl transferase, it
Legends: undergoes the conversion of your bilirubin from your
unconjugated to your conjugated bilirubin.
REMEMBER Previous Trans Clinical
Lecturer Book
(Exams) Trans Com Correlation • XOnce na naconjugate na sya, it is stored in your gallbladder.
Tapos dun sa gallbladder, it is excreted to the small intestine to
% X & 4 ! ¤ help in the digestion of fats. Eventually, ineexcrete sya sa
kaawan through kidneys or through fecal excretion. May iba din
From the Subject Head / Trans Group / Review of Concepts na nirereuptake ng katawan through enterohepatic circulation.
Kaya may narerecycle padin na part ng bilirubin.

I. JAUNDICE
• Also known as “Icterus”; elevation in serum bilirubin
• Yellow skin pigmentation usually seen in sclerae
® XSclerae is composed of elastin and has high affinity to your
bilirubin
• Scleral icterus becomes clinically evident at a serum bilirubin
level of > 51 umol/ L (> 3mg/ dL)
® XClinically evident meaning makikita mo talaga na naninilaw
na yung mata; when you check the base of the tongue and
palm, nagye- yellow na din sya. Pwede kasing mataas yung
bilirubin pero hindi sya nagmamanifest sa itsura.
• Differential diagnosis: yellow skin discoloration due to evelated
serum carotene levels (Xcarotenemia)
® Without pigmentation of the sclerae.
• & Jaundice is a yellowish discoloration of body tissues
resulting from the deposition of bilirubin.
• & Tissue deposition of bilirubin occurs only in the presence of
serum hyperbilirubinemia and is a sign of either liver disease,
hemolytic disorder or bilirubin metabolism disorder.
• & The degree of serum bilirubin elevation can be estimated
by physical examination.

BILIRUBIN METABOLISM
• & Bilirubin, a tetrapyrrole pigment, is a breakdown product
of heme (ferroprotoporphyrin IX).
Figure 1. Metabolism of Bilirubin
• & About 80–85% of the 4 mg/kg body weight of bilirubin
produced each day is derived from the breakdown of hemoglobin
in senescent red blood cells.

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 ® Increased bilirubin production
§ Massive blood transfusion
§ Resorption of hematoma
® Drugs
§ Rifampin
§ Probenecid
§ Ribavirin
§ Protease inhibitors (Atazanavir, Indinavir)
- XFor viral diseases like HIV
® Inherited conditions
§ Crigler-Najar types I and II
§ Gilbert’s syndrome
• Direct hyperbilirubinemia (Inherited conditions)
® Dublin- Johnson syndrome
® Rotor syndrome
® XUsually mas nakikita sa mga bata. Many of them
nahihirapan magthrive on the first few months of their life.

Hepatocellular Conditions Causing Jaundice

Figure 2. Uptake, Conjugation, and Secretion of Bilirubin
• XFromthe blood, hepatocytes take up the bilirubin. Bilirubin
undergoes conjugation forming the bilirubin diglucoronide or
the conjugated bilirubin. Then it is brought to the gallbladder
then eventually, sinesecrete sya ng gallbladder.
• About 80-90% are excreted in feces
• 10- 20% undergo enterohepatic cycling
• A small fraction (< 3mg/dL) escapes hepatic uptake – urine
ETIOLOGY
• Overproduction of bilirubin
• Impaired (Xhepatic) uptake, conjugation, or excretion of bilirubin
• Regurgitation of unconjugated or conjugated bilirubin from
damaged hepocytes or bile ducts.
® X This usually happens when you have obstruction in your
biliary tract or kung nasisira na yung hepatocytes nyo.
® X This is common in patients with viral hepatitis, drug-
induced hepatitis, chronic liver disease, or multiple liver
masses.
• & The terms direct and indirect bilirubin—that is, conjugated
and unconjugated bilirubin, respectively—are based on the
original van den Bergh reaction.
• & Unconjugated bilirubin is always bound to albumin in the
serum, is not filtered by the kidney, and is not found in the urine.
Conjugated bilirubin is filtered at the glomerulus, and the
majority is reabsorbed by the proximal tubules; a small fraction is
excreted in the urine. Any bilirubin found in the urine is
conjugated bilirubin.
Causes of Isolated Hyperbilirubinemia
• XIsolated hyperbilirubinemia means you only have elevation of
your bilirubin. Either your indirect or unconjugated bilirubin
(parehas lang sila). Or if you have isolated elevation of your direct
or conjugated bilirubin.
• XHindisumasabay yung ibang liver function tests. So kapag
chineck yung ALT, AST, alkaline phosphatase, and GGT, normal
yun. Even yung albumin. Bilirubin lang talaga yung abnormal.
• Indirect Hyperbilirubinemia
® Hemolytic disorders
® Ineffective erythropoiesis
• Viral Hepatitis
® Hepatitis A, B, C, D, and E
® Epstein- Barr virus
® Cytomegalovirus
® Herpes simplex virus
• Alcoholic Hepatitis
• Chronic liver disease and cirrhosis
• Drug toxicity
® Predictable, dose- dependent (e.g., acetaminophen)
® Unpredictable, idiosyncratic (e.g.; isoniazid)
• Environmental toxins
® Vinyl chloride
® Jamaica bush tea- pyrrolizidine alkaloids
® Kava Kava
® Wild mushrooms- Amanita phalloides, A. verna
• Wilson’s disease
® XThe problem here is copper .
• Autoimmune hepatitis
® XUsually these patients, you have to work them out for
possible systemic lupus erythematosus as well as other
autoimmune diseases. Hindi basta basta gagana yung mga
anti-viral sakanila.
• XHepatocellular conditions are bilirubinemia that usually
presents as both na mataas yung direct and indirect. Although
may mas mataas lang na isa kesa sa isa, pero parehas silang
mataas. Also, you can notice na hindi lang yung bilirubin yung
mataas sakanila. Mataas din sakanila yung ibang liver
function test parameters like AST, ALT, and alkaline
phosphatase.
• XWhen we say hepatocellular conditions, usually you have
damage in your hepatocytes. Kapag nasira ang hepatocytes,
aside from your liver not being able to convert your unconjugated
bilirubin to conjugated bilirubin, nag aaccumulate lang yung
unconjugated bilirubin. Eventually, sort nagbabackflow sya sa
bloodstream.
• XYung conjugated bilirubin na nagsstay sa gallbladder,
nagdidifuse back papunta sa liver then papasok din sa
bloodstream as conjugated bilirubin because of the damage sa
tight junctions and sa hepatocytes na part ng heptobiliary tree.
• XSa conjugated bilirubin kasi, aside from bilirubin, may mga
kasama pa syang amino acids and cholesterol salt na part na
talaga ng bile. And usually pag napunta na sa bloodstream ang

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 bile, makati yun. Kaya pag ang mga pasyente may liver disease ® Benign
like cirrhosis or hepatocellular carcinoma, many of them hindi § Choledocholithiasis
lang naninilaw, nangangati din. And that is because of the § Postoperative biliary strictures
cholesterol. § Primary sclerosing cholangitis
• XKaya part of the treatment of these patients na may mixed § Chronic pancreatitis
bilirubinemia, particularly kung ang mataas talaga is direct § AIDS cholangiopathy
bilirubin, is to give anti-lipid agents like Rosuvastatin or § Mirizzi’s syndrome
Atorvastatin aside from also trying to induce a negative feedback § Parasitic disease (ascariasis)
by giving cholic acid.
EVALUATION OF JAUNDICE
Cholestatic Conditions Causing Jaundice
(Intrahepatic and Extrahepatic) Measurement of SERUM bilirubin
• Intrahepatic
® Viral Hepatitis Van den Bergh Test
§ Fibrosing cholestatic hepatitis – Hepa B and C
- XAmong the different types of viral hepatitis, Hepa B
and C yung pwedeng maging chronic. Unlike Hepa A or
E na nagreresolve eventually.
§ Hepatitis A, Epstein- Barr virus infection, cytomegalovirus
infection
® Alcoholic Hepatitis
® Drug toxicity
§ Pure cholestasis- anabolic and contraceptive steroids
§ Cholestatic hepatitis- chlorpromazine, erythromycin
estolate
§ Chronic cholestasis- chlorpromazine and prochlorperazine
® Primary biliary cholangitis
® Primary sclerosing cholangitis
® Vanising bile duct syndrome
§ Chronic rejection of liver transplants
§ Sarcoidosis
§ Drugs
® Congestive hepatopathy and ischemic hepatitis
Figure 3. Van den Bergh Test
® Inherited conditions
• Sulfanilic acid and sodium nitrite
§ Progressive familial intrahepatic cholestasis
• Principle: diazotized sulfanilic acid reacts with bilirubin to form a
§ Benign recurrent intrahepatic cholestasis
purple colored azobilirubin
® Cholestasis of pregnancy
• XMine measure natin yung intensity ng azobilirubin
® Total parenteral nutrition
• NV: 17-26 umol/L (1-1.5 mg/dL)
§ XAlot of patients given this eventually develop jaundice
because pwedeng cholestatic condition sya or pwedeng
Measurement of URINE bilirubin
sepsis.
® Nonhepatobiliary sepsis
Urine dipstick test (Ictotest)
® Benign postoperative cholestasis
® Paraneoplastic syndrome
® Veno-occlusive disease
® Graft-versus-host disease (GVHD)
§ XCommon among post-transplant patients, kapag may
organ or transplant rejection.
® Infiltrative disease
§ Tuberculosis
§ Lymphoma
§ Amyloidosis
® Infections
§ Malaria
§ Leptospirosis
• Extrahepatic
® Malignant
§ Cholangiocarcinoma
§ Pancreatic cancer
§ Gallbladder cancer
§ Ampullary cancer
§ Malignant involvement of the porta hepatis lymph nodes Figure 4. Urine dipstick test

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• (+) presence of conjugated bilirubin – presence of • XHowever if your results are negative, don gagawin additional
hepatobiliary disease virologic testing. If negative again, liver biopsy
• XCommon if you have conjugated hyperbilirubinemia • XUsually, autoimmune hepatitis, isa yan sa mga parang kung
• XTea-colored pee walang ibang mag e explain ng jaundice ng patient mo
• XCholestatic pattern
• XIf you have dilated ducts sa ultrasound, consider extrahepatic
Algorithm cholestasis
• XMRCP – checks your biliary tree, kasama na din ang
gallbladder, yung pancreas
• XIf ducts are not dilated sa ultrasound, baka Intrahepatic
cholestasis
• XAgain you need to work up the patient for possible viral
etiologies

Figure 6. Algorithm Pt. 2 (see appendix)

Figure 5. Algorithm for Patient with Jaundice (See appendix)

• XImportante pa rin sa atin ang history

• XAlways ask for exposures. Hindi lang drug exposures,
syempre risky behaviors. Kasi Hepatitis B and Hepatitis C can
cause jaundice
• XAlso ask for vices, malakas ba uminom alak?
• XAsk for medication history, naka TB medication ba?
• XKung baby, malamang wala pa sya sa sinasabing exposure,
baka inherited disorder
• XAfter that, do your physical examination.
• XSa sclera, tingnan ninyo. Palms, under the tongue
• XSome are having difficulty in checking the skin of jaundice
patients, kasi iba color yellow talaga. Like Chinese or Figure 7. Algorithm Pt. 3
mapuputla lang talaga.
• XSo one way to resolve this, compare the skin of that patient to • XYung sa physical examination, since cirrhosis can be a cause,
you need to check for stigmata of liver disease, like Spider
the skin of their offsprings.
Angiomata
• XPatients that are yellow don’t know that they have yellow skin
• XSpider Angiomata – all over the body
• XAng makakapansin ay ang mga taong nakapaligid sa kanila
• XSpider Angiomata happens when you have elevated estrogen
• XCompare ang complexion nya sa mga anak nya and ask if sa katawan mo dahil hindi na nga sya na re regulate ng liver mo
ganon ba talaga ang kulay nya
• XYour liver is one of the organs responsible for the
• XHepatocellular ibig sabihin sira ang liver cells mo, ALT/AST differentiation and production ng mga lipid/hormones
elevated out of proportion to alkaline phosphatase
• XKaya kung may cirrhosis ka, isa sa mga tumataas sayo ay
• XSerologies ay mga testing nyo for Hepa A etc. estrogen in the form of estrone
• XCeruloplasmin if you want to check for Wilsons disease
• XANA, SMA, SPEP if we are considering autoimmune hepatitis
• XANA ginagamit for SLE

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 Example # 1: Palmar Erythema
Figure 8. Example of Palmar Erythema
• XRedness – Hypothenar and thenar areas, paikot tas may
central pallor
• XPalmar erythema – one of the earliest findings of cirrhosis and
one of the reasons of this is hyperestrogenism
• XSo kapag may patient kayo na mukha may cirrhosis, tingnan
nyo agad yung kamay
Example # 2 – Video – Spider Hemangioma
• XPag pinisil nawawala, pag nirelease namumula ulit
• XPag malapitan, para syang spider
LIVER FUNCTION TESTS
• X The term “Liver Function Test” is a misnomer especially
when you coin it with your ALT, AST, alkaline phosphatase as
well as your GGT kasi nga they do not basically tell you the
function of the liver ang mas sinasabi nya is kung gaano kasira
ang atay mo. So ang totoong liver function test mo lang talaga
in reality is yung Albumin and Coagulation Factors mo, kasi
yung clotting factors ninyo especially your Vitamin K dependent
factors are produced by your Liver
• Lack sensitivity and specificity.
• Liver tests rarely suggests a specific diagnosis; rather, they
suggest a general category of liver disease (hepatocellular or
cholestatic) which then further directs the evaluation.
• To increase the sensitivity and specificity of biochemical tests in
the detection of liver disease, it is best to use them as a battery.
• Tests usually employed in clinical practice (bilirubin,
aminotransferases, alkaline phosphatase, albumin and
prothrombin time tests). When more than one of these tests
provide abnormal findings the probability of liver disease is high.
EVALUATION OF LIVER FUNCTION
• Biochemical Tests (Liver Function Tests)
® Detect the presence of liver disease (diagnosis)
® Distinguish among different types of liver diseases
(differentials)
® Gauge the extent of known liver damage (chronicity)
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® Follow the response of treatment (monitoring)
• Radiologic Tests (UTZ, CT, MRI, etc)
• Pathologic Tests (liver biopsy)
• X Kunwari may patient tayo na may idiosyncratic reaction sa
anti-TB meds particularly sa Isoniazid and Rifampicin, what we
do is we check the AST and the ALT after a week to check if
elevated parin or bumaba na yung levels after mo tanggalin yung
gamot.
DIFFERENT LIVER FUNCTION TESTS
Serum Bilirubin
• Unconjugated (Indirect) VS Conjugated (Direct)
® & Bilirubin- breakdown product of porphyrin ring of heme
containg proteins found in the blood in two fraction
(conjugated and unconjugated
® & The unconjugated (indirect fraction)- insoluble in
water and bound to albumin
® & The conjugated (direct)- is water soluble and can be
excreted by the kidney.
® & NV= 1-1.5 mg/dL with 95% of normal population falling
between 0.2 -0.9 mg/dL
• % Elevation of the unconjugated bilirubin is rarely due to
liver disease and is usually due to hemolytic disorders.
® X Usually sa adult life, ang reason for that is more of hemolytic
disorders.
® X Yung unconjugated bilirubin, it commonly involve yung
Gilbert Syndrome and Crigler Najjar (in pediatric age group)
• % Meanwhile, conjugated hyperbilirubinemia almost
always implies liver or biliary tract disease.
® X In pediatric age group dito papasok yung Dubin or Rotor
Syndrome.
• % Any bilirubin found in the urine is conjugated, hence
bilirubinuria implies the presence of liver disease
® X So if makikita nyo nangingitim yung pagihi ng pasyente
ninyo and jaundice yung patient ninyo means mataas yung
bilirubin niya and if you catch them na ganun nga think of a
liver disease
® X In the laboratory what we usually ask is your total bilirubin,
your direct and indirect bilirubin so you need to indicate that.
Kasi may mga ibang laboratories na hindi nila naiinidicate
which is which, so kelangan nyo iinidicate yan sa mga
requests ninyo kapag nag rerequest kayo for your bilirubin
® X May mga laboratory rin na what they do is since
namemeasure lang nila is yung direct and the total
isusubstract nyo lang yung direct sa total para makuha nyo
yung indirect. Kasi tatandaan ninyo yung total bilirubin is the
sum of your direct and indirect bilirubin
• & Urine dipstick test can theoretically give the same
information as fractionization of serum bilirubin. This test is
almost 100% accurate
• & In patients recovering from jaundice, urine bilirubin clears
prior to the serum bilirubin
Serum Enzymes
• & These enzymes have no known function in the serum and
behave like other serum proteins.
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• & They are distributed in the plasma and in interstitial fluid and
have characteristics half-lives which are measured in days.
• & The elevation of a given enzyme activity in the serum is
thought to primarily reflect its increased rate of entrance into
serum from damaged liver cells
• %Enzymes that reflect damage to hepatocytes
(aminotransferases)
® Aspartate aminotransferase (AST; SGOT) & Alanine
aminotransferase (ALT; SGPT)
!AST=SGOT ALT=SGPT
® %ALT is a more specific indicator of liver injury than AST
® Greatest elevations seen in hepatocellular necrosis and
complete biliary obstruction
§ X Kung makikita mo na out of proportion yung taas nila
(AST and ALT) over your alkaline phosphatase mag iisip
ka talaga na nasisira yung hepatocytes (hepatocellular
necrosis)
§ X
Kung mataas naman si alkaline phosphatase, usually
cholestatic diseases
® No prognostic significance in acute hepatocellular disorders
• & AST is found in multiple organs: the liver, cardiac muscle,
skeletal muscle, kidneys, brain, pancreas, lungs, leukocytes, and
erythrocytes in decreasing order of concentration.
• & ALT is found primarily in the liver and is therefore more
specific indicator of liver injury
• & Aminotransferases are normally present in the serum in low
concentrations and if released into the blood in greater amounts
when there is damage to the liver cell membrane. There is also
poor correlation between degree of liver cell damage and level of
aminotransferases. Thus no prognostic significance in acute
hepatocellular disorders
• & NV of Aminotransferase= 10-40 IU/L
• & 300 IU/L of aminotransferase- nonspecific; found in any
type of disorder
• & >1000 IU/L of aminotransferase= exclusively in disorders
associated with viral hepatitis, ischemic liver injury, or toxin or
drug-induced liver injury
• & in most acute hepatocellular disorders, ALT is higher or
equal to AST
• & AST:ALT ratio is <1 in patients with chronic viral hepatitis
and nonalcoholic liver disease.
• & AST:ALT ratio >2:1 is suggestive and >3:1 is highly
suggestive of alcoholic liver disease
• & Low level of ALT- alcohol-induced deficiency of pyridoxal
phosphate
• & 1000-2000 IU/L of aminotransferase- acute biliary
obstruction caused by gallstone
• Enzymes that reflect cholestasis
® AlkP and 5’-NT are found in or near the bile canalicular
membrane of hepatocytes
® Alkaline phosphatase
§ Sensitive indicator of cholestasis, biliary obstruction, and
liver infiltration
§ Limited specificity due to wide tissue distribution
§ X Hindi lang sya indicator na may problem ka sa biliary
tract mo, usually if you have bone disorders tumataas din
sya
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§ & Normal serum alkaline phosphatase consists of many
distinct isoenzymes found in the liver, bone, placenta, and
less commonly in the small intestine
§ & It is also elevated in children and adolescents
undergoing rapid bone groeth because of bone alkaline
phosphatase and late in normal pregnancies due to influx
of placental alkaline phosphatase
§ & Alkaline phosphatase elevations greater than 4x
normal occur primarily in patients with cholestatic liver
disorders, ifiltrative liver disease (cancer and amyloidosis)
and bone conditions characterized by rapid bone turnover
(Paget’s disease)
§ & In the absence of jaundice or elevated
aminotransferases an elevated alkaline phosphatase of
liver origin often but not always suggests early cholestasis
§ & Other conditions that cause isolated elevations of
alkaline phosphatase including Hodgkin’s disease,
diabetes, hyperthyroidism, CHF, amyloidosis and
inflammatory bowel disease
§ & The level of serum alkaline phosphatase elevation is
not helpful in distinguish between intrahepatic and
extrahepatic cholestasis
® 5’-nucleotidase
§ Greater specificity for liver disorders
® y-glutamyl transpeptidase (GGT)
§ GGT is located in the endoplasmic reticulum and bile duct
epithelial cells
§ less specific than alkaline phosphatase or 5’-NT
Tests that measure biosynthetic function of the liver
• Serum Albumin
® & Synthesized exclusively by hepatocytes
® & Has a long half-life: 18-20 days with 4% degraded per
day
® & Should not be measured for screening patients in whim
there is no suspicion of liver disease
® Not a good indicator of acute or mild hepatic dysfunction
® Hypoalbuminemia is common in chronic liver disease
§ X An acute phase reactant they are usually elevated during
state of inflammation regardless if that is because of
infection or kung meron kang flare sa isang autoimmune
disease or acute critical event like stroke or heart attack
tataas yung mga acute phase reactants mo (CRP,ESR)
ang tawag sa kanila Positive Acute Phase Reactant.
§ X Negative acute phase reactant is kapag may
inflammation ka bumabagsak sila (acute phase reactants)
and the example of that is Albumin. Kaya nga even for
septic patient and those with acute critical illness isa sa
mga tinitingnan is Albumin. And if bagsak si Albumin, may
ingoing inflammation si patient and pwede nagkakaroon ng
problem sa liver.
§ X In acute phase, like acute viral hepatitis or acute or mild
hepatic dysfunction you cannot use your Albumin
§ X
But if in chronic illness like CLD gamit na gamit si
Albumin
• Serum Globulin
® &Group of proteins made up of y-globulins
(immunoglobulins) produced by B lymphocytes and a- and B-
globulins primarily produced by hepatocytes.
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 ® & Y-globulins are increased in chronic liver disease, such
as chronic hepatits and cirrhosis.
® & Increases in the concentration of specific isotypes of y-
globulins are often helpful in the recognition of certain chronic
liver diseases
® Increase in CLD
® Diffuse polyclonal increases in IgG: Autoimmune hepatitis
® Increase IgM: Primary biliary cirrhosis
® Increased IgA: Alcoholic liver Disease
• Ammonia
® & Produced in the body during normal protein metabolism
and by intestinal bacteria primarily those in the colon.
® & The liver plays a role in the detoxification of ammonia by
converting it to urea which is excreted by the kidneys
® & Striated muscle also plays a role in detoxification of
ammonia, where it is combined with glutamic acid to form
glutamine
® & It can be occasionally useful for identifying occult liver
disease in patients with mental status changes
® & Elevated arterial ammonia levels have been shown to
correlate with outcome in fulminant hepatic failure
® Elevated blood levels result from deficiency of hepatic
detoxification pathways and portal-systemic shunting
® Elevation does not correlate well with hepatic function or the
presence or degree of acute encephalopathy
® X Isa sa mga main function ng liver is to detoxify waste and if
meron kang liver disease isa sa maapektuhan is the
detoxification pathways so you are prone to have
hyperammonemia and yung ayaw natin dito is magkaroon ka
ng hepatic encephalopathy dahil di nacliclear ng katawan mo
yung ammonia and pumupunta na sya sa brain mo
• Coagulation Factors
® Made exclusively in hepatocytes except factor 8 made in
vascular endothelial cells
® Their serum half-lives are much shorter than albumin, ranging
from 6hrs for factor 7 to 5 days for fibrinogen
® Measurement of clotting factors is the single best acute
measure of hepatic synthetic function and helpful in both
diagnosis and assessing the prognosis of acute parenchymal
liver disease
® The single best acute measure of hepatic synthetic function in
both diagnosis and assessing prognosis
§ X albumin = chronic measure; coagulation factors= acute
measure
§ X A lot of patients with liver diseases subderanged
coagulation factors and many of them have problematic
bleeding disorder
§ Serum Prothrombin Time
- Collectively measures factors II, V, VII & X
- Elevated in hepatitis, cirrhosis, and disorders with
vitamin K deficiency
§ International normalized ratio (INR)
- To express the degree of anticoagulation on warfarin
therapy
- X Usually ginagamit ang INR sa maga patients na need
ang warfarin. So sila yung mga may valvular heart
diseases like mitral valve, tricuspid valve or aortic valve
- A component of MELD score
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§ % MELD score (Reading assignment)
- “Model for End-Stage Liver Disease” score; a tool
used to estimate survival of patients with end-stage liver
disease and assess operative risk of patients with
cirrhosis. An elevated total serum bilirubin in patients
with drug induced liver disease indicates more severe
injury
- Used as a measure of hepatic decompensation and to
allocate organs for liver transplantation
- The INR along with the total serum bilirubin and
creatinine are components of the MELD score
o INR- indicates whether your liver is making the
proteins necessary to blood clot
o Creatinine- how well kidneys are working
o Bilirubin- how well your liver is clearing the bile
o Serum sodium- how well your body is regulating
fluid balance
IMAGING TESTS
Ultrasound (UTZ / US)
• &First diagnostic test to use in patients whose liver tests
suggests cholestasis
® Rapid, noninvasive, (-) radiation exposure; relatively low cost,
portable equipment
® For detecting biliary duct dilation & gallbladder stones
(>95%) and Ascites
® Useful in directing percutaneous needle biopsies
• & Enables to distinguish between cystic and solid masses
• & With doppler imaging, it can detect patency of portal vein,
hepatic artery and hepatic veins and determine the direction of
blood flow
• & First test ordered in patients suspected of having Budd-
Chiari syndrome
® X There are cases that your ultrasound may be of limited
value. For example if may bukol sa atay ng patient mo you
want to check if that is metastatic or tumubo lang ba talaga
sya sa liver at ang primary cancer mo is sa liver. So the
ultrasound cannot give you the nature ng bukol
CT scan
• For detecting, differentiating, and directing percutaneous needle
biopsy
• Less sensitive than US for detecting gallbladder stones but
more sensitive for choledocholithiasis
® X Dito mo malalaman yung nature ng bukol and usually ang
ineemphasize natin dun is yung triphasic CT scan.
MRI
• Most sensitive detection of hepatic masses/cysts
• Most accurate non invasive means of assessing hepatic and
portal vein patency and vascular invasion by tumors
• MRCP: for visualizing the head of the pancreas and the
pancreatic & biliary ducts
® X The problem with both CT scan and MRI, you need to utilize
contrast dye (substances that you inject to visualize further on
different phases ng blood circulation yung bukol sa atay para
dun malalaman kung during hepatic phase ba, or arterial
phase or venous phase. Kasi dun mo makikita anong klaseng
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 bukol) pwede maapektuhan yung kidney pwede magkaroon
ng contrast-induced nephropathy

Radionuclide Scanning
• Assessment of:
® Biliary excretion (HIDA, PIPIDA, DISIDA scans)
® Parenchymal changes (technetium sulfur colloid liver /
spleen scan)
® Selected inflammatory and neoplastic processes (gallium
scan)

Cholangiography
• Most sensitive means of detecting biliary ductal calculi, biliary
tumors, sclerosing cholangitis, choledochal cysts, fistulas and
bile duct leaks
® X in short , in your hepatobiliary tree apart from your liver and
gallbladder. It is in the form of your MRCP and ERCP

Angiography
• Most accurate means of determining portal pressures &
assessing patency and direction of flow in portal and hepatic
veins
• “Gold Standard” for differentiating hemangiomas from solid
tumors
• Most accurate in studying vascular anatomy and determining
resectability of hepatobiliary and pancreatic tumors
Figure 9. Evaluation of Abnormal Liver Tests (see appendix)

Percutaneous Liver Biopsy Etiology: A Recall

• & Safe procedure that can be easily be done at the bedside • Overproduction of bilirubin
with local anesthesia and UTZ guidance • Impaired uptake, conjugation, or excretion of bilirubin
• Most accurate in sa causing diffuse changes throughout the liver • Regurgitation of unconjugated or conjugated bilirubin from
• Should not be the initial procedure in the diagnosis of cholestasis damaged hepatocytes or bile ducts
® X Ginagamit lang to kapag ginawa mo na lahat ng tests pero
wala ka parin nakukuhang conclusive na sagot Table 1. Hepatocellular Conditions causing Jaundice
• Contraindications: significant ascites and prolonged Hepatocelular conditions causing Jaundice
international normalized ratio (INR)
Viral Hepatitis
® X Kasi pwede mag bleed yung patient and pwede nya - Hepatitis A,B,C,D and E
ikamatay - Epstein-Barr Virus
§ Can be performed via the transjugular approach - Cytomegalovirus
• & Liver biopsy is of proven value in the following situations: - Herpes simplex virus
® Hepatocellular disease of uncertain cause Alcoholic hepatitis
® Prolonged hepatitis with the possibility of autoimmune Chronic liver disease and cirrhosis
hepatitis Drug toxicity
® Unexplained hepatomegaly - Predictable, dose-dependent (e.g., acetaminophen)
- Unpredictable, idiosyncratic (e.g., isoniazid)
® Unexplained splenomegaly
Environmental toxins
® Hepatic lesions uncharacterized by radiologic imaging
- Vinyl chloride
® Fever of unknown origin
- Jamaica bush tea- pyrrolizidine alkaloids
® Staging of malignant lymphoma
- Kava kava
- Wild mushrooms- Amanita phalloides, A, verna
SUMMARY Wilson’s disease
• X In acute, under Hepatitic makikita ninyo na sa Diagnostic Autoimmune hepatitis
Evaluation part nito mostly kinoconsider is yung viral hepatitis
• X On the other hand if you are suspecting cholestatic disease or
process, mataas yung AlkP, gGT, ALT tingnan mo yung mga
diagnostic evaluation
• X And if di mo na talaga alam, ginawa mo na lahat di mo parin
alam yung sagot then you do your liver biopsy
• % Please study the table below

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 • Same signs and symptoms as acute
• Muscle and joint ache
• Weakness
• Signs and symptoms of cirrhosis
• Signs and symptoms of liver cancer
® X Always keep in mind na if ang patient nyo is may
hepatocellular carcinoma and alam nyo na matagal na syang
may hepatitis B or C it is more common na nagkaroon muna
siya ng cirrhosis bago magkacancer

HIGH RISK POPULATION

Figure 10. Evaluation of Chronically Abnormal Liver Tests (see appendix)

Figure 13. High Risk Population

• X Ang alkaline phosphatase hindi lang sa liver meron din sa
ibang tissues like sa bones so you also need to do survey of the • X So usually yung mga patients na nagkaroon ng blood
bone, xray, review the history or do bone scintigraphy transfusion especially those na nagkatransfusion before 1992

TYPES OF HEPATITIS
HAV
• RNA virus (hepatovirus); usually involves children and
young adults
® & Nonenveloped 27-nm, heat-, acid-, and ether-resistant
RNA virus in the Hepatovirus genus of the picornavirus family
® & Incubation period of ~4 weeks, its replication is limited to
the liver, but the virus is present in the liver, bile, stools, and
blood during the late incubation period and acute
preicteric/presymptomatic phase of illness.
® & Diagnosis of hepatitis A is made during acute illness by
demonstrating anti-HAV of the IgM class.
• Has not been demonstrated to evolve into chronic hepatitis (X or
Figure 12. Liver Test patterns in Hepatobiliary Disorders (see appendix) chronic liver disease or cirrhosis)
• Treatment: Supportive (X patient recovers eventually)
• X
Depending on the type of liver disorder makikita mo rin dun
yung degree ng pag akyat iba’t iba mong laboratory tests
• % Please read! Kasi lalabas to sa exam HBV
• & Only Hepatitis infection that is a DNA virus but replicates
HEPATITIS PROFILE like a retrovirus
SIGNS AND SYMPTOMS • Typically acute with complete recovery
® X Happens in immunocompetent age (meaning they have
Acute Infection strong immune system)
• Tiredness or “flu-like symptoms ® X In young adults who are sexually active, the presentation will
just be acute and they recover
• Nausea or stomach ache
• Chronic infection in: (X many of them got it when they were
• Diarrhea
young)
• Skin rash
® 1-3% of healthy adults
• Jaundice
® 5-10% of immunocompromised adults
• Light-colored stools (“clay/cholic”)
§ X in patients with HIV, instead of having just an acute
• Dark yellow urine
infection, it becomes chronic since they are
immunocompromised
Chronic Infection
® 90% of neonates
• Asymptomatic

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 § X thru vertical transmission
® 300M chronic carriers worldwide
§ X Philippines is one of the countries with highest Hepatis B
infection; highly endemic
§ X OFWs need to be checked for Hep B status before
leaving the country at least every 6 months or at least
annually if high their viral load is; as clinicians this is
important to check if we need to give them antivirals or not
- Treatment same for HIV: Lamivudine and Tenofovir
§ X There are only 2 endpoints of a Hep B patient:
- Acute disease with complete resolution: 80-90% of
patients
- Chronic disease: 10-20% (more common in the PH)
o Many of Hepa B patients here in the PH, are passed
on thru vertical transmission
• Natural Course of Chronic HBV Infection
® Immune tolerance
§ X Body becomes tolerant of the presence of the Hep B in
their body
® Immune clearance phase
§ Hepatitis flares complicated by hepatic decompensation
§ Result of human leuokocyte antigen-class I antigen
restricted, cytotoxic T-lypmphocyte (CLT) mediated
Figure 14. High-Risk Populations for Whom HBV Infection Screening is
cytolysis against HBV antigens recommended
§ Seroconversion
® Residual phase Table 2. Markers for Stage of Hepatitis Infections

Marker Incubation Acute Past Chronic Vaccination

Pre-Core Mutant Chronic Hepatitis B infection infection infection
• A naturally occurring variant that enables the virus to escape the HbsAg
immune elimination
+ + - + -
® X Some viruses stay in the body and they are not eliminated HBeAg + + - +/- -
• Mutation: in the pre-core region; does not affect the binding HBV-
pocket of the viral polymerase
+ + - +/- -
DNA
® X Usually these are patients with: AntiHBc
• HbsAg (+) (X surface antigen; protein of HBV you
- + - +/- -
IgM
can find in the surface of the virus) AntiHBc
• HbeAg (-)
- + - + -
Total
• AntiHBe (+) Anti Hbe
• HBVDNA (+) (X this is the genetic material of the
- - +/- +/- -
virus you can find in the body of the patient) AntiHBs - - - - +
• Elevated serum ALT (+/-)
• Pre-core mutant HBV exist worldwide but is particularly common • X These are the ones that you will request for the patient
in Mediterranean region (estimated 40-80%) and in Asia • & After a person is infected with HBV, the first virologic marker
(estimated 40-50%)
detectable in serum within 1–12 weeks, usually between 8 and
12 weeks, is HBsAg.
! Serologic Diagnosis of Hepatitis B • X When you say antigen these are proteins present in the HBV
® So you have surface antigen (outside of the HBV)
® Then you also have core antigen (this is what we call HBcAg);
but in actuality this is hard to measure
§ This is attached to the genetic material or in the DNA
of the HBV
§ This is not measured in real life but what we can
measure is the exctractable soluble portion of core
antigen which is the HBeAg
• The antibody on the otherhand are proteins that the body
produces in defense against the HBV
® Basically the body tries to make an antibody against the
HBsAg, core antigen (AntiHBe and AntiHBcIgM)
• Interpreting results:
® When you have HBsAg (+), HBeAg (+), HBVDNA (+) but no
antibodies detected: incubation period; the Hep B infection is
Figure 15. Commonly Encountered Serologic Patterns of Hepatitis B
infections (See Appendix) just starting

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 ® HBsAg (+), HBeAg (+), HBV-DNA (+), AntiHBcIgM (+) and since they already have a chronic liver disease because of the
AntiHBcTotal (+): acute/active infection because basically you chronic HBV infection
have the antigens but your body is now starting to produce • Diagnosis: HDV-RNA (not readily available)
antibodies and the first antibodies produced is for the core • Treatment: Interferon (15-20% clearance)
antigens (remember core antigens can never be measured) • Prevention: Vaccination vs HBV
® Negative antigens and AntiHBcIgM but AntiHBcTotal (+), ® X You cannot have HDV if you do not have HBV infection
AntiHBe (+/-), AntiHBs (+): past infection, meaning no active ® X HDV cannot exist on its own
infection; more of the antibodies that are made are left
® In the PH the most common result is for the chronic infection Table 3. Coinfection vs. Superinfection
which has HBsAg (+), HBeAg (+/-), HBV-DNA (+/-),
AntiHBcIgM (+/-), AntiHBcTotal (+), AntiHBe (+/-), AntiHBs (- Hepatitis B Hepatitis D
): the body becomes immunotolerant and the body’s response
is suboptimal to the virus Coinfection HBsAg + AntiHDV +
AntiHBcIgM
® Only result is AntiHBs (+) the rest (-): Vaccination basically
using the surface antigen that makes antibodies for it Super- HBsAg + AntiHDV +
infections AntiHBcIgM -
X Hepatitis B Virus has 2 proteins:
• Antigen ! Diagnostic Approach to Acute Hepatitis
® Surface antigen: Antigen that is found outside the HBV
® Core antigen (HBc): on the inside you can find the DNA which Table 5. Hepatitis Markers for Hepatitis Infections
has proteins attached to it as well; this is not being detected
by normal tests
HbsAg AntiHAV AntiHBc AntiHCV Interpretation
IgM IgM
§ Surface antigens can be found in the serum when you
+ - + - Acute Hepatitis B
extract blood but the core antigen cannot be detected
usually it is just inside virus and the virus is inside your + - - - Chronic Hepatits B
hepatocytes (liver cells)
+ + - - Acute Hep A
® When you extract blood from the patient, you will get HBsAg
Superimposed on
(surface antigen) and HBeAg (somehow reflective of the core
+ + + - Acute Hepatitis A and B
antigen)
§ HBsAg: most commonly requested marker for HBV Acute Hepatits A
- + - -
® Complete Hepatitis Profile: You will request all the parameters
in the table above - + + - Acute Hep A and B (HbsAg
below detection threshold)
® When you have increased HBeAg, it means virus is
multiplying (since it is part of the core) - - + - Acute Hep B (HbsAg below
§ If you have (+) HBeAg, it means the patient has high viral detection threshold)
load or it shows that the patient is infective because the - - - + Hepatitis C
virus is replicating in the body
• Antibody • ! Review this table
® HBcIgM: basically tells you if you have acute or active • X In real life it happens that you do not only have 1 Hepatitis
infection infection
• HBVDNA is not a protein: this directly measures the viral load ® X You could have Acute Hep A Superimposed on Chronic Hep
meaning how high the virus is in the blood B: HBsAg (+) and AntiHAVIgM (+)
® X Acute Hepatitis A and B: HBsAg (+), AntiHAVIgM (+), and
HDV AntiHBcIgM (+)
• Superinfection or Co-Infection
® X Acute Hepatitis A: AntiHAVIgM (+)
• Only with HEPATITIS B ® X Acute Hep A and B (HBsAG below detection threshold):
® & Delta hepatitis agent, or HDV, the only member of the AntiHAVIgM (+) and AntiHBcIgM (+)
genus Deltavirus, is a defective RNA virus that co-infects with § In HBV infection we have window period that you can
and requires the helper function of HBV (or other have HBsAg (-) but the body already produces
hepadnaviruses) or its replication and expression antibodies particularly against HBV
® X Co-infection simply says previously the patient has no viral § Most likely you still have acute HBV infection but
hepatitis then he/she is infected with viral hepatitis then when window period only, to confirm repeat Hepatitis profile
you test the hepatitis profile, the patient has HBsAg (+) + ® X Acute Hep B (HBsAg below detection threshold):
AntiHBcIgM (+) meaning patient is positive with HBV infection AntiHBcIgM (+)
then patient also has AntiHDV (+) result
® X Hepatitis C: AntiHCV (+)
§ So this means that while you have HBV infection you also
have HDV infection which eventually resolves
® X Superinection: this happens in patients with chronic HBV HCV
infection, patient has HBsAg (+) + antiHBcIgM (+) because • X Just like HBV, you can also have cirrhosis because of HCV
you don’t have an acute HBV infection but a chronic HBV • & The only member of the genus Hepacivirus in the family
infection then patient also gets infected with HDV shows Flaviviridae.
antiHDV (+); usually it is more difficult to treat these patients • Approximately 100M people infected worldwide
• No effective vaccine yet

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• Usually acquired parenterally, although sporadic cases
sometimes occur
® X Blood transfusion
® X Others thru sec
• Acute vs Chronic Hepatitis

Figure 16. High-Risk Populations for Whom HCV-Infection Screening is

Recommended

Table 6. Tests for Hepatitis Infections

Tests Uses Comments

AntiHCV Initial diagnosis, Can be positive after

ELISA screening test several weeks of exposure
HCV RIBA Confirms ELISA Useful in low-risk
results populations
HCV PCR Confirms HCV May be helpful in
qualitative infection seronegative patients;
confirms virologic
response to therapy
HCV PCR Assesses viral load Less sensitive, more
quantitative reproducible
Genotype Epidemiology and May have a role in
research predicting treatment and
response

HEV
• & Previously labeled epidemic or enterically transmitted non-A,
non-B hepatitis, HEV is an enterically transmitted virus that
causes clinically apparent hepatitis primarily in India, Asia, Africa,
and Central America;
® & The most common cause of acute hepatitis in these areas;
one-third of the global population
• Appears to have been infected
• Spread by contaminated drinking water
® X Feco-oral route
• % High mortality rates for pregnant women during the third
trimester of pregnancy
• Diagnosis: Anti-HEV

HGV
• Common among blood donors
• Does not worsen the course of concurrent HCV
• Does not lead to chronic infection
• Of questionable pathogenicity

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 APPENDIX

Figure 5. Algorithm for Patient with Jaundice

Figure 6. Algorithm Pt. 2

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 Figure 9. Evaluation of Abnormal Liver Tests

Figure 10. Evaluation of Chronically Abnormal Liver Tests

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 Figure 12. Liver Test patterns in Hepatobiliary Disorders (see appendix)

Figure 15. Commonly Encountered Serologic Patterns of Hepatitis B infections (See Appendix)

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