MEDICINE 1: Jaundice and GI Bleeding
Dr. Stephen Wong exposed! The upper sclerae are not sun-exposed
JAUNDICE
(Harrison’s 19th ed., page 279)
Bilirubin Metabolism
• 70-80% of bilirubin comes from heme (from breakdown of
hemoglobin in senescent RBCs)
• 20-30% comes from bone marrow (prematurely destroyed
erythroid cells), myoglobin, cytochromes
• Reticuloendothelial cells in the spleen and liver convert
heme to bilirubin using 2 enzymes
o Heme oxygenase: heme à biliverdin, CO, Fe
o Biliverdin reductase: biliverdin à
unconjugated/indirect bilirubin (B1)
• B1 then non-covalently binds to albumin to become water-
soluble to be able to travel in the blood.
• B1 is then taken up by the liver, conjugated to glucoronic
acid using the enzyme UDPGT into conjugated/direct
bilirubin or B2, and excreted by the biliary system as bile to
the second portion of the duodenum
• B2 cannot be absorbed by the intestine. It is hydrolyzed
back to B1 by bacterial B-glucuronidases
o Some of the resulting B1 is reduced by bacteria to
form urobilinogens
o 80-90% of the urobilinogens are excreted in feces
unchanged or oxidized to orange urobilins
o The remaining 10% of urobilinogens are absorbed,
enter the portal venous blood, and are re-excreted by
the liver
o A small fraction (<3 mg/dL) escapes hepatic uptake,
filters across the renal glomerulus, and is excreted in
urine.
o The kidney cannot filter out B1 (bilirubin-albumin). It
can filter out conjugated bilirubin (B2)
• Urinary bilirubin is usually B2, and its presence is
suggestive of liver disease
Hyperbilirubinemia
• Overproduction OR impaired uptake, conjugation and
excretion of bilirubin, OR regurgitation of unconjugated or
conjugated bilirubin from damaged hepatocytes/bile ducts
• If predominantly B2, d/t obstruction of bile duct
• If predominantly B1, d/t increased RBC destruction
• If both B1 and B2, d/t destruction of liver parenchyma
• Bilirubin has high affinity to fat tissue. Hyperbilirubinemia in
infants poses a risk of kernicterus (lots of fat tissue in the
brain) due to the immaturity of the blood-brain barrier,
allowing entry of bilirubin
Jaundice (icterus)
• Yellow discoloration of skin and sclerae, and mucous
membranes
• Scleral icterus (>= 51 mmol/L or 3 mg/dL serum bilirubin)
o No scleral icterus if lower levels of bilirubin
o Icteric: the ENTIRE sclera must be yellow!!!
o Checking for icteresia: check the UPPER sclerae!!!
o Sometimes the sclerae can turn brownish-yellow (dirty
sclera) because of sun exposure. Usually the lower
MEDIC INE 1: Jaundice and GI Bleeding
sclerae are those affected because they are sun-
Serum bilirubin concentration
• Normal total: <17 mmol/L (1 mg/dL)
• B1 – unconjugated/indirect – up to 70% in blood
• B2 – conjugated/direct – up to 30% in blood
• Based on the van der Bergh reaction, an assay that
determines serum bilirubin level
o Bilirubin is exposed to diazotized sulfanilic acid
o The direct fraction is that which reacts with diazotized
sulfanilic acid in the absence of alcohol. It is an
approximation of the level of B2 in serum.
o The total serum bilirubin is the amount that reacts
after addition of alcohol
o The indirect fraction is the difference between total
and direct, and is an approximation of the level of B1
Delta Bilirubin/Biliprotein
• Part of the direct bilirubin fraction includes B2 that is
COVALENTLY bound to albumin – DELTA fraction, or
biliprotein
• Usually found in patients with prolonged
jaundice/cholestasis and is detected as B2
• Because of its binding to albumin, the half-life of delta
bilirubin is the same as the half life of albumin (18-21 days),
compared to just B1 or B2 (~4 hours)
• The prolonged half-life of this albumin-bound B2 explains 2
previously unexplained phenomena in liver disease:
o Some Px with conjugated hyperbilirubinemia do not
have bilirubinuria in the recovery phase because this
albumin-bound B2 is not filtered by the glomerulus
o The elevated serum bilirubin levels appear to decline
more slowly than in other patients who appear to be
recovering satisfactorily
• Early sign of improvement: no more tea-colored urine
Is yellowing always jaundice?
• Yellowing without jaundice: carotenoderma
o Caused by too much dietary intake of yellow/orange
food
o No clinical significance
o Yellowing on forehead, nasolabial folds, palms, and
soles
o Exposure to phenols or quinacrine (mango, papaya,
carrots)
o The urine will be tea-colored – usually a manifestation
of B2 bilirubinemia, but B1 bilirubinemia can also
cause B2 bilirubinemia as a compensatory action by
the liver (liver will produce more conjugated bilirubin
from the increased B1 levels)
1 IMDJ, FMRE, C MPL // B Med 2020
 APPROACH TO A PATIENT WITH JAUNDICE o Arthralgias, myalgias – viral infection, autoimmune
hepatitis
o Rash – viral hepatitis
• Medications: augmentin, co-amoxiclav, rifampin – can
cause jaundice
• Risk factors for cirrhosis
o Alcohol consumption – cirrhosis, HCC, pancreatitis
o Blood transfusion – HBV, HCV, HIV
o Medications (including herbals)
§ Ask about medications, especially those that
have been there in the past 3 to 6 months
o Drug abuse – HBV, HCV, HIV
o Sexual partner/s – HBC, HCV, HIV
o Travel – malaria, sepsis
o Family History – HBV, inherited disorders

Laboratory Tests
• Liver function tests
o Albumin, PT, bilirubin, platelet count
• Liver enzymes
o ALT, AST
o Alkaline phosphatase (Alk Phos)
§ Increased also in patients with bone disease (due
to osteoblast activity)
§ Increased in pregnant patients
§ Increased in patients who did not fast before test
• Other tests
o GGTP
o 5’-nucleotidase
History Taking
• SINGLE MOST IMPORTANT part of the evaluation Physical Examination
• Onset • Signs of liver disease
• Progression • Signs of malignancy
• Accompanying symptoms o Cachexia, temporal and proximal muscle wasting
o Abdominal pain – malignancy, biliary obstruction • HEENT: eyes
§ Biliary pain: usually at least 15 minutes, slowly o Sclerae – icteric (if total serum bilirubin >= 3 mg/dL),
increasing then plateaus then slowly descending under the tongue, parotid gland (parotid gland swelling
then recurs. Think of biliary obstruction. is a stigmata of hepatitis)
o Fever – infection, malignancy • Dark-skinned patients: check oral mucosa for jaundice
§ Choledocholithiasis • Lymphadenopathy
§ Cholangitis o Virchow’s nodes
o Pruritus – due to cholestasis, biliary obstruction § Jaundice and Virchow’s nodes may be telling of
§ Caused by the bile salts, not the bilirubin gastric CA
§ Bile acids are conjugated with taurine/lysine in o Sister Mary Joseph nodules
the liver, and the sodium or potassium salts of • Heart and Lungs – signs of congestion
these bile acids are the bile salts. • Abdomen
o Stool/urine color – liver disease, biliary obstruction o Tenderness
§ Tea-colored urine USUALLY because of biliary o Mass
obstruction o Organomegaly
§ Blockage of intrahepatic bile ducts, or o Size and consistency of liver
extrahepatic biliary obstruction, can cause o Palpable spleen
acholic (no color, no stercobilin) stools o Ascites
ú Acholic stools tell you that there is § Enlarged globular abdomen
obstruction of bile flow into the intestines; § Inverted umbilicus, venous collaterals in abd. wall
you cannot tell where the obstruction is • Extremities
(intrahepatic? Extrahepatic? Etc) o Edema of limbs
o Weight loss – malignancy
o Pallor – hemolysis, bleeding (ampullary [ampulla of
Vater] CA, varices)
o GI bleeding – ampullary CA, cirrhosis

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 • Signs of portal hypertension
o Ascites
o Splenomegaly – Traube’s space obliteration
o Edema
o Caput medusa – dilated lateral epigastric vessels
• Stigmata of liver cirrhosis
o Spider angiomata
§ Pressing on the area will cause blanching;
releasing the finger will restore the appearance of
the angioma
o Palmar erythema
§ Redness of palms more prominent in the medial
and lateral part of palms
o Gynecomastia (increased estrogen)
o Parotid gland enlargement!!!
§ Reason is unknown, could be hormone-related
o Testicular atrophy (increased estrogen)
o Loss of body hair (increased estrogen)
o Dupuytren’s contracture
Check if bilirubin increase is isolated
• Isolated: only bilirubin is increased!
• If isolated: is it B1 (indirect) or B2?
o Indirect or B1: rifampicin, probenecid; inherited
disorders (Gilbert’s, Criggler-Najar); hemolytic
disorders; ineffective hemopoeisis
§ Type I Criggler-Najar is fatal in newborns if left
untreated (can lead to kernicterus)
o Direct or B2: Dubin-Johnson or Rotor syndrome
CHECK THE ALGORITHM on the previous page!!!
Differentiating patterns of drug-induced liver injury
• R ratio = ALT x ULN / Alk Phos x ULN
o ULN = upper limit of normal
• If R ratio >5, hepatocellular (hepatitis)
o Isoniazid, paracetamol, pyrazinamide
• If R ratio <2, cholestatic
o Rifampicin, OCP
• If mixed pattern
o Co-amoxiclav, erythromycin
Imaging Studies
• UTZ/EUS (Endoscopic UTZ)
o Gold standard for Dx of cholelithiasis
o Looking at the bile ducts and gall bladder
o Posterior acoustic shadowing
o Intrahepatic ducts cannot be seen in UTZ.
o Endoscopic UTZ
§ Endoscope with ultrasound probe inserted into
the UGIT
• ERCP (Endoscopic retrograde cholangiopancreatography)
o Gold standard for Dx of choledocholithiasis
o Therapeutic as well as diagnostic
o Procedure: insert an endoscope and release dye
o The scope can reach up to 2nd part of duodenum
because of the ampulla of Vater
MEDIC INE 1: Jaundice and GI Bleeding
• MRI and MRCP (Magnetic Resonance Cholangio-
pancreatography)
o Very clear if you are looking at the biliary system
o Can be used to visualize the entire ductal system and
surrounding structures
• CT Scan
o Can visualize dilated bile ducts
• PTC (percutaneous transhepatic cholangiography)
o Insert needle through a skin to the common bile duct
and inject a dye to see the entire course of the bile
• PTBD (percutaneous transhepatic biliary drainage)
o Used if ERCP is unsuccessful
o Bile duct is drained through your skin
• PRUDENT use of ancillary tests IS IMPORTANT! Wag
gawa lang nang gawa ng tests!
GASTROINTESTINAL BLEEDING
(Harrison’s 19th ed., page 276)
Overt GI Bleeding
• Visible signs of blood loss
• Either the patient has hematemesis, melena, or
hematochezia
• Hematemesis: vomiting of blood or coffee-ground material
o ALWAYS indicates bleeding from the upper GI tract
o Bleeding from lower GI portions will never go back up,
unless there is reverse peristalsis
o Coffee-ground emesis
§ Vomiting of dark brown granular material
§ Results from bleeding that has stopped/slowed
ú Stomach acids convert it into a brown
material
ú Hemoglobin to brown material by HCl
o Blood emesis
§ Arterial or variceal bleeding
• Melena: black tarry stools
o Can be from the upper GI tract up to the cecum
(sometimes)
o If the blood has been in the GI tract for a long time (at
least 14 hrs), it can become black
o Black, tarry (dark and paste-like), foul smelling stool,
results from degradation of blood to hematin by
intestinal bacteria
o Usually indicates upper GI bleeding but may be from
distal small intestine or right side of colon (cecum)
o >= 100-200 mL blood in the upper GIT is required
§ But how can you measure this, beh
o Indicates blood has been in the GIT for >=14 hours
o Diff Dx: iron consumption (but iron causes constipation
and the stool is solid, not pasty or tarry), bismuth,
various foods
• Hematochezia: blood in the stool (red)
o Usually from the lower GI tract, but can be from the
upper GI tract
o Massive bleeding can lead to hematochezia, because
aside from the rapid bleeding, the blood can activate
GI peristalsis to expel the blood from the lumen
o Passage of red or maroon-colored stools (if latter,
small intestine) through the rectum
3 IMDJ, FMRE, C MPL // B Med 2020
 o Usually indicates lower GI bleeding, but can also
indicate vigorous acute upper GI bleeding (with
hemodynamic instability or rapidly dropping Hgb)
o Ask patient is the bleeding is mixed with the stool or
not!!!
§ If the blood just coats the outside of the stool, this
means that the bleeding has happened in the
later areas of the colon, where most of the water
has been absorbed from the stool and the stool is
solid; the blood will most likely not mix with the
stool and will only cover the stool!
§ If the blood is mixed with the stool, the bleeding
is most likely in the transverse colon or on the
right side of the colon (most of the water has not
yet been absorbed, so blood can still mix with the
“wet” stool)
o Ask if there is mucus
§ Mucus is a sign of irritation!! Can be a sign of
colitis etc
o Ask if there is diarrhea
§ Gives you another set of differentials
• Manifestations depend on the location and rate of bleeding
Obscure GI Bleeding
• GI bleeding of uncertain cause after a non-diagnostic
upper GI endoscopy, colonoscopy, and small bowel
radiography or enteroscopy – you have already done the
tests to detect bleeding but you still do not know where the
bleeding is coming from
• May or may not be visible bleeding
• Obscure overt bleeding
o Visible GI bleeding with uncertain cause
o You can differentiate if hematemesis, melena,
hematochezia
• Obscure occult GI bleeding
o Patients with:
§ No overt sign of GI bleed
§ (+) fecal occult blood test (FOBT)
§ (+) unexplained iron deficiency anemia – with
high reticulocyte count
o Symptoms
§ Depend on rapidity and amount of blood loss
§ Pallor, lightheadedness, dizziness/confusion,
syncope, easy fatigability, angina, dyspnea
Ligament of Treitz
• Band of smooth muscle found at the junction of duodenum
and jejunum to the left crus of the diaphragm
• Functions as a suspensory ligament
• Separates upper and lower GI
MEDIC INE 1: Jaundice and GI Bleeding
UPPER GI TRACT BLEEDING
• Above the ligament of Treitz
• BUN is usually elevated because of hypovolemia
o Blood is acted upon by bacteria, and the proteins in
the blood will be absorbed, increasing BUN
• Presents as
o Overt GI bleeding
§ Hematemesis
§ Melena
§ Hematochezia – if massive
o Obscure GI bleeding
• Caused by
o Peptic ulcer disease – most common
§ Epigastric pain, night distress MAY BE present
(not all!!)
§ Complications: bleeding, perforation, penetration,
gastric outlet obstruction
§ NSAID-induced peptic ulcer disease will present
with asymptomatic disease (because pain is not
felt)
§ Forrest Criteria and Risk of Rebleeding
ú Tells us the risk of rebleeding
ú Do not memorize this! Pang-resident ito
ú Decreasing score, increased risk of
rebleeding
o Gastritis/duodenitis
§ Usually causes very mild bleeding only
o Erosive esophagitis
§ Usually causes very mild bleeding only
o Portal hypertension varices, portal hypertensive
gastropathy
§ Present when you have liver cirrhosis
§ Tx: rubber band ligation (gold standard) of
esophageal varices
§ Histoacryl injection of gastric varices
o Malignancy
§ Can reach a certain size to cause symptoms
§ Esophageal
ú Symptoms: progressive dysphagia (most
common symptom if in esophagus),
bleeding/anemia, weight loss
§ Gastric
ú Manifestations
• Epigastric pain/mass,
hematemesis/melena/anemia,
vomiting, early satiety, weight loss
ú Use esophagogastroduodenoscopy
§ Duodenal
ú If upper GI bleeding and you insert an NGT
and there is no bleeding or coffee-ground
material coming out, the bleeding is most
probably in the duodenum (because NGT is
inserted in the stomach) – but this is not
always the case, because the blood from the
duodenum can go up into the stomach
o Mallory-Weiss tear
§ Preceded by vomiting/retching/coughing
§ Tear is usually in the gastric side, there is
bleeding from the gastric side of the GE junction
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 § Retching causes mechanical trauma, and part of o Ischemic colitis
the stomach (the cardia) goes up into the § Lack of blood flow into superficial cells of colon
esophagus very similar to intussusception. There § Usually happens in older patients
is resulting mechanical trauma causing a tear § Risk factors: hypercoagulable states (usually Px
§ Bleeding stops in 80-90% of patients, recurs in on OCPs, malignancies)
0% to 7%. o AV malformations
§ Tx: endoscopic sclerotherapy, hemoclip, § Vascular ectasias of small intestines or right side
embolization, surgery of colon
o Vascular lesions/ectasias § Usually happens in elderly patients and patients
§ Angiodysplasias on dialysis
ú Dilated blood vessels o Malignancy
ú No pain § Colonic neoplasms
§ Dieulafoy lesion § Apple-core deformity on barium enema
ú “Jew-lah-fwah” lesions § Usually do not bleed very briskly, usually no
ú A large caliber arteriole that runs hematochezia
immediately beneath the GI mucosa and o Inflammatory bowel disease
bleeds through a pinpoint mucosal erosion § Crohn’s disease
ú Most often, endoscopy cannot find the ú There are ulcers but they are shallower
source of bleeding; it will sometimes stop § Ulcerative colitis
bleeding spontaneously ú More likely to present with bleeding
o Infectious colitis
LOWER GI TRACT BLEEDING § Amoebic, salmonellosis, Campylobacter sp.
• Below the ligament of Treitz § Usually bleeding is not brisk
• Presents as § Sometimes with pain
o Overt GI bleeding o Drug-induced colitis
§ Melena § NSAIDs – most common drug cause
§ Hematochezia ú NSAIDs can affect the ENTIRE GI tract!
o Obscure GI bleeding § Gold
• Caused by § Penicillamine
o Hemorrhoids § Pain if the ulceration is big
§ Most common cause of lower GI bleeding
regardless of age
§ Presents with bleeding and/or protrusion EVALUATION OF PX WITH GI BLEEDING
§ Only painful when thrombosed
ú Otherwise, no pain on defecation History
§ External hemorrhoids are painful because it is • Quantity, frequency of bleeding
covered by the anoderm (with pain receptors) • Melena
§ Internal hemorrhoids are usually asymptomatic o Ask for consistency
§ Bright red blood in the toilet or upon wiping their o Give patients examples of what melena looks like
ass after taking a shit • Hematemesis
§ Bleeding may cause anemia o Blood with initial vomiting or after an initial non-bloody
o Anal fissures emesis? (Mallory-Weiss)
§ Longitudinal cut into the anoderm (very painful!!) o Is patient alcoholic? (Mallory-Weiss)
ú PAIN ON DEFECATION!! • Hematochezia
§ Starts at the anal verge can extend into dentate o Mixed with stools or not?
line o Pure blood?
§ Seen in all ages, most prominent in 3rd to 5th o Mixed with mucus, pus, or coated stool?
decades o Diarrhea – history of travel?
§ Caused by trauma • Ask patient if the blood can fill up a glass. If the blood can
o Diverticulosis fill up half a glass, it can be ~100 mL
§ Second most common cause of hematochezia
§ Not a true diverticulum because it is not covered Severe GI Bleeding
by muscularis propria, mucosa and submucosa • Documented GI bleeding accompanied by:
only, makes it more likely to bleed o Shock or orthostatic hypotension
§ Commonly affects the sigmoid o Decrease in hematocrit by >= 6% or a decrease in
§ Not all patients will bleed hemoglobin of >=2 g/dL
§ Usually self-limited o Transfusion of >=2 units packed RBC
§ *** Diverticulitis: if with inflammation; this is when
patients bleed! And have pain!

MEDIC INE 1: Jaundice and GI Bleeding 5 IMDJ, FMRE, C MPL // B Med 2020
Accompanying symptoms • Lymphadenopathy
• Abdominal pain o Sister Mary Joseph nodes
• Weight loss – can point towards malignancy § Stomach malignancy
• Easy bleeding/bruising o Virchow’s nodes
• Symptoms of anemia: diaphoresis, syncope, etc § Malignancy
• Urine output • Stigmata of liver cirrhosis
o Prerenal azotemia o See Jaundice topic
• Stigmata of portal HPN
Past Medical History o See Jaundice topic
• Previous GI bleeding • RECTAL EXAM IS A MUST!!!
• Known IBD o Stool color
• Bleeding diathesis o Masses
• History of liver disease o Fissures
o Cirrhosis
o Significant alcohol intake Red Flags of Hypovolemia/Hemorrhagic Shock
• Confusion/syncope
Medications • Pallor
• NSAIDs • Diaphoresis
• Aspirin • Hypostension
• Steroids • Tachycardia
o Alone do not cause ulcers
o Increases risk of NSAID-induced ulcers Laboratory Tests
• Heparin, warfarin • CBC
• Clopidogrel • Blood typing/crossmatching
• FOBT (if overt bleeding is not present) – to diagnose
Physical Examination obscure bleeding
• General survey • Bleeding parameters
o Is patient ambulatory? • Platelet count
o Wheelchair-borne? • Liver Enzyme tests
o Stretcher-borne?
o Alert/confused? Diagnostic Tests
o Pallor/diaphoresis? • Endoscopy – gold standard
• Vital Signs o Esophagogastroduodenoscopy
o Hypotensive? o Colonoscopy
o Tachycardic? o Flexible sigmoidoscopy
o Tachypneic? – because of decreased Hgb o Enteroscopy
o Orthostatic Hypotension o Capsule endoscopy
§ Only checked if the patient does not have resting § Let patient swallow a capsule with a small
hypotension/if the BP is normal camera
§ Get BP first supine, then ask patient to sit up, § Do not give in patients with obstruction
wait 3 mins before taking BP again. If there is o Radionuclide scan/red cell tagging
decrease in SBP >= 20 or DBP >= 10 mmHg, § Radiolabeled RBCs reinjected into the patient’s
orthostatic hypotension blood
§ Unwise to do this in severe bleeding (if Px is § For overt obscure GI bleeding
already hypotensive) § Detects bleeding of 0.04 mL/min!!!
§ Lacks sensitivity/specificity as measure of § Cannot identify exactly where the bleeding is
intravascular volume – in cases of autonomic coming from; can only identify the quadrant
insufficiency (DM, Parkinsons), elderly, o Angiography
food/medications § Angiogram: injecting a dye and see if the dye will
o Orthostatic tachycardia extravasate into the GI lumen
§ Increase in HR >15-20 bpm § Can sometimes detect angiodysplasia
§ Means acute blood loss of >= 2 units § Diagnoses/treat severe bleeding especially when
• Look for stigmata of bleeding disorders the cause cannot be determined by endoscopy
o Petechiae § Needs copious bleeding in order to detect
o Ecchymosis bleeding! As compared to red cell tagging (can
• Tenderness, organomegaly, mass detect 0.04 mL/min)

MEDIC INE 1: Jaundice and GI Bleeding 6 IMDJ, FMRE, C MPL // B Med 2020