Liver, Pancreas & Gall Bladder Dr.
Payawal
LIVER
-exocrine- secretes Bile
-endocrine- secretes plasma proteins (albumin)
Exocrine vs Endocrine
Exocrine glands are glands that secrete their products
through the ducts, and discharge it into the external
environment, to organs or the outside the body. Exocrine
glands differ from endocrine glands, because they have ducts
that deliver the products in the superficial part of the body,
such as the skin, or in the inner part where they are
necessary, such as the pancreatic juice that is carried into the
intestine to aid digestion. The glands that are found in the
body are mostly exocrine glands. Examples of exocrine glands
are sweat, saliva and mammary glands, as well as oil and
enzymes. There are glands which function as both endocrine
and exocrine glands
-largest organ in the body
-very silent in liver disease
-degrades worn-out proteins and red cells
-prepares hydrophobic materials for excretion
Hydrophobic=against water
Hydrophilic=attracts water
-secretes bile = exocrine
-plays a major protective role in preparing lipid soluble
synebiotics/materials for excretion such as...
st
-first organ responsible in excreting alcohol(1 pass effect)
-inter-conversion of fats, sugars and amino acids
-synthesis of heme and cholesterol
* heme responsible for bilirubin metabolism
- pathway of colored products
- jaundice
Dual Blood Supply of the Liver
-highly significant in clinical practice
-so due to this, most of the metastasis is seen in the liver
Eg. Prostate / breast /colon CA
-lodges to the liver
-20% = Hepatic artery ( carries oxygenated blood )
-80% = Portal vein
- main vein ONLY VEIN IN THE BODY THAT
SUPPLIES( the rest drains )
- drains the stomach, intestines, except Rectum
- supplies proteins
* Hepatic Vein- drainage(blood leaves liver)
-exocrine function : from the liver to the intestine:BILE
via the bile ducts ( right, left , common )
-no lymph is formed in the parenchyma of the liver (there are
some in the portal tree, in cases of malignancy)
4 vesicles:
Portal Vein + Hepatic Artery+Bile duct+Lymphatics
-all enters the PORTA HEPATIS
- very significant to patients with
malignancy, if mass is formed here = End Stage kagad
- obstruction of the four vesicles
Once inside the liver, the vessels run a matrix of connective
tissue and assemble the so called Portal Tract, each branch
contains the four vesicles.
TRIAD
-Hepatic Vein branches into a tree, which it
Interdigitates(connects)
Intrahepatic duct- supplied by the hepatic artery and the
direction is opposite to that of the bile(which goes to the
intestine down)..
Since there is high molecular weight that passes the
bile duct, some of the contents traverse to the hepatic
artery so then it goes back
Parenchyma
- no lymphatics
Sinusoids
-liver capillaries- aka
-have filtration role, allows protein to pass the space of disce
-hepatic sinusoids- hepatocytes that filters
How is Bile formed
-bile consists of bile acids and bile salts
-responsible for digesting, lysing thefat
-entero hepatic re-circulation
-conjugates formed:
*Glocoronide
* Glutathione- only 0.5% for whithening
-secreted normally to the body, so no need to inject
-bile acids and salts are excreted and passes the small spaces
in the hepatocytes- bile canaliculi
Hepatocytes
-epithelial cells
-with central nuclei
-can be Binucleate or polypiod
-have an organize microtubule and a golgi apparatus
-has Mitochondria(oxygen bearing)
Liver- degrades antibiotics and vitamins or iron which heats
the Cytochrome p450 which is concentrated in the
centrilobular zone, cells rich in peroxizomes
-thats why acetaminophen is the number 1 drug destroying
the liver since it attacks the Cp450..
Blood from the portal tract, as it goes away, oxygenation is
degraded, so synthesis is done in the peri-portal area..
Kupffer Cells
-sinusoids, cells , FIXED MACROPHAGE, removes alcohol etc..
ITO cells
-fat/lipid storring cells
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Liver, Pancreas & Gall Bladder Dr. Payawal

-stellate cells
-store retinoic acid(vit a)= tx of pimples LABORATORY TEST
-normally is quiet, quiescence
-always activated in liver disease I.Transaminases
st
-if activated, in a liver disease, releases collagen, 1 step
towards cirrhosis, so if SGPT is elevated, stellate cells are 1.SGPT / ALT
activated. -search enzyme / tracing enzyme
-modified fibroblast, revert to type strategy, or quiescence -found at zone 1 ( peri-portal zone ) :so oxygenated
-half life is 48 hrs.
*breakdown of hepatocytes,stimulated by the TGF- -released by the hepatocytes into the liver as it is injured
alpha(autocrine factor made in the hepato cells) ang -found int the cyrosol of the liver
HGF(hepatocyte growth factor) by fat storage cells and tumor -only seen in the liver
cells -slight elevation is needed attention, something happening to
the liver
st
*Hepatocytes-able to regenerate back -1 enzyme released in liver damage
-inflammation of the liver
*Transformation of the fat storing cells into fibrocytes is -liver is normal even elevated
released by the Kupher cells
2.SGOT / AST
*repeated damage = fibrosis -found both in the cytosol and mitochondria
-mitochondria is the oxygen bearing in the cell
if affected means Necrosis
-abundant in other organs like Heart, skelatal muscles and
blood
eq. Hazing : release sgot from muscles
st
Summary of the 1 lec: if high, look for PASA
Major functions of the Liver -if SGOT is higer than the SGPT = Necrosis than inflammation
excretion of bilirubin === liver disease of the patient
synthesis of plasma proteins : Albumin is in worst setting
synthesis of Vit K dependent clotting factors like
2,7,9,10 2 questions: / 2 conditions Sgot>Sgpt :
1.Is this a bad liver
Minor functions: 2.Is the patient dringking alcohol
bile production
porphyrin metabolism -increased in heart attacts, jogs a lot, exercise, muscle
-colored pigment (yellowing ) building
stores vitamins ang sugars
glucose metabolism: gluco............ -will only tell the kind of activity your liver has

HY's Law:
in taking drugs and SGPT increases, correlate it with your
HISTORY AND P.E. Total Bilirubiin, and log it together:
1.if SGOT is high but there is no jaundice, no elavation of
I.High Risk Behavior Bilirubin = Temple's Corollary
-risk for IV drugs 2.SGPT is elevated and Increased Bilirubin = Impending Liver
-multiple sexual partners failure ( problematic )
-tatoo : needles and solutions are not changed
: Hepa C (not B ) II.BILIRUBIN
-vertical transmission -degradation of heme and globin
-non sterile body piercing -heme is excreted predominantly via the bile
-alocohol abuse -to liver, to intestines, to urine

II.Systemic Illness -whitish sclerae becomes yellow = jaundice

-diabetes
-10 % excess body weight ??? RES degrades heme, (liver BM spleen)
-high cholesterol
-high serum ferritin -Gilbert's Disease : problem with Glucoronyl-transferase
-metastatic liver diseases
-chronic inflamatory bowel diseases -heme oxygenase system acts on the macrophage

III.Medications Causes of an Isolated Unconjugated Hyperbili:

*hmg-coa reductase inhibitors 1.Gilbert's Dis.
*anti-tb drugs 2.Hemolysis
*isotretinoic acid 3.Large Blood Transfussion
4.Large Hematoma

Causes of Conjugated Bilirubin:

1.Hematomas
2.Blood discrasia
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Liver, Pancreas & Gall Bladder Dr. Payawal

3.absence of glucoronyl trnsferase Conjugated and unconjugated types

o Conjugated B2, direct, obstructive
Medications causing elevation of Bili and ALP Pre-hepatic, hepatic and post
hepatic types
o Unconjugated B1, indirect
CHOLESTASIS Need glucoronyl transferase to
-formation of the bile is impared either due to convert to B2
infection,drugs, or metabolic disorder Obstructive and Non- obstructive (clinical)
*Jaundice is not necessarily a liver disease but is the
bile secretion: alteration of unconjugated bilirubin
3 ways of barrier(traversing the nutriotion):
1.Calcium waves HEPATITIS
2.Regurgitation into the plasma
3.Peri-canular actin and myosin Hepatitis: inflammation of liver
this will form the bile Viral, Alcohol, Immune, Drugs and toxins
Biliary Obstruction Gall stones
-from the transport from the plasma to the sinusoidal space Acute, Chronic and Fulminant types
of the hepatocyte and the canalicullar surface of the Viral Hepatitis
hepatocyte o Specific Hepatitis A, B, C, D, E and other
-Na-K ATPase pump o Systemic CMV, EBV, other
-Na-Hco3 ATPase pump
*traverses the hepatocytes into the bile ducts Pattern of viral hepatitis
*Na goes in and goes out, tight junction Carrier state/ Asymptomatic phase
*BILE is Formed Acute hepatitis
Chronic hepatitis
in liver disese: o Chronic Persistent Hepatitis (CPH)
-inflammation of the bile ducts, fluids inside goes back, bile o Chronic Acute Hepatitis (CAH)
plugs are present, accumulation of bile inside coz of the loss Fulminant hepatitis
of the junction, there is disorganized actin-myosin...= Cirrhosis
Cholestasis
*small ducts in the hepatocytes are inflammed

ALP
-immunolocalized microvilli in the bile
-the only test to asssess inflammation of the Bile
-non-hepatic in origin, incresed in cholestasis, causing
obstruction of the billiary tract

LIVER
1.5 kg, wedge shape
4 lobes right, left, caudate, quadrate
Double blood supply
o Hepatic artery 20% of blood flow is 02
rich Diagrammatic representations of the morphologic features of
o Portal vein 80%, nutrient rich acute and chronic hepatitis. Bridging necrosis may also occur
Hepatic arteries in acute hepatitis.
Portal- Venous blood
Acini/ portal triad ACUTE HEPATITIS
Lobules- Central vein Swelling and Apoptosis
Piecemeal or bridging, panacinar necrosis
Inflammation- Lymphocytes, Macrophages
Ground glass hepatocytes HBV
Mild fatty change HCV
Portal inflammation and Cholestasis

FULMINANT HEPATITIS
*Zone 1 is adjacent to the portal triad. Hepatic failure within 2-3 weeks
Reactivation of chronic or acute hepatitis
Liver function Massive necrosis, shrinkage, wrinkled
Metabolism- Carbohydrate, Fats and Protein Collapsed reticulin network
Secretory- Bile, Bile acids, salts and pigments Only portal tracts visible
Excretory- bilirubin, drugs, toxins Little or massive inflammation time
Synthesis- albumin, coagulation factors More than a week regenerative activity
Detoxification- toxins, ammonia, etc
CHRONIC HEPATITIS
JAUNDICE Persistent and active types (CPH/CAH)
Yellowish discoloration of skin and sclera due to Lymphoid aggregates
excess serum bilirubin > 40umol/l(3mg/dl) Periportal fibrosis
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Liver, Pancreas & Gall Bladder Dr. Payawal

Necrosis with fibrosis bridging fibrosis o Conjugated/ direct bilirubin, high colored
Cirrhosis regenerating nodules urine

Acute Viral Hepatitis neutrophils along portal triad CIRRHOSIS

Chronic Persistent hepatitis inflammation to cells; with
fibrosis to Hepatic vein DEFINITION
Cirrhosis fibrosis + nodule formation 1. Diffuse disorder of liver characterized by
2. Complete loss of normal architecture
VIRAL HEPATITIS: microbiology 3. Replaced by extensive fibrosis with
Virus Hep-A Hep-B Hep-C 4. Regenerating parenchymal nodules
Agent ssRNA dsDNA ssRNA
Transmis Feco-oral Parenteral Parenteral INTRODUCTION
Carrier state None 0.1-1.0% 0.2-1.0% Cirrhosis is common end result of many chronic liver
Chronic None 5-10% >50% disorders
Hepatitis Diffuse scarring of liver- follows hepatocellular
necrosis of hepatitis
ALCOHOLIC LIVER INJURY Inflammation- healing with fibrosis- regeneration of
remaining hepatocytes form regenerating nodules
Ethyl alcohol common cause of acute/chronic liver
Loss of normal architecture and function
disease
Alcoholic liver disease- patterns ETIOLOGY of CIRRHOSIS
o Fatty change Alcoholic liver disease 60-70%
o Acute hepatitis (Mallory Hyalin) Viral hepatitis 10%
o Chronic hepatitis with portal fibrosis Biliary disease 5-10%
o Cirrhosis, chronic liver failure Primary hemochromatosis 5%
All reversible except Cirrhosis stage Cryptogenic cirrhosis 10-15%
Wilsons, a1AT deficiency rare
*women have higher risk for alcoholic liver injury; dose
dependent and frequency Pathogenesis
Hepatocyte injury leading to necrosis
PATHOGENESIS o Alcohol, virus, drugs, toxins, genetic etc
Acetaldehydemetabolitehepatotoxic Chronic inflammation- (hepatitis)
Diversion of metabolism fat storage Bridging fibrosis
Oxidation of ethanol NAD to NADH. NAD is required Regeneration of remaining hepatocytes. Proliferate
for the oxidation of fat as round nodules
Increased peripheral release of fatty acids Loss of vascular arrangement results in regenerating
Inflammation: portal bridging fibrosis hepatocyte ineffective
Stimulated collagen synthesis fibrosis
Micronodular cirrhosis

Bilirubin Metabolism DISEASE OF THE BILIARY TRACT

Blood
o Conjugated and conjugated
Anatomy review
Urine Urobilinogen
Biliary tract
Stool Stercobilin
Intra-hepatic bile duct
Extra-hepatic bile duct
Gallbladder
Oddi sphincter
*right and left hepatic duct- a part of it is in the intra-hepatic
duct and some are in the extra-hepatic duct
From bile canaliculi to the ampulla of Vater
Intra-hepatic bile duct
Bile canaliculi
Segmental bile duct
Lobal bile duct
Hepatic part of left and right hepatic duct

Extra-hepatic bile duct

Left and right hepatic duct
The common hepatic duct
Diameter: 0.4-0.6 cm ;length:2-4 cm
COMMON CAUSE OF JAUNDICE
Common bile duct
Pre- Hepatic (Acholuric)- hemolytic
o Unconjugated/Indirect Bil, pale urine Diameter: 0.6-0.8cm ; length: 7-9cm
Hepatic- Viral, alcohol, toxins, drugs Gallbladder: the body, the fundus, the neck
o Liver damage- unconjugated Cyst duct
o Swelling, canalicular obstruction-
Conjugated
Post hepatic (Obstructive)- Stone, tumor

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o Oral cholecystography:
Biliary contrast medium
A fatty meal- to contract the bile
duct
o Intravenous cholangiography
o Percutaneous transhepatic cholangiography
(PTC)
Show intra and extra hepatic
biliary duct clearly
Complication: bile leakage
o Cholangitis
Gallbladder: body, fundus, neck
o Hemorrhage
Level of the Stones: o Endoscopic retrograde
Gallbladder-dyspeptic symptoms cholangiopancreatography
Cyst duct-acute cholecystitis Outline the biliary tree and
Common bile (not fully obstructed) -dyspepesia or pancreatic duct
abdominal pain Inspect the biliary tree and
pancreatic duct
The level of the symptoms depend where the stone is located Inspect the ampulla of vater
*Common bile duct theory: the pancreatic duct and the Exam of fluid of duodenum, bile,
common bile duct joins together to form single opening
pancreatic fluid
Carlot triangle:
The triangle bounded by the common hepatic duct o Endoscopic sphincterotomy (EST)
medially, the cystic duct inferiorly and the inferior o Endoscopic naso-biliary drainage (ENBD)
surface of the liver superiorly is known as calot o Computed tomography (CT)
triangle. o Magnetic resonance
The fact that cystic artery, right hepatic artery and cholangiopancreatography (MRCP)
para-right hepatic duct run within the triangle makes o Cholangiopancreatography during
an important area of dissection during operation
cholecystectomy. o Percutaneous transhepatic cholangiography

Anatomy Cholelithiasis
The sphincter of Oddi: Including: gallstones and biliary duct stones
In China:
o The proximal bile and pancreatic ducts and
Before 1981
the common channel are surrounded by Gallstones < biliary duct stones
circular and longitudinal smooth muscle, Cholesterol stones < pigment stones
this muscle complex is known as the Now
sphincter of Oddi. Gallstones >biliary duct stones
Cholesterol stones > pigment stones
*a sphincter dysfunction can cause an additional pin to the
patient Classification of stones
1. Cholesterol stones: yellow stones, hard, layed on
Special investigation of the biliary tract cross-section, usully caused by infections
Ultrasound 2. Pigment stones: crumble when squashed
Non-invasive, painless, easily performed 3. Mixed stones: radio-opaque
First choice for biliary tract disease 4. Black stones
Bile duct stones: *left hepatic duct=more pigment stones
Stones in gallbladder:
High echo which cast an acoustic shadow and which LOCALIZATION OF STONES
move with changes in posture SITE TYPE PERCENT
Jaundice differential diagnosis: Gallstones Cholesterol stones or
mixed stones 50%
Dialation of the ducts distl part
(cholesterol mainly)
CBD: diameter>1.0cm
Extra hepatic bile Primary stones: pigment
Other disease: cholecystitis, tumor etc. duct stones stones and mixed stones
During surgery: to detect bile duct stones (bile pigment mainly)
20-30%
secondary stones:
*sensitivity-the disease is there you can see it cholesterol stones (from
*specificity-the disease is not there, cannot be seen gallbladder)
Radiology Intra hepatic bile Primary bile duct
o Plain abdominal radiograph: duct stones (left > stones: pigment stones
20-30%
Radio-opaque gallstones right) and mixed stones (bile
Air in the biliary tree pigment mainly)

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Liver, Pancreas & Gall Bladder Dr. Payawal

Occurs in the mid or the upper-right portion of the

Formation of cholesterol stones: upper abdomen
Cholesterol insoluble in water and relative proportion of Severe pain starts abrubtly, continuous, with
cholesterol, bile saltes, and phospholipid in bile. restlessness, vomiting, sweating
Increase of cholesterol and decrease of bile saltes leads to Pain radiate to the right back and shoulder
supersaturation of bile with cholesterol, which results in the Mirizzi syndrome:
formation of liquid crystalline phase of cholesterol -Obstruction of the common hepatic duct
Nucleation: cholesterol will crystallize if there is a nidus on by a stone impacted in the cystic duct or
which the crystals can form. hartmanns pouch
Nucleating factors: mucus glycoproteins from cyst wall and
bilirubinate -press on the bile duct or (more commonly)
Alteration of the gallbladder function: the motility of the ulcerate into the ducts leads to
cyst wall cholecystocholedochal fistula

Formation of stones -cholecystitis, cholangitis, and obstructive

jaundice
Extraheptic duct: contains either primary pigment stones or
cholesterol stones -cholangiography: narrow of the bile duct at
Intrahepatic stone: primary pigment stones the portahepatis

Pigment stones:- due to infection -anatomy variation: cyst duct runs parallel
form of calcium bilirubunate to the hepatic duct
bilirubin conjugated with glucuronide B-
glucoronidase produced by E. coli can split the molecule Mucoceole of the gallbladder:
unconjugated bilirubin precipitates as salt. -a stone impacts in the cystic duct without
bacterial infection
Gallstones ( cholecystolithiasis)
Risk factor: -bile reabsorbed
Women are three times more likely than men to
develop stones -the epithelium continues to secrete
Obesity mucous, which is called white bile
Pregnancy
Dietary factors: high energy, low in fiber Stones migrate though the cystic duct into the
Fasting common bile duct: infection, jaundice
Biliary infection Impaction of a small stone at the ampulla of Vater
Parasitic infestation and occlusion of the pancreatic duct causes
Deaibetes mellitus pancreatitis
TPN
Gastric surgery o Painjaundicefever= charcots triad, obstruction
Cirrhosis of liver of common bile duct
Chronic haemolyticanaemia o Feverpainjaundice= viral hepatitis/ infection
o Jaundicefeverpain= pancreatic cancer

Sign
Right upper area of the abdomen tenderness,
rigidity, rebound tenderness
Gallbladder palpable
Murphy sign: inspiratory arrest during subcostal
palpation
Jaundice: common bile duct stones or Mirizzi
syndrome
Fever and chill with infection

Treatment

Clinical feature of gallstones The first choice is operation:

20-40% patient without symptom which is called -symptomatic gallstones
asymptomatic gallstones -gallstones with complications
Chronic cholecystitis
Biliary colic
Acute cholecystitis
Symptoms

Biliary colic: most common symptom

A large or fatty meals and changing in position when
sleeping can precipitate the pain
Due to impaction of stone in the neck of the
gallbladder: the pressure increase.

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Liver, Pancreas & Gall Bladder Dr. Payawal

Signs and Symptoms

Severe epigastric abdominal pain- abrupt onset (may
radiate to back)
Nausea & vomiting
Weakness
Tachycardia
+/- Fever, +/- hypotension or shock
Grey turner sign-flank discoloration due to
retroperitoneal bleed in pt. with pancrearic necrosis
(rare)
Cullens sign- periumbillical discoloration (rare)

Ranson Criteria

Admission
o Age > 55
o WBC > 16, 000
o Glucose > 200
o LDH > 350
o AST >250

During first 48 hrs

o Hematocrit drop >10%
o Serum calcium <8
o Base deficit > 4.0
o Increase in BUN > 5
o Fluid sequestration > 6L

PANCREATITIS 5% mortality risk with <2 signs

15-20% mortality risk with 3-4 signs
40% mortality risk with 5-6 signs
99% mortality risk with >7 signs
Therapy
Remove offending agent (if possible)
Supportive
#1- NPO (until pain free)
-NG suction for patients with ileus or emesis
- TPN may be needed
#2 aggressive volume repletion with IVF
o Keep an eye on fluid balance/ sequestration
and electrolyte disturbances
Pathophysiology- insult leads to leakge of pancreatic
enzymes into pancreatic and peripancreatic tissue leading to >1cm = dilation of the bile duct
acute inflammatory reaction Alcohol/gallstone= leading cause of pancreatitis
Gray turner sign= seen in the flanks
Etiologies Cullen sign= seen in the periumbillical area
o Idiopathic Somatostatin= is the only gastric peptide that has an
o Gallstones(or other obstructive lesions inhibitory effect
o EtOH
o Trauma
o Steroids
o Mumps(& other viruses CMV, EBV)
o Autoimmune (SLE, polyarthritis nodosa) God bless!
o Scorpion sting
o Hyper Ca, TG
o ERCP (5-10% of points undergoing
procedure)
o Drugs (thiazides, sulfonamides, ACE-I,
NSAIDs, azathioprine)

EtOH and gallstones account for 60-70% of cases

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