Absite review basic science session 5

UNIVERSITY OF FLORIDA
DEPARTMENT OF SURGERY
AMERICAN BOARD OF SURGERY
IN-SERVICE TRAINING EXAM
(ABSITE)
BASIC SCIENCE 101
By
MATTHEW J. DELANO
1

A BASIC SCIENCE REVIEW OF THE CORE TOPICS IN
GENERAL SURGERY FOR THE AMERICAN BOARD
OF SURGERY IN-SERVICE TRAINING EXAM
© 2008 MATTHEW J. DELANO
2

"WEAKNESS OF ATTITUDE BECOMES WEAKNESS OF CHARACTER"
Albert Einstein
“CHANCE FAVORS THE PREPARED MIND"
Louis Pasteur
3

ACKNOWLEDGMENTS
RICHARD E. DEAN, M.D.
JOHN ARMSTRONG, M.D.
GEORGE SAROSI, M.D.
KEVIN BEHRNS, M.D.
MICHAEL E. MAHLIA, M.D.
WILLIAM CANCE, M.D.
LYLE L. MOLDAWER, Ph.D.
4

TABLE OF CONTENTS
Page
ACKNOWLEDGMENTS ...............................................................................................................4
CHAPTER
1 COURSE DESCRIPTION AND SYLLABUS: BASIC SCIENCE 101..................................7
2 AMERICAN BOARD OF SURGERY IN-SERVICE TRAINING EXAM (ABSITE) ........10
3 BODY AS A WHOLE: SESSION 1
6 GASTROINTESTINAL SYSTEM: SESSION 4
7 GASTROINTESTINAL SYSTEM: SESSION 5...................................................................13
Colon/Rectum.........................................................................................................................13
Preferred Energy Source Colonocyte ..............................................................................13
Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Lynch Syndrome .....................14
Colon Bacteria.................................................................................................................15
Site of Colon Absorptive Activity...................................................................................16
Spleen .....................................................................................................................................17
Diagnosis/Treatment for Immune Thrombocytopenic Purpura (ITP).............................17
Rationale for Splenectomy for ITP..................................................................................18
Overwhelming Post Splenectomy Infection (OPSI)........................................................19
Site of Extramedullary Hematopoiesis in Myelofibrosis ................................................20
Pancreas..................................................................................................................................21
Arterial Supply to the Head of the Pancreas ...................................................................21
Pancreatic Enzymes – Characteristics of Secretion.........................................................22
Physiology of Secretin Release .......................................................................................23
Activation of Pancreatic Proenzymes..............................................................................24
Electrolytes in Pancreatic Exocrine Secretion with Stimulation.....................................25
Characteristics of Pancreatic Divisum.............................................................................26
Results of Acinar Cell Injury in Acute Pancreatitis ........................................................27
Biliary/Liver ...........................................................................................................................28
Bile Salt Metabolism.......................................................................................................28
Hormonal Stimulation of Hepatic Bile Flow...................................................................29
Characteristics of Lithogenic Bile...................................................................................30
Composition of Primary Common Bile Duct Stones ......................................................31
Biochemistry of Hepatic Lipid Degradation ...................................................................32
Differential Diagnosis of Jaundice with Non-Dilated Ducts...........................................33
5

Diagnostic Test for Symptomatic Gall Bladder Disease Without Stones – Biliary
Dyskinesia....................................................................................................................34
Segmental Anatomy of the Liver ....................................................................................35
Best Test of Hepatic Biosynthesis...................................................................................36
Hepatic Acute Phase Response .......................................................................................37
Venous Tributaries of the Portal System.........................................................................38
Susceptibility to Hepatoma (Hepatocellular Carcinoma)................................................39
Principles Associated with Chemo Embolization of Liver Metastases...........................40
Location of Anomalous Hepatic Arteries........................................................................41
Anatomy of Aberrant Right Hepatic Artery....................................................................42
Prognostic Test of Liver Function Reserve.....................................................................43
Preoperative Treatment of Obstructive Jaundice ............................................................44
Etiology of a Sudden Increase in End Tidal CO2 After Evacuating CO2 in a
Laparoscopic Cholecystectomy Procedure..................................................................45
Findings Associated with the Hepatorenal Syndrome.....................................................46
Anatomy of Common Bile Duct......................................................................................47
Characteristics Hepatocytes.............................................................................................48
Bile Acid Synthesis .........................................................................................................49
Characteristics of Chylomicrons .....................................................................................50
Biliary Tract Bacteria ......................................................................................................51
Preoperative Measure of Portal Venous Pressure ...........................................................52
Best Test of Hepatic Biosynthesis...................................................................................53
Abnormal Liver Function Test in Metastatic Colon Cancer ...........................................54
Hepatocellular Cancer in Chronic Hepatitis B (Complications Hepatitis B)..................55
Pathophysiology of Ascites in Alcohol Cirrhosis ...........................................................56
Basis for Chemoemboliztion of Hepatic Metastases.......................................................57
Etiology of Liver Failure/Diagnosis of Ligation of Hepatic Artery (Unintended
Hepatic Artery Ligation at Operation).........................................................................58
6

CHAPTER 1
COURSE DESCRIPTION AND SYLLABUS: BASIC SCIENCE 101
Goals:
1. Understand the historical significance and current purpose of the ABSITE.
2. Understand and comprehend the five fundamental areas of surgery related basic science
knowledge that the ABSITE test.
3. Improve individual ABSITE scores by 10-20%.
4. Promote personal lifelong habits of scientific surgical learning and self education.
Basic Science 101 will focus on building and reinforcing the fundamentals of surgical basic
science knowledge which will serve as a foundation for further clinical and operative knowledge
growth and ABSITE success.
Audience
All categorical and preliminary surgical residents (PGY-1 - PGY-7+)
Review Session Time/Location:
Dates: Sun. December 7, 2008 Dr. Kevin Behrns’s Residence
Sun. December 14, 2008 Dr. Kevin Behrns’s Residence
Sun. December 21, 2008 Dr. Kevin Behrns’s Residence
Sun. January 4, 2009 Dr. Kevin Behrns’s Residence
Behrns Residence:
Assessment:
1. Course attendance and participation
2. Individual accountability: Pre-course test score, Post-course test score, ABSITE Score
3. Team accountability: Jeopardy Champion
Expectations:
1. Take an on-line learning styles inventory at: http://www.engr.ncsu.edu/learningstyles/ilsweb.html.
2. Attend each review session.
3. Review ABSITE appropriate surgery related basic science for each group session.
4. Be prepared to answer basic science questions during each session.
5. Take pre-course test and post-course test, take the ABSITE.
Course Directors:
Matthew J. Delano, M.D., Ph.D., delanmj@surgery.ufl.edu
cell: 352-514-9451
John H. Armstrong, M.D., F.A.C.S., john.armstrong@surgery.ufl.edu
office: 273-5675, pager: 413-5666, cell: 786-255-4820
George Sarosi, M.D., george.sarosi@surgery.ufl.edu
7

Course Schedule:
Review Session Date: Topics to be covered: Course materials:
December 7, 2008 BODY AS A WHOLE Chapter 3
January 4, 2009 GASTROINTESTINAL TRACT Chapter 6
January 11, 2009 GASTROINTESTINAL TRACT Chapter 7
January 18, 2009 CARDIOVASCULAR AND PULMONARY Chapter 8
January 25, 2009 GU, HEAD AND NECK, SKIN, Chapter 9
MUSCULOSKELETAL, NERVOUS, ENDOCRINE,
HEMATIC AND LYMPHATIC SYSTEMS AND
BREAST
How to use the course materials:
Before arriving at the first session you should take the on-line learning styles inventory at:
http://www.engr.ncsu.edu/learningstyles/ilsweb.html, which will provide feedback for you regarding
your personal learning style. This will enable you to better understand how you learn and prepare your
own focused study plan. Please bring the results of your online learning inventory to the first review
session so that we can review them and accommodate all your learner styles.
The course is broken down by basic science knowledge category as tested by the
ABSITE. The course material has been concentrated, fermented, and distilled from the past ten
years worth of Michigan State Integrated ABSITE Reviews, by Richard E. Dean. These are not
my topics of interest rather the topics that appear yearly on the ABSITE. Each review session
will concentrate on the information and topics as related in the chapters as listed above from the
aforementioned compiled source. Each chapter contains relevant basic science questions with
answers at the end that frequently appear on the ABSITE in some form from year to year. Use
these to test your knowledge and guide your studies.
Each individual is expected to have covered the relevant information prior to each review
session just as each individual is expected to review the pertinent details of a general surgery
case prior to entering the operating room. No Exceptions.
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9
At the review sessions the information presented in this text will not be covered in a
didactic nauseating fashion allowing you to irresponsibly coast, sleep, hide, flail, flake and slide
away from excellence, rather you will be asked questions directly from the course content
presented here and your answers will immediately impact you, and more importantly your team
members. The team that answers the most questions correct over the seven review sessions will
be the intellectual winner and will also receive a substantial prize to be decided.
Jeopardy Teams:
Team Dragstedt: Team Woodward: Team Copeland
Robert Browning, M.D. Khayree Butler, M.D. Adrienne Buckman, M.D.
Alice Coker, D.M.D., M.D. Nicole Croley, M.D. Peter Fiester, M.D.
Trevan Fischer, M.D. Lori Filichia, M.D. Lindsey Goldstein, M.D.
Gregory Gerber, M.D. Claire Griffin, M.D. Ramy Nasr, M.D.
Peter Salerno, D.O. Craig Wengler, M.D. Robert Timmerman, M.D.
Matthew Warrick, M.D. Mark Wilson, M.D. Luke Gutwein, M.D.
Josef Braun, M.D. Trajan Cuellar, M.B. Michael Hong, M.D.
Damian Dyer, M.D. Makesha Miggins, M.D. Matthew Hughes, M.D.
Bo Neichoy, M.D. Georgios Rossidis, M.D. Darrell Hunt, M.D., Ph.D.
Alyson Waterman, M.D. Robert Winfield, M.D. Dean Yamaguchi, M.D.
Nicole Kissane, M.D. Vincent Mortellaro, M.D. Brady McDonald, M.D.
Chad Stasik, M.D. Omeni Osian, M.D. Angel Caban, M.D.
Stancie Rhodes, M.D. Jason Wilson, M.D. Skeeter Salcedo, M.D.
Alex Cuenca, M.D. Tad Kim, M.D. Constance Lee, M.D.
Elizabeth Warner, M.D.
Reference Material:
The Physiologic Basis of Surgery. 3rd
Ed. by J. Patrick O’Leary, 2002, Lippincott Wiliams &
Wilkins, ISBN 0-7817-3839-3.
Sabiston Textbook of Surgery: The Biloigical Basis of Modern Surgical Practice. 17th
Ed. by
Courney M. Townsend Jr, R. Daniel Beauchamp, B. Mark Evers, Kenneth L. Mattox, 2004,
Elsevier Saunders, ISBN 0-7216-0409-9

CHAPTER 2
AMERICAN BOARD OF SURGERY IN-SERVICE TRAINING EXAM (ABSITE)
Introduction
The American Board of Surgery offers annually to surgery residency programs the In-Training
Examination (ABSITE), a written, multiple-choice examination designed to measure the
progress attained by residents in their knowledge of basic science and the management of clinical
problems related to general surgery. The ABSITE is furnished to program directors as an
evaluation instrument to assess residents' progress. The results are released only to program
directors. It is not available to individual residents and is not required as part of the certification
process.
Reporting of Results
ABSITE results are made available to program directors in early March. The ABS provides
program directors with various reports, including a resident's individual score report. Residents
are strongly encouraged to keep copies of their score report for their records, as the ABS does
not retain this information. The ABS will not provide residents with a score report or
"transcript." Residents who request this information will be directed to contact their general
surgery residency program.
If you have questions once you have received your individual score report, your program director
can help with the interpretation of the results. The ABS will not discuss examination results with
residents. The ABS also will not regenerate any report as a result of miscoding of information,
such as PGY level, name, etc. Any inquiries regarding the ABSITE must come directly from the
program.
Examination Content
Since 2006 the ABS offers the ABSITE as a junior level (PG-1 and -2) and senior level (PG-3 to
-5) examination. Both the junior- and senior-level versions consist of 225 multiple-choice
questions; examinees are given five hours to take the exam. For the junior-level exam, 60% of
the examination focuses on basic science, while 40% centers on the management of clinical
surgical problems. In the senior-level exam, 20% of the exam focuses on basic science and 80%
on clinical management. The relative emphasis on clinical content categories in the two
examinations is shown in the following tables.
Table 1. Junior and Senior ABSITE basic science and clinical medicine breakdown.
Junior ABSITE Senior ABSITE
% (# questions) % (# questions)
Basic Science 60% (135) 20% (45)
Clinical Medicine 40% (90) 80%(180)
Total 100%(225) 100%(225)
10

Table 2. Knowledge categories comprising the Junior and Senior ABSITE
Knowledge Category Junior ABSITE Senior ABSITE
% of Test % of Test
BODY AS A WHOLE 66.60% 25%
GASTROINTESTINAL TRACT 10% 25%
CARDIOVASCULAR AND PULMONARY SYSTEMS 7.80% 16.70%
GU, HEAD AND NECK, SKIN, MUSCULOSKELETAL, AND
NERVOUS SYSTEMS
7.80% 16.70%
ENDOCRINE, HEMATOLOGIC, AND LYMPHATIC
SYSTEMS , AND BREAST
7.80% 16.7
Table 3. Junior and Senior ABSITE basic science and clinical medicine breakdown by
knowledge category.
Knowledge Category Junior ABSITE Senior ABSITE
# questions # questions
BODY AS A WHOLE Basic Science 90 10
Clinical Medicine 60 45
GASTROINTESTINAL TRACT Basic Science 15 10
CARDIOVASCULAR AND PULMONARY SYSTEMS Basic Science 11 8
GU, HEAD AND NECK, SKIN, MUSCULOSKELETAL,
AND NERVOUS SYSTEMS
Basic Science 11 8
ENDOCRINE, HEMATOLOGIC, AND LYMPHATIC
SYSTEMS , AND BREAST
Basic Science 11 8
Adapted from the American Board of Surgery: http://home.absurgery.org/
11

12
Table 4. Breakdown of the 2007 Junior ABSITE.
BODY AS A WHOLE: NUMBER OF QUESTIONS
Basic Science 47
Clinical Management 57
GASTROINTESTINAL:
Basic Science 29
CARDIOVASCULAR AND RESPIRATORY:
Basic Science 25
GU, HEAD AND NECK, SKIN,
MUSCULOSKELETAL, NERVOUS, SYSTEMS:
Basic Science 11
ENDOCRINE, HEMATIC, LYMPHATIC, BREAST
Basic Science 14
As you can see the Junior ABSITE is over 60% basic science while the Senior ABSITE is
predominantly clinical medicine.

CHAPTER 7
GASTROINTESTINAL TRACT: SESSION 5
Colon/Rectum
Preferred Energy Source Colonocyte
Short-chain fatty acids (SCFAs) are produced in the colon by fermentation of dietary fiber by
colonic bacteria. The major SCFAs produced are acetate, propionate, and butyrate. Butyrate is
the major source of fuel for the colonic epithelial cells. Substrates are metabolized by the
colonic mucosa in the order of butyrate>glucose>ketone bodies>glutamine. A lack of butyrate
has been shown to result in colonic inflammation as seen in diversion colitis. Butyrate enemas
have been used satisfactorily as a treatment for this.
It has been hypothesized that impaired metabolism of butyrate may be present in the colonocytes
of patients with ulcerative colitis (UC). Use of SCFA enemas in the treatment of UC patients has
been promising in early studies.
Roedinger WE. “Utilization of nutrients by isolated epithelial cells of rate colon,”
Gastroenterology 83:424-9
Ahmad MS, et al. “Butyrate and glucose metabolism by colonocytes in experimental colitis in
mice,” Gut 46:493-9
Simpson EJ, et al. “In vivo measurement of colonic butyrate metabolism in patients with
quiescent ulcerative colitis,” Gut 46:73-7
13

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Lynch Syndrome
HNPCC is an autosomal dominant familial colorectal cancer arising in discrete adenomas but
polyposis does not occur.
Variations in the MLH1, MSH2, MSH6, and PMS2 genes increase the risk of developing Lynch
syndrome. All of these genes are involved in the repair of mistakes made when DNA is copied
(DNA replication) in preparation for cell division. Mutations in any of these genes prevent the
proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the
accumulated mistakes can lead to uncontrolled cell growth and possibly cancer. Although
mutations in these genes predispose individuals to cancer, not all people who carry these
mutations develop cancerous tumors.
Lynch Syndrome I is an autosomal dominant, site-specific colon cancer.
Main Features: No associated polyposis, right-sided colon cancer, multiple colon
cancers, and long survival. Familial predisposition to colorectal cancer with right-sided
predominance. Predominantly early-onset proximal colon carcinomas.
Lynch Syndrome II
Main Features: The same as Lynch Syndrome I with increased risk for cancer of the
female genital tract (endometrial, ovarian), stomach and urinary tract. This group is at
greater risk for recurrence.
Familial predisposition for other primary cancers in addition to the predisposition for
colon cancer; site is often female reproductive organs. Predominantly early onset
proximal colon carcinoma associated with other extracolonic adenocarcinomas,
particularly endometrial carcinoma.
HNPCC Criteria: Females must have at least three relatives with colorectal CA, one of
whom is a first degree relative of the other two. Colorectal CA must involve at least two
generations, at least one CA case must occur before 50 years of age. Adenomas and
carcinomas occur at an early age (adenomas in 20’s and 30’s—carcinomas 40-45 years of
age) and are often proximal in location and multiple.
Diagnosis: Screening sigmoidoscopy every 3-5 years with yearly fecal occult blood tests
beginning at age 50.
Treatment: Colonoscopy with polypectomy (to clear entire colon from possible synchronous
adenomas).
Colonoscopy: Every 3 years in patients w/out evidence of high-grade dysplasia or CA.
Surgery: If < 2mm clear margins on polypectomy, CA is poorly differentiated or
vascular/lymphatic invasion is present.
Greenfield, Surgery, Scientific Principles & Practice, 2nd
Edition
14

Colon Bacteria
As opposed to disease-causing bacteria in the small intestine, in which adherence is an important
property, the long transit time in the colon makes adherence a much less important attribute.
Anaerobes are favored 1000:1 versus aerobes in the colon.
The bacterial density increases as one moves down the colon. A perforated appendix contains
about 106
to 107
bacteria per gram of content. Sigmoid colon contains 1010
to 1011
bacteria per
gram of content. The most common components of fecal flora are listed below. One should note
that there are no pathogenic species among the most common 25 organisms.
Relative Frequency of Bacterial
Species in Fecal Flora
Rank Percent Organism(s)
1 12 Bacteroides vulgatus
2 7 Fusobacterium prausnitzii
3 6.5 Bifidobacterium adolescentis
4 6 Eubacterium aerofaciens
5 6 Peptostreptococcus productus II
6 4.5 Bacteroides thetaiotaomicron
7 3.6 Eubacterium eligens
8 3.3 Peptostreptococcus productus I
9 3.2 Eubacterium biforme
10 2.5 E. aerofaciens III
11 2.3 Bacteroides distasonis
28 0.7 B. ovatus
29 0.6 B. fragilis
59-75 0.13 Streptococcus faecalis
76-113 0.06 Escherichia coli, Klebsiella
pneumonia
and 37 other bacterial species
Simmons & Steed, p 190
O’Leary, p 62
15

Site of Colon Absorptive Activity
The major absorptive function of the colon is final regulation of water and electrolyte balance in
the intestine. The colon absorbs greater than 90% of the water and electrolytes presented to it.
The majority of water absorption occurs in the ascending colon.
Schwartz, Principles of Surgery, 7th
Edition, p 1272
16

Spleen
Diagnosis/Treatment for Immune Thrombocytopenic Purpura (ITP)
Idiopathic thrombocytopenic purpura (immune thrombocytopenic purpura ITP)) is an acquired
disorder caused by the destruction of platelets exposed to circulating IgG antiplatelet factors.
The spleen is the source of these factors. It is also the major site for sequestering sensitized
platelets. The term ITP should be reserved for a hemorrhagic disorder characterized by a
subnormal platelet count in the presence of bone marrow containing normal or increased
megakaryocytes and in the absence of any systemic disease or history of ingestion of drugs
capable of inducing thrombocytopenia. Female patients outnumber males at a ratio of 3:1.
Platelet counts are generally reduced to 50,000 or less and at times approach zero. Acute ITP
has an excellent prognosis in children under the age of sixteen. Approximately 80% of these will
recover completely without specific therapy.
The generally accepted protocol for managing patients with diagnosed ITP includes an initial 6-
week to 2-month period of steroid therapy. If the patient does not respond, splenectomy is
performed. If the patient does respond, the steroid therapy is tapered off, and if
thrombocytopenia recurs, splenectomy is carried out. Any manifestations suggestive of
intracranial bleeding demand emergency splenectomy. In one series, 5 of 6 patients with ITP
and life-threatening intracranial bleeding were saved by splenectomy. Platelets should be
available for the procedure but should only be administered in patients who continue bleeding
following removal of the spleen.
Occasionally, the disease recurs and patients achieve permanent cure following removal of an
accessory spleen. Approximately 20% of patients have an accessory spleen. Common sites are
the splenic hilus, adjacent to the splenic vessels and tail of the pancreas, greater omentum, and
gastrosplenic and gastrocolic ligaments. A Technetium scan may be useful in identifying the
accessory spleen.
In most series, the results by splenectomy are significantly more impressive than are the results
from steroids. Approximately 80% of the patients treated with splenectomy respond
permanently and require no further steroid therapy. In most patients, the platelet count rises to
over 100,000/mm3 in 7 days.
Edition
O’Leary, Physiologic Basis of Surgery, 2nd
Edition
Sabiston, Textbook of Surgery, 15th
Edition, p 1196
17

Rationale for Splenectomy for ITP
Immune thrombocytopenic purpura, formerly called idiopathic thrombocytopenic purpura, is a
syndrome characterized by a persistently low platelet count. The thrombocytopenia is caused by
a circulating anti-platelet factor that causes platelet destruction by the reticuloendothelial system.
In most patients, the anti platelet factor is an immune globulin (IgG) antibody directed toward a
platelet associated antigen. The spleen is an important site of antibody production, and splenic
cells from patients with chronic ITP produce 5-6 times more IgG in culture than control splenic
cells. Platelet destruction in ITP requires sufficient quantities of antigen (platelets), antibody and
phagocytic cells in an environment that provides time for antibody binding and subsequent
platelet phagocytosis. The spleen is ideally suited for this function, because 30% of the total
circulating platelet mass is within the spleen at all times and serves as an exchangeable platelet
pool. The spleen is the most active site of platelet destruction. The stagnant blood flow allows
sensitized platelets to be readily removed by phagocytic cells.
Treatment: Considering the immune mechanisms involved, initial treatment normally consists of
corticosteroid therapy (1 mg per kg per day). Most patients with ITP are improved with
administration of this drug. Intravenous gamma globulin is also useful, but requires several days
for beneficial platelet increase to occur. Most patients, however, are improved after splenectomy
even if their platelet counts were not significantly increased by corticosteroid therapy.
Sabiston, 15th
ed., p 1193-95
18

Overwhelming Post Splenectomy Infection (OPSI)
Asplenic patients are at risk for developing OPSI, the most common fatal complication of
splenectomy. The infection is due to encapsulated bacteria. S. pneumonia is the most frequently
involved organism (50-90% of cases). Others include haemophilus influenza, neisseria
meningitis, streptococcus, and other pneumonia species.
Asplenics have defective activation of complement, subnormal levels of IgM and a suppressed
peripheral immunoglobin response. The opsonization of encapsulated bacteria, which involves
immunoglobulin and complement, is impaired following splenectomy.
OPSI has a prodromal phase with fever, chills, malaise, myalgia, and other nonspecific
symptoms. The infection progresses rapidly to hypotension, DIC, respiratory distress, coma, and
death. The mortality is 50-70% in fully developed cases in spite of appropriate antibiotics.
OPSI is greater when splenectomy is completed for malignant or hematologic diseases and is a
high risk for children less than 4 years of age. OPSI continues as a risk and may be greater after
2 years and approaches 50% after 5 years.
Prophylaxis for OPSI includes immunization for S. pneumonia species and H. influenza.
Immunization should precede splenectomy by 2 weeks if possible or soon after surgery when
preimmunization is not possible. High-risk asplenic patients should be reimmunized within 3-6
years.
Edition, pp 1146, 1162
19

Site of Extramedullary Hematopoiesis in Myelofibrosis
Myelofibrosis, or Agnogenic Myeloid Metaplasia (AMM), is believed to be a response to a
clonal proliferation of hematopoietic stem cells. Marrow failure often ensues. Extra-medullary
hematopoiesis is manifest by splenomegaly and hepatomegaly in two thirds. 35% have massive
splenomegaly. Nucleated red blood cells and immature myeloid elements in blood are present in
96% of the cases. Splenomegaly related symptoms are best treated with splenectomy.
Edition, p 1304
20

Pancreas
Arterial Supply to the Head of the Pancreas
The blood supply to the head of the pancreas is largely from the anterior and posterior
pancreaticoduodenal arcades. The anterior superior and posterior superior pancreaticoduodenal
arteries arise from the gastroduodenal artery, a branch of the hepatic artery. The superior
mesenteric artery gives rise to the inferior anterior and posterior pancreaticoduodenal arteries to
complete the two arcades. These vessels provide the blood supply to the head of the pancreas
and duodenum.
Hollinshead, Anatomy for Surgeons, 2nd
Edition, Vol. 2, pp 418, 430
21

Pancreatic Enzymes – Characteristics of Secretion
The digestive enzymes are synthesized and stored in the pancreatic acinar cells and are released
in response to cholecystokinin and vagal stimulation. Pancreatic enzymes are
• Proteolytic – trypsin, chymotrypsin, carboxypeptidase, ribonuclease, deoxyribonuclease,
elastase
• Lipolytic – lipase, colipase, phospholipase A2
• Amylolytic – amylase
Lipase and amylase are secreted in their active forms. The proteolytic enzymes and
phospholipase A2 are secreted as inactive “zymogens.” Activation of trypsinogen to trypsin
occurs when the zymogen is exposed to the duodenal enzyme enterokinase. Trypsin then
converts the other zymogens to their active forms. In the intestine, the proteolytic enzymes
digest proteins into peptides, lipase breaks fats into glycerol and fatty acids, phospholipase A2
catalyzes the conversion of biliary lecithin to lysolecithin, and amylase converts starch to
disaccharides and dextrans.
Secretin is the principal stimulant of pancreatic water and electrolytes secretion. Water and
electrolytes originate from the central acinar and intercalated duct cells. At basal secretory rates
of .2 to .3mL per minute, concentrations of chloride and bicarbonate ions are equivalent to
plasma. However, with neurohumoral stimulation the bicarbonate component increases in
concentration while the chloride concentration falls. The end product is a clear, isotonic solution
with a pH of 8.
Cholecystokinin (CCK) and vagal stimulation (acetylcholine) are the principal stimulants for the
secretion of pancreatic enzymes.
Physiologic Basis of Surgery, 2nd
Edition, pp 452-5
22

Physiology of Secretin Release
Secretin is a 27 amino acid helical peptide that is found in the S cells of the duodenum and
jejunum. It is a true hormone and is released by acidification of the duodenum (pH below 4.5) or
by contact with bile or perhaps fat. It acts to stimulate release of water and bicarbonate from
pancreatic ductal cells. The bicarbonate neutralizes gastric acid. Secretin also acts to stimulate
the flow of bile, inhibit gastrin release, gastric acid secretion, and gastrointestinal motility. Its
unique ability to release gastrin from gastrinomas allows parenteral secretion to be used as a
diagnostic test in those patients suspected of having Zollinger-Ellison syndrome.
Greenfield, 2nd
Edition, 1997, p 807
Schwartz, 7th
Edition, 1999, p 1228
23

Activation of Pancreatic Proenzymes
Pancreatic proteolytic enzymes are essential for protein digestion. These enzymes are secreted
as proenzymes and require activation for proteolytic activity. The proenzymes of trypsin and
chymotrypsin are trysinogen and chymotrypsinogen. They are activated primarily by a duodenal
enzyme, enterokinase, which converts trypsinogen to trypsin. Trypsin, in turn, activates
chymotrypsin, elastase, carboxypeptidase, and phospolipase. Trypsinogen can also be activated
by a fall in pH below 7.0. Within the pancreas, enzyme activation is prevented by antiproteolytic
enzyme secreted by the acinar cells. This enzyme inactivates trypsin by direct binding, which
protects the pancreatic tissue from autodigestion.
Trypsinogen is a 229-amino acid polypeptide that hydrolyzes proteins and also acts as
thrombokinase, accelerating coagulation of the blood. Trypsinogen can convert spontaneously to
trypsin, but the change is accelerated by enterokinase, by acid, or by the active trypsin itself.
Chymotrypsinogen is a 246-amino acid polypeptide converted to the active form, chymotrypsin,
by trypsin or, indirectly by enterokinase. The enzyme hydrolyzes proteins in a mechanism
similar to that of trypsin but cleaves the proteins at a different site. The optimal activity of
chymotrypsin and trypsin occurs at a pH of 8.0 to 9.0. Other proteolytic enzymes, such as
carboxypeptidases A and B, are enzymes that further digest proteins that have been digested by
trypsin and chymotrypsin. The nucleolytic enzymes ribonuclease and deoxyribonuclease,
hydrolyze nucleic acids into mononucleotides.
Greenfield, 2nd
Edition, pp 866-67
24

Electrolytes in Pancreatic Exocrine Secretion with Stimulation
The pancreas secretes 1 to 2 liters per day of a clear, watery, alkaline (ph 8.0-8.3) liquid
containing more than 20 digestive enzymes. The cation of this juice is sodium and potassium,
which are always found in concentrations similar to plasma. The concentration of the principle
anions (bicarbonate and chloride) varies. With minimal stimulus to secrete, the chloride
concentration is high (e.g. 110mm/L), and that of bicarbonate low (e.g. 50mm/L). With maximal
stimulus, the bicarbonate concentration rises to approximately 140mm/L and the chloride
concentration falls.
The secretion of bicarbonate at high levels requires active transport and originates from the
centroacinar and intercalated duct cells. As the bicarbonate rich secretion passes through the
larger pancreatic ducts toward the duodenum, bicarbonate is passively reabsorbed and replaced
with chloride when there is minimal stimulus. During the maximal pancreatic exocrine stimulus
(secretin) the bicarbonate rich fluid is flushed through the pancreatic ducts, reducing
opportunities for electrolyte equilibriation with plasma.
Edition, p. 1470
Edition, pp 452-453
25

Characteristics of Pancreatic Divisum
The pancreas appears at about the fifth or sixth week of gestation and is composed of a ventral
and dorsal appendage. Both appendage possess ducts; the ventral duct is related to the common
bile duct and the dorsal duct empties more proximally into the duodenum. Both ducts (when
present) empty into the second part of the duodenum. At about seven weeks the anlage fuse
secondary to asymmetric gut rotation. The ventral anlage forms the uncinate process and a
portion of the head. The dorsal component forms the body, tail, and the remainder of the head.
Fusion of dorsal and ventral ductal elements produces the major duct of Wirsung. Patency of the
dorsal duct beyond the site of fusion forms the accessory duct of Santorini, this occurs in about
70% of individuals. In the other 30%, the proximal aspect of the dorsal duct (Santorini)
regresses after anastomosis with the ventral duct (of Wirsung).
In 4 – 10% of individuals there is failure of fusion of the dorsal and ventral ducts: this is termed
pancreatic divisum. Drainage of the dorsal and ventral aspects of the pancreas remains separate
and the majority of pancreatic exocrine secretion exits via the accessory duct. In this case the
“main” pancreatic duct empties through the minor papilla. Only pancreatic drainage from the
uncinate process drains through the ampulla of Vater. It is felt by many authors that pancreatitis
can result from relative outflow obstruction as the minor papilla is not able to adequately
accommodate such a large volume.
Ed, pp 1402, 1408
Simmons/Steed, pp 257-59
O’Leary, pp 63-65
26

Results of Acinar Cell Injury in Acute Pancreatitis
The acinar cells of the pancreas contain zymogen granules that are responsible for the exocrine
enzyme secretion. Enzyme synthesis has been estimated at 107
enzyme molecules per acinar cell
per minute.
In acute pancreatitis, proteolytic enzymes, along with amylase and lipase, are liberated from the
acinar cell by extravasation into the surrounding tissues where the enzymes are activated causing
an intense inflammatory reaction.
Edition, pp 1114-17
Results of Acinar Cell Injury with Acute Pancreatitis (Pathogenesis of Acute Pancreatitis)
The pancreatic acinar cell synthesizes a number of proteases (trypsin, chymotrypsin,
carboxypeptidase, and elastase, and phospholipases) in an inactive zymogen form. These pro
enzymes are packaged into a cytoplasmic zymogen granule. Through a process of exocytosis,
the zymogen granule is evacuated into the pancreatic duct lumen. The precursors are transported
with water and bicarbonate into the duodenum, where they are converted enzymatically into
active forms by enterokinase at the brush border.
In acute pancreatitis, this normal orderly secretory sequence is disrupted. The zymogen granules
fuse with the lysosomes, to form an autophagic cytoplasmic vacuole (zymogen lakes). These
vacuoles preferentially move to the basal lateral aspect of the acinar cell rather than the luminal
apex. These zymogen/lysosome vacuoles discharged through the basal lateral cell membrane
where the proenzymes are activated resulting in extension of the inflammatory process and
proteolysis of adjacent acinar cells. The increasing activation of the proteolytic enzymes results
in acute pancreatitis.
Collectively, these findings suggest that the outcome of acinar cell injury involves the
intracellular activation of endogenous proteases leading to further injury and local extracellular
discharge of acinar cell contents.
Greenfield, 2nd
Edition, pp 874-875
27

Biliary/Liver
Bile Salt Metabolism
Bile salt synthesis requires high-energy expenditure. The body therefore reduces this energy cost
by recycling the bile salt pool (of 2-5gms) 6 to 15 times per day depending on dietary habits. 0.2
to 0.5gm of bile acid is lost each day in the stool and is replaced by the synthesis of bile acids
from cholesterol in the canicular ducts of the liver. The major bile acids are cholic and
chenodeoxy cholic, which are conjugated with glycine and taurine in the bile. Conjugation
creates a more neutral charged molecule, which allows for rapid diffusion into enterocytes of the
terminal ileum. The bile salts combine with a protein in the enterocyte and enter the portal
circulation where they are extracted by the liver with great efficiency (80% in a single pass).
Edition, pp 428-429
Edition, pp 1008-1009
28

Hormonal Stimulation of Hepatic Bile Flow
Bile flow is dependent on bile acid/salt output and the term “bile acid-dependent flow” has been
applied. The bile acid pool is 2 – 5gms and the bile acids recirculate 6 – 15 times per day. Only
0.2 – 0.5gms of bile acids are lost in stool daily and replaced by de Novo synthesis. Secretin will
stimulate canicular bile flow in bile stasis or in cystic fibrosis. Cholangiocytes contain receptors
for epidermal growth factor Secretin and Somatostatin.
Edition, 1008
29

Characteristics of Lithogenic Bile
In the United States, cholesterol stones account for 70% of gallstones and pigmented stones
account for the remaining 30%. The formation of cholesterol stones is dependent on 3 factors:
Cholesterol saturation, nucleation, and stone growth.
Maintenance of cholesterol in solution is dependent on presence of sufficient amounts of bile
salts and phospholipids. Alterations which result in a relative increase in cholesterol predispose
to stone formation. 30% of cholesterol is carried in micelles and the remaining 70% is carried in
vesicles in a lipid bilayer arrangement. The stability of these vesicles is thought to be the key
determinant in saturation and stone formation. Nucleation is an unclear event that may be
precipitated by calcium, stasis, abnormal gallbladder wall absorption, mucous, or glycoproteins,
or may be due to a lack of antinucleation substances. Once nucleation has occurred, further
precipitation is enhanced by the stones themselves.
Pigmented stones are thought to be induced by infection creating “brown” stones and are
primarily found in Asia. “Black” stones are created in individuals with hemolytic disorders
where the bile becomes supersaturated with unconjugated bilirubin and then precipitates as the
calcium salt.
Schwartz, 7th
Edition, pp 1447
30

Composition of Primary Common Bile Duct Stones
Primary bile duct calculi form within the biliary tract whereas calculi forming within the
gallbladder are called secondary calculi. Primary common duct stones are associated with biliary
stasis and infection. These stones are usually brown pigment type, which are soft and crumble
easily with manipulation.
The composition of primary bile duct stones is a result in stasis, which allows bacterial
glucuronidases to deconjugate bilirubin diglucuronide and the precipation of bilirubin as a
calcium salt.
Treatment must include identification of the abnormality leading to biliary stasis.
Edition, p 1089
31

Biochemistry of Hepatic Lipid Degradation
Fatty acids, which are the major source of energy in the human, are oxidized by β-oxidation.
Fatty acids in the blood are derived from triglycerides of the blood lipoproteins or from those of
adipose stores. The process of β-oxidation occurs in mitochondria. In a series of four steps that
produces FADH2 and NADH, two carbons are cleaved from a fatty acyl CoA and released as
acetyl CoA. This series of steps is repeated until the fatty acid is completely converted to acetyl
CoA. ATP is obtained when the products of β-oxidation are oxidized further. In liver, acetyl
CoA is converted to ketone bodies, which may be oxidized by tissues such as muscle and kidney
or by the brain during starvation. Fatty acid oxidation by tissues increases whenever the
concentration of fatty acids in the blood increases, that is, during fasting and during starvation.
Marks, Biochemistry, 1990, p 228
32

Differential Diagnosis of Jaundice with Non-Dilated Ducts
The etiology of jaundice can be divided on the basis of bile conjugation:
A. Jaundice with high concentrations of unconjugated bile is found with:
1. hemolysis of RBCs
2. hereditary defects, i.e. Gilbert’s Syndrome
3. neonatal jaundice
4. transferase deficiencies, i.e. drug inhibition (Chloramphenicol), or hepatocellular disease,
i.e. hepatitis or cirrhosis
B. Jaundice with conjugated bile and with non-dilated ducts is found in:
1. hereditary disorders, i.e. Dubin-Johnson Syndrome
2. acquired disorders such as hepatocellular disease, i.e. hepatitis or cirrhosis
3. drug-induced cholestasis, i.e. TPN, oral contraceptives, and androgens
4. alcoholic liver disease
5. sepsis
Harrison’s Principles of Internal Medicine, 14th
Edition, p 253
33

Diagnostic Test for Symptomatic Gall Bladder Disease Without Stones – Biliary Dyskinesia
A subgroup of patients presenting with typical biliary colic do not have evidence of gallstones,
and the complete workup excludes any other pathology. The Cholecystokinin-Tc-HIDA Scan
will be useful in confirming the diagnosis of biliary dyskinsea.
Cholecystokinin (CCK) is administered IV after the gall bladder is filled with 99
TC-labeled
radionuclide. Twenty minutes later, the gall bladder ejection fraction is calculated. An ejection
fraction less than 35% at 20 minutes is considered abnormal.
A cholecystectomy in these patients brings relief of symptoms in 85 – 94%.
Edition, p 1087
34

Segmental Anatomy of the Liver
The segmental anatomy of the liver is determined by the sequential branching of the portal vein,
hepatic artery and biliary tree. This bifurcation divides the liver into right and left lobes which,
in turn, are in line with the fossa for the inferior vena cava (IVC) posteriorly and the gallbladder
fossa anteriorly. The segmental anatomy of the liver defined by Couinaud (The French system) is
based on hepatic vein drainage and segmental branching of the portal vein, hepatic artery and
biliary ducts as they enter the hepatic parenchyma.
Segment I Caudate Lobe
Segment II & III Lateral Left Lobe Anterior & Posterior
Segment IV Medial Left Lobe
Segment V & VI Right Lobe, Inferior Anterior & Posterior
Segment VII & VIII Right Lobe, Superior Anterior & Posterior
Figure 14. Segmental liver anatomy. Depicted is segmental liver anatomy as originally described by Couinaud. The
right lobe consists of segments 5 through 8, the left lobe of segments 2 through 4, and the left lateral segment of
segments 2 and 3.
O’Leary, Physiologic Basis of Surgery, 2nd
Ed., pp 441-3
Sabiston, 25th
Ed., pg 1048
35

Best Test of Hepatic Biosynthesis
The liver is responsible for many biologic functions including bile formation, the reprocessing of
biliary salts through the enterohepatic circulation, and the breakdown and metabolism of
hemoglobin to bilirubin. Other major metabolic functions of the liver have to do with
carbohydrate, lipid, and protein metabolism.
Protein synthesis is the most common measure used to determine hepatic synthesis. At least 17
of the major human proteins are synthesized and secreted by the liver. Although albumin is the
most abundant serum protein (it accounts for up to 15% of total hepatic synthesis) the half-life of
albumin (45 days) limits its ability to determine active hepatic synthesis of protein. Transferrin
is a protein commonly used to assess hepatic synthesis. The half-life of this protein is 4 to 5
days, thus a positive anabolic state can be determined by a rise in the serum transferrin levels.
Other proteins that are markers of hepatic biosynthesis include the coagulation proteins. Of
these factors, 7 has the shortest half-live of 5 to 7 hours and because it is a Vitamin K dependent
protein, absence of Vitamin K or blockage of the γ-carboxylation by Coumadin can be assessed
by monitoring the prothrombin. This test is dependent upon adequate amounts of functional
Factor 7.
Although the liver synthesizes hepatic glycogen after eating and is responsible for burning lactic
acid to pyruvate which is subsequently converted back to glucose, these synthetic functions are
difficult to monitor. Likewise, lipid metabolism which generates triglycerides from fatty acids,
ketones (acetoacetate), lipoproteins, and cholesterol are synthesized by the liver but difficult to
monitor.
Acute phase proteins produced by the liver in response to a systemic inflammatory state initiate a
sudden transient rise in C reactive protein compliment and coagulation proteins. Albumin
synthesis is decreased.
Sabiston, 15th
36

Hepatic Acute Phase Response
During any inflammatory process (chemical or physical, tissue injury, bacterial or viral or
parasitic infection or neoplastic growth), the liver produces the acute-phase proteins (C3,
fibrinogen, ceruloplasmin, and other globulins) while albumin synthesis is decreased. (See
Table) The role of these proteins is to promote host defense against tissue damage and infection
(e.g. C3 and C-reactive protein opsonize bacteria, parasites, foreign particles, and immune
complexes and facilitate their clearance by phagocytic cells); to promote clotting mechanisms
and wound healing; to provide transport shuttles for nutrients and metabolites; to function as
radical scavengers; and to enhance biotransformation reactions.
This acute phase response is primarily mediated by hormone, autocrine, and paracrine
messengers (tumor necrosis factor-α
, interleukin -1, interleukin -6, and interferon) produced by
activated macrophages, monocytes, fibroblasts, and endothelial cells and hormones such as
cortisol.
The amino acids used for protein synthesis are either dietary or the products of degradation of
endogenous proteins from other body compartments, such as muscle, or from hepatocytes
themselves when inadequate nutrients are present. The amino acids are cleared by the
hepatocytes through energy-dependent transport systems and are used as energy sources and for
protein synthesis. Liver protein synthesis is also sensitive to exogenous amino acids and can be
enhanced by their administration.
Functions of Acute-Phase Proteins during the Inflammatory Response
Acute-Phase Protein Response
Major Increase in Production Leukocyte Migration
Complement
C-reactive protein Opsonization
α2 – Macroglobulin Antiproteinase, cytokine transport
Cysteine proteinase inhibitor Antiproteinase
α1 – Acid glycoprotein Transport, such as drugs
Some Increase in Production
Haptoglobin Hemoglobin binding, particularly iron
Ceruloplasmin Oxygen radical scavenger, transport
Fibrinogen Coagulation
Hemopexin Hemoglobin binding, particularly iron
α1 – Proteinase inhibitor Antiproteinase
Decrease in Production
Albumin Transport
Transferrin Transport
Weigelt and Lewis, Surgical Critical Care, 1996, pp 411-412
37

Venous Tributaries of the Portal System
Numerous tributaries of the portal vein connect outside the liver with the systemic venous
system. With portal hypertension, these rudimentary communicating systems develop into large
collateral veins. These collateral systems are
1. Submucosal veins of the stomach and esophagus carry venous blood to the coronary vein and
then to the azygous vein and SVC
2. Umbilical and periumbilical veins are recanalized from the obliterated umbilical vein, which
forms the ligamentum teres of the liver.
3. Branches of the inferior mesenteric veins drain to the superior hemorrhoidal veins
4. Retroperitoneal veins drain via the adrenal and renal veins
Edition, p 1001
38

Susceptibility to Hepatoma (Hepatocellular Carcinoma)
Hepatocellular carcinoma (HCC) is the most prevalent malignant disease in the world, and the
incidence of this tumor has doubled in the United States since the early 1980s.
Cirrhosis of the liver plays an important role in the development of HCC in any part of the
world. Hepatitis B is strongly associated with HCC. Alcoholic cirrhosis ingestion of aflatoxin
and chronic Hepatitis C are well-documented risks for HCC. Other risk factors include Wilson’s
disease, tyrosinemia, and glycogen storage disease. Oral contraceptives, androgens, thorotrast,
parasites, and vinyl chloride have been implicated as risk factors.
The role of Hepatitis C in the etiology of HCC is largely due to the development of cirrhosis,
which is common in chronic Hepatitis C. Hepatitis C also acts in synergy with Hepatitis B in the
development of HCC.
Edition, pp 1020-1
39

Principles Associated with Chemo Embolization of Liver Metastases
Most liver metastases are not amenable to surgical excision. Systemic chemotherapy or hepatic
arterial chemotherapy is the most common intervention for patients with non-resectable hepatic
metastases.
Hepatic artery embolization and chemo embolization have therapeutic advantages in that tumor
metastases to the liver derive their metabolic survival from the hepatic artery and its branches.
The challenge is to selectively identify and embolize the feeding artery, thereby eliminating
widespread destruction of hepatic tissue.
Ablative techniques are generally considered in patients who cannot undergo complete removal
of their lesions because of anatomic location, which might require extensive removal of normal
liver. Ablative techniques include cryoablation or radio frequency ablation. These procedures
are conducted at laparotomy with ultrasound guidance.
Schwartz, 7th
Edition, p 353
Current Surgical Therapy, 7th
Edition, p 333
40

Location of Anomalous Hepatic Arteries
Anomalous arterial blood supply to the liver may be the source of hepatic failure in that these
vessels are located in abnormal locations and may be inadvertently ligated. Anomalous hepatic
arteries are characterized by the following terms:
Accessory – These vessels are additional blood supply to the liver segments and may be ligated
without risk of liver injury.
Replacement Arteries – These vessels are anomalous in origin and are the total arterial blood
supply to the liver segments which they supply.
Anomalous Blood Supply to the Liver
Common Hepatic Artery – Arises from the celiac trunk in 90% of the cases; however, the
common hepatic artery may arise from the superior mesenteric artery, or the aorta. Most
commonly the superior mesenteric artery is the origin of an anomalous blood supply.
Right Hepatic Artery – The right hepatic artery may arise from the superior mesenteric artery
in as many as 26% of individuals. Approximately 80% of aberrant right hepatic arteries are
“replacing arteries,” and thus are the sole arterial blood supply to the right lobe of the liver. The
aberrant vessel commonly runs an anomalous course and passes behind the common duct, and
even behind the portal vein, and may be closely related to the posterior lateral aspects of the
common duct. Thus, in performing a “Whipple procedure,” an “aberrant replacing” right hepatic
artery might easily be ligated with resultant liver injury.
Left Hepatic Artery – The left hepatic artery receives two or more main arteries in up to 35% of
the cases. In the majority of these individuals, these are accessory vessels, and arise from the
branches of the celiac trunk, left gastric artery, splenic artery, superior mesentery artery, proper
hepatic artery, or aorta.
Hollingshead, Anatomy for Surgeons, 2nd
Edition, pp 348-352
41

Anatomy of Aberrant Right Hepatic Artery
The arterial supply to the liver is quite variable. In 55% of individuals, the common hepatic
artery arises from the celiac trunk; gives off three branches; gastroduodenal, right gastric,
supraduodenal; then continues as the proper hepatic artery. This artery then branches: first the
cystic artery, then a trifurcation into right, middle and left hepatic arteries.
In 11% of individuals the right hepatic artery arises from near the base of the superior mesenteric
artery and travels through or posterior to the head of the pancreas.
In 10% the left hepatic artery arises from the left gastric artery. In 8% there is an accessory left
hepatic artery in addition to the more common left hepatic artery. In 7% there is an accessory
right hepatic artery.
Variations in arterial anatomy are important in hepatic, biliary, pancreatic and gastric procedures
in which this vasculature is at risk of damage or insufficiency. As an example, the right hepatic
artery may lie anterior to the hepatic duct and be confused with the cystic artery during
cholecystectomy.
Greenfield, 2nd
Edition
42

Prognostic Test of Liver Function Reserve
Routine liver function tests, i.e. transaminases, bilirubin, alkaline phosphatase are used to detect
and monitor liver disease. Albumin and transferring are useful clinical markers of synthetic
function. Quantitative assessments of liver reserve are Bromsulphalein and Indocyanine Green.
They are the measure of liver excretion as these agents are removed from circulation by the liver.
These tests are more specific quantitative tests than any of the routine tests of liver function.
Other quantitative tests include galactose elimination, lidocaine metabolic formation (MEGX
test), and prothrombin time or a ratio of Factor VIII to V.
Edition, pp 1010-12
43

Preoperative Treatment of Obstructive Jaundice
Obstructive jaundice causes many physiologic abnormalities, which increase the risk of surgery.
Altered cell mediated immunity, coagulation disorders, impaired protein synthesis, and wound
healing are but a few of the changes associated with obstructive jaundice. Preoperative biliary
drainage has been used to improve liver function prior to surgery, and thus reduces the operative
risk. Endoscopic sphincterotomy and extraction of common duct stones is now commonly used
as definitive treatment pre-op. Placement of endoscopic stents or catheters via endoscopy or
percutaneous transhepatic route is also used.
Recent studies have identified higher risk of infectious complications and morbidity and
mortality when preoperative biliary drainage is routinely used. However, this therapy may be
used successfully in selected patients with advanced malnutrition or biliary sepsis.
Edition, p 1082
44

Etiology of a Sudden Increase in End Tidal CO2 After Evacuating CO2 in a Laparoscopic
Cholecystectomy Procedure
CO2 is the preferred agent for most laparoscopic procedures because it is readily available,
inexpensive, readily absorbed, and will suppress combustion. The high diffusion coefficient of
CO2 may also lessen the severity of any gas emboli introduced into the vascular system. Its rapid
clearance from the blood stream results in an extremely fast rate of excretion from the body.
This rapid diffusion property of CO2 allows it to be readily absorbed across the peritoneum,
which may result in a rise in PCO2, which is readily eliminated through the lungs. An increased
ventilatory rate is usually sufficient to compensate for this elevated PCO2 in exhaled air.
The combination of residual CO2 being absorbed within the peritoneal cavity, extubation of the
patient who may be sedated and have diminished respiratory drive, could lead to an elevated end
tidal CO2 in the post cholecystectomy patient.
CO2 embolism resulting from residual intra-peritoneal CO2 entering open (torn or lacerated)
large veins must be considered. The high diffusion coefficient results in rapid clearing from the
pulmonary venous system.
Zucker, Surgical Laparoscopy, pp 313-14
45

Findings Associated with the Hepatorenal Syndrome
Biliary disease and major biliary reconstruction are associated with a form of renal failure termed
the hepatorenal syndrome. The acute renal failure associated with jaundice and liver disease
initially presents as prerenal, but persists despite volume expansion. Some patients progress to
severe renal failure, while others respond to improved liver function.
The mechanism of the hepatorenal syndrome is unclear, although it is likely that elevated
bilirubin and bile acids make the kidney more susceptible to ischemia and hypoperfusion.
Sabistion, Textbook of Surgery, 16th
Edition, p 212
46

Anatomy of Common Bile Duct
The common bile duct is approximately 8-9 cm long and begins at the junction of the common
hepatic duct and the cystic duct. It lies within the hepatoduodenal ligament, to the right of the
hepatic artery and anterior to the portal vein. The distal segment is in intimate contact with the
duodenum, passing behind the second portion of the duodenum through a groove on the surface
of the pancreas. Usually, the distal common bile duct lies within the pancreas. This
intrapancreatic portion usually joins the pancreatic duct (Wurshung), and empties into the
duodenum at the papilla of Vater. This structure surrounds the orifice, and is composed of the
muscular elements that make up the sphincter of Oddi. The common bile duct’s blood supply is
composed of a rich arterial plexus derived primarily from the retroduodenal or posterior superior
pancreaticoduodenal artery. Considerable variation is possible.
Edition, p 1368
Anson and McVay, Surgical Anatomy, 6th
Edition, pp 649-56
Netter, Atlas of Human Anatomy Plates, pp 276-78
47

Characteristics Hepatocytes
The hepatocytes perform the major metabolic and excretory functions of the liver. They are
arranged in cords or plates of one cell thickness and are surrounded by the sinusoids. The
function of any individual hepatocyte depends upon the position of the cell within the lobule and
the proximity of the cell to the blood supply. Hepatocytes can be divided into three zones. Zone
1 hepatocytes lie in closest proximity to the periportal region and contain the highest
concentration of enzymes involved in glycogenesis. They also produce the majority of proteins
and are responsible for protein metabolism. Cells in Zone 3, an area with decreased oxygen
tension, are equipped for glycolysis and lipogenesis. Ureagenesis occurs in Zones 2 and 3. The
enzymes responsible for gluconeogenesis are much more abundant in the periportal area.
Hepatocytes replicate rapidly, and it is estimated that the entire cell mass of the liver could be
replaced every 50 days. This accounts for the rapid growth of the hepatic remnant after major
liver resections.
Simmons & Steed, Basic Science Review for Surgeons, 1992, pp 247-8
48

Bile Acid Synthesis
The enterohepatic circulation is a cyclic process in which bile salts are secreted into the intestine,
effectively absorbed in the ilium, and reabsorbed in the liver from portal blood. Secretion into
the intestine is mediated by cholecystokinin, which is released from endocrine cells in the
duodenum in response to peptide, amino acids, and lipid. The major bile acids are cholic and
chenodeoxycholic acieds, which are synthesized in the liver from cholesterol. The secondary
bile acids, deoxycholic and lithocholic acids, are formed by anaerobic bacteria in the intestine
and are eventually involved in the entero-hepatic circulation. All bile acids secreted by the liver
are conjugated with glycine or taurine.
Reabsorption of the bile acids in the distal small bowel occurs by passive absorption and active
absorption as a sodium dependent process. The bile salt pool is approximately 2 grams and is
recycled 5 to 6 times a day. With ileal resection or dysfunction, the amount of bile salts reaching
the colon is increased with a result in diarrhea. Furthermore, the liver is unable to compensate
for the fecal losses of bile salts, thus leading to steatorrhea, which amplifies the bile salt
deficiencies needed for fat absorption.
Edition, pp 428-29
49

Characteristics of Chylomicrons
Chylomicrons consist of an inner core containing 90% triglycerides, a lesser amount cholesterol,
cholesterol esters, and fat-soluble vitamins. The outer layer consists of 80-90% phospholipid
and specialized apolipoproteins. The apolipoproteins, while accounting for only 1% of the mass,
are essential for fat absorption. The intestinal mucosal cells synthesize Apolipoprotein A and B,
and they are added before the chylomicrons enter the golgi apparatus. A congenital disorder,
abetaliproproteinemia, leads to triglyceride accumulation within the endoplasmic reticulum and
leads to the inability to digest fat.
Reformed triglycerides within the golgi apparatus of intestinal enterocytes are transported out of
the cell across the basolateral membrane as chylomicrons, which enter the central lacteal of the
villus. From the lacteals, chylomicrons pass via larger lymphatic channels, draining from
intestine to thoracic duct, eventually into the left subclavian vein. Because of their size,
chylomicrons cannot cross intercellular junctions of the intestinal capillaries and are, therefore,
excluded from the portal blood.
O’Leary, 2nd
Edition, pp 427-28
50

Biliary Tract Bacteria
The role of bacteria in the pathogenesis of acute cholecystitis is not clear; positive cultures of
bile or gallbladder wall are found in 50 to 75% of patients.
Patients suspected of having acute cholecystitis should receive empiric antibiotic coverage
against those organisms found in the bile of approximately 80% of patients. These organisms
include both Gram-positive and Gram-negative aerobes and anaerobes. Those present most
frequently are E. coli, Klebsiella aerogenes, Streptococcus faecalis, Clostridium welchii, Proteus
species, Enterobacter species and anaerobic Streptococci. A single organism is found in
approximately 40% of cases, two species in about 30%, three in 20%, and four or more in the
remainder.
Edition, pp 1126-29
51

Preoperative Measure of Portal Venous Pressure
The normal pressure in the portal vein is between 3 and 5mmHg. Pressures above 5 to 8mmHg
stimulate portosystemic collateralization.
In patients with cirrhosis and possible portal hypotension, a hepatic venous wedge pressure will
reflect the portal pressure. If prehepatic portal hypertension is suspected, direct measurement of
the portal system is required by umbilical venous cannulation or percutaneous puncture of the
spleen.
Edition, pp 1061-3
Edition, p 1141
52

Best Test of Hepatic Biosynthesis
The liver is responsible for many biologic functions including bile formation, the reprocessing of
biliary salts through the enterohepatic circulation, and the breakdown and metabolism of
hemoglobin to bilirubin. Other major metabolic functions of the liver have to do with
carbohydrate, lipid, and protein metabolism.
Protein synthesis is the most common measure used to determine hepatic synthesis. At least 17
of the major human proteins are synthesized and secreted by the liver. Although albumin is the
most abundant serum protein (it accounts for up to 15% of total hepatic synthesis) the half-life of
albumin (45 days) limits its ability to determine active hepatic synthesis of protein. Transferrin
is a protein commonly used to assess hepatic synthesis. The half-life of this protein is 4 to 5
days, thus a positive anabolic state can be determined by a rise in the serum transferrin levels.
Other proteins that are markers of hepatic biosynthesis include the coagulation proteins. Of
these factors, 7 has the shortest half-life of 5 to 7 hours and because it is a Vitamin K dependent
protein, absence of Vitamin K or blockage of the γ-carboxylation by Coumadin can be assessed
by monitoring the prothrombin. This test is dependent upon adequate amounts of functional
Factor 7.
Although the liver synthesizes hepatic glycogen after eating and is responsible for burning lactic
acid to pyruvate which is subsequently converted back to glucose, these synthetic functions are
difficult to monitor. Likewise, lipid metabolism which generates triglycerides from fatty acids,
ketones (acetoacetate), lipoproteins, and cholesterol are synthesized by the liver but difficult to
monitor.
Acute phase proteins produced by the liver in response to a systemic inflammatory state initiate a
sudden intransient rise in C reactive protein compliment and coagulation proteins. Albumin
synthesis is decreased.
Sabiston, 15th
53

Abnormal Liver Function Test in Metastatic Colon Cancer
The Lactic Dehydrogenase Study is reported to have the highest sensitivity (85%) of all standard
liver function tests for the presence of hepatic metastases. However, it also has the highest false
positive rate (about 50%). Other blood tests that can reflect the presence of metastases include
GGT levels, 5´ –necleotidase and alanine transaminase.
The CEA, a tumor marker, can also be useful in detecting metastatic colon cancer. However, an
elevated CEA can occur with other malignancies and benign conditions.
The screening protocol for determining liver metastases in colon cancer recommends a single
liver imaging study, plus selected blood tests.
Edition, pp 1029-30
54

Hepatocellular Cancer in Chronic Hepatitis B (Complications Hepatitis B)
Evidence of a causal relationship between chronic Hepatitis B and the development of
Hepatocellular carcinoma is compelling. Studies from Africa and Asia suggest that Hepatitis B
virus is present in 70 – 80% of individuals with Hepatocellular carcinoma. The risk of
developing Hepatocellular carcinoma in Hepatitis B virus carriers is 10%. In a 5-year study of
Hepatitis B antigen positive patients, the risk of developing hepatocellular carcinoma was
increased by 1000 fold.
The role of Hepatitis C virus in the development of Hepatocellular carcinoma is less clear.
Hepatitis B & C virus act as independent risk factors but may act synergistically. Japanese
studies have identified Hepatitis C virus in 51 % of patients with Hepatocellular carcinoma.
Sabiston, 15th
Edition, pg 1070
55

Pathophysiology of Ascites in Alcohol Cirrhosis
A number of theories persist; however, certain factors are known which are responsible for the
development of Ascites.
Abnormal Renal Function
Shunting of renal blood flow to the medullary nephrons with decreased glomerular filtration
leads to renin release and elevated aldosterone levels. Water and sodium retention occurs.
Abnormal Liver Function
Abnormal liver function causes hypoalbuminemia and reduced rates in the metabolism of
circulating aldosterone leading to hyperaldosteronism.
Reduced Portal Blood Flow
Reduced portal blood flow occurs due to fibronodular changes in the liver. The increased
hydrostatic pressure promotes transfer of intravascular fluid into the interstitial space which
results in weeping of lymphatic fluid from the liver, bowel, and mesentery.
Ascites Formation
Ascites formation is thus the result of sodium and water retention, hyperaldosteronism,
hypoalbuminemia and portal obstruction.
Greenfield, pp 986-987
56

Basis for Chemoemboliztion of Hepatic Metastases
The term chemoembolization describes a variety of techniques used to embolize the arterial
supply to a tumor and simultaneously infuse chemotherapeutic agents. In theory, the
combination of embolization and chemotherapy should increase the local concentration and time
of exposure of the drug to the malignancy while decreasing systemic exposure and toxicity. The
arterial supply can be occluded by gelfoam particles, stainless steel coils or starch microspheres.
Only the steel coils permanently occlude while the others are temporary. The chemotherapeutic
agent can be bound to the occluding agent or administered separately. To date, no randomized,
prospective trials have been performed to test the survival advantage of this technique. Thus, it
remains an experimental procedure.
Harvey JC, Beattie EJ. Cancer Surgery, 1996, pp. 106-107
57

58
Etiology of Liver Failure/Diagnosis of Ligation of Hepatic Artery (Unintended Hepatic
Artery Ligation at Operation)
Liver failure without evidence of sepsis occurring in the post operative period following a
major resection of the pancreas, difficult common duct operation, or extended gastrectomy for
cancer, should suggest ligation of the hepatic artery. Anomalous blood supply to the liver is well
known. However, at operation these aberrant vessels may not be recognized and thus
inadvertently ligated.
The proper hepatic artery is an “end vessel” in which there is little collateral blood supply
other than through portal venous circulation. Ligating the common hepatic artery near the celiac
axis allows for collateral circulation to the proper hepatic artery through gastroduodenal vessels.
Similarly, ligation of the common hepatic artery between gastroduodenal and the right gastric
arteries can allow collateral circulation to the proper hepatic arteries via the right gastric artery.
However, ligation above this point, i.e. the “proper hepatic artery,” deprives the liver of all
arterial blood, save the small amounts occurring through variable small anastomoses from the
phrenic arteries.
Anomalous arterial blood supply to the liver may be the source of hepatic failure in that these
vessels are located in abnormal locations and may be inadvertently ligated. Anomalous hepatic
arteries are characterized by the following terms:
Accessory – These vessels are additional blood supply to the liver segments and may be ligated
without risk of liver injury.
Replacement Arteries – These vessels are anomalous in origin and are the total arterial blood
supply to the liver segments which they supply.
Anomalous Blood Supply to the Liver
Common Hepatic Artery – Arises from the celiac trunk in 90% of the cases; however, the
common hepatic artery may arise from the superior mesenteric artery, or the aorta. Most
commonly the superior mesenteric artery is the origin of an anomalous blood supply.
Right Hepatic Artery – The right hepatic artery may arise from the superior mesenteric artery in
as many as 26% of individuals. Approximately 80% of aberrant right hepatic arteries are
“replacing arteries,” and thus are the sole arterial blood supply to the right lobe of the liver. The
aberrant vessel commonly runs an anomalous course and passes behind the common duct, and
even behind the portal vein, and may be closely related to the posterior lateral aspects of the
common duct. Thus, in performing a “Whipple procedure,” an “aberrant replacing” right hepatic
artery might easily be ligated with resultant liver injury.
Left Hepatic Artery – The left hepatic artery receives two or more main arteries in up to 35% of
the cases. In the majority of these individuals, these are accessory vessels, and arise from the
branches of the celiac trunk, left gastric artery, splenic artery, superior mesentery artery, proper
hepatic artery, or aorta.
Hollingshead, Anatomy for Surgeons, 2nd
Edition, pp 348-352

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