UNIVERSITY OF FLORIDA

DEPARTMENT OF SURGERY

AMERICAN BOARD OF SURGERY IN-SERVICE TRAINING EXAM

(ABSITE)

BASIC SCIENCE 101

By

MATTHEW J. DELANO

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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

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"WEAKNESS OF ATTITUDE BECOMES WEAKNESS OF CHARACTER"

Albert Einstein

“CHANCE FAVORS THE PREPARED MIND"

Louis Pasteur

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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.

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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 4 BODY AS A WHOLE: SESSION 2 5 BODY AS A WHOLE: SESSION 3 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 

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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 

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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 Sun. January 11, 2009 Dr. Kevin Behrns’s Residence Sun. January 18, 2009 Dr. Kevin Behrns’s Residence Sun. January 25, 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

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Course Schedule: Review Session Date: Topics to be covered: Course materials: December 7, 2008 BODY AS A WHOLE Chapter 3 December 14, 2008 BODY AS A WHOLE Chapter 4 December 21, 2008 BODY AS A WHOLE Chapter 5 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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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)

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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 SYSTEMS7.80% 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 10Clinical Medicine 60 45

GASTROINTESTINAL TRACT Basic Science 15 10Clinical Medicine 9 45

CARDIOVASCULAR AND PULMONARY SYSTEMS Basic Science 11 8Clinical Medicine 6 30

GU, HEAD AND NECK, SKIN, MUSCULOSKELETAL, AND NERVOUS SYSTEMS

Basic Science 11 8

Clinical Medicine 6 30ENDOCRINE, HEMATOLOGIC, AND LYMPHATIC

SYSTEMS , AND BREASTBasic Science 11 8

Clinical Medicine 6 30

Adapted from the American Board of Surgery: http://home.absurgery.org/

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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 Clinical Management 9 CARDIOVASCULAR AND RESPIRATORY:

Basic Science 25 Clinical Management 7 GU, HEAD AND NECK, SKIN, MUSCULOSKELETAL, NERVOUS, SYSTEMS:

Basic Science 11 Clinical Management 7 ENDOCRINE, HEMATIC, LYMPHATIC, BREAST

Basic Science 14 Clinical Management 7

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

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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

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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

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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

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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. Schwartz, Principles of Surgery, 6th Edition O’Leary, Physiologic Basis of Surgery, 2nd Edition Sabiston, Textbook of Surgery, 15th Edition, p 1196

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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

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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. Sabiston, Textbook of Surgery, 16th Edition, pp 1146, 1162

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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. Schwartz, Principles of Surgery, 8th Edition, p 1304

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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

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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

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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

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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

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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. Schwartz, Principles of Surgery, 7th Edition, p. 1470 Physiologic Basis of Surgery, 2nd Edition, pp 452-453

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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. Schwartz, Principles of Surgery, 6th 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. Sabiston, Textbook of Surgery, 16th 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). Physiologic Basis of Surgery, 2nd Edition, pp 428-429 Sabiston, Textbook of Surgery, 16th 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. Sabiston, Textbook of Surgery, 16th 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. Sabiston, Textbook of Surgery, 16th 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 99TC-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%. Sabiston, Textbook of Surgery, 16th 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 Edition, pp 1055-1060

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 Sabiston, Textbook of Surgery, 16th 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. Sabiston, Textbook of Surgery, 16th 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. Sabiston, Textbook of Surgery, 16th 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. Sabiston, Textbook of Surgery, 16th 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. Schwartz, Principles of Surgery, 6th 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. Physiologic Basis of Surgery, 2nd 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. Sabiston, Textbook of Surgery, 15th 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. Sabiston, Textbook of Surgery, 16th Edition, pp 1061-3 Schwartz, Principles of Surgery, 8th 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 Edition, pp 1055-1060

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. Sabiston, Textbook of Surgery, 16th 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