Ebook General surgery prepare for the MRCS key articles from the surgery journal Part 1

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General Surgery: 
Prepare for the MRCS 
Key articles from the Surgery Journal 
 

 
Series Editor 
W E G Thomas MS FRCS FSACS(Hon) 
Consultant Surgeon, Honorary Senior Lecturer, Sheffield University; Member of Council and 
past Vice President of the Royal College of Surgeons of England 
 
Clinical Editor 
Michael G Wyatt MSc MD FRCS FRCSEd (ad hom) 
Consultant Surgeon, Freeman Hospital, Newcastle‐upon‐Tyne; Honorary Reader, Newcastle 
University; Clinical Editor, SURGERY; Honorary Secretary, The Vascular Society of Great 
Britain and Ireland; Member of the Court of Examiners for the Intercollegiate MRCS 
 
 
 
 
 

 
Edinburgh   London   New York   Oxford   Philadelphia   St Louis   Sydney   Toronto 2015 


 
 
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This book and the individual contributions contained in it are protected under copyright by the 
publisher (other than as may be noted herein). 
First edition 2015 
First published in Surgery: 2012‐2014 
ISBN978‐0‐7020‐6802‐7 
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A catalogue record for this book is available from the British Library 
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Notices 
Knowledge and best practice in this field are constantly changing. As new research and experience broaden 
our understanding, changes in research methods, professional practices, or medical treatment may become 
necessary. 
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using 
any information, methods, compounds, or experiments described herein. In using such information or 
methods they should be mindful of their own safety and the safety of others, including parties for whom they 
have a professional responsibility. 
With respect to any drug or pharmaceutical products identified, readers are advised to check the most current 
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administered, to verify the recommended dose or formula, the method and duration of administration, and 
contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of 
their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, 
and to take all appropriate safety precautions. 

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material herein. 

 

Content Strategist:   Laurence Hunter 
Content Development Specialist:  Kim Benson 
Designer:  Miles Hitchen 


 
Preface 
Surgery has been at the forefront of providing quality articles especially designed for candidates 
sitting the Intercollegiate examinations for over 20 years. Now technology is making these quality 
articles available not only in printed form but also on‐line. However the increasing demand for easy 
access to quality information, has prompted the preparation of a series of ‘e‐books’ based on 
surgical specialisation bringing together articles written by experienced authorities on each topic as 
published in Surgery. The journal Surgery covers the whole of the surgical syllabus as represented by 
the Intercollegiate Surgical Curriculum. Each topic is covered in an up‐to‐date article by an 
acknowledged authority on the subject every three years, thus ensuring contemporaneous coverage 
of the core curriculum. These collections of articles for each surgical specialty are not only ideal for 
revision for the Intercollegiate examinations, but will also be invaluable for the specialist registrar in 
each surgical specialty. We warmly welcome this innovative approach and trust that this collection 
of ‘e‐books’ will significantly enhance the learning experience of all surgical trainees and also provide 
a useful update for all seeking to keep abreast with the latest advances in their particular branch of 

surgery. 
 
WEGT 
MGW 
Sheffield and Newcastle 
2015 
 

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About The Surgery Journal 
Surgery is a continually updated, evidence‐based, learning resource for trainees. Based entirely on 
the Intercollegiate Surgical Curriculum, Surgery gives you high‐calibre and concise articles designed 
to help you pass the MRCS exams. Surgery also provides consultant surgeons with a clear didactic 
framework to help train residents and junior staff. 
Each issue of Surgeryis themed and contains both basic scientific and clinical sections. The basic 
science articles cover anatomy, physiology and pathology while the clinical sections cover all of the 
skills across all of the topics required for and tested in the MRCS exams. The authors are all 
recognized specialists and Surgery is curated by a highly qualified team of Editors. 
This ebook brings together a comprehensive collection of all the articles on general surgery. Over 
100articles in total create a comprehensive compendium of surgical knowledge that will be a perfect 
resource for anyone preparing for the MRCS. Also included are MCQ and extended matching 
questions to test your understanding of the contents of this ebook. 
If after reading this ebook you would like to subscribe to Surgery please go to 
www.surgeryjournal.co.uk.  
 
 

 
Issue Editors forGeneral Surgery 
 
Sean Carrie MB ChB FRCS (ORL) 
Consultant Ear, Nose & Throat Surgeon, Freeman Hospital, Newcastle upon Tyne, UK 
 
Umesh Khot MBBS, MS, FRCS (England), FRCS (Gen) 
Consultant General and Colorectal Surgeon, Singleton and Morrison Hospitals, Swansea, UK 
 
Peter Lamb MBBS MD FRCS 
Consultant Upper Gastrointestinal Surgeon, Royal Infirmary, Edinburgh, UK 
 
Anthony Lander FRCS (Paed) 
Consultant Paediatric Surgeon, Birmingham Children’s Hospital, Birmingham, UK 
 
Soroush Sohrabi MD, PHD, MRCS 
Specialist Registrar in Vascular Surgery, Hull Royal Infirmary, Hull, UK 
 
Helen M Sweetland MD FRCS (Ed) 
Reader in Surgery and Honorary Consultant Surgeon, Cardiff and Vale University LHB,Cardiff, UK 
 
W E G Thomas MS FRCS FSACS(Hon) 
Consultant Surgeon, Honorary Senior Lecturer, Sheffield University; Member of Council and Past 
Vice President of the Royal College of Surgeons of England, UK 
 
Peter Vowden MS FRCS 
Consultant Vascular Surgeon, Bradford Teaching Hospitals NHS Foundation Trust; Visiting Professor 
of Wound Healing Research, University of Bradford, Bradford, UK 

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Surgery is an authoritative, comprehensive collection of educational reviews that present the current knowledge and practice of
surgery. Surgery also indicates recent advances that improve the understanding of disease and the safe and effective treatment of
patients. It comprises concise and systematically updated contributions that are produced over a three-year cycle. Surgery is an
excellent didactic tool to help consultant surgeons train their junior staff to become safe and competent surgeons.

Series editor

W E G Thomas MS FRCS FSACS(Hon) Consultant Surgeon, Honorary Senior Lecturer, Sheffield University, Member of Council and
past Vice President of the Royal College of Surgeons of England

Clinical editor

Michael G Wyatt MSc MD FRCS FRCSEd (ad hom) Consultant Surgeon, Freeman Hospital, Newcastle upon Tyne; Honorary Reader, Newcastle
University; Clinical Editor, SURGERY; Honorary Secretary, The Vascular Society of Great Britain and Ireland, and Member of the Court
of Examiners for the Intercollegiate MRCS.

Editorial adviser
Harold Ellis CBE DM FRCS FRCOG
Emeritus Professor of Surgery, London University
Clinical Anatomist, Guy’s, King’s and St Thomas’s
School of Biomedical Science, London, UK

Editorial Board

Mary Murphy MB BCh, BAO, FRCS (SN)
Consultant Neurosurgeon
Royal Free Hospital, London, UK
Ian Nesbitt MBBS FRCA DICM(UK)
Consultant in Anaesthesia and Critical Care
Freeman Hospital, Newcastle-upon-Tyne, UK

Andreas Adam FRCP FRCR FRCS
Professor of Interventional Radiology
King’s College London, UK

Joseph Shalhoub BSc MBBS MRCS (Eng) FHEA PhD
Specialty Registrar in General Surgery, London Deanery
and Joint Vice President, Association of Surgeons in Training

Jon Anderson FRCS(CTh)
Consultant Cardiothoracic Surgeon
Hammersmith Hospital NHS Trust, London, UK

Frank CT Smith BSc MD FRCS
Consultant Senior Lecturer in Surgery
Bristol Royal Infirmary, Bristol, UK

Emily Jane Baird MBChB MRCS (Glasgow)
Trauma and Orthopaedic Specialty Registrar,
West of Scotland Rotation; and President of
the British Orthopaedic Trainees Association

Helen Sweetland MD FRCS(Ed)
Reader in Surgery and Honorary Consultant Surgeon

Cardiff and Vale NHS Trust, UK

Frank Carey FRCPath
Professor and Consultant Histopathologist
Ninewells Hospital, Dundee, UK
Christopher R Chapple MD FRCS(Urol) FEBU
Visiting Professor, Sheffield Hallam University
Consultant Urological Surgeon,
Royal Hallamshire Hospital, UK
Ben Cresswell MBChB FRCS(Gen Surg)
Consultant Hepatopancreatobiliary Surgeon
The Basingstoke Hepatobiliary Unit
North Hampshire Hospital, UK
Michael J Kelly MChir FRCS MRCP(UK)
Consultant Colorectal Surgeon, Leicester, UK and National
Advisor Colorectal Cancer, NHS Improvement. Court of
Examiners RCSEng.

William Wallace MBChB(Hon) PhD FRCPE FRCPath
Consultant Pathologist and Honorary Senior Lecturer
Royal Infirmary of Edinburgh, UK
Robert Wilkins MA DPhil (Oxon)
Lecturer in Physiology
Department of Physiology, Anatomy & Genetics
St Edmund Hall, University of Oxford, UK
Mark Wilkinson PhD FRCS(Orth)
Senior Lecturer in Orthopaedics
University of Sheffield, UK
Consultant Orthopaedic Surgeon
Northern General Hospital, Sheffield, UK

Surgical and Clinical Anatomy for the MRCS exam

Peter Lamb MBBS FRCS(Eng) MD FRCS(Gen)
Consultant Upper GI and General Surgeon
Royal Infirmary of Edinburgh, UK

Series editors

Anthony Lander PhD DCH FRCS(Paed)
Senior Lecturer in Paediatric Surgery and Consultant
Paediatric Surgeon, Birmingham Children’s Hospital, UK

This series is available only on the website:
www.surgeryjournal.co.uk

Harold Ellis CBE DM MCh FRCS FRCOG London
Vishy Mahadevan MB BS PhD FRCS London

Founder editors
John S P Lumley MS FRCS London
John L Craven MD FRCS York

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Abdominal Surgery

Volume 30:6 June 2012

A great revision guide for the MRCS and beyond

290

Anatomy of the anterior abdominal wall
and groin
Vishy Mahadevan

257

Adult groin hernias
Terry Irwin
Alison McCoubrey

296

Secretory functions of the gastrointestinal
tract
Henrik Isackson
Christopher C Ashley

261

Investigation of the acute abdomen
Janette K Smith
Dileep N Lobo

306

Physiology of malabsorption
Jonathan D Nolan

Ian M Johnston
Julian RF Walters

268

Investigation of abdominal masses
Quat Ullah
Richard A Nakielny
Gynaecological causes of abdominal pain
Shehnaaz Jivraj
Andrew Farkas

310

BASIC SCIENCE

ABDOMINAL SURGERY

TEST YOURSELF

Abdominal access techniques (including
laparoscopic access)
Cara Baker
Ralph Smith
Sukhpal Singh

275

Wound dehiscence and incisional hernia
Nicholas J Slater

Robert P Bleichrodt
Harry van Goor

282

MCQs

315

Based entirely on the
Intercollegiate Surgical Curriculum
Issue Editor
W E G Thomas ms frcs fsacs(hon)
Consultant Surgeon, Honorary Senior Lecturer,
Sheffield University, Member of Council and Past Vice
President of the Royal College of Surgeons of England.

www.surgeryjournal.co.uk
ONLINE, IN PRINT, IN PRACTICE

© 2012 Elsevier Ltd

ISSN 0263-9319


BASIC SCIENCE

Anatomy of the anterior
abdominal wall and groin

The superficial fascia: comprises two distinct layers.
 An outer, adipose layer immediately subjacent to the
dermis and similar to superficial fascia elsewhere in the
body. This layer is also sometimes referred to as Camper’s
fascia.
 An inner fibroelastic layer termed Scarpa’s fascia (the
membranous layer of superficial fascia). Scarpa’s fascia is
more prominent and better defined in the lower half of the
anterior abdominal wall. Also, it is more prominent in
children (particularly infants) than in adults.
Superiorly, Scarpa’s fascia crosses superficial to the costal margin
and becomes continuous with the retromammary fascia. Laterally it fades out at the mid-axillary line. Inferiorly, it crosses
superficial to the inguinal ligament and blends with the deep
fascia of the thigh about 1 cm distal to the inguinal ligament.
Below the level of the pubic symphysis, in the male, Scarpa’s
fascia is prolonged quite distinctly into the scrotum and around
the penile shaft. This prolongation of Scarpa’s fascia into the
perineum is known as the superficial perineal fascia or Colles’
fascia. A similar, but less distinct and less readily demonstrable
extension of Scarpa’s fascia occurs in the female perineum. As in
the male this extension is known as superficial perineal fascia.

Vishy Mahadevan

Abstract
This article describes, in a systematic manner, the anatomy of the anterior
abdominal wall, with emphasis being placed on clinical and surgical
aspects. This knowledge should help the reader understand the anatomical basis to various laparotomy incisions. Also described in this article is
the anatomy of the inguinal canal and inguinal herniae and the anatomical distinction between direct and indirect inguinal herniae.

Keywords anterolateral abdominal muscles; inguinal canal; inguinal
herniae; rectus sheath

The outline of the anterior abdominal wall is approximately
hexagonal. It is bounded superiorly by the arched costal margin
(with the xiphisternal junction at the summit of the arch). The
lateral boundary on either side is, arbitrarily, the mid-axillary line
(between the lateral part of the costal margin and the summit of
the iliac crest). Inferiorly, on each side, the anterior abdominal
wall is bounded in continuity, by the anterior half of the iliac crest,
inguinal ligament, pubic crest and pubic symphysis.

Musculo-aponeurotic ‘plane’ (Figures 1 and 2):
The rectus abdominis e is a long, strap-like muscle one on
either side of the vertical midline. Each muscle arises by two
tendons; a lateral tendon from the pubic crest, and a medial
tendon from the upper and anterior surfaces of the pubic
symphysis. The two tendons unite a short distance above the
pubis to give rise to a single muscle belly which runs upwards to
attach to the anterior surfaces of the seventh, sixth and fifth
costal cartilages. The upper part of the muscle usually shows
three transverse tendinous intersections; one at the level of the
umbilicus, one at the level of the xiphoid tip and one halfway
between the two (Figures 1a and 2).
On either side of the rectus abdominis, the musculoaponeurotic plane is made up of a three-ply (overlapping)
arrangement of flat muscular sheets. The outermost of these is the
external oblique muscle, the innermost is the transversus
abdominis muscle and the intermediate layer is the internal oblique muscle. Of these, only the external oblique has an attachment
above the level of the costal margin. Followed anteromedially,
each of these muscles becomes aponeurotic. These aponeuroses,

between them, enclose the rectus abdominis muscle; the envelope
is termed the rectus sheath.
The external oblique muscle e arises by fleshy digitations
from the outer aspect of each of the lower eight ribs near their
costochondral junctions (Figure 2). From this origin the muscle
fibres fan downwards and forwards. The fibres that arise from
the lower two ribs run downwards to insert onto the anterior half
of the outer lip of the iliac crest; the posterior edge of this mass of
fibres constitutes the free posterior border of the muscle. The
remainder of the muscle ends in a broad aponeurosis. The lower
edge of this aponeurosis extends between the anterior superior
iliac spine and the pubic tubercle. It is rolled inwards to form
a narrow and shallow gutter, and constitutes the inguinal ligament. The fascia lata (deep fascia of the thigh) attaches to the
distal surface of the inguinal ligament. The rest of the external
oblique aponeurosis runs in front of the rectus abdominis muscle

Layers of the anterior abdominal wall
The anterior abdominal wall is a many-layered structure (Figure 1).
From the surface inwards, the successive layers are:
 skin
 superficial fascia (comprising two layers)
 a musculo-aponeurotic ‘plane’ (which is architecturally
complex and composed of several laminae).
 transversalis fascia
 a properitoneal adipose layer
 parietal peritoneum.
Skin: the skin covering the anterior abdominal wall is thin
compared with that of the back, and is relatively mobile over the
underlying layers except at the umbilical region, where it is fixed.
Natural elastic traction lines of the skin (also known as skin

tension lines or Kraissl’s lines) of the anterior abdominal wall are
disposed transversely. Above the level of the umbilicus these
tension lines run almost horizontally, while below this level they
run with a slight inferomedial obliquity. Incisions made along, or
parallel to, these lines tend to heal without much scarring,
whereas incisions that cut across these lines tend to result in
wide or heaped-up scars.

Vishy Mahadevan FRCS(Ed) FRCS is the Barbers’ Company Professor of
Surgical Anatomy at the Royal College of Surgeons of England, London,
UK. Conflicts of interest: none declared.

SURGERY 30:6

257

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Ó 2012 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

Rectus abdominis muscle and rectus sheath

Rectus abdominis

Aponeurosis of
external oblique

a

Aponeurosis of
internal oblique

b
Tendinous
intersections

Linea semilunaris

Aponeurosis
of transversus abdominis

Linea alba

Peritoneum

Transverse
abdominis

c
Anterior
superior
iliac spine

Rectus
abdominis

Inguinal ligament

Pubic tubercle

Skin
Superficial
fascia
External oblique
Internal oblique

Peritoneum
Extraperitoneal fat
Transversalis fascia

a Right rectus abdominis after removal of the anterior layer of its sheath. b and c Transverse sections of the anterior abdominal wall showing the
interlacing fibres of the aponeuroses of the right and left oblique and transversus abdominis muscles, above b and below c the arcuate line.
Source: Moore K L. Clinically oriented anatomy. Baltimore: Williams and Wilkins, 1992.

Figure 1

of its side and interdigitates with the contralateral aponeurosis
along the vertical midline. Below the level of the xiphoid process
this interdigitation helps to form a raphe, the linea alba
(Figure 1).
The internal oblique muscle e lies immediately deep to the
external oblique. It arises, in continuity, from the lateral twothirds of the guttered inguinal ligament, from a central strip
along the anterior two-thirds of the iliac crest, and from the

lateral margin of the lumbar fascia along the lateral border of the
quadratus lumborum muscle (a muscle of the posterior abdominal wall). The muscle fibres arising from the lumbar fascia
run upwards to attach along the length of the costal margin.
The remainder of the muscle fibres run upwards and medially

from their origin, becoming aponeurotic lateral to the outer
border of the rectus abdominis. At the outer edge of the latter, the
aponeurosis of the internal oblique splits into two laminae
(anterior and posterior), which run medially, respectively, in
front of, and behind the rectus abdominis muscle, to interdigitate
with their counterparts in the vertical midline, at the linea alba.
The anterior lamina of the internal oblique is thus immediately
deep to the external oblique aponeurosis. The posterior lamina
running behind the rectus abdominis muscle is immediately in
front of the transversus abdominis aponeurosis, down to the
arcuate line (see below: rectus sheath).
Transversus abdominis e arises in continuity from the lateral
half of the guttered surface of the inguinal ligament (immediately
deep to the origin of the internal oblique), from the inner lip of
the anterior two-thirds of the iliac crest, from the lateral margin
of the lumbar fascia and from the inner surfaces of the cartilages
of the lower six ribs. From this origin, the muscle fibres run
forwards and medially, closely applied to the inner surface of the
internal oblique. The fibres become aponeurotic at the lateral
edge of the rectus abdominis, and the aponeurosis continues
medially behind the posterior lamina of the internal oblique
aponeurosis (and therefore behind the rectus abdominis) to meet
its counterpart at the linea alba. A few finger-breadths below the
level of the umbilicus, however, the aponeuroses of all three
muscles run in front of rectus abdominis (see below: rectus
sheath) (Figures 1c and 2).
The linea alba (Figures 1 and 2) e is a longitudinally
disposed, midline interdigitation of the aponeuroses of the threeply muscles (external oblique, internal oblique and transversus
abdominis) of one side with those of the other side. The linea
alba extends from the xiphoid process above, to the pubic

Figure 2 Anterior and anterolateral muscles of the abdominal wall (the
rectus and pyramidalis muscles have been removed on the right side to
reveal the posterior wall of rectus sheath and the epigastric vessels).

SURGERY 30:6

258

Ó 2012 Elsevier Ltd. All rights reserved.


BASIC SCIENCE

symphysis below. Lying between the medial edges of the recti,
the linea alba is a pale band of fibro-aponeurotic tissue, considerably wider and thicker above the level of the umbilicus than
below. In some individuals the linea alba may become weak
through abnormal attenuation and widening, thereby allowing
exaggerated lateral deviation of the two rectus sheaths whenever
intra-abdominal pressure is raised. This condition is termed
divarication of recti.
The rectus sheath (Figure 1b and c) e is the aponeurotic
envelope that ensheathes the rectus abdominis muscle. Thus,
the rectus sheath may be said to possess an anterior wall
and a posterior wall. The anterior wall of the rectus sheath is
composed of two adherent layers; a superficial layer made up of
the external oblique aponeurosis and a deep layer made up of
the anterior lamina of the internal oblique aponeurosis. The
posterior wall of the rectus sheath is, likewise, composed of two
adherent layers. The anterior layer of the posterior wall is the

posterior lamina of the internal oblique aponeurosis, while the
posterior layer is the transversus abdominis aponeurosis. This
arrangement holds true only from the level of the costal margin
down to a level about 5e6 cm below the umbilicus. Below this
level, all three aponeuroses run in front of the rectus abdominis
muscle, with the result that below this level, there is no
aponeurotic posterior wall to the rectus sheath. This abrupt
change in the relationship of the aponeuroses to the rectus
abdominis, results in the posterior wall of the rectus sheath
having a sharp, free border, a short distance below the level of
the umbilicus (Figure 2). This border is called the arcuate line.
Thus, below the arcuate line the posterior surface of the rectus
abdominis muscle is in direct relationship to the fascia
transversalis.
Above the level of the costal margin, the rectus abdominis is
covered on its anterior surface only, by the external oblique
aponeurosis alone. The transverse tendinous intersections in the
rectus abdominis muscle blend with the anterior wall of the
rectus sheath.

iliohypogastric nerve (L1) and the ilioinguinal nerve (also L1)
supply a strip of skin immediately above the inguinal ligament
and pubic symphysis.
Because there is considerable overlap in the dermal territories
of adjacent cutaneous nerves, damage to one or two of these
nerves will usually not produce detectable anaesthesia.
The posterior intercostal arteries (which accompany the
intercostal nerves) supply the three-ply muscles in the lateral
part of the anterior abdominal wall, and in this function are
reinforced by the lumbar arteries, which are branches of the

abdominal aorta.
The rectus abdominis has a different blood supply. The upper
half of the muscle is supplied by the superior epigastric artery
(a branch of the internal thoracic artery). The artery enters the
rectus abdominis alongside the xiphisternal junction with its
companion veins. The lower half of the rectus abdominis is
supplied by the inferior epigastric artery, a branch of the external
iliac artery.
Myocutaneous rotation flaps may be fashioned using the
upper or lower halves of the rectus abdominis muscle; the former
being based on the superior epigastric vascular pedicle and the
latter being based on the inferior epigastric vascular pedicle.

Innervation and blood supply of the muscles of the anterior
abdominal wall (Figure 2)

Inguinal region

Transversalis fascia: the transversalis fascia is the anterior part
of the general endo-abdominal fibrous layer that envelops the
peritoneum. It is thicker and less expansile in the lower part of
the anterior abdominal wall. The transversalis fascia is closely
applied to the deep surface of the transversus abdominis muscle
but is easily separable from the latter.
Properitoneal adipose layer: the properitoneal adipose layer
(also known as fascia propria) is interposed between the transversalis fascia and the parietal peritoneum. This layer offers little
resistance to the spread of infection and, consequently, cellulitis
secondary to surgical wound infections may spread rapidly
within it.

The groin or inguinal region denotes the area adjoining the
junctional crease between the front of the thigh and the lower
part of the anterior abdominal wall, and includes the inguinal
and femoral canals.

The muscles of the anterior abdominal wall are supplied
segmentally by the seventh to 11th intercostal nerves and the
subcostal nerve. These nerves (accompanied by their corresponding posterior intercostal vessels) cross the costal margin
obliquely to run in the neurovascular plane of the anterior
abdominal wall, between the internal oblique and transversus
abdominis muscles. The nerves supply these muscles and divide
into lateral and anterior branches. The former penetrate the
overlying internal oblique to supply the external oblique muscle,
while the anterior branches run medially, before entering the
rectus abdominis through its posterior surface. Having supplied
the muscles, these nerve branches eventually supply the overlying skin. Cutaneous innervation of the anterior abdominal wall
by the seventh to 11th intercostal nerves and subcostal nerve is
represented by a series of oblique band-shaped dermatomes. The
dermatome corresponding to the 10th intercostal nerve is at the
level of the umbilicus; that of the seventh intercostal nerve is at
the epigastric level. The 11th intercostal and subcostal nerves
supply strips of skin below the umbilical level, while the

SURGERY 30:6

The inguinal canal (Figure 3): is an obliquely placed slit-like
space within the lower part of the anterior abdominal wall. It
may be represented on the surface by a 1.5 cm-wide band, above
and parallel to the medial half of the inguinal ligament. The
inguinal canal starts laterally at the deep (internal) inguinal ring

(a defect in the fascia transversalis), and runs downwards and
medially to open at the superficial (external) inguinal ring
(a triangular defect in the external oblique aponeurosis). In
adults, the inguinal canal is about 5e6 cm long. In males, the
inguinal canal contains the spermatic cord and the ilioinguinal
nerve; in females, it contains the round ligament of the uterus
and the ilioinguinal nerve. Another nerve which runs within the
inguinal canal is the genital branch of the genitofemoral nerve.
This slender nerve enters the inguinal canal through the deep
inguinal ring. In the male, it travels as a constituent of the

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The inguinal canal consists of a floor, a roof, an anterior wall
and a posterior wall. The floor of the inguinal canal is the upper
surface of the in-rolled inguinal ligament; the floor being
completed medially by the upper surface of the lacunar ligament
(a curved extension of the medial end of the inguinal ligament).
The anterior wall of the inguinal canal is the external oblique
aponeurosis, reinforced on the lateral part of its inner surface by
those fibres of internal oblique which arise from the inguinal
ligament. The roof of the canal is formed by those fibres of
internal oblique and transversus abdominis which, originating
from the inguinal ligament, run superomedially arching above

the spermatic cord (or round ligament), before fusing to form the
conjoint tendon.
The posterior wall of the inguinal canal is the fascia transversalis, reinforced on its anterior surface medially by the
conjoint tendon. The deep inguinal ring is thus a natural defect in
the posterior wall of the canal, while the superficial ring is a
natural defect in the anterior wall.
Running obliquely in a superomedial direction behind the
posterior wall of the inguinal canal, medial to the deep inguinal
ring, are the inferior epigastric vessels.

Right inguinal canal
a

External oblique
aponeurosis

Inguinal
ligament

Femoral

External ring
Artery
Vein
Canal

llioinguinal
nerve
Spermatic cord
Inferior epigastric vessels

b

Internal oblique

Internal ring
Transversalis
fascia

Conjoint tendon
Ilioinguinal nerve

Inguinal hernia: is an abnormal protrusion of the peritoneal
cavity into the inguinal canal. When this protrusion enters the
inguinal canal through the deep inguinal ring, it is termed an
‘indirect inguinal hernia’. Such a hernia has the potential to
enlarge and emerge through the superficial inguinal ring and, in
men, the hernia may enter the scrotum. The neck of an indirect
inguinal hernia sac lies in the deep inguinal ring and thus is
situated lateral to the inferior epigastric artery. When the peritoneum protrudes into the inguinal canal, medial to the inferior
epigastric artery, through an attenuated and weakened posterior
wall, it is termed a ‘direct inguinal hernia’. The neck of a direct
hernial sac is therefore medial to the inferior epigastric artery.
Occasionally, an inguinal hernia may possess two sacs, one
direct and the other indirect. Such a hernia is termed a pantaloon hernia.
A

a With the external oblique aponeurosis intact
b With the aponeurosis removed
Source: Ellis H. Clinical anatomy. 10th edition. Oxford: Blackwell Science,

2002.

Figure 3

spermatic cord and innervates the cremaster muscle. It also
provides sensory innervation to the coverings of the spermatic
cord. In the female, the nerve runs alongside the round ligament
of the uterus and emerges at the superficial inguinal ring to
supply vulval skin. The ilioinguinal and genitofemoral nerves are
branches of the lumbar plexus.

SURGERY 30:6

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Secretory functions of the
gastrointestinal tract

juice of pH as low as 2.0, mucous secreting columnar and neck
cells, and pepsinogen secreting chief cells. Secretory cells in the
epithelium also secrete HCO3À protecting the mucosa from the
luminal HCl (Figure 2A).
The parietal cells secrete the intrinsic factor (IF). IF is a 55 kDa
glycoprotein complexing with vitamin B12 facilitating ileal B12
absorption. Surgical resection of the fundus or gastritis can leave

the patient dependent on lifelong parenteral supply of B12 to
avoid deficiency-related anaemia and neuropathy.
Mucus is mainly secreted from columnar epithelium through
exocytosis or desquamation of epithelial surface cells during
churning, but also from the mucous neck cells upon vagal stimulation. Pyloric glands contain mucus-secreting cells identical to the
mucous neck cells. The mucus layer of the stomach is 80e280 mm
thick and made up from mucins, a tetramer glycoprotein family
protected from pepsin digestion by long galactose and N-acetyl
glucosamine chains, but also small amounts of nucleic acid, lipids,
and other proteins including immunoglobulin, all suspended in an
alkaline saline. HCO3À is secreted from non-parietal epithelial cells.
The small HCO3À confining volume enables the pH at the epithelial
membrane to be neutral whereas the stomach lumen pH w 2.0.4
Pepsinogen is the 42.5 kDa precursor of pepsin. It exists in two
isoforms: pepsinogen I and II. Storage as inactive precursors prevents
autodigestion of the stomach mucosa.4 Pepsinogen I is released
through exocytosis from chief cells in the oxyntic glandular stomach
area and pepsinogen II from mucous and glandular cells in the
oxyntic and pyloric mucosa.5 35 kDa pepsin I is formed through aciddependent pepsinogen I hydrolysis. Pepsin I degrades about 20% of
ingested protein and is especially important due to its ability to digest
collagen in meat products. Gastric acid establishes the optimum
working pH range for pepsin: 1.8e3.5. Pepsin denatures at pH > 5.

Henrik Isackson
Christopher C Ashley

Abstract
The intestine is an organ of functional diversity. The absorption of water,
nutrients, minerals, and vitamins is made possible through the coordinated
action of the intestine, stomach, exocrine pancreas and hepatobiliary system.

Keywords GI-tract; secretory mechanisms; luminal nutrient sensing;
gastric secretion; regulation

Introduction
As food stuff passes through the alimentary canal it is manipulated through mechanisms controlled via endocrine, paracrine,
and neural elements. The cephalic phase of digestion is mainly
under neural control mechanisms whereas hormonal mechanisms dominate the gastric and intestinal. The process whereby
the release of such hormones is controlled is termed luminal
nutrient sensing (LNS; Figure 1).
Luminal nutrient sensing
Amino acids have shown to stimulate glucagon-like peptide-1
(GLP-1) secretion from gut L-cells, although their potency is
lower than that of glucose and fat. Fatty acids are potent stimuli
for both glucose-dependent insulinotropic polypeptide (GIP) and
GLP-1 secretion. The digestion of triglycerides to fatty acids is
crucial as pancreatic lipase inhibition reduces the GIP and GLP-1
response seen from fat ingestion. Suggested effects from bile
acids come from experiments with perfused explanted rat colon,
in which increasing the luminal presence of bile acids increases
the concentration of GLP-1 in the portal venous effluent. The
G-protein coupled bile acid receptor-1 (GPBAR1), was found
highly expressed in mouse colonic L-cells. High fat diet in
Gq-protein coupled free fatty acid receptors (GPR40)-null mice
fails to induce an increase in plasma GIP and GLP-1 levels.1,2

Regulation of gastric secretion
Gastrin, acetylcholine (Ach), and histamine are major stimulants of
gastric secretion via independent G-coupled receptors on oxyntic
cells. 80% of gastrin is secreted from G-cells in the pyloric antrum

mucosa and duodenum. It exists in two main isoforms: G34 (34
amino acids) and G17. 90% of gastrin present in the antral mucosa
is G17. This indicates that G17’s main site of action is the stomach
mucosa. Gastrin is also produced in the pancreas and is a diverse
player in GI-regulation; involved in parietal cell HCl secretion and
maturation, promoting pepsinogen secretion, stomach contractions, and constriction of the lower oesophageal sphincter (LOS).
Stomach lumen gastrin promotes histamine release from
enterochromaffin-like (ECL) cells via cholecystokinin-2 (CCK-2)
receptor, but also acts directly on the parietal cell CCK-2 receptors
causing apical membrane Hþ/Kþ-ATPase translocation.5 Gastrin
and CCK share the same five C-terminal amino acid residues.
Vagal action releases Ach and gastrin-releasing peptide (GRP)
to induce gastric acid secretion. There is little evidence from
‘sham-feeding’ in man of cephalic phase-gastrin release. However,
gastric phase distension of the stomach wall induces gastrin
release from wall neurons. Ach acts directly on parietal cell M3
receptors causing acid secretion. It also facilitates HCl secretion by
inhibiting inhibitory somatostatin release from antral D-cells. GRP
is released from vagal neurons stimulating G-cells to gastrin
secretion.5 Histamine H2 blockers, such as cimetidine, block the
action of histamine on the oxyntic cells, and acid release by Ach
and gastrin, illustrating histamine’s key role in these events. The

Gastric secretions
Most secretory cells in the stomach mucosa are situated in gastric
pits. These comprise oxyntic (parietal) cells secreting parietal

Henrik Isackson MD received his clinical training from Lund University
and is currently doing doctoral work at the Department of Cardiovascular Medicine, University of Oxford, Oxford, UK. Conflicts of interest:
none declared.

Christopher C Ashley DSc (Oxon) Hon MRCP FMedSci is a Professor and
Medical Tutor Emeritus at Corpus Christi College, University of Oxford,
Oxford, UK. Conflicts of interest: none declared.

SURGERY 30:6

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Proposed intracellular mechanisms of luminal nutrient sensing in K- and L-cells
Luminal nutrient sensing dependent incretin release
glucose

Na+
Na+

FFA

bile acid
G-coupled receptors

SGLT-1
Mitochondrion

Δψ

↑cAMP

Endoplasmatic
reticulum (ER)

↑[Ca2+]

Ca2+

Voltage-gated L-type
Ca2+ channel
K+ATP

PKC
exocytosis

↑ATP/ADP

blood stream

IP3

GIP

GLP-1

Figure 1 Secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) through exocytosis is dependent on a rise
in [Ca2þ]i. Glucose is absorbed through sodium-coupled glucose transporters (SGLT-1). The rise in [glucose]i increases the ATP level which inhibits the
activity of the ATP-sensitive Kþ channel (Kþ-ATP). Naþ influx as well as decreased Kþ efflux depolarizes the cell membrane which increases the opening
probability of the voltage sensitive L-type Ca2þ channels, causing an influx of Ca2þ. Free fatty acids (FFA) and bile acids bind G-protein coupled receptors

which activate intracellular pathways raising levels of cyclic adenosine monophosphate (cAMP). Their downstream activating pathways cause a rise in
cAMP which results in increased opening probability of voltage gated Ca2þ channels, and also protein kinase C (PKC) and inositol(1,4,5)-trisphosphate
(IP3) causing Ca2þ-release from intracellular stores to initiate exocytosis.1,2

Hþ/Kþ-ATPase inhibitor omeprazole is also highly effective at
controlling acid production by the parietal cell.
Histamine is secreted from ECL cells deep in the gastric pits closely
associated with parietal cells. It works in a paracrine fashion stimulating HCl secretion via parietal cell H2 receptors and induces translocation of Hþ/Kþ-ATPase to the apical membrane via increased
[cAMP]i. Histamine secretion is mainly induced by gastrin.5
Pepsinogen secretion is induced by substances including Ach,
CCK, gastrin, and secretin. Ach is regarded as the most potent
inducer through the association with M3 receptors causing activation of phospholipase C (PLC) and increased [Ca2þ]i.6
Somatostatin is the main inhibitor of HCl secretion. It is
released from d-cells throughout the gut mucosa as well as in the
endocrine pancreas, and from submucosal and myenteric
neurons. Gastric release is mainly from antral and fundal cells in
close proximity to parietal, ECL, and G-cells. The release is stimulated by acid, free fatty acids (FFA), glucose and distension.
Somatostatin acts directly on parietal cells and indirectly by
inhibiting histamine and gastrin release.7

Luminal gastric acid stimulates HCO3À secretion from secretory cells in the proximal duodenum neutralizing gastric acid
(Figure 2B).
Mucus formation is a process of mucin exocytosis from goblet
cells throughout the intestinal epithelium. In intracellular vesicles
these are associated with Ca2þ and Hþ. Dissociation of these ions is
important in the protein’s expansion and formation of luminal
mucus. The process is probably aided by the enterocyte secretion of
HCO3À. This has been proposed as a mechanism underlying the
highly viscous mucus in cystic fibrosis (CF), the primary phenotype
of the disease of dysfunctional cystic fibrosis transductance regulator (CFTR) where a local deficiency of HCO3À contributes to

increased mucus viscosity.8 For nutrients to reach the absorptive
enterocyte villi, they have to move through the mucus. In coeliac
disease, where a cross-reaction towards tissue protein is initiated by
an immunological response towards gliadin in wheat, villus atrophy
occurs causing reduced stirring and transport of nutrients across the
mucosa to the epithelium brush border, adding to an already
reduced absorptive capacity. The result is reduced absorption of fats
causing steatorrhoea, weight loss, reduced absorption of fat soluble
vitamins A, D, E, and K, and anaemia due to iron, folic acid and B12
malabsorption. Gluten-free diet restores absorptive capacity.

Secretions from the intestinal wall
Brunner’s glands, found in the proximal duodenum, secrete
alkaline mucus to lubricate chyme and protect the duodenal wall
from digestion by gastric acid. Mucus is also secreted from goblet
€ hn along the whole intestine, the
cells in the crypts of Lieberku
stomach excluded.

SURGERY 30:6

Regulation of small intestine secretion
Neurotransmitters Ach and vasoactive intestinal polypeptide
(VIP) stimulate HCO3À secretion together with luminal

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BASIC SCIENCE

Figure 2 A: ATP-dependent Hþ/Kþ-exchange, ClÀ extrusion, and Kþ recycling, are central for HCl secretion. Hþ is derived from H2CO3 which forms from H2O
and CO2 under the influence of carbonic anhydrase (CA). The Hþ/Kþ-ATPase is the major Hþ-extruder consuming approximately 1500 calories per litre of
secreted gastric juice generating a 106 times concentration gradient over the apical membrane. It is effectively inhibited by omeprazole. The Naþ/Hþ
exchange (NHE) transporter in the apical membrane transports Naþ down its concentration gradient in exchange for Hþ.3 Together with the ClÀ/HCO3À
exchange (CHE)-transporter the cystic fibrosis transductance regulator (CFTR) promotes the transport of ClÀ against its electrochemical gradient into the
stomach lumen. The voltage gated Kþ channel (Kv) is required to sustain the action of the Hþ/Kþ-ATPase. HCO3À is secreted basolaterally down
a concentration gradient into the blood, in exchange for ClÀ. The NHE of the basolateral membrane also helps to regulate pH. The NKCC conveys the
electroneutral inward transport of one Naþ, one Kþ, and two ClÀ. ClÀ also passes down its concentration gradient via exclusive ClÀ-channels. Naþ/KþATPase generates the electrochemical gradient of Naþ and Kþ. Tight junctions in the gastric epithelium are electrically tight, preventing paracellular ion
diffusion. B: In the duodenal epithelial cell apart from paracellular access of HCO3À from the blood to the duodenal lumen over leaky tight junctions,
there are facilitating transport mechanisms over the apical membrane together with ClÀ. ClÀ-transport also occurs through the CFTR.4 An electroneutral
NHE prevents intracellular pH decrease. Processes supporting the apical export of HCO3À include the NKCC, NHE, the Naþ/Kþ pump, a Naþ/HCO3À cotransporter (NBC), and an outward exclusive Kþ channel.

prostaglandin E2 (PGE2). Ach acts via an increase in [Ca2þ]i, and
PGE2 and VIP act via G-protein coupled receptor activation,
raising [cAMP]i. Stimulatory factors include luminal acid,
glucose, and bile salts, but also wall distension. Stretch reflexes
involve the parasympathetic as well as intrinsic enteric nervous
system. The sympathetic neurotransmitters noradrenaline (NA)
and neuropeptide Y (NPY) inhibit secretion. Somatostatin in the
duodenal wall works as a neurohormonal inhibitor released from
enteric nerve endings. It acts directly on crypt cells by decreasing
[cAMP]i levels via a G-protein coupled receptor (SSTR1).4 Mucin
release is closely associated with that of HCO3À through the

SURGERY 30:6

CFTR, and is stimulated by PGE2 and serotonin.9 The cholera
toxin enters secretory cells through receptor-mediated endocytosis causing permanent activation of G-protein receptors

elevating [cAMP]i, activating the CFTR, and increasing ClÀ and
associated Naþ secretion with watery diarrhoea as a result.
Excessive loss of HCO3À generates metabolic acidosis.

Pancreatic exocrine secretion
Pancreatic exocrine secretion contains digestive enzymes and
alkaline saline. Electrolytes are secreted from ductal and

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Regulation of pancreatic exocrine secretion
Pancreatic exocrine secretion is mainly under autonomic nervous
control in the cephalic phase of ingestion and hormonal and
enteropancreatic reflex control during the gastric and intestinal.10
In this phase, mainly enzymes are secreted but a vasodilatory
response is initiated through kallikrein secretion catalysing the
production of vasodilatory bradykinin, increasing the pancreatic
blood flow and consequently fluid secretion. Ach from secondary
nerve endings stimulates muscarinic receptors causing a release of
Ca2þ from intracellular stores and zymogen granule exocytosis.
Without increased electrolyte flow, large quantities of digestive
enzymes remain in the pancreatic ducts until the increased flow in
the intestinal phase moves them towards the Papilla Vateri. Only
25% of total pancreatic enzyme secretion is released during the

cephalic phase. During the gastric phase, hormonal stimulants
stimulate pancreatic enzyme secretion by another 5e10%,
together with cholinergic neural stimulation. CCK is responsible for
70e80% of the total pancreatic enzyme secretion during a meal. It
is released from EEC of I-type in the duodenal and upper jejunal
mucosa, when these are stimulated by fatty and amino acids during
the intestinal phase. HCl is less potent a stimulant. CCK-I receptor
stimulation induces increased [Ca2þ]i and zymogen exocytosis.
Trypsin exerts negative feedback by inhibiting CCK release.10
Secretin is a 27 amino acid inducer of electrolyte secretion. It
has been suggested to act by augmenting inward potassium
currents in acinar cells increasing ClÀ and HCO3À-secretion. Acid
released in the duodenum stimulates S-cells in the intestinal wall
to release secretin stimulating alkaline fluid secretion from ductal
and centroacinar cells. The [HCO3À] can reach 150 mM. Fatty
acids, less potently, contribute to the release of secretin. HCl
reacts with HCO3À and Naþ to form H2CO3 and NaCl. H2CO3
dissociates into H2O and CO2, the latter subsequently expired
through respiration. CCK and Ach potentiates the secretion of
alkaline fluid induced by secretin.10
Somatostatin inhibits secretion through suppression of CCK
and secretin release. Its release, stimulated by the same
hormones and gastrin, illustrates another negative feedback
mechanism. The identification of somatostatin receptors on
acinar cells suggests an independent action.10,11

centroacinar cells whereas enzymes originate from acinar cells at
the terminal end of the secretory units. HCO3À protects the
duodenal mucosa from acid and establishes an optimal pH for
digestive enzymes, and facilitates micelle formation, a process

described below. The pancreatic juice, as it enters the
duodenum, holds a pH of 7.4e8.3 contributing to the settling of
duodenal chyme at approximately pH 7, inactivating pepsin.
HCO3À is secreted to the pancreatic duct lumen in analogy with
the duodenal secretory process. Protons from H2CO3 dissociation
are transported across the basolateral membrane making the
postprandial pancreatic effluent slightly acidic reducing the effect
of the stomach alkaline tide. The electrolyte fluid also contains
Naþ, and Kþ which travels via the paracellular route down the
electric gradient increasing water flow through osmotic mechanisms. With increased flow the secretion entering the duodenum
becomes similar to the primary pancreatic composition due to
reduced ductal cell modification. ClÀ stands in reciprocal relationship with HCO3À due to antitransport in the CFTR channel of
the apical membrane. Hence, with an increase in flow [HCO3À]
increases due to decreased reuptake, whereas [ClÀ] is reduced as
less is secreted.
Proteolytic enzymes are stored in intracellular zymogen
granules in the terminal acinar cells of the secretory lobules and
secreted as inactive precursors to avoid pancreatic tissue autodigestion. Trypsin and chymotrypsin have a strict endopeptidase
cleavage pattern whereas carboxypolypeptidase releases single
amino acids from the carboxyterminal end of proteins reducing
polypeptides to single amino acids. The trypsin precursor trypsinogen is initially activated by enterokinase, situated on the
intestinal epithelium brush border. Activating trypsinogen causes
an autoactivation cascade which if it occurs in the pancreas
causes tissue autodigestion. To prevent premature activation
pancreatic juice contains pancreatic secretory trypsin inhibitor
(PSTI). Trypsin also activates other enzyme precursors in the
duodenal lumen. Elastase is the only enzyme which is capable of
degrading connective tissue elastin.
Postnatally intestinal cells can absorb protein by endocytosis,
a process designed to transfer passive immunity from the mother.

Even adult intestines can absorb small amounts of protein and
polypeptide. Although the majority of protein is absorbed eventually via specific amino acid co-transporter systems and defects
in these systems are responsible for Hartnup disease and cystinuria, the enterocyte can absorb di-, tri-, and tetra-peptides, these
being subsequently intracellularly hydrolysed. The transporter for
this process is the oligopeptide transporter (PepT1) which is
effective at transporting multiple amino acids, rather than a single
amino acid, and is dependent upon Hþ inward co-transport.
Pancreatic a-amylase, the main carbohydrate-degrading
enzyme, hydrolyses sugars, starch, and glycogen to glucose and
disaccharides. Pancreatic lipase is dependent on a coenzyme,
pancreatic colipase, in order to reach full activity as this counteracts biliary acids’ inhibitory effects on pancreatic lipase.
Pancreatic lipase hydrolyses triglycerides, forming FFA and
monoglycerides. Cholesterol esterase hydrolyses ester linkages
between fatty acids and cholesterol, enabling micelle utilization.
It forms proteolysis-resistant dimers when present in the
duodenal lumen. Activated phospholipase hydrolyses phospholipids to FFA and lysophospholipids. It is the only non-proteolytic
enzyme stored as an inactive precursor before secretion.

SURGERY 30:6

Hepatobiliary secretions
Bile aid fat digestion through emulsification and micelle formation, and carries metabolic waste products and toxins from the
blood. The efficacy of the former task is increased through the meal
synchronized-contraction of the gall bladder and entry of this
concentrated bile into the duodenum. The concentrating effect is
achieved through the osmotic absorption of water through electrically ‘leaky’ tight junctions driven by active absorption of
sodium over the apical and basolateral membrane of the epithelial
cell to the blood, and through aquaporin channels.
Bile secretions are divided in two groups: hepatocyte secretion
consisting of bile salts as the major component, along with

cholesterol, lecithin, bilirubin, fatty acids, excreted conjugated
metabolites, albumin, immunoglobulin A (IgA), and plasma
electrolytes, and cholangiocyte secretion containing alkaline
saline. The liver parenchyma shows functional hexagone shaped
microscopic units in which hepatocytes modify contents of
arterial and portal blood (Figure 3).

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Schematic representation of the liver hexagone
space of Disse

hepatocyte
lymphatic duct

central vein
cholangiocyte

bile canaliculi

bile ductule

venous sinusoid

Kupffer cell

portal vein
endothelial cell
hepatic artery

Figure 3 The liver parenchyma is organized in hexagones where hepatocytes modify contents of arterial and portal blood. In each corner is a hepatic triad
consisting of distal portal vein, hepatic artery, and proximal bile ductule. The arrows indicate the direction of flow. This counter-current system allows for
hepatocytes to absorb substances for modification from the blood and excrete metabolites along with bile constituents into the bile ductule. Excess fluid
in the space of Disse beneath endothelial cells drains into the lymphatic ducts.

Bile acids are derived from cholesterol, and combine with
sodium or other monovalent cations. The main bile acids are
cholic and chenodeoxycholic acids which combine with taurine
or glycine before sodium. Bile salts emulsify fat, increasing the
fat water-interface and enzymatic fat digestion.
Bile salts are taken up from the enterohepatic circulation via
hepatocyte basolateral sodium co-transporters. A concentration
gradient is created by Naþ/Kþ-ATPase Naþ-extrusion. Apical
secretion into the canaliculi occurs through an active transport.
As they enter the canaliculi they are stored in micelles.
Lecithin is the major phospholipid secreted with bile. It is
mainly derived from the hepatocyte cell membrane. Cholesterol
is to a major extent derived from a circulating pool, but a liver de
novo synthesis provides a fraction.
Bilirubin is derived from erythrocyte haemoglobin and muscle
myoglobin in the reticuloendothelial system (RES). The intermediate metabolite biliverdin, which is reduced to bilirubin, is
also present in hepatic secretion. Gall bladder stored bilirubin
tends to reoxidize generating the bile’s characteristic green
colour. To increase bilirubin’s water solubility, bilirubin hepatocyte conjugation is mainly to glucoronic acid, whereas
a minority is conjugated to sulphate. It is actively secreted into
the canaliculi. Bilirubin is partly excreted with faeces. Intestinal

bacteria convert unconjugated bilirubin to stercobilinogen which
is more readily absorbed to the blood stream and excreted via the
liver. Exposure of stercobilinogen to air reoxidizes it to stercobilin, giving faeces its dark colour. Urinary secretion of bilirubin
occurs in the form of urobilinogen which is oxidized to urobilin.

SURGERY 30:6

A minority of conjugated bilirubin will also be deconjugated by
bacteria and pass back into the enterohepatic circulation.
Along with hepatocyte bile secretion, cholangiocytes secrete
an alkaline saline into the ducts neutralizing the duodenal pH,
optimizing conditions for pancreatic digestive enzymes as well as
aiding micelle formation. This adds as much as 100% to the
initial hepatocyte derived secretory volume. With increased flow,
the time of contact for the hepatobiliary secretion decreases and
the pH of the bile rises due to a reduced chloride/bicarbonate
exchange. In post-hepatic jaundice an obstruction of the bile duct
prevents entry of gall into the duodenum. As a result fat emulsification and absorption will be impeded, along with a loss of
stercobilinogen causing steatorrhoea of pale colour. In the classic
case the patient will also display darkened urine, and jaundice
due to increased systemic levels of conjugated bilirubin.
Fat emulsification
For efficient digestion it is crucial to achieve fat emulsification.
Lecithin is a major component in the micelle and also acts
emulsifying in its free state. Its hydrophobic acyl side-chain
resides in the fat and its hydrophilic phosphorylcholine group
projects towards the water face which reduces surface tension.
The amphiphilic nature of conjugated bile salts also aids this
process. Lipase hydrolyses triacylglycerol forming FFA and
monoacylglycerides, both used in micelle formation. Micelles

have a diameter of 3e6 nm and contain 20e40 bile salt molecules. Micelle bile salts have their hydrophilic side facing the
periphery and the hydrophobic sterol in the centre. With lecithin

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The colonic epithelium regulates bodily Kþ-levels, providing
an accessory excretion pathway to the kidney. This occurs down
a concentration gradient through the passive conductance
potassium BK channel after its active absorption across the
basolateral membrane by the Naþ/Kþ pump and Naþ/Kþ/2ClÀ
co-transporter. In the distal colon Kþ is absorbed by Hþ/KþATPase, similar to that seen in the parietal cell. A paracellular Kþ
transport has also been suggested, driven by the electric
gradient.14 Electrolyte balances is a consideration in colonic
irrigation where external osmotically active volumes may initiate
colonic movements and increased potassium secretion. This is of
particular importance in patients where multiple pharmacologic
agents, along with age, may already reduce kidney homeostatic
capacity, causing an increased dependence on the colon.

incorporation the primary micelle expands into a secondary
micelle harbouring larger quantities of hydrophobic cholesterol
molecules in its core. Their negative shells causes inter-micelle
repulsion, emulsifying the fat. The micelle also aids fat absorption in the small intestine by effectively keeping the concentration of relatively water insoluble fatty acids, of more than C12, at
a saturation level in the aqueous phase.

FFA are absorbed through diffusion. Once in the enterocyte
triglycerides are re-synthesized from fatty acids and monoglycerides. In the circulation, these lipids are transported as
chylomicrons to their site of storage or utilization. Bile salts
are then reabsorbed into the enterohepatic circulation from
the terminal ileum by a secondary active transport system.
Fatty acids of less than C12 in length are sufficiently
water soluble and do not necessarily need this system for
absorption.

Regulation of colonic secretion
The main stimulus for mucus secretion in the colon is tactile
stimulation of goblet cells. Reflexes also occur via the pelvic
nerves involved in defecation, co-eliciting an increase in peristalsis. Sympathetic nervous stimulation decreases colonic
peristalsis and secretion.
In kidney failure, an upregulation of colonic Kþ secretion
describes the regulatory function of the organ to maintain
a stable serum [Kþ]. Net colonic Kþ secretion is variable and
responds to increased dietary intake by increasing secretion via
increased plasma aldosterone. BK-KO mice fail to reduce plasma
levels of Kþ on aldosterone administration, suggesting a regulatory role of this channel. Colonic Kþ secretion through the BK
channel increases on adrenalin and PGE2 stimulation via
increased cAMP levels. Aldosterone is also an inhibitor of the
Hþ/Kþ-ATPase, adding to the net Kþ efflux effect. Somatostatin
inhibits Kþ secretion through a decrease in [cAMP]i.14
A

Regulation of hepatobiliary secretion
Gall bladder emptying requires the contraction of the bladder to be
synchronized with sphincter of Oddi relaxation. Ach from vagal
secondary neurons acts on the biliary tree interprandially and

during the cephalic and gastric phases of digestion causing
contractile pulses in the gall bladder, a slight secretion of alkaline
fluid from cholangiocytes, and antegrade peristalsis of the sphincter
of Oddi, reducing the risk of gall stone formation. During the gastric
phase, vagal action is supported by gastrin from ventricle G-cells.
CCK, the most potent inducer of gall bladder contraction, is
released from EEC of the duodenum in response to luminal fatty
acids. It acts on CCK-I receptors on gall bladder smooth muscle cells
but also facilitates release of Ach from gall bladder ganglia initiating
contraction through a rise in [Ca2þ]i. The same hormone inhibits
the contractions of the sphincter Oddi which ensures release of bile
into the duodenum. Sympathetic neurotransmitters such as
adrenaline and NA relaxes the gall bladder.12 Bile acids inhibit
further CCK release from the duodenum.
Secretin is the major stimulant of cholangiocyte alkaline
secretion. It is released from S-cells in the duodenum and induces
an increase in cholangiocyte [cAMP]i, activation of PKA and
opening of the CFTR and ClÀ/HCO3À exchanger increasing
HCO3À secretion. Ach potentiates the secretin effect by eliciting
cAMP activity. Its sole effect appears limited. Somatostatin has
an inhibitory effect on cholangiocyte secretion by interaction
with the somatostatin receptor 2 (SSTR2) preventing secretininduced increase in cyclic adenosine monophosphate (cAMP)
activity.13

REFERENCES
1 Parker HE, Reimann F, Gribble FM. Molecular mechanisms underlying
nutrient-stimulated incretin secretion. Expert Rev Mol Med 2010;
12: e1.
2 Reimann F. Molecular mechanisms underlying nutrient detection by
incretin-secreting cells. Int Dairy J 2010 Apr; 20: 236e42.

3 Kopic S, Murek M, Geibel JP. Revisiting the parietal cell. Am J Phys
2010 Jan; 298: C1e10.
4 Flemstrom G, Isenberg JI. Gastroduodenal mucosal alkaline
secretion and mucosal protection. News Physiol Sci 2001 Feb; 16:
23e8.
5 Schubert ML. Gastric exocrine and endocrine secretion. Curr Opin
Gastroenterol 2009 Nov; 25: 529e36.
6 Xie G, Drachenberg C, Yamada M, Wess J, Raufman JP. Cholinergic
agonist-induced pepsinogen secretion from murine gastric chief cells
is mediated by M1 and M3 muscarinic receptors. Am J Physiol
Gastrointest Liver Physiol 2005 Sep; 289: G521e9.
7 Corleto VD. Somatostatin and the gastrointestinal tract. Curr Opin
Endocrinol Diabetes Obes 2010 Feb; 17: 63e8.
8 De Lisle RC. Pass the bicarb: the importance of HCO3À for mucin
release. J Clin Invest 2009 Sep; 119: 2535e7.
9 Garcia MA, Yang N, Quinton PM. Normal mouse intestinal mucus
release requires cystic fibrosis transmembrane regulator-dependent
bicarbonate secretion. J Clin Invest 2009 Sep; 119: 2613e22.

Colonic secretion
Some acidic material is formed throughout the gut by bacterial
metabolism, and also by the activity of a colonic Hþ/Kþ-ATPase.
Due to HCO3À secretions the mucus still has an alkaline pH. The
HCO3À secreting epithelial cells of the colon occur sparsely
compared to the proximal gut, but also utilizes the CFTR and
HCO3À/ClÀ exchanger. As water is absorbed throughout the gut,
the chyme becomes progressively more viscous causing a higher
mechanical stress on the intestinal walls. Goblet cells in the colon
secrete mucins to produce a lubricating viscoelastic gel. The
mucus also serves the purpose of protecting the intestinal

epithelium from adhesion of harmful bacteria, and toxins.

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10 Nathan JD, Liddle RA. Neurohormonal control of pancreatic exocrine
secretion. Curr Opin Gastroenterol 2002 Sep; 18: 536e44.
11 Morisset J. Negative control of human pancreatic secretion:
physiological mechanisms and factors. Pancreas 2008 Jul; 37: 1e12.
12 Portincasa P, Di Ciaula A, Wang HH, et al. Coordinate regulation of
gallbladder motor function in the gut-liver axis. Hepatology
(Baltimore, Md.) 2008 Jun; 47: 2112e26.
13 Marzioni M, Fava G, Alvaro D, Alpini G, Benedetti A. Control of
cholangiocyte adaptive responses by visceral hormones and neuropeptides. Clin Rev Allergy Immunol 2009 Feb; 36: 13e22.

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14 Sorensen MV, Matos JE, Praetorius HA, Leipziger J. Colonic potassium
handling. Pflugers Arch 2010 Apr; 459: 645e56.

Acknowledgements
The authors are grateful to Dr Gabor Czibik, for critically reading
the manuscript.

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Physiology of malabsorption

suspected from the clinical history and examination: all patients
undergoing any procedure except the most trivial should have
been screened for nutritional impairment, and this may be due to
unsuspected malabsorption (although there are many other
causes). The malnutrition universal screening tool (MUST) is in
wide-spread use for adults in the UK,1 and requires only simple
questioning (weight loss, acute disease) and common measurements (height and weight) (Box 1).
Many patients with malabsorption will have diarrhoea or
steatorrhoea, but this is not always the case. Careful questioning
should detect frequency of stools and/or the passage of lipids
which have not been absorbed. Use of the Bristol stool chart2
helps to define the precise nature of a patient’s bowel habits.
Other specific blood tests may detect deficiencies of other nutrients such as Fe or B12 that have been malabsorbed.
This article will review the principles of normal absorption,
and the pathophysiology of some of the common disorders that
result in malabsorption.

Jonathan D Nolan
Ian M Johnston
Julian RF Walters

Abstract
Malabsorption occurs when the function of the gastrointestinal tract is
suboptimal and nutrient absorption is reduced. Malnutrition, weight loss,
diarrhoea, steatorrhoea, anaemia and other specific nutrient deficiencies
can be produced. This article will review the principles of normal nutrient
absorption and the pathophysiology in disorders which result in malabsorption. Normal absorption needs coordinated processes of motility,
hormone release, digestive secretion from the salivary glands, stomach,
pancreas, liver and intestine, and the expression of specific enzymes and
transporter molecules. Gastric, pancreatic and intestinal disorders can all
produce malabsorption. These can be complications of surgical procedures,
or be due to inflammatory and autoimmune disorders such as coeliac
disease, Crohn’s disease, small intestinal bacterial overgrowth, chronic
pancreatitis, or autoimmune gastritis. Understanding the mechanisms
involved and how these are affected by surgical procedures and disease
will enable malabsorption to be recognized, investigated and treated
appropriately.

Principles of normal absorption
Normal absorption relies on multiple processes, some starting as
soon as food is seen, smelt and tasted. Chewing starts the
physical transformation of food, and secretions from the salivary
glands, stomach, pancreas, liver and intestine dissolve components of the meal and lubricate its passage. These secretions
include key digestive enzymes. Coordinated muscle function is
needed to swallow the bolus, and gastric motility is critical for
mixing food in the stomach and emptying the semiliquid chyme
into the small intestine. Intestinal peristalsis mixes and propels
these nutrients which are further digested and mostly absorbed.

Keywords Absorption; bile; carbohydrates; coeliac disease; digestion;

lipids; micronutrients; minerals; proteins; short bowel syndrome

Introduction
The principal function of the gastrointestinal tract is the digestion
and absorption of nutrients consumed in the diet. To achieve
adequate nutrition, specialized and coordinated functions have
evolved throughout the gastrointestinal tract and its associated
organs such as the pancreas and liver. Malabsorption occurs
when these digestive and absorptive functions are suboptimal,
usually as a result of acquired disease or surgery.
Malabsorption may be generalized, affecting many types of
nutrients, or may be limited to one specific nutrient. It can be

Screening by MUST for malnutrition, which may be
due to malabsorption. See The ‘MUST’ Explanatory
Booklet for full explanations1
The 5 ‘MUST’ steps
Step 1
Measure height and weight to get a body mass index score using
chart provided. If unable to obtain height and weight, use the
alternative procedures shown in this guide.
Step 2
Note percentage unplanned weight loss and score using tables
provided.

Jonathan D Nolan BSc MB BS MRCP is a Clinical Research Fellow,
Department of Gastroenterology, Imperial College NHS Trust,
Hammersmith Hospital, and Section of Hepatology & Gastroenterology,
Imperial College, London, UK. Conflicts of interest: none declared.

Step 3
Establish acute disease effect and score.

Ian M Johnston MB ChB MRCP is a Clinical Research Fellow, Section of
Hepatology & Gastroenterology, Imperial College and Department of
Gastroenterology, Imperial College NHS Trust, Hammersmith Hospital,
London, UK Conflicts of interest: none declared.

Step 4
Add scores from steps 1, 2 and 3 together to obtain overall risk of
malnutrition.
Step 5
Use management guidelines and/or local policy to develop care
plan.

Julian R F Walters MA MB BChir FRCP is Professor of Gastroenterology at
Section of Hepatology & Gastroenterology, Imperial College and
Department of Gastroenterology, Imperial College NHS Trust,
Hammersmith Hospital, London, UK. Conflicts of interest: none
declared.

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MUST, malnutrition universal screening tool.

Box 1

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The important non-enzymatic secretions are acid from the
stomach and bicarbonate from the pancreas, intestine and bile.
The enzymes in the stomach function best at acidic pH whereas
those in the intestine are more active at alkaline pH. Bile acids
and phospholipids from the liver form micelles with ingested
lipids and by increasing the surface area at the lipid/water
interface improve their digestion and absorption.

Neuroendocrine regulators of digestion
Type

Component

Actions

Neuronal

Vagus

Gastric acid secretion
Gastric emptying
Motility
Motility
Peristalsis
Secretion
Gastric acid secretion

Gastric acid secretion
Bile secretion
Gallbladder contraction
Pancreatic exocrine secretion
Pancreatic exocrine secretion
Gastric emptying
Gastric emptying

Enteric nervous
system
Endocrine

Gastrin
Histamine
Cholecystokinin

Secretin
Motilin
Glucagon-likepeptide 1 (GLP1)
Peptide YY (PYY)

Absorption
The digested components of a meal are absorbed by the small intestinal enterocyte, and cross the apical brush-border microvillus
membrane, the cytoplasm and the basolateral membrane of this cell.
Specific carrier proteins, usually known as transporters, are involved
in many of these steps. There are important differences in the
handling of various types of nutrient.4
Lipids: Triglycerides and phospholipids are not completely
digested but are absorbed as monoglycerides and lysophospholipids, along with free fatty acids. Cholesterol esters are digested
to cholesterol and fatty acids. Major functions of the enterocyte

are to re-esterify these and to synthesis apolipoproteins, which
are then added to form chylomicrons and very low-density
lipoproteins (VLDL). These are secreted at the basolateral
membrane of the enterocyte and usually enter the lacteals in the
villus, and travel via the lymphatic system and the thoracic duct.

Gastric emptying

Table 1

These processes are controlled by nerves and hormones
(Table 1). Reabsorption of secreted water, electrolytes and bile
acids occurs in the distal intestine. Bacterial action releases some
further nutrients which can be absorbed in the colon.3

Carbohydrates: these are relatively easily digested. Monosaccharides are absorbed rapidly in the upper small intestine
(duodenum and proximal jejunum). Sucrose is split by sucrase to
glucose and fructose which have their own brush-border membrane
transporters. Lactose, the main sugar in milk, is broken down by
lactase to galactose and glucose, before being easily absorbed. The
expression of lactase is lost in most adults (see below). Starches take
longer to digest and absorb; poorly absorbed non-starch polysaccharides form the basis for dietary fibre and prebiotics.

Digestion
The exocrine secretion of enzymes is essential for digestion.
Digestive enzymes are also present on the brush-border apical
membrane of the intestinal enterocyte, and in the cytoplasm. The
main enzymes involved in digestion of lipids, carbohydrates and
proteins are shown in Table 2. Proteolytic enzymes are secreted
as inactive precursors; intestinal brush-border enterokinase

activates trypsinogen to trypsin, which then activates the other
pancreatic proteases.

Proteins: proteins are highly variable in structure, and there are
numerous enzymes and brush-border membrane transport

Enzymatic digestion of different types of nutrient
Site

Lipids

Carbohydrates

Proteins

Salivary glands
Stomach
Pancreas

e
Gastric lipase
Lipase
Colipase
Phospholipase
Cholesterol esterase
(Bile acids and phospholipids form micelles)
e

Salivary amylase
e

Pancreatic amylase

e
Pepsins
Trypsin
Chymotrypsin
Elastase
Carboxypeptidases
e
Enterokinase
(activates trypsin)
Aminopeptidases
Endopeptidases
Oligopeptidases
Dipeptidylpeptidase

Liver
Intestine

e
Sucrase
Lactase
Maltase

Table 2

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systems which have evolved to cope with this diversity. Short
peptides (dipeptides, tripeptides and oligopeptides) are absorbed
in addition to single aminoacids and these peptides then undergo
digestion in the cytoplasm of the enterocyte. Monosaccharides,
aminoacids and most absorbed nutrients leave the intestine in the
portal venous system, passing to the liver for further metabolism.

metabolite, 1a,25-dihydroxycholecalciferol. Vitamin B12 (cobalamin) is notable for the need to bind to intrinsic factor, produced
by the stomach, and the limited region for B12 absorption in the
terminal ileum. This region is also the site of reabsorption of
conjugated bile acids. More than 90% of bile acids are absorbed
into the portal vein and are then taken back up by the liver and
resecreted. This is known as the enterohepatic circulation.

Electrolytes and water: water absorption is governed by electrolyte absorption e principally that of sodium and chloride.
Considerable secretion of these occurs in the upper gastrointestinal tract and many litres have to be absorbed each day. Sodium
is co-transported with many nutrients (glucose, amino acids,
etc.) and this forms the basis for rehydration solutions used in
diarrhoea. There are also specific sodium and chloride absorptive
processes in the ileum and colon.

Pathophysiology of malabsorption in disease
The mechanisms responsible for nutrient malabsorption vary in
the differing conditions that can cause this. These are summarized in Table 3. We will describe various conditions affecting the

stomach, pancreas and intestine conditions, and how they affect
absorption.
Gastric causes
Gastric surgery: the storage function of the stomach is particularly
important during digestion, as it allows for controlled gastric
emptying of an ingested meal into the duodenum and the rest of the
small intestine. Gastric emptying is under negative feedback
control from gut hormone signals from the small bowel and colon.
This feedback control ensures that the rate at which further

Minerals, vitamins and other micronutrients: these nutrients
usually have specific absorptive transport mechanisms. Iron and
calcium are more soluble in the acidic conditions produced by
the stomach and are absorbed in the proximal intestine. Their
bioavailability can easily be reduced by binding to other
components. Iron absorption is regulated by hepcidin and
calcium absorption is regulated by the active vitamin D

Mechanisms of malabsorption in various conditions
Site

Condition

Mechanisms

Stomach

Gastric surgery
Autoimmune gastritis

Pancreas

Chronic pancreatitis or pancreatic surgery

Liver
Intestine

Biliary disease
Short bowel syndrome

Altered storage, mixing and emptying
Loss of acid and pepsin
Reduced intrinsic factor (and acid)
Reduced enzyme secretion
Impaired acid neutralization
Reduced bile acids for micelle formation and lipid absorption
Loss of absorptive area and intestinal digestive enzymes
Rapid transit through intestine
Reduced area for absorption from villous atrophy
Reduced enterocyte digestive enzymes
Impaired intestinal hormonal secretion
Loss of functioning intestinal area
(especially TI for B12/bile acids)
Bypassed gut (fistulae)
Small intestinal bacterial overgrowth (SIBO)
Reduced brush border enzymes
Metabolic effects on enzymes, bile acids and nutrients
Normal genetic non-persistence of lactase
Secondary forms from mucosal injury
Secondary to impaired bile acids (BA) reabsorption

Overproduction in primary BA diarrhoea
Villous atrophy, metabolic effects, lymphangiectasia and others
Altered gastric storage and emptying
Loss of acid and pepsin
Delayed mixing with pancreatico-biliary secretions
Reduced intestinal length
Altered intestinal hormone secretion

Coeliac disease

Crohn’s disease

SIBO
Lactose intolerance
Bile acid malabsorption

Bariatric surgery

Infections
Roux-en-Y gastric bypass

Table 3

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nutrients leave the stomach does not exceed the digestive and
absorptive capacity of the small intestine. Gastric surgery often
results in accelerated transit of nutrients through the small intestine due to loss of these functions.5 This leads to a shorter time for
the integration of digestive enzymes and bile salts with the ingested
macronutrients (carbohydrate, protein and fats) within the small
intestine. There will also be less time for absorption, resulting in
some nutrients entering the colon unabsorbed.
The mixing and grinding functions of the antrum and pylorus
will be lost if they have been resected (e.g. Bilroth I or II
gastrectomy). This will result in food particles that are larger
than normal entering the small intestine. The luminal digestive
enzymes and bile salts will therefore have a smaller surface area
with which to interact with macronutrients and fat droplets. This
may be particularly relevant for the absorption of iron that is
bound in the solid phase of muscle myoglobin ingested meat.6
Gastrectomy can specifically interfere with iron absorption via
other mechanisms, including reduced gastric acid secretion
decreasing solubility. Proximal gastrectomy will selectively
interfere with B12 absorption through the loss of intrinsic factor
production from the fundal parietal cells.

Causes of exocrine pancreatic insufficiency
Chronic pancreatitis
Alcoholic
Metabolic
Hypercalcaemia
Hyperlipidaemia
Genetic

Cystic fibrosis (CFTR mutations)
Hereditary pancreatitis (PRSS1 mutations)
Autoimmune
Isolated autoimmune pancreatitis
IgG4 autoimmune disease (often associated with other
autoimmune disease)
Tropical
Tropical calcific pancreatitis
Idiopathic
Pancreatic duct obstruction

Autoimmune atrophic gastritis: pernicious anaemia is a macrocytic anaemia caused by B12 deficiency, resulting from autoimmune
gastritis. In this form of chronic gastritis, there is autoimmune
destruction of gastric parietal cells, responsible for the secretion of
hydrochloric acid, pepsin and intrinsic factor. Malabsorption of B12
occurs due to the loss of secretion of intrinsic factor into the lumen.
Impaired acid secretion (hypochlorhydria) also results from the
damage to the gastric parietal cells, and the increase in pH will
reduce the solubility and absorption of polyvalent cations such as
iron, calcium and magnesium. Other vitamins such as vitamin C
can also malabsorbed due to reduced acid secretion. Similar
consequences of hypochlorhydria are occasionally observed with
prolonged courses of gastric anti-secretory drugs such as proton
pump inhibitors (PPIs) or histamine antagonists.

Benign causes
Post-traumatic stricture
Pancreas divisum
Malignant causes
Pancreatic head carcinoma

Intraductal papillary mucinous tumour (IPMT)
Impaired pancreatic stimulation
Truncal vagotomy
Total gastrectomy
Table 4

Pancreatic insufficiency
Maldigestion: maldigestion refers to defects in the digestive
processes throughout the gastrointestinal tract. Pancreatic
digestive enzymes (amylase, lipases and proteases) are essential
for this process. Any impairment in their secretion will therefore
lead to maldigestion and ultimately, malabsorption of nutrients.
Impairment in the secretion of pancreatic enzymes is usually
referred to as exocrine pancreatic insufficiency (EPI). The most
clinically important causes of EPI result from loss of functioning
pancreatic tissue such as chronic pancreatitis or surgical resection. Other causes include obstruction of the pancreatic duct
(strictures, neoplasm) and impaired stimulation of secretion
(vagotomy, gastrectomy). Causes are listed in Table 4. Loss of
pancreatic tissue usually also results in loss of islets and endocrine deficiency and diabetes.

precede carbohydrate and protein maldigestion. Several reasons
may explain this: (i) the pancreas is the main source of lipase,
with the stomach only contributing a small proportion (gastric
lipase); (ii) lipase production is the first enzyme to become
deficient as chronic pancreatitis progresses; and (iii) reduced
bicarbonate secretions from the pancreas will lower the pH in the
duodenum. Pancreatic lipases are more sensitive to acid
destruction than the other pancreatic enzymes.8 It is not
surprising, therefore in clinical practice to find that steatorrhoea
is an early symptomatic manifestation of EPI. Other important

biochemical manifestations of EPI are deficiencies in fat-soluble
vitamins (A, D, E, K).
Post-surgical pancreatic insufficiency: resective pancreatic
surgery is often performed in patients who have developed
complications from chronic pancreatitis. These indications
include uncontrolled pancreatic pain, carcinoma or pseudocysts
that have failed non-invasive techniques. EPI due to an already
diseased and damaged pancreas will be further compounded by
surgical resection of pancreatic tissue. Maldigestion can also
occur following operations that result in the asynchronous

Chronic pancreatitis: chronic pancreatitis is characterized by
gradual irreversible damage to the pancreas. The most common
cause in the western world is alcohol, contributing to as much as
70e90% of cases.7 Diseases affecting the pancreatic acinar cells
result in EPI due to decreased volume or quality of secreted
pancreatic juices (as in cystic fibrosis). Fat maldigestion tends to

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