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Gastrointestinal Medicine

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Gastrointestinal Medicine Powered By Docstoc
					Gastrointestinal
  Medicine
     Liver disease

    Large intestine

    Small intestine

  Gall bladder disease
                                          Learning Objectives

Dom         LO Title                                               LO Detail
BCS   Anatomy of portal   1. To describe the anatomy of the portal venous system.
      venous system       2. To outline the changes that occur to the portal venous system with portal hypertension
BCS   Hepatobiliary       1. To describe the pathology of hepatobiliary diseases, including cirrhosis and liver
      disease             tumours.
                          2. To describe the vascular and biliary causes of hepatobiliary disease.
                          3. To list infective and toxic causes of hepatobiliary disease.
                          4. To outline the principles of management of common liver diseases
                          5. To describe the underlying principles and be able to interpret results from liver function
                          tests
BCS   Upper GI bleeding   1. To outline the causes of upper gastrointestinal bleeding.
                          2. To describe the principles of its medical, endoscopic and surgical management
                          3. To be able to explain the risks of blood transfusion
EPPD Stereotyping         1. Recognise and avoid stereotyping and judgmental behaviour.
ICCP Clinical reasoning   1. Assessment of haemodynamic status and resuscitation
ICCP Examination skills   1. Demonstrate proficiency in clinical examination of the patient with liver disease
ICCP Assessment of        1. Demonstrate basic proficiency in the assessment of substance dependence
     substance abuse
ICCP Laboratory           1. Demonstrate proficiency in the interpretation of liver function tests
     investigations
PPH   Alcohol (Public     1. Describe the range of morbidity (bio-psycho-social) associated with hazardous and
      Health)             harmful levels of alcohol intake at the individual, family and population levels.
                          2. What public health strategies are in place in Australia to reduce alcohol-related
                          morbidity?
PPH   Viral hepatitis     Describe:
      (Public Health)     1. The notifiable disease process and its objectives;
                          2. The burden of disease caused by viral hepatitis;
                          3. Risk factors for acquiring viral hepatitis; and
                          4. Population approaches to the primary and secondary prevention of morbidity
                          associated with Hepatitis A, B and C infection.
PPH   Treatment and       1. Using hepatitis as an example, demonstrate skills in finding and appraising studies of
      prognosis (EBM)     treatment and prognosis, and applying the results to individual management through a
                          weighing up of individualised absolute benefits and risks.
Another Hard Day At The Office
THE PORTAL VENOUS SYSTEM
   1.   Describe the anatomy of the portal venous system.
             Portal Vein.
                     Collects blood from the abdominal part of the GIT, gallbladder, pancreas,
                        spleen.
                     Carries blood to liver and branches into expanded capillaries: sinusoids.
                     The blood is then collected by the hepatic veins that drain into the IVC.
                     Carries blood from three major veins: superior and inferior mesenteric veins
                        and the splenic vein.
                     Forms posterior to the neck of the pancreas by the union of the splenic and
                        superior mesenteric veins.
                     Inferior mesenteric vein ends posterior to the pancreas by joining the splenic
                        vein (it may join the portal vein or even the superior mesenteric vein).
                     The portal vein ascends to the liver in the free margin of the lesser
                        omentum, posterior to the bile duct and hepatic artery.
                     The portal vein divides into right and left branches at the porta hepatis.
                     The branches then empty into hepatic sinusoids.
             Portal Systemic Anastomoses.
                     The portal venous system communicates with the systemic venous system.
                     When the portal circulation is obstructed, blood from the GIT can still reach
                        the right side of the heart through the IVC via collateral routes.
                     As the portal vein has no valves, blood can flow from the liver to the IVC
                        via three alternate routes.
                     In portal hypertension, venous pressure in the portal venous system is
                        increased, consequently some blood in the portal venous system may
                        reverse its direction and pass through the portal-systemic anastomoses into
                        the systemic venous system.
                     This causes the veins in the portal-systemic anastomotic areas to dilate and
                        become varicose.
                     The main portal-systemic anastomotic areas:
                                       a. Gastroesophageal region.
                                                 Oesophageal tributaries of the left gastric vein
                                                      anastomose with the oesophageal veins, which
                                                      empty into the azygos vein.
                                       b. Anorectal region.
                                                 The superior rectal vein anastomoses with the
                                                      middle and inferior rectal veins, which are
                                                      tributaries of the internal iliac and internal
                                                      pudendal veins, respectively.
                                       c. Paraumbilical region.
                                                 The paraumbilical veins in the falciform ligament
                                                      anastomose with subcutaneous veins in the
                                                      anterior abdominal wall.
                                       d. Retroperitoneal region.
                                                 Tributaries of the splenic and pancreatic veins
                                                      anastomose with the left renal vein. Short veins
                                                      also connect the splenic and colic veins to the
                                                      lumbar veins of the posterior abdominal wall.
                                                      The veins of the bare area of the liver also
                                                      communicate with the veins of the diaphragm
                                                      and the right internal thoracic vein.

   2.   Describe the changes that occur with portal hypertension.
             Splenomegaly: Splenic enlargement is caused by passive venous congestion.
             Development of Portosystemic Venous Anastomoses, Bypassing the Obstructed
                Portal Circulation: Venous anastomoses occur wherever the portal and systemic
                venous drainages commingle, resulting in dilated, tortuous veins at the following
                sites:
                         In the lower oesophagus and stomach (gastro-oesophageal varices) – these
                          frequently rupture, causing severe upper gastrointestinal bleeding 
                          haematemesis;
                      In the rectum (haemorrhoids);
                      Around the umbilicus, where the collateral veins radiate outward in the
                          abdominal wall (“caput medusae”).
                 Entry of portal venous blood into the systemic circulation through these collateral
                 channels may result in hepatic encephalopathy because blood bypassing the liver
                 eludes detoxification. Portacaval anastomoses created surgically to relieve portal
                 hypertension may have the same effect.
                Ascites: Ascites is due to increased transudation fluid across the peritoneal
                 membrane, particularly over the surface of the liver. The major factor leading to
                 severe ascites in chronic liver disease is a decrease in serum albumin level, with
                 portal hypertension playing only a contributory role.
                      Transudation of fluid decreases blood volume and initiates the normal
                          neurohormonal release of renin. This stimulates the formation of AT 2 which
                          in turn stimulates the release of aldosterone. Aldosterone stimulates the
                          retention of salt and water, and helps to normalise blood volume.
                      There is also impairment of hepatic lymphatic drainage

LIVER DISEASE
    1.   Describe the pathology of cirrhosis and the causes and complications of chronic liver
         disease.
              Fibrosis:
                      An accumulation in the liver of connective tissue resulting from an
                         imbalance between production and degradation of the extracellular matrix
                         and accentuated by the collapse and condensation of pre-existing fibers.
                      The normal liver is made up of hepatocytes and sinusoids distributed within
                         an extracellular matrix composed of collagen (predominantly types I, III and
                         IV) and non-collagen proteins, including glycoproteins (e.g. fibronectin,
                         laminin) and several proteoglycans (e.g. heparan sulphate, chondroitin
                         sulphate, dermatan sulphate, hyaluronate). Fibroblasts, normally found only
                         in the portal tracts, can produce collagen, large glycoproteins, and
                         proteoglycans.
                      Other liver cells (particularly hepatocytes and fat-storing Ito cells, Kupffer
                         cells and endothelial cells) also can produce extracellular matrix
                         components. Fat-storing cells, located beneath the sinusoidal endothelium
                         in the space of Disse, are precursors of fibroblasts, capable of proliferating
                         and producing an excess of extracellular matrix. The development of
                         fibrosis from active deposition of collagen is a consequence of liver cell
                         injury, particularly necrosis, and inflammatory cells. The precise factors
                         released from these cells is not known, but one or more cytokines or
                         products of lipid peroxidation are likely. Kuppfer cells and activated
                         macrophages produce inflammatory cytokines. New fibroblasts form
                         around necrotic liver cells; increased collagen synthesis leads to scarring.
                         Fibrosis may derive from active fibrogenesis and from impaired degradation
                         of normal or altered collagen. Fat-storing cells, Kupffer cells, and
                         endothelial cells are important in the clearance of type I collagen, several
                         proteoglycans, and denatured collagens. Changes in these cells’ activities
                         may modify the extent of fibrosis. For the histopathologist, fibrous tissue
                         may become more apparent from passive collapse and condensation of pre-
                         existing fibers.
                      Thus, increased synthesis or reduced degradation of collagen results in
                         active deposition of excessive connective tissue, which affects hepatic
                         function:
                              1. Pericellular fibrosis impairs cellular nutrition and results in
                                   hepatocellular atrophy.
                              2. Within the space of Disse, fibrous tissue accumulates around the
                                   sinusoids and obstructs the free passage of substances from the
                                   blood to the hepatocytes.
                 3.    Fibrosis around hepatic venules and the portal tracts disturbs
                       hepatic blood flow.
            Venous resistance across the liver increases from portal vein branches to
            sinusoids and finally to hepatic veins. All three routes can be involved.
         The fibrous bands that link portal tracts with central veins also promote
            anastomotic channels: Arterial blood, bypassing the normal hepatocytes, is
            shunted to efferent hepatic veins, which further impairs hepatic function and
            can accentuate hepatocellular necrosis. The extent to which these processes
            are present determines the magnitude of hepatic dysfunction: e.g. in
            congenital hepatic fibrosis, large fibrous bands involve predominantly the
            portal regions but usually spare the hepatic parenchyma. Congenital hepatic
            fibrosis thus presents as portal hypertension with preserved hepatocellular
            function.
   Cirrhosis:
         Diffuse disorganization of normal hepatic structure by regenerative nodules
            that are surrounded by fibrotic tissue.
         Cirrhosis is the end stage of many forms of liver injury characterized
            initially by fibrosis. The progression from fibrosis to cirrhosis and the
            morphology of the cirrhosis depend on the extent of injury, the presence of
            continuing damage, and the response of the liver to damage. Cirrhosis is
            related not so much to the injurious agents as to the kind of injury and the
            liver’s response to it. The liver may be injured acutely and severely (as in
            sub-massive necrosis with hepatitis), moderately over months or years (as in
            biliary tract obstruction and chronic active hepatitis), or moderately but
            continuously (as in alcohol abuse). Cytokines and hepatic growth factors
            (e.g. epidermal growth factor) are presumably responsible for the response
            to injury: fibrosis plus regenerating nodules.
         During the repair process, new vessels form within the fibrous sheath that
            surrounds the surviving nodules of liver cells; these “bridges” connect the
            hepatic artery and portal vein to the hepatic venules, restoring the
            intrahepatic circulatory pathway. Such interconnecting vessels receive
            blood from the sinusoids and provide relatively low-volume, high-pressure
            drainage that is less efficient than normal and results in increased portal vein
            pressure (portal hypertension). Disordered blood flow to the nodules and
            compression of hepatic venules by regenerating nodules also contribute to
            portal hypertension.
         Cirrhosis is not static; its features depend on the disease activity and stage.
            Morphologic classification does little to reveal its cause.
   Histopathologic classification:
         Micronodular cirrhosis is characterized by uniformly small nodules (< 3
            mm in diameter) and regular bands of connective tissue. Typically, nodule
            lack portal organization; terminal (central) hepatic venules or portal tracts
            are difficult to identify.
         Macronodular cirrhosis is characterized by nodules that vary in size (3
            mm to 5 cm in diameter) and contain some normal lobular structure (portal
            tracts, terminal hepatic venules). Broad fibrous bands of varying thickness
            surround the large nodules. Collapse of the normal liver architecture is
            suggested by the concentration of portal tracts within the fibrous scars.
         Mixed cirrhosis (incomplete septal cirrhosis) combines elements of
            micronodular and macronodular cirrhosis. Regeneration in micronodular
            cirrhosis can result in macronodular or mixed cirrhosis. Conversion from
            micronodular to macronodular cirrhosis takes  2 years.
   Causes:
         Toxins and drugs, e.g. alcholic (60 – 70%), methyldopa, methotrexate,
            isoniazid.
         Infections, e.g. viral hepatitis (10%).
         Autoimmune diseases, e.g. chronic active hepatitis, primary biliary cirrhosis
            (5 – 10%).
         Metabolic disorders, e.g.
                 1. Wilson’s disease (due to defective biliary Copper excretion) (rare)
                          2.  Haemochromatosis (due to excessive iron absorption) (5%)
                          3.  1-antitrypsin deficiency (look for concomitant respiratory
                              disease)(rare)
                         4. Glycogen storage diseases – history of failure to thrive, exercise
                              intolerance, BSL abnormalities.
                 Vascular disorders, e.g. hepatic venous outflow obstruction (Budd-Chiari
                    syndrome – associated with thrombotic states – OCP, pregnancy), veno-
                    occlusive disease, congestive heart failure.
                 Cryptogenic cirrhosis (10 – 15%).
            Complications:
                 Many severe complications of cirrhosis are secondary to portal hypertension
                    because hypertension leads to the development of collateral flow from the
                    portal venous system to the systemic circulation. Portal hypertension is
                    associated with splenomegaly and hence hypersplenism; the development of
                    collateral vessels lining the oesophagus and stomach produce varices.
                    Oesophageal varices and, less often, gastric varices are particularly prone to
                    bleeding, which is often massive  massive haematemesis and often death.
                 Another complication is hypoxemia with reduced arterial O2 saturation,
                    secondary to pulmonary shunting, ventilation-perfusion mismatch, and
                    reduced O2 diffusing capacity.
                 In addition, jaundice, ascites, renal failure, and hepatic encephalopathy may
                    develop because of portal hypertension, portal-systemic shunting, other
                    circulatory disturbances, and impaired hepatic metabolic function.
                 Lastly, hepatocellular carcinoma frequently complicates cirrhosis associated
                    with chronic hepatitis B and C viruses, hemochromatosis, and long-standing
                    glycogen storage disease.

2.   What are the principles of management of common liver diseases?
        Management of cirrhotic patients includes:
                  Withdrawal of the causative agent (e.g. alcohol).
                  Where possible, treatment of the underlying causes – hepatitis and
                     interferon.
                  Treatment of manifestations of hepatic failure, e.g. jaundice, ascites,
                     peripheral oedema, hepatic encephalopathy, coagulopathy, renal failure and
                     infection.
        Withdrawal of offending agent:
                  Once identified, the causative agent should be withdrawn indefinitely.
                  Venesections for hemochromatosis – 1mg Fe2+ per mL of blood removed
                  Oral corticosteroids for chronic active hepatitis.
                  D-penicillamine for Wilson’s disease.
        Ascites and peripheral oedema:
                  Dietary salt and fluid restriction.
                  Diuretics.
                  Therapeutic paracentesis with IV fluid support.
        Hepatic encephalopathy:
                  Search for precipitating factors, e.g. dehydration, electrolyte imbalance,
                     infection, occult GI bleeding.
                  Dietary protein restriction.
                  Antibiotics e.g. neomycin.
                  Occasionally, dexamethasone to reduce cerebral oedema.
        Coagulopathy:
                  IM vitamin K given for three days.
                  If no improvement, maybe fresh frozen plasma or platelet infusion.
        Bacterial infection:
                  Cultures of blood, urine, ascitic fluid etc.
                  Treatment with a broad spectrum antibacterial agent.
        Renal failure:
                  May be due to dehydration, ATN or the hepatorenal syndrome.
                               1.Hepatorenal syndrome – appearance of renal failure in patients
                                 with hepatic disease – unknown aetiology -  renal perfusion with
                                 renal vasoconstriction. Oliguria with low sodium, no protein.
                     Withdrawal of diuretics.
                     Patient made euvolaemic with appropriate intravenous fluids.
               Malnutrition:
                     Institution of a high caloric diet.
                     Nasogastric or parenteral feeding may be necessary if caloric deficiencies
                         cannot be corrected with oral feeding.
               Upper gastrointestinal bleeding:
                     Blood volume replacement.
                     Endoscopic sclerosis of varices.
                     IV vasopressin or octreotide.
                     Balloon tamponade.
                     Sclerotherapy – varices injected with sclerosing agent
               Liver transplantation:
                     Advanced cirrhosis < 65 years old.
                     CI in patients with active alcoholism, sepsis, CRF and malignancy.
                     70 to 80% survival rate at 12 months (greater in paediatric patients).
                     Major physical and emotional stress – pre-transplantation psychiatric
                         assessment is essential.
                     Require life-long immunosuppressive drugs.

GASTROINTESTINAL BLEEDING
   1.   Outline the causes of upper gastrointestinal bleeding.
            More common:
                      Chronic peptic ulcer (40%), gastric ulcer (20%).
                      Acute peptic ulcer (erosions) (30%).
                      Gastritis.
                      Portal hypertensive gastropathy.
                      Mallory-Weiss tear.
                      Oesophageal and/or gastric varices.
                      Drugs: NSAIDs, steroids, thrombolytics, anticoagulants.
            Rarer:
                      Haemobilia.
                      Nose bleeds (swallowed blood).
                      Esophageal/gastric malignancy.
                      Erosive or ulcerative esophagitis.
                      Angiodysplasia – Dieulafoy Malformation.
                      Haemangiomas.
                      Ehlers-Danlos or Peutz-Jeghers’ syndrome.
                      Bleeding disorders.
                      Aorto-enteric fistulas (in those with an aortic graft).

   2.   Describe the principles of its medical, endoscopic and surgical management.
            Management of oesophageal varices
               The object of therapy is to stop acute bleeding as soon as possible and manage
                persistent varices with medical and procedural therapies. Bleeding must be
                controlled quickly to prevent shock.
               In endoscopic therapy, an endoscope (a device with a light that can look inside of a
                body cavity) is used. The health care provider may directly inject the varices with a
                clotting agent, or may place a rubber band around the bleeding veins. This procedure
                is used in acute bleeding episodes and as prophylactic (preventative) therapy.
               Acute bleeding may also be treated by a balloon tamponade – a tube that is inserted
                through the nose into the stomach and inflated with air to produce pressure against
                the bleeding veins.
               In transjugular intrahepatic portosystemic shunting, a catheter is extended through
                the vein into the liver where it connects the portal system to the systemic venous
                system and decreases portal venous pressure.
                Vasopressin is a medication that may be used to decrease portal blood flow and slow
                 bleeding.
                Emergency surgery for patients refractory to medical treatment may be necessary.
                 Portocaval shunts (that pass blood to the vena cava from the portal vein by a graft) or
                 resection of part of the oesophagus are two treatment options, but these procedures
                 have a high death rate.

            Medical management of all upper GI bleeds
                While waiting for endoscopy or if not indicated:
                    1) Decide if a central line is indicated (shock; significant co-morbidity; re-
                         bleed; poor peripheral access).
                    2) Monitor vital signs hourly until stable, then 4 hourly – you are watching for
                         re-bleed.
                    3) Daily U&E; clotting studies if >4 units blood needed (keep 2 units in
                         reserve).


BLOOD TRANSFUSIONS
   1.   Describe the assessment of haemodynamic status and principles of resuscitation.
             Bleeding as a cause of acute illness should be considered in a number of groups of
                patients:
                      Trauma victims.
                      Recent surgery or invasive procedures.
                      Altered coagulation states.
                      Acute abdomen.
                      Gynaecological problems.
                      History of upper gastrointestinal symptoms.
             Postural hypotension (i.e. significant fall in systolic BP > 10 mmHg when patient
                moves from supine to erect position) is only certain to be present after more than
                15% of blood volume (70 ml/kg) is lost.
             There are several causes of postural hypotension other than hypovolaemia, viz:
                      Drugs – narcotics, vasodilators.
                      Autonomic neuropathies (diabetes).
                      Increasing age.
                      Prolonged blood rest.
                      Spinal cord injuries.

            Symptoms and signs of acute blood loss
             Blood loss                Systolic blood pressure      Symptoms and signs
             (% of blood               (mmHg)
             volume)
             10 – 15                   Normal                       Postural hypotension
                                                                    Mild tachycardia
             15 – 30                   Slight fall                  Tachycardia
                                                                    Thirst
                                                                    Weakness
             30 – 40                   60 – 80                      Pallor
                                                                    Oliguria
                                                                    Confusion
                                                                    Restlessness
             > 40                      40 – 60                      Anuria
                                                                    Air hunger
                                                                    Coma
                                                                    Death
            Management of blood loss
                The urgency of volume replacement and the rate of resuscitation are both functions
                 of the amount and rate of loss. The initial assessment will suggest how much
                 replacement is needed. If after this replacement is given the patient is still not stable,
                 then it should be assumed that there is on-going, unrecognized bleeding.
             In the initial phase of resuscitation in the emergency department cross-matched blood
              is usually not available. It is appropriate to use a colloid initially and then to use a
              mixture of packed red cells and clotting factors later as they become available. Since
              the patient usually has no oral intake in this situation it is important to consider
              maintenance fluid requirements as well.
             Guidelines:
                    Attend to the priorities of intravascular volume and tissue perfusion. Don’t
                        wait for blood to be available – start volume replacement with colloid.
                    Determine the required rate of replacement (slow onset of haemorrhage
                        allows some compensation).
                    Titrate to an appropriate patient end-point.
                    Correct ½ the abnormality and then re-evaluate.
                    Replace deficits.
                    Cover continuing losses.
                    Provide maintenance.
         Massive blood loss
             When 50% of the circulating blood volume has been lost in a short period the
              optimal fluid for replacement is fresh whole blood, but volume replacement with
              colloid must commence while determining the patient’s blood group. Blood cross-
              matching takes time and group-specific uncross-matched blood is very safe
              serologically, and if available can be given until fresh cross matched blood is
              procurable.
             A review of the priorities in management of massive bleeding:
                    Cardiopulmonary resuscitation (CPR).
                    First-aid control of haemorrhage.
                    Restitution of circulating volume.
                    Restitution of oxygen carrying capacity.
                    Medical and surgical hemostasis.
                    Management of specific injuries.

2.   Explain the risks of blood transfusion.
         Haemolytic Transfusion Reactions:
                   The most dreaded complication and can be fatal.
                   The most severe reactions are those involving mismatches in the ABO
                      system.
                   Hemolysis is rapid and intravascular, releasing free haemoglobin into the
                      plasma.
                   Severity depends on the dose of RBCs given.
                   Anesthetized surgical patients have the most severe reactions, as they are
                      unable to give early warning signs of myalgias and chills.
                   Also backache and headache and in severe reactions, dyspnea, hypotension
                      and vascular collapse.
                   The transfusion must be stopped immediately. Hydration to prevent acute
                      tubular necrosis if haemoglobinemia is present.
         Leukoagglutinin Reactions:
                   Most transfusion reactions are not haemolytic but represent reactions to
                      antigens present on WBCs in patients who have been sensitized to the
                      antigens through previous transfusions or pregnancy.
                   Chills and fever within 12 hours of transfusion.
                   Severe cases show cough, dyspnea and transient pulmonary infiltrates on X-
                      ray.
                   Respond to acetominophen and diphenhydramine and corticosteroids.
         Anaphylactic Reactions:
                   Rarely, patients will develop hives or bronchospasm.
                   These reactions mostly due to plasma proteins (not WBCs).
                   Patients who are IgA-deficient may develop these reactions due to
                      antibodies to IgA.
                   Future reactions may be avoided using washed or frozen RBCs.
         Contaminated Blood:
                   Rarely, blood is contaminated with gram-negative bacteria.
                       Transfusion can lead to septicaemia and shock from endotoxin.
                       Antibiotics as indicated.
                 Diseases Transmitted Through Transfusion:
                       All blood products can transmit viral diseases (RBCs, platelets, plasma,
                          cryoprecipitate).
                       Donors are screened to detect those at high risk of transmitting diseases.
                       All blood is routinely screened for HBV, HCV and HIV.
                       Risk of post-transfusion hepatitis B is 1:200,000.
                       Risk of post-transfusion HIV is 1:250,000.
                       Risk of post-transfusion HCV is 1:3,300.
SOCIAL MEDICINE
    1.   Recognize the professional and domestic effects of alcoholism.
             Alcohol is a significant co-factor in disease. It is very obvious to practitioners that
                alcohol abuse lowers inhibitions, and is often associated with exposure to venereal
                diseases and to HIV infections. The chronic alcoholic’s lifestyle, malnutrition, and
                often bleak living conditions greatly enhance the chance for acquisition of such
                chronic diseases, both viral and tubercular. Further, in such patients, compliance
                therapy is a significant problem, contributing to the growing problem of M.
                tuberculosis drug resistance.

             Domestic effects
                 Low frustration tolerance.
                 Dysphoria.
                 Anxiety.
                 Poor quality sleep.
                 Financial difficulties.
                 Cognitive impairment.
                 Gastritis.
                 Fatty liver – hepatic steatosis.
                 Erectile dysfunction.
                 Marital difficulties.

             Professional effects
                 Alcohol use/abuse has been estimated to effect as much as 10-15% of physicians.
                 Historically, drug abuse has been linked to physicians because of their close
                  proximity to mind-altering drugs, narcotics, and drugs that elevated the mood, often
                  initiated during long arduous hours of training as interns or residents.
                 The AMA’s definition of “impairment” is “inability to practice medicine with
                  reasonable skill and safety to patients” because of a physician’s illness (illness or
                  illnesses including alcohol or drug dependence). These individuals provide a risk in
                  care for their patients.
                 Much of the susceptibility relates to the physicians personality. Their premorbid
                  compulsive personalities, rigid life schedule, excessively long hours and subsequent
                  fatigue often result in mood-altering drug experimentation as a release from stress.

    2.   Explain the public health aspects of chronic viral infections.
             Chronic persistent viral hepatitis
                 A more common clinical syndrome due to infection with hepatitis B and C viruses.
                 The patient usually has mild symptoms or only slight abnormalities in LFTs lasting
                  for 6 months or more (an arbitrarily defined period).
                 A benign self-limited disease that may last for several years but does not progress to
                  cirrhosis.
                 Represents the chronic carrier state – hepatitis B or C virus is present in the blood,
                  and the patient is infective.
                 Occurs frequently in immunocompromised patients (chronic renal failure and
                  Down’s syndrome).
                 Also in vertical transmission, common in SE Asia and Africa, where the carrier rate
                  for hepatitis B is 10-15%.
             Histologically, increased numbers of lymphocytes and plasma cells confined to the
              portal tracts, and the limiting plate of hepatocyte is intact. There is no active necrosis
              of liver cells. In hepatitis B, liver cells stain positive for HBsAg.

         Chronic active viral hepatitis
             Caused by hepatitis B, C and delta agent (delta requires B). An identical syndrome
              occurs as a toxic reaction to certain drugs (oxyphenisatin, methyldopa, isoniazid) or
              with alpha-1-antitrypsin deficiency, Wilson’s disease, and autoimmune chronic viral
              hepatitis.
             Diagnosis of the specific virus involved is by serologic tests. Antinuclear auto-
              antibodies are present in the serum of patients with autoimmune chronic active
              hepatitis, in whom viral serology is negative.
             Clinically, it is characterized by a chronic illness associated with marked elevation of
              liver enzymes (AST, ALT, GGT). Episodes of acute hepatitis may be superimposed,
              and portal hypertension may develop.
             Progresses to cirrhosis and chronic liver failure. It has a bad prognosis.
             Histologically, the hallmark is continuing focal necrosis of liver cells. The portal
              tracts show widening due to lymphocytic and plasma infiltration and fibrosis. The
              inflammation extents into the liver lobule, disrupting the limiting membranes of
              hepatocytes, with entrapment and necrosis of liver cells in the periphery of the lobule
              (“piecemeal necrosis”).
             Patients with chronic hepatitis B and C have an increased incidence of hepatocellular
              carcinoma.

         Prevention of viral hepatitis
             Preventative measures may be necessary for:
                   Individuals with known exposure to hepatitis A virus-contaminated food or
                        water.
                   Hospital employees exposed to blood products that are at risk of developing
                        hepatitis B or C.
                   Patients receiving transfused blood and blood products, again at risk for
                        hepatitis B and C.
             Hepatitis A: hyperimmune gamma globulin provides passive protection against
              hepatitis A and can be used to prevent a clinical attack after exposure to the virus.
              There is also a vaccine available that provides lifelong immunity.
             Hepatitis B: a recombinant DNA vaccine is effective in preventing infection and has
              been recommended for high-risk groups such as hospital employees who have
              contact with patients’ blood and tissues.
             Blood transfusions: screening of blood donors for hepatitis B and C has virtually
              eradicated transmission of viral hepatitis via blood transfusion.
             Needle exchanges: prevention of IVDU re-using non sterile needles, sharing of
              needles is important to reduce the transmission of HCV.

3.   Discuss the recognition and avoidance of stereotyping and judgmental behavior.
          Deeply held attitudes may create resistance to assessing alcohol use fully. For
              example, the problems faced by patients with alcohol problems can be viewed in a
              judgmental manner as self-inflicted, the implication being that they are less worthy
              in some way of further assistance than other groups of patients. The reality of
              contemporary medical practice however reflects hospitals being full of patients who
              are ill because of the lifestyles they have led whether the primary agents involved in
              their illnesses are diet, poor exercise, smoking or alcohol.
          Other attitudes frequently expressed about patients with alcohol problems reflect the
              futility of conducting assessments given that such patients will lie about the extent of
              their consumption or deny that they have a problem. While proponents of the disease
              model have placed much emphasis on alcohol denial, empirical examination of this
              issue through correlating patient self-reports with those of spouses or biochemical
              indices of drinking indicate that the vast majority of patients report alcohol
              consumption and negative consequences of drinking relatively accurately.
CLINICAL SKILLS
    1.   Describe the clinical examination of the patient with liver disease.
              There may be no symptoms or signs. In compensated disease there may be
                 Dupuytren’s contracture (fibrous thickening of the palmar fascia, with digital
                 contracture), parotid enlargement (alcohol abuse, not cirrhosis per se), hepatomegaly
                 (but a small, hard liver in advanced cirrhosis), palmar erythema, gynaecomastia,
                 testicular atrophy (all attributed to  oestrogen levels), clubbing, xanthelasmata,
                 xanthomata, and spider naevi. These consist of a central arteriole with leg-like
                 branches, which blanch on central pressure and are usually confined to skin drained
                 by the SVC (face, neck, upper chest and back). Ascites (shifting dullness); abnormal
                 abdominal veins; bleeding varices; splenomegaly. Jaundice; scratch marks; hepatic
                 encephalopathy (e.g. hepatic flap) and if there is hypoalbuminaemia, leuconychia and
                 pitting oedema. Altered vitamin D metabolism may cause osteomalacia.
              Hepatomegaly:
                       Congestive heart failure.
                       Secondary carcinomatous deposits.
                       Cirrhosis (usually alcoholic).
                       Also infections - glandular fever, infectious hepatitis; leukaemia and
                           reticuloendothelial disorders; tumors (primary hepatoma, amoebic and
                           hydatid cysts); amyloid, sarcoid and storage diseases; primary biliary
                           cirrhosis (large regular liver in women with jaundice and xanthelasmata);
                           haemachromatosis (look for pigmentation).
              Hepatosplenomegaly:
                       Chronic leukaemia.
                       Cirrhosis with portal hypertension.
                       Reticuloendothelial disease, e.g. Hodgkin’s disease and chronic lymphatic
                           leukaemia.
                       Myelofibrosis.
              Ascites:
                       Intra-abdominal neoplasms (remember gynaecological lesions).
                       Hepatic cirrhosis with portal hypertension (relatively late in the disease).
                       Congestive heart failure and rarely constrictive pericarditis.
                       Nephritic syndrome (and other low albumin states).
                       Tuberculous peritonitis
              Jaundice:
                       Acute viral hepatitis.
                       Bile duct obstruction.
                       Drugs.
                       Multiple secondary deposits of carcinoma in the liver.
                       Intrahepatic cholestasis.
                       Infectious mononucleosis.
                       Gilbert’s syndrome / Crigler-Najjar syndrome.
                       Also haemolytic anaemia, congenital hyperbilirubinaemia, stricture or
                           carcinoma of the major bile ducts or ampulla.

    2.   Outline the assessment of substance dependence.
             Narrowing of the drinking repertoire.
                       Do you tend to drink the same amount of alcohol each day of the week?
                       Stereotyped pattern of drinking should be deduced from the drinking
                          history.
             Salience of drinking (primary over other activities).
                       Do you skip meals because you are drinking?
                       Have you failed to do what was expected of you because of drinking?
                       Also refers to primacy over activities previously enjoyed and preferred to
                          drinking.
             Subjective awareness of compulsion to drink.
                       Have you experienced that you were not able to stop drinking once you had
                          started?
                       Enquiries about “loss of control” considered to be a classical early warning
                          indicator of evolving dependence.
            Increased tolerance to alcohol.
                  Have you needed more alcohol than previously to get the desired effect?
                  One of the more difficult elements to enquire specifically about in a single
                      question. Often best inferred from speed of drinking and ability to drink
                      large amounts of alcohol without becoming intoxicated.
            Repeated withdrawal symptoms.
                  Do your hands shake a lot in the morning after drinking?
                  Tremor and nausea occasionally after drinking do not necessarily imply
                      dependence.
            Relief or avoidance of withdrawal symptoms by further drinking.
                  Have you needed a first drink to settle you down the morning after
                      drinking?
                  A slightly disguised question such as this is useful before asking specific
                      questions on relief of morning tremor, sweating and nausea.
            Reinstatement after abstinence.
                  Think back to when you restarted drinking after having none for a few days
                      or weeks. How long does it take you until you are drinking as heavily as
                      before?
                  Reinstatement means the rapid return to the pre-abstinence level of drinking
                      and dependence symptomatology if and when the person resumes drinking.
                      Usually inferred from the longitudinal drinking history.

CAGE Questionnaire
       Are you or others CONCERNED about the level of your drinking?
       Do you or others get ANGRY when confronted about your drinking?
       Do you ever feel GUILTY about drinking?
       Do you ever have an EYE-OPENER in the morning?

         Answering YES to 2 or more is highly suggestive of a substance abuse problem.

3.   Discuss the interpretation of liver function tests.
          Functions of the liver
                   Detoxification – bilirubin, drugs
                   Protein synthesis – coagulation, serum proteins
                   Metabolism – glucose control, fat
          Alanine aminotransferase (ALT).
                   ALT is an enzyme produced in hepatocytes, the major cell type in the liver.
                      ALT is often inaccurately referred to as a liver function test, however, its
                      level in the blood tells little about the function of the liver. The level of
                      ALT in the blood (actually enzyme activity is measured in the clinical
                      laboratory) is increased in conditions in which hepatocytes are damaged or
                      die. As cells are damaged, ALT leaks out into the bloodstream. All types of
                      hepatitis (viral, alcoholic, drug-induced etc.) cause hepatocyte damage that
                      can lead to elevations in the serum ALT activity. The ALT level is also
                      increased in cases of liver cell death resulting from other causes such as
                      shock or drug toxicity. The level of ALT may correlate roughly with the
                      degree of cell death or inflammation; however, this is not always the case.
                      An accurate estimate of inflammatory activity or the amount of cell death
                      can only be made by liver biopsy.
          Aspartate aminotransferase (AST).
                   AST is an enzyme similar to ALT but less specific for liver disease as it is
                      also produced in muscle and can be elevated in other conditions (for
                      example, early in the course of a heart attack). Many physicians also
                      inaccurately refer to AST as a liver function test. In many cases of liver
                      inflammation, the ALT and AST activities are elevated roughly in a 1:1
                      ratio. In some conditions, such as alcoholic hepatitis or shock liver, the
                      elevation in the serum AST level may be higher than the elevation in the
                      serum ALT level.
          Alkaline phosphatase.
            Alkaline phosphatase is an enzyme, or more precisely a family of related
             enzymes, produced in the bile ducts, intestine, kidney, placenta and bone.
             An elevation in the level of serum alkaline phosphatase (actually enzyme
             activity is measured in the clinical laboratory), especially in the setting of
             normal or only modestly elevated ALT and AST activities, suggest disease
             of the bile ducts. Serum alkaline phosphatase activity can be markedly
             elevated in bile duct obstruction or in bile duct diseases such as primary
             biliary cirrhosis or primary sclerosing cholangitis. Alkaline phosphatase is
             also produced in bone and blood activity can be increased in some bone
             disorders.
   Gamma-glutamyltranspeptidase (GGT).
          An enzyme produced in the bile ducts that, like alkaline phosphatase, may
             be elevated in the serum of patients with bile duct diseases. Elevations in
             serum GGT, especially with elevations in alkaline phosphatase, suggest bile
             duct disease. Measurement of GGT is an extremely sensitive test, however,
             and it may be elevated in virtually any liver disease and even sometimes in
             normal individuals. GGT is also induced by many drugs, including alcohol,
             and its serum activity may be increased in heavy drinkers even in the
             absence of liver damage or inflammation.
   Bilirubin.
          Bilirubin is the major breakdown product that results from the destruction of
             old red blood cells (as well as some other sources). It is removed from the
             blood by the liver, chemically modified by a process called conjugation,
             secreted into the bile, passed into the intestine and to some extent
             reabsorbed from the intestine. Bilirubin concentrations are elevated in the
             blood either by increased production, decreased uptake by the liver,
             decreased conjugation, decreased secretion from the liver or blockage of the
             bile ducts. In cases of increased production, decreased liver uptake or
             decreased conjugation, the unconjugated or so-called indirect bilirubin will
             be primarily elevated. In cases of decreased secretion from the liver or bile
             duct obstruction, the conjugated or so-called direct bilirubin will be
             primarily elevated. Many different liver diseases, as well as conditions
             other than liver diseases (e.g. increased production by enhanced red blood
             cell destruction), can cause the serum bilirubin concentration to be elevated.
             Most adult acquired liver diseases cause impairment in bilirubin secretion
             from liver cells that cause the direct bilirubin to be elevated in the blood. In
             chronic, acquired liver diseases, the serum bilirubin concentration is usually
             normal until a significant amount of liver damage has occurred and cirrhosis
             is present. In acute liver disease, the bilirubin is usually increases relative to
             the severity of the acute process. In bile duct obstruction, or diseases of the
             bile ducts such as primary biliary cirrhosis or sclerosing cholangitis, the
             alkaline phosphatase and GGT activities are often elevated along with the
             direct bilirubin concentration.
   Albumin.
          Albumin is the major protein that circulates in the bloodstream. Albumin is
             synthesized by the liver and secreted into the blood. Low serum albumin
             concentrations indicate poor liver function. The serum albumin
             concentration is usually normal in chronic liver diseases until cirrhosis and
             significant liver damage is present. Albumin levels can be low in conditions
             other than liver diseases including malnutrition, some kidney diseases and
             other rare conditions. Albumin has a half life of days-weeks and thus
             disease of the liver must be present for a long time before significant
             alterations in albumin will be evident.
   Prothrombin time (PT).
          Many factors necessary for blood clotting are made in the liver. When liver
             function is severely abnormal, their synthesis and secretion into the blood is
             decreased. The prothrombin time is a type of blood clotting test performed
             in the laboratory and it is prolonged when the blood concentrations of some
             of the clotting factors made by the liver are low. In chronic liver diseases,
             the prothrombin time is usually not elevated until cirrhosis is present and the
              liver damage is fairly significant. In acute liver diseases, the prothrombin
              time can be prolonged with severe liver damage and return to normal as the
              patient recovers. Prothrombin time can also be prolonged in cases of
              vitamin K deficiency, by drugs (warfarin, used therapeutically as an anti-
              coagulant, prolongs the prothrombin time) and in non-liver disorders.
   Platelet count.
         Platelets are the smallest of the blood cells (actually fragments of larger
              cells known as megakaryocytes) that are involved in clotting. In some
              individuals with liver disease, the spleen becomes enlarged as blood flow
              through the liver is impeded. This can lead to platelets being sequestered in
              the enlarged spleen. In chronic liver diseases, the platelet count usually falls
              only after cirrhosis has developed. The platelet count can be abnormal in
              many conditions other than liver diseases.
   Serum protein electrophoresis.
         In this test, the major proteins in the serum are separated in an electric field
              and their concentrations determined. The four major types of serum
              proteins whose concentrations are measured in this test are albumin, alpha-
              globulins, beta-globulins and gamma-globulins. Serum protein
              electrophoresis is a useful test in patients with liver diseases as it can
              provide clues to several diagnostic possibilities. In cirrhosis, the albumin
              may be decreased and the gamma-globulin elevated. Gamma-globulin can
              be significantly elevated in some types of autoimmune hepatitis. The alpha-
              globulins can be low in alpha-1-antitrypsin deficiency.
                                            Learning Objectives

Dom            LO Title                                                 LO Detail
BCS    Normal anatomy and        1. To describe anatomy of the large intestine and of the anorectal area
       physiology                2. To list the main functions of the terminal ileum
                                 3. To outline the anatomical and physiological factors affecting fluid exchange in the
                                 gastro-intestinal tract
BCS    Causes and treatment      1. To list the principle microbiological causes of gastroenteritis and dysentery and to
       of diarrhoea              recognise their major pathological manifestations
                                 2. To describe the different pathophysiological processes that are responsible for
                                 diarrhoea.
                                 3. Discuss how the choice of therapy for diarrhoea depends upon the underlying
                                 cause of the disease.
BCS    Pathology and             1. To describe the pathology of ulcerative colitis and Crohn’s disease and other
       treatment of IBD          diseases of the large intestine
                                 2. To be able to distinguish between the clinical features of ulcerative colitis and
                                 Crohn’s disease
                                 3. To describe the principles of the management of IBD and outline the
                                 pharmacology of drugs used in its management
                                 4. To outline the genetic aspects of large bowel disease
EPPD Clinical trials             1. Be aware of the related psychological, ethical and doctor-patient issues
                                 concerning the enrolment of patients in clinical trials.
ICCP Psychological impact of 1. Describe the psychological impact of chronic disease
     chronic disease
ICCP Examination skills          1. To develop basic skills in rectal examination and proctoscopy
PPH    Per rectal bleeding       1. How does the prevalence of the conditions responsible for per rectal bleeding vary
       (Public Health)           according to patient age and gender?
                                 2. Discuss the pros and cons of screening for colorectal cancer.
                                 3. Who should and who shouldn’t be screened?
                                 4. What are the recommended screening guidelines for colorectal cancer?
PPH    Chronic illness (Social   Using inflammatory bowel disease as an example, discuss:
       Sciences)                 1. the range of responses to the diagnosis of a chronic disease;
                                 2. the life-style and psychosocial implications of chronic disease;
                                 3. strategies to assist patients to accept and optimally manage their chronic illness;
                                 4. the role of community organisations in assisting persons with chronic diseases;
                                 and
                                 5. the importance of a strong partnership between patient, general practitioner,
                                 specialists and other health professionals in the holistic management of people with
                                 chronic disease.
It Returns To Haunt Me
ANATOMY AND PHYSIOLOGY OF THE LARGE INTESTINE
   1.   Outline the anatomical and physiological factors affecting fluid exchange in the gastro-
        intestinal tract.
        Daily water turnover (mL) in the gastrointestinal tract

             Ingested                                                         2000
             Endogenous secretions                                            7000
                 Salivary glands                      1500
                 Stomach                              2500
                 Bile                                  500
                 Pancreas                             1500
                 Intestine                            1000
             Total input                                                      9000
             Reabsorbed                                                       8800
                 Jejunum                              5500
                 Ileum                                2000
                 Colon                                1300
             Balance in stool                                                  200

        Secretions of the small intestine
                  Mucus by Brunner’s glands:
                        Located in the first few centimeters of the duodenum.
                        Secrete an alkaline mucus in response to (1) tactile stimuli or irritating
                            stimuli of the overlying mucosa; (2) vagal stimulation, which causes
                            secretion concurrently with increase in stomach secretion; and (3)
                            gastrointestinal hormones, especially secretin.
                        Protects the duodenal wall from digestion by the gastric juice.
                        Contains a large excess of bicarbonate ions.
                        Inhibited by sympathetic stimulation.
                  Intestinal digestive juices by the Crypts of Lieberkühn:
                        Located on the entire surface of the small intestine.
                        Lie between the intestinal villi.
                        Crypts and villi covered by an epithelium composed of two cell types: (1) a
                            moderate number of goblet cells, which secrete mucus the lubricates and
                            protects the intestinal surfaces, and (2) a large number of enterocytes, which
                            in the crypts secrete large quantities of water and electrolytes and, over the
                            surfaces of the villi, reabsorb the water and electrolytes along with the end
                            products of digestion.

        Secretions of the large intestine
                  Mucus secretion:
                        Mucosa has many Crypts of Lieberkühn, but there are no villi.
                        Consists mainly of mucous cells that secrete only mucus.
                        Contains large amounts of bicarbonate ions.
                        Rate of secreted regulated by direct, tactile stimulation of the mucous cells
                            and by local nervous reflexes. Also stimulation of the pelvic nerces, which
                            carry the parasympathetic innervation to the distal one half to two thirds of
                            the large intestine, also causes marked increase in the secretion of mucus
                            (associated with increased motility).
                        Mucus protects from wall against excoriation and it provides the adherent
                            medium for holding fecal material together. Furthermore, it protects the
                            wall from bacterial activity and provides a barrier to acid.
                  Secretion of water and electrolytes in response to irritation:
                        Rampant bacterial infection (as in enteritis) causes irritation which results in
                            the mucosa secreting large amounts of water and electrolytes in addition to
                            the normal viscid solution of alkaline mucus.
                    Dilutes the irritating factors and causes rapid movement of the feces toward
                     the anus.
                    Diarrhea, results in loss of large quantities of water and electrolytes.
                    Also washes away the irritant factor, which promotes earlier recovery than
                     would otherwise occur.

Anatomical basis of absorption
         Absorptive surface of the intestinal mucosa – the villi:
               Absorptive surface of the intestinal mucosa has many folds called valvulae
                  conniventes (or folds of Kerckring), which increase the surface area of the
                  absorptive mucosa about threefold.
               Located over the entire surface of the small intestine are literally millions of
                  small villi. These enhance the absorptive area another 10-fold.
               A brush border consisting of as many as 1000 microvilli characterizes each
                  intestinal epithelial cell. This increases the surface area exposed to the
                  intestinal materials at least another 20-fold.
               Combination of the folds of Kerckring, the villi, and the microvilli increases
                  the absorptive area of the mucosa perhaps 1000-fold.
               Within the villi, the arrangement of the vascular system for the absorption of
                  fluid and dissolved material into the portal blood and the central lacteal for
                  lymph is especially advantageous – prevents a build-up of digestive
                  products and hence ensures a favourable concentration gradient for
                  diffusion.

Absorption in the small intestine
         Absorption of water:
               Isosmotic absorption: water is transported through the intestinal membrane
                   entirely by diffusion.
               As ions and nutrients are absorbed, so also is an isosmotic equivalent of
                   water absorbed.
         Absorption of ions:
               Active transport of sodium:
                         Small intestine must absorb 25 to 35 grams of sodium each day (20
                             to 30 grams in endogenous secretions, 5 to 8 grams orally).
                         Sodium plays an important role in the absorption of sugars and
                             amino acids (co-transport).
                         Active transport of sodium from inside the epithelial cells through
                             the basolateral walls into the paracellular spaces.
                         Part of the sodium is absorbed with chloride ions.
                         Part of the sodium is absorbed while potassium or hydrogen ions
                             are transported in the opposite direction.
                         Sodium moves down a steep electrochemical gradient from the
                             chyme through the brush border of the epithelial cell into the
                             epithelial cell cytoplasm.
                         Osmosis of water creates a flow of fluid into and through the
                             paracellular space and, finally, into the circulating blood of the
                             villus.
               Aldosterone greatly enhances sodium absorption:
                         Dehydration causes large amounts of aldosterone to be secreted by
                             the adrenal glands.
                         Enhances all the enzyme and transport mechanisms for all aspects
                             of sodium absorption by the intestinal epithelial cells.
                         Secondary increases in absorption of chloride ions, water and some
                             other substances.
                         Action also on kidney to retain Na
         Secretion of bicarbonate ions in the ileum and large intestine – simultaneous
          absorption of chloride ions:
               Provides alkaline bicarbonate ions to buffer acidic products formed by
                   bacteria, especially in the large intestine.
                      An exchange protein in the luminal membrane exchanges bicarbonate ions
                       formed inside the cell for chloride ions in the intestinal lumen.
                    The excess chloride is transported by facilitated diffusion through the
                       basolateral membrane.
              Extreme secretion in Cholera and other types of diarrhoea:
                    Normally, immature epithelial cells deep within the Crypts of Lieberkühn
                       secrete small quantities of sodium chloride and water into the intestinal
                       lumen. This secretion is normally reabsorbed by the older epithelial cells
                       outside the crypts, thus providing a watery solution for absorbing intestinal
                       digestates.
                    Toxins of cholera and some other types of diarrheal bacteria can stimulate
                       the crypt secretion so greatly that this secretion inundates the reabsorption.
                       The toxin stimulates the formation of excess cAMP, which opens
                       tremendous numbers of chloride channels, allowing chloride to flow into the
                       crypts. In turn, this activates a sodium pump. All this excess sodium
                       chloride causes extreme osmosis of water into the crypts as well.
                    Characteristic “rice-water diarrhoea”
              Absorption of glucose:
                    Glucose is basically transported by a sodium co-transport mechanism – the
                       transport protein will not transport the sodium to the interior until it also
                       combines with some other substance such as glucose.
                    The initial active transport of sodium through the basolateral membrane
                       provides the eventual motive force for moving glucose through the
                       enterocyte to the paracellular space.
                    Transport of glucose causes a high osmotic pressure in the paracellular
                       space, which causes water to be absorbed osmotically through the cell
                       junctions. At high concentrations, the osmotic flow increases and carries
                       with it anything dissolved in the fluid (“solvent drag” mechanism).

     Absorption in the large intestine
              Absorption and secretion of electrolytes and water:
                    High capacity for active absorption of sodium, and the electrical potential
                       created causes chloride absorption as well.
                    The tight junctions are much tighter, preventing back-diffusion of ions,
                       allowing the mucosa to absorb sodium ions against a much higher
                       concentration gradient.
                    The mucosa secretes bicarbonate ions while it simultaneously absorbs
                       chloride ions. The bicarbonate helps neutralize the acidic end products of
                       bacterial action in the colon.
                    The absorption of sodium and chloride ions creates an osmotic gradient
                       across the large intestinal mucosa, which in turn causes absorption of water.
              Maximum absorption capacity:
                    Able to absorb a maximum of about 5 to 7 litres of fluid and electrolytes
                       each day.
                    When the total quantity exceeds this amount (by way of the ileocecal valve
                       or by large intestinal secretions), the excess appears in the feces as
                       diarrhoea.

2.   Describe the function of the terminal ileum.
          In the terminal ileum, Na+ is cotransported with bile salts.
          Vitamin B12 absorption from food involves a series of steps in which B12 is released
             from food, binds to R factors from saliva, and forms a complex with intrinsic factor
             in the stomach that is absorbed by specific receptors in the terminal ileum.
                   Resorption of bile salts
                   Absorption of Vitamin B12

3.   Describe the surgical anatomy of the large intestine and of the anorectal area.
     Caecum
              Location: lies below the junction of the ileum with the large intestine. It is a blind-
               ended pouch in the right iliac fossa about 6 cm long.
          Relations:
                Anteriorly: small intestine, sometimes the greater omentum, and the
                    anterior abdominal wall in the right iliac region.
                Posteriorly: psoas and iliacus muscles, femoral nerve, lateral cutaneous
                    nerve of the thigh, the appendix.
                Medially: the appendix.
          Blood supply:
                Arteries: from the anterior and posterior caecal arteries, which are
                    branches of the ileocolic artery, a branch of the superior mesenteric artery.
                Veins: the ileocolic vein, a tributary of the superior mesenteric vein which
                    then unites with the splenic vein to form the portal vein.
          Lymph drainage: pass to lymph nodes in the mesoappendix and to ileocolic lymph
           nodes that lie along the ileocolic artery. Efferent lymph vessels pass to the superior
           mesenteric lymph nodes.
          Nerve supply: branches from the sympathetic and parasympathetic (vagus) nerves
           from the superior mesenteric plexus.

Appendix
          Location: varies from 8-13cm long, the base is attached to the posteromedial surface
           of the cecum about 2.5cm below the ileocecal junction. The appendix lies in the
           right iliac fossa, its base is situated one-third of the way up the line joining the right
           anterior superior iliac spine to the umbilicus (McBurney’s point). Internally, the base
           is found by identifying the teniae coli and tracing them back to where they converge
           to form a continuous longitudinal muscle coat.
          Blood supply:
                 Arteries: the appendicular artery, a branch of the posterior cecal artery.
                 Veins: the appendicular vein joins the posterior cecal vein.
          Lymph drainage: the lymph vessels drain into nodes lying in the mesoappendix, then
           passes through a number of mesenteric nodes to reach the superior mesenteric nodes.
          Nerve supply: from sympathetic and parasympathetic (vagus) nerves from the
           superior mesenteric plexus. Afferent nerve fibers concerned with the conduction of
           visceral pain from the appendix accompany the sympathetic nerves and enter the
           spinal cord at the level of T10.

Ascending colon
          Location: about 13 cm long and lies in the right lower quadrant. At the inferior
           surface of the right lobe of the liver, it turns left, forming the right colic flexure.
          Relations:
                 Anteriorly: coils of small intestine, the greater omentum, anterior
                    abdominal wall.
                 Posteriorly: the iliacus, the iliac crest, the quadratus lumborum, the origin
                    of the transverse abdominis muscle, lower pole of the right kidney,
                    iliohypogastric and the ilioinguinal nerves.
          Blood supply:
                 Arteries: from the ileocolic and right colic arteries, branches of the
                    superior mesenteric artery.
                 Veins: the ileocolic and right colic veins, tributaries of the superior
                    mesenteric vein.
          Lymph drainage: lymph vessels pass to the paracolic and epicolic lymph nodes and
           from them to the superior mesenteric lymph nodes.
          Nerve supply: derived from the coeliac and superior mesenteric ganglia.

Transverse colon
          Location: about 38 cm long and occupies the umbilical region, suspended by the
           transverse mesocolon. The left colic flexure is higher than the right colic flexure and
           is suspended form the diaphragm by the phrenicocolic ligament.
          Relations:
                 Anteriorly: the greater omentum, anterior abdominal wall.
                 Posteriorly: duodenum, head of the pancreas, coils of the jejunum and
                    ileum.
        Blood supply: proximal two-thirds by the middle colic artery, a branch of the
         superior mesenteric artery; distal third by the left colic artery, a branch of the
         inferior mesenteric artery.
        Lymph drainage: proximal two-thirds drain into the superior mesenteric nodes;
         distal third drains into the inferior mesenteric nodes.
        Nerve supply: proximal two-thirds innervated by sympathetic and vagal nerves
         through the superior mesenteric plexus; distal third innervated by sympathetic and
         parasympathetic pelvic splanchnic nerves through the inferior mesenteric plexus.

Descending colon
        Location: about 25 cm long and lies in the left upper and lower quadrants. From the
         left colic flexure to the pelvic brim, where it becomes continuous with the sigmoid
         colon.
        Relations:
                Anteriorly: coils of small intestine, the greater omentum, anterior
                   abdominal wall.
                Posteriorly: lateral border of the left kidney, origin f the transverses
                   abdominis muscle, quadratus lumborum, iliac crest, the iliacus, the left
                   psoas. The iliohypogastric and the ilioinguinal nerves, the lateral cutaneous
                   nerve of the thigh, and the femoral nerve.
        Blood supply:
                Arteries: the left colic and the superior sigmoid arteries of the inferior
                   mesenteric artery.
                Veins: drained by the inferior mesenteric vein.
        Lymph drainage: lymph vessels pass to the intermediate colic lymph nodes, then to
         the inferior mesenteric lymph nodes. Those from the left colic flexure also drain to
         the superior mesenteric lymph nodes.
        Nerve supply: sympathetic supply from the lumbar part of the sympathetic trunk and
         the superior hypogastric plexus. The parasympathetic supply is derived from the
         pelvic splanchnic nerves.

Sigmoid colon
        Location: about 25-38 cm long and is a continuation of the descending colon. At the
         level of S3 it becomes continuous with the rectum.
        Relations:
               Anteriorly: in the male, urinary bladder; in the female, the posterior surface
                   of the uterus and upper part of the vagina.
               Posteriorly: the rectum and the sacrum, also the terminal ileum.
        Blood supply:
               Arteries: from the sigmoid branches of the inferior mesenteric artery.
               Veins: the inferior mesenteric vein returns blood from the sigmoid colon.
        Lymph drainage: to the inferior colic lymph nodes on the branches of the left colic
         arteries, and from them to the inferior mesenteric lymph nodes around the inferior
         mesenteric artery.
        Nerve supply: sympathetic supply from the lumbar part of the sympathetic trunk and
         the superior hypogastric plexus by means of the plexuses on the branches of the
         inferior mesenteric artery. The parasympathetic supply is derived from the pelvic
         splanchnic nerves.

Rectum
        Location: about 13 cm long and begins in front of the third sacral vertebrae. It ends
         2.5 cm in front of the coccyx by piercing the pelvic diaphragm and becoming
         continuous with the anal canal.
        Relations:
               Posteriorly: the sacrum and coccyx; piriformis, coccygeus, and levatores
                  ani muscles; the sacral plexus; the sympathetic trunks.
               Anteriorly: in the male, sigmoid colon and coils of ileum in the rectovesical
                  pouch, the posterior surface of the bladder, the termination of the vas
                  deferens and the seminal vesicles on each side, the prostate; in the female,
                                           sigmoid colon and coild of ileum that occupy the rectouterine pouch (Pouch
                                           of Douglas), posterior surface of the vagina.
                                Blood supply:
                                       Arteries: from the superior, middle, and inferior rectal arteries. Superior
                                           rectal artery is a direct continuation of the inferior mesenteric artery.
                                           Middle rectal artery is a small branch of the internal iliac artery. Inferior
                                           rectal artery is a branch of the internal pudendal artery.
                                       Veins: the superior, middle, and inferior rectal veins.
                                Lymph drainage: drain into the pararectal lymph nodes. Lymph vessels draining the
                                 upper half accompany the superior rectal artery to the inferior mesenteric nodes.
                                 Lymph vessels from the lower part follow the middle rectal artery to the internal iliac
                                 nodes.
                                Nerve supply: the middle rectal plexus is an offshoot of the inferior hypogastric
                                 plexus. The parasympathetic nerves are derived from S2, S3, and S4 nerves and run
                                 with the pelvic splanchnic nerves to join the inferior hypogastric plexus. The sensory
                                 fibers follow the path of the parasympathetic nerves; their fibers are stimulated by
                                 distention of the rectum.

                         DIARRHOEA
COMPLAINT                    ASSOCIATED CLINICAL                       INCUBATION                EPIDEMIOLOGICAL                  ORGANISMS          FIRST LINE
                             FEATURES                                  PERIOD                    FEATURES                                            TREATMENT
                             COMMON       OTHERS
ACUTE                        Vomiting          Sever dehydration       24-72 hours               Infants and young                Rotavirus          Rehydration therapy
WATERY                       Fever             in some
DIARRHEA                                                                                         children
                                                                                                 Common world-wide in all
                                                                                                 socio-economic groups
                                                                                                 Peak in colder seasons in
                                                                                                 temperate climates
                             Nausea            Fever                   6-72 hours                Infants and young children in    Enterotoxigenic    Rehydration therapy
                             Vomiting          Malaise                                           developing countries             Escherichia coli
The stool takes the          Abdominal         Severe dehydration                                Traveler’s diarrhea in adults
shape of the                 pain
container                    Nausea            Malaise                 8-36 hours                Children                         Non-typhoid        Rehydration therapy
                             Vomiting                                                            Common world-wide                Salmonellae
                             Fever                                                               Food-borne outbreaks (animal
                             Chills                                                              products)
                             Abdominal                                                           Warmer seasons
                             pain
                             Abdominal         Chills                  3-5 days                  World-wide distribution          Campylobacter      Rehydration therapy
                             pain              Blood and pus in                                  In developed countries may                          Erythromycin in severe
                             Fever             the stools                                        be food-borne (animal                               cases
                             Malaise                                                             products) or transmitted by
                                                                                                 handling of animals
                             Vomiting          Severe dehydration      1-3 days                  Children in endemic areas        Vibrio cholerae    Rehydration therapy
                             Abdominal         Circulatory                                       Adults in newly affected areas                      Tetracycline
                             pain              collapse, “shock”                                 Not found in Latin America
                             Nausea            Fever                   6-72 hours                Nursery outbreaks in             Enterpathogenic    Rehydration therapy
                             Vomiting                                                            developed countries              Escherichia coli
                                                                                                 Uncertain in developing
                                                                                                 countries
DYSENTRY                     Fever             Malaise                 36-72 hours               Children                         Shigellae          Rehydration therapy
The stool is soft            Abdominal         Vomiting                                          Poor hygiene                                        Ampicillin or
and watery with              pain              Urgency to                                        Malnutrition                                        Trimethoprim-
blood and/or pus                               defaecate                                         Institutions                                        Sulfamethoxazole
                                               Painful spasm on                                  Warmer seasons
                                               defaecation
PROLONGED                    Abdominal                                 2-6 weeks                 All age groups                   Entamoeba          Metronidazole
DIARRHEA (or                 discomfort                                                          World-wide distribution          histolytica*
DYSENTRY)                    Abdominal         Anorexia                1-3 weeks                 Young children                   Giardia lambia*    Metronidazole
For at least 7 days,         distention        Nausea                                            Some travelers
stools have been             Flatulence        Malabsorption                                     Poor hygiene
more frequent or of                            Frothy stools                                     World-wide distribution
softer consistency
(with or without
blood or pus)
                         * Can be identified on examination of stools with a light microscope.
                      Blood and pus from Shigellae and Campylobacter can also be identified.



       1.      Outline the main microbiological causes of gastroenteritis and dysentery.
               Viral gastroenterocolitis
                                Rotavirus (group A): 70-nm dsDNA virus, person-to-person transmission via food
                                 and water, affects 6- to 24-month-old infants. Worldwide, 140 million cases and 1
                                 million deaths occur per year. Minimal infective inoculum is 10 particles. Outbreaks
                                 are characteristic.
                                       Detect using the rotavirus latex agglutination test.
                                Enteric adenoviruses: 80-nm dsDNA virus, person-to-person transmission, children
                                 younger than 2 years.
          Astroviruses: ssRNA viruses affecting children; person-to-person transmission via
           water, cold foods, and raw shellfish.
          Small round structured viruses, of which Norwalk virus is the prototype, classified
           in the family Caliciviridae: 27-nm ssRNA viruses; person-to-person transmission
           via cold food, water, and raw shellfish; affects school-age children to adults.
           Outbreaks are common after exposure to a common food source.
          Morphology: the small intestine exhibits modestly shortened villi, lamina propria
           inflammation, and damage to surface cells.
          Clinical findings: incubation periods range from hours to several days; acute illness
           occurs from 1 to 7 or more days. In addition to diarrhea, anorexia, headache, and
           fever may develop.

Bacterial enterocolitis
          Mechanisms of bacterial illness are as follows:
                 Ingestion of preformed toxin in contaminated food (food poisoning):
                     Staphylococcus aureus, Vibrios, Clostridium perfringens. Botulism is
                     neurotoxic, nor diarrheogenic.
                 Infection by toxigenic organisms, which proliferate in gut lumen and
                     elaborate an enterotoxin.
                 Infection by enteroinvasive organisms, which proliferate, invade, and
                     destroy mucosal epithelial cells.
          The key bacterial properties by which disease can be produced are:
                 Bacterial adhesion and replication: to produce disease, ingested organisms
                     must adhere to the mucosal epithelial cells; otherwise, they are swept away.
                     Adherence depends on plasmid-encoded adhesions; proteins are expressed
                     on the bacterial surface.
                           Peristalsis, diarrhoeal tide
                 Bacterial enterotoxins: these are polypeptides that cause diarrhea. Two
                     mechanisms:
                           Secretagogues (e.g. cholera toxin from Vibrio cholerae), which
                               stimulate fluid secretion by activation of endogenous secretion
                               systems.
                           Cytotoxins (e.g. Shiga toxin), which cause direct tissue damage
                               through epithelial cell necrosis.
                           E. coli produce both forms of toxins.
                 Bacterial invasion: microbe-stimulated endocytosis permits intracellular
                     proliferation, cell lysis, cell-to-cell spread, and spread to circulation. This is
                     typical of enteroinvasive E. coli, Shigella, Salmonella, and Yersinia
                     enterocolitica.
          Morphology: morphologic manifestations are extremely variable. Nonspecific
           features include damage to surface epithelium, increased mitotic rate, lamina propria
           hyperemia and edema, and neutrophilic infiltration of lamina propria and epithelium.
                 Salmonella: ileum and colon with Peyer patch involvement, S. typhimurium
                     causes typhoid fever (bacteremia and dissemination to biliary tree, joints,
                     bones, and meninges).
                 Shigella: colonic inflammation, erosion, and exudates.
                 Campylobacter jejuni and other species: small intestine, appendix, colon,
                     ulcers, inflammation, and exudates.
                 Y. enterocolitica and Y. pseudotuberculosis: ileum Peyer patches,
                     appendix, colon, and mesenteric lymph nodes with necrotizing granulomas
                     and systemic spread.
                 V. cholerae: essentially normal small intestine.
                 Clostridium perfringens: usually mild; some strains cause severe
                     necrotizing enterocolitis (pigbel).
                 E. coli: enterotoxigenic E. coli produce cholera-like toxin;
                     enterohemorrhagic produce shiga-like toxin; enteropathogenic attach and
                     efface epithelium but do not invade; enteroinvasive are like shigellosis. All
                     cause traveller’s diarrhea.
          Clinical findings:
                     Ingestion of preformed toxins: explosive diarrhea and abdominal pain
                      within hours.
                     Infection with enteric pathogens: incubation period of hours to days,
                      followed by diarrhea and dehydration or dysentery, depending on the
                      pathogenic mechanism.
                     Insidious infection: Yersinial and mycobacterial infection. All
                      enteroinvasive organisms can mimic (or coexist with) acute onset of
                      inflammatory bowel disease.

2.   Summarize the different mechanisms that cause diarrhea and how they relate to choice
     of therapy.
             Pathophysiologic mechanisms
            Secretory diarrhea:
                  Associated with cAMP increase:
                            Enterotoxin of Vibrio cholerae.
                            Enterotoxin of Escherichia coli.
                            Vasoactive intestinal polypeptide (from pancreatic islet cell
                               neoplasms).
                            Bile acids.
                  Not associated with cAMP:
                            Enterotoxin of Staphylococcus aureus.
                            Enterotoxin of Clostridium perfringens.
                            Some laxatives (bisacodyl, phenolphthalein).
                            AIDS (unknown mechanism).
                  Mucosal injury:
                            Infections: viral and Salmonella gastroenteritis, Shigella, E. coli,
                               Campylobacter colitis.
                            Inflammatory bowel disease.
                  Neoplasms:
                            Gastrinoma (gastrin).
                            Carcinoid syndrome (serotonin, prostaglandins).
                            Villous adenoma.
            Osmotic diarrhea:
                  Disaccharidase deficiency (lactose or sucrose intolerance).
                  Postgastrectomy.
                  Postvagotomy.
                  Laxatives (lactulose, magnesium salts).
            Motility disorders:
                  Irritable bowel syndrome.
                  Autonomic neuropathy (diabetes mellitus).
                  Laxatives.
            Failure of colonic water absorption:
                  Total colectomy – surface area
                  Irritable bowel syndrome.
            Malabsorption:
                  Inadequate digestion:
                            Postgastrectomy.
                            Deficiency of pancreatic enzymes (chronic pancreatitis, cystic
                               fibrosis, pancreatic resection).
                            Zollinger-Ellison syndrome (high acid inhibits lipase).
                  Deficient bile salt concentration:
                            Obstructive jaundice.
                            Bacterial overgrowth leading to bile salt deconjugation (stasis in
                               blind loops, diverticula, fistulas, hypomotility states e.g. diabetes,
                               scleroderma, visceral myopathy).
                            Interrupted enterohepatic circulation of bile salts (terminal ileal
                               resection, Crohn’s disease).
                            Precipitation of bile salts (neomycin, cholestyramine (therapeutic
                               intent)).
                  Primary mucosal abnormalities:
                  Celiac disease.
                  Tropical sprue.
                  Whipple’s disease.
                  Amyloidosis.
                  Radiation enteritis.
                  Abetalipoproteinemia.
                  Giardiasis.
            Inadequate small intestine:
                  Intestinal resection (Crohn’s disease, mesenteric vascular disease
                     with infarction).
                  Jejunoileal bypass.
            Lymphatic obstruction:
                  Intestinal lymphangiectasia.
                  Malignant lymphoma.
                  Macroglobulinemia.

Treatment
 Acute diarrhea:
        In the younger patient, maintenance of hydration is particularly important.
        The aim of treatment is to keep patients functioning while minimizing
          symptoms. Antiemetics and antidiarrheal agents constitute practical
          therapy.
        Avoid antimicrobial drugs. They are usually not indicated and can mask or
          delay a diagnosis where stool cultures are not carried out.
 Chronic diarrhea:
        Aim for a documented diagnosis.
        Endoscopic diagnosis is much simpler than in the past and should be used
          earlier.
        Realize that some patients may never be “diagnosed”. Symptom relief may
          be the best that can be achieved.
 Pharmacological agents:
        Rehydration:
                Oral (clear liquids, sodium and glucose-containing oral rehydration
                    solutions). (One teaspoon salt, 5 teaspoons of glucose/L)
                Intravenous (normal saline or lactated Ringer’s solution, especially
                    if severely dehydrated or patient has intractable vomiting).
        Absorbents (Kaopectate, aluminium hydroxide): These do not alter the
          course of the disease or reduce fluid loss but allow the patient more control
          over the timing of defecation. Other medications should be taken ½ hour
          before or 2 hours after absorbents are used.
        Antisecretory agents such as bismuth subsalicylate (Pepto-Bismol). Usual
          dose is 30 ml every 30 minutes for 8 doses.
        Antiperistaltics, such as opiate derivatives. Do not use in patients with
          fever, systemic toxicity, or bloody diarrhea. Discontinue if no improvement
          or if patient deteriorates.
                Diphenoxylate with atropine (Lomotil). Available in tablets (2.5
                    mg of diphenoxylate) and liquid (2.5 mg of diphenoxylate/5 ml).
                    The initial dose for adults is two tablets QID (20 mg/day). For
                    children the dose is 0.1 mg/kg/dose QID. The dose is tapered as
                    diarrhea improves. It is not indicated for diarrhea caused by
                    pseudomembranous colitis or enterotoxin-producing or invasive
                    bacteria. Lomotil should not be used in ulcerative colitis or in
                    children under 2 years of age.
                Loperamide (Imodium). Available over the counter in 2 mg
                    capsules and liquid (1 mg/5 ml). It increases the intestinal
                    absorption of electrolytes and water and decreases intestinal
                    motility and secretion. The dose in adults is 4 mg initially,
                    followed by 2 mg after each diarrhea stool, not to exceed 16 mg in
                    one 24-hour period. In children the dose is based on age, with 2 to
                    5 year olds receiving 1 mg TID, 6 to 8 year olds 2 mg BID, and 9
              to 12 year olds 2 mg TID on the first day of treatment. Thereafter
              0.1 mg/kg is administered after each diarrhea stool, not to exceed
              the total daily dose recommended for the first day of therapy.
              Loperamide is safe and decreases the number of unformed stools
              and the duration of diarrhea in patients with Shigella-induced
              dysentery who are treated with ciprofloxicin.
   Antibiotics. Not necessary for most episodes of diarrhea but should be
    directed against known or strongly suspected pathogens. Once cultures are
    done, empiric with an agent that covers Shigella and Campylobacter is
    reasonable in those with severe diarrhea with systemic signs. A 3-day
    course of a fluoroquinolone (ciprofloxacin 500 mg PO BID or norfloxacin
    400 mg PO BID) is the first-line therapy. TMP/SMP (Pactrim DS 2 tab PO
    QD) is an alternative therapy, but resistant organisms are common in the
    tropics. If the diarrhea is caused by seafood ingestion, infection with either
    Vibrio cholerae or Vibrio parahaemolyticus is possible and can be treated
    with either a fluoroquinolone or with doxycycline 100 mg PO BID.
   Traveler’s diarrhea. Prophylaxis not routinely recommended because of
    the risk of adverse effects from the drugs (rash, anaphylaxis, vaginal
    candidiasis) and the development of resistant gut flora. Possible regimens
    for prophylaxis include bismuth subsalicylate (Pepto-Bismol) 524 mg PO
    BID with meals and QHS, doxycycline 100 mg PO QD (resistance
    documented in many areas of the world), TMP/SMX 160 mg/800 mg (1
    double strength tablet) PO QD, or norfloxacin 400 mg PO QD
    (fluoroquinolones should not be prescribed to children or pregnant women).
    No significant resistance to fluoroquinolones has yet been reported in high-
    risk areas, and they are the most effective antibiotics in regions where
    susceptibilities are not known. Loperamide can be added to the
    fluoroquinolones or TMP/SMX when treating traveler’s diarrhea. These
    medications should be continued for 1 or 2 days after patient returns home.
   Fluid repletion. A simple oral rehydration solution may be composed of 1
    level teaspoon of salt and 4 heaping teaspoons of sugar added to 1 liter of
    water. Bottled flavored mineral water with saltine crackers is an acceptable
    alternative.
INFLAMMATORY BOWEL DISEASE

                                      Ulcerative Colitis                Crohn’s Disease
Clinical features
   Rectal involvement                 Over 90%                          Rectum spared in > 50%
   Distribution of lesions            Continuous                        Skip lesions
   Mucosal appearance                 Friable, purulent, diffusely      Aphthous, linear ulcers with
                                      involved                          cobblestoning
   Associated ileal disease           10%, mild, terminal ileal         50% have combined ileal and
                                      inflammation                      colonic involvement
   Perianal abscess, fistulas         Rare                              Common
   Intestinal strictures and          Not seen                          Common
   Obstruction
   Intestinal fistulas                Not seen                          Common
   Fissures (radiologic)              Not seen                          Common
   Intestinal perforation             Rare                              Rare
   Intestinal hemorrhage              Common                            Rare
   (severe)
   Toxic megacolon                    Rare                              Very rare
Extraintestinal manifestations
   Sclerosing pericholangitis         Common                            Rare
   Uveitis or arthritis               Common                            Common
   Pyoderma gangrenosum               Rare                              Not seen
Pathologic features
   Depth of inflammation              Mucosal (submucosal rarely)       Transmural
   Creeping mesenteric fat            Not seen                          Common
   Fibrous thickening of wall         Not seen                          Common (“lead pipe”)
   Crypt abscesses                    Common                            Common
   Pseudopolyps                       Common                            Common
   Granulomas (epitheloid,            Not seen                          Common
   noncaseating)
   Fissures (microscopic)             Not seen                          Common
   Dysplasia                          Common                            Rare
   Carcinoma                          10%                               Rare

     1.   Describe the clinical features of inflammatory bowel disease.
          Ulcerative colitis
                     The major symptoms of UC are bloody diarrhea and abdominal pain, often with fever
                      and weight loss in more severe cases. With mild disease, there may be one or two
                      semiformed stools per day, containing little blood, and there may be no systemic
                      manifestations. In contrast, the patient with severe disease may have frequent liquid
                      stools containing blood and pus, complain of severe cramps, and demonstrate
                      symptoms and signs of dehydration, anemia, fever and weight loss. With
                      predominantly rectal involvement, constipation rather than diarrhea may be present,
                      and tenesmus (ineffective straining at stool) may be a major complaint. On occasion,
                      intestinal symptoms may be overshadowed by fever, weight loss, or one of the
                      extracolonic manifestations of the disease.
                     Complications of acute disease include toxic dilatation of the colon, perforation and
                      massive hemorrhage.
                     The risk of carcinoma of the colon is increased in patients with disease of more than
                      seven to ten years duration.

          Crohn’s disease
                     The clinical features of Crohn’s disease depend largely upon the site of involvement.
                     Abdominal pain is the predominant symptom in patients with ileal disease, and they
                      may present with an illness indistinguishable from acute appendicitis.
                     Patients with colitis develop diarrhea, but with rectal bleeding in only 50%. Patients
                      with both colonic and ileal disease have a combination of symptoms.
               Fever, weight loss and malaise are common. Anemia and nutritional impairment
                occur more often than in ulcerative colitis.
               The disorder may be complicated by stricture formation, fistulae and perianal
                disease.
               Growth retardation is an important manifestation in children.

2.   Distinguish and describe the pathology of ulcerative colitis and Crohn’s disease and
     other diseases of the large intestine.
     Congenital aganglionic megacolon – Hirschsprung disease
               Failure of development of ganglion cells in the myenteric and submucosal plexuses
                of the colon.
               Results in failure of peristalsis in the affected segment – remains narrow and spastic
                and represents a zone of functional intestinal obstruction.
               Rectum is always affected; proximal involvement is more variable.
               Proximal colon dilates – often massively – leading to abdominal distention.

     Enterocolitis
               See above.

     Collagenous and lymphocytic colitis
               Chronic watery diarrhea in middle-aged and older women.
               Benign clinical course.
               Collagenous colitis: patches of band-like collagen under the surface epithelium.
               Lymphocytic colitis: prominent intraepithelial infiltrate of lymphocytes and is
                associated with autoimmune diseases and celiac sprue.

     Crohn’s disease
               See below.

     Ulcerative colitis
               See below.

     Vascular disorders
               Ischaemic bowel disease:
                     Transmural infarction: sudden and total occlusion of a major vessel,
                       infarction of all bowel layers. Bowel segment is haemorrhagic as a result of
                       blood reflow into damaged area. Bowel appears rubbery and dusky,
                       bacteria produce gangrene, and perforation develops within days. Imparts
                       50 to 75% death rate.
                     Mural and mucosal infarction: incomplete necrosis or necrosis of mucosa
                       only. Mucosa appears haemorrhagic, but serosa may be normal.
                       Distribution is frequently patchy; inflammation depends on duration of
                       injury. Ischemic changes may be due to any cause (occlusive or
                       nonocclusive).
                     Chronic ischaemia: causes mucosal inflammation, ulceration, fibrosis, and
                       stricture. Ischemia has a segmental patchy distribution.
                     Nonspecific abdominal complaints, easily confused with acute and chronic
                       inflammatory conditions.
               Angiodysplasia:
                     Tortuous, abnormal dilations of submucosal veins that extend into the
                       lamina propria, cecum, and ascending colon and tend to bleed. They range
                       from small, focal ectasias to large, dilated, tortuous formations.
                     Acquired ectasias are attributed to partial, intermittent occlusion of
                       submucosal veins in the cecum and ascending colon, the site of maximal
                       wall tension because of its greater diameter.
               Hemorrhoids:
                     Variceal dilation of anal and perianal submucosal venous plexuses.
                     Associated with constipation, venous stasis of pregnancy, and cirrhosis (and
                       other causes of portal hypertension).
                      Ectasia of the inferior hemorrhoidal plexus below the anorectal line
                       (external haemorrhoids) is seen as well as in superior hemorrhoidal plexus
                       (internal haemorrhoids). Secondary thrombosis (with recanalization),
                       strangulation, or ulceration with fissure formation may develop.

Diverticular disease
         Colonic diverticular (diverticulosis) are uncommon in patients younger than age 30
          but present in 50% of adults older than age 60 in Western populations.
                Multiple flask-like outpouchings 0.5 cm to 1 cm in diameter are seen,
                   usually in distal colon.
                Occur alongside teniae coli and dissect into appendices epiploicae.
                The thin wall is lined by mucosa and submucosa and an attenuated-to-absent
                   muscularis propria.
                Muscularis of intervening bowel wall is hypertrophic.
         Pathogenesis includes the following mechanisms:
                Focal weakness in bowel wall at sites of penetrating blood vessels (vasa
                   rectae).
                Increased intraluminal pressure resulting from exaggerated peristaltic
                   contractions, possibly the result of decreased bulk in diet (low fibre diet).
         Diverticulitis – inflammation of diverticulum after obstruction or perforation.
                May lead to pericolic abscesses, sinus tracts, and peritonitis.

Tumors of the colon and rectum
         Polyps:
               Non-neoplastic polyps: polyps resulting from abnormal mucosal maturation,
                  inflammation, or architecture; no malignant potential.
                        Hyperplastic polyp.
                        Juvenile polyp.
                        Peutz-Jeghers polyp.
                        Other polyps.
         Adenomas:
               Arise as a result of epithelial proliferative dysplasia; adenocarcinoma
                  generally arises from adenomas.
               Three histologic appearances are characteristic:
                        Tubular adenoma: tubular glands, smooth surface.
                        Villous adenoma: villous frondlike projections.
                        Tubulovillous adenoma: a mixture of the first two.
               Risk of coexistent malignancy is correlated with three interdependent
                  features:
                        Polyp size.
                        Histologic architecture.
                        Severity of dysplasia.
               Adenomas are slow growing; doubling time is approximately 10 years.
               Most adenomas are in the colon (90%).
               All adenomas exhibit dysplastic epithelium (tall, hyperchromatic disorderly
                  cells with increased nuclear-cytoplasmic ratio, cigar-shaped nuclei).
               Tubular adenomas:
                        Smooth contoured bumps in the mucosa involving only a few
                            adjacent crypts.
                        With growth, they become bulky neoplasms (up to 4 cm diameter)
                            and protrude into the lumen – traction creates a submucosal stalk
                            lined by normal mucosa.
                        Branching dysplastic glands are embedded in lamina propria.
               Villous adenomas:
                        Larger when discovered and may carpet up to 10 cm of colonic
                            mucosa.
                        Finger-like projections are lined by dysplastic epithelium with a
                            lamina propria core.
               Tubulovillous adenomas:
                      Intermediate in size, with likelihood of having a stalk, and mixture
                      of architecture.
         The only adequate treatment for any adenoma is resection, regardless of
            whether carcinoma is present. Any residual adenomatous tissue is still a
            premalignant lesion or may yet harbor invasive adenocarcinoma.
   Familial syndromes:
         Familial adenomatous polyposis coli is the archetype of autosomal
            dominant polyposis syndromes.
         Innumerable adenomatous polyps in colon (and elsewhere in the gut); risk
            of progression to adenocarcinoma is 100%.
         Minimum of 100 colon adenomas required for diagnosis.
         Prophylactic colectomy is curative for colonic risk of cancer; adenomas
            elsewhere create continued problems.
         Average age of onset is teens to twenties. Progression to cancer occurs in
            10 to 15 more years without surgery.
         Defect in APC gene and interactions with cadherins.
         Also non-APC familial colon cancer – associated with satellite repair genes.
   Colorectal carcinoma:
         98% are adenocarcinomas.
         Peak incidence occurs at age 60 to 79 years except in young adults with
            polyposis syndromes.
         Most arise in polypoid adenomas, also a hereditary nonpolyposis colorectal
            cancer syndrome exists.
         Diet may be important; risk is associated with low fiber intake, high content
            of refined carbohydrates, high intake of red meat, decreased intake of
            protected micronutrients (vitamins A, C, E).
         Caecum/ascending colon, 38%; transverse colon, 18%; descending colon,
            8%; rectosigmoid, 35%; multiple sites at presentation, 1%.
         Polypoid, fungating masses (especially in capacious cecum and right colon)
            or annular, encircling masses with napkin-ring obstruction (characteristic of
            distal colorectum). Both forms penetrate bowel wall over years.
         Microscopically, tall, columnar cells resembling neoplastic epithelium of
            adenomas but now invasive as glands or cell clusters into submucosa and
            muscularis propria; carcinoma also may be poorly differentiated.
         Tumors incite a desmoplastic stromal response: inflammation and fibrosis of
            mesenchyme.
         A minority of tumors produces copious mucin; less commonly, foci of
            neuroendocrine differentiation, signet-ring features, or squamous
            differentiation are apparent.
         Clinically, fatigue, weakness, iron deficiency anemia, abdominal
            discomfort, progressive bowel obstruction, and liver enlargement
            (metastases) eventually occur.
         Abdominal X-ray shows “apple core” sign
         Prognosis is based on extent of invasion at diagnosis (100% for lesions
            limited to the mucosa; 25% for extensively invasive tumors). Surgery is the
            only hope for cure.
   Carcinoid tumors:
         Tumor of gut endocrine cells.
         Peak incidence is in the fifties.
         Ileal, gastric, and colonic carcinoids are frequently aggressive.
         Many elaborate bioactive products (e.g., amines or peptides).
         Intramural or submucosal masses are seen – small, firm and yellow-tan.
         Rectum, masses tend to be solitary; elsewhere, there tend to be multiple
            nodules.
         Nodules may cause kinking and obstruction of intestine.
         Microscopically, discrete islands, trabeculae, glands, or sheets of
            monotonous uniform cells with scant, pink, granular cytoplasm and oval,
            stippled nuclei are seen, separated by a fibrous stroma.
         Clinically, carcinoid tumors are usually asymptomatic; local symptoms
            occur from obstruction and bleeding.
                       Inconstant secretory products include gastrin, ACTH, insulin and others.
                              Ectopic ACTH  Cushing’s syndrome
                     Rectal carcinoids are always innocuous.
                     Five-year survival rate for other carcinoids is 90%.
               Gastrointestinal lymphoma:
                     Primary GI lymphomas occur more frequently in chronic sprue-like
                        malabsorption syndromes, natives of Mediterranean region, congenital
                        immunodeficiency states, HIV infection, and after organ transplantation
                        with immunosuppression.
                     Sporadic lymphoma:
                              B-cell lymphomas also may rise from MALT.
                              Adults are affected.
                              Stomach, 55 to 60%; small intestine, 25 to 30%; colon, 20 to 25%.
                     Sprue-associated lymphoma:
                              Younger individuals (30 to 40 years of age), after long duration oof
                                  malabsorptive disorder; usually T-cell lymphoma.
                              Prognosis is poor.
                     Mediterranean lymphoma:
                              B-cell lymphoma in children and adults of Mediterranean ancestry;
                                  background of chronic diffuse mucosal plasmacytosis.
                              Also called immunoproliferative small intestinal disease.
                              Prognosis is poor.
                     Early lesions, plaque-like expansions of mucosa and submucosa.
                     Advanced lesions, full-thickness mural lesions or polypoid, fungating
                        masses protruding into the lumen.
                     Microscopically, atypical lymphocytes infiltrate mucosa and wall, replacing
                        normal structure. Extreme numbers of lymphocytes may populate the
                        epithelium (lymphoepithelial lesion). B-cell lesions (95%) may be low or
                        high grade; T-cell lesions are all high grade.
                     Clinically, sporadic lymphomas are amenable to surgical resection and are
                        chemoresponsive. Outcome depends on size, grade, and invasiveness of
                        tumor at time of resection.
                     Small intestine masses  risk of intussusception (telescoping of bowel –
                        produces gut obstruction)

3.   Outline the natural history of inflammatory bowel disease (IBD).
     Ulcerative colitis
               The clinical course is variable.
               Most patients suffer a relapse within 1 year of the first attack, reflecting the recurrent
                nature of the disease. There may, however, be prolonged periods of remission with
                only minimal symptoms.
               The severity of symptoms reflects the extent of colonic involvement and the intensity
                of the inflammation.
               Patients who present with limited involvement of the rectum (ulcerative proctitis) or
                rectum and sigmoid (ulcerative proctosigmoiditis). Their disease is usually mild,
                with minimal systemic or extracolonic manifestations, although ulcerative proctitis is
                sometimes difficult to treat, exhibiting protracted bleeding and tenesmus. The major
                symptoms are rectal bleeding and tenesmus. Most of these patients, especially those
                with only rectal involvement, do not develop more extensive disease. In the
                remainder, the disease may extend proximally with variable involvement.
               Perhaps 85% of patients with UC have mild to moderate disease of an intermittent
                nature and can be managed without hospitalization.
               In approximately 15% of patients, the disease becomes more fulminant, involves the
                entire colon, and presents with severe bloody diarrhea and systemic signs and
                symptoms. These patients are at risk of developing toxic dilation and perforation of
                the colon and represent a medical emergency.
               Mortality appears greatest early in the disease.
               Complications:
                      Severe bleeding.
                      Toxic megacolon.
                  Extraintestinal manifestations (arthritis, uveitis, skin lesions and sclerosing
                   pericholangitis).
                  Colon carcinoma.
                  Epithelial dysplasia.

Crohn’s disease
        Prognosis for CD is not as favorable as for UC (except acute regional enteritis; this
         has an excellent prognosis).
        In the majority of patients with CD, the course is chronic and intermittent regardless
         of the site of involvement.
        Responds less well to medical therapy with time.
        Two-thirds of patients develop complications requiring surgery at some point.
        Mortality rate increases with the duration of the diseases and probably ranges from 5
         to 10 percent.
        Most deaths occur from peritonitis and sepsis.
        Following surgery, patients often have recurrence and relapses.
        Therapy will result in reasonably stable and productive lives for most CD patients.
        Complications:
               Intestinal obstruction or fistula.
               Malabsorption syndrome.
               Extraintestinal manifestations (arthritis and uveitis).

Complications of IBD
        Fistulas: forms between involved loops of bowel and adjacent viscera.
               Ileum and colon: malabsorption due to bacterial colonization.
               Ileal loops: short circuit the bowel, resulting in malabsorption.
               Enterovesical: UTI and passage of gas and feces with urine.
               Enterovaginal: fecal vaginal discharge.
        Malabsorption syndromes: a complication of disease involving the terminal ileum, in
         which there may be failure to absorb vitamin B12 and bile acids, resulting in
         macrocytic anemia and fat malabsorption.
               May be iatrogenic – post-surgical resection
               Need to ensure adequate nutrition – IM B12 supplements
        Perforations: can occur in severe UC since with extensive ulceration of the bowel
         wall may become extremely thin. Clinical features include acute peritonitis with
         signs of peritoneal inflammation and the demonstration of free air under the
         diaphragm on upright film of the abdomen.
               Phlegmon formation – perforation leading to localised sepsis. Rapidly
                   enveloped by the omentum and infection is sequestered. The gut is
                   inflamed, oedematous and painful – treated conservatively with antibiotics.
                   Can be treated surgically but there is a risk of creating a “short-gut
                   syndrome”. Phlegmon is bypassed – proximal normal gut is anastomosed
                   distally, affected gut can then heal in situ and the gut re-joined later.
        Toxic dilatation: may occur in CD but is more common in UC. Can be considered a
         severe form of UC with the additional feature of colonic dilatation. The
         neuromuscular tone of the bowel is affected by the severe inflammation, resulting in
         dilatation.
        Carcinoma: increased incidence of carcinoma in patients with chronic IBD,
         especially in those who have more extensive mucosal involvement (i.e., pancolitis)
         and those who have had their disease for extended periods of time. In colitis patients,
         the tumors are more often multiple, flat, and infiltrating and appear to have a higher
         grade of malignancy. Early warning signs (i.e., rectal bleeding, change in bowel
         habits) will be difficult to interpret in the setting of colitis.
        Extraintestinal manifestations: their cause is currently unknown.
               Joint manifestations occur in 25% of patients. May range from arthralgia
                   only to an acute arthritis with painful, swollen joints. The non-deforming
                   arthritis is mono- or polyarticular and often migratory. Knees, ankles and
                   wrists are most commonly involved, but any joint may be affected.
                       Skin manifestations are more common with colonic disease. Occur in
                        about 15% of patients, and when present, severity correlates with activity of
                        the bowel disease.
                              Erythema nodosum may be seen and heals without scarring.
                              Pyoderma gangrenosum an ulcerating lesion often occurring on the
                                 trunk, is relatively painless and may heal without scarring.
                              Aphthous ulcers resemble “canker sores” of the mouth, and in
                                 approximately 5 to 10% of patients they are present during periods
                                 of active disease and then resolve.
                       Ocular manifestations such as episcleritis, recurrent iritis, and uveitis occur
                        in approximately 5% of patients and may represent a severe manifestation of
                        the disease. Activity parallels the course of the bowel disease, and the
                        lesions may respond dramatically when colectomy is done.
                       Extra-hepatic manifestations:
                              Sclerosing cholangitis, a chronic inflammation of unknown cause
                                 involving the extrahepatic and intrahepatic bile ducts that may
                                 produce varying degrees of extrahepatic biliary obstruction.
                                 Corticosteroids and immunosuppressive therapy are not beneficial
                                 while results after colectomy are inconsistent.
                              Cholangiocarcinoma, arising in the extrahepatic biliary tree, has an
                                 increased incidence in patients with UC. Biliary obstruction must
                                 be distinguished from sclerosing cholangitis.
                              Chronic active hepatitis which may progress to cirrhosis may be
                                 seen in IBD although the relationship between these disorders is
                                 unknown. Colectomy does not influence the course of this form of
                                 liver disease.

4.   Describe the principles of the management of IBD and outline the pharmacology of
     drugs used in its management.
     Management principles
             The treatment of an acute exacerbation of ulcerative colitis or Crohn’s disease
              depends upon:
                    The severity of the attack.
                    The extent of the disease.
             Mild attacks can usually be managed out of hospital. Severe episodes require
              inpatient treatment.
             In severe disease, attention must be paid to fluid and electrolyte balance, correction
              of anaemia and maintenance of nutrition. Clinical status and vital signs must be
              carefully monitored looking for early evidence of toxic dilatation and deterioration.

     Pharmacological agents
             5-Aminosalicylic acid (5-ASA) derivatives are effective in acute ulcerative colitis
              and in Crohn’s disease affecting the colon. They are also able to reduce the risk of
              relapse in ulcerative colitis approximately four-fold when taken long-term, and this
              effect does not diminish with time.
                    Sulfasalazine consists of 5-ASA linked by an azo bond to sulfapyridine, a
                       sulfonamide. 5-ASA is the active component, whereas sulfapyridine acts as
                       a carrier molecule preventing absorption in the small intestine. The latter is
                       responsible for most of the side effects of headache, nausea, vomiting and
                       malaise, which can be managed by reintroduction at a lower dose; and non-
                       dose related effects, e.g. fever, rash and agranulocytosis, which require
                       withdrawal of the drug. Reversible reduction in fertility occurs in a small
                       proportion of male patients.
                    Olsalazine (azodisalicylate sodium) is a dimmer of 5-ASA, and does not
                       contain a sulfonamide component. It may produce a secretory diarrhea in
                       up to 10% of patients, but this can be minimized by titrating the dose and
                       taking it after meals.
                    Mesalazine (5-ASA) is available in an oral, polymer coated form which is
                       designed to be released at the pH of the terminal ileum (i.e. pH 6). It has a
                       low incidence of adverse effects. At present, mesalazine and olsalazine are
                       only approved for use in patients who are allergic to sulfonamides or
                       intolerant of sulfasalazine.
             Corticosteroids may be used topically, orally or parenterally. Topical preparations
              include suppositories, retention enemas or rectal foam. The latter is easier to retain
              than the enema form. The usual oral corticosteroids given are prednisone and
              prednisolone. Side effects are usually not troublesome because these agents are
              mostly used for short periods in reducing doses. However, care needs to be taken in
              patients with diabetes, hypertension or heart disease, or if they are to be used long-
              term.
             Immunosuppressive drugs, e.g. azathioprine and its active metabolite 6-
              mercaptopurine (6-MP), are indicated:
                    In chronic active disease not responding to more conventional therapy.
                    In patients who require continuous low dose corticosteroids to maintain
                       remission.
                    In an attempt to lower the corticosteroid dose in those who develop side
                       effects.
                    In the treatment of fistulae in Crohn’s disease.
              During therapy with these drugs, the white cell count must be monitored for possible bone marrow
              toxicity, although this is uncommon with the low doses used (1 to 2 mg/kg/day). Other possible side
              effects include pancreatitis, cholestasis and potential for neoplasia.
              Methotrexate is also used – DHFR inhibitor folate impaired pyrimidine synthesis
             Antibiotics: metronidazole is used in perianal Crohn’s disease and also in some
              patients with Crohn’s colitis. The most common side effect of this agent is
              gastrointestinal upset. Peripheral neuropathy, first manifested by paraesthesias, can
              occur with long-term use and may be irreversible; if it occurs, the drug must be
              stopped.
                    No benefit has been shown for broad spectrum antibiotics per se in either
                       ulcerative colitis or Crohn’s disease.

5.   Outline the genetic aspects of large bowel disease.
     Inflammatory bowel disease
             While the causes of ulcerative colitis and Crohn’s disease remain unknown, certain
              features of these diseases have suggested several areas of possible importance. These
              include familial or genetic, infectious, immunologic, and psychological factors.
             These diseases are more common in whites than in blacks or Asians, and Jews have
              an incidence three to six times greater than that of non-Jews.
             The increased incidence of IBD in whites and in Jews and the occurrence of familial
              clustering suggest a genetic predisposition to the development of the disease. An
              increased incidence of CD in monozygotic twins also is strong evidence for a genetic
              component.
             A search for genetic markers that might be of value in identifying susceptible
              individuals has not identified any single marker (i.e., a histocompatibility antigen) in
              patients with IBD.

     Adenomas and colon carcinomas
             Familial adenomatous polyposis and Gardner syndrome patients exhibit a somatic
              mutation in the tumor-suppressor APC gene (adenomatous polyposis coli).
              Mutations occur in the tissue of sporadic cancers as well.
             Inherited mutations in DNA mismatch repair genes occur in a hereditary
              nonpolyposis colorectal cancer syndrome. This leads to faulty DNA proofreading,
              widespread alterations in the genome, and predisposition to cancer. Sporadic cancers
              can exhibit the same defect.
             DNA methylation: loss of DNA methyl groups occurs early in colonic adenomas.
             K-ras gene and other oncogenes are mutated with increasing frequency as adenoma
              size increases and in carcinomas.
             Allelic loss on 18q is common in colon cancer at the DCC locus (deleted in colon
              cancer). This is a cell adhesion protein.
             Losses at 17p (site of p53 gene) are common in cancers.
             Telomerase is an enzyme that maintains chromosome telomere length and cell
              replicative ability; it is expressed in cancers but not in adenomas.
                 Cumulative alterations in the genome appear to lead to progressive increases in size,
                  level of dysplasia, and invasive potential of neoplastic lesions. No single event or
                  sequence of events is requisite, but a multihit genetic mechanism appears to be
                  operative.

CHRONIC DISEASE
   1.   Describe the psychological impact of chronic disease.
             Chronically ill patients experience more depressive symptoms, more anxiety, less
                self-esteem, and a lower ability to control many aspects of their lives than people
                without any disease.
             Disorders of psychological functioning may be caused by biological factors, such as
                structural and neurochemical changes in the brain (stroke and Parkinsonism) or
                aberrations of immune system functioning (in rheumatoid arthritis), as well as by
                changed psychosocial factors as a consequence of the disease. Examples of the latter
                are loss of function and role (family, social, financial), negative body image and
                sense of identity, loss of independence, promoted sense of helplessness and effects on
                interpersonal relationships.
             Functional impairment: Increased levels of both depressive and anxiety symptoms
                among people with functional impairment. As functionally disabled people
                encounter difficulties that are relatively unresponsive to problem-solving efforts, a
                sense of mastery may also be particularly difficult to achieve and maintain. Patients
                with diseases involving more functional impairment, e.g. arthritis or stroke, have a
                less favorable psychological status than patients with diseases involving relatively
                little functional impairment, such as diabetes or lung disease. Additional losses, such
                as the loss of function, role, and body image and a more negative view of themselves,
                their future, and their world, may lead to more feelings of depression and anxiety.
             Illness controllability: In contrast to cardiac disease and diabetes, which are quite
                responsive to self-administered diet and medication, cancer and arthritis offer few
                opportunities for personal and medical control and, therefore, these patients may be
                more at risk for low feelings of mastery and for depressive and anxiety feelings.
             Degree of life threat: Patients with an uncertain prognosis, e.g. recently diagnosed
                cancer patients, may have a higher risk of being psychologically distressed, because
                they are uncertain about their chance of remission or cure.
             Demographics: More psychological dysfunction for women, for people of low
                education, and for people without a partner. For anxiety, the association with age
                becomes negative, possibly because older people are more likely than younger people
                to have developed effective coping strategies for dealing with life events because
                these are more common and normative in old age.

   2.   Discuss the skills in managing uncertainty and adverse outcomes.

   3.   Discuss the issues relating to the shared care management of patients.
             Integrated care for health disorders, particularly chronic diseases, is a long-term and
                 complex challenge, particularly because of the involvement of many individuals with
                 different beliefs, attitudes, assumptions and reward structures. Two basic conceptual
                 models of disease - the biomedical and psychosocial - underlie many of these
                 differences.
             The biomedical model views humans as the sum of multiple individual 'subsystems,'
                 and disease represents dysfunction of one or more of these subsystems. This model is
                 'reductionist' and 'individualistic' in nature in that if 'THE' defective subsystem can be
                 identified, studied and improved, it is assumed that health would return. The
                 biomedical model focuses primarily on the individual with ill-health and has added
                 greatly to our basic understanding of disease processes.
             The psychosocial model is 'interactive' and dynamic, and sees the 'whole' as more
                 than the sum of its parts. This model values elements outside of the individual, e.g.
                 work and home environment, as important in maintaining or establishing health.
             Because of fundamental differences between these 2 models of health and disease,
                 conflicts, e.g. efficacy vs. exposure; role of individual vs. environment; etc., may
                 exist among varying professionals regarding the nature, purpose, targets, structure,
                 and consequences of integrated care programs. These fundamental conflicts, if
                  unrecognized and ignored, can significantly attenuate the benefits of well-intentioned
                  prevention and treatment integrated care programs.

PHYSICAL EXAMINATION OF THE LOWER GI TRACT
    1.   Outline the fundamentals of the rectal examination and proctoscopy.
         Method of exam
                 Have the patient stand and lean forward, resting his hands on the examination table.
                  Place a small amount of lubricant on your gloved index finger.
                 Place your finger at the anus and wait for reflex sphincter relaxation.
                 Gently insert your finger and examine as much of the rectal wall as possible.
                  Sequentially examine the right lateral, posterior and left lateral surfaces felling for
                  pelvic structures.
                 Evaluate the prostate gland in men along anterior wall.
                        Examine the anterior surface of the prostate.
                        Evaluate the lateral lobes and the sulcus.
                        Note the size, shape, consistency and tenderness.
                 Note the rectal contents.
                 Remove the finger and evaluate the faeces on the gloved finger and save it for Guaic
                  testing.

         Alternative method
                 The rectal exam can also be done in the left lateral decubitus.

         Normal findings
                 Rectal exam is unpleasant.
                 The sphincter has sufficient tone to grasp your finger.
                 Soft stools may be felt.
                 The prostate gland is about 2.5 cm in length, with a medial sulcus, is firm and non-
                  tender.
                 Stools can be seen on the gloved finger and retain it for Guaic testing.

         Abnormal findings
                 Sphincter: loss of tone and patulous (Cauda equina syndrome).
                 Contents: hard impacted stools, foreign body.
                 Rectal wall: pelvic masses (ovary, uterus) in women.
                 Mucous membrane: irregular, mass (cancer).
                 Prostate in men:
                       Smooth, large, firm and non-tender (benign enlargement).
                       Hard, irregular nodule or fixed hard mass (cancer, stone, chronic prostatitis).
                       Large, boggy and tender (acute prostatitis).
                 Stools:
                       Bloody (hemorrhoids, bleeding rectal lesion).
                       Black (upper GI bleed, iron, some antacids).



ISSUES IN CLINICAL TRIALS
    1.   Discuss the related psychological, ethical and doctor-patient issues concerning the
         enrolment of patients in clinical trials.
         Ethical dilemma
                 Defining management options of future patients vs. safeguarding the patient’s best
                  interest.
                 Utilitarianism: In the absence of RCT, it is not possible to be certain that a new drug
                  or clinical intervention is actually beneficial to patients with a particular disease or
                  condition, compared either to a “standard” (accepted or approved) therapeutic
                  strategy or to no treatment at all (an untreated control population).
                              versus
                 Kantian philosophy: The individual physician’s principal ethical responsibility is to
                  the individual patient that he or she is treating, and not to future patients who may
          benefit from the potentially important information gained through a well-designed
          and well-conducted randomized trial.

Beneficence and non-malificence
         If it is the physician’s best judgment – based on his or her interpretation of this data,
          personal experience, and knowledge of the individual patient’s specific medical
          condition – that one regimen would be preferred over the other(s), then the physician
          should not recommend that the patient participate in this trial, no matter how
          important the information gained may be to society.
         If the physician has no opinion about whether the new treatment is acceptable, then
          random assignment is ethically acceptable, but such lack of enthusiasm does not
          augur well for either the patient or the study.
         When the physician believes that the severity and likelihood of harm and good are
          evenly balanced, randomization may be ethically acceptable.
         If the patient has no preference for either treatment, then randomization is acceptable.
          If, however, he or she believes that the new treatment may be either more or less
          successful or more or less toxic, the use of randomization is not consistent with
          fidelity to the patient.
         New agents not FDA-approved (available only to clinical trials): A physician who
          believes, based on previously reported clinical data (usually from phase 2 drug trials),
          that a new drug is potentially superior to the standard therapy has no choice but to
          recommend that the patient participate in the trial. The patient would have a 50%
          chance of receiving the new therapy (and a 50% chance of being placed in the control
          group), compared to a 0% chance if he or she does not participate in the study.

Informed consent issues
         An individual gives a genuinely informed consent to some medical intervention when
          he both understands the risks and possible benefits of the treatment.
         It is quite unlikely that any patient-subject can see himself accurately within the
          broad context of the situation, to weigh the inconveniences and hazards that he will
          have to undergo against the improvements that the research project may bring to the
          management of his disease and to his own particular case.
         It would be impractical and probably unethical for the investigator to present the
          nearly endless list of all possible contingencies; in fact, he may not himself be aware
          of every untoward thing that might happen.
         Patient-subjects who are incapacitated and hospitalized because of illness, frightened
          by strange and impersonal routines, and fearful for his health and perhaps life are far
          from exercising a free power of choice when the person to whom he anchors all his
          hopes asks him to volunteer for a clinical trial.
         When a man or woman agrees to act as an experimental subject, his or her consent is
          marked by neither adequate understanding nor total freedom of choice.

Non-compliance
         Subjects have a legal right to “discontinue participation at any time without penalty
          or loss”.
         Largely due to the frailty inherent in human nature – carelessness, despair of getting
          better, or adverse reactions.
         Lying: Participants lie to get into studies (often with the help of their own physicians)
          and, once enrolled, lie about their medical condition and level of compliance. They
          could be taking a place that could have been taken by someone else just as needy
          who also fits the required medical profile, thus constituting an injustice to them.
         Breaking promises: frustrate the use of placebos by dropping out if randomized to
          the placebo arm or by analyzing the drugs they receive or by pooling drugs, which
          ensures they receive some portion of the active substance – thereby playing havoc
          with assigned dosage levels.
         Researchers may forbid subjects from taking prophylactic drugs that might confound
          the effects of experimental agents.
         The approval of desperately needed effective therapies could be slowed or side-
          tracked forever, while many initially promising but unacceptably toxic drugs could
          command center stage for years before their true effects are revealed.
         By delaying the successful and timely completion of vitally important clinical trials,
          noncompliance thus threatens to deprive present and future sufferers of effective
          palliative, curative, and preventative measures.

Coercion or enticement?
         Participants may see themselves as having “no real choice” but to accept the
          researcher’s offer – back against the wall.
         Their circumstances may constrain their will and vitiate the validity of their consent.
         Researchers are offering participants the prospect of improving their baseline
          situation; and most potential subjects are more than happy to move from what might
          be called their “pre-proposal baselines” to the situation created by the proposal to
          participate (“If you play by the rules, we will give you access (or at least the
          possibility of access) to promising new drugs”).

Justice
         Significant gaps in knowledge about diseases due to overrepresentation of white men
          in research populations.
         Physicians now frequently lack adequate evidence on whether women and people of
          color will be harmed, helped, or not affected at all by numerous therapies now
          endorsed as promoting “human health”.
         Gender and racial inequality is unethical.
         Maternal-fetal protection: in the name of potential protection for potentially
          pregnant women and their fetuses, all women have lost opportunities to improve and
          extend their lives. This does not apply to the potential damages to sperm, thereby
          creating the possibility of birth defects.
         Diseases disproportionately affecting females and people of color are given low
          funding priority, knowledge that could alter current ineffective or detrimental routine
          medical care is never produced.
         Extrapolating results from white males to everyone else can be dangerous due to
          numerous factors like physiological differences.
                                          Learning Objectives

Dom             LO Title                                                LO Detail
BCS   Anatomy of upper GI          1. Recognise the main anatomical features of the oesophago-gastric junction
                                   2. Describe the anatomy of the biliary tract
BCS   Physiology of the upper GI   1. Outline the major physiological factors that control the oesophago-gastric
                                   junction
                                   2. Describe the process of bile secretion
                                   3. Describe the physiological processes involved in GI motility and secretion.
BCS   Pathology and treatment of   1. Describe the underlying pathology of major diseases of the upper GI tract
      upper GI disease             (including mouth, salivary glands, oesophagus and stomach) and biliary tree.
                                   2. Discuss how bile secretion is deranged in cholelithiasis and outline the
                                   complications of this condition
                                   3. Discuss the mechanism of action of drugs that control GI motility and
                                   secretion.
EPPD Decision-making               1. Understand the risks and benefits of common GI procedures and operations
                                   and how these influence patient/doctor decision making
ICCP History taking                1. To understand the importance of history in determining the cause of
                                   abdominal pain
ICCP Clinical reasoning            1. To make the clinical distinction between functional and structural GI disorders
ICCP Laboratory investigations     1. Describe the selection and interpretation of GI investigations for common
                                   upper GI symptoms
ICCP Managing uncertainty          1. Describe strategies that assist in coping with clinical situations in which there
                                   are high levels of uncertainty, iatrogenic morbidity, and undesired outcomes
PPH   Upper abdominal pain         1. What is the prevalence of upper abdominal pain in the community?
      (Public Health)              2. Outline the distribution and determinants of conditions causing upper
                                   abdominal pain in the community. How does this vary according to age and
                                   gender?
                                   3. Discuss the psychosocial aspects of functional gastrointestinal disease.
PPH   Opportunistic health         1. Be aware of the importance of opportunistic health promotion in medical
      promotion (Public Health)    consultations.
                                   2. List those evidence-based health promotional activities recommended for
                                   females in the following broad age categories: 20-40, 40-60, > 60.
It's All in Your Mind!

Know the main anatomical and physiological factors which control the oesophago-gastric junction and how this is
deranged in gastro-oesophageal reflux. BCS

The oesophagus descends through the posterior mediastinum and pierces the diaphragm just left of the
median plane (at the level of T10), travels about 1cm in the abdomen forming a groove in the left lobe
of the liver anteriorly and entering the stomach at the cardiac orifice. At this point, the oeophagus is
covered anteriorly and laterally by peritoneum and encircled by the oesophageal plexus of nerves. At
the inferior end of the oesophagus, the oesophagogastric junction, there is a physiological mechanism
known as the oesophageal sphincter, which contracts and relaxes. Food normally pauses momentarily
here and the sphincter is usually quite efficient at preventing reflux of gastric contents superiorly.

Physiologically, the pressure exerted by the contracted LOS is greater than either the intraoesophageal
pressure or the intragastric pressure. Gastric contents therefore do not normally reflux into the
oesophagus.

The normal anti-reflux mechanisms consist of the Lower Oesophageal Sphincter (LOS) and the
anatomic configuration of the gastroesophageal junction. Reflux occurs only when the gradient of
pressure between the LOS and the stomach is lost. It can be caused by increased intragastric pressure or
by a transient or sustained decrease in LOS tone. The decrease in sphincter tone may be due to muscle
weakness or to inappropriate sphincter relaxation mediated by inhibitory nerves. Abnormal activity of
the diaphragmatic crural muscle also predisposes to gastroesophageal reflux. Normally the crura of the
diaphragm act as a “pinch-cock” mechanism.



Review and examine in more detail, the anatomy of the biliary tract, the physiology of bile secretion, and how this
is deranged in cholelithiasis and its complications. BCS

Bile is secreted by hepatocytes into minute channels called bile canaliculi, which drain into the the
hepatic duct. When food is not being digested, bile is diverted by way of the cystic duct into the
gallbladder. Following a meal, bile is moved through the common bile duct and the sphincter of Oddi
into the small intestine where it plays a role in digestion and the absorption of fat. Bile consists of bile
salts (glycocholic and taurocholic acids) (important in digestion and absorption of fat through
facilitation of emulsification), bile pigments (from the breakdown of Hb, excreted in faeces), cholestrol
lecithin, Na+, Cl- and HCO3-. The sphincter of oddi, a ring of smooth muscle surrounding the common
bile duct in the region where the duct enters the duodenum, prevents bile from entering the small
intestine between meals. When food enters the upper small intestine, fat and protein digestion products
stimulate the release of CCK from the duodenal mucosa into the blood, permitting relaxation of the
sphincter of oddi and contraction of the gallbladder.

While in the gallbladder, bile is concentrated by the active removal of Na + from the lumen to the blood,
and the consequent (passive) movement of Cl- and HCO3-. The gallbladder mucosa is a simple
columnar absorptive epithelium. This results in concentration of the contents of the gallbladder, as the
organic constituents are not absorbed. The water insoluble lipid components of the bile usually remain
in solution, but sometimes this doesn't occur, resulting in the precipitation of gallstones.

Bile salts are synthesised by hepatocytes and actively transported by these cells into the bile canaliculi.
These bile salts enter the small intestine, play an essential role in the digestion and absorption of fat,
traverse most of the small intestine and are absorbed from the terminal ileum. They are returned to the
blood, then removed from the blood by the liver, then secreted back into the bile where the recycling
process starts again. This is called the enterohepatic circulation of bile salts, which is not 100%
efficient, as some salts are lost in the faeces, but the capacity for the liver to resynthesise these
molecules from cholesterol far exceeds the loss.

Bile salts are the main stimuli for the secretion of bile. Portal blood concentrations of bile salts are
greatest, and thus bile flow is at its highest level when food is being digested, at which time bile salts
are being circulated between the liver and the small intestine. Between meals, when the concentration
of bile salts in the portal blood is low and bile salts are being stored in the gallbladder, the liver bile
flow is low.

Secretin also stimulates the secretion of bile, but the secreted fluid is a basic HCO 3--rich fluid from the
epithelium of the bile ducts that plays a part in neutralising the acid that enters the small intestine from
the stomach.

Cholelithiasis
                  Cholesterol salts  yellow
                  Pigment salts (bilirubin complexed with Ca2+)  black

There are 4 conditions that must be met to produce gallstones:
      1. The bile must be supersaturated with cholesterol
      2. The gallbladder motility is reduced  crystal formation
      3. Cholesterol nucleation is accelerated
                   need focus or nidus to seed crystal growth
      4. Mucous hypersecretion traps crystals so they can coalesce into stones

Risk factors
                  Age
                  Female (M:F = 1:2)
                  Oestrogens
                  Obesity
                  Stasis
                         i. Stasis will produce calculi (gall bladder, urinary bladder)
                  Hypercholesterolaemic

                   Bilirubin production
                         i.  RBC breakdown
                  Ileal disease (resection or bypass)
                         i. Impaired bile salt resorption  bile salt recycling  synthesis



Understand the importance of history in determining the cause of abdominal pain. DC

The correct interpretation of acute abdominal pain is one of the most challenging demands made of any
physician. Few other clinical situations demand greater experience and judgment, because the most
catastrophic of events may be forecast by the subtlest of symptoms and signs.

There are few abdominal conditions that require such urgent operative intervention that an orderly
approach need be abandoned, no matter how ill the patient. Nothing will supplant an orderly,
painstakingly detailed history, which is far more valuable than any laboratory or radiological
examination. This kind of history is laborious and time-consuming, making it unpopular, even though a
reasonably accurate diagnosis can be made on the basis of the history alone in the majority of cases. In
cases of acute abdominal pain, a diagnosis is readily established in most instances, whereas success is
not so frequently achieved in patients with chronic pain. Since the irritable bowel syndrome is one of
the most common causes of abdominal pain, the possibility of this diagnosis must always be kept in
mind. The chronological sequence of events in the patient's history is often more important than
emphasis on the location of pain. If the examiner is sufficiently open-minded and unhurried, asks the
proper questions, and listens, the patient will usually provide the diagnosis. Careful attention should be
paid to the extraabdominal regions that may be responsible for abdominal pain. An accurate menstrual
history in a female patient is essential.

As in history taking, there is no substitute for sufficient time spent in the examination. It is important to
remember that abdominal signs may be minimal but nevertheless, if accompanied by consistent
symptoms, may be exceptionally meaningful.

Some Points on History:
               A frequent misconception is that pain associated with intraabdominal vascular
                disturbances is sudden and catastrophic in nature. The pain of embolism or thrombosis of
                the superior mesenteric artery or that of impending rupture of an AAA certainly may be
                severe and diffuse. Yet, just as frequently, the patient with occlusion of the superior
                mesenteric artery has only mild continuous diffuse pain for 2 or 3 days before vascular
                collapse or findings of peritoneal inflammation appear. Abdominal pain with radiation to
                the sacral region, flank, or genitalia should always signal the possible presence of a
                rupturing AAA. This pain may persist over a period of several days before rupture and
                collapse occur.
               Pain arising from the abdominal wall is usually constant and aching. Movement,
                prolonged standing, and pressure accentuate the discomfort and muscle spasm.
               Pain referred to the abdomen from the thorax, spine, or genitalia may prove a vexing
                diagnostic problem, because diseases of the upper part of the abdominal cavity such as
                acute cholecystitis or perforated ulcer are frequently associated with intrathoracic
                complications. A most important, yet often forgotten dictum is that the possibility of
                intrathoracic disease must be considered in every patient with abdominal pain, especially
                if the pain is in the upper part of the abdomen. Diaphragmatic pleuritis resulting from
                pneumonia or pulmonary infarction may cause pain in the right upper quadrant and pain
                in the supraclavicular area, the latter radiation to be sharply distinguished from the
                referred subscapular pain caused by acute distention of the extrahepatic biliary tree.
               The ultimate decision as to the origin of abdominal pain may require deliberate and
                planned observation over a period of several hours, during which time repeated
                questioning and examination will provide the proper explanation. Whenever the cause of
                abdominal pain is obscure, a metabolic origin always must be considered.
               The problem of DDx is often not readily resolved. The pain of porphyria and of lead colic
                usually is difficult to distinguish from that of intestinal obstruction, because severe
                hyperperistalsis is a prominent feature of both. The pain of uremia or diabetes is
                nonspecific, and the pain and tenderness frequently shift in location and intensity.
                Diabetic ketoacidosis may be precipitated by acute appendicitis or intestinal obstruction,
                so if prompt resolution of the abdominal pain does not result from correction of the
                metabolic abnormalities, an underlying organic problem should be strongly suspected.
               Causalgic pain may occur in diseases that injure nerves of sensory type. Pain arising from
                spinal nerves or roots comes and goes suddenly and is of a lancinating type. Severe
                muscle spasm is common but is either relieved or is not accentuated by abdominal
                palpation. Psychogenic pain conforms to none of the aforementioned patterns of disease,
                varying enormously in type and location but usually has no relation to meals. It is often at
                its onset markedly accentuated during the night. Nausea and vomiting are rarely observed,
                although occasionally the patient reports these symptoms. Spasm is seldom induced in the
                abdominal musculature and, if present, does not persist, especially if the attention of the
                patient can be distracted.


Understand the psycho-social aspects of functional bowel disease. DC

Higher rates of psychiatric comorbidity as well as more impaired psychosocial adjustment occur with
the functional bowel disorders and are particularly high in self-selected referral patients compared with
community populations. Reciprocally, some studies show higher rates of functional bowel disturbances
in patients with psychiatric diagnoses.

Remaining alert for and addressing coexisting psychiatric illness will enhance treatment outcome
(increased patient compliance, functioning, and satisfaction). Additionally, psychological factors affect
the clinical expression of structural disease. Resetting treatment goals from cure to coping with chronic
illness and setting personal limits are important.


Understand the risks and benefits of common GI procedures and operations and how these influence
patient/doctor decision making. EPPD/BCS

Benefits:
                        To help diagnose treatable conditions.
Risks/costs:
                  Radiation exposure
                  The more laparoscopic or laparotomy procedures, the more chance of adhesions
               developing.
                  Costs:
                      Procedural costs and following up false negatives.
                  Medical Risks:
                      Anaphylactic reaction to barium or contrast dyes.
                  Surgical Risks:
                      Bleeding.
                      Inadvertent spread of tumour – along biopsy track.

When managing uncertainty in clinical situations, it must be remembered that:
         Clinical diagnosis is an inexact science.
         Harmful investigations must be balanced with missing diagnoses.
         Strategies must be used to best combine these factors - what is the degree of necessity?

Influences on clinical decision-making:
                                                    Doct
                                                    or
      Doctor's role                               Clinical                                 Patient
      as                                          Decision                                 values,
      gatekeeper                                                                           concerns and
      to medical                                                                           expectations
      tests                               Doctor's concern of
                                          litigation
Why do we need certainty?
        Management is dependent on certainty.
        To exclude life (or life-style) threatening diseases.
        To be sure that we use treatment that is available to reverse the threat of disease.
        Patients want their disease to be labeled.
        Sick-role legitimisation.
        Certification

Diagnostic strategy
         Make probability diagnosis.
         But serious disorders are not to be missed.
         Remember, the pitfalls diagnoses are often missed, as are the seven masquerades.
         Always ask is the patient trying to tell me something?

The seven masquerades are;
         Depression
         Diabetes
         Drugs
         Anaemia
         Thyroid disease ( or )
         Spinal dysfunction
         UTI




Recognise the importance and high frequency of functional disturbances as a cause of GI symptoms.
Functional disturbances are the most common presenting conditions to general practitioners,
accounting for 50% of consultations for digestive complaints and 10% of all consultations. Functional
disturbances occur where there is no clear defined organic lesion. However, most involve motor
dysfunction of the stomach, SI, colon or anorectum.

Irritable bowel syndrome (IBS)
               Most common functional GIT disorder.
               Chronic disorder characterised by disordered motor and/or secretory function of the GIT
                (particularly small and large intestines) in the absence of identifiable disease.
               Ratio of women:men = 2:1 with most presentations before the age of 40 years, however
                any age is possible.
Pathogenesis:
     Numerous factors have been postulated to affect GIT sensorimotor function. Abnormalities in
      fasting and stimulated motility in both the small intestine and the large intestine have been
      reported.
     Primary phenomenon may be sensitisation of afferent neural pathways from gut to CNS, producing
      heightened perception of normal gut distension & contraction (this heightened perception may then
      reflexly trigger disordered motor activity)
     Cost to the community in terms of absenteeism from work, unnecessary investigations, etc

Psychological factors:
   IBS patients are usually more neurotic, anxious and depressed than normal population and those
    with organic GIT disorders.

Dietary factors:
                      No uniformity, with some foods causing diarrhoea in an idiosyncratic, probably
                       non-immunogenic fashion (intolerance).
                      Low fibre might be important if constipation is important.
                      Sugars (lactose in milk or fructose and sorbitol in fruits and some confectionery)
                       can cause diarrhoea, flatulence & bloating.
Postinfective factors:
Attack of IBS can be preceded by infectious diarrhoea (damage to ENS by pathogen) and symptoms
can last for months or years.

        Cardinal symptoms:
                 1. Abdominal pain or discomfort  felt in 1 or both iliac fossae, often relieved by
                    defecation or flatus passage
                 2. Distension or bloating
                 3. Disordered bowel habits, intermittent or continuous  diarrhoea or constipation
                    or both. Morning rush syndrome is common – patients have the urge to defecate
                    after breakfast
        These symptoms can be in various combinations with exacerbations and remissions.
        The presence of blood in the stool requires investigation and should not be ascribed to IBS

        Diagnosis:
                     The big question: How far to investigate, and how much to leave the diagnosis
                      up to exclusion factors.
                     In young people, perform a sigmoidoscopy, ESR and FBC.
                     In people older than 40 years, with recent change in bowel habits  FOB,
                      colonoscopy (looking for colon CA)
                     Severe diarrhoea (consider infection  stool culture)
                     In IBD (rectal biopsy) and malabsorption (faecal fats) before IBS diagnosis
        Differential diagnosis:
                     colonic CA
                     inflammatory bowel disease
                     coeliac disease
                     GIT infection
                     PID & endometriosis

        Treatment:
                         antispasmodics
                         check for food intolerance
                         bulking agents

          Summary:
                         IBS is troublesome GIT symptoms with no recognizable organic pathology.
                         Affects women more than men.
                         Diagnosis by exclusion (no structural pathology, no test & no cure).
                         Lifetime prevalence >20%
                         Experience different forms of abdominal pain, distension and altered bowel
                          habits and potentially other associated GIT/systemic symptoms (dysphagia,
                          nausea, dyspareunia, urinary frequency, etc)
                         Pathophysiology includes abnormal smooth muscle activity and heightened
                          awareness of bowel movement


Understand the pharmacology and physiology of drugs affecting GI motility and secretion.

NSAIDs:
              Inhibit prostaglandin synthesis, which is crucial in stimulation of secretion of mucous and
               bicarbonate from the gastric mucosa.
              Therefore, NSAIDs will decrease the protective effect of the barrier accounting for the
               observation that these agents have a tendency to cause gastric ulceration and bleeding.

H2-receptor Antagonists:
         These drugs competitively inhibit histamine actions at all H2-receptors, the clinically
             important part of which is their inhibition of gastric acid secretion.
         Cause inhibition of histamine-stimulated and gastrin-stimulated acid secretion and
             decrease ACh-stimulated acid secretion.
         Drugs:
                     Cimetidine - Cimehexal, Cimetimax, magicul, SBPA Cimetidine, Sigmetadine,
                      Tagamet. Oral, IM or IV. Half-life is shorter than ranitidine. Has been noted to
                      occasionally cause gynaecomastia in men and a decrease in sexual function.
                      Binds androgen receptors and inhibits CYP450 and therefore decrease the
                      metabolism of numerous drugs. May cause confusion in the elderly. Reduces
                      renal tubular secretion of basic drugs. Unwanted effects of diarrhoea, dizziness,
                      muscle pains, transient rashes and hypergastrinaemia have been reported. Single
                      daily doses are sufficient.
                     Ranitidine - DBL Ranitidine, Rani 2, Zantac, Zantac 75. Oral, IM or IV. Less
                      effect on CYP450 and androgen receptors than Cimetidine. Reduces renal
                      tubular secretion of basic drugs. Unwanted effects of diarrhoea, dizziness,
                      muscle pains, transient rashes and hypergastrinaemia have been reported. Single
                      daily doses are sufficient.
                     Nizatidine - Tazac. Oral. Unwanted effects of diarrhoea, dizziness, muscle pains,
                      transient rashes and hypergastrinaemia have been reported. Single daily doses
                      are sufficient.
                     Famotidine - Amfamox, Pepcid, Pepcidine. Oral. Unwanted effects of diarrhoea,
                      dizziness, muscle pains, transient rashes and hypergastrinaemia have been
                      reported. Single daily doses are sufficient.

Proton-pump inhibitors:
               Act by irreversibly blocking H +/K+-ATPase which is the terminal step in the acid
               secretory pathway, thereby markedly inibiting both basal and stimulated gastric acid
               secretion.
               Drugs:
                         Omeprazole - Acimax, Losec Tablets, Losec Capsules, Losec Intravenous,
                         Maxor. Works preferentially at low pH, so that accumulation occurs in the
                         secretory canaliculi of the gastric parietal cells. Half-life is about an hour, but the
                         effects last for 2-3 days. Unwanted effects are not common, but include
                         headache, diarrhoea, rashes, dizziness, somnolence, mental confusion,
                         impotence, gynaecomastia, myalgias and arthralgias.
                           Pantoprazol - Somac.
                           Lansoprazol - Zoton.

Muscarinic-receptor antagonists:
                  The main effect of stimulating muscarinic-receptors in the GIT is an increase in secretion
                  and an increase in motility. Therefore, antagonism will produce, amongst other effects,
                  antisecretory action.
                 Drugs:
                          Pirenzipine. Acts at M1-receptor found in parasympathetic ganglia and possibly
                           also on the histamine secreting cell and the gastric parietal cell. It reduces basal
                           and stimulated gastric acid secretion and has minimal extra-gastric effects, but
                           those that do occur can be more disturbing than that of the other anti-secretory
                           drugs. It is given orally.

Antacids:
                 Act by neutralising gastric acid secretion and therefore raising gastric pH, thus inhibiting
                  peptic activity, which practically ceases above pH 5. There is also thought to be
                  enhancement of prostaglandin synthesis and reduction of Helicobacter pylori replication,
                  both of which help in the healing of ulcers.
                      Antacids in common use are salts of Aluminium or Magnesium. Magnesium salts
                  cause diarrhoea, Aluminium salts cause constipation, therefore mixtures of the two are
                  used to preserve normal bowel function.

            Drugs:
                           Magnesium hydroxide - insoluble powder that forms MgCl2 in the stomach, but
                            does not cause metabolic alkalosis since Mg++ is poorly absorbed.
                           Magnesium trisilicate - insoluble powder which reacts slowly with gastric juice
                            forming MgCl2 and colloidal silica. Has a prolonged antacid effect.
                           Aluminum Hydroxide gel - forms AlCl3 in the stomach, then releases Cl- in the
                            stomach where it is reabsorbed. Has prolonged effects.
                           Sodium bicarbonate acts rapidly and is said to raise the pH of the gastric juice to
                            about 7.4. Carbon dioxide gas is liberated, however the increased carbon dioxide
                            tension stimulates gastric secretion and can result in a secondary rise in acid
                            secretion. Sodium bicarbonate can be absorbed by the intestine, frequent
                            administration may cause metabolic alkalosis.

Bulk Laxatives:
                  These are Methylcellulose, Sterculia, Agar, Bran and Ispaghula Husk.
                  These agents are all polysaccharide polymers that are not broken down in the normal
                  processes of digestion in the upper GIT and act by virtue of their capacity to retain water
                  in the gut lumen, and thereby promote peristalsis.
                  They take a couple of days to start working, but have no serious unwanted effects – may
                  help to prevent diverticular disease

Osmotic Laxatives:
    These consist of poorly absorbed solutes - the Saline Purgatives and Lactulose.
    These maintain an increased volume of fluid in the lumen of the bowel by osmosis, which
     accelerates the transfer of the gut contents through the small intestine, transfers a large amount of
     fluid into the large intestine, which causes purgation shortly afterwards.
    The main salts used are magnesium sulphate and magnesium hydroxide.
    Lactulose is a semi-synthetic disaccharide of fructose and galactose, which are converted to lactic
     and acetic acid by bacteria. It may take 2-3 days to act and can causes excessive flatulence,
     cramps, diarrhoea and electrolyte disturbances.

Stimulant Purgatives:

            These are agents that stimulate the mucosa of the gut and thereby increase peristalsis. The
            important purgatives in this group are:
                        Bisacodyl - stimulates sensory nerve endings in the colon, resulting in peristaltic
                         activity and defecation within 15-30 minutes.
                         Sodium picosulphate - stimulates sensory nerve endings in the colon, resulting in
                          peristaltic activity and defecation within 15-30 minutes.
                         Preparations of senna - has laxative effect because it contains derivatives
                          anthracene. The drug passes unchanged into the colon where bacteria hydrolyse
                          the glycoside bond, releasing free anthracene derivatives which are absorbed and
                          have a direct stimulatory effect on the myenteric plexus. This stimulation leads
                          to smooth muscle activity and defecation.
                    These agents can cause abdominal cramps and prolonged use can lead to
                 deterioration of intestinal function.

D2-Antagonists:
            Used as an anti-emetic and is also effective in increasing gastrointestinal motility.
            Drugs:
                    Domperidone - thought to enhance motility by blocking -adrenoceptors, and
                     decreasing their relaxant effect. Also increases LOS pressure (thus inhibiting
                     gastrooesophageal reflux), increases gastric emptying and enhances duodenal
                     peristalsis. Useful in disorders of gastric emptying and in chronic gastric reflux
                    Metoclopramide – acts centrally as an anti-emetic. Also has a local effect on
                     gastric motility, causing marked acceleration of gastric emptying with increased
                     gastric acid secretion. Useful in GOR and in disorders of gastric emptying.
                    Cisapride – stimulates ACh release in the myenteric plexus in the upper GIT.
                     Raises oesophageal sphincter pressure and increases gut motility. Used in reflux
                     oesophagitis and in disorders of gastric emptying. No anti-emetic action. May
                     cause life-threatening arrhythmias when interactions occur.

Antimotility agents:
                Agents in this class are generally employed as primary therapy for diarrhoea.
                Drugs:
                        Opiates:
                                   Morphine –  tone,  rhythmic contractions of the intestine, 
                                    propulsive action. Overall effect is constipating. The sphincters (anal,
                                    pyloric, ileocolic) contract and the tone of the colon is increased.
                                   Codeine –  tone,  rhythmic contractions of the intestine,  propulsive
                                    action,  secretion. Overall effect is constipating. The sphincters (anal,
                                    pyloric, ileocolic) contract and the tone of the colon is increased.
                                   Diphenoxylate –  tone,  rhythmic contractions of the intestine, 
                                    propulsive action. Overall effect is constipating. The sphincters (anal,
                                    pyloric, ileocolic) contract and the tone of the colon is increased.
                                   Loperamide –  tone,  rhythmic contractions of the intestine, 
                                    propulsive action,  secretion. Overall effect is constipating. The
                                    sphincters (anal, pyloric, ileocolic) contract and the tone of the colon is
                                    increased. Loperamide  passage of faeces and  duration of traveller’s
                                    diarrhoea.
                                   Side-effects include include nausea, vomiting, abdominal cramps,
                                    drowsiness and dizziness
                        Muscarinic receptor antagonists – seldom used against diarrhoea specifically,
                         because of the widespread systemic effects, however small doses of atropine are
                         used in combination with diphenoxylate.

Adsorbents:
                Used extensively to treat diarrhoea:
                        Kaolin
                        Pectin
                        Chalk
                        Charcoal
                        Methyl cellulose
                        Activated attapulgite

Fluid and Electrolyte Transport Modifiers (secretory agents):
                Zaldaride maleate:
                     Inhibits calmodulin, and reduces secretion of water and electrolytes. Effective in
                      traveller’s diarrhoea
                     Not clinically available
              NSAIDs:
                     Aspirin.
                     Indomethacin.
                     Inhibit prostaglandin synthesis, and so have significant antidiarrhoeal actions.
                      Other mechanisms may be involved.

Oral Rehydration:
              Isotonic solutions of NaCl plus glucose or starch-based cereal (important in infants)



Be able to describe the pathology of major diseases of the upper GI tract and biliary tree. BCS

Oesophagus:
             Atresia and fistulas:
                      Uncommon. Must be repaired early to maintain life.
                      An atresia is a non-canalised cord instead of the oesophagus, with blind pouches
                       connected to the lower part of the pharynx and the upper part of the stomach.
                      A fistula may attach any part of the oesophagus to the trachea or a bronchus.
                      Other congenital abnormalities are generally present concurrently.
             Stenosis, webs and rings:
                      Non-neoplastic constrictions are most often acquired.
                      Stenosis: fibrous thickening of the oesophageal wall, particularly of the
                       submucosa with atrophy of the muscularis propria. Thin, ulcerated epithelium.
                       Results from severe oesophageal injury with inflammatory scarring, such as
                       following GOR. Usually manifest by dysphagia.
                      Mucosal Webs: Uncommon, ledgelike semicircumferential protrusions of the
                       mucosa into the lumen. In the upper oesophagus they are denoted webs, in the
                       lower oesophagus, schatzki rings.
             Achalasia:
                      Characterised by:
                                Aperistalsis
                                Partial or incomplete relaxation of the Lower Oesophageal Sphincter
                                 with swallowing.
                                Increased resting tone of the Lower Oesophageal Sphincter.
                      Pathogenesis is not well understood, but thought to involve intrinsic and
                       extrinsic (vagus and dorsal motor nucleus of the vagus) degeneration or
                       destruction of neural innervation.
                      Manifest by progressive dysphagia.
             Hiatal Hernia:
                      Characterised by:
                                Separation of the diaphragmatic crura and widening of the space
                                 between the muscular crura and the oesophageal wall.
                                The two types of hiatus hernia are sliding (95% cases - protrusion of the
                                 stomach above the diaphragm creates a bell shaped dilation) and
                                 paraoesophageal (= rolling) (5% cases - a separate portion of the
                                 stomach enters the thorax through the widened foramen).
                                Aeitiology is unknown, but gastro-oesophageal reflux is commonly
                                 seen in association with hiatal hernia, thought it is thought to be a
                                 result, not a cause.
          Diverticula:
                      Outpouching of the ailimentary tract that contains all visceral layers. They
                       develop in three regions:
                                Zenker diverticulum - immediately above the upper oseophageal
                                 sphincter. Disordered cricopharyngeal motor dysfunction is implicated
                                 in the genesis of this disorder.
                      Traction diverticulum - near the midpoint of the oesophagus. Traction
                       may be caused by scarring resulting from mediastinal lymphadenitis or
                       motor dysfunction or a congenital lesion.
                      Epiphrenic diverticulum - immediately above the lower oesophageal
                       sphincter. This is thought to be caused by dyscoordination of peristalsis
                       and Lower Oesophageal Sphincter relaxation

Mallory-Weiss Syndrome - lacerations:
          Longitudinal tears in the oesophagus at the oesophagogastric junction are called
           mallory-weiss tears. They are believed to be the consequence of severe retching,
           and morphologically usually cross the oseophagogastric junction.
          Encountered most commonly in alcoholics due to refluxing of gastric contents in
           the setting of an alcoholic stupor, but may be associated with hiatal hernias.
          May be a cause of massive haematemesis, but tends to resolve with supportive
           therapy.

Oesophagitis:
            Injury to the oesophageal mucosa with subsequent inflammation.
            Reflux Oesophagitis:
                      Reflux of the gastric contents into the lower oesophagus is the first and
                       foremost cause of oesophagitis.
                      Some causative factors are:
                                Decreased effectiveness of the anti-reflux mechanisms such as
                                 decreased tone of the lower oesophageal sphincter, which itself
                                 may be caused by CNS depression, alcohol, tobacco,
                                 hyothyroidism or pregnancy.
                                Presence of a sliding hiatal hernia.
                                Inadequate or slowed clearance of refluxed material.
                                Delayed gastric emptying and increased gastric volume
                                 thereby increasing the volume of refluxed material.
            Barrett Oesophagus:
                      Complication of long-standing gastrooesophageal reflux.
                      Distal squamous mucosa is replaced by metastatic columnar
                       eptithelium, as a response to prolonged injury. In order for the
                       diagnosis of Barrett’s Oesophagus there must be histological evidence
                       of colonic mucosa (with goblet cells) not gastric mucosa, although the
                       two may coexist.
                      Inflammation and ulceration followed by ingrowth of pluripotent stem
                       cells, then differentiation to columnar epithelium which is more
                       resistant to the peptic effects of gastric acid is the proposed aetiology.
                      Looks hyperaemic and velvety on endoscopy.
                      Barrett's mucosa is a known risk factor for the development of
                       adenocarcinoma (30 times  risk).
            Infectious and Chemical Oesophagitis:
                      Oesophageal inflammation may have other origins, such as: ingestion
                       of mucosal irritants (alcohol, corrosive acids, heavy smoking, etc),
                       cytotoxic therapy and infection.

Oesophageal Varices:
           Sufficiently prolonged or severe portal hypertension induced the formation of
            collateral bypass channels wherever the portal and caval systems communicate,
            those in the region of the lower oesophagus cause varices.
           Portal blood flow is diverted through the coronary veins of the stomach 
            plexus of oesophageal mucosa  submucosal veins of oesophagus  azygous
            veins  systemic circulation.
           Symptomless until rupture  causing massive haematemesis, shock etc.
           Greater than 90% of cirrhotic patients have varices - these are most often
            associated with alcoholic cirrhosis.

Tumours
                   Benign tumours:
                           Mostly mesenchymal in origin and lie within the oesophageal wall.
                           Most common: leiomyomas. Fibromas, lipomas, hemangiomas,
                            neurofibromas and lymphangiomas may also occur.
                           Mucosal polyps are usually composed of a combination of fibrous,
                            vascular or adipose tissue covered by an intact mucosa, called
                            fibrovascular polyps or pedunculated lipomas depending on
                            composition. Squamous papillomas are sessile lesions with a central
                            core of connective tissue and a hyperplastic papilliform squamous
                            mucosa.

                   Malignant tumours:
                           Generally asymptomatic throughout development.
                           Generally arise from the epithelial layer. There are rare exceptions.
                           Squamous cell carcinoma:
                                   Dietary and environmental factors are involved in the
                                    aetiology of this cancer. Alcohol and tobacco are thought to be
                                    involved due to polycyclic hydrocarbon content.
                                   SCC of the oesophagus begin as in situ lesions. Early lesions
                                    appear as small, grey-white plaque-like thickenings or
                                    elevations of the mucosa.
                                   Morphology may be protruded (polypoid exophytic), flat
                                    (diffuse, infiltrative tending to spread within the wall of the
                                    oesophagus, narrowing lumen and causing mural thickening
                                    and rigidity) or excavated (necrotic cancerous ulceration that
                                    excavates deeply into surrounding structures.
                                   Metastasis to cervical, middle third mediastinal, paratracheal,
                                    tracheobronchial, gastric and coeliac lymph nodes occurs
                                    early.
                           Adenocarcinoma:
                                   Highly correlated with Barrett mucosa - point mutations in p53
                                    are evident in dysplastic foci allowing clonal progression to
                                    frank adenocarcinoma.
                                   Usually in the distal oesophagus, arising from Barrett's
                                    mucosa, may invade the adjacent gastric cardia, initially
                                    appearing as flat or raised sections of an otherwise intact
                                    mucosa. Progress to large nodular masses that are diffusely
                                    infiltrative or deeply ulcerative.

Stomach:
          Congenital abnormalities:
                    Pancreatic heterotopia - nodules of essentially normal pancreatic tissue may be
                     present in the gastric or intestinal submucosa, muscle or subserosa.
                    Gastric heterotopia - small patches of ectopic gastric mucosa in the duodenum or
                     in more distal sites may present as perplexing sources of bleeding.
                    Diaphragmatic hernia may result from congenital absences of regions of the
                     diaphragm, usually on the left side.
          Pyloric stenosis:
                    Congenital hypertrophic pyloric stenosis. Familial occurrence indicates a
                     multifactorial pattern of inheritence.
                    Clinically present with regurgitation and persistent projectile non-bilious
                     vomiting. Usually visible peristalsis and palpable mass in region of pylorus.
                    May be acquired in adults after chronic antral gastritis or pyloric peptic ulcers.
                     Carcinoma may be a more sinister cause.
          Gastritis:
                    Inflammation of the gastric mucosa, being acute with neutrophilic infiltration or
                     chronic, with lymphocytes, plasma cells or both.
                    Acute gastritis:
                    Acute mucosal inflammatory process, usually of a transient nature. May
                     be accompanied by haemorrhage into the mucosa, and in severe erosive
                     form may be a cause of acute GI bleeds.
                    Aetiology includes heavy use of NSAIDs, excessive alcohol
                     consumption, heavy smoking, Rx with chemotherapeutics, uraemia,
                     systemic infection. The mechanism by which these operate is thought to
                     be increased acid production, decreased production of bicarbonate,
                     reduced blood flow and disruption of the mucosal protective layer.
            Chronic gastritis, including Helicobacter infections:
                    Chronic gastritis is the presence of chronic mucosal inflammatory
                     changes leading eventually to mucosal atrophy and epithelial
                     metaplasia, usually in the absence of erosions. Epithelial changes may
                     become dysplastic and constitute a background for the development of
                     carcinoma.
                    Aetiology: chronic infection by Helicobacter pylori, autoimmune
                     (pernicious anaemia – anti-intrinstic factor Ab  target parietal cells),
                     toxic (alcohol, smoking), post-surgical, obstruction, radiation,
                     granulomatous conditions.

   Peptic ulcer disease:
            Ulcers are defined as a breach in the mucosa of the alimentary tract, which
             extends through the muscularis mucosa into the submucosa or deeper.
            Peptic ulcers:
                     Chronic, most often solitary, lesions that occur in any portion of the
                      gastrointestinal tract exposed to the aggressive action of acid-peptic
                      juices. Both the acid and the pepsin are critical, but production is a
                      result of the imbalance between gastroduodenal defence mechanisms
                      and the damaging forces.
                     May come and go, heal then recur. Propensity to recur remains. Men
                      are more affected than women, but less so after menopause.
                     Helicobacter pylori is very important in the pathogenesis of peptic
                      ulcers - present in all duodenal ulcers and 70% gastric ulcers. Secretes
                      urease than generates ammonia and proteases which breakdown gastric
                      mucous. Causes inflammatory reactions that make the cells more liable
                      to acid injury. Causes damage to the mucosa that permits the leakage of
                      tissue nutrients into the surface microenvironment thereby sustaining
                      the bacillus.
                     Zollinger-Ellison Syndrome exhibits multiple peptic ulcerations in the
                      stomach, duodenum and jejunum, owing to excess gastrin secretion by
                      a tumour and hence excess gastric acid production (similar
                      classification to carcinoids).
                     NSAIDs suppress mucosal prostaglandin synthesis and therefore
                      mucosal protection, asprin is a direct irritant, cigarette smoking impairs
                      blood flow, any cause of hypercalcaemia stimulates gastric production
                      and therefore acid release.
                     Most peptic ulcers are in the anterior wall of the first part of the
                      duodenum. Morphologically they are usually round-to-oval, sharply
                      punched-out defect with relatively straight walls. Histological picture
                      may vary from active necrosis to chronic inflammation and scarring to
                      healing. Malignant transformation is unknown in duodenal ulcers and
                      rare in gastric ulcers.
            Acute gastric ulceration:
                     Focal, acutely developing gastric mucosal defects are a known
                      complication of NSAID therapy and physiological stress.
                     Multiple lesions located in the stomach and possibly the duodenum,
                      ranging from erosions (shedding of superficial endotehlium) to deep
                      ulcerations (deeper lesions - complete mucosal thickness).
                     Commonly encountered in patients with shock, extensive burns, sepsis,
                      severe trauma and any cause of  ICP (stimulation of CNX).
Miscellaneous conditions:
           Gastric dilation:
                    May arise from gastric outlet obstruction or functional atony of the
                     stomach and intestines (paralytic ileus from generalised peritonitis) or
                     hairball (trichobezoar) or fibrous material collections (phytobezoar).
                    May contain up to 15 litres of fluid and lead to catastrophic rupture.
           Hypertrophic gastropathy:
                    Group of uncommon conditions characterised by giant cerebriform
                     enlargement of the rugal folds of the gastric mucosa by hyperplasia.
                    Three variants: Ménétrier disease, Hypertrophic-hypersecretory
                     gastropathy and Gastric gland hyperplasia secondary to excessive
                     gastrin secretion.
                    Great risk of peptic ulceration due to increased acid production. These
                     conditions may be mistaken for infiltrative carcinoma or lymphoma of
                     the stomach radiologically.

Tumours:
            Tumours arising from the mucosa are more common than mesenchymal and
             stromal tumours.
            Benign tumours:
                     In the alimentary tract, the term polyp is applied to any nodule or mass
                      that projects above the level of the surrounding mucosa. Polypoid
                      lesions include more layers than just the mucosa.
                     Most polyps are non-neoplastic, appearing to be of a hyperplastic
                      nature. Seen frequently on a back-ground of chronic gastritis.
            Gastric carcinoma:
                     Most frequent malignant tumour - 90%. Less common in UK, USA,
                      Canada, Australia. More common in men. More common in lower
                      socioeconomic groups. Diet and environmental factors are highly
                      implicated as risk factors.
                     Can be divided into two histologic subtypes - intestinal morphology
                      (formation of bulky, glandular tumours - neoplastic intestinal glands)
                      and diffuse morphology (infiltrative growth of poorly differentiated
                      discohesive malignant cells - neoplastic gastric type mucous cells).
                     Dysplasia of the gastric mucosa represents the final common pathway
                      by which intestinal type gastric cancers arise. The diffuse type appears
                      to arise de novo without evolution through dysplasia.
                     Allelic genetic losses in the intestinal type of gastric cancer show
                      similarities to colon cancer, however disparities in mutation point to
                      unique pathogenic pathways.
                     Favoured location is the lesser curvature of the anteropyloric region.
                      Classification is made on the basis of depth of invasion, macroscopic
                      growth pattern and histologic subtype. Early gastric carcinoma is
                      confined to the mucosa and submucosa, irrespective of lymph nodal
                      involvement. Carcinoma-in-situ is confined to the surface epithelial
                      layer. Advanced gastric carcinoma is a neoplasm that has extended
                      below the submucosa into the muscular wall.
                     Macroscopic growth patterns are exophytic (protrusion), flat or
                      depressed (extensive malignancy or metastasis  linitis plastica) or
                      excavated.
                     Prognosis is poor. Few signs (weight loss, abdominal pain, anorexia,
                      vomiting) till late in course.


        Less common gastric tumours:
                  Gastric lymphomas - 5% of gastric malignancies.
                  Gastric neuroendocrine cell (carcinoid) tumours are rare.
                  Smooth muscle mesenchymal tumours - leiomyoma (benign) and
                   leiomyoarcoma (malignant)
                  Metastatic involvement of the stomach is rare.
Small and Large Intestines:
           Duplication, malrotation, omphalocoele (abdominal musculature fails to form - abdominal
            contents herniate) and gastroschisis (portion of abdominal wall fails to form completely -
            abdominal contents extrude) are congenital abnormalities.
           Atresia and stenosis:
                     Congenital intestinal obstruction is uncommon - duodenal atresia is most
                      common - may be imperforate mucosal diaphragm or stringlike segment of
                      bowel connecting proximal and distal segments.
                     Stenosis is less common - may be due to narrowed intestinal segment or
                      diaphragm with a narrow central opening.
                     Failure of the cloacal membrane to rupture leads to an imperforate anus.
           Meckel diverticulum:
                     Failure of the involution of the vitelline duct, which connects the lumen of the
                      developing gut to the yolk sac, produces a Meckel diverticulum.
                     Usually 2 inches long, 2 feet from the ileocaecal valve. Contains all three layers
                      of the normal bowel wall: mucosa, submucosa and muscularis propria. May have
                      heterotopic rests of pancreatic or gastric tissue.
           Congenital aganglionic megacolon - Hirschprung disease:
                     Characterised by the absence of ganglion cells in the large bowel  functional
                      obstruction and colonic dilation proximally.
                     Can be sporadic, but familial cases occur and gene defect is thought to be in
                      genes controlling migration and survival of neuroblasts and neurogenesis.
                     Rectum is always affected. Commonly occurs with other wide-spread serious
                      neurological disorders.
           Enterocolitis:
                     Diarrhoea and dysentry:
                              Precise definitions are elusive, but an increase in stool mass, stool
                               frequency or stool fluidity is perceived as diarrhoea by most patients.
                               Usually >250g containing 70-95% water.
                              Dysentery is low-volume, painful, bloody diarrhoea.
                              Secretory Diarrhoea: Net intestinal fluid secretion leads to output of
                               greater than 500mL of fluid stool per day, which is isotonic with plasma
                               and persists during fasting.
                              Osmotic Diarrhoea: excessive osmotic forces exerted by luminal
                               solutes lead to output of greater than 500mL of stool per day which
                               abates on fasting. Stool osmolality exceeds electrolyte concentration by
                               >50mOsm.
                              Exudative Diseases: mucosal destruction leads to output of purulent,
                               bloody stools which persists on fasting. Stools are frequent, but may be
                               small or large volume.
                              Malabsorption: Improper absorption of gut nutrients produces
                               voluminous, bulky stools with increased osmolarity combined with
                               steatorrhoea. Usually abates on fasting.
                              Deranged Motility: Improper gut neuromuscular function may produce
                               highly variable patterns of increased stool volume. This is usually a
                               diagnosis of exclusion.
                     Infectious enterocolitis:
                              Intestinal diseases of microbial origin are marked principally by
                               diarrhoea and sometime ulceroinflammatory changes.
                              E. coli is a common pathogen, but the spectrum varies with age,
                               nutrition, immune status, environment. Commonly not isolated.
                     Viral gastroenteritis:
                              Caused by a distinct group of viruses - Rotavirus is the most common.
                               Clinical syndrome: incubation period of 2 days followed by several
                               days of watery diarrhoea.
                              Morphologic changes consist of shortening and blunting of the villi and
                               infiltration of the lamina propria by lymphocytes.
           Bacterial enterocolitis:
                    Diarrhoeal illness of bacterial form is caused by several pathogenic
                     mechanisms:
                              Ingestion of preformed toxin, present in contaminated food
                               (major offenders are Staphylococcus aureus, Vibrio cholerae
                               and Clostridium perfringens)
                              Infection by toxigenic organisms, which proliferate within the
                               gut lumen and elaborate an enterotoxin.
                              Infection by enteroinvasive organisms, which proliferate,
                               invade and destroy mucosal epithelial cells.
                    Bacteria must have the ability to adhere to the mucosal epithelial cells
                     (so they don't get swept away) and replicate, the ability to elaborate
                     eneterotoxins (polypeptides that cause diarrhoea) and the capacity to
                     invade. Bacterial invasion is followed by intracellular proliferation, cell
                     lysis and cell-to-cell spread.
                    Pathologic manifestations may be insignificant, despite dramatic or
                     lethal diarrhoea. Most bacterial infections exhibit a general non-specific
                     pattern of damage to the surface epithelium, decreased epithelial cell
                     maturation, increased mitotic rate, hyperaemia and oedema of the
                     lamina propria.
                    Clinical picture will depend on the pathophysiology of the organism -
                     can be severe complications when there is massive fluid loss or
                     destruction of the intestinal mucosal barrier and resultant dehydration,
                     sepsis and perforation or minor where there is extreme discomfort.
                     Enteroinvasive organisms may mimic acute onset IBD.

           Necrotising enterocolitis:
                    An acute, necrotising inflammation of the small and large intestine and
                     is the most common acquired GIT emergency of neonates.
                    Causes: Immaturity of the GIT, Intestinal mucosa cytokine release on
                     initiation of solid foods, bacterial colinisation of the gut on onset of oral
                     feeding, mucosal injury, deranged intestinal blood flow.
                    Usually affects the terminal ileum and the ascending colon, but may
                     incorporate all of both intestines. Full thickness of bowel wall becomes
                     haemorrhagic, inflamed and gangrenous.
                    Varies in presentations depending on stage and severity of the disease.

           Antibiotic associated colitis or pseudomembranous colitis:
                    Acute colitis characterised by formation of an adherent inflammatory
                     exudate (pseudomembrane) overlying sites of mucosal injury, usually
                     caused by protein exotoxins of Clostridium difficile – Type A and Type
                     B toxins – usually only Type A is assessed in the laboratory.
                    Occurs primarily in adults as an acute or chronic diarrhoeal illness,
                     although it has been recorded as a spontaneous infection in young
                     adults without predisposing influences.

           Collagenous and lymphocytic colitis:
                   Collagenous colitis is characterised by chronic watery diarrhoea and
                    patches of band-like collagen deposits directly under the surface
                    epithelium.
                   Lymphocytic colitis is characterised by chronic watery diarrhoea and a
                    prominent intraepithelial infiltrate of lymphocytes.
                   Collagenous colitis is more in middle-aged and older women,
                    lymphocytic occurs in men and women equally. Mucosa is normal
                    despite 3-20 watery non-bloody motions per day.

   Miscellaneous intestinal inflammatory disorders
           Parasites and protozoa:
                    Entamoeba histolytica is a dysentry-causing protozoan parasite spread
                     by the faecal-oral route. Amoebae invade the colonic crypts and lamina
                      propria then make flask-shaped ulcers. These parasites may penetrate
                      portal vessels, embolise the liver and produce multiple hepatic
                      abscesses. May also occur in lung, heart kidneys and brain.
                     Giardia lamblia is an intestinal protozoan spread by faecal
                      contaminated water. It attached to the intestinal mucosa, but does not
                      appear to invade. Villi range from normal to marked blunting with a
                      mixed inflammatory infiltrate of the lamina propria. Clinically, this
                      produces a malabsorptive diarrhoea.
            AIDS:
                    Some patients exhibit a malabsorptive syndrome with small intestine
                     villius atrophy or a colitic syndrome resembling ulcerative colitis, in the
                     absence of demonstrable pathogens. Often infected with opportunistic
                     infections  Cryptosporidium parvum
            Transplantation:
                    Diarrhoea is a significant complication of bone marrow transplantation.
                     Pre-transplant conditioning may cause direct toxic injury - villus
                     blunting and degeneration of crypts in small intetsinal mucosa.
                    Severe watery diarrhoea is a feature of acute graft-versus-host disease -
                     there will be focal crypt cell necrosis, eventually leading to total
                     sloughing of mucosa, causing life threatening derangement of
                     electrolytes and possibly leading to sepsis and intestinal haemorrhage.
            Drug-induced intestinal injury:
                    Focal ulceration may occur if a pill adheres to the mucosa and releases
                     all of its contents locally (such as when no water is used).
                    The small and large intestines are susceptible to drug-induced
                     enterocolitis, commonly associated with the use of NSAIDs.
                     Malabsorption may result after a non-specific inflammation.
                    Ulceration and stricture may occur. This must always be a DDx when
                     abdominal illness is encountered.
            Radiation enterocolitis:
                    Abdominal irradiation may severely impair the normal proliferative
                     activity of the small intestine and colonic mucosal epithelium.
                    Acute radiation enteritis manifests as anorexia, abdominal cramps and
                     malabsorptive diarrhoea. Chronic radiation enteritis or colitis may
                     exhibit more indolent symptoms.
                    May be perpetuated by radiation induced vascular injury leading to
                     ischaemic fibrosis and strictures.


Malabsorption Syndromes:
           Malabsorption is characterised by suboptimal absorption of fats, fat-soluble and
            other vitamins, proteins, carbohydrates, electrolytes, minerals and water. It is the
            result of disturbance of intraluminal digestion, terminal digestion or
            transepithelial transport. There may be many clinical presentations in various
            systems as a result of malabsorption:
           Stools may be abnormally bulky, frothy, greasy, yellow or grey (steatorrhoea).
            Bacterial overgrowth within the intestines may occur, futher damaging epithelial
            cells and impairing absorption. Diarrhoea is usually osmotic, due to increase
            undigested intraluminal intestinal contents.
                     Alimentary tract - Diarrhoea, flatus, abdominal pain, weight loss.
                     Haematopoietic system - anaemia from iron, pyridoxine, folate of
                      Vitamin B12 deficiency and bleeding from Vitamin K deficiency.
                     Musculoskeletal system - osteopenia and tetany from calcium,
                      magnesium, vitamin D and protein malabsorption.
                     Endocrine system - amenorrhoea, impotence, infertility and
                      hyperparathyroidism.
                     Epidermis - purpura, petechiae, oedema, dermatitis, hyperkeratosis.
                     Nervous system - peripheral neuropathy from vitamin A and B 12
                      deficiency.
                  Celiac Sprue:
                                 Also called celiac disease, it is characterised by mucosal lesions of the
                                  small intestine and impaired nutrient absorption which improves on
                                  withdrawal of wheat gliadins and related grain proteins from the diet.
                                 Sensitivity to gluten is thought to be the pathogenic factor and cell-
                                  mediated immunity appears to be important. Cytokines released during
                                  the immunological interactions damages the enterocytes.
                                 Mucosa may be flat or scalloped with marked atrophy or total loss of
                                  villi. Crypts are elonged, hyperplastic and tortuous. Lamina propria has
                                  an overall increase in plasma cells, lymphocytes, macrophages,
                                  eosinophils and mast cells.

                     Tropical or post-infectious sprue:
                              Celiac-like disease that occurs almost exclusively in people living in or
                               visiting the tropics. No specific causal agent has ever been identified,
                               but bacterial overgrowth (E. coli) has been implicated.
                              Morphologically variable - near-normal to severe diffuse enteritis.

                     Whipple disease:
                             Rare systemic condition - can involve any organ, but principally the
                              intestine, CNS and joints. Causative organism is a gram positive
                              actinomycete, Tropheryma whippelii.
                             Small intestinal mucosa is laden with distended macrophages in the
                              lamina propria. Shaggy gross appearance. Inflammation is essentially
                              absent.
                             Lymphadenopathy and hyperpigmentation may occur.

                     Disaccharidase (lactase) deficiency:
                             Lactase remains in the intestinal lumen as it is not broken down
                              properly - causes an osmotic diarrhoea.
                             Malabsorption usually becomes clinically obvious with the initiation of
                              milk feeding - explosive, watery, frothy diarrhoea with abdominal
                              distension. No visible micro- or macroscopic pathology.

                     Abetalipoproteinaemia:
                             Characterised by a defect in the synthesis and export of lipoproteins
                              from the intestinal mucosa - FFA and monoglycerides resulting from
                              hydrolysis of dietary fat enter the epithelial cells are re-esterified but
                              can't be turned into chylomicrons.
                             TGs are therefore stored within the cells causing lipid vacuolation and
                              there is complete absence from plasma any lipoprotein containing
                              apolipoprotein B - VLDL, LDL and chylomicrons.

Idiopathic inflammatory bowel disease:
   Crohn and UC - known as inflammatory bowel diseases. They are chronic, relapsing inflammatory
    disorders of unknown origin. Crohn disease is a granulomatous disease that may affect any portion
    of the GIT from oesophagus to anus but most often involves the small intestine and colon.
    Ulcerative colitis is a non-granulomatous disease limited to the colon. Both exhibit extra-intestinal
    inflammatory manifestations.
   Is a perturbation in the state of physiological inflammation that is the normal steady-state of the
    intestine, a mix between inflammation due to microbes, dietary antigens, etc and mucosal
    protection mechanisms.
   There is no clear Mendelian inheritance pattern, but 15% patients have IBD affected first degree
    relatives.
   Causes may be stimulation of host mucosal immunity that then fails to down-regulate. Clinical
    manifestations of IBD and the diagnostic pathology are ultimately the result of activation of
    inflammatory cells whose products cause non-specific tissue injury. Neutrophils are the most
    important contributor of these mediators, then eosinophils and mast cells.
   Crohn disease:
          Crohn disease is characterised pathologically by:
                      Sharply delimited and typically transmural involvement of the bowel by an
                       inflammatory process with mucosal damage
                      The presence of non-caseating granulomas.
                      Fissuring with formation of fistulas.
            Affects 40% small intestine alone, 30% both small and large and 30% large alone.
            Serosa is dull, mesenteric fat wraps around the intestine (creeping fat). The intestinal wall
             is rubbery and thick from oedema, inflammation, fibrosis and hypertrophy of the
             muscularis propria.
            There is sharp demarcation of diseased bowel segments from adjacent uninvolved
             segments. When multiple segments are involved, the intervening bowel is essentially
             normal (skip lesions).
            Chronic mucosal damage with architectural distortion is manifest in the small intestine as
             variable villus blunting and in the colon as crypts exhibit irregularity and branching.
             Mucosa may undergo metaplasia. Granulomas have been documented throughout the
             length of the alimentary tract, but absence does not preclude diagnosis.
            May be marked loss of albumin, generalised malabsoroption, malabsorption of bile salts,
             migratory polyarthritis, ankylosing spondylitis, clubbing of the fingertips.

   Ulcerative colitis:
         Ulceroinflammatory disease limited to the colon and affecting only the mucosa and
             submucosa. Ulcerative colitis extends in a continuous fashion proximally from the
             rectum. If it involves the entire colon, it is a pancolitis. Well formed granulomas are
             absent.
                               May have skin lesions, sacroiliitis, migratory polyarthritis, ankylosing
                                spondylitis, pericholangitis and hepatic involvement.
                               Mucosa may exhibit slight reddening and granularity with friability and
                                easy bleeding. Pseudopolyps may appear - islands of regenerating
                                mucosa. Mural thickening does not occur in ulcerative colitis and the
                                serosal surface is usually completely normal.
                               Toxic damage to the muscularis propria and the neural plexuses may
                                lead to complete neuromuscular shutdown in most severe cases (the
                                colon swells and becomes gangrenous). This condition is called toxic
                                megacolon.
                               Lamina propria has a mononuclear inflammatory infiltrate.
                               When patients are having an attack, there is stringy mucus in bloody
                                diarrhoea with lower abdominal pain and cramps.
                               Long-term complication is cancer as underlying inflammatory disease
                                can mask the symptoms and signs. The rate of progression to dysplasia
                                and carcinoma is in fact quite low provided that initial examinations are
                                negative for dysplasia.
Vascular disorders
            Ischaemic bowel disease:
                               Are restricted to the distribution of the affected vessel(s). Rich
                                anastomotic connections may render single vessel occlusions harmless
                                but blockage of coeliac, superior or inferior mesenteric arteries may
                                infarct metres of intestine.
                               Ranges of injury:
                                         Transmural infarction - all visceral laeyrs.
                                         Mural infarction - mucosa and submucosa.
                                         Mucosal infarction - no deeper than muscularis mucosae.
                               Predisposing conditions for ischaemia:
                                         Arterial thrombus from atherosclerosis, systemic vasculitis,
                                          dissecting aneurysm, angiographic proceedures and
                                          hypercoagulable states.
                                         Arterial embolism from cardiac vegetations, angiographic
                                          proceedures and aortic atheroembolism.
                                         Venous thrombosis from hypercoagulable states, OCP,
                                          antithrombin III deficiency, intraperitoneal sepsis,
                                          postoperative state, neoplasia and cirrhosis.
                                         Non-occlusive ischaemia from cardiac failure, shock
                                          dehydration and vasoconstrictive drugs.
                                         Radiation injuries, volvulus, herniation and stricture.

   Infarctions appear haemorrhagic (whether arterial or venous) because of the blood reflow back into
    the affected area. Arterial occlusions show sharp demarcations, venous occlusions do not.
   Both acute and chronic mucosal ischaemia are notoriously segmental and patchy, on a micro- and
    macroscopic scale.

   Angiodysplasia:
           Tortuous dilations of submucosal and mucosal blood vessels are seen most often in the
           caecum and right colon and account for 30% of significant lower intestinal bleeding;
           intestinal haemorrhage may be chronic and intermittent or acute and massive.
           The vascular channels may only be separated from the inteswtinal lumen by the vascular
           wall and a layer of attenuated epithelial cells, explaining the propensity toward bleeding.
           Thought to be caused by vascular degeneration and mural tension due to lumenal
           pressure and large diameter.

   Haemorrhoids:
           Variceal dilations of the anal and peri-anal plexuses that develop secondary to
           persistently elevated venous pressure within the haemorrhoidal plexus.
           Most frequent predisposing factor is constipation with straining at stool and the venous
           stasis of pregnancy. May also develop as collateral anastomotic channels resulting from
           portal hypertension.

   Diverticular disease:
         A diverticulum is a blind pouch leading off the alimentary tract, lined by mucosa that
             communicates with the lumen of the gut. Discounting Meckel's, they tend to be acquired
             and either lack or have attenuated muscularis propria. Unless specified, diverticular
             disease refers to acquired outpouchings of the colonic mucosa and submucosa.
         Most are small, spherical or flask-like outpouchings of the sigmoid colon, descending or
             entire colon, tending to occur alongside taeniae coli.
         Two factors are important in their pathogenesis - focal weakness in the colonic wall and
             increased intraluminal pressure.
         Only 20% of those affected ever develop manifestations such as intermittent cramps,
             continuous lower abdominal discomfort, constipation.

   Intestinal obstruction:
             Occurs most commonly in the small intestine due to its small lumen.
             80% of obstructions are caused by hernias, intestinal adhesions, intussusception and
             volvulus. This leads to abdominal pain, distension, vomiting, obstipation and failure to
             pass flatus.

   Hernias:
              A weakness or defect in the wall of the peritoneal cavity may permit protrusion of a
               pouch-like, serosa-lined sac of peritoneum called a hernial sac, usually occur at inguinal
               and femoral canals, umbilicus, surgical scars and occasionally retroperitoneally at the
               ligament of trietz.
              Hernias are of concern chiefly because segments of viscera frequently protrude and
               become trapped in them (external herniation)
              Inguinal hernias have small orifices, large sacs and may consume small bowel loops
               (often), omentum or large bowel.
              If venous return is compromised, trapped viscus may swell and prohibit removal, called
               incarceration. The consequent compromise of arterial and venous supply (strangulation)
               leads to infarction.

   Adhesions:
        Develop post-peritonitis, i.e. after surgical procedures, infection (PID), endometriosis, as
            healing is taking place.
           Adhesions can develop between bowel segments, abdominal wall and operative site
            creating fibrous bridges and loops through which other viscera may slide and become
            trapped (internal herniation).

   Intussusception:
          Occurs when one segment of the small intestine, constricted by a wave of peristalsis
             suddenly becomes telescoped into the immediately distal segment of bowel. This segment
             continues to propagate by peristalsis, dragging its mesentery with it.
          Usually a suspicious cause in adults at the point of traction. Intestinal obstruction ensues
             and trapping of mesenteric vessels leads to infarction.

   Volvulus:
         Complete twisting of a loop of bowel about its mesenteric base of attachment produces
            obstruction and infarction.
         Occurs most often in large redundant loops of sigmoid, followed in frequency by the
            caecum, small bowel, stomach or rarely transverse colon.


Tumors of the small intestine:
            75% of the length of the GIT only 3-6% of the GIT tumours.
                     Adenomas:
                              Account for 25% of the benign small intestinal tumours, with
                               leiomyomas, lipoma and neuromatous lesions following in frequency.
                               Most occur in the region of the ampulla of vater.
                     Adenocarcinoma:
                              The large majority of these occur in the duodenum and jejunum. They
                               grow in a napkin ring encircling pattern or as polypoid fungating
                               masses.
                              Tumors in the duodenum, around the ampulla of vater may present with
                               obstructive jaundice early in their course. Also cramping pain, nausea,
                               vomiting and weight loss.
                              Many have penetrated bowel wall, invaded mesentery and spread to
                               regional nodes, possible liver metastasis.

Tumours of the colon and rectum
                    Adenocarcinomas constitute the vast majority of colorectal cancers and represent
                     70% of all malignancies arising in the GIT.

                     Non-neoplastic polyps:
                            A polyp is a tumourous mass that protrudes into the lumen of the gut.
                             Begin sessile (flat) and progress to pedunculated. May be formed as the
                             result of abnormal mucosal maturation, inflammation or architecture.
                             They are non-neoplastic and do not have malignant potential per se.
                            Occur sporadically, particularly in the colon, occur in greater frequency
                             with age and represent 90% of all epithelial polyps.
                            Hyperplastic polyps can arise at any age, but they usually have no
                             malignant potential.

                     Adenomas:
                           Epithelial polyps that arise as the result of proliferation and dysplasia
                            are termed adenomatous polyps or adenomas - these are true neoplastic
                            lesions (new growth) and are carcinoma precursors.
                           Three subtypes, based on epithelial architecture: tubular adenomas,
                            villous adenomas and tubulovillous adenomas.
                           All adenomatous lesions arise as the result of epithelial proliferative
                            dysplasia, which may range from mild to so severe as to constitute
                            carcinoma in situ. There is strong evidence that adenomas are a
                            precursor lesion for invasive colorectal adenocarcinoma.
                           Malignant risk is correlated with polyp size, histologic architecture and
                            severity of epithelial dysplasia. It is rare in tubular adenoma smaller
                                 than 1 cm in diameter., it is high in sessile villous adenomas greater
                                 than 4 cm in diameter and severe dysplasia is often found in villous
                                 areas.
                       Familial syndromes
                       Colorectal carcinogenesis
                       Colorectal carcinoma
                       Carcinoid tumours
                       Gastrointestinal lymphoma
                       Mesenchymal tumours

Biliary Tract:
                  Congenital abnormalities
                  Disorders of the gallbladder
                      Cholelithiasis
                      Cholecystitis
                  Disorders of the extrahepatic bile ducts
                      Choledocholithiasis and ascending cholangitis
                      Biliary atresia
                      Choledochal cysts
                  Tumours:
                      Carcinoma of the gallbladder
                      Carcinoma of the extrahepatic bile ducts.


Ability to cope with clinical situations in which there are high levels of uncertainty, iatrogenic morbidity, and
undesired outcomes. ICSCRP/EPPD

Health care workers have a moral obligation to ensure, wherever possible, that their intervention will
result in a net benefit to the patient. This means that any associated treatment risks and probabilities
must be taken into account when determining potential harms and benefits. The division between
beneficence and non-maleficence is not clear and the best ethical approach requires speculation and
anticipation.

In these sort of clinical situations, one must stick to a diagnostic strategy. Based on the evidence, a
probability diagnosis has to be made. However, it should be ensured that serious disorders not to be
missed. Special consideration must be given to the pitfalls, which are diagnosis that are often missed.
The Seven Masquarades are seven diseases that present themselves in atypical ways or don't have a
typical presentation and must be considered in unclear situations. These are:
              Depression
              Diabetes
              Drugs
              Anaemia
              Thyroid Disease
              Spinal Dysfunction
              UTI
As part of this diagnostic strategy, always ask the question: Is the patient trying to tell me something?
Inherent in the concept that probabilities can guide decision making is the assumption that one can
arrive at a reasonable threshold by knowing the relative risks and benefits of various options and
deciding at what probability this ratio changes to favor an alternative strategy. In performing any
decision analysis, the relevant probabilities must be known or estimated, a process that sometimes
requires guesswork. A major practical limitation of decision analysis is the subjective judgment often
required to estimate utilities. If the conclusions of an analysis were altered by relatively minor changes
in the assumptions on which it was based, the analysis would not be sufficiently reliable to become the
basis for decision making.

Decision analysis sometimes demonstrates a clear and dramatic advantage with one particular option.
In other circumstances, there may be little difference between two options. Either option may be
reasonable, or secondary issues that cannot be taken into account in the formal analysis (Patient's
feelings about risks; recent local experience with particular interventions) should be the final
determinants in the decision. Even when the outcome of the analysis seems clear, the physician or the
patient may believe that the situation in question is an exception to the rule. Other reasonable
alternatives must also be considered. Furthermore, even the best analyses, like all clinical intuition, are
based on assumptions that may be open to debate.


Making clinical distinctions between functional and structural GI disorders. ICSCRP

Functional gastrointestinal disorders are somatic complaints relating to the gastrointestinal tract that are
manifestations of psychosocial factors. The primary symptoms of functional gastrointestinal disease
may be dyspepsia, intermittent diarrhoea or constipation. Structural or organic gastrointestinal disease
may have symptoms of weight loss,

Abdominal pain may be structural or functional

Selection and interpretation of GI investigations. ICSCRP
                                           Learning Objectives

Dom               LO Title                                                LO Detail
BCS Fluid and electrolyte balance       1. To detect fluid and electrolyte imbalance and understand its
                                        correction/prevention
BCS Pain management                     1. To revise the physiological mechanisms of pain and describe, in principle,
                                        how pain is managed.
BCS Anatomy                             1. To describe the embryology and anatomy of the inguinal canal
                                        2. To describe the anatomy of the femoral canal
BCS Gut obstruction                     1. Describe the major pathology of the small intestine
                                        2 .To describe the pathophysiology of gut obstruction including:
                                        (a) differences in consequences between pyloric, high intestinal and low
                                        intestinal obstruction and strangulation;
                                        (b) relationship between pathophysiology and clinical course of different
                                        types of obstruction;
                                        (c) relationship of pathophysiological mechanisms to planning of treatment
                                        3. To outline the principles of operative management of strangulated hernia
                                        with gangrenous gut
ICCP Clinical reasoning                 1. To list the appropriate investigations in the patient with an acute abdomen
                                        and how to interpret them
ICCP Clinical and radiological features 1. Describe and be able to demonstrate the clinical and radiological features
     of small bowel obstruction         of small bowel obstruction.


ICCP Procedural skills                  1. Be able to perform nasogastric tube insertion, intravenous cannulation
                                        and fluid administration
ICCP Decision making in emergencies 1. Describe the rationale that underlies decision making in the emergency
                                    situation
PPH Patient values and concept of       1. Demonstrate an ability to determine and integrate patients’ values and lay
    illness (Social Sciences)           concepts of illness and health care activities, into clinical management.
Party Hard
ANATOMY OF INGUINAL REGION
    1.   Describe the embryology and anatomy of the inguinal canal.
             Development of the inguinal canal
                 Prior to the descent of the testis and the ovary from their site of origin high in the
                  posterior abdominal wall (L1), a peritoneal diverticulum call the processus vaginalis
                  is formed. The processus vaginalis passes through the layers of the lower part of the
                  anterior abdominal wall and, as it does so, acquires a tubular covering from each
                  layer. It traverses the fascia transversalis at the deep inguinal ring and acquires a
                  tubular, the internal spermatic fascia. As it passes through the lower part of the
                  internal oblique muscle, it takes with it some of its lowest fibres, which form the
                  cremaster muscle. The muscle fibres are embedded in fascia, and thus the second
                  tubular sheath is known as the cremasteric fascia. The processus vaginalis passes
                  under the arching fibres of the transversus abdominis muscle and therefore does not
                  acquire a covering from this abdominal layer. On reaching the aponeurosis of the
                  external oblique, it evaginates this to form the superficial inguinal ring and acquires a
                  third tubular fascial coat, the external spermatic fascia. It is in this manner that the
                  inguinal canal is formed in both sexes. (In the female the term “spermatic” fascia
                  should be replaced by the covering of the round ligament of the uterus.)
                 Meanwhile, a band of mesenchyme, extending from the lower pole of the developing
                  gonad through the inguinal canal to the labioscrotal swelling, has condensed to form
                  the gubernaculum.
                 In the male the testis descends through the pelvis and inguinal canal during the
                  seventh and eighth months of foetal life. The normal stimulus for the descent of the
                  testis is testosterone, which is secreted by the foetal testes. The testis follows the
                  gubernaculum and descends behind the peritoneum on the posterior abdominal wall.
                  The testis then passes behind the processus vaginalis and pulls down its duct, blood
                  vessels, nerves, and lymph vessels. The testis takes up its final position in the
                  developing scrotum by the end of the eighth month.
                 Since the testis and its accompanying vessels, ducts, and so on follow the course
                  previously taken by the processus vaginalis, they acquire the same three coverings as
                  they pass down the inguinal canal. Thus, the spermatic cord is covered by three
                  concentric layers of fascia: the external spermatic fascia, the cremasteric fascia, and
                  the internal spermatic fascia.
                 In the female the ovary descends into the pelvis following the gubernaculum. The
                  gubernaculum becomes attached to the side of the developing uterus, and the gonad
                  descends no further. That part of the gubernaculum becomes attached to the side of
                  the developing uterus, and the gonads descends no further. That part of the
                  gubernaculum extending from the uterus into the developing labium majus persists as
                  the round ligament of the uterus. Thus, in the female only the structures that pass
                  through the inguinal canal from the abdominal cavity are the round ligament of the
                  uterus and a few lymph vessels. The lymph vessels convey a small amount of lymph
                  from the body of the uterus to the superficial inguinal nodes.

Inguinal canal
                 The inguinal canal is an oblique passage through the lower part of the anterior
                  abdominal wall and is present in both sexes. It allows structure to pass to and from
                  the testis to the abdomen in males. In females it permits the passage of the round
                  ligament of the uterus from the uterus to the labium majus. In addition, it transmits
                  the ilioinguinal nerve in both sexes.
                 The canal is about 4 cm long in the adult and extends from the deep inguinal ring, a
                  hole in the fascia transversalis, downward and medially to the superficial inguinal
                  ring, a hole in the aponeurosis of the external oblique muscle. It lies parallel to and
                  immediately above the inguinal ligament. In the newborn child, the deep ring lies
                  almost directly posterior to the superficial ring, so that the canal is considerably
                  shorter at this age. Later, as the result of growth, the deep ring moves laterally.
                 Deep inguinal ring: an oval opening in the fascia transversalis, lies about 1.3 cm
                  above the inguinal ligament midway between the anterior superior iliac spine and the
                  symphysis pubis. Related to it medially are the inferior epigastric vessels, which
                  pass upward from the external iliac vessels. The margins of the ring give origin to
                  the internal spermatic fascia (or the internal covering of the round ligament of the
                  uterus).
                 Superficial inguinal ring: a triangular-shaped defect in the aponeurosis of the
                  external oblique muscle and lies immediately above and medial to the tubercle. The
                  margins of the ring, sometimes called the crura, give origin to the external
                  spermatic fascia.
                 Anterior wall of the canal: is formed along its entire length by the aponeurosis of the
                  external oblique muscle. It is reinforced in its lateral third by the fibres of origin of
                  the internal oblique. This wall is therefore strongest where it lies opposite the
                  weakest part of the posterior wall, namely the deep inguinal ring.
                 Posterior wall of the canal: is formed along its entire length by the fascial
                  transversalis. It is reinforced in its medial third by the conjoint tendon, the common
                  tendon of insertion of the internal oblique and transversus, which is attached to the
                  pubic crest and pectineal line. This wall is therefore strongest where it lies opposite
                  the weakest part of the anterior wall, namely, the superficial inguinal ring.
                 Inferior wall or floor of the canal: is formed by the rolled-under inferior edge of the
                  aponeurosis of the external oblique muscle, namely, the inguinal ligament and, at its
                  medial end, the lacunar ligament.
                 Superior wall or roof of the canal: is formed by the arching lowest fibres of the
                  internal oblique and transversus abdominis muscles.




    2.   Describe the anatomy of the femoral canal.

Femoral canal
                 This short, conical medial compartment of the femoral sheath lies between the medial
                  edge of the femoral sheath and the femoral vein. This space allows the femoral vein
                  to expand during times of increased venous return from the lower limb. It contains a
                  few lymph vessels, sometimes a deep inguinal lymph node, loose connective tissue,
                  and fat. It is also the route by which the efferent lymph vessels from the deep
                  inguinal lymph nodes pass to the external iliac lymph nodes. The canal is widest at
                  its abdominal end, the femoral ring, and extends distally to the level of the proximal
                  end of the saphenous opening.
                 Femoral ring: is the small superior end or mouth of he femoral canal. It is about 1
                  cm wide and is closed by extraperitoneal fatty tissue called the femoral septum,
                  which is pierced by the lymph vessels connecting the inguinal and external iliac
                  lymph nodes. The four boundaries of the femoral ring are: laterally, the partition
                  between the femoral ring and the femoral vein; posteriorly, the superior ramus of the
                  pubis covered by the pectineus muscle and its fascia; medially, the lacunar ligament
                  and conjoint tendon; and anteriorly, the medial part of the inguinal ligament.

PATHOPHYSIOLOGY OF GUT OBSTRUCTION
   1. Describe the differences in consequences between pyloric, high intestinal and low
      intestinal obstruction and strangulation.

             General consequences of obstruction of a hollow tube
              Dilatation.
              Hypertrophy (long term).
              Diverticula formation.
              Mucosal necrosis, with distension.
              Retention of secretions.
              Infections.
              Stone formation.
              Atrophy.

             In general, the higher the site of the obstruction within the intestinal tract, the more severe the symptoms.
         Pyloric obstruction/stenosis
          Dilation of the stomach and active peristalsis, which may be visible.
          Severe vomiting with hypochloraemic/hypokalaemic alkalosis results.
          Pyloric stenosis may occur as a congenital anomaly or may be associated with PUD
             or gastric neoplasms, mainly carcinoma.

         High intestinal obstruction
          Small bowel obstruction:
                  Auscultation may reveal high-pitched rushes or tinkles that coincide with
                      episodes of cramping.
                  Pain is epigastric or periumbilical.
          Proximal obstruction:
                  Frequent non-bilious vomiting is prominent if the obstruction is proximal to
                      the ampulla of Vater.
                  Colicky pain occurs at frequent intervals (2-5 mins).
                  Constipation may not occur until later, and distension is minimal or absent.
          Distal obstruction:
                  Vomiting is bilious and less frequent.
                  The vomiting may be feculent if the obstruction has been long-standing.
                  Colicky pain occurs at intervals of 10 minutes or more, and it is less intense.
                  A dull ache may persist between cramps.
                  Distension increases gradually.

         Low intestinal obstruction
          Colonic obstruction:
                  Colon cancer 60-70% of cases.
                  Diverticulitis and volvulus 30% of cases.
                  Milder attacks of pain often occur in the weeks preceding the acute episode.
                  Colic is perceived in the lower abdomen or supra-pubically, and
                     constipation and distension are characteristic.
                  Nausea is common, and vomiting may occur.
                  Tenderness is usually mild in uncomplicated colonic obstruction.
                  Rectal exam or sigmoidoscopy may detect the obstructing lesion.
          Colonic pseudo-obstruction (Ogilvie’s syndrome):
                  Elderly, bedridden or institutionalised individual, often after recent cardiac,
                     abdominal or orthopaedic surgery.
          Strangulated obstruction:
                  Constant pain, fever, tachycardia, peritoneal signs, a tender abdominal mass,
                     and leukocytosis.

2.   Describe the relationship between pathophysiology and clinical course of different types
     of obstruction.
         Acute small bowel obstruction
             Obstruction may occur at any level – most common in small intestine.
             Tumours and infarction are the most serious, but only ~10-15%.
             Four main causes (80%):
                    Hernias.
                    Intestinal adhesion.
                    Intussusception.
                    Volvulus.
             Most obstructions result in simple occlusion of intestinal lumen, resulting in
              distension and enormous loss of fluid into the gut.



         Aetiology
          Mechanical obstruction:
                  Causes outside the wall (extramural):
                        Tumour (mass).
                        Constriction:
                         Adhesions – post-PID, post-OP.
                         Hernia (internal or external).
                         Volvulus.
         Causes inside the wall (intramural):
                 Tumour.
                 Inflammation e.g., diverticulitis (colon).
                 Strictures (ischaemic, congenital).
         Causes inside lumen (luminal):
                 Intussusception.
                 Obstructive gallstones, fecaliths, foreign bodies.
                 Congenital malformations:
                         Atresias.
                         Stenoses.
                         Bands.
                 Meconium.
                 Imperforate anus.
   Pseudo obstruction:
         Paralytic ileus (e.g. post-operative).
         Vascular – bowel infarction.
         Myopathies and neuropathies (e.g., Hirschsprung’s)
                 Congenital absence of myenteric plexus ganglion cells
                         Colostomy




Hernias
 Weakness or defect in peritoneal wall  protrusion of pouch-like hernial sac (lined
   by peritoneum).
 Usual sites:
         Inguinal and femoral canals.
         Umbilicus.
         Surgical scars.
         Retroperitoneal (usually at ligament of Treitz).
 Main concern is that segments of viscera (usu. small intestine) protrude through and
   become trapped (external herniation), particularly inguinal hernias.
 Incarceration: particularly at neck of pouch   venous drainage of trapped viscus
    stasis and oedema and permanent trapping (no cough reflex).
 Strangulation: compromise of arterial supply and venous drainage  infarction.

Adhesions
 Surgery, infection, endometriosis (may be congenital)  peritonitis which may heal
   with adhesions between bowel segments/anterior abdominal wall and segment
   (fibrous bridges).
 May create closed loops through which other viscera may slide/be trapped (internal
   herniation)  incarceration OR strangulation (as in external herniation).

Intussusception
 One segment constricted by peristalsis is telescoped into distal segment of bowel.
             Usually no underlying lesion in kids (adults - signifies intraluminal mass/tumour at
              point of traction)  mechanical obstruction and trapping of mesenteric vessels, can
               infarction.
                   Infection  hypertrophic enlargement of Peyer’s patches  forms a solid
                        mass
                   Children have larger Peyer’s patches

         Volvulus
          Complete twisting of loop of bowel about its mesenteric base of attachment 
             mechanical obstruction and infarction.
          Most common in sigmoid, then caecum, small intestine, stomach or transverse colon
             (rarely).

         Clinical course of obstruction
             Mechanical obstruction.
             Dilation, oedema and interference with neurovascular supply.
             Stranglation  intervention to relieve obstruction.
         Or
             More congestion, oedematous.
             Ischaemia.
             Necrosis – death of a group of cells or of tissue usually in a localized area.
             Gangrene – cell and tissue death on a widespread basis, resulting from loss of
              nutritive supply and by bacterial infection.
             Perforation – non-viable wall is friable and easily perforated.
             Peritonitis and sepsis.
             Death.

3.   Describe the relationship of pathophysiological mechanisms to planning of treatment.
         Treatment principles
          Treatment of mechanical obstruction consists in relieving the obstruction surgically
             at the earliest time consistent with safety of the patient.
          The distension must be corrected by suction-decompression (NGT)
          Fluid-electrolyte-blood deficits repaired (IV saline).
          Operation should be done as soon as possible when the patient is in satisfactory
             condition and before ischaemic necrosis develops.
          Strangulation of the bowel is a dangerous complication which is the cause of most
             deaths from obstruction. When blood supply is compromised, the involved segments
             become necrotic, perforate easily with diffuse soiling of the peritoneal cavity, and
             resection of the gangrenous bowel will be required.

         Hypovolaemic shock caused by plasma loss
          Intestinal obstruction is often a cause of severely reduced plasma volume. The
            distention of the intestine in obstruction partly blocks venous blood flow in the
            intestinal circulation, which increases intestinal capillary pressure. This in turn
            causes fluid to leak from the capillaries into the intestinal walls and intestinal lumen.
            Also, the lost fluid has a high content of protein, thereby reducing the total plasma
            protein as well as the plasma volume.

         Pain of obstruction
          Intestinal obstruction:
                   Pain is felt if the bowel or any other hollow viscus is distended or if its
                      muscle coat goes into spasm.
                   The cause of visceral pain is tension in the muscle fibres produced by
                      stretching of the wall, spasm of the muscle or stretching of the capsule of
                      the organ.
                   Violent peristaltic contractions occur in an attempt to force luminal contents
                      through an obstruction.
                   Colic: described as severe and cramping in nature, but intermittent, with
                      pain-free intervals.
   Intestinal ischaemia:
          Gives rise to pain because the gut loses motility and becomes distended.
          Visceral pain of ischaemic origin is caused most often by strangulation of
              the bowel in hernia or volvulus.
   Narcotics: except in a case of severe prostrating pain, narcotics should not be used
    until diagnosis is established because they may mask important clinical features of
    the pain.
PATHOLOGY OF THE SMALL INTESTINES
   1. Describe the major pathology of the small intestine.
          Congenital
           Intestinal atresia:
                   Rare disorder – failure of development of lumen in one part of the intestine.
                           Jejunum and ileum are most commonly affected.
                           Multiple bowel segments may be affected.
                   Present with intestinal obstruction in the first week of life.
                   Surgery is curative.
           Meckel’s diverticulum:
                   Diverticulum: a blind pouch leading off the alimentary tract, lined by
                      mucosa that communicates with the lumen of the gut.
                   Persistence of the omphalomesenteric duct (connects yolk sac with gut
                      lumen) leaves solitary diverticulum 30cm from the ileocecal valve,
                      consisting of:
                           A pouch of mucosa.
                           Submucosa.
                           Muscularis propria.
                           40% of cases have heterotopic gastric or pancreatic mucosa.
                                      Gastric mucosa may present with peptic ulceration.
                                      Bleeding from an ulcerated Meckel’s diverticulum causes
                                        chronic intestinal blood loss, resulting in iron deficiency
                                        anaemia.
                   Diverticula may intussuscept, incarcerate, or perforate.
                           Infection (Meckel’s diverticulitis) presents very similar to acute
                               appendicitis.
                   Present in 2% of the normal population and are usually asymptomatic.

             Ischaemic
              Acute small intestine infarction:
                     Pathogenesis:
                             Arterial thrombosis: atherosclerosis, vasculitis, dissecting
                                 aneurysm, angiography, surgery, and hypercoagulable states.
                             Arterial embolism: cardiac vegetations, angiography, aortic
                                 atheroembolism.
                             Venous thrombosis: hypercoagulable states, cirrhosis, sepsis,
                                 surgery and abdominal trauma, neoplasms.
                             Nonocclusive ischaemia: cardiac failure, shock, dehydration,
                                 vasoconstrictive drugs.
                             Miscellaneous: radiation, volvulus, stricture, herniation.
                     Morphology:
                             Transmural infarction: sudden and total occlusion of a major
                                 vessel, infarction of all bowel layers. Bowel segment is
                                 haemorrhagic as a result of blood reflow into damaged area.
                                 Bowel appears rubbery and dusky, bacteria produce gangrene, and
                                 perforation develops within days. More common in the small
                                 bowel (completely dependent on mesenteric blood supply).
                             Mural and mucosal infarction: incomplete necrosis or necrosis of
                                 mucosa only. Mucosa appears haemorrhagic, but serosa may be
                                 normal. Distribution is frequently patchy; inflammation depends
                                 on duration of injury. Ischaemic changes may be due to any cause
                                 (occlusive or nonocclusive). Large bowel has posterior abdominal
                                 wall collaterals.
                             Chronic ischaemia: causes mucosal inflammation, ulceration,
                                 fibrosis, and stricture. Ischaemia has a segmental patchy
                                 distribution.
                     Clinical findings:
                             Total infarction imparts 50 to 70% death rate. It usually occurs in
                                 severely ill patients and features severe abdominal pain and
                      tenderness, blood diarrhoea or gross malaena, nausea, vomiting,
                      bloating, and abdominal wall rigidity.
                     With incomplete infarction, there are non-specific abdominal
                      complaints, easily confused with acute and chronic inflammatory
                      conditions.

Malabsorptive
 Celiac disease:
        Pathogenesis:
                A sensitivity to gluten, which contains the gliadin protein
                  component, shared by wheat, oat, barley, and rye, is present.
                Genetic susceptibility: Familial clustering; 90 to 95% of patients
                  express the DQw2 (and HLA B8) histocompatibility antigen.
                Immune-mediated injury: Serum antibodies to gliadin and potential
                  cross-reactivity to type 12 adenovirus.
        Morphology:
                Diffuse enteritis is present with flattened (atrophic) villi, elongated
                  regenerative crypts, surface epithelial damage with intraepithelial
                  lymphocytes, and robust lamina propria inflammation
                  (lymphocytes, plasma cells, macrophages). Severity decreases in
                  proximal-to-distal intestine and reverts to near-normal upon
                  withdrawal of dietary gluten.
        Clinical findings:
                Symptoms: diarrhoea, flatulence, weight loss, fatigue. Celiac sprue
                  present in infants up to mid adult life. Other causes must be
                  excluded; disease responds to withdrawal of dietary gluten.
                Complications: iron and vitamin deficiencies, 10 to 15% risk of
                  gastrointestinal lymphoma, usually T-cell.

   Tropical sprue:
         Pathogenesis:
                  Almost exclusively in people living in or visiting the tropics.
                  Cause is unknown; enterotoxigenic E. coli is a possibility.
                  Responds to long-term broad-spectrum antibiotic therapy.
         Morphology:
                  Extremely variable intestinal changes are seen, ranging from
                     normal to resembling celiac disease.
                  In contrast to celiac disease, the brunt of injury is distal.
                  Lamina propria has abundant lymphocytes and more eosinophils
                     than celiac disease.
   Whipple’s disease:
         Pathogenesis:
                  A rare, systemic condition principally involving intestine, central
                     nervous system, and joints.
                  Attributed to infection by Tropheryma whippelii, a gram-positive
                     actinomycete.
         Morphology:
                  Small intestinal mucosa is laden with distended macrophages in
                     lamina propria, which contain rod-shaped bacilli by electron
                     microscopy.
                  Similar macrophages are present in lymphatics, lymph nodes,
                     joints, and brain.
                  Inflammation is essentially absent.
         Clinical findings:
                  Malabsorption occurs with diarrhoea, steatorrhoea, abdominal
                     cramps, distension, fever, and weight loss; migratory arthritis and
                     heart disease may be presenting problems.
                  Usually whites 30s-40s are affected; the male-female ratio is 10:1.
                  Whipple disease usually responds to antibiotic therapy.
Intestinal obstruction
 Hernias:
          Protrusion of a sac of peritoneum through a defect or weakness in the
             abdominal wall.
          Hernias occur:
                   Through the internal inguinal ring (indirect inguinal hernia).
                   Through the posterior wall of the inguinal canal (direct inguinal
                       hernia).
                   Into the femoral canal (femoral hernia).
                   Around the umbilicus (periumbilical hernia).
                   Through areas weakened by surgical scars (incisional hernia).
                   In the posterior abdominal wall (lumbar hernia).
                   Through the diaphragm (diaphragmatic hernia).
          The peritoneal sac of a hernia may contain a variety of abdominal tissues,
             commonly omentum and intestine and more rarely bladder.
          When intestine constitutes part of the contents, intestinal obstruction
             (“obstructed hernia”) may occur as well as strangulation – occlusion of
             venous drainage and arterial supply to the segment because of constriction
             at the neck, causing infarction and gangrene.

   Adhesions:
        Localised peritoneal inflammation (peritonitis) after surgery, infection,
           endometriosis, or radiation.
        Healing leads to fibrous bands between viscera.
        Complications include internal herniation (within peritoneal cavity),
           obstruction, and strangulation of viscera.
        Adhesions may be congenital.

   Intussusception:
         Refers to telescoping of one segment of intestine into the immediately distal
            segment, usually small bowel.
         In infants, intussusception is spontaneous and reversible.
                  During weaning, exposure to new antigens or infectious agents is
                     believed to cause hypertrophy of lymphoid follicles in the terminal
                     ileum.
                  Hypertrophied follicles are pushed into the lumen as the apex of an
                     intussusception.
         In adults, point of traction is usually a tumour.
         Causes intestinal obstruction, haemorrhagic infarction and gangrene.

   Volvulus:
         Complete twisting of a bowel loop about is mesenteric base or around an
            abnormal fibrous band (i.e., adhesions).
         Leads to intestinal obstruction and often strangulation of the vascular
            supply, causing infarction.
         Volvulus commonly occurs in the sigmoid colon in elderly individuals.
         Caecal volvulus occurs in younger people who have developmental
            malrotation of the bowel.

Tumours
 Rare.
 Benign lesions:
       Leiomyomas.
       Adenomas.
       Lipomas.
       Neuromas.
       Vascular malformations.
       Hamartomatous lesions.
 Adenomas:
                       Frequently occur in the region of the ampulla of Vater, especially in patients
                        with polyposis syndromes.
                     Silent, unless they obstruct the intestinal lumen or common bile duct.
                Adenocarcinomas:
                     Usually present with obstruction (cramping pain, nausea, vomiting), weight
                        loss, and bleeding.
                     Spread to mesentery, regional lymph nodes, and liver is as with colonic
                        adenocarcinoma.
                     Five-year survival is 70% with wide en bloc excision.

FLUID AND ELECTROLYTE BALANCE
   1. Explain the detection of fluid and electrolyte imbalance and its correction/prevention.
            Clinical estimation of fluid loss
                Mild (<2 litres in adult):
                      Thirst.
                      Concentrated urine.
                Moderate (2-3 litres in adult):
                      As above, plus:
                                Dizziness, weakness.
                                Oliguria (<400 ml/day).
                                Postural hypotension > 20 mmHg systolic.
                                Low JVP.
                Severe (> 3 litres in adult):
                      As above, plus:
                                Confusion, stupor.
                                Systolic BP < 100 mmHg.
                                Tachycardia (not elderly), low pulse volume.
                                Cold extremities, poor capillary return.
                                Reduced skin turgor (“doughy”).

            Normal serum reference ranges
             Sodium            137 – 147 mmol/L.
             Potassium                  3.5 – 5.0 mmol/L.
             Chloride                   96 – 109 mmol/L.
             Bicarbonate                25 – 33 mmol/L.
             Glucose (fasting) 3.0 – 5.0 mmol/L.
             Urea (age dep.) 2.0 – 8.5 mmol/L.
             Creatinine (age dep.)      0.04 – 0.14 mmol/L.

            Resuscitation in hypovolaemic shock
             Use the largest veins with which you are familiar, i.e., antecubital fossa – otherwise
               do a cutdown or ventral venous cannulation. Rate of flow is inversely proportional to
               length of cannula, and CVP lines are long. Cutdowns are rarely used, but if you
               forget about them entirely, you stand to lose the occasional life.
             Use 2 large-bore cannular (14G or 16G): it takes 20 mins to infuse 1 litre through a
               18G cannula, but only 3 mins through one of 14G.
             Raise the drip stand and squeeze the bag, or use an inflatable pressure device to 
               infusion rate.
             Estimate and anticipate the fluid loss.
             Crystalloid (e.g., Hartmann’s solution) has intravascular t½ of only 30-60 mins and
               must be given in three times the volume to that lost; colloid (e.g., Haemaccel) lasts
               several hours and is replaced 1:1 with blood lost. Consider blood if haemorrhage and
               over 15% volume lost (adult blood volume = 70 mL/kg; child = 80-90 mL/kg) –
               crossmatched blood is ideal, but time-consuming; group compatible is a compromise,
               only takes 10 mins to prepare and is preferable to O Rh – ve.
             Give fluid rapidly; slow only when pulse falls, BP rises and urine flows (> 30 mL/hr
               adult and >1 mL/kg/hr child). Catheterise the bladder. Consider CVP line to
               monitor progress. A satisfactory response might be a 2cm rise after IV infusion of
               250mL colloid over 15 mins.
                Don’t forget to give O2 (at 12L/min via tight-fitting face mask with reservoir in all
                 trauma, unless strong contraindication).
                Monitor pulse, BP, and ECG continuously. Remain at bedside.
                GI obstruction: 0.9 % saline until BP rises.

ACUTE ABDOMEN
   1. List the appropriate investigations in the patient with an acute abdomen and how to
      interpret them.
           Laboratory tests
            Urgency of acute abdominal conditions usually precludes prolonged investigation.
               There are only a few specific tests or examinations which may be relied upon to give
               clear-cut answers to the exact cause of the acute condition.
            Urine and blood should be examined routinely.
            Urine analysis:
                     Pus or blood in the urine suggest disease of the urinary tract and can also
                        result form an inflamed appendix lying in proximity to the ureter or bladder.
                     In dehydration, the specific gravity of the urine may be increased – urine is
                        more concentrated
            Blood analysis:
                     In dehydration, the red cell and haemoglobin levels increased as a result of
                        haemoconcentration.
                     The total leukocyte count and percentage of polymorphonuclear cells are
                        usually elevated in acute inflammatory conditions, whereas early in the
                        course of intestinal obstruction there may be no significant alterations.
                     Conditions in which tissue necrosis occurs, as in a strangulated intestinal
                        obstruction, are generally associated with a marked polymononuclear
                        leukocytosis. With acute appendicitis, the leukocytosis isn’t great unless
                        you already have a perforated appendix.
            Serum amylase:
                     The serum amylase test is essential when the possibility of acute pancreatitis
                        exists. This possibility should be kept in mind in all patients with acute
                        severe upper abdominal pain.
            Other tests:
                     Certain tests are indicated when extra-abdominal conditions are suspected as
                        the cause of an acute abdomen. These include:
                              Blood and urine sugar determinations in diabetic ketoacidosis.
                              Haemoglobin electrophoresis in possible sickle cell crisis.
                              Chest X-ray in pneumonia.
                              ECG in coronary artery disease.
                              Lead levels in children with pica and anaemia  chronic lead v
                                  poisoning.
            Serum electrolytes:
                     Serum electrolytes to determine the degree of dehydration and electrolyte
                        imbalance should be done when fluid loss has been significant.

             X-ray examination
              Plain X-rays:
                      Plain X-ray films of the abdomen in the supine and upright positions can
                        often provide immediate information which helps to confirm a diagnosis or
                        exclude certain diagnoses which have been considered.
                      Gas below the diaphragm in the upright film is almost pathognomonic or
                        perforation of a hollow viscus, usually a ruptured peptic ulcer or a traumatic
                        perforation.
                      In mechanical small bowel obstruction, plain films in the upright position
                        reveal dilated distended loops of gut with fluid levels above the obstruction,
                        and absence of gas below the obstruction, i.e., terminal ileum and colon.
                              Ladder pattern
                      Generalised distention of large and small bowel occurs in paralytic ileus.
              Barium studies:
                    Usually upper GI barium studies are contraindicated because of the
                     possibility of barium leakage into the peritoneal cavity when perforation is
                     impending or perforation exists.
                  Barium enema is an important diagnostic aid in intussusception in infants
                     and children, and sometimes is used therapeutically under low pressure to
                     reduce the intussusception. May also be helpful in diverticulosis of the
                     colon and in large bowel neoplasms, where sigmoidoscopy and biopsy may
                     be helpful.
             Cholangiography:
                  When acute cholecystitis is suspected, IV cholangiography is useful for
                     differential diagnosis.

2.   Recognize the clinical and radiological features of small bowel obstruction.
         Clinical features
             Acute obstruction of the small bowel in adults is caused most commonly either by
              incarcerated hernia or by post-operative adhesions within the peritoneal cavities.
             Age has a significant influence upon the cause of small bowel obstruction.
                    In newborns, congenital problems such as atresia and meconium ileus are
                        important causes of obstruction.
                    In young children, intussusception is encountered with frequency.
             In general, the higher the site of the obstruction within the intestinal tract, the more
              severe the symptoms.
             Pain is usually sudden in onset, severe, and spasmodic in nature because it results
              from vigorous peristaltic activity of the bowel as it attempts to propel the intestinal
              contents through the site of obstruction. The patient will often double up with pain
              during cramping distress and then a brief period of freedom from distress.
             Copious vomiting occurs early in high intestinal obstruction. Initially the vomitus
              contains gastric contents, followed by small intestinal contents later, usually bile
              coloured. If persistent vomiting occurs, and if the obstruction is in the lower part of
              the small bowel, the vomitus becomes faecal in character (feculent vomitus).
             Usually with established intestinal obstruction the patient is unable to pass flatus or
              stools spontaneously. Bowel contents beyond the obstruction may be passed,
              however, and in children with intussusception, this material contains blood mucous
              which gives it the characteristic “currant jelly” appearance.
             In the early stages, temperature, pulse rate and respiratory rate are normal, as is the
              white count.
             Increased temperature with elevated white cell count suggests that strangulation-
              obstruction is developing.
             On examination, inspection will reveal the presence or absence of surgical scars or
              evidence of inguinal or femoral hernia.
             Palpation is usually not revealing but with intussusception, a sausage-shaped mass
              may be felt in the right abdomen. This mass is the invaginated segment of the small
              intestine.
             Progressive distention occurs.
             Tenderness and muscle rigidity in the presence of intestinal obstruction are
              suggestive of peritoneal inflammation and strangulation-obstruction.
             Auscultation will reveal increased bowel sounds. During episodes of pain, loud high-
              pitched peristaltic rushes occur.
             As distention progresses, interference with neurogenic and vascular elements of the
              bowel develop, motility is reduced and bowel sounds are decreased.
             Vomiting with high intestinal obstruction is associated with significant loss of fluid
              and electrolytes, and dehydration and electrolyte imbalance ensue rapidly unless the
              obstruction is relieved.
             Circulatory impairment leads to ischaemia and necrosis of the gut wall and
              progressive reduction in all bowel functions.

         Radiological features
          Plain X-ray films are often diagnostic.
                 The bowel loops above the obstruction are distended with gas and fluid with absence
                  of gas seen below the level of obstruction.
                 In the upright film, fluid levels are found in the dilated loops.
                 Proximal jejunal obstruction may not cause dilatation.
                 Distal obstruction is characterised by a ladder pattern of dilated loops of bowel in the
                  mid-abdomen.

             Differential diagnosis
              The conditions most likely to be confused with bowel obstruction are those in which
                 colicky pain in a smooth muscle organ is the outstanding symptom; thus diseases of
                 the gall bladder, the urinary tract, and the female pelvic organs may resemble an
                 intestinal obstruction.
              Paralytic ileus or functional intestinal obstruction must also be considered. Surgery
                 is not indicated for paralytic ileus and may adversely affect its course.
              Examination of the abdomen with a stethoscope is most helpful. Bowel sounds in
                 paralytic ileus are hypoactive to absent, in contrast to the hyperactive sounds
                 associated with mechanical obstruction.

MANAGEMENT OF OBSTRUCTION
   1. Outline the principles of pain management.
         Analgesic ladder
          Selection of drug:
                    Patient’s allergies/side effects.
                    Duration of action.
                    Mode of administration.
          Aspirin and NSAIDs:
                    May provide relief equivalent to oral codeine; in some instances are
                       equivalent to parenteral morphine.
                    If relief of pain is insufficient, may be combined with:
                             Orally effective morphine-like agents, e.g., codeine.
                             Agonist/antagonist opioids.
                    Because of differing MOAs, combinations can achieve an analgesic effect
                       that would otherwise require a higher dosage of opioid, but with fewer side
                       effects.
          Opiates:
                    Morphine:
                             Major drug for moderate-to-severe pain.
                             Subcutaneous or IM for moderate-to-severe pain.
                             Doses need to be tailored to the patient based on individual
                                sensitivity to the drug and the pain-sparing needs of the individual.
                             IV for severe pain – continuous infusion or intermittent dosing.
                             Patient-controlled analgesia (PCA) – valuable post-operatively.
                             Epidurally and intrathecally in selected situations.
                             Orally, subjected to first pass metabolism – two to six-fold less
                                potent than parenterally.
                    Codeine:
                             Oral administration.
                             May be used with aspirin or Panadol for additive actions.
                    Adjuvants:
                             Opioid with amphetamine: reduce sedative effects.
                             Opioid with antidepressants: enhance analgesia.
                             Opioid and antihistamine, anticonvulsant and glucocorticoids.

    2.   Demonstrate nasogastric tube insertion and intravenous cannulation insertion.
             When the patient is acutely ill, investigation and supportive treatment should proceed
                concurrently, if a specific diagnosis is not immediately apparent.

             Nasogastric tube
                 Indications:
                       Diagnose a type of disorder.
         Relieve accumulated digestive secretions and gas.
         To empty the tract to allow healing.
   Decompression:
         Process of removing gaseous and liquid substances form the GIT.
         Attempt to relieve pressure caused by an accumulation of gas and intestinal
             contents because of a lack of GIT motility or an obstruction.
   Compression:
         Process of applying pressure internally, using a specifically designed tube
             placed at a specific site.
         Most commonly, applying pressure on haemorrhagic oesophageal varices at
             the gastro-oesophageal junction.
   Gavage:
         Gastric feeding is an artificial method of giving patients fluid and nutrients
             via an NGT, when oral intake is inadequate or impossible.
   Lavage:
         Wash out the stomach.
         Used frequently as an emergency treatment in gastric dilatation and
             poisoning.
         Also used to cleanse the stomach prior to gastric surgery.
   Gastric analysis:
         Laboratory examination of the contents of a fasting stomach and is
             important in the diagnosis of gastric pathology.
         Increase in gastric acidity usually coincides with presence of duodenal
             ulcers.
         Decreased gastric acidity indicates possible carcinoma or pernicious
             anaemia.
         Normal fasting contents of the stomach are clear and watery.
         Gastric contents that are tinged green may indicate a combination of bile
             and hydrochloric acid.
         Golden yellow contents may indicate achlorhydria (absence of free
             hydrochloric acid in the gastric juice).
   Principles:
         Acquire knowledge of patient’s history.
         Patient education.
         Patient safety.
         Universal precautions.
         Decreasing the risk of aspiration.
         Evaluating clinical status.
   Procedure:
         Write an order/check for order.
         Explain to the patient.
         Establish a distress signal.
         Assemble equipment.
         Ensure privacy.
         Routine hand wash.
         Position the patient.
         Assess patient nares.
         Determine length of tubing to be used.
         Lubricate the tube.
         Insert the tube.
         If resistance is felt ask the patient to take a deep breath in.
         Never force the tube.
         Instruct the patient to lower their chin to their chest.
         The tube should be advanced as your patient swallows.
         The tube should be tested for location:
                   Aspirating the stomach contents and testing for acidity with blue
                      litmus paper.
                   Auscultating the left upper quadrant of the patient’s abdomen with
                      injecting 10-20 mls of air into the tube.
         Secure the tube to the patient.
                            Close the end of the tube with a spigot or attach to a drainage bag.
                            Dispose of equipment.
                            Routine hand wash.
                            Document the procedure.


   3.   Outline the principles of operative management of strangulated hernia with gangrenous
        gut.
            Surgery
                 Strangulation requires urgent surgery (within 1 hr), as does large bowel obstruction
                  with gross dilatation (>8 cm) and tenderness over the caecum – as perforation is
                  close.
                 At surgery, dead bowel must be removed. Revascularization may be attempted but is
                  difficult and often necessitates a second laparotomy.
                        Bowel can last 3-4 hours without perfusion.
                        Recovery – 5 mins in warm, moist packs to restore blood flow.
                        If still ischaemic, no contraction on poking then its gangrenous and resected
                            with end-to-end anastomosis.
                 Usually large volumes of IV fluid must be given.
DECISION MAKING
   1.   Discuss issues in decision making in the emergency situation
            Surgical vs non-surgical acute abdomen
                 Severe abdominal pain in patients who have been fairly well, and which persists as
                  long as six hours.
                 Persistent localised tenderness with muscle spasm, indicative of localised peritoneal
                  inflammation. The tenderness may be best determined by rectal or pelvic exam.
                 Characteristic, severe, intermittent cramping, colicky pain, with obstruction of a
                  hollow viscus.
                 Markedly hyperactive bowel sounds with small intestinal obstruction, or decreased to
                  absent bowel sounds with paralytic ileus. Paralytic ileus not secondary to other
                  abdominal pathology is treated non-surgically. Paralytic ileus as an end-result of
                  mechanical small bowel obstruction or perforated duodenal ulcer requires surgical
                  intervention to relieve the underlying pathology.
                 Repeated vomiting of copious amounts of bile-stained or faecal material – in small
                  bowel obstruction.
                 Palpation of a mass. In RLQ or RUQ – with intussusception. Adnexal mass by
                  pelvic exam – ectopic pregnancy. Tender and thickened adnexae by pelvic in PID.
                  An irreducible incarcerated inguinal hernia. A tender RLQ mass by abdominal
                  palpation or rectal exam – appendiceal abscess.
                 Certain tests when associated with characteristic clinical features:
                        Markedly elevated serum amylase levels – acute pancreatitis.
                        Free air under diaphragm in an upright X-ray film perforation of a hollow
                           viscus – usually duodenal ulcer.
                        Distended loops of small bowel above the level of obstruction in small
                           bowel obstruction with absence of gas below by X-ray; generalised
                           distention of large and small bowel – paralytic ileus.

            Priority I
                 Priority I indicates catastrophic events, such as perforation of a viscus, massive
                  haemorrhage, sudden arterial occlusion with extensive tissue necrosis, all of which
                  are characterised by sudden onset of severe prostating continuous pain, moderate to
                  extreme abdominal tenderness and muscle spasm, and rapid development of shock.
                  There is marked tissue damage and fluid loss from traumatic chemical or vascular
                  insult. Immediate institution of supportive and resuscitative measures (i.e.,
                  intravenous correction of fluid and electrolyte imbalance, blood replacement, gastric
                  suction, vasopressor agents, oxygen, narcotics) is imperative. Emergency operation
                  as soon as the patient’s condition permits must be done to repair a perforated viscus,
                  to restore blood supply by relief of strangulation-obstruction, or to control
                  haemorrhage in a ruptured ectopic pregnancy, ruptured spleen and (hopefully when
                  condition permit) a dissecting aneurysm.
    Acute pancreatitis, which may have a sudden catastrophic onset, is treated non-
     operatively with supportive and resuscitative measures, as outlined above, with
     nasogastric suction to control or prevent paralytic ileus, and with antibiotics to
     control or prevent infection. The pathophysiology of acute pancreatitis involves
     intrapancreatic activation of digestive enzymes and autodigestion of the pancreas
     with oedema, haemorrhage and necrosis of the gland. Surgical treatment for acute
     pancreatitis is no longer strictly taboo due to better fluid and electrolyte management.
    It may be difficult to differentiate acute pancreatitis from other catastrophic
     conditions. The clinical picture and markedly elevated serum amylase with be
     helpful. Differentiation of an acute myocardial infarction is ordinarily not a difficult
     diagnostic problem and the ECG will be helpful. An acute dissecting aneurysm may
     progress with such rapidity that there may be little or no time for diagnosis or
     surgical treatment.
    In this catastrophic group, emergency treatment is imperative. Without treatment,
     rapid and progressive deterioration of the patient occurs, and the prognosis is very
     guarded.

Priority II
    Priority II includes conditions associated with vigorous smooth muscle contractions
     in an attempt to propel luminal contents past an obstruction. This is the so-called
     colic group, which is characterised by severe intermittent recurrent cramping pain
     and serious disturbance in gastrointestinal function when the obstruction is in the
     small bowel.
    Marked systemic reactions are not generally encountered in the early stages of gut
     obstruction, but become severe as the process advances. In bowel obstruction the
     need for surgical treatment is urgent to prevent ischaemic necrosis of the gut, but not
     as critical as in the catastrophic category. There is more time for studies and
     preparation of the patient. Diagnosis can usually be established by careful clinical
     evaluation of the patient, characteristic hyperactive bowel sounds, and demonstration
     by X-ray of distended loops of gut above the level of obstruction. Fluid and
     electrolyte imbalance must be corrected and distention relieved by nasogastric
     suction before operation. The prognosis is good in cases seen early but much more
     serious when ischaemic necrosis of gut occurs and resection of gangrenous bowel is
     required.
    Biliary and renal colic are treated conservatively with use of meperidine (Demerol)
     for relief of pain and relaxation of smooth muscle spasm to facilitate passage of the
     calculus. Both renal and biliary colic are treated medically with diet, fluids and
     narcotics, and surgery is usually not required, at least for the acute episode of colic.
    At times a marked gastroenteritis or a faecal impaction may cause severe colicky
     pain, but history, physical examination, and the benign course will obviate any
     serious consideration of ill-advised surgery.

Priority III
    Priority III, the lowest category of urgency, includes inflammatory conditions
     associated with abdominal pain and a possible acute abdomen. The progression of
     inflammation changes occurs over a period of several hours to a few days. Initially
     the systemic and abdominal manifestations are not severe and there is considerably
     more time to observe and evaluation the patient. With progression of inflammation
     and infection, pain and tenderness increase, become more localised, and fever and
     leukocytosis increase. Without treatment, there is further tissue damage, and
     perforation and peritonitis may occur. Clinical diagnosis is usually possible on the
     basis of clinical features and tests.
    Until a diagnosis or a decision to operate is made, narcotic analgesics should not be
     used lest they mask the pain which is an important diagnostic feature of the disease.
     Similarly, antibiotics may alter the course and they should be deferred until diagnosis
     is established. Operative and non-operative measures should be instituted, according
     to the diagnosis and indications, and the prognosis is generally favourable.
    Acute appendicitis is prototypic of the acute inflammatory group. Diagnosis is
     clinical and early operation is indicated before suppuration and perforation occur.
            Diverticulitis is an inflammatory process occurring in diverticulosis of the colon in
             older adults. It is usually treated medically with antispasmodics, intestinal antibiotics
             and diet. Colostomy or colectomy may become necessary for patients with repeated
             attacks who fail to respond to medical therapy. When the lumen of a diverticulum
             becomes obstructed, inflammation occurs within the diverticulum and spreads to
             adjacent bowel wall. The most common complication is perforation with localised
             peritoneal inflammation. This causes the so-called LLQ appendicitis for which
             surgery is required.
            Acute cholecystitis is generally a complication of chronic cholecystitis and occurs
             when the gall bladder outlet is suddenly and completely occluded, usually by a stone.
             Plain film of the abdomen may reveal radio-opaque stones and gall bladder studies
             with contrast media show a non-functioning gall bladder. When the patient is in
             good condition and the acute attack is of short duration, cholecystectomy is the
             treatment of choice. In more seriously ill patients with more chronic infection,
             operation may be deferred 6 weeks, until the acute process has subsided due to
             medical treatment. The important non-operative measures include gastrointestinal
             decompression, parenteral fluids, antibiotics and close observation of the patient for
             evidence of progression of disease or impending rupture.
            Nonsurgical diseases in the inflammatory category include the following:
                   A child who has moderately high fever, with abdominal pain, and RLQ
                       tenderness (although it may be LLQ or bilateral) will have acute mesenteric
                       adenitis 80% of the time, rather than appendicitis. Mesenteric adenitis is
                       associated with an acute pharyngitis, often with leukocytosis and surgical
                       intervention is not required. Sometimes the diagnosis cannot be made with
                       certainty except at operation. When the danger of laparotomy is
                       considerably less than that of a possible perforated appendix, operation is
                       justified, and 4 out of 5 is a pretty good batting average.
                   Regional enteritis is a chronic granulomatous inflammation of the terminal
                       ileum, characterised by chronicity, weight loss and bouts of infection,
                       diarrhoea, and cramping abdominal pain. Occasionally acute exacerbations
                       may mimic an acute abdomen. Barium study of the small intestine give a
                       characteristic “string” appearance in the involved segment. Medical
                       treatment is symptomatic and supportive.
                   Acute pelvic inflammatory disease can be readily diagnosed by its clinical
                       features and by culture of cervical discharge. Treatment is medical and
                       includes vigorous appropriate antibiotic therapy along with general
                       supportive measures.

2.   Demonstrate an ability to determine and integrate into clinical management patients’
     values and lay concepts of illness and health care activities.

3.   Be skilled at finding, appraising studies of prognosis and treatment, and applying the
     results to individual management through a weighing up of individualized absolute
     benefits and risks.
         Pubmed search:
             http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=&DB=PubMed

				
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posted:8/17/2011
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