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Biology of Disease CH0576
Disordered Physiology of the Digestive Tract I
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Digestive Tract
• The various activities of the digestive tract can be divided into six basic functions:-
• Ingestion• Movement of foodstuffs through the tract.• Mechanical preparation of food for
digestion.• Chemical digestion• Absorption of digested food • Defecation
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Digestive System
• The organs of the digestive system are divided into two main groups:-– The Alimentary Canal, or digestive
tract. A continuous tube which comprises:- • mouth, • pharynx, • oesophagus,• stomach, • small intestine, • and large intestine
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Digestive System
• Accessory Organs which includes:-• the teeth, • salivary glands, • liver,• pancreas, • and the gall bladder.
– These generally produce or store secretions which are necessary for the chemical digestion of the food.
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General Histology of Tract• Important to remember that the
abdominal cavity is lined by parietal peritoneum.
• The organs within the cavity are covered by the visceral peritoneum.
• Organs are suspended in the cavity by membranes referred to as mesenteries.
• These are double layered extensions of the parietal peritoneum.
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General Structure
• From the oesophagus to the anus the wall of the digestive tract has four layers/tunics.
• There are complex networks of nerves (plexuses) interconnecting the various layers.
• Although each region of the tract has modifications and specialised structure the four layers are represented in each.
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General Structure
• The four basic layers which are represented throughout the tract are:-– Tunica mucosa– Tunica submucosa– Tunica muscularis– Tunica serosa/adventitia.
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Tunica Mucosa
• This refers to the mucous membrane that lines the gastrointestinal tract. It is composed of three layers:-– An epithelial layer which borders on
the lumen.– The lamina propria, external to the
epithelium.–Muscularis mucosae, a thin layer of
smooth muscle fibres.
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Tunica Submucosa
• A thick layer of either dense or loose connective tissue which is located deep to the mucosa.
• This region contains blood vessels, lymphatic vessels, nerve fibres, and, in some regions of the G.I.T, secretory glands.
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Tunica Muscularis
• In most regions of the G.I.T this layer is a double layer of smooth muscle fibres.
• The inner layer of fibres are arranged in a circular fashion.
• The outer layer is one of longitudinal muscle fibres.
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Tunica Muscularis
• At several places along the length of the tract the fibres of the circular muscle layer are thickened.
• These form sphincters which control the movement of food and chyme from one region to another.
• In upper oesophagus this layer is composed of voluntary skeletal muscle.
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Tunica Muscularis
• Elsewhere in the tract the fibres are of smooth muscle (involuntary).
• The rhythmical contractions of these muscles move the contents along the tract.
• In the stomach this muscular tunic is made up of three layers of fibres: an inner layer of oblique fibres in addition to the other two.
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Tunica Serosa: Adventitia
• The outermost layer of the G.I.T wall.
• It is composed primarily of a layer of connective tissue.
• In the oesophagus this connective tissue layer merges with the connective tissue of the surrounding tissues, and is called the adventitia.
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Tunica Serosa: Adventitia
• Along the rest of the tract the connective tissue is covered by a serous membrane made up of a single layer of squamous epithelial cells.
• This membrane forms the visceral peritoneum.
• Here this outer layer is referred to as the serosa.
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Intrinsic Nerve Plexuses
• The wall of the alimentary canal contains complex interconnections of neurones that re organised into three intrinsic nerve plexuses:-– Submucosal plexus, within the
submucosa.–Myenteric plexus, lying between the
circular and longitudinal muscles.– Subserous plexus, within the serosa.
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Nerve Plexuses
• These nerve networks are responsible for much of the co-ordination of the activity of the digestive tract.
• Two types of reflex pathway are of importance in this control.– Short reflexes,– Long reflexes.
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Haematemesis & Malaena
• Acute G.I.T haemorrhage is one of the most common medical emergencies, with an annual mortality rate of 5-10%
• With increasing age in the population, more people are falling into the high risk category.
• Old age is the predominant feature. 19/04/23 17
Haematemesis & Malaena• Old age is associated with an increased
incidence of other disorders, such as chronic bronchitis and IHD.
• These give bleeding from peptic ulcers in the over 50’s a poorer prognosis.
• Although varices and gastric carcinoma are each responsible for only 3% of bleeds, they carry a high mortality (19% and 14% respectively).
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Haematemesis & Malaena
• Establishing that bleeding has occurred– The most important factors to be
considered are:-• The rate at which blood is lost.• The total amounts of blood lost.
– The effectiveness of the patient’s compensatory mechanisms will depend upon age, and the extent of any associated cardiorespiratory and cerebrovascular disease present.
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Haematemesis & Malaena
• It should be remembered that acute blood loss may be superimposed upon a chronic blood loss.
• Initially the consequence of blood loss is one of reduced circulatory volume i.e. shock rather than anaemia.
• The more rapid the bleeding the more likely the patient is to present with haematemesis.
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Haematemesis & Malaena
• Conversely the slower and more gradual the blood loss the more likely the patient is to present with malaena.
• In severe cases blood replacement with transfusion will be necessary.
• The actual decision regarding transfusion being based on age, general condition, pulse rate and B.P.
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Haematemesis & Malaena
• In addition to these consideratons, an initial [Hb] of < 10 g/dl is usually regarded as an indication for transfusion.
• Due to compensatory mechanisms the initial [Hb] will be normal, only over the next 24 hours will haemodilution occur and pulse rate increase and blood pressure fall, as the compensatory mechanisms start to deteriorate.
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Haematemesis & Malaena
• By this time a young patient, with good compensatory responses, may well have lost some 50% of total blood volume.
• There is a potential risk from any blood transfusion and so it should not be entered into lightly.
• Particularly in the elderly.
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Transfusion Risk
• In the elderly there is a potential risk of over-transfusing a patient.
• This can precipitate left heart failure and pulmonary oedema.
• Where rapid transfusion is required and the patient is bordering on heart failure a short acting diuretic such as Frusemide should be administered.
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Transfusion
• This should help prevent circulatory overload.
• Digoxin may also be required to be administered to help overcome atrial fibrillation.
• Blood transfusion will obviously combat hypovolaemic shock, and help prevent ischaemic damage to other organs.
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Transfusion• A further important reason for
transfusion is that some 15 - 20% of patients either continue to bleed or re-bleed following admission to hospital.
• This produces a potentially dangerous deterioration in those patients who were previously able to compensate for their blood loss.
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Transfusion
• The potential problems of blood transfusion are obvious and well publicised.
• When large volumes of blood are transfused there is an additional problem of inducing a bleeding tendency:– There is a lack of coagulation factor
activity in stored blood.
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Transfusion
– Additionally, citrate, used as an anticoagulant will chelate Ca2+ and cause further potential problems.
– Calcium ions are important co-factors in a number of important coagulation stages.
– To help prevent these problems a unit of FFP should be administered for every 4-5 units of blood transfused.
– Platelet concentrates may also be needed.
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Differential Diagnosis
• Once it has been established that GIT bleeding has occurred, blood samples should be taken for grouping, FBC and potentially cross-matching.
• An intravenous infusion line is usually set up.
• A full history needs to be taken from the patient and the family.
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Diagnosis
• A complete medical examination needs to be performed to try and establish a cause for the bleeding, as well as the extent and effects of the blood loss.
• Acute and chronic peptic ulcers are responsible for some 90% of bleeding admissions.
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Diagnosis
• It is important that the less common causes of blood loss are investigated and ruled out, as they may indicate a specialised treatment protocol
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Peptic Ulceration & Gastric Cancer
• Introduction:• The stomach and duodenum are the
sites of some extremely common disorders, ranging in severity from gastritis via peptic ulceration to gastric cancer.
• About 10% of the population will suffer from duodenal ulcers
• Gastric cancer is one of the most common causes of death from cancer.
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Functional Anatomy: Stomach
• Stomach is divided into three main regions: the fundus, body and the antrum.
• The mucosal cells of the stomach have a range of secretory functions, they are arranged into gastric glands, penetrating into the stomach mucosa
• Glands associated with the body of the stomach are mainly populated by parietal cells
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Functional Anatomy:Stomach
• The parietal cells are mainly involved with the secretion of high concentrations of HCl and the release of intrinsic factor into the gastrointestinal tract.
• HCl is required to activate the secreted enzyme precursor, pepsinogen, into pepsin.
• Pepsinogen is secreted by chief cells or peptic cells located at the base of the gastric glands.
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Functional Anatomy:Stomach
• Due to the high levels of HCl in the stomach the mucosa is protected by the production of mucus from mucous neck cells.
• The mucus forms a continuous protective covering to the mucosa.
• Additionally the epithelial cells secrete high levels of HCO3
- ions, in order to maintain a more alkaline pH beneath the protective mucus layer.
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Peptic Ulcers
• A peptic ulcer is a full thickness defect in the surface of the G.I.T that is exposed to the erosive actions hydrochloric acid and the proteolytic enzyme pepsin.
• Peptic ulcers can occur in any area of the stomach and the upper part of the small intestine, the duodenum.
• About 80% of peptic ulcers occur within the duodenum, near its connection to stomach.
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Peptic Ulcers
• The remaining 20% of peptic ulcers are located within the stomach itself.
• Most cases of peptic ulceration seem to be due to an imbalance between the various protective mechanisms and the opposing aggressive forces, including:-– Acid secretion– Use of NSAID’s– Pepsin enzyme activity– H.pylori infection
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Peptic Ulcers
• The opposing defensive forces which strive to prevent damage and ulceration of the mucosa includes:-– Secretion of the protective layer of mucus.
– Secretion of bicarbonate ions into and beneath the mucus layer.
– Production of prostaglandins by the mucosal cells.
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Peptic Ulceration
• Peptic ulceration is a classical example of a chronic inflammatory response:– with repair,– regeneration –and the damaging forces all
exerting their effects together.
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Peptic Ulceration
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Classical chronic inflammatory site: stalemate
Outcome of Peptic Ulcer
• The damaging stimuli are overcome by the healing processes and the result is that the defect becomes filled with a fibrous scar and is recovered by the proliferation of gastric mucosa
• The healing and repair processes may be overwhelmed by the damaging stimuli and as a result there is a continuous erosion of the stomach walls, ultimately resulting in perforation
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Ideal Outcome
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Balance tips in favour of the healing process: repair and healing
Worst Outcome
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Damaging forces overwhelm defences: Perforation
Peptic Ulceration
• Peptic ulcers seem to be caused by either disturbances to acid and pepsin production or to defective defensive mechanisms.
• In some individuals there is evidence of increased parietal cell mass and defective regulation of gastric acid secretion
• In others, where acid and pepsin production are normal and no evidence of H.pylori infection, NSAID’s have been implicated.
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Peptic Ulceration• No specific dietary factors have been
associated with this form of ulceration.• Prevalence of peptic ulceration seems
to be diminishing, having reached a peak in the 1920’s.
• There has been a steady reduction in hospital admissions and reduced levels of surgery for the treatment of peptic ulceration.
• Mainly reflecting advances in drug therapy.
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Peptic Ulceration:Symptoms
• Most usual symptom of peptic ulceration is a ‘gnawing’ or ‘burning’ pain usually occurring around 1-3 hours following a meal.
• The pain often wakes the individual during the night.
• Very often the pain is only alleviated by either the ingestion of an antacid preparation or by the intake of food.
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Peptic Ulceration:Symptoms
• A minority of patients are asymptommatic until a potentially fatal complication of their condition occurs - perforation.
• If a vessel is eroded in the base or side of the crater there can be massive haemorrhage
• There can be a chemical peritonitis, with the release of concentrated acid and pepsin into the abdominal cavity, associated with a sudden and excruciating pain.
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Gastric Ulcers• Comprise some 20% of peptic ulcers.• A chronic gastritis or inflammation of a
region of the stomach is often a prelude to gastric ulceration.
• Most gastric ulcers appear on the boundary between the inflamed non-acid secreting antral mucosa and the acid secreting mucosa of the body of the stomach.
• They are associated with an H.pylori positive chronic gastritis.
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Duodenal Ulcers
• Comprise some 80% of peptic ulcers.• Mainly located in the first part of the
duodenum, immediately beyond the gastro-duodenal sphincter.
• Vast majority of patients with duodenal ulceration also have H.pylori associated gastritis.
• A positive family history is seen in some 40% of cases of duodenal ulceration.
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Duodenal Ulceration
• Individuals with blood group O seem to have a 30% greater risk of duodenal ulceration than other individuals.
• Around some 40% of patients with duodenal ulcers secrete excessive amounts of hydrochloric acid.
• Hence in the majority of cases excessive acid secretion is not the cause of ulceration.
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