Peptide production Medical Assignment Help

The hormone-producing cells of the gut are scattered diffusely throughout its length and also occur in the pancreas. The cells that synthesize these hormones are derived from neural ectoderm and are known as APUD (amine recursor uptake and decarboxylation) cells. Many of these hormones have very similar structures. Although they can be detected by radioimmunoassay in the circulation, their action is often local.

Gastrointestinal peptides.

Gastrointestinal peptides.

 shows some gut hormones and their possible physiological actions. Many are also found in other tissues, particularly the brain. A number do not act as true hormones but act as neurotransmitters or have local effects on adjacent cells only (paracrine effects).
The exact physiological role of these peptides is still being evaluated. Their importance clinically is that they may be secreted in excess, particularly in endocrine turn ours of the pancreas . Growth factors, like transforming growth factor e, are also produced by intestinal cells.

Gut motility

The contractile patterns of small intestinal muscles are primarily determined by integrated neural circuits within the gut wall-the enteric nervous system. The central nervous system and gut hormones also have a modulatory role on motility. During fasting, a distally migrating sequence of motor events termed the migrating motor  complex (MMC) occurs in a cyclical fashion. The MMC consists of a period of motor quiescence (phase I) followed by a period of irregular contractile activity (phase II), culminating in a short (5-10 min) burst of regular phasic contractions (phase III). Each MMC cycle lasts for approximately 90 min. In the duodenum, phase III is associated with increased gastric, pancreatic and biliary secretions. The role of the MMC is unclear, but the strong phase III contractions propel secretions, residual food and desquamated cells towards the colon, acting as an ‘intestinal housekeeper’.
After a meal, the MMC pattern is disrupted and replaced by irregular contractions. This seemingly chaotic fed pattern lasts typically for 2-5 hours, depending on the size and nutrient content of the meal. The irregular contractions of the fed pattern have a mixing function, moving intraluminal contents to and fro, aiding the digestive process.

PRESENTING FEATURES OF SMALL BOWEL

DISEASE

Regardless of the cause, the common presenting features of small bowel disease are:

DIARRHOEA. This is a common feature of small bowel disease but approximately 10-20% of patients will have no diarrhoea or any other gastrointestinal symptoms. Steatorrhoea is occasionally present.
ABDOMINAL PAIN AND DISCOMFORT. Abdominal distension can cause discomfort and flatulence. The pain has no specific character or periodicity and is not usually severe.
WEIGHT LOSS. Weight loss is due to the anorexia that invariably accompanies small bowel disease. Although malabsorption occurs, the amount is small relative to intake.
NUTRITIONAL DEFICIENCIES. Deficiencies of iron, vitamin B]2>folate or all of these, leading to anaemia, are the only common deficiencies. Occasionally malabsorption of other vitamins or minerals occurs, causing bruising (vitamin K deficiency), tetany (calcium deficiency), osteomalacia (vitamin D deficiency), or stomatitis, sore tongue and aphthous ulceration (multiple vitamin deficiencies). Ankle oedema may be seen and is partly nutritional and partly due to intestinal loss of albumin.

PHYSICAL SIGNS OF SMALL BOWEL DISEASE

These are few and non-specific. If present they are associated with anaemia and the nutritional deficiencies described above.
Abdominal examination is often normal, but sometimes distension and, rarely, hepatomegaly or an abdominal mass are found. In the severely ill patient gross malnutrition with muscle wasting is seen. A neuropathy, not always due to vitamin B12deficiency, can be present.

INVESTIGATION OF SMALL BOWEL DISEASE

Blood tests

FULL BLOOD COUNT and film. Anaemia can be microcytic (low mean corpuscular volume [MCV]) or macrocytic (high MCV). The blood film may also show other abnormal cells, e.g. Howell-Jolly bodies, which are seen in splenic atrophy associated with coeliac disease.
SERUM IRON. If the MCV is low, serum iron and total iron-binding capacity or serum ferritin are determined.
SERUM VITAMIN BI2/FOLATE. If the MCV is high, serum vitamin B12,serum and red cell folate are determined. However, with mixed deficiencies, the MCV may be normal. The red cell folate is a good indicator of the presence of small bowel disease. It is frequently low in both coeliac disease and Crohn’s disease which are the two commonest causes of small bowel disease in developed countries.
SERUM ALBUMIN gives some indication of the nutritional status.
Low SERUM CALCIUM and raised alkaline phosphatase may indicate the presence of osteomalacia.
AUTOANTIBODIES. In countries with a high incidence of coeliac disease, measurement in the serum of antireticulin and/or endomysial antibodies are a useful adjunct for the diagnosis of coeliac disease. If the clinical suspicion of malabsorption is high, the structure of the small bowel should be studied next.

Small bowel anatomy

SMALL BOWEL FOLLOW-THROUGH . This detects gross anatomical defects such as diverticula, strictures and Crohn’s disease. Dilatation of the folds and a changed fold pattern may suggest malabsorption but, as these are not specific findings, the diagnosis should not be based on these alone. Gross dilatation is seen in pseudo-obstruction.
JEJUNAL BIOPSY (Practical box 4.4). This is used to assess the microanatomy of the small bowel. Biopsies can be obtained via an endoscope passed into the duodenum either with a Crosby-Kugler capsule inserted retrogradely up the endoscope or with a grab biopsy using large forceps. Alternatively, specimens can be obtained by swallowing a Crosby-Kugler capsule. With either technique, an adequate piece of tissue, well orientated, is necessary for correct evaluation initially under a dissecting microscope. The histological appearances will be described in the sections on individual diseases.
A smear of the jejunal juice or a mucosal impression can also be made and is helpful in the diagnosis of Giardia lamblia .

Tests of absorption

These are only required in complicated cases.

Flow diagram for investigation of patients with suspected small bowel disease. MCV; mean corpuscular volume.

Flow diagram for investigation of patients with
suspected small bowel disease. MCV; mean corpuscular volume.

FATMALABSORPTIONTh. e confirmation of the presence of steatorrhoea is occasionally necessary. The fat content of stools is measured using a 3-day collection of faeces with the patient on a diet containing 100 g of fat daily. Normal faecal fat excretion is less than 17 mmol (6 g) per day. To avoid faecal collections, fat absorption can also be measured using breath analysis. Following oral administration of a radiolabelled fat load, the amount of “C02 in the expired breath gives an indication of the amount of fat malabsorption. Comparison between a labelled triglyceride ([“Cltriolein) and a labelled fatty acid ([3Hloleic acid) is used to diagnose pancreatic disease, when fatty acid absorption will be normal.

D-XYLOSE TOLERANCE TEST. Xylose is a sugar which is absorbed from the proximal small intestine. The urinary xylose excretion and the blood xylose level following an oral dose reflect its absorption. This test tends to produce many false-positives and although still used in some centres it should be phased out.
LACTOSE TOLERANCE TEST. This involves the oral ingestion of 50 g of lactose and the measurement of blood glucose. The test is oflittle use in adults as lactose intolerance is not a clinical problem since these patients avoid milk by choice. There is a high incidence of lactase deficiency in many parts of the world, e.g. the Mediterranean countries, and parts of Africa and Asia. It should be remembered that a glass of milk only contains approximately 11 g of lactose. A glucose tolerance test should not be performed, as it is influenced by many factors other than absorption.

SCHILLING TEST. This is performed to look for vitamin Bl2 malabsorption. It is described in detail . In gastrointestinal disease it is used to detect:
• Pernicious anaemia
• Ileal disease (when oral vitamin Bl2 is given with intrinsic factor)
• Bacterial overgrowth (measurement of vitamin Bl2 plus intrinsic factor absorption is repeated after antibiotics)

Jejunal biopsy.

Jejunal biopsy.

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Gastroenterology

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