Definition of the malabsorption syndrome
The malabsorption syndrome represents a pathological situation characterized by a disorder of absorption, at small bowel level, of different nutritive compounds.
Malabsorption may be of pancreatic, hepatic or intestinal origin. Malabsorption syndrome may be caused by digestion disorder, with the secondary disorder of absorption(by hepatic, pancreatic causes) or may by ower directly to absorption disorder at the enteral level (in intestinal diseases).
In malabsorption, the most typical sign is steatorrhea, defined as a more than 5g fats/24 hours loss by stool.
The etiopathogenesis of the malabsorption syndrome
Different disease of the digestive tract may provoke disorders of digestion of alimentary principles and/ or disorders of absorption.
The protein digestion is modified in the pancreatic failure (decreasing of trypsin and chymotrypsin), in accelerated transit speed (enzymatic contact time reduced). The deficitary absorption of aminoacids appears in different intestinal diseases.
Glucide malabsorption is generated by maldigestion , especially in the disaccharidase deficit (lactase, maltase, sucrase) or in the chronic pancreatic insufficiency (deficit of pancreatic amylase). The chronic intestinal sufferance will generate disorders in the monosaccharide absorption.
Lipid malabsorption is generated by lipid maldigestion (gastric resection with Billroth II anastomosis), where billiary salts and lipase get into contact with food nonphysiologically; the Zollinger-Ellison syndrome, where excessive gastric acidity inactivates the pancreatic lipase; the insufficiency of pancreatic lipase in the chronic pancreatitis; the lack of lipid mycellisation by decreasing the billiary acids-pool in chronic hepatic diseases; intestinal bacterial overpopulation or reabsorption failure in the terminal ileon inflammation).
Etiology of the malabsorption syndrome
Causes of maldigestion:
a. Gastric causes:
- gastrectomia Billroth II
- gastroenteroanastomosis
- Zollinger - Ellison syndrome;
b. Billiary causes:
- chronic hepatic diseases
- chronic billiary obstruction
c. Pancreatic causes:
- chronic pancreatitis
- pancreatic cystic fibrosis
d. Intestinal causes:
- disaccharidases deficit (lactase, maltase, sucrase, trehalase)
- afferent loop syndrome (by bacterial overpopulation).
Causes of intestinal malabsorption
a. Abnormal intestinal epithelium absorption:
- celiac disease
- Whipple disease
- intestinal amiloidosis
- chronic intestinal ischemia
- Crohn’s disease of the intestine
- tropical sprue
- intestinal tuberculosis
B. Syndrome of short intestine
- after surgery
- enterocolic fistulas
- surgical intestinal by-pass
c. Abnormal intestinal transport:
- intestinal lymphoma
- idiopathic intestinal lymphangectasia
- congenital cystic pneumatosis
d. Increased intestinal transit speed:
- hypertiroidia
- chronic diarrhea
Clinical forms of malabsorption syndrome
- malabsorption syndrome maldigestion
- malabsorption syndrome by disorders of intestinal absorption (malabsorption)
- mixt malabsorption syndrome- when digestive disorders sre associated with those of absorption.
Clinical features
- chronic diarrhea weight loss up to generalized malnutrition
- steatorrhea (soft stools, light colored, smelling, adherent)
- the abdominal distension
- bloating
- flatulence
- abdominal discomfort
- weight loss
- the Bichat-bulk disappears
- muscle atrophy
- tegument changing
- together with paleness, rough and dried skin,sometimes with pelagroid pigmentation
- the tongue mucosa is red; lacking its small glands (glossitis), cheilosis
- the nails decolorize and break easily
- axilar and pubian hair reduces, in the latest stages, alopecia
- the disorders in calcium absorption may generate osteomalacia bones pain and tetania
- the deficiency of K vitamin generates tendency to bleeding
- ascites
- anemia
- endocrine disorders: hypofisary failure (with troubles in children growth), corticosuprarenalian failure (Addison disease), gonadic failure (impotence and sterility).
Diagnosis of malabsorption syndrome
- steatorrhea is a cardinal sign. Represent the elimination of more than 5g lipids/24 hours.
- the coloring of a stool probe with Sudan III and numbering of fat corpuscles
- creatorrhea = the proteic loss by stool
The etiology of malabsorption syndrome requires the evaluation:
a. Gastric:
- barium examination, for the diagnosis of gastrocolic fistula, gastroenteroanastomosis, gastrectomy with Billroth II anastomoses
- gastroscopy: multiple ulcers in Zollinger Ellison syndrome
- dosing gastrinemia possibly gastric chemism stimulated with Pentagastrine
b. Billiar:
- the biologic diagnosis of billiary obstruction, possibly completed with pancreatic computed tomography and endoscopic retrograde colangiopancreatography (ERCP)
c. Pancreatic:
- pancreatic enzymes (amylase, lipase) may be increased
- the imagistic modified aspect of pancreas or evalution by ERCP of pancreatic ductal aspect
- altered pancreartic functional tests (PABA or Fluorescein diluarat)
- more recently, determination of I (first) faecal elastase mey demonstrate incipient stages of pancreatic failure
- determining VIP level (vasoactive intestinal polypeptide) may establish the diagnosis of VIP-oma or pancreatic cholera (severe, watery diarrhea), with hypokaliemia
d. Intestinal:
- barium examination,with intestinal following up or enema-may evaluate the intestinal aspect and motility
- duodenoscopy with duodenal biopsy ( celiac disease) or endoscopy may visualize the mucosal aspect (biopsy).
- D-xilosis test
- Schilling test-evaluates the absorption of B12 vitamin
- small bowel biopsy of jejunal area may show the villous atrophies in celiac disease
- colonoscopy may show changing of rectocolitis, Crohn’s disease may be diagnosed
- the lactose tolerance test (LTT) which may show a lactase deficit
Differential diagnosis
- The malabsorption syndrome differential diagnosis may be done with different causes of chronic diarrhea, which have not attained malabsorption. In these cases, the weight loss and the modifying of biologic sanguine parameters (proteinemia, albuminemia) do not appear.
- The colon neoplasm is accompanied by weight loss, diarrhea, iron-deficiency anemia and it must be differentiated from malabsorption syndrome.
- In case of hepatic metastase, jaundice may be signaled and a tumoral liver may be palpated.
- The neoplasm syndromes of different causes evolve with excessive weight loss, hypoproteinemia and hypoalbuminemia, but without diarrhea.
Evolution
- malabsorption syndrome evolution is chronic, progressive, when the etiology is not discovered and treated. Denutrition evolves to excessive weight loss, and the uncorrected biological disorders aggravate.
Complication
- hypoalbuminemia with edema and sever ascites
- the decrease of protrombin index with multiple bleedings
- anemia
- the sever decrease of serum electrolytes: K, Na, Ca, Mg
- the decrease of vitamins
Treatment
The therapeutic attitude in malabsorption syndrome is mostly related to its etiology.
The alimentary diet : in celiac disease( where wheat, barley, oat and rye will be compulsory avoided, but replaced with rice and flour,potatoes) or the lactase defocot(where milk and dairy products will be completely avoided).
In chronic pancreatitis , the diet will completely avoid the alcohol intake and will drastically reduce fats.
On chronic diarrheas, the food rich in hard vegetal fibers will be avoided(radish, cabbage).
Medical therapy
- in Zollinger - Ellison syndrome the resection of gastrinoma and intense blocking of acid secretion will be done, using H / K ATP-ase pump proton blockers
- Omeprazole 40-160mg/day
- Lansoprazole or Pantoprazole
- Sandostatin 200mg/day subcutaneous
- in chronic pancreatitis – the enzyme substitution
- Creon
- Nutrizym
- Cotazym
- Panzytrat
- Digestal forte
- in intestinal causes of malabsorption of malabsorption, the medical treatment has to have two compounds the dismicrobism which is treated with intestinal eubiotics: Saprosan 3x1 tb/day
Antinal 4x1 tb/day
Intetrix 4x1 tb/day
and on the other hand the intestinal protection with products like Smecta 3x1 packet/day
or reduction of transit speed in case of the acute diarrhea with Loperamid (Imodium) 1-2 tb when needed.
in cesa of excessive flatulence - Dimeticone
in Crohn’s disease - Mesalazina
- corticotherapy
- Azathioprine
- in the Verner - Morrison syndrome – octreotide (Sandostatin) 200-300 mg/day
- in the Whipple disease - antibiotics
- Tetracycline 4x250mg/day
- Ampicilline
- Trimetoprim/ Biseptol,10-12 months
- the following deficits must be corrected :
- hypoalbuminemia by administration plasma
- iron- deficiency anemia by administrating iron
- macrocytic anemia by administrating B12 vitamin /folic acid
- the electrolytic deficits (Na, K) will be corrected parenterally and those of Ca and Mg usually by oral medication.
- the vitamin deficits (B complex, D and K) will be corrected, as well as the hormonal ones, when they appear.
Gastric neoplasia represents the second cause of mortality by cancer in the world, after the pulmonary one.
Epidemiology
Linked to the alimentary habits (in Japan the frequency is especially high). In Europe, it is more frequent in the northern zones, also relater to the alimentary habits (canning).
This cancer is 2-3 times more frequent in men than in women, and its frequency increases with age (average age at the moment of diagnosis is over 60 years). It rarely appears under 45 years.
Risk factors is gastric cancer
- alimentary habits: the high content in nitrosamine in canned food by salt and smoke, are favoring factors to the gastric neoplasm; by contrary, the alimentation rich in fruit and vegetables containing C and A vitamins, protects the stomach.
- the genetic factor: the existence of a familial predisposition to this type of neoplasia
- the low socio-economic standard - may be a favoring factor, probably because of the alimentation, infection Helicobacter Pylori etc.
- the Helicobacter Pylori infection. Helicobacter Pylori was recently appointed by WHO as a first range carcinogen, thus assessing its involvement in the etiopathogenesis of this neoplasm. The Helicobacter Pylori intervention is realized by induction of atrophic gastritis with intestinal metaplasia, which represents a potential evolution towards dysplasia and neoplasia.
Gastric affections predisposing to gastric cancer
- atrophic chronic gastritis: mostly related to the Helicobacter Pylori infection; on this background dysplasic lesions show quite often, evolving from an easy to severe dysplasia (the latter considered in fact an intra-epithelial cancer).
- gastric adenomatous polyps: represent a premalignant stage, especially those with bigger dimensions (over 1 cm, and those over 2 cm have big chances of malignization). Therefore, endoscopic polypectomia of these polyps is indicated at the very moment of their discovery.
- gastric resection in the antecedents (for ulcer) represent a risk factor, generally over 15 years from resection. Usually, an inflammatory stomitis is noticed, as well as lesions of gastritis in the gastric segment left, which may degenerate to malignancy. Therefore, the necessity of endoscopic following of operated stomach after more than 15 years from resection.
- gastritis with giant folds Menetriere has a risk of approx. 15% of malignant transformation.
- gastric ulcer. It is compulsory to take multiple biopsies from each gastric ulcer at every endoscopy and the gastric ulcer healing must be endoscopically checker (with biopsy from the scar). To be mentioned the possibility of some ulcerated cancers, susceptible of scarring under medical treatment.
Clinical picture of gastric cancer
It may be heterogeneous, depending on how advanced the cancer is. The most frequent symptoms are epigastralgia, freakish appetite leading to total anorexia (sometimes the complete refusal to eat meat), progressive weight loss, and iron deficiency anemia. The epigastric pain may mimic the ulcer symptoms, appearing after meals, often disappearing with gastric protectives. Weight loss may get in the advanced forms to a neoplasic extreme weakness. More rarely, a digestive hemorrhage may appear, endoscopically confirming the diagnosis of gastric cancer. In the advanced forms there might be an epigastric palpable abdominal mass.
Rarely the gastric neoplasia may be discovered starting with an anemic symptoms. Paraneoplasic syndromes may appear migratory phlebitis, acantosis nigricans etc.
Precocious gastric cancer is usually asymptomatic, or there may appear some discrete dyspeptic symptoms. Therefore, it is most often randomly discovered, by occasion of an endoscopy done for an epigastric symptomatology.
Pathological picture in gastric cancer
Histological, the gastric cancer is an adenocarcinoma, with different degrees of differentiation. The less differentiated, the more aggressive it is. There are some neoplasms with histological aspect of “sealed ring”.
Macroscopically: the neoplasm may be protrusive, ulcerated infiltrative. The protrusive aspect, bleeding, is typical to malignity. The ulcerated has irregular margins, infiltrated, rough and must be differentiated via endoscopy from gastric ulcer (b multiple endoscopic biopsies). The infiltrative type of cancer (linitis plastica) realizes a diffuse, extensive infiltration of gastric wall, conferring rigidity to this one, and it must be differentiated by gastric lymphoma.
The transparietal extension of gastric cancer is usually precocious, invading the neighbor organs. The lymphatic extension is also rapid, with the involvement of territories of gastric lymphatic drain and then to a certain distance. The metastases are more often in the liver and lung. Sometimes a carcinomatous peritonitis may appear.
The TNM stadialization (tumor, ganglionar node, and metastasis) allows the establishment of prognosis and of therapeutic approach:
- tumor
- T1 involves the mucosa and submucosa
- T2 penetrates into the muscularis propria
- T3 involving of serosa
- T4 penetrates into the surrounding organs
- lymph nodes:
- N0 lack of ganglionar invasion
- N1 involvement if nodes in the neighborhood
- N2 involvement of distant lymph nodes
- metastases:
- M0 lack of metastases
- M1 distant metastases
The diagnosis of gastric cancer
It most often starts with a dyspeptic syndrome, epigastralgia, progressive weight loss or an anemic unexplained syendoscondrome. The familial aggregation, or already known premalignant lesions may turn the attention to the disease.
Clinical examination usually brings poor arguments, but in the advanced stages an epigastric mass or/and some supraclavicular lymph nodes involvement may be present.
Paraclinical findings of gastric cancer
- biologically, an iron – deficiency anemia is the rule or severe). There are still gastric neoplasias that may evolve without anemia (linitis plastica).
- Gastroscopy is the election diagnostic method. It allows the visualization of the lesion, signals its characteristics (friability, bleeding) and prelevation of multiple biopsies for the compulsory histological diagnosis confirmation.
Acording to endoscopy, the advanced gastric cancer may be: protrusive, ulcerated or infiltrative (sometimes these types may intricate).
The early gastric cancer (superficial – involving only the mucosa and submucosa) is endoscopically classified.
- Type I – protrusive
- Type II – superficial II a - overplane, II b – plane, III c – depressed
- Type III – excavated
In early gastric cancer the five – years survival after the operation 95%.
- gastric barium-examination is generally a diagnostic surpassed method,generally addressed to the advanced neoplasms or cases with plastic linita(where the diagnostic-help is useful,often superior to the endoscopy.The X-ray examination cannot diagnose all the early stages of the disease and does not allow biopsy prelevation.Diagnostics endoscopy per primam is preferred to a checking-out of an nuclear radiological examination,due to the risks of radiological diagnosis failure.
- echoendoscopy permits the T and M stadialization
- transabdominal ultrasonography may show hepatic metastases or perigastric adenopaties.Sometimes, a casual abdominal ultrasonography may discover an epigastricmass “in cockade”, which may suggest a gastric neoplasia (the subsequent endoscopic check-out is compulsory).
Prognosis of gastric cancer
The gastric cancer prognosis depends on the TNM extensions, histological type (poor oe well-differentiated), and patient’s age.
The survival is very good only in the superficial cancers (95% in 5 years). The radical surgery may be done in only 1/3 of cases, in which the 5 year-survival is approx.25%.
Treatment of gastric cancer
A. Surgical. Surgery is the best and radical therapy in gastric cancer. A gastrectomy with lymphadenectomy is performed.Usualy, a subtotal gastrectomy or total (with esojejunostomy) is done, depending on the location and extension of the tumor.
B. Endoscopic. The surgically over passed cancers may still benefit from an endoscopic haemostatic treatment with argon Beamer.
A mucosectomia may also be done in the early stages of cancer (“in situ”). It consists into serum injection under the neoplasia lesion thus transforming it into a sessile polyp, which will be polypectomised afterwards. The piece obtained will be examine by a pathologist.
C. Chemotherapy. Post surgical chemotherapy is generally indicated, almost in more advanced cases, and it includes more cures of Adriamycine with 5- Fluorouracil.
Definition of Irritable bowel syndrome
Irritable bowel syndrome represents a functional disease, characterized by transit disorders, generally constipation alternating with diarrhea, diffuse abdominal pain, sometimes mucus emission.
Clinical features
- diffuse abdominal pain, or located along the colon. They may be smothered, but often have a cramp character, duration of seconds to minutes. Other times the patient feels only an abdominal discomfort. The most often symptoms disappear in the relaxing periods, holiday etc.
- transit disorders are frequent, characteristic being the alternation constipation-diarrhea. The stool emission is often hard, fragmented, covered with mucus.
- mucus emission accompanies the hard stool. Blood does not appear in stool in the irritable bowel syndrome, but the hard, rough stools may create anal fissures that may bleed.
- bloading
Diagnosis
Manning criteria:
- abdominal pain that disappear after stool emission
- stool becoming more frequent and soft in the presence of pain
- bloating, flatulence
- sensation of incomplete evacuation of the rectum
- elimination of mucus in stools
- imperious character of defecation
Clinical data of the irritable bowel syndrome diagnosis
- elevated ESR
- leukocytosis
- pus, blood or fat in the stools
- more than 200g of stool per day
- persistent diarrhea
- hipokaliemia
- no spastic response to rectal distension during manometry
Paraclinic diagnosis
- anoscopy, rectoscopy, colonoscopy (sometimes barium enema), to evidence the organic pathology of colon;
- gastroscopy, to show the possible gastric lesions;
- abdominal and pelvic ultrasonography, to show the gallbladder, pancreas and genital organs;
- radiologic evaluation of intestine (enteroclysis or barium examination) or enteroscopy for small bowel pathology.
Differential diagnosis
- ano-rectal and colon neoplasm
- inflammatory bowel disease(ulcerative colitis, Crohn’s disease)
- colonic diverticulosis and diverticulitis
- lactase deficit
- functional dyspepsia
Evolution
The irritable colon evolution is favorable, since there are no complications.
In general, the disease evolves for a long time, with periods of silence or with exacerbations, usually related to stress.
Treatment of irritable colon
1. Diet. When the constipation predominates, the diet will be rich in alimentary fibers. If the diet is not sufficient, constipation will be controlled with laxatives type Forlax (that increase the stool volume). The patients should avoid consuming certain food that induces symptoms.
2. Medication. The therapy consists in:
- antidiarrheic drugs - Smecta(smectitis) or Imodium(loperamid)
- antispastic - Spasmomen
-Debridat
-Dicetel
-No-Spa
-the medication is given only when needed
- sedatives - Hidroxizin
-Rudotel
Treatment of gastroesophageal reflux disease
A. Diet
- dietary restrictions: avoiding bulky meals, avoiding food that decreases LES pressure:coffee, chocolate, carbonated drinks, mint products, fatty foods, alcohol or foods that increase the acid secretion: orange juice, carbonated drinks, white vine, and acid food);
- avoiding smoking. It is said that smoking increases the acid secretion and lowers the LES pressure;
- avoiding lying recumbent immediately after eating;
- weight loss in the obese patients (reducing the abdominal pressure);
- avoiding medications that decrease the LES pressure: nifedipin (calcium channel blockers), nitrates, aminophylline, caffeine and anticholinergics. These are also studies suggesting that NSAIDS and aspirin are associated with esophageal lesions, being able to induce esophagitis and even esophageal strictures.
B. Medication – involves 2 types of drugs:
1. Antisecretory drugs. This treatment decreases the acid secretion:
Proton pump blockers are the most potent antisecretory drugs:
- Esomeprazole (Nexium) 40 mg/day.
- Omeprazole (Losec, Ultop, Antra) 20 mg bid;
- Pantoprazole (Controloc) 40 mg/day;
- Lanzoprazole (Lanzap) 30 mg/day;
- Rabeprazole 20 mg/day;
The duration of treatment is 4-8 weeks, or a few months in resistant cases.
H2 blocking agents:
Ranitidine 150 mg bid;
Famotidine 40 mg/day;
Nizatidine (Axid) 150 mg bid.
H2 blocking agents; they may be used 2-6 weeks or even more in resistant cases.
2. Prokinetic
- Metoclopramide, 10 mg tid, 30 bid minutes before meals. Its effect is the increasing of LES tone; it also increases the esophageal clearance and hastens the gastric emptying.
- Domperidone (Motilium) is effective on the LES and gastrokietic; the effect on the reflux is lower than that of Metoclopramide.
3. Antiacids - medication with direct neutralizing effect: Maalox, Novalox, Rennie, Dicarbocalm, containing magnesium and aluminium salts; the patients se them when the symptoms appear, with a spectacular disappearance of symptoms. They effect is only symptomatic, the esophagitis lesions persisting. An interesting drug of this group is the sodium alginate (Gaviscon, Nicon), which forms a protective layer over the esogastric mucosa.
4. Mucosal protectives. Sucralfate is an aluminium polisulfatate sucrose, which links the billiary acids and pepsin and stimulates the gastric secretion of prostaglandins and epidermic growth factor, thus favoring the epithelium healing. It is sometimes indicated in esophagitis.
The strategy of treatment is to begin, generally, in case of acid reflux, with PPI, in case of failure, a prokinetic is added. If the patients complain of billiary reflux, the therapy will be prokinetic.
C. Endoscopic
- Esophageal structures. The most preffered treatment in peptic strictures is done endoscopically, by Savary probe dilators or pressure balloons.
- Superior digestive hemorrhage. The severe cases require endoscopic hemostasis by Adrenaline injections, Argon Beamer photocoagulation or hemoclips application.
- Barrett’s esophagus. The columnar epithelium patches with different degrees of dysplasia may be destroyed by Argon plasma photocoagulation.
- Endoscopic fondoplicature – represents a new noninvasive method, in which the gastric fundus is wrapped around the esophagus thus creating a very sharp His angle.
D. Surgical
In rare cases with severe esophagitis without response to drug therapy, surgery may be needed.
Definition of Gastroesophageal reflux disease
Gastroesophageal reflux disease (GERD) includes all the symptoms that result from ferux of gastric content into the esophagus.
Gastroesophageal reflux (GERD) represents the physiologic phenomenon of gastric content passage into the esophagus, which becomes pathological when the antireflux mechanisms are surpassed.
Reflux esophagitis (RE) consists of esophageal lesions induced by GER, occurring only in certain cases of pathological GER.
Etiopathogenesis (causes)
A. Physiologic causes:
- Decreasing of the lower esophageal sphincter (LES) pressure. Normally the LES pressure is 20-25 mmHg and it only disappears during swallowing. GER occurs either when LES transiently relaxes because of swallowing, or when the LES basal pressure decreases less than 6 mmHg, thus allowing the castric content to pass into the esophagus. LESpressure can be reduced by drugs (anticholinergic, aminophylline, nitrates, benzodiazepines, calcium channel blockers), food (chocolate, fatty foods, onion, citric, tomato juice mint), coffee, smoking, alcohol.
- Decreasing of gastric motility with delayed gastric emptying.
- Disorder of esophageal clearance by refluxed acid gastric content.
B. Mechanical causes:
- Hiatal hernia – produces a decrease in LES tonus, which allows the reflux.
- Increasing of intraabdominal pressure: pregnant women, obese, patients with giant abdominal tumors or ascites.
- The widening of his angle. This angle between the esophagus and stomach is usually very sharp, having the role of a valve at the stomach entrance. In the obese, it enlarges.
- The relaxation of diaphragmatic crura, the muscular channel through which the esophagus passes from thorax into the abdomen. The relaxation cavity volume increases (emphysema).
- Sclerodermia. The motor disorders of the esophagus are the result of fibrosis and atrophy of the smooth muscle, the so-called “glass-esophagus”.
The development and severity of reflux esophagitis depend on 3 conditions:
- the increasing of reflux frequency
- the increasing of reflux duration
- the action of aggressive gastric content of the esophageal mucosa
Clinical features (symptoms)
- Pyrosis is characterized by burning retrosternal discomfort, climbing up the throat. It is aggravated by maneuvers that increase intraabominal pressure (bending forward, load straining, lying recumbent immediately after eating) accompanied sometimes by acid regurgitations as well. If the LES incompetence is severe, solid food can also be regurgitated.
- Retrosternal pain is often a problem of differential diagnosis with the cardiac pathology. It may appear isolated, without pyrosis, mainly when ingesting irritating food. Odynophagia (painful swallowing) appears during spastic contractions of LES. Dyspagia – difficult swallowing.
- Respiratory symptoms (stifling, nocturnal dyspneea, asthma crises) or ENT (laryngitis, pharyngeal paralysis, dysphonia) are due to the regurgitation of refluxed acid gastric content and its aspiration.
Paraclinical findings (investigations)
- Superior digestive andoscopy (esogastrocopy). When confronting with annoying, persistent esophageal symptoms (mainly pain or dysphagia), an esogastroscopy will be done. It will reveal or exclude the possible esophageal lesions (esopagitis, stenosis)., gastroduodenal lesion. Also by means of endoscopy, a discovered lesion may be diopsied.
- Barium examination it may show the esophageal motor disorders (achalasia, esophageal diffuse spasm), a possible esophageal stenosis, a hiatal hernia.
- Esophageal pH – metry is very useful to discover the reflux duration.
- Esophageal manometry allows the subtle discovering of esophageal motor disorders and their possible linking to the clinical symptoms.
Other tests, more rarely used are esophageal scintigraphy or the Berstein test.
Diagnosis of Gastroesophageal reflux disease
Positive diagnosis – is mainly clinical, but most be paraclinical confirmed.
Differential diagnosis
A. With digestive diseases:
- gastroduodenal ulcer having as typical symptom the epigastric pain;
- the differenciation between the acid reflux and the alkaline one (mostly after colecistectomy), when the patient complains of bitter taste in the morning.
- the esophageal diverticula’s, achalasia, esophageal ulcer or cancer.
B. With nondigestive digeases:
- retrosternal or thoracic pain must be differentiated from a cardiac pain (ECG or the effort test is necessary; in doubtful cases, coronarography is useful)
- the bronchic asthma crisis may be sometimes induced by the acid reflux, therefore, correlating the crises with pH – metry may be useful for the therapy.
Evolution, complications
The evolution is prolonged with good periods alternating with less good ones, generally because of food intake and life style.
The complications of reflux disease are:
- reflux esophagitis, of different degrees, resulting in esophageal peptic ulcer and esophageal stenosis.
- The Barrett epithelium (endobranchiesophagus) is a columnar epithelial metaplasia of normal squamous mucosa, because of reflux disease healing, after acid exposure, and it represents a premalignant condition to the esophageal cancer.
- Superior digestive hemorrhage (hematemesis and/or melena) is a rare complication. It generally appears as melena, because the hemorrhages are mild, produced by ulcer or severe esophagitis.
Treatment of Gastroesophageal reflux disease
A. Diet
- dietary restrictions: avoiding bulky meals, avoiding food that decreases LES pressure:coffee, chocolate, carbonated drinks, mint products, fatty foods, alcohol or foods that increase the acid secretion: orange juice, carbonated drinks, white vine, and acid food);
- avoiding smoking. It is said that smoking increases the acid secretion and lowers the LES pressure;
- avoiding lying recumbent immediately after eating;
- weight loss in the obese patients (reducing the abdominal pressure);
- avoiding medications that decrease the LES pressure: nifedipin (calcium channel blockers), nitrates, aminophylline, caffeine and anticholinergics. These are also studies suggesting that NSAIDS and aspirin are associated with esophageal lesions, being able to induce esophagitis and even esophageal strictures.
B. Medication – involves 2 types of drugs:
1. Antisecretory drugs. This treatment decreases the acid secretion:
Proton pump blockers are the most potent antisecretory drugs:
- Esomeprazole (Nexium) 40 mg/day.
- Omeprazole (Losec, Ultop, Antra) 20 mg bid;
- Pantoprazole (Controloc) 40 mg/day;
- Lanzoprazole (Lanzap) 30 mg/day;
- Rabeprazole 20 mg/day;
The duration of treatment is 4-8 weeks, or a few months in resistant cases.
H2 blocking agents:
- Ranitidine 150 mg bid;
- Famotidine 40 mg/day;
- Nizatidine (Axid) 150 mg bid.
- H2 blocking agents; they may be used 2-6 weeks or even more in resistant cases.
2. Prokinetic
- Metoclopramide, 10 mg tid, 30 bid minutes before meals. Its effect is the increasing of LES tone; it also increases the esophageal clearance and hastens the gastric emptying.
- Domperidone (Motilium) is effective on the LES and gastrokietic; the effect on the reflux is lower than that of Metoclopramide.
3. Antiacids - medication with direct neutralizing effect: Maalox, Novalox, Rennie, Dicarbocalm, containing magnesium and aluminium salts; the patients se them when the symptoms appear, with a spectacular disappearance of symptoms. They effect is only symptomatic, the esophagitis lesions persisting. An interesting drug of this group is the sodium alginate (Gaviscon, Nicon), which forms a protective layer over the esogastric mucosa.
4. Mucosal protectives. Sucralfate is an aluminium polisulfatate sucrose, which links the billiary acids and pepsin and stimulates the gastric secretion of prostaglandins and epidermic growth factor, thus favoring the epithelium healing. It is sometimes indicated in esophagitis.
The strategy of treatment is to begin, generally, in case of acid reflux, with PPI, in case of failure, a prokinetic is added. If the patients complain of billiary reflux, the therapy will be prokinetic.
C. Endoscopic
- Esophageal structures. The most preffered treatment in peptic strictures is done endoscopically, by Savary probe dilators or pressure balloons.
- Superior digestive hemorrhage. The severe cases require endoscopic hemostasis by Adrenaline injections, Argon Beamer photocoagulation or hemoclips application.
- Barrett’s esophagus. The columnar epithelium patches with different degrees of dysplasia may be destroyed by Argon plasma photocoagulation.
- Endoscopic fondoplicature – represents a new noninvasive method, in which the gastric fundus is wrapped around the esophagus thus creating a very sharp His angle.
D. Surgical
In rare cases with severe esophagitis without response to drug therapy, surgery may be needed.
Treatment of ulcerous disease
1.The diet
A diet with avoidance of acid, hot or seasoned food might still be recommended. The exclusion of coffee during the acute period may be recommended.
Aspirin intake, as well as NSAIDS and corticoids should be forbidden.
2. Medical therapy
Administration of:
A) Antisecretory drugs
- H2 histaminic receptor blockers:
- Cimetidine 1000mg/day
- Ranitidine 300 mg/day
- Nizatidine(Axid) 300 mg/day
- Famotidine (Quamatel) 40mg/day
Famotidine will be preferred, given once or twice a day and without drug interferences of Cimetidine(cytochrome P450).
- HK ATP - ase pump blockers:
- Esomeprazole(Nexium) 40mg/day
- Omeprazole (Losec, Antra, Ultop) 40 mg/day
- Pantoprazole(Controloc) 40 mg/day
- Lanzoprazole(Lanzap) 30mg/day
- Rabeprazole(Pariet) 20mg/day
The duration of antisecretory therapy will be for 6-8 weeks.
B) Gastric mucosal protectives
- sucralfate 4g/day (qid)might be associated.
C) Antacids
To neutralize the acid excess and reduce the painful symptoms, symptomatic medication such as Maalox, Almagel, Alfogel etc. are used.
Schemes of treatment in Helicobacter Pylori infection
- The schemes including proton pump blockers (zomeprazole, lanzoprazole or pantoprazole), associated with two antibiotics are indicated, triple or even quadruple schemes are used.
-The triple therapy includes OAM=Omeprazole(40mg/day)+Amoxicillin(2g/day)+Metronidazole(1500mg/day);
- or the ideal association is OAC=Omeprazole+Amoxicilline+Claritromicine(macrolide in dose of 1000mg/day).
- The quadruple therapy is composed of Omeprazole+Subcitric bismuth (De-Nol)+Tetracycline+Metronidazole.
The anti HP therapy duration is for 7 day.
Some authors treat a newly discovered Helicobacter Pylori positive ulcer, only with 7 days of anti Helicobacter Pylori therapy. It is still generally preferred that this therapy be followed by one month of antisecretory medication-proton pump inhibitors.
The check-out of Helicobacter Pylori eradication may be done by endoscopy with biopsy (where Helicobacter Pylori may be ditectly pointed out) or by indirect tests (the ideal one being the respiratory test, or possibly the evidence of Helicobacter Pylori in the stool).
3. Endoscopic treatment – endoscopic hemostasis
Hemostasis by injecting adrenaline 1/10.000 or sclerosant agents (etoxysclerol or even alcohol 90%) determines the stopping of hemorrhage by their vasoconstrictor effect and by compressive mechanic effect, resulted by injection.
Plasma photocoagulation with argon or laser produces a hemostasis by contact coagulation, up to a depth of 3-4 mm. It is used mostly in the diffuse bleedings.
The Rockall Score’is an externally validated mortality risk assessment score for patients admitted with upper gastrointestinal bleeding. It is simple and practical to use, helping identify those at highest risk of dying and needing active intervention. It also identifies those for safe, early discharge (initial score 0, final 2). The Rockall score quantifies the following parameters : age, pulse, systolic blood pressure, co-morbidity and endoscopic findings.
The endoscopic dilatation of pyloric stenosis may be made with small pneumatic balloons or sparking plugs, thus avoiding the trauma of a surgical intervention.
Mucosectomia of gastric ulcerous lesions with dysplasia or even with gastric cancer “in situ” is a method in full expansion, introduced by Japanese endoscopists, which allows the whole excision of premalignant or malignant lesions “in situ”. It has the advantage of avoiding the trauma of surgical intervention, but requires a precise preinterventional staging by echoendoscopy.
4. Surgical treatment
The indications are even more limited: hemorrhages that cannot be stopped endoscopically or pyloric stenosis that cannot be dilated endoscopically. The perforation and penetration are of course absolute indications for surgical intervention.
Definition of gastric-duodenal ulcer
Gastric ulcer and duodenal ulcer represent limited interruptions, unique or multiple of the gastro-duodenal wall continuity, accompanied by a fibrous reaction, penetrating through the mucosa, submucosa and even to the serosa.
Peptic ulcer epidemiology
The clinical prevalence is 5-10% of the population. The real prevalence, based on necroptic studies, is 20-30% in men and 10-20% in women. Nowadays there is an important decreasing tendency of the disease prevalence.
Gastro-duodenal ulcer etiopathogenesis
Approximately 10% of the adult population suffers or have suffered from gastro-duodenal ulcer. Helicobacter Pylori-this germ affecting over 2 billions of people! The infection is produced via faecal-oral or possibly oral-oral.
The Helicobacter Pylori acute infection manifests it self like an acute gastroduodenitis, with self-limited evolution. There remains a chronic gastritis, which will be involved in the ulcer genesis. In case of antral gastritis(inflammation), this will lead to the increase of gastrin secretion and implicitly to acid hypersecretion. As a response to the acid secretory excess, which will get into the duoden, a gastric metaplasia will appear into the duodenum, a compulsory stage in the duodenal ulcerogenesis. In case of gastric body gastritis, this will lower the mucosal resistance to the aggressive factors, thus generating gastric ulcer. The prevalence of Helicobacter Pylori infection in duodenal ulcer is 90-95% and approximately 70-80% in the gastric ulcer.
Gastric and duodenal ulcer physiopathology
A. Aggressive factors.
They are increased in the peptic ulcer genesis. There are three important aggressive factors.
1. The Helicobacter Pylori infection
The most probable mechanism of transmission is faecal-oral, the source of infection in the underdeveloped countries being the water. Its location in the stomach is between the apical membrane and the mucus layer, thus it is well adapted to the acid stomach environment. Its pathogenetic factors are the enzymes and cytotoxines secreted:urease(eliminating ammonia, which creates an alkaline pH, phospholipase and protease(digest the mucus and gastric and duodenal apical mucosa), the vacuolising cytotoxin.
Ulcerogenesis induced by Helicobacter Pylori is by direct action on the gastroduodenal mucosa and indirectly by increasing the clorhidropeptic secretion. The direct mechanism is determined by the inflammatory process initiated by Helicobacter Pylori toxins, which induces an acute gastritis that becomes chronic subsequently. Helicobacter Pylori does not grow on the duodenal mucosa, but only on the islands of gastric metaplasia in the duoden; these appear as a protection mucosal reaction to the increasing acid secretion. The indirect mechanism of Helicobacter Pylori is realized by the urease secretion which creates an alkaline environment around the gastrin secretory cells, thus stimulating the gastrin secretion and so the hypersecretion.
2. The clorhydropeptic hypersecretion
Neither gastric ulcer nor duodenal ulcer can appear without acid secretion, with a higher role in duodenal ulcer. The most importante causes of HCl hypersecretion are: the increasing in number of secretory parietal cells by a genetic mechanism or by hypergastrinemia; the vagal hipertony; the hypersensitivity of parietal cells to vagal stimuli; gastric motility disorders(grown up in duodenal ulcer; with a permanent flux of acid into the duoden, and low in gastric ulcer with gastric stasis).
In addition to the increasing of HCl secretion, pepsin.
3. Billiary acids
They represent another aggressive factor, with ulcerogenous effect by the detergent mechanism on the lipids in the mucosal cells.
B.Defensive factors.
They are low in the ulcer disease, especially in gastric ulcer.Didactically, they are topographically grouped in three:
1. Preepithelial, represented by:
- surface mucus,important in gastric and duodenal mucosal defense,forming a viscous “unshaken” insolubre mucus gel layer, opposed to the retro diffusion of H ions, and lubricating the mucosa;
- bicarbonate ions secreted, which create a neutral pH gradient (7) compared to the acid pH (1-2)in the gastric lumen.
2. Epithelial, represented by the integrity of apical membrane of gastroduodenal mucosa.
3. Postepithelial – vascular, the capillaries having a nutritive role (they bring bicarbonate ions and take away H+ ions).
C. Environmental and individual factors:
Environmental factors, which are considered ulcerogeneous, are:
cigarette smoking by lowering the pancreatic alkaline secretion and canceling the inhibiting mechanisms of acid secretion;
drugs with ulcerogenous potential: aspirin and NSAIDS
other factors: stress, chronic alcohol intake and different alimentary diets.
Individual factors are genetic; there is definite proof of familial aggregation and the existence of genetic markers.
Diagnosis of gastro-duodenal ulcer
The clinical diagnosis. The characteristic pain, linked to food intake (“painful hunger” in duodenal ulcer), the apparition of pain mostly in spring and autumn are typical signs that may suggest an ulcer. However, lately, ulcers discovered endoscopically in the absence of typical symptoms have been reported more and more frequently. Other times, the onset may be dramatic, by a superior digestive hemorrhage (hematemesis and/or melena) or an ulcerous perforation.
Pain is the cardinal symptom in ulcer.
Other symptoms :
- vomiting
- abdominal indigestion
- weight loss
- fatigue
Paraclinic diagnosis is established by endoscopy (gastroduodenoscopy). In the same time, endoscopy allows the biopsy in gastric ulcer, which will show the benign or malignant character of the ulcerous crater. It also evaluates the healing of the ulcer, by proving the scar.
The X-ray
Helicobacter Pylori detection - causal agent in most gastroduodenal ulcers, is a compulsory diagnostic element in the strategy of ulcer evaluation, having as a purpose a subsequent therapeutic attitude. The Helicobacter Pylori detection is made by direct and methods:
- direct methods require endoscopy with obtaining a series of gastric biopsies from which Helicobacter Pylori is histological determined by urease test (based on the changing of a pH indicator color in the presence of Helicobacter Pylori which produces a high quantity of urease), or by culture on special media-in microaerophile medium).
- indirect methods: determination of antibodies anti Helicobacter Pylori in serum or blood or the respiratory tests. The anti Helicobacter Pylori antibodies may be determined also in the saliva and the eradication of Helicobacter Pylori infection may be more recently determined by the bacteria detection in stool.
Differential diagnosis
Based on the clinical symptomatology, the differential diagnosis of gastroduodenal ulcer must be done with other sufferings of the upper abdomen, such as gastric neoplasia, gastric lymphoma (diagnosed compulsory by endoscopy with biopsy), gallstones (diagnosed by ultrasonography), chronic pancreatitis or functional dyspepsia – (“ulcer-like”).
The endoscopic differentiation of a gastric ulcer must be done with an ulcerated neoplasm, which makes the prelevation of biopsies compulsory in every gastric ulcer, at diagnosis and at healing check-out.
Evolution of gastro-duodenal ulcer
The evolution of gastroduodenal ulcer has sensitively improved, thanks to the apparition of new antisecretory drugs extremely potent (H2 blockers or H+ K+ ATP-ase pump blockers); the evolution is favorable in most cases, the complications have been reduced, and the cases requiring surgery are relatively rare. In addition the introduction of anti-Helicobacter Pylori therapy has brought to a maximal decreasing of ulcerous recurrences.
Complications
- superior digestive hemorrhage (hematemesis and/or melena).
- ulcerous perforation with acute abdomen picture. Penetration is a covered perforation in the neighbor organs.
- pyloric stenosis
- ulcer malignization (possible in gastric ulcer, but never in the duodenal ulcer).
Prognosis
Ulcerous disease prognosis has improved a lot in the last decades, and mostly in the last decade,when, by a correct therapy of Helicobacter Pylori eradication, the risk of ulcerous recurrence has decreased fewer that 10% / year,compared to an annual recurrence of over 70% in the absence of Helicobacter Pylori eradication. The, mortality in ulcerous disease is increased mostly in the patients aged over 75 years with superior digestive hemorrhage.
