Gastroenterologylecture II-2Irritable Bowel SyndromeMalabsorbtion SyndromInflammation Bowel Disease

Clinical anatomy and physiology of small and large intestineFunctions:digestionabsorptionexcretionmotility

Calcium MagnesiumIronMonosaccharides

Water-soluble vitamins

Vitamin B12

Electrolytes StomachSmall intestineLarge intestineBile Pancreatic enzymesOil-soluble vitamins

Amino acids

Fatty acids

Bile acids

Wather

Visceral sensytivity - Serotonin - Calcitonin - Neurokinin A - EnkephalinSecretion - Serotonin - Acetylcholine

Motility - Serotonin - Acetylcholine - Nitric oxide - Substance C - Vasoactive intestinal peptide - CholecystokininSerotonin is the main neuromediator that regulates the gut activity

Cardinal symptoms of lower part of gastrointestinal tract disorders

SymptomsSyndromesDiseasesDiarrheaConstipationAnorexiaWeight lossAbdominal pain BloatingMeteorism

Syndrome of intestinal dyspepsiaMaldigestion syndromeMalabsorbtion syndromeBleeding from lower part of GI tractAcute abdomenIrritable bowl syndromeCeliaciaWhipples diseaseLactase insufficiencyInflammatory bowl diseases: Crones disease Ulcerative colitis

DiarrheaTransit of soft stools with a lot of fluid> 3 times per day Imperative demand of defecation

Without blood or mucus

Without tenesmus

Polyfecalia but not very frequentA touch of blood or mucus

Tenesmus

Stool is frequent but with small portionssmall intestinelarge intestineDiarrhea

Diarrhea: types, etiology, pathogenesisAcute (up to 1-2 weeks)Food poisoning (due for microbs or not)Bacterial infections: E.coli, Shigella, Salmonella, Campylobacter, Yersinia Viral infections: RotavirusProtozoan infections: Entamoeba, Giardia lamblia Drugs:antibiotics (l.deficile)laxativesantacids (Mg)anticholinesterase drugscolchicinpreparations with Auquinidinecardiac glycosides

Chronic (> 4 weeks)

Osmotic diarrhea (osmotic laxatives and lactose)Secretory diarrhea (bacterial toxins, hormones, fatty and bile acids, laxatives)Inflammatory diarrhea (infections, inflammatory bowl diseases, celiacia, lymphoma, iscemia)Hypermotoric diarrhea (irritated bowl syndrome)

Diagnosis of diarrheaIf chronic full investigation in every caseAcute investigation is indicated if there are signs of anxiety or special anamnesis' dataPlan of investigation depend on anamnesis data

Symptoms >48 hours Severe pain Body temperature >38,9 Blood or helminthes in stool Signs of dehydration (dry mouth, thirst, reduction of skin turgor, oligo- or anuria, vertigo)Signs of anxiety

Principles of treatment of diarrheaElimination of the causeCorrection of water and electrolytes disordersIn some cases - antidiarrheal agents

Diagnostic criteria of constipation

1) 2 or more of criteria listed below:Straining efforts in course of defecation at least in 25% of defecationsSolid stool at least in 25% of defecationsFeeling of incomplete evacuation at least in 25% of defecationsFeeling of anorectal obstruction at least in 25% of defecationsNeed in hand manipulation to facilitate the defecation at least in 25% of defecations Less than 3 defecations per week2) Liquid [watery] stool without laxatives a very rare event

Malabsorbtion syndrome

Causes of malabsorptionInadequate digestionReduced intestinal bile salt concentrationInadequate absorptive surfaceLymphatic obstructionCardiovascular disordersPrimary mucosal absorptive defectsBiochemical or genetic abnormalities

Maldigestion syndrome insufficiency of digestionMaldigestion impaired digestion of foodCause enzymes deficiency (congenital or acquired) It may be due to impairment of: luminal digestion, membrane digestion, intracellular digestion, mixed formsClinical manifestation: diarrhea, meteorism, other dyspeptic disordersIt is a component of malabsorption syndrome

Malabsorption syndrome: key pointsMalabsorption - disorder of absorption of one or more nutritive materials in small intestine with impairment of metabolic processes

There are congenital and acquired forms

Intestinal manifestations: diarrhea, polyfecalia, steatorrhea, creatorrhea, amylorrhea

Malabsorption syndrome affects the metabolism of proteins, carbohydrates, fat, vitamins, minerals, water and electrolytes

Malabsorption syndrome: causesPathogenic factors enzimopathy damage of specific transport mechanisms immunologic disorders small intestine bacterial overgrowth motility abnormalities morphologic changes of mucose

Enterogenic enteritis, Crones disease, infections, parasites, ischemia Gastrogenic peptic ulcer, gastritis, cancer Pancreatogenic pancreatitis, mucoviscidosis, tumors Hepatogenic acute and chronic liver diseases Postresection stateEndocrinogenic DM, disthyreosis Drugs Radiation

ASSESTMENT OF THE NUTRITIONAL STATEGross malnutrition is usually easy to recognizeLesser degrees may be difficult to detect, particularly if oedema is presentMalnutrition may be due to starvation, to maldigestion of food or to malabsorption

WAYS TO ASSESS THE NUTRITIONAL STATEThe clinical history The physical examinationMore subtle indices of malnutrition include muscle function tests and evaluation of creatinine excretion and levels of albumin, hemoglobin, ferritin and iron-binding capacity, prothrombin time

Diagnosis of malabsorptionBlood tests detection of nutrients deficiency albumin, cholesterol, iron, calcium, magnesium, vitamin A, folic acid

Stool tests steatorrhea, creatorrhea, amylorrhea, 500 g/day), amount of fat in stool >6 g/day

Assessment of absorption function with specific testsabsorption test with D-xiloseSchilling test

Instrumental methodsX-ray investigation of small intestine abdominal ultrasound endoscopy of small intestine with biopsy

Treatment of malabsorption syndrome1. Treatment of basic disease2. Correction of absorption disorders:Diet with high protein and low fat intake or special nutritionReplacement therapy with vitamins A, D, , , 12, folic acid and iron preparationsenzymesIn case of increased peristalsis loperamid, in sever cases - octreotidbinding and enveloping (smekta and other)

Genetic disease- deficiency of peptidase that hydrolise the protein gluten of cereals (wheat, rye, and barley)

Accumulation of gluten and gliadin autoimmune inflamation death of villi and damage of intestine mucosa

Clinical picture: malabsorption. Commonly minimal signs: osteoporosis, anemia without gastrointestinal manifestations

Diagnosis: biopsy of small intestineserological tests: antibodies to gliadin, endomiosin, reticulinTreatment: aglutenic diet, in sever cases - glucocorticoides

Celiac disease (gluten enteropathy): key points

Celiac diseasebiopsy of small intestinenormalpathology

Whipples diseaseFirst described in 1907

Etiology: Tropheryma Whipplei [trophi (nutrition) eryma (barier)], first successful culture was received in 2000.

Prevalence: a rare disease, male:female8:1, mean age 50

Clinical manifestations: malabsorption syndrome, diarrhea, weight loss, fever, arthritis and arthralgias, cardiac involvment

Diagnosis: biopsy of small intestine. Specific sign infiltration of mucosa with big macrophages with SHIK-positive granules. In the cells - T. Whipplei.

Treatment: antibiotics

Whipples disease

Functional bowl disorders Functional meteorism Functional constipation Functional diarrhea Irritable bowl syndrome Undifferentiated functional bowl disorders

Irritable Bowel

Syndrome

Irritable bowel syndrome IBS has probably existed for a long time and under many names. There is increasing awareness of its importance in the community, family practice, and gastroenterology.IBS is not a disorder defined by an unequivocal pathophysiology or a uniform clinical presentation. The definition of IBS is based on the clinician recognizing a frequently occurring symptom cluster. The general acceptance of that cluster has been formalized in consensus conferences, creating the regulary updated 'Rome criteria'.

Etiopathogenesis of IBS: evolutionMecanismsMotilityVisceral hypersensitivityInflammationInteractions brain-intestineMioelectric markers200019501960197019801990Sensation of painStress disorders of GISGroup contractionAutonomic reactivityCharacter of nutritionPain/motilityVisceral hypersensitivityPostinfectional IBS

Irritable Bowl syndromePrevalence15% of adult populationEtiology not clear

Visceral hypersensitivity Motility disorder Neurotransmitter inbalance Infection Psychosocial factors

Interaction gut brain results in reflex responses : prevertebral ganglia spinal cord brainstem limbic system .

Neurotransmitters : serotonin, substance , norepinephrine, NO.

Physiology of sensation in the gut

Ascending pain pathwayVisceraBrain stemSpinal cordDorsal root ganglionVisceral Sensitivity in IBSPain

Diagnostic criteria of IBSRome criteria III (2006 .)Recurrent abdominal pains or discomfort:3 days per month 3 previous months+Any 2 or more of down listed criteria:

Relief after defecation; and/or

Start is associated with changed frequency of stool; and/or

Start is associated with changed consistency of stool* Presence of named criteria during last 3 months, if first manifestation appeared 6 months before diagnosis

Clinical variants of IBS

pain syndrome + diarrhea

pain syndrome + constipation

pain syndrome + diarrhea / constipation

Diarrhea &painConstipation &painDiarrhea, constipation &pain

Abdominal pain and discomfort usually not localized, variableChange of frequency and/or character of stool bloating urgencyfeeling of incomplete evacuationmucous in the stool

chest pain, headacheheartburnnausea or dyspepsiadifficult swallowingsensation of a lump in the throatIBS: clinical manifestations

Red FlagsAnemiaFeverPersistent diarrheaRectal bleedingSevere constipationWeight lossAdditional diagnostic screening needed for atypical presentations such as:Nocturnal symptoms of pain and abnormal bowel functionFamily history of GI cancer, inflammatory bowel disease, or celiac diseaseNew onset of symptoms in patients 50+ years of age

Differential DiagnosisInflammatory bowel diseaseInfection (Giardia lamblia ) Peptic ulcer diseaseMotility disordersChronic pancreatitisMalabsorption/Bacterial OvergrowthGynecological disorders

Management of IBS

Positive diagnosis of the syndrome, exclusion of organic disordersLife style modification fibers consumption, change of nutrition character, assessment of patients psychological statusSymptomatic therapyAntagonists/agonists of serotoninergic receptorsAlternative therapyAnti-diarrhealsAlosetron (Lotronecs)(in case of diarrhea)HypnotherapyLaxativesTegaserod (Zelnorm)(in case of constipation)Holistic therapyAntispasmodics Correction cognitive changesAciolitics Antidepressants

A general term for a group of chronic inflammatory disorders of unknown cause involving the gastrointestinal tract.

may be divided into two major groups chronic nonspecific ulcerative colitis (UC) Crohn's disease (CD)While the occurrence of both diseases peaks between the ages of 15 and 35, they have been reported from every decade of life.While the causes of UC and CD remain unknown, certain features of these diseases have suggested several areas of possible importance. These include familial or genetic, infectious, immunologic, and psychological factorsInflammatory bowel disease (IBD)

Inflammatory bowel diseaseNonspecific ulcerative colitis (UC)Crohns disease (CD) Nonspecific ulcerative colitisCrohns disease

Colitis of unknown etiology

PathogenesisEtiology is unknownGenetic and immunological factors lead to abnormalities in recognizing auto antigens in GIT

Crohns diseaseNonspecific ulcerative colitis

Ulcerative colitisCrohns diseaseLocalization of damageVolume of damageDepth of damage

Ulcerative colitisComplications: Toxic megacolon (dilation of the gut with thinning of gut wall, high risk of perforation) Large intestine carcinoma (constant regeneration of epithelium---> displasia). Chronic diffuse inflammation of large intestine with edema and superficial ulceration of mucosa Starts always from damage of rectum, and than the process involves other parts of large intestine

Symptoms: rectal bleeding, fever, diarrhea, abdominal pain, moderate anemia.

Crohns diseaseChronic granulematose (in some cases transmural) inflammation of the gut wall of unknown originDamage may be localized in any part of GIT from oral cavity up to anus, damaged areas, crypt abscesses 45%: terminal ilea involvement and larg intestine33%: small intestine25%: large intestineSymptoms: abdominal pain, diarrhea, feverComplications: Strictures, fistulasPerforation Gall bladder stones (abnormalities of bile acids absorption) Hydronephrosis (adhesion of ureter to stricture) Adenocarcinoma of large intestine, anal zone)

Extraintestinal manifestations of inflammatory diseases of intestine

Differential diagnosis of IBD

CDUCAbdominal pain++++Trasmural damage++Granulomas++-Cobblestoning mucosa+++Asymmetria+++Involvement of ilea+++Rectal damage20%100%Rectal bleeding50%++Strictures, fistulas+++Crypt abscesses+++-

Treatment of IBDIncrease of agressionExperimental treatment (IL 10, azathioprin iv)Inhibitor of tumor necrosis factor (TNF )CytostaticsCorticosteroidsAntibioticsSulfonamides, salysilates

- , . , , , . . . . *1. Postgastrectomy steatorrheaDeficiency or inactivation of pancreatic lipaseExocrine pancreatic insufficiency2. Liver diseaseParenchymal liver diseaseCholestasis (intrahepatic or extrahepatic)Abnormal bacterial proliferation in the small bowel , , , . (, , .), ( ), . ( , , .) , (, , ) (, ), (, .) . () , , , . , , , . , . : : , ( , ), , ( , ), ( , , , ), (, ) [2]. , . , , , -, , , - . , (, , ), , -. - . , ( I , , , , ), - , .

D-: 5 per os (25 ). 5 , 5

Celiac disease is a digestive disease that damages the small intestine and interferes with absorption of nutrients from food. People who have celiac disease cannot tolerate a protein called gluten, found in wheat, rye, and barley. When people with celiac disease eat foods or use products containing gluten, their immune system responds by damaging the small intestine. Without healthy villi, a person becomes malnourished, regardless of the quantity of food eaten. Celiac disease is a genetic disease. Sometimes the disease is triggeredor becomes active for the first timeafter surgery, pregnancy,childbirth, viral infection, or severe emotional stress.

*Although Whipples disease was first described in 1907,1 the first successful culture of T. whipplei was performed nearly a century later, in 2000. Whipples disease is in the differential diagnosis for a wide spectrum of diseases that includes inflammatory rheumatic diseases, malabsorption with small-intestine involvement (celiac disease, sarcoidosis, and lymphoma), Addisons disease, connective tissue diseases, and a variety of neurologic diseases. The most common gastrointestinal symptom of classic Whipples disease is weight loss, often associated with diarrhea. Joint involvement has been reported in 65 to 90% of patients with classic Whipples disease. The presenting symptom in most patients with joint involvement is intermittentmigratory arthralgia, arthritis, or both.Polyarthritis is most common, but oligoarthritis may occur. Neurologic involvement has been reported in6 to 63% of patients with classic Whipples disease. Cardiac involvement has been reported in a wide range of patients with classic Whipples disease (17 to 55%).T. whipplei might be acquired through fecaloral transmission. , , . . . . - , - . - T. Whipplei. - , , .

*Colonic and rectal hypersensitivity (also called visceral hyperalgesia) are also important factors in the causation of symptoms. Enteric propulsion and sensation are, in part, mediated by acetylcholine and serotonin (5HT). The physiology of sensation in the gut is multifaceted. Enteroendocrine cells transmit mechanical and chemical messages. The communication between gut and brain results in reflex responses mediated at three response to visceral stimulation (Figure 5). Sensation is conveyed from the viscus to the conscious perception via neurons in vagal and parasympathelevelsprevertebral ganglia, spinal cord and brainstem. 5-HT, substance P, CGRP, norepinephrine, kappa opiate and nitric oxide are all involved in the perception and autonomic tic fibers. Afferent nerves in the dorsal root ganglion synapse with neurons in the dorsal horn. These signals result in reflexes that control motor and secretory functions as they synapse with efferent paths in the prevertebral ganglia and spinal cord. Pain is processed through spinal afferents in the dorsal horn. Ultimately, stimulation of the brainstem brings sensation to a conscious level (Figure 6). Bidirectional signaling between the brainstem and the dorsal horn mediate sensation. The descending pathways are primarily adrenergic and serotonergic and affect incoming stimuli. End organ sensitivity, stimulus intensity changes or receptive field size of the dorsal horn neuron and limbic system modulation are the mechanisms involved in visceral hypersensitivity. Enteric inflammatory cells may also play an important role in the pathophysiology of Irritable Bowel Syndrome. Clinicians have for many years recognized that the onset of IBS often follows an episode of acute gastroenteritis. Inflammation may alter intestinal cytokine milieu and motility, both of which can result in an increase in a patients pain sensation. The menstrual cycle may also affect gut sensation and motility. Other factors, such as malabsorption of sugars (lactose, fructose, and sorbitol), probably aggravate underlying IBS, rather than serving as root causes of the disorder. In patients with rapid transit times, short or medium chain fatty acids can reach the right colon and cause diarrhea. **Visceral hypersensitivity is now well-accepted as the biological marker for IBSIt is important to note that this hypersensitivity is not site specificIBS patients also have heightened sensitivity to distension of other areas of the gut including the esophagus, stomach, and small bowelSensory signals (pain) originating in the viscera are received at nerve endings of primary sensory neurons in the gutThe signal travels through the cell bodies of sensory neurons in the dorsal root ganglion and terminates in the spinal cord The signal is further processed and relayed along ascending pain pathways to the brainThe hallmark of IBS is abdominal pain or discomfort associated with either a change in bowel habits or disordered defecation. The pain or discomfort associated with IBS is often poorly localized and may be migratory and variable. It may occur after a meal, during stress or at the time of menses. In addition to pain and discomfort, altered bowel habits are common, including diarrhea, constipation, and diarrhea alternating with constipation. Patients also complain of bloating or abdominal distension, mucous in the stool, urgency, and a feeling of incomplete evacuation. Some patients describe frequent episodes, whereas others describe long symptom-free periods. Patients with irritable bowel frequently report symptoms of other functional gastrointestinal disorders as well, including chest pain, heartburn, nausea or dyspepsia, difficulty swallowing, or a sensation of a lump in the throat or closing of the throat **To rule out alternative or coexisting disease, there are some red flags that may appear either during the intake or physical exam that would suggest a condition other than IBS.

*The following categories should be considered in the differential diagnosis of recurrent abdominal discomfort and bowel dysfunction. Malabsorptive conditions, such as postgastrectomy, intestinal diseases (e.g., sprue), or pancreatic insufficiency. These conditions may cause cramps and/or diarrhea.1Dietary factors, such as lactose (in lactose-intolerant patients), caffeine, alcohol, and fat-containing or gas-producing (e.g., cruciferous vegetables) foods. Some foods may act as triggers and may therefore cause and/or intensify symptoms.2 Infections due to bacteria (e.g., Campylobacter jejuni, Salmonella spp) or common parasites like Giardia lamblia.1Inflammatory bowel disease, like Crohns disease or ulcerative colitis. Symptoms of these diseases can often mimic those of IBS. Other less common microscopic colitides such as collagenous colitis or mast-cell disease can be diagnosed by colonic biopsy.1Psychological disorders, including panic disorder, depression, and somatization. These disorders may be associated with an increase in symptom reporting.1 Miscellaneous conditions, including gynecological conditions such as endometriosis or dysmenorrhea,3 as well as endocrine tumors (e.g., carcinoid, Zollinger-Ellison syndrome, VIPoma) and HIV disease and other associated infections.1

Management of patients with Irritable Bowel Syndrome is based on a positive diagnosis of the syndrome, exclusion of organic disorders, and specific therapies. Treatment for IBS should address the three main pathophysiologically important factorspsychosocial disturbances, visceral hypersensitivity, and dysmotility. Treatment should be patient oriented and geared towards symptom specific relief. The majority of conventional IBS treatments currently used is empiric and has not been formally reviewed and approved by the FDA. Therapies may include fiber consumption for constipation, anti-diarrheals, smooth muscle relaxants for pain, and psychotropic agents for pain, diarrhea and depression. Female patients with diarrhea predominant-IBS may benefit from alosetron, a new 5-HT3 agonist, while female patients with constipation predominant-IBS may benefit from Tegaserod Maleate, a partial 5HT4 agonist. Patients with mild or infrequent symptoms may benefit from the establishment of a physician-patient relationship, patient education and reassurance, dietary modification, and simple measures such as fiber consumption. Patients with constipation-predominant IBS can generally be treated with osmotic mild laxatives such as Milk of Magnesia. Stronger laxatives should be reserved for patients who do not respond to fiber consumption and gentle osmotic laxatives.*Adenocarcin Immune-mediated complications:

: , , , There are, however, important pathological and clinical differences that distinguish these inflammatory disease processes. Clinically, Crohn's disease tends to present more frequently with abdominal pain and perianal disease, whereas ulcerative colitis is more often characterized by gastrointestinal bleeding. ents with Crohns disease characteristically show fistulae, asymmetry, and ileal involvement. In contrast, radiographic studies of patients with ulcerative colitis show continuous disease without fistulizing or ileal disease. Pathologically, Crohn's disease features mucosal discontinuity, transmural involvement, and granulomas, whereas ulcerative colitis does not. Crypt abscesses and granulomas are present only in Crohn's disease. Figure 3 compares the anatomic distribution of Crohns disease and ulcerative colitis.