07 diarrea

Fisiopatologia 7) DIARREA Antonio Nenna

DIARREA Diarrea = emissione di feci semisolide o liquide, con frequenza aumentata, di peso maggiore a 200g/24h diarrea acuta: meno di 2 settimane, causa acuta, generalmente autorisolvente diarrea persistente: tra 2 e 4 settimane, esito di acuta o fase iniziale di cronica diarrea cronica: più di 4 settimane, cause croniche, non autorisolvente In caso di feci semisolide o liquide, ma con peso inferiore a 200g/24h: - pseudodiarrea (“proctite”, infiammazione del retto; s. del colon irritabile) - incontinenza fecale (neuromuscolare da diabete; trauma) - sindrome da iperafflusso di feci (ritardo l’alvo => massivo riassorbimento di acqua => fecaloma => occlu-sione intestinale => emissione espulsiva dopo la rimozione del fecaloma)

DIARREA ACUTA E’ pericolosa poichè spesso bambini e anziani si disidratano, e possono avere IRA prerenale da ipovolemia. - agenti infettivi virali (adenovirus,...) => autorisolvente - agenti infettivi non virali (antibiotici, antipertensivi, FANS, antidepressivi, antineoplastici, lassativi,...) - colite ischemica [infarto intestinale] (dolore crampiforme, rettorragia) - diverticolite acuta [m. diverticolare del colon] (dolore, febbre, diarrea) - rigetto d’organo - tossine (insetticidi, amanita, arsenico, frutti di mare)

DIARREA CRONICA Classificazione:

diarrea funzionale [basso volume delle feci] [s. del colon irritabile]

diarrea organica [alto volume delle feci] o secretoria (gli enterociti secernono acqua) o osmotica (le feci riassorbono acqua)

Inizialmente metto il pz in una dieta senza lattosio, poichè la diarrea (organica) può essere causata dal defi-cit della lattasi, frequente negli adulti per inattivazione genica o per infezione virale. Se la diarrea persiste, è necessario trovare la causa. La diarrea organica è suggerita da (almeno tre criteri, altrimenti è funzionale): - durata inferiore a tre mesi - diarrea prevalentemente notturna - diarrea continua [la diarrea funzionale è intermittente] - esordio improvviso - perdita di almeno 5 kg dall’esordio - indici di flogosi aumentati (VES, anemia normocromica normocitica, ipoalbuminemia) - peso fecale maggiore di 400g/24h. Steatorrea: feci untuose, odore cattivo. Si mette il pz a dieta con 80-100g di lipidi (dieta normale) e valuto i grassi eliminati. Il coeff di assorbimento intestinale di grassi è 95%. Normalmente, a livello basale, vengono eliminati 2g di lipidi al giorno per lo sfaldamento degli enterociti. Quindi, in una dieta normale si hanno:

di lipidi nelle feci

Con lipidi maggiori di 14g/24h => steatorrea


Cause di diarrea cronica organica:

infezioni croniche o recidivanti del tratto gastrointestinale o virali => autorisolventi o jardia => dolore in epigastrio, feci schiumose o clostridium difficile (per riattivazione antibiotico-dipendente) o amebiasi => sangue nelle feci, inibita dal bario usato per il clisma del colon

malattie infiammatorie intestinali (IBD) o m. di Crohn (ileite terminale) => sangue, muco o retto-colite-ulcerosa (RCU) => sangue, muco o colite collagenosa o colite linfocitica

steatorrea [feci untuose, odore cattivo] o pancreatite cronica (pz alcolista) => aumento delle lipasi pancreatiche

malassorbimento dei carboidrati o deficit di lattasi o disaccaridasi => pH feci < 5,3 (diarrea da zuccheri)

diarrea da farmaci (antibiotici) o modifica della flora batterica intestinale, con minore riassorbimento di acqua. Se smetto

l’antibiotico, termina la diarrea. L’antibiotico inibisce la formazione della flora batterica intestina-le, e questa non può trasformare i carboidrati in acidi grassi a catena breve (che verranno poi rias-sorbiti). Si accumulano carboidrati, che richiamano acqua per osmosi, causando la diarrea osmoti-ca. Si ha quindi diarrea osmotica da malassorbimento per eliminazione della flora batterica. La pa-togenesi è analoga alla diarrea da intolleranza ai carboidrati (deficit di lattasi, disaccaridasi,...)

o modifica della flora batterica intestinale, con riattivazione del Clostridium difficile. Il C.difficile è una frequente infezione ospedaliera; il pz può avere una infezione latente che viene risvegliata dall’antibiotico. Se smetto l’antibiotico, non termina la diarrea (poichè è dovuta ad un batterio pa-togeno presente). Sono presenti segni e sintomi della colite pseudomembranosa.

interventi chirurgici o colecistectomia => meno bile, meno superficie di azione della lipasi, grassi non digeriti formano un

corpo osmotico, steatorrea o gastrectomia => passaggio troppo veloce da esofago a intestino o colectomia => sindrome da intestino corto

resezione intestinale maggiore di 1 m => minore superficie di assorbimento, minore tempo di transito, minore riassorbimento degli acidi biliari, minor pool di acidi biliari => diarrea osmotica, steatorrea, non responsiva alla colestiramina (resina che riassorbe gli acidi bilia-ri), feci maggiori di 1000g/24h con rischio di IRA prerenale da ipovolemia

resezione intestinale minore di 1 m => malassorbimento di acidi biliari, secrezione di acqua ed elettroliti per osmosi => diarrea osmotica da acidi biliari, postprandiale, responsiva alla colestiramina e al test del digiuno, feci di 300g/24h, pH > 6,8 (diarrea da lipidi)

endocrinopatie o ghiandola surrenale

feocromocitoma (eccesso di adrenalina, ipertensione arteriosa grave 200/120, ipotensione ortostatica per ipovolemia)

m. di Addison (insufficienza di aldosterone, perdita di acqua e sodio per l’azione sulla pom-pa sodio-potassio degli enterociti)

o tiroide ipertiroidismo (diarrea secretoria) ipotiroidismo (diarrea osmotica)

o pancreas diabete mellito (causa neuropatia viscerale che dà stipsi o diarrea)


abuso di lassativi o diarrea voluta/provocata (bambino che non vuole andare a scuola) o disordine alimentare (anoressia, bulimia) o isteria o disordine dell’emotività o s. di Munchausen o s. di Polle

malattia ischemica intestinale

colite attinica

diarrea paradossa

tumori ormonosecernenti o gastrinoma => tumore secernente gastrina, dà ulcere recidivanti come la s. di Zollinger-Ellison, di-

spepsia ulcerosa alleviata da alimenti e antiacidi o vipoma => tumore secernente VIP, s. di Verner-Morrison (colera pancreatico), ipokaliemia, acidosi

metabolica non-AG, rischio di IRA, fino a 20 litri di feci al giorno (più di 3 litri in media) o adenoma villoso del retto e del colon sinistro (PGE2) o carcinoma midollare della tiroide (calcitonina) o carcinoide (fegato, tenue, bronchi) (rash, flush, diarrea) o mastocitosi (5HIAA)

disordini infiltrativi o amiloidosi => deposito nei tessuti di placche amiloidi, simili alle Ig (analogia con mieloma), che si

colorano in rossoCongo; causa ectasie, che portano a emorragie sottocutanee e macchie rosse sulle guance (faccia da procione), albuminuria, neuropatia (paraparesi), insufficienza cardiaca, diarrea

o slerodermia

diarrea cronica epidemica (acqua infetta)

diarrea idiopatica

incontinenza fecale grave

allergia alimentare

VALUTAZIONE DEL PAZIENTE CON DIARREA CRONICA 1) storia + EO + out-patient (ambulatoriale) liv. 1 2) out-patient liv. 2 3) in-patient (ricovero) VALUTAZIONE OUT-PATIENT LIVELLO 1

studi fecali o leucotest: infiammazione (IBD), non infiammazione (vipoma) o ricerca uova e parassiti o pH fecale < 5,3 => diarrea da carboidrati o pH fecale > 6,8 => diarrea da lipidi (steatorrea)

studi ematici o emocromo, VES, elettroliti, BUN, creatinina, TSH, FT3, FT4, gastrina, VIP, sostanza P, calcitonina

studi endoscopici o sigmoidoscopia con biopsia (se sospetto di colite collagenosa o linfocitica)


VALUTAZIONE IN-PATIENT giorno 1: rivalutazione del peso fecale, screening per lassativi, elettroliti, gap osmotico fecale giorno 2-4: “test del digiuno” per 72h (idratazione ev) *d. osmotica non passa, d. secretoria passa+ giorno 5-8: dieta con 100g di grassi per 24h, monitoraggio del grasso fecale TEST DEL DIGIUNO responsivo in caso di: - incontinenza - diarrea da acidi biliari - steatorrea - diarrea osmotica (malassorbimento) - allergia alimentare

non responsivo in caso di: - abuso di lassativi - IBD (celiachia) - colite collagenosa o colite microscopica - linfoma - tumori neuroendocrini - adenoma villoso del sigma - infezioni croniche (ameba, giardia,…) - diarrea congenita (deficit degli scambiatori) - ipertiroidismo

Gap osmotico fecale: 290 – 2*(Na + K)feci Normale: < 45 mOsm (35 mEq/24h) Lassativi: > 50 mOsm


DIARRHEA AND CONSTIPATION1 Worldwide, more than one billion individuals suffer one or more episodes of acute diarrhea per year. About 10% consult physician, 250.000 require hospidalization and 5.000 die. Acute diarrhea remains one of the most common cause of mortality in developing countries, particularly among children. Constipation, by contrast, is rarely associated with mortality and is exceedingly common in developed contries. Even mild symptoms may signal a serious GI lesion, such as colorectal cancer or tyroid disease.

PHYSIOLOGY The intrinsic innervation of the GI is carried by the enteric nervous system, and comprises myenteric, sub-mucosal and mucosal neuronal layers. The modulation is carried through peptides such as Ach, VIP, opioids, epinephrine, serotonine, ATP and NO. The myenteric plexus regulates smooth-muscle function, and the submucosal plexus affects secretion, absorption and mucosal blood flow. The extrinsic innervation is part of the autonomic nervous system. The parasympathetic nerves convey vis-ceral sensory and excitatory pathways to the colon. Parasympathetic fibers via the vagus nerve reach the small intestine and proximal colon along the branches of the superior mesenteric artery. The distal colon is supplied by sacral parasympathetic nerves (S2-S4). About 9 L of fluid enter the GI tract; the stool excretion is about 200g/24h. The colon can partially compen-sate for excess fluid delivery to the colon because of intestinal absorptive or secretory disorders. Sodium absorption is predominantly electrogenic, through the Na/K pump. Angiotensin and aldosterone also influence colon absorption, reflecting the common embryologic devel-opment of the distal colon epithelium and the renal tubules. Diarrhea and constipation may result from alteration in the reservoir function of the proximal colon or the propulsive function of the left colon. Constipation may result also from disturbances of the rectal or sigmo-id reservoir, as a result of a dysfunction of the pelvic floor. After meal ingestion, colon phasic and tonic contractility increase for about 2h. The initial phase is me-diated by the vagus nerve in response to mechanical distention of the stomach. The subsequent response of the colon requires hormones (gastrin, serotonin). DEFECATION: tonic contraction of the puborectalis muscle, which form a sling around the anorectal junc-tion, is important to maintain continence; during defecation, sacral parasympathetic nerves relax this mus-cle, facilitating the straightening of the anorectal angle. Distention of the rectum results in transient relaxa-tion of the internal anal sphincter via intrinsic and reflex sympathetic innervation. Rectal contraction increases the pressure within the rectum, and the rectosigmoid angle passes from 80° to 140°, the pelvic floor muscles (including the puborectal) relax, and the perineum descends by 1-3 cm. The external anal sphincter relaxes voluntarily (striated muscle is innervated by the pudendal nerve) in re-sponse to the distention and reduces pressure on the anal canal, permitting the evacuation of the feces. This evacuation process can be augmented by an increase in the abdominal pressure created by Valsalva maneuver. Defecation can also be delayed by contraction of the external anal sphincter.

DIARRHEA Diarrhea is the passage of liquid or unformed stools at an increased frequency, more than 200g/24h. With less than 200g/24h, the situation is different from diarrhea: - pseudodiarrhea, frequent passage of small volumes of stool, associated with rectal urgency, is usually as-sociated with IBS or proctitis - fecal incontinence, involuntary discharge of feces, caused by traumatic or neuromuscolar disorder - overflow diarrhea, in nursing home patients due to fecal impaction

1 Diarrhea and Constipation, Harrison, cap. 40


ACUTE DIARRHEA More than 90% of cases of acute diarrhea are caused by infectious agents; these cases are accompained by vomiting, fever and abdominal pain. The remaining 10% are caused by medications, toxins or ischemia. Flu-id and electrolyte replacement are central to all forms of acute diarrhea. Acute diarrhea can also be a major symptom of several systemic infections such as viral hepatitis, listeriosis, legionellosis, toxic shock syndrome. Most episodes of acute diarrhea are mild and self-limited. At microbiologic analysis of stools, workup in-cludes cultures for bacterial and viral pathogens, ova and parasites. Persistent diarrhea is commonly due to Giardia or Clostridium difficile (especially if antibiotics had been administred). A patient usually complains of: - profuse watery diarrhea secondary to bowel hypersecretion - vomiting - fever - abdominal cramping or pain (mimicking acute appendicitis)

INFECTIOUS AGENTS Infectious diarrhea are acquired by fecal-oral transmission or ingestion of contaminated food or water. Res-ident fecal microflora in rarely the source of diarrhea, and usually suppress the growth of ingested patho-gens. Disturbances of the flora by antibiotics can lead to diarrhea by reducing the digestive function or al-lowing the overgrowth of pathogens, such as Clostridium difficile. TRAVELERS. Escherichia coli, Camphylobacter, Shigella, Aeromonas, Salmonella, Giargia, coronavirus FOOD. Salmonella, Camphylobacter, Shigella, enteroemorragic Escherichia coli, Staphylococcus aureus, Ba-cillus cereus, Vibrio, HAV IMMUNODEFICIENTS. Mycobacterium, CMV, HSV, adenovirus, protozoa, Neisseria gonorrhoear, Trepone-ma pallidum, Chlamydia DAYCARE ATTENDEES. Clostridium difficile, Shigella, Giardia, Cryptosporidium, rotavirus

OTHER CAUSES - medications (antibiotics, antidysrhythmics, antihypertensives, NSAIDs, antidepressant, chemotherapic agents, bronchodilators, antiacids, laxatives) - ischemic colitis (occlusive or non-occlusive) - diverticulitis - toxins (insecticides, amanita, arsenic, seafood)

CHRONIC DIARRHEA Diarrhea lasting more than 4 weeks warrants evaluation to exclude serious pathology. In contrast to acute diarrhea, most of the causes of chronic diarrhea are non-infectious. The history, physical examination and routine blood studies should characterize the mechanism of diarr-hea. Patient should be asked about the onset, duration, pattern, aggravating and relieving factors, and stool characteristics. The presence or absence of fecal incontinence, fever, weight loss, pain, certain expo-sures (travel, medications,...) should be noted. The patient must also be put in a lactose-restricted diet. Quantitative stool collection and analyses can yield data for the diagnosis. When suggested by history, screens for peptide hormones should be pursued (gastrin, VIP, calcitonin, TSH, FT3, FT4, histamine). Treatment of chronic diarrhea depends on the specific etiology.

OSMOTIC CAUSES Osmotic diarrhea occurs when ingested, poorly absorbable, osmotically active solutes draw enough fluid into the lumen to exceed the reabsorptive capacity of the colon. Fecal water output increases in proportion to such a solute load. Osmotic diarrhea ceases with fasting or with discontinuing the causative agent. - osmotic laxatives (Mg2+, PO4

3-, SO42-) [with stool anion-gap > 50 mOsm/L]

- enzyme deficiency (lactase, disaccharidase) => elimination of dietary lactose - non-absorbable CHO (sorbitol, lactulose, xilulose)


SECRETORY CAUSES Secretory diarrheas are due to derangements in fluid and electrolyte transport across the enterocolonic mucosa. They are characterised by watery, large-volume feces, typically painless and persist with fasting. - exogenous stimulant laxatives - chronic ethanol ingestion [enterocyte injury with impaired water absorption and rapid transit] - drugs and toxins - idiopathic secretory diarrhea - bacterial infections - bowel resection, disease, fistula [inadequate surface for reabsorption] - bowel obstruction - hormone-producing tumors (carcinoid, VIPoma, medullary cancer of the thyroid, mastocytosis, gastrino-ma, colorectal villous adenoma) [loss of up to 20 L, risk of dehydration; neuromuscolar dysfunction due to associated hypokalemia, hypomagnesemia, hypercalcemia] - Addison’s disease - congenital defects [defective Cl-/HCO3

- exhanger, with alkalosis and defective Na+/H+ exchange]

STEATORRHEAL CAUSES Fat malabsorption may lead to greasy, foul-smelling, difficult-to-flush diarrhea, often associated with weight loss and nutritional deficiencies due to concomitant malabsorption of aminoacids and vitamins. Steatorrhea is defines as stool fat exceeding the normal 7g/24h. - intraluminal maldigestion (pancreatic exocrine insufficiency, bacterial overgrowth, liver disease) - mucosal malabsorption (celiac disease, Whipple’s disease, infections, abetalipoproteinemia, ischemia)

INFLAMMATORY CAUSES Inflammatory diarrheas are accompanied by pain, fever, bleeding and generalised edema. - inflammatory bowel disease, IBD (Crohn’s disease, chronic ulcerative rettocolitis) [uveitis, arthralgias, scle-rosing cholangitis, erythema nodosum] => glucocorticoids, NSAIDs - lymphocitic and collagenous colitis [biopsy needed also for normal-appearing colon] - immune-related mucosal disease (food allergy, eosinophilic gastroenteritis, graft-vs-host disease) - infections (bacteria, virus, parasites, Brainerd diarrhea) - radiation injury

DYSMOTILITY CAUSES - irritable bowel syndrome, IBS [symptoms cease at night, alternate with periods of constipation, abdominal pain relieved by defecation, rarely weight loss] - visceral neuromyopathies (diabetes) - hyperthyroidism

FACTITIAL CAUSES - Munchausen syndrome [self-injury for secondary gain, self-administration of laxatives] - eating disorders (anorexia, bulimia)

IATROGENIC CAUSES - cholecystectomy - ileal resertion - bariatric surgery - vagotomy


CONSTIPATION Constipation is a common compliant in clinical practice, and is difficult to define precisely. Chronic constipation results from inadequate fiber or fluid intake or from disordered colonic transit or ano-rectal function. These result from neurogastroenterologic disturbance, certain drugs, advancing age ro sys-temic disease. Recent-onset constipation: - colon obstruction (neoplasm, ischemic, diverticular, inflammation) - anal sphincter spasm (anal fissure, painful hemorrhoids) Chronic constipation: - irritable bowel syndrome, IBS (alvo alternans) - medications (Ca++blockers, antidepressants) - colon pseudo-obstruction (slow-transit constipation, megacolon, Chagas) - disorders of rectal evacuation (pelvic floor dysfunction, anismus, descending perineum syndrome, rectal mucosal prolapse, rectocele) - endocrinopathies (hypothyroidism, hypercalcemia, pregnancy) - psychiatric disorders (depression, eating disorders) - neurologic disease (parkinsonism, multiple sclerosis) - muscle disease (progressive systemic sclerosis)

07 diarrea

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