l’apparato digerente (parte 1) - castronovo vincent
TRANSCRIPT
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L’apparato digerente
Vincent Castronovo, MD, PhD
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Perché
dobbiamo
mangiare?
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L’apparato digerente
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Digerire bene Sminuzzare gli
alimenti in piccole molecole
Assorbire le piccole molecole
Impedire l’accesso di
1. microrganismi,
2. macromolecole
3. composti tossici.
Le sue funzioni
Digestione
Assorbimento Barriera
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Digestione meccanica
e chimica
Secrezione della bile,
stoccaggio di nutrienti
Secrezione di saliva
enzimi (amilasi)
Secrezione HCl e
pepsina
denaturazione proteine
Le cellule esocrine
producono enzimi digestivi e
ormoni
Digestione dei nutrienti+
assorbimento di acqua,
ioni, vitamine…
Stoccaggio e
concentrazione della
bile
Flora – immunità >>>
disidratazione - stoccaggio
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Un lavoro a catena
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Un lavoro a catena
La legge dell’anello debole
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DIGESTIONE
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Obiettivi della digestione
Polimeri
Monomeri
assorbibili
senza identità antigenica
Non assorbibili
Con identità antigenica
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Le tappe della digestione
Bocca-masticazione
Deglutizione
Stomaco
Duodeno e intestino tenue
Pancreas
Fegato e cistifellea
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I. Bocca – masticazione - saliva
Masticazione Saliva α-amilasi e lipasi
Parotide
Sotto mascellare
Sublinguale
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Interactions of the salivary and gastrointestinal systems.
I. The role of saliva in digestion.
Valdez IH, Fox PC.
Clinical Investigations and Patient Care Branch, National
Institute of Dental Research, National Institutes of Health,
Bethesda, Md.
Dig Dis. 1991;9(3):125-32.
Considerable evidence now demonstrates that saliva and its
components have multiple functions in the GI tract. Saliva
aids in bolus formation; it lubricates, protects and cleanses
the pharyngeal and esophageal mucosa. Salivary bicarbonate
buffers esophageal acid in common reflux. Normal salivary
flow decreases the duration of acid contact with esophageal
mucosa, an important factor in the development of GERD. If
salivary flow is depressed or if the esophagosalivary reflex is
lost, a patient may be predisposed to develop GERD.
Salivary EGF stimulates GI mucosal proliferation via a
direct lumenal effect in the esophagus and stomach. The
salivary enzymes LL and salivary amylase initiate fat and
starch digestion. They are particularly significant in patients
with pancreatic insufficiency such as neonates and patients
with cystic fibrosis.
La saliva contiene
lipasi e amilasi
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Cellulosa
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L’essenziale
Masticare bene
Mangiare lentamente
Una buona
digestione
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Relationship of physical fitness to chewing in an 80-year-old population.
Takata Y, Ansai T, Awano S, Hamasaki T, Yoshitake Y, Kimura Y, Sonoki K, Wakisaka M,
Fukuhara M, Takehara T.
Departments of Internal Medicine, Kyushu Dental College, Kitakyushu, Japan.
Oral Dis. 2004 Jan;10(1):44-9.
Capacità di masticazione
Pronostico
favorevole
per la forma fisica
Prevenzione dentale
Conservazione
Capacità di masticazione
Importante
Qualità di vita e attività
quotidiane
Dei pazienti anziani
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Relationship of number of remaining teeth to health-related quality of life in community-dwelling elderly. Akifusa S, Soh I, Ansai T, Hamasaki T, Takata Y, Yohida A, Fukuhara M, Sonoki
K,Takehara T. Department of Preventive Dentistry, Kyushu Dental College, Fukuoka, Japan. akifusa@kyu-
dent.ac.jp Gerodontology. 2005 Jun;22(2):91-7.
I risultati di questo studio indicano che
I soggetti di 85 anni con > o = 20
denti
Hanno una miglior salute
fisica soggettiva
Di quellli con < o = 19 denti.
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L’educazione a una
masticazione efficiente è
fondamentale per la
presa in carico dei
pazienti dal punto di vista
sia preventivo sia
curativo
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DALLA BOCCA ALLO STOMACO La deglutizione
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La deglutizione fa ricorso a quattro organi e a 22 gruppi muscolari
diversi.
Deglutizione
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II. Lo stomaco – miscelazione meccanica– succhi gastrici
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Stomaco
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Cellule principali
• Pepsinogeno pepsina (effetto a pH 2-4) predigestione delle proteine
• Una lipasi digestione trigliceridi (soprattutto neonato)
Cellule parietali
• HCl
• Conversione del pepsinogeno pepsina
• Denaturazione delle proteine facilitazione azione pepsina
• Agente antibatterico
• Favorirà la secrezione della bile e dei succhi pancreatici
• Fattore intrinseco
• Assorbimento della Vit B12 a livello intestinale
Cellule mucose
• Protezione dello stomaco contro
• HCL
• Pepsina
Cellule G
• Gastrina secrezione HCL
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HCl indispensabile per la digestione!!!
HCl
Modificazione delle cariche
Denaturazione delle proteine
Indispensabile per
Azione della pepsina
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Cattiva digestione
↑ caratteristica immunogena degli alimenti
Rischio infezione e
disbiosi
↓ assorbimento di ferro
↓ Assorbimento vit B12 (fattore
intrinseco)
Carenza Ca++ e Mg++
Invecchiamento IPP Ipocloridria
• Infezione da clostridium difficile
• Rischio di proliferazione batterica di IG diarrea
• Modificazione della flora colica
• Rischio di infezione
• Anemia microcitaria
• Deficit di sintesi di
• serotonina,
• dopamina
• noradrenalina
• Anemia macrocitaria
• Deficit di sintesi di
• serotonina,
• dopamina
• noradrenalina
• Disordini muscoloscheletrici
• Ansia
• Nervosismo
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IPP & COMPLICAZIONI
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IPP & DISBIOSI
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Gli inibitori di pompa protonica peggiorano le lesioni all’intestino tenue
prodotte dai FANS inducendo disbiosi.
Wallace JL, Syer S, Denou E, de Palma G, Vong L, McKnight W, Jury J, Bolla M, Bercik P, Collins SM, Verdu E,
Ongini E.
Gastroenterology. 2011 Oct;141(4):1314-22, 1322.e1-5.
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs)
are among the most commonly used classes of drugs, with the former frequently coprescribed to reduce
gastroduodenal injury caused by the latter. However, suppression of gastric acid secretion by PPIs is unlikely to
provide any protection against the damage caused by NSAIDs in the more distal small intestine.
METHODS: Rats were treated with antisecretory doses of omeprazole or lanzoprazole for 9 days, with
concomitant treatment with anti-inflammatory doses of naproxen or celecoxib on the final 4 days. Small intestinal
damage was blindly scored, and changes in hematocrit were measured. Changes in small intestinal microflora
were evaluated by denaturing gradient gel electrophoresis and reverse-transcription polymerase chain reaction.
RESULTS: Both PPIs significantly exacerbated naproxen- and celecoxib-induced intestinal ulceration and
bleeding in the rat. Omeprazole treatment did not result in mucosal injury or inflammation; however, there were
marked shifts in numbers and types of enteric bacteria, including a significant reduction (∼80%) of jejunal
Actinobacteria and Bifidobacteria spp. Restoration of small intestinal Actinobacteria numbers through
administration of selected (Bifidobacteria enriched) commensal bacteria during treatment with omeprazole and
naproxen prevented intestinal ulceration/bleeding. Colonization of germ-free mice with jejunal bacteria from PPI-
treated rats increased the severity of NSAID-induced intestinal injury, as compared with mice colonized with
bacteria from vehicle-treated rats.
CONCLUSIONS: PPIs exacerbate NSAID-induced intestinal damage at least in part because of significant shifts
in enteric microbial populations. Prevention or reversal of this dysbiosis may be a viable option for reducing the
incidence and severity of NSAID enteropathy.
IPP & DISBIOSI
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IPP & DISBIOSI
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Comunicazione sulla sicurezza dei farmaci della FDA : Bassi
livelli di magnesio possono essere associati a un uso
protratto di farmaci Inibitori di pompa protonica (PPIs)
[3-2-2011] The U.S. Food and Drug Administration (FDA) is informing the public that prescription proton pump
inhibitor (PPI) drugs may cause low serum magnesium levels (hypomagnesemia) if taken for prolonged periods of
time (in most cases, longer than one year). In approximately one-quarter of the cases reviewed…
PPIs work by reducing the amount of acid in the stomach and are used to treat conditions such as
gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus.
In 2009, approximately 21 million patients filled PPI prescriptions at outpatient retail pharmacies in the United
States.2 Patients who take prescription PPIs usually stay on therapy for an average of about 180 days (6
months).3
Low serum magnesium levels can result in serious adverse events including muscle spasm (tetany), irregular
heartbeat (arrhythmias), and convulsions (seizures); however, patients do not always have these symptoms.
Treatment of hypomagnesemia generally requires magnesium supplements. Treatment in patients taking a PPI
and who have hypomagnesemia may also require stopping the PPI.
Information about the potential risk of low serum magnesium levels from PPIs will be added to the WARNINGS
AND PRECAUTIONS sections of the labels for all the prescription PPIs.
Today's communication is in keeping with FDA's commitment to inform the public about its ongoing safety review
of drugs. FDA is continuing to review reports of possible adverse events and drug interactions with PPI drugs
submitted to our Adverse Event Reporting System.
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IPP & MAGNESIO
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IPP & MAGNESIO
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IPP & VITAMINA B12
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IPP & FERRO
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III. Intestino tenue – pancreas –fegato – cistifellea un lavoro coordinato
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Sfintere di Oddi– 2o duodeno
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Fegato Ciclo entero-epatico dei sali
biliari Struttura epatica
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Intestino tenue
secretina ↑ secrezione
biliare
CCK contrazione della
cistifellea
Il chimo acido duodeno secretina.
AG e AA del chimoduodeno CCK
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A livello dell’intestino tenue
Duodeno
• Bile+ enzimi pancreatici continuano la
digestione
Orletto a spazzola duodeno
digiunale
• Numerosi enzimi portano a termine la
digestione
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La digestione degli alimenti
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A. Digestione delle proteine
La digestione delle proteine ha inizio nello stomaco,
dove prima di tutto esse subiscono la denaturazione da
parte dell’ HCl e in seguito vengono idrolizzate dalla
pepsina.
A livello del duodeno arrivano gli enzimi pancreatici, tra
cui la tripsina e la chimotripsina che continueranno la
digestione. I peptidi ottenuti saranno, a livello
intestinale, degradati dalle amino peptidasi specifiche
Amminoacidi
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Da notare la complementarietà della pepsina (idrolisi estremità N-terminale)
e della chimotripsina (idrolisi estremità C-terminale) degli AA aromatici
(tirosina, fenilalanina e triptofano) la cui disponibilità è importante per la
sintesi dei neurotrasmettitori.
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Digestione delle proteine
Gli enzimi digestivi vengono inizialmente secreti sotto forma di precursore
inattivo.
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B. Digestione dei glucidi
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Nella bocca
Amilasi (pH : 7) predigestione
dell’amido
L’azione dell’amilasi salivare viene
bloccata dall’acidità gastrica
Il chimo gastrico entra nel duodeno
amido amilasi pancreatica maltosio…
Maltosio maltasi dell’orletto a spazzola
monosaccaridi (glucosio)
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Il saccarosio, il maltosio e il lattosio
vengono ingeriti come tali e non sono
trasformati che nell’intestino tenue
dato che gli enzimi (sucrasi, maltasi
e lattasi) si trovano a livello
dell’orletto a spazzola.
Digestione dei glucidi
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LATTOSIO
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Intolleranza al lattosio
A causa di un deficit relativo (fisiologico o patologico) di lattasi, il lattosio, disaccaride,
può essere mal assorbito, con due consequenze: l’ effetto osmotico e la
fermentazione da parte della flora colica con manifestazioni cliniche di
intolleranza molto variabili (gonfiori, dolori addominali e persino diarrea
osmotica).
In Francia, il deficit di lattasi riguarda dal 20 al 40% della popolazione, di cui solo la
metà presenta segni clinici di intolleranza al lattosio.
Molti studi che utilizzano la tecnica del "breath test" hanno confermato che numerosi
soggetti colpiti da disturbi funzionali intestinali si considerano a torto intolleranti al
lattosio e che esiste un netto effetto placebo della soppressione del lattosio.
A fini pratici, nei soggetti che lamentano disturbi funzionali e consumano notevoli
quantità di latte è logico proporre di provare a ridurre l’apporto di lattosio, in
particolare del consumo di latte la mattina a digiuno. Nei pazienti che soffrono di una
reale intolleranza i latticini fermentati e soprattutto lo yogurt vengono meglio tollerati,
dal momento che la lattasi batterica contenuta nello yogurt compensa il deficit di
lattasi intestinale.
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Digestione dei lipidi
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I lipidi = trigliceridi (TG) vengono digeriti
a livello dell’ intestino tenue.
I sali biliari spezzettano i globuli di TG in
goccioline = emulsificazione ↑↑ superficie
esposta alla lipasi pancreatica
monogliceridi + Acidi grassi
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Digestione dei lipidi
I MG e AG passano la barriera intestinale enterociti o MG + AG TG per
raggrupparsi con Colesterolo + Fosfolipidi Chilomicroni linfa circolazione
sanguigna.
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Conseguenze della cattiva digestione
Malnutrizione
Allergie
Malattie autoimmuni
Disimmunità
Disbiosi
Problemi intestinali
Sovraccarico epatico
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Nutrienti che alleviano la digestione
1. Supplementazione
Enzimi digestivi di origine fungina
Sali biliari
2. Stimolazione
Sostanze colagoghe
(carciofo, curcuma, cardo mariano)
3. Protezione
Estratto d’orzo
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ENZIMI MICELLARI
Attività enzimatica e pH
ENZIMI DIGESTIVI FUNGINI
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Enzimi digestivi e sali biliari
Devono essere assunti al
momento del pasto (verso la fine)
per mescolarsi al cibo.
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Stress e digestione
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Stress e digestione
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Muco acido-resistente dell’epitelio gastrico
La produzione di muco acido-resistente dipende
dalla presenza di prostaglandina PGI2
La somministrazione di antinfiammatori steroidei
o meno inibisce la produzione di PGI2
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TRATTAMENTO GASTRITI E ULCERE:
INIBITORI DI POMPA PROTONICA
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TRATTAMENTO GASTRITI E ULCERE: INIBITORI DI POMPA PROTONICA
↓ pH gastrico
↓ attività pepsina
↓ digestione proteine
Enzimi micellari
↑ attività Tra pH 3 e
pH 12
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La digestione nell’anziano Incidenza elevata di difficoltà digestive
Cattiva masticazione
Ipocloridria
Deficit di lipasi
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Consigli per digerire bene
Mangiare lentamente
Masticare bene
Mangiare preferibilmente cotto (a vapore)
Mangiare in forma premasticata
• Minestre
• Purè
• Carne macinata