The pancreas

Digestive enzymes The missing link in people with

systemic disease

Prof. Leo Pruimboom MSc

President of the International Association for Clinical PNI
University of Gerona and Graz
 The pancreas in CPNI
Outline

1. The evolutionary role of the pancreas in mamalians

2. Anatomy
3. Function
4. Physiology
5. The Insulino-Acinar connection
6. The Liver-Pancreas-Brain-Fat axos
7. Pathology
* epidemiology
* EPI
* Pancreatitis
* Pancreatic cancer
8. Treatment
9. Conclusions
 Causes Activation 7
senses
Activation
sympathicus > HPA

Chronic
Resistence cortisol/leptin/ activation
insulin innate immune
system

Second/ Low grade Mental diseases

CVD
Third inflammation
Fatigue
hit Obesity

Symptoms =
Auto-immune
disorders The medical visit
6 kilo of ATP/24 hours
100.000 beats/24 hours
10.000 liter of blood/24 hours
 CVD
Depression
Diabetes
Obesity
Autoimmun Krankheiten
FM, CFS

Cancer
Infektion
Burn out
Pancreatitis
Rosas-Ballina, M., and Tracey, K.J. (2009). Cholinergic control of inflammation. J
10/7/10 9
Intern Med 265, 663-679.
Nance, D.M., and Sanders, V.M. (2007). Autonomic innervation and regulation of the
immune system (1987-2007). Brain Behav Immun 21, 736-745.
 Tracey, K. J. Physiology and immunology of the cholinergic antiinflammatory
10/7/10 11
pathway. J Clin Invest 117, 289-296 (2007).
10/7/10 12 Immunol 9, 418-428.
Tracey, K.J. (2009). Reflex control of immunity. Nat Rev
 Oke, S.L., and Tracey, K.J. (2007). The Inflammatory Reflex and the Role of
10/7/10 13
Complementary and Alternative Medical Therapies. Ann N Y Acad Sci
 PGD2 is degraded to 15d-PGJ2 (through COX-2), a strong
ligand to PPAR and has strong anti-inflammatory
properties

Rossi, A. G. & Sawatzky, D. A. The resolution of inflammation ( Birkhuser, Basel ,

2008), p. 7.
Luyer, M.D., Greve, J.W., Hadfoune, M., Jacobs, J.A., Dejong, C.H., and Buurman,
W.A. (2005). Nutritional stimulation of cholecystokinin receptors inhibits
10/7/10 15
inflammation via the vagus nerve. J Exp Med 202, 1023-29.
 Effect of
different
fatty
acids on
CCK
secretion

Hand, K.V., Bruen, C.M., O'Halloran, F., Giblin, L., and Green, B.D. (2010). Acute
and chronic effects of dietary fatty acids on cholecystokinin
10/7/10 16 expression, storage
and secretion in enteroendocrine STC-1 cells. Mol Nutr Food Res 54, S93-S103.
 Effect of different liquid fatty
meals on CCK secretion

Maljaars, J., Romeyn, E.A., Haddeman, E., Peters, H.P., and Masclee, A.A. (2009).
10/7/10
Effect 17 intake. Am J Clin
of fat saturation on satiety, hormone release, and food
Nutr 89, 1019-024.
 Effect of FAs on cell metabolism

!!!

Hand, K.V., Bruen, C.M., O'Halloran, F., Giblin, L., and Green, B.D. (2010). Acute
and chronic effects of dietary fatty acids on cholecystokinin
10/7/10 18 expression, storage
and secretion in enteroendocrine STC-1 cells. Mol Nutr Food Res 54, S93-S103.
 Effect of FAs on cytotoxicity

Hand, K.V., Bruen, C.M., O'Halloran, F., Giblin, L., and Green, B.D. (2010). Acute
and chronic effects of dietary fatty acids on cholecystokinin
10/7/10 19 expression, storage
and secretion in enteroendocrine STC-1 cells. Mol Nutr Food Res 54, S93-S103.
nicotine as a potential remedy for
inflammatory diseases
10/7/10 21 Immunol 9, 418-428.
Tracey, K.J. (2009). Reflex control of immunity. Nat Rev
so its nicotinergic...
10/7/10 23 Immunol 9, 418-428.
Tracey, K.J. (2009). Reflex control of immunity. Nat Rev
Cui, W.Y., and Li, M.D. (2010). Nicotinic Modulation of Innate Immune Pathways
10/7/10 24
Via alpha7 Nicotinic Acetylcholine Receptor. J Neuroimmune Pharmacol
Cui, W.Y., and Li, M.D. (2010). Nicotinic Modulation of Innate Immune Pathways
10/7/10 25
Via alpha7 Nicotinic Acetylcholine Receptor. J Neuroimmune Pharmacol
 Studies

McClernon, F.J., Hiott, F.B., Westman, E.C., Rose, J.E., and Levin, E.D.
(2006). Transdermal nicotine attenuates depression symptoms in
nonsmokers: a double-blind, placebo-controlled trial.
Psychopharmacology (Berl) 189, 125-133.

Kalra, R., Singh, S.P., Pena-Philippides, J.C., Langley, R.J., Razani-

Boroujerdi, S., and Sopori, M.L. (2004). Immunosuppressive and anti-
inflammatory effects of nicotine administered by patch in an animal
model. Clin Diagn Lab Immunol 11, 563-68.

Bruchfeld, A., Goldstein, R.S., Chavan, S., Patel, N.B., Rosas-Ballina, M.,
Kohn, N., Qureshi, A.R., and Tracey, K.J. (2010). Whole blood cytokine
attenuation by cholinergic agonists ex vivo and relationship to vagus
nerve activity in rheumatoid arthritis. J Intern Med

10/7/10 26
...but also cholinergic!
 metabolism of acetylcholin

+ Acetyl CoA

10/7/10 http://www.cerefolin.com/template/img/
28
chart_hcycycle.gif
 cholin in food

http://dgk.de/gesundheit/mikronaehrstoffebiosubstanzen/lexikon/weitere-
10/7/10 29
biosubstanzen/cholin-und-phosphatidylcholin-lecithin.html
 degredation of Ach by acetylcholinesterase

10/7/10 http://wiki.medpedia.com/Image:Acetylcholinesterase.png?
30
filetimestamp=20080827183700
 Plants with high acetylcholinesterase
inhibitory activities

Salvia officinalis (ethanol extract)

Piper nigrum (methanol extract)

Estragon (essential oil)

(Artemisia drancunculus)

Lavandula officinalis (essential oil)

Huperzia serrata
(syn. Lycopodium serratum)
influencing the parasympathetic tone one
step closer to resolution
 Pace, T.W., Negi, L.T., Adame, D.D., Cole, S.P., Sivilli, T.I., Brown, T.D., Issa,
M.J., and Raison, C.L. (2009). Effect of compassion meditation on
neuroendocrine, innate immune and behavioral responses to
psychosocial stress. Psychoneuroendocrinology 34, 87-98.

Kiecolt-Glaser, J.K., Christian, L., Preston, H., Houts, C.R., Malarkey, W.B.,
Emery, C.F., and Glaser, R. (2010). Stress, inflammation, and yoga
practice. Psychosom Med 72, 113-121.

10/7/10 33
Hamer, M., and Steptoe, A. (2007). Association between physical fitness,
parasympathetic control, and proinflammatory responses to mental stress.
Psychosom Med 69, 660-66.
 Endocannabinoids in
inflammation

Pacher, P., and Hask, G. (2008). Endocannabinoids and cannabinoid receptors in

ischaemia-reperfusion injury and preconditioning. Br J Pharmacol 153, 252-262.
 Copaiba Oil a possible
helper

Gomes, N.M., Rezende, C.M., Fontes, S.P., Matheus, M.E., and Fernandes, P.D. (2007).
Antinociceptive activity of Amazonian Copaiba oils. J Ethnopharmacol 109, 486-492.
 PUFAs stimulate the production of endocannabinoids ->
activation of the CB2-receptor -> antiinflammatory &
proresolutive!

Banni, S., and Di Marzo, V. (2010). Effect of dietary fat on endocannabinoids and
related mediators: consequences on energy homeostasis, inflammation and
mood. Mol Nutr Food Res 54, 82-92.
The polyvagal theory one connection between
behaviour and inflammation
Steven Porges in 1995
 The polyvagal theory

phylogenetic approach
three stages in the evolution of the autonomic nervous
system each associated with different behavioural
possibilities
 neural regulation of the heart

chroman dorsal vagal sympathe*c ventral vagal

*ssue complex nervous complex
system
primi1ve sh x+ - - -
car1laginous sh x+ x- - -
amphibians x+ x- x+ -
mammals x+ x- x+ x-

adapted from: Porges, S.W. (1998). Love: an emergent property of the

mammalian autonomic nervous system. Psychoneuroendocrinology 23, 837-861
and Porges, S.W. (2001). The polyvagal theory: phylogenetic substrates of a
social nervous system. Int J Psychophysiol 42, 123-146.
 consists of main input behaviour
dorsal vagal unmyelinated part vagal aerents freezing / death
complex (DVC) of the Vagus vasopressinergic & feigning
NTS oxytocinergic brain
dorsal motor regions (especially bradycardia
nucleus of the Vagus the PVN) apnoe
Area postrema neural tone of the
gut
diges1on
sympathe*c sympathe1c nerves amygdala ght/ight reac1on
nervous system hypothalamus PAG
(SNS) cingulate cortex
ventral vagal myelinated part of motor areas of the prosocial
complex (VVC) the Vagus frontal cortex
Ncl. ambiguus facial & oral vocaliza1on
motor pathways to aerents communica1on
IX & XI aerents gesture
sensory & motor termina1ng in the vagal brake for the
pathways of V & VII NTS heart
 Important
parts of the
VVC

Important
parts of the
DVC

10/7/10 42
VVC - the social engagement system

Immune system

Porges, S.W. (2007). The polyvagal perspective. Biol Psychol 74, 116-143.
Porges, S.W. (2001). The polyvagal theory: phylogenetic substrates of a social nervous
system. Int J Psychophysiol 42, 123-146.
Porges, S.W. (2001). The polyvagal theory: phylogenetic substrates of a social nervous
system. Int J Psychophysiol 42, 123-146.
Porges, S.W. (2001). The polyvagal theory: phylogenetic substrates of a social nervous
system. Int J Psychophysiol 42, 123-146.
 =NTS
catecholaminergic
neurons

afferents
from IX & X
A & C-fibres
Craig, A.D. (2002). How do you feel? Interoception: the sense of the physiological
condition of the body. Nature Reviews Neuroscience 3, 655-666.
 hedonic valuation

dominant non-dominant hemisphere

hemisphere gets sympathetic input
gets
parasympathetic
input

Nuclei of the thalamus

Craig, A.D. (2002). How do you feel? Interoception: the sense of the physiological
condition of the body. Nature Reviews Neuroscience 3, 655-666.
vagal input and behaviour
 + sensoric information through lamina I
(sensing disruption of homeostasis!)

Goehler, L.E., Lyte, M., and Gaykema, R.P. (2007). Infection-induced viscerosensory signals from
the gut enhance anxiety: implications for psychoneuroimmunology. Brain Behav Immun 21,
721-26.
influences on the autonomic
nervous system
Zautra, A.J., Fasman, R., Davis, M.C., and Craig, A.D. (2010). The effects of slow
breathing on affective responses to pain stimuli: An experimental study. Pain
sympathetic
segments

parasympathetic
segments

Liem (2001). Kraniosakrale Osteopathie (Stuttgart:

10/7/10 53 Hippokrates).
Esch, T., Guarna, M., Bianchi, E., Zhu, W., and Stefano, G.B. (2004). Commonalities
in the central nervous system's involvement with complementary medical
10/7/10 54
therapies: limbic morphinergic processes. Med Sci Monit 10, MS6-M17.
Forsythe, P., Sudo, N., Dinan, T., Taylor, V.H.,
and Bienenstock, J. (2010). Mood and gut
feelings. Brain Behav Immun 24, 9-16.
 Evolution of the pancreas
500 million year
Free energy regulation without thinking
JULY 2002 | VOLUME 3 www.nature.com/reviews/genetics
JULY 2002 | VOLUME 3
www.nature.com/reviews/genetics
The human pancreas

Islet cellls = cells of Langerhans

= insulin, glucagon,
somatostatin

Acinar cells = digestive

enzymes

Duct cells = carbon-anhydrase

HCO3
enteropeptidase

Pancreatic juices

HCO3
Chymotrypsin
Zymogene amylase,
lipase and protease
 Function of the exocrine pancreas

Roxas, M. "The Role of Enzyme Supplementation in Digestive Disorders." Alternative medicine review: a journal of clinical
therapeutic 13, no. 4 (2008): 308.
 Konturek, Stanislaw J, Romuald Zabielski, Jan W , and John Czarnecki.
"Neuroendocrinology of the Pancreas; Role of Brain-Gut Axis in Pancreatic
Secretion." European journal of pharmacology 481, no. 1 (2003): 1-14.

Food intake

Uptake macronutrients Glandular cells Stomach acid-juice

Secretine releasing
peptide
Activation
amylases, lipases
and proteases Duodenal
Cholecystokinin secretin

Trypsin
Acinar-cells
Zymogenic enzyms
Chymotrypsin Duct cells HCO3
Carbon
anhydrase
Buffering of HCl
Enteropeptidase dependent (Zn)
Cleaves chymotrypsin
Konturek, Stanislaw J, Romuald Zabielski, Jan W , and John
Czarnecki. "Neuroendocrinology of the Pancreas; Role of Brain-Gut Axis
in Pancreatic Secretion." European journal of pharmacology 481, no. 1
(2003): 1-14.

The pancreas
distributes food during
day and night
 Konturek, Stanislaw J,
Romuald Zabielski, Jan W
Konturek, and John
Czarnecki.
"Neuroendocrinology of
the Pancreas; Role of
Brain-Gut Axis in
Pancreatic Secretion."
European journal of
pharmacology 481, no. 1
(2003): 1-14.

Regulation of
pancreatic juice
production
 pH, carbon
anhydrase, zinc
and digestion
Konturek, Stanislaw J, Romuald Zabielski, Jan W , and John
Czarnecki. "Neuroendocrinology of the Pancreas; Role of Brain-Gut Axis
in Pancreatic Secretion." European journal of pharmacology 481, no. 1
(2003): 1-14.
 The long vagal-loop,
CCK, Tryptophan and
Melatonin

Comparison of central administration of melatonin precursor L-tryptophan

on caerulein-induced pancreatitis (CIP) in ratsGastroenterology, Volume
124, Issue 4, Pages A265-A265J. Jaworek, A. Leja-Szpak, J. Bonior, M. Kot, A.
Dembinski, Z. Warzecha, J. Stachura, R. Tomaszewska, S. Konturek, W.
Pawlik
 Causes of exocrine dysfunction
Polymorphism
Systemic disease
Severe trauma
Physical overload
Aging
Toxic overload
Alcohol abuse
Smoking
Cereal Fibres??
Anti-nutrinten (Legumes = Bowman-Birk factors)
Kunnitz factors in potatoes
Psychoemotional trauma
Cooking

J Sci Food Agric 1998, 78, 225231

The American Journal of Clinical Nutrition 34: JUNE 1981, pp.
1034- 1035.
The American Journal of Clinical Nutrition 34: JUNE 1981, pp. 1034- 1035.
The American Journal of Clinical Nutrition 37: JUNE 1983, pp 954-960.
 The complication of EPI

Malabsorbtion of vitamin D, vitamin A,

vitamin E, DHA, EPA and biotin, affecting the
prognosis of systemic diseases people

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2007;5:484488

n engl j med 357;3
www.nejm.278 org july
19, 2007
n engl j med 357;3
www.nejm.278 org
july 19, 2007
 Osteoporosis, arthrosis, rachitis

EPI

Moran CE, Sosa EG, Martinez SM, Geldern P, Messina D, Russo A: Bone
mineral density in patients with pancreatic insufficiency and
steatorrhea. Am J Gastroenterol
92:867 871, 1997

Cavalot Diabetes Care, volume 29, number 3, march 2006

 Clinical symptoms of EPI

Fatty, steaky stool

Diahrrea
Smelling stool
Gases, inflammation
Bad breath
Pancreatic cephalia
Pain below the sternum
Fatigue
Endocrine malfunction
Malabsorbtion syndrome (vitamin D, vitamin A, DHA, EPA,
vitamin E)
Macronutrient deficiency (fatty acids and amino acids)
Alternative Medicine Review Volume
13, Number 4 2008
1 year pancreatic enzym suppletion

RBP = retinol
binding protein

CLINICAL
GASTROENTEROLOGY
AND HEPATOLOGY
2007;5:484488
De insulino-acinar connection
Insulin and the exocrine pancreas

Hypo-insulinemia
Pancreatic Atrophy
Steatose of the pancreas
Loss of CCK receptors

Insulin resistance

Decrease of HCO3
Decrease of CCK production
Lack of vagal activity

Hyperglycemia

Decrease of HCO3
Overall inhibition
 Disorders: Mode of action endo - exo

1.Glucagon and somatostatin >> Insuline; atrophia

2.Loss of gap junctions

3.Hypoxia; fibrotic changes

4.Sympathetic >> Parasympathetic

Pancreatology 2009;9:351359
Clin Gastroenterol Hepatol. 2008 January ; 6(1): 7681. doi:
10.1016/j.cgh.2007.10.007.Insulin resistance and incident
gallbladder disease in pregnancy Cynthia W. Ko1, Shirley
A.A. Beresford2, Scott J. Schulte3,*, and Sum P. Lee1
Berry SM, Fink AS. Insulin inhibits secretin stimulated
pancreatic bicarbonate output by a dosedependent
neurally mediated mechanism. Am J
Physiol 1996; 270:G163-170.

Lam WF, Masclee AA, Souverijn JH, Lamers CB.

Effect of acute hyperglycemia on basal, secretin and
secretin + cholecystokinin stimulated exocrine
pancreatic secretion in humans. Life Sci 1999;
64:617-626.

Lam WF, Muller ES, Souverijn JH, et al. Effect of

acute hyperglycaemia on basal and fat-induced
exocrine pancreatic secretion in humans. Clin Sci
(Lond) 1997; 93:573-580.

Lam WF, Gielkens HA, Coenraad M, et al. Effect of

insulin and glucose on basal and cholecystokininstimulated
exocrine pancreatic secretion in humans.
Pancreas 1999; 18:252-8.
 The interaction

Pancreatology 2009;9:351359
 The pancreas weight

Newborn 5 gramm
1 year 14 15 gramm
Male adult < 40 jaar 112,4 gramm
Male average 80 jaar 68,4 gramm
Female adult < 40 jaar 92 gramm
Female average 80 jaar 66 gramm
Over-stimulated (alcohol-pancreatitis) 180 gramm?

The normal weight of the pancreas in the adult human being: A biometric
study. John H. Schaefer :Fellow in Pathology, The Mayo Foundation,
Rochester, Minnesota. From the Mayo Foundation for Medical Education and
Research, and the Department of Anatomy, University of Minnesota.Read by
title before the American association of anatomists, Cleveland, April 9 to 11,
1925.
The pancreas-
liver-brain-fat
axis

Protecting the
pancreas
 Glucose clearance capacity
Eatron B, Cordain L. Preventive Medicine 49 (2009) 283285
 Achim Peters1* and
Glucosa clearance capacity Dirk Langemann2
Frontiers in
neuroenergetics.
2009 (1): 1 - 15
200 gr glucose/24 hours

130 gr to the brain (66 - 70%)

70 gr to the periphery (33%)

Actual intake 350 gr + 150

gr endogenous
A surplus of 300 gr has to be stored in
Muscle
Fat
Ectopic
Blood vessels
 Input en output
van de lever

Hepatic T cells and liver tolerance

Ian Nicholas Crispe
Nature Reviews Immunology 3, 51-62
(January 2003)
 GLUCOneogenesis = Default

Inhibition is active function of

Pancreas-Liver axis 20%

Pancreas-Liver-Brain axis 50%
Pancreas-Liver-Fat axis 30%

Insulin repairs exo- and endocrine pancreas

IR is adaptive and regenerates death causing pancreas damage

AUGUST 2006 VOL 2 NO 8
NATURE CLINICAL
PRACTICE
ENDOCRINOLOGY &
METABOLISM
Diabetologia (2000) 43: 946952
Endocriene Exocriene pancreas

Ectopic fat, vagal tone and apnea

Hahn PY, Somers VK.
Sleep apnea and
hypertension.
In: Lip GYH, Hall JE,
eds.
Comprehensive
Hypertension. St.
Louis, MO: Mosby;
2007:201207.
Copyright Elsevier
2007
JACC Vol. 52, No. 8, 2008 Somers et al.
691
August 19, 2008:686717
 Epidemiology
Acute pancreatitis
Acta Cirrgica Brasileira - Vol 23
(Supplement 1) 2008 - 143
Mode of action
Why Does Pancreatic
Overstimulation Cause
Pancreatitis?
Ashok K. Saluja,1 Markus M. Lerch,2
Phoebe A. Phillips,1 and Vikas Dudeja1

Annu. Rev. Physiol. 2007. 69:24969

114
Alcohol-induced acute pancreatitis: The
critical mass conceptMedical Hypotheses,
In Press, Corrected Proof, Available online 23
February 2010Savio G. Barreto, Gino T.P.
Saccone
Causes and complications of pancreatitis
Sudden cardiac death, heart failure and
energy distribution
Europe
Approximately 14 million people in Europe currently suffer from heart
failure and this number is forecast to increase to 30 million by the year
20201

Nearly 40% of heart failure patients will die within one year of first
hospitalisation and only 25% of men and 38% of women will survive more
than five years following diagnosis2, 3

Over 3.6 million new cases of heart failure are reported each year in
Europe1

Heart failure is more common than most cancers, including breast,

testicular, cervical and bowel cancers4

Admission to hospital with heart failure has more than doubled in the last
20 years1

Heart failure patients experience a lower quality of life than patients

suffering from any other chronic disease1

By 2020 the number of deaths in Europe each year attributed to heart

failure will be nine million1
International Journal of Obesity 34,
989-1000 (June 2010)
A microarray analysis of sexual dimorphism
of adipose tissues in high-fat-diet-induced
obese mice
K L Grove, S K Fried, A S Greenberg, X Q
Xiao and D J Clegg
The sphincter of Oddi
 Sphincter of Oddi resistance

High calorie diet

Gallstones
Carbohydrates
Alcohol
Bili-inflamation
Distress
Sympathetic overreactivitys
Insulin resistance

S.G. Barreto, G.T.P. Saccone / Medical

Hypotheses xxx (2010) xxxxxx
Gallstones epidemiology
Gallstones epidemiology
Gallstones epidemiology
 Gallstones epidemiology

70
60
50
40
30 mannen
20 vrouwen
10 Totaal
0

Best Practice & Research Clinical Gastroenterology

Vol. 20, No. 6, pp. 981e996, 2006

Journal of Gastroenterology and Hepatology 23

(2008) 13391348
 Treatment of the spasm of the spincter of Oddi
Green tea, coffee and chocolate

Pap, A, and G Forr. "[The Effect of Theophylline Preparations on

Morphine-Induced Spasm of Oddi's Sphincter in Man]." Orvosi hetilap 139,
no. 23 (1998): 1411-4.
Lancet 2008; 371: 14352 Ethanol Conversion
Oxidation Fructose
High fat diet

Activation (FAEES)
Activation CYP2E1
Fatty acid ethyl
esters synthetases
Activation ADHIII
(alcohol dehydrogenase)
Fatty acid ethyl esters

Acetaldehyde

Free radicals
Destabilisation lysosomes
Damage to chymo-enzymes
Activation NFkB
Depletion glutathion Increase cytoplasmatic Ca

Vonlaufen, Alain, Jeremy S Wilson, and Minoti V Apte. "Molecular Mechanisms of Pancreatitis: Current Opinion."
Journal of gastroenterology and hepatology 23, no. 9 (2008): doi:10.1111/j.1440-1746.2008.05520.x.
The consequence: Damaged
World J Gastroenterol. 2009 December
Pancreas 7; 15(45): 5732-5739
Curcumin Decreased Oxidative Stress,Inhibited NF-B Activation, and
Improved Liver Pathology in Ethanol-Induced Liver Injury in Rats.

Journal of Biomedicine and

Biotechnology
Volume 2009, Article ID 981963, 8 pages
Pancreatitis, Tryptophan and Melatonin
Melatonin and its precursor, L-tryptophan: influence on pancreatic
amylase secretion in vivo and in vitro
Jolanta Jaworek, Katarzyna Nawrot, Stanisaw J. Konturek, Anna Leja-
Szpak, Piotr Thor, Wiesaw W. Pawlik
Journal of Pineal ResearchVolume 36 , Issue 3 , Pages155 - 1642004
Synergestic interventions - Zinc

Exp. Biol. Med. 2001;226:103-111

 Irritable bowel syndrome

Irritable bowel syndrome-A Diahrrea, obstipation

Irritable bowel syndrome-B Bile (gal) deficiency
Irritable bowel syndrome-C Obstipation
Irritable bowel syndrome-D Diahrrea

Dobson, Brian C. "The Small Intestine and Irritable Bowel

Syndrome (IBS): A Batch Process Model." Medical hypotheses
71, no. 5 (2008): doi:10.1016/j.mehy.2008.06.015.
 Irritable bowel syndrome

Naim M., Zechman J. M., Brand J. G., Kare M. R., Sandovsky

V. Effects of sodium saccharin on the activity of trypsin,
chymotrypsin, and amylase and upon bacteria in small
intestinal contents of rats. Proc Soc Exp Biol Med 1985;
178:392401.
Mallett A. K., Rowland I. R., Bearne C. A. Modification of rat
caecal microbial biotransformation activities by dietary
saccharin. Toxicology 1985; 36: 253262.
Arnold D. L., Krewski D., Munro I. C. Saccharin: a
toxicological and historical perspective. Toxicology 1983;
27: 179256.
Some Patients With Irritable Bowel Syndrome May Have Exocrine
Pancreatic Insufficiency.
Clinical Gastroenterology and Hepatology, Volume 8, Issue 5, Pages
433-438J.
Leeds, A. Hopper, R. Sidhu, A. Simmonette, N. Azadbakht, N. Hoggard, S.
Morley, D. Sanders

Pancreas. 2009 Mar;38(2):232-3.Treatment of irritable bowel syndrome-

diarrhea with pancrealipase or colesevelam and association with
steatorrhea.Money ME, Hofmann AF, Hagey LR, Walkowiak J, Talley NJ.
 Beta glucuronidase deficiency

Colitis ulcerosa
Morbus Crohn
Irritable Bowel Syndrome

Three identities of the same disease?

 100% *
E
n
z 75% *
y *
m *
*
e 50%

*
A * *
c 25%

t
I 0% *
v
i
t
y Control 1.25 mmol 2.5 mmoll 5 mmol 10 mmoll

Prograde gut transit

Quantity of free bilirubin

Beta-glucuronidase activity
 Beta glucuronidase
Activates Bilirubin

Function Inactivate pancreatic enzymes

Protection of tight junctions
Protection cell-membrane
Source Mucosa
E. Coli (in acid gut, maintained
through lactobacilles and
bifidobacteries)

Journal, Indian Academy of Clinical Medicine Vol. 6, No. 1 January-March,

2005
Probiotics
Gut 2010;59:325-332 doi:10.1136/gut.2008. Irritable bowel syndromeThe
efficacy of probiotics in the treatment of irritable bowel syndrome: a
systematic review
P Moayyedi1, A C Ford1, N J Talley2, F Cremonini3, A E Foxx-Orenstein3, L J Brandt4, E M M Quigley5

Results 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial
quality was generally good, with nine reporting adequate methods of
randomisation and six a method of concealment of allocation. There were
10 RCTs involving 918 patients providing outcomes as a dichotomous
variable. Probiotics were statistically significantly better than placebo (RR
of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to
treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity
(2=28.3, p=0.001, I2=68%) and possible funnel plot asymmetry. Fifteen trials
assessing 1351 patients reported on improvement in IBS score as a
continuous outcome (SMD=0.34; 95% CI 0.60 to 0.07). There was
statistically significant heterogeneity (2=67.04, p<0.001, I2=79%), but this
was explained by one outlying trial.
The solution
Indications of pancreas enzyme
supplementation

Acute, chronic pancreatitis

IBS, Colitis, Crohn
Alcohol-abuse
Steatorrhea (vette ontlasting)
Putrifactors
Lactose intolerance
Celiac disease
Malabsorbtion syndrome
Modern life
Systemic disease
 Causes Activation 7
senses
Activation
sympathicus > HPA

Chronic
Resistence cortisol/leptin/ activation
insulin innate immune
system

Second/ Low grade Mental diseases

CVD
Third inflammation
Fatigue
hit Obesity

Symptoms =
Auto-immune
disorders The medical visit
Thanks for your attention