The Gut- the incredible organ : the story of Gut immunology Yoshinobu Namihira MD, FACG 300 Halls Ferry road Vicksburg, MS 39180 Ph 601-638-9800, fax 601-638-9808.

The Gut-the incredible organ :

the story of Gut immunology

Yoshinobu Namihira MD, FACG 300 Halls Ferry road Vicksburg , MS 39180 Ph 601-638-9800, fax 601-638-9808 E mail: namihira @ vicksburg.com

Acute pancreatitis

• The existing problem:

• The patient can not keep the foods in the stomach because of severe ongoing abdominal pains

The important clinical question

•Should I feed or not feed the patient with

acute pancreatitis with jejunal tube placement (small bowel ) ?

• Do I keep on giving Total parenteral nutrition ( TPN) ?

• All the nutritions by IV route (carbohydrates, proteins, fats ,vitamins, trace minerals)

• No foods go through GI tract.• “GI tract is put to rest “= is it right

thing to do?

• Am I doing favor to GI system ?• or am I doing disservice or harm

to the whole body?

•What is the correct answer to the question at hand?

Use it orLose it

The normal sequence of degestion(1)

1. Foods on the table 2. Mouth 3. Teeth 4. Oro-pharynx

5. Mechanism of swallowing –complex, miracle of God’s wisdom

6. Esophagus7. Stomach (cardia-fundus-body- antrum)8. pylorus

Teeth16 at the top 8 on the right, 8 the left16 at the bottom8 on the right , 8 on the left 32 total

Pyloric opening5mm=1/4 inch

The normal sequence of degestion(2)

9. Duodenum (bulb, 2nd part, 3rd part, 4th part)10. Jejunum11. Ileum12. Colon13. Cecum-ascending-

transverse,descending,sigmoid,14. Rectum15. Anus

16.Anal sphincters –internal , external 17. Final defecation 18. Bathroom commode !

Acute pancreatitisCan not keep foods in the stomachHow do I keep the patient alive ?Do I give foods by IV route?Do I give foods by small bowel tube Placement ?

The old concept of “gut rest “• The time of acute pancreatitis =do not feed• The gut is passive tube , that is it !• Stress gastropathy = stomach need rest ?• GI bleeding = need rest ?• ileus ( abdominal distention ) = no feeding at all ?

• The Old thinking= the GI tract is previously

considered as “organ of inconvenience “

• You have to go to bathroom for bowel movements !

What happens when there are no foods in the stomach ?

1. No foods in the stomach, ( GI tract )2. No stimuli to the GI tract at all !3. Bacterial overgrowth 4. Gut bacteria engaging with gut epithelia (bacteria-

epithelium interaction )5. Proliferation of dendritic macrophages ,lymphocytes6. Release of IL -12{interleukin } ( pro inflammation )7. Migration along lamina propria

8. Gut epithelium programmed death ( apotosis )—death of the epithelium cells

9. Increased gut permeability !!!10. Bacteria translocation from gut into blood stream

1. Gut epithelium programmed death ( apotosis )—death of the epithelium cells

2.Increased gut permeability !!!

3. Bacteria translocation from gut into blood stream

epithelium

Innate gut immune response(4)

20.Window of opportunity to rescue !!!

21. 4-6 hr—burns patient

22. 24-48 hr—pancreatitis patient

23. 48-72 hr– after major elective surgery patient

When channels open !, (1)

1. When the channels between epithelium open

2. Bacteria move across and walk toward the lungs ( bacteria translocation concept )

3. Bacteria do not have to go through the portal vein ! ( gut –portal vein-liver –systemic circulation)= no !!

When channels open !, (2)

4. Opening of the channels allows

bacteria to engage macrophages and

neutrophils at the surface of the gut

5. Cytokine and activated neutrophils released into lymphatic channels

6. Lymphatic systems carry them to distant sites ( lungs)

7. Immune system activation at the distant sites ( lungs, liver ,kidney )

When channels open !, (3)

8. Pro-inflammatory response ensues

9. Oxidative stress on the tissues (lungs, liver, kidney, heart )

10. “Oxidative burst “ at lungs, kidney, liver, heart

11. {The leaky membrane syndrome }12.The multi organ failures (lungs,

liver ,heart, kidney, sepsis )

Oxidative Burst• Bombs, missals and grenades =very

dangerous explosives

• Are produced and are transported from GI tract to the distant sites ( lungs, liver, heart, kidney, circulation ),& still restrained

• Restrictions are released at the sites

• Explosion takes place at the distant sites

• Damage = “leaky membrane syndrome”

Take home point

•When the gut goes down,

•It will pull other organs with it !!!

The gut

The lungsLiverHeart

KidneyCirculation

sepsis

Take home point

• No foods in the GI tract !!!

• Increased sepsis

• Increased septic shock

• ARDS (adult respiratory distress syndrome)

• Increased death rate !!!

starvation

•Starvation ( no foods in the GI tract ) activates T H-1 Pahway.

T H 1 pathway

13.Helper 1 T lymphocytes pathway14.IL-12 release

15.Macrophages back to lamina propria

16.CD-4 helper lymphocytes17.Cytokine shower !!!

18.Pro-inflammatory reaction !!!

19. Cells release 1) interferon , 2) tumor necrosis factor (TNF) !!! {bad news }

20.Spill over systemic circulation

The Bottom line

•TH-1 pathway activation = a bad news for you !

• Is not good for your health.

What happens after you eat food?

TH-2 pathway starts

TH-2 pathway

1. Foods in the GI tract (eating, feeding GI )

2. Shut down the TH-1 pathway !3. Less inflammatory response 4. Less tumor necrosis factor (TNF-factor )5. T cell regulatory type 1 (TR-1 )

6. Th-3 pathway activates oral-tolerance7. Release of beneficial cytokines (reduce inflammation ) =

{ anti inflammation }

8. { cooling effect in immune system }!!!

The end result of foods in the GI tract

1. Mitigate immune system

2. Cool off or calm down immune system!

3. Less inflammation

4. Less oxygen free radical damage on the tissues ( lungs, kidneys, heart, circulation)

5. Less pneumonia, less ARDS (respiratory failure)

5. Less pneumonia, less ARDS (respiratory failure)

6. Less infection (down by 50 % )

7. Low incidence of surgical anastomosis breakdown

8. Shorter length of stay (LOS) in hospital

No food in the GI tract

TH-1 pathwayActivation

Pro-inflammatory responses

Leaky membrane syndrome

Infection, organ failure(lung,kidney,heart)

Foods in the GI tract

TH-1 pathway-shut down

Cooling off , calming effect on activated immune system

Less inflammatory responses

Less infection, less organ failures

Take home point

•The foods in the GI tract are essential for good health !

FoodsIn the GI tract

Spiritualapplication

John 6:35

• “ I am the bread of life. “

• “ He who comes to me shall never hunger ,and he who believes in me shall

never thirst “.

•Hunger= eat foods= GI tract !

•Thirst= dehydration = drink water

John 6:51,

•“ I am the living bread which came down from

heaven .

John 6:47-48

• “ he who believes in Me (Jesus Christ ) has everlasting life. “

• “ I am the bread of life “

• “this is the bread which comes down from

heaven, that one may eat of it and not die.”

John 6: 51

• I am the living bread which came down from heaven. If anyone eats of this

bread , he will live for ever, and the bread that I shall give is My flesh, which I shall give for the life of the world. “

John 6:57

• “As the living Father sent Me ( Jesus Christ ) , and I live because of the Father ,so he

who feeds on Me ( Jesus

Christ ) will live because of Me

( Jesus Christ )”

Connecting dots

• Feeding on Jesus Christ= digesting the words of God=bile study

• Living for ever= eternal life

The GI tractEating foods

DigestionBible study

Everlasting life

Matthew 6:9-13

• Our father in heaven. • Hallowed be your name.• Your kingdom come.• Your will be done on earth as it is in heaven. • Give us this day our daily bread. • And forgive us our debts• As we forgive our debtors. • And do not lead us into temptations• But deliver us from the evil one. • For yours is the kingdom and the power and the glory

for ever. Amen

John 6:10

•Give us this day our daily bread.

• Time of need= today !• Frequency of need=each

day ,1x , 2x , 3x• Party involved= individual • Subject matter= GI tract

matter= eating !!!

Psalm 139:14

• “I will praise you, for I am fearfully and wonderfully made;

• Marvelous is Your works, and that my soul knows very well ”

• The design and function of the GI tract are, indeed, fearfully, and wonderfully made, and executed smoothly .

• The every detail of the mechanism of action for each component of the GI tract is just beyond comprehension .

• But I am eternally grateful that God is in control of every detailed mechanism of action of the complex human machinery .

• for the time being, I continue to trust in God’s wisdom and His mercy and keep on going , maintaining good health with good habits.

Conclusions 1

1. Normal sequence of the GI tract

2. The old concept of gut rest = wrong

3. Epithelium cell death = apotosis

4. Increased gut epithelial permeability

5. Pro-inflammatory response=lnterleukin 12

6. Cytokine shower into systemic circulation

Conclusions 2

6. Leaky membrane syndrome7. Multi-organ failure (lungs ,liver, kidney,

heart, circulation )8. No foods in the GI tract= increased

infection, multi-organ failure, death rate 9. “when the gut goes down, it will pull other

organ with it “10.TH-1 pathway= very dangerous, bad

news

Conclusions 3

11.TH-2 pathway= cooling effect on the immune system, good news !

12.Foods in the GI tract= less infection, less organ failure, less surgical anastomosis breakdown

13.Foods in the GI tract= essential for good health!

14.Jesus Christ= the bread of life

Conclusions 4

15.Feeding on Jesus=digestion of God’s words=== eternal life

16.Human machinery is fearfully and wonderfully made and works very well according to God’s design and his blue print.

References

1. Feeding the critically ill patient- Steven A. McClave,MD, professor of medicine,University of Louisville school of Medicine, Louisville, KY

2. Audio digest gastroenterology 21:08,the 42nd annual Gastroenterology Update,held November 16-17,2006 in Cleveland ,OH

3. Hendon DN et al: increased mortality with intravenous supplemental feeding in severely burned patients. J Burn Rehabil 10:309,1989

4. Lewis SJ et al: Early enteral feeding versus “nil by mouth “ after gastrointestinal surgery: systematic review and meta-analysis of controlled trials. BMJ 323:773,2001

5. Mark PE et al: Early enteral nutrition in acutely ill patients: systematic review. Crit Care Med 29:2264,2001

6. McClave SA et al: Enteral tube feeding in the intensive care unit :factors impeding adequate delivery . Crit Care Med 27:1252.1999

7. McClave SA et al: Nutrition management in actue and chronic pancreatitis . Gastroenterology Clin North Am 27:421,1998

8. Stanga Z et al: Effect of jejunal long term feeding in chronic pancreatitis .JPEN J Parenter Enteral Nutr 29:12,2005

9. Taylor SJ et al: Prospective randomized ,controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury. Crit Care Med 27:2527,1999

10.Zeigler TR et al: Increased intestinal permeability associated with infection in burn patients. Arch Surg 123:1313,1988

•The END•Thank you for coming !

Sermon details

• Opening hymn :499 ,what a friend we have in Jesus

• Scripture reading: John 6:35

• Special music: the namihira’s

• Sermon “the gut- incredible organ, the story of gut immunology “

• Closing hymn: 632, until then

The place of visit

• 12-1-2007,vicksburg MS