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Colonic function in cirrhosis of liver and in healthy controls
April 1995
• COLONIC FUHCTIO~ IN C I R R H O S I S OF LIVER AND IN H E & L T H Y CONTROLS. A.P. J a c o b , A. C h a c k o . Dept. of G.I.Sciences, CMC Hospital, Vellore 632004, S.India Increased stool frequency is c o m m o n l y s e e n in cirrhosis with portal hypertension. T h e r o l e of the c o l o n in c a u s a t i o n of this d i a r r h e a is u n k n o w n . Aims: i) E s t i m a t e total and segmental colonic transit times (CTT) in c i r r h o s i s and healthy controls. 2) E v a l u a t e the e f f e c t of C T T on s t o o l frequency and stool weight (wet, dry and stool water). 3) A s s e s s the e f f e c t of p o r t a l c o l o p a t h y on CTT. Method: T o t a l a n d s e g m e n t a l C T T ( r a d i o o p a q u e m a r k e r mete), daily stool weight, water and frequency were estimated in I0 d e c o m p e n s a t e d nonalcoholic m a l e c i r r h o t i c s a n d i0 m a l e c o n t r o l s . All s u b j e c t s underwent colonoscopy with segmental mucosal biopsies. R e s u l t s : i) The m e a n total, left a n d r e c t o s i g m o i d w e r e s i g n i f i c a n t l y s h o r t e r in c i r r h o t i c s w h i l e right CTT was similar to c o n t r o l s [Cirrhosis V C o n t r o l s ; M e a n + SE; T o t a l C T T : 18.5 + 3.7 V 31.3 + 3.7 p < 0.05~Left C T T : 4.4 + 0.8 V--9.2 + 1.5 p 0.05; R e c t o s i g m o i d C T T : 3.8 +--1.2 V 9.4 ~ 2.7 p = 0.05; R i g h t C T T : 10.3 + 2.2--V 12.3 + 1 . 8 hrs]. 2) S t o o l frequency was slgnificantly--higher in cirrhosis compared to c o n t r o l s (p < 0 . 0 1 ) a n d showed a significant negative correlation (r =0.73; P < 0.02) w i t h C T T in c i r r h o s i s . 3) The m e a n d a i l y s t o o l w e t w e i g h t a n d s t o o l w a t e r c o n t e n t were significantly higher in c i r r h o s i s compared to controls (Cirrhosis vs C o n t r o l s ; M e a n + SE; Wet w e i g h t : 3 1 8 + 3 7 V 1 8 3 + 3 2 g p = 0.01; S t o o T w a t e r : 273+35 V 146~26gm p < ~.01). T h e r e w a s h o w e v e r no cor~elation-~etween stool weights (wet, d r y a n d stool water) a n d C T T in c i r r h o s i s . 4) P o r t a l colopathy (colonoscopic and mucosal biopsy scores) d i d n o t c o r r e l a t e w i t h C T T in c i r r h o s i s . Concluslons: Colonic transit is a c c e l e r a t e d in cirrhosis and may be a n important hitherto unrecognised factor in the e t i o p a t h o g e n e s i s of cirrhotic diarrhea. P o r t a l c o l o p a t h y d o e s not s e e m to i n f l u e n c e c o l o n i c t r a n s i t .
• THE CORRELATION OF ANO-RECTALMANOMETRIC DATA(ARM) A N D S U R F A C E A N A L E M G R E C O R D I N G (s-EMG) O F T H E A N A L S P H I N C T E R S IN P A T I E N T S W I T H F E C A L I N C O N T I N E N C E (FI) A N D C O N S T I P A T I O N S Y N D R O M E S (CS). B a r r y W. J a f f i n , T h e r e s a S h a l l e y . M o u n t S i n a i M e d i c a l C e n t e r , NY NY 10029 INTRODUCTION: Biofeedback techniques are being used to t r e a t F e c a l I n c o n t i n e n c e ( F I ) and Constipation Syndromes(CS). To date, there has been no systematic comparison between different modalities to m e a s u r e a n a l s p h i n c t e r p a r a m e t e r s in t h e s a m e p a t i e n t o n t h e s a m e day. M E T H O D S : M e a s u r e m e n t s of t h e r e s t i n g ( R ) a n d s q u e e z e (S) p r e s s u r e of t h e a n a l s p h i n c t e r s in p a t i e n t s with FI and CS w e r e performed using standard Anorectal manometry (Narco Biosystem/Arndorfer system) a n d c o m p a r e d t o m i c r o v o l t (MicroV) r e a d i n g s using the Perry-Orion surface anal EMG sensor d e v i c e p e r f o r m e d w i t h i n o n e h o u r of e a c h other. Linear regression analysis was performed using mmHg (ARM) vs. M i c r o V (s-EMG) data. R E S U L T S : 28 c o n s e c u t i v e patients (18 FI, i0 CS) u n d e r w e n t b o t h A R M a n d S E M G p r i o r to b i o f e e d b a c k r e t r a i n i n g . M e a n age: F I ( 6 0 . 4 ) , C S ( 2 9 . 8 ) . 16/18 FI p a t i e n t s w e r e f e m a l e w h i l e 9 / 1 0 CS p a t i e n t s w e r e female. Mean Mean R-coefficient mmHg MicroV INCONTINENCE Resting: 32.5 2.0 .579 Squeeze: 95.5 9.1 .852 CONSTIPATION Resting: 47.0 3.1 .614 Squeeze: 126.0 13.6 .745 C O N C L U S I O N : T h e r e is a s t r o n g c o r r e l a t i o n b e t w e e n ARM and s-EMG measurements u s e d in b i o f e e d b a c k retraining. This correlation is stronger with c o n t r a c t i o n of t h e a n a l s p h i n c t e r .
Motility and Nerve-Gut Interactions
A621
• CHANGES IN ENTERIC NEURAL FUNCTION IN EXPERIMENTAL COLITIS ARE NOT T LYMPHOCYTE DEPENDENT. K.Jacobson and S.M.Collins. Intestinal Diseases Research Programme, McMaster University, Hamilton, Ontario, Canada. Intestinal inflammation in animals and man is accompanied by extensive changes in enteric neural function, resulting in physiological dysfunction. Previous studies in the inflamed jejunum of nematode-infected rats have shown that inflammation-associated changes in tissues such as nerve or muscle reflect different components of the inflammatory or immune response, and that improvement in one parameter does not predict improvement in another (Vermillion et al Gastro 101:31-38,1991 and Collins et al AIP 263 G198-201,1992). These observations may not necessarily apply to other models. We have recently described extensive changes in adrenergic nerve function in the myenteric plexus in rats with colitis induced by intrarectal (ir) administration of trinitrobenzene sulfonic acid (TNB). We found substantial suppression of 3H-noradrenaline release not only in the inflamed distal colon, but also in the non inflamed transverse colon. In this study, we examined the role of T lymphocytes in the development of these changes in adrenergic neural function in TNB-induced acute colitis. Distal colitis was induced by intrarectal TNB (30 mg in 0.25 ml 50% ethanol) in congenitally athymic (rnu/rnu) rats and their heterozygous (rnu/÷) euthymic littermates, while control rats received 0.25 ml 0.9% saline. One group of animals was sacrificed on day 5, and a second group allowed to recover for 6 weeks. We measured the evoked release of 3H-NA from longitudinal muscle-myenteric plexus preparations (LM-MP) from the distal and transverse colon in response to electrical field stimulation (EFS). Studies were carried out on: (a) day 5 post-TNB or (b) day 42 post-TNB. On day 5, the release of 3H-NA in euthymics was suppressed by 39% in the inflamed distal colon, and by 51% in the non-inflamed transverse colon relative to controls. Athymics demonstrated a similar pattern with a 42% and 47% suppression in distal and transverse colon respectively. By day 42 post-TNB, there was partial recovery from the suppression of 3H-NA release in euthymic rats: However no recovery was seen in athymic rats at day 42 post TNB perhaps due to the greater degree of inflammation observed during the acute colitis (see Jacobsen Gastro this volume). These results indicate that the suppression of adrenergic myanteric nerve function in the inflamed distal colon is independent of functional T cells, and that T cells do not mediate the alteration in nerve function observed at non-inflamed sites in the colon. Supported by MRC Canada.
ESOPHAGEAL MOTILITY DISORDERS: A PATHOPHYSIOLOGICAL CONCEPT. J. Janssens, D. Sifrim, A. Lerut. Center for Gastroentero]ogical Research K.U. Leuven. Belgium. The motor function of the esophagus is regulated by a balanced action of inhibitory and excitatory neurons. Aim: To present evidence in man for the concept that failure of inhibition leads to primary motility disorders, while failure of excitation results in reflux disease. Methods: Manometry with 4 perfused catheters and a sleeve; pH recording at 5 cm above LES. Inhibition in esophageal body examined at various levels using a small balloon inflated sufficiently to create an artificial high pressure zone (AHPZ) of + 20 mm Hg; inhibition measured as % fall in pressure in AHPZ. Twenty patients with primary motility disorder (9 achalasia, 6 diffuse spasm, 5 intermediate forms: (earlier study)); 12 patients with reflux esophagitis (RE): i0 normal controls. Results: In patients with primary motility disorder the degree of inhibition after wet swallows was inversely related to the progression velocity of the contraction (p < 0.001): 100% inhibition preceded normal peristalsis; 0% inhibition resulted in simultaneous contractions (GE 1994; 106: 875). RE and controls had normal inhibition (90.16 ~ 3.1% vs 91.6 ! 8.3%) and normal peristalsis after wet swallows. Monitored during lh fasted and 2h pestprandial]y the rate of transient LES relaxations (TLESR's) was similar in RE and controls (3.8 ~ 6.4 vs 4.0 0.4) but the % TLESR's accompanied by reflux was higher in RE (64.05 Z 6.6% vs 35.74 Z 7.8%. p < 0.05). When TLESR's were accompanied by acid reflux the AHPZ was inhibited in RE (favoring rise of acid) and contracted in controls (as to prevent rise of acid). This absence of contraction in the TLESR's with reflux Changes in AHPZ increase no change inhibition controls n=23 56.5% 26.2% 17.3% RE n=44 9.1% 31.8% 59.1% AHPZ during acid reflux and the presence of normal inhibition after wet swallows suggests a deficient excitation in RE. Conclusion: We propose the concept that dysfunction of inhibitory innervation results in primary esophageal motility disorders while failure of excitatory innervation leads to reflux disease.
• COLONIC FUHCTIO~ IN C I R R H O S I S OF LIVER AND IN H E & L T H Y CONTROLS. A.P. J a c o b , A. C h a c k o . Dept. of G.I.Sciences, CMC Hospital, Vellore 632004, S.India Increased stool frequency is c o m m o n l y s e e n in cirrhosis with portal hypertension. T h e r o l e of the c o l o n in c a u s a t i o n of this d i a r r h e a is u n k n o w n . Aims: i) E s t i m a t e total and segmental colonic transit times (CTT) in c i r r h o s i s and healthy controls. 2) E v a l u a t e the e f f e c t of C T T on s t o o l frequency and stool weight (wet, dry and stool water). 3) A s s e s s the e f f e c t of p o r t a l c o l o p a t h y on CTT. Method: T o t a l a n d s e g m e n t a l C T T ( r a d i o o p a q u e m a r k e r mete), daily stool weight, water and frequency were estimated in I0 d e c o m p e n s a t e d nonalcoholic m a l e c i r r h o t i c s a n d i0 m a l e c o n t r o l s . All s u b j e c t s underwent colonoscopy with segmental mucosal biopsies. R e s u l t s : i) The m e a n total, left a n d r e c t o s i g m o i d w e r e s i g n i f i c a n t l y s h o r t e r in c i r r h o t i c s w h i l e right CTT was similar to c o n t r o l s [Cirrhosis V C o n t r o l s ; M e a n + SE; T o t a l C T T : 18.5 + 3.7 V 31.3 + 3.7 p < 0.05~Left C T T : 4.4 + 0.8 V--9.2 + 1.5 p 0.05; R e c t o s i g m o i d C T T : 3.8 +--1.2 V 9.4 ~ 2.7 p = 0.05; R i g h t C T T : 10.3 + 2.2--V 12.3 + 1 . 8 hrs]. 2) S t o o l frequency was slgnificantly--higher in cirrhosis compared to c o n t r o l s (p < 0 . 0 1 ) a n d showed a significant negative correlation (r =0.73; P < 0.02) w i t h C T T in c i r r h o s i s . 3) The m e a n d a i l y s t o o l w e t w e i g h t a n d s t o o l w a t e r c o n t e n t were significantly higher in c i r r h o s i s compared to controls (Cirrhosis vs C o n t r o l s ; M e a n + SE; Wet w e i g h t : 3 1 8 + 3 7 V 1 8 3 + 3 2 g p = 0.01; S t o o T w a t e r : 273+35 V 146~26gm p < ~.01). T h e r e w a s h o w e v e r no cor~elation-~etween stool weights (wet, d r y a n d stool water) a n d C T T in c i r r h o s i s . 4) P o r t a l colopathy (colonoscopic and mucosal biopsy scores) d i d n o t c o r r e l a t e w i t h C T T in c i r r h o s i s . Concluslons: Colonic transit is a c c e l e r a t e d in cirrhosis and may be a n important hitherto unrecognised factor in the e t i o p a t h o g e n e s i s of cirrhotic diarrhea. P o r t a l c o l o p a t h y d o e s not s e e m to i n f l u e n c e c o l o n i c t r a n s i t .
• THE CORRELATION OF ANO-RECTALMANOMETRIC DATA(ARM) A N D S U R F A C E A N A L E M G R E C O R D I N G (s-EMG) O F T H E A N A L S P H I N C T E R S IN P A T I E N T S W I T H F E C A L I N C O N T I N E N C E (FI) A N D C O N S T I P A T I O N S Y N D R O M E S (CS). B a r r y W. J a f f i n , T h e r e s a S h a l l e y . M o u n t S i n a i M e d i c a l C e n t e r , NY NY 10029 INTRODUCTION: Biofeedback techniques are being used to t r e a t F e c a l I n c o n t i n e n c e ( F I ) and Constipation Syndromes(CS). To date, there has been no systematic comparison between different modalities to m e a s u r e a n a l s p h i n c t e r p a r a m e t e r s in t h e s a m e p a t i e n t o n t h e s a m e day. M E T H O D S : M e a s u r e m e n t s of t h e r e s t i n g ( R ) a n d s q u e e z e (S) p r e s s u r e of t h e a n a l s p h i n c t e r s in p a t i e n t s with FI and CS w e r e performed using standard Anorectal manometry (Narco Biosystem/Arndorfer system) a n d c o m p a r e d t o m i c r o v o l t (MicroV) r e a d i n g s using the Perry-Orion surface anal EMG sensor d e v i c e p e r f o r m e d w i t h i n o n e h o u r of e a c h other. Linear regression analysis was performed using mmHg (ARM) vs. M i c r o V (s-EMG) data. R E S U L T S : 28 c o n s e c u t i v e patients (18 FI, i0 CS) u n d e r w e n t b o t h A R M a n d S E M G p r i o r to b i o f e e d b a c k r e t r a i n i n g . M e a n age: F I ( 6 0 . 4 ) , C S ( 2 9 . 8 ) . 16/18 FI p a t i e n t s w e r e f e m a l e w h i l e 9 / 1 0 CS p a t i e n t s w e r e female. Mean Mean R-coefficient mmHg MicroV INCONTINENCE Resting: 32.5 2.0 .579 Squeeze: 95.5 9.1 .852 CONSTIPATION Resting: 47.0 3.1 .614 Squeeze: 126.0 13.6 .745 C O N C L U S I O N : T h e r e is a s t r o n g c o r r e l a t i o n b e t w e e n ARM and s-EMG measurements u s e d in b i o f e e d b a c k retraining. This correlation is stronger with c o n t r a c t i o n of t h e a n a l s p h i n c t e r .
Motility and Nerve-Gut Interactions
A621
• CHANGES IN ENTERIC NEURAL FUNCTION IN EXPERIMENTAL COLITIS ARE NOT T LYMPHOCYTE DEPENDENT. K.Jacobson and S.M.Collins. Intestinal Diseases Research Programme, McMaster University, Hamilton, Ontario, Canada. Intestinal inflammation in animals and man is accompanied by extensive changes in enteric neural function, resulting in physiological dysfunction. Previous studies in the inflamed jejunum of nematode-infected rats have shown that inflammation-associated changes in tissues such as nerve or muscle reflect different components of the inflammatory or immune response, and that improvement in one parameter does not predict improvement in another (Vermillion et al Gastro 101:31-38,1991 and Collins et al AIP 263 G198-201,1992). These observations may not necessarily apply to other models. We have recently described extensive changes in adrenergic nerve function in the myenteric plexus in rats with colitis induced by intrarectal (ir) administration of trinitrobenzene sulfonic acid (TNB). We found substantial suppression of 3H-noradrenaline release not only in the inflamed distal colon, but also in the non inflamed transverse colon. In this study, we examined the role of T lymphocytes in the development of these changes in adrenergic neural function in TNB-induced acute colitis. Distal colitis was induced by intrarectal TNB (30 mg in 0.25 ml 50% ethanol) in congenitally athymic (rnu/rnu) rats and their heterozygous (rnu/÷) euthymic littermates, while control rats received 0.25 ml 0.9% saline. One group of animals was sacrificed on day 5, and a second group allowed to recover for 6 weeks. We measured the evoked release of 3H-NA from longitudinal muscle-myenteric plexus preparations (LM-MP) from the distal and transverse colon in response to electrical field stimulation (EFS). Studies were carried out on: (a) day 5 post-TNB or (b) day 42 post-TNB. On day 5, the release of 3H-NA in euthymics was suppressed by 39% in the inflamed distal colon, and by 51% in the non-inflamed transverse colon relative to controls. Athymics demonstrated a similar pattern with a 42% and 47% suppression in distal and transverse colon respectively. By day 42 post-TNB, there was partial recovery from the suppression of 3H-NA release in euthymic rats: However no recovery was seen in athymic rats at day 42 post TNB perhaps due to the greater degree of inflammation observed during the acute colitis (see Jacobsen Gastro this volume). These results indicate that the suppression of adrenergic myanteric nerve function in the inflamed distal colon is independent of functional T cells, and that T cells do not mediate the alteration in nerve function observed at non-inflamed sites in the colon. Supported by MRC Canada.
ESOPHAGEAL MOTILITY DISORDERS: A PATHOPHYSIOLOGICAL CONCEPT. J. Janssens, D. Sifrim, A. Lerut. Center for Gastroentero]ogical Research K.U. Leuven. Belgium. The motor function of the esophagus is regulated by a balanced action of inhibitory and excitatory neurons. Aim: To present evidence in man for the concept that failure of inhibition leads to primary motility disorders, while failure of excitation results in reflux disease. Methods: Manometry with 4 perfused catheters and a sleeve; pH recording at 5 cm above LES. Inhibition in esophageal body examined at various levels using a small balloon inflated sufficiently to create an artificial high pressure zone (AHPZ) of + 20 mm Hg; inhibition measured as % fall in pressure in AHPZ. Twenty patients with primary motility disorder (9 achalasia, 6 diffuse spasm, 5 intermediate forms: (earlier study)); 12 patients with reflux esophagitis (RE): i0 normal controls. Results: In patients with primary motility disorder the degree of inhibition after wet swallows was inversely related to the progression velocity of the contraction (p < 0.001): 100% inhibition preceded normal peristalsis; 0% inhibition resulted in simultaneous contractions (GE 1994; 106: 875). RE and controls had normal inhibition (90.16 ~ 3.1% vs 91.6 ! 8.3%) and normal peristalsis after wet swallows. Monitored during lh fasted and 2h pestprandial]y the rate of transient LES relaxations (TLESR's) was similar in RE and controls (3.8 ~ 6.4 vs 4.0 0.4) but the % TLESR's accompanied by reflux was higher in RE (64.05 Z 6.6% vs 35.74 Z 7.8%. p < 0.05). When TLESR's were accompanied by acid reflux the AHPZ was inhibited in RE (favoring rise of acid) and contracted in controls (as to prevent rise of acid). This absence of contraction in the TLESR's with reflux Changes in AHPZ increase no change inhibition controls n=23 56.5% 26.2% 17.3% RE n=44 9.1% 31.8% 59.1% AHPZ during acid reflux and the presence of normal inhibition after wet swallows suggests a deficient excitation in RE. Conclusion: We propose the concept that dysfunction of inhibitory innervation results in primary esophageal motility disorders while failure of excitatory innervation leads to reflux disease.