1. 이창균 경희대학교 의학전문대학원 경희대학교 병원 소화기내과
만성변비의 진단과 내과적 치료
이창균
경희대학교 의학전문대학원
경희대학교 병원 소화기내과

2. Egyptian papyrus
“The body is poisoned by material released from decomposing waste in the intestines…”
Constipation as the “the disease of diseases”
“Autointoxication”
“Autointoxication theory”
the 16th century BC

3. 1920s: advertisement for a “candy cathartic”

4. An abdominal massage machine

5. Rectal dilators for constipation, 1938

6. Total colectomy for as a cure of “autointoxication”
Constipation related to “civilization”

7. x
Misconceptions 1
Daily bowel movements are important for overall health.
Chronic constipation may result in poor general health because of failure to empty toxins from the colon in a timely fashion.

8. Dietary fiber hypothesis and “Western diseases”
Don’t forget fiber in your diet !
- Dr. Denis Burkitt

9. Geographic prevalence of constipation

10. Let’s start to talk about current management of constipation.
Jump forward to 2011
High prevalence
15% in adults (9% in children)
High health care burden
6.3 million patient visits to medical centres
total costs of $1.7 billion (in US)
Let’s start to talk about
current management of constipation.

11. What causes constipation?

12. Rome Criteria * ≥25% of defecations
Symptoms ≥3 mo; onset ≥6 mo prior to diagnosis
* ≥25% of defecations

13. Dynamics of defecation

14. 3 types of functional constipation
Normal transit constipation
Slow transit constipation
Pelvic floor dysfunctions

15. Diagnostic algorithm

16. Radioopaque marker (KolomarkTM)
Colonic transit time
Initial screening test:
Normal- or slow transit constipation vs
Pelvic floor dysfunction
7th day Rt Lt
Radioopaque marker (KolomarkTM) RS

17. Diagnosis of pelvic floor dysfunctions
Balloon expulsion test
Anorectal manometry
Defecography

18. Balloon Expulsion Test
Balloon expulsion test is a simple, office-based screening test for defecatory disorders.
After insertion of the latex balloon into the rectum, 50 ml of water or air is instilled into the balloon, and the patient is asked to expel the balloon into a toilet.
Inability to expel the balloon within 2 or 3 minutes suggests a defecatory disorder.
Lembo A et al. NEJM 2003;349:1360-8

19. Anorectal manometry

20. Normal Defecogram
102˚
129˚

21. Anismus

22. What are the medical therapy for constipation?
Basic advice
Laxative agents
Prokinetic agents
Biofeedback treatment
Normal or Slow transit C
Pelvic floor dysfunctions

23. Basic advice Correct position for defecation
Increasing dietary fiber intake
Increasing water intake
Adequate exercise
Bulk-forming laxatives

24. Correct position for defecation
“semi-squatting” position << natural squatting position ?

25. Basic advice

26. x
Misconceptions 2
Constipation is the result of a diet poor in fiber, low fluid intake, and/or lack of exercise.
Evidence가 없다고 하여 evidence가 아닌 것은 아니다.

27. Bulk-forming laxatives
Stepwise approach
Basic advice
Dietary fiber
Water ingestion
Bulk-forming laxatives
Psyllium
Bran
Methylcellulose
Calcium polypcarbophil
Osmotic laxatives
Magnesium salts
Sorbitol
Lactulose
Polyethylene glycol
Stimulant laxatives
Senna
Bisacodyl
뮤타실 (일양)
아기오 (부광)
웰콘 (건일)
산화 마그네슘 (삼천당)
락티톨
두팔락(중외)
아락실 (부광)
둘코락스 (베링거)

28. Bulk-forming laxatives
Usual Adult Dose
Onset of
Action
Psyllium
Up to 1 tsp TID
12-72 h
Methylcellulose
Calcium
polycarbophil
2-4 tablets/day
24-48 h
부피형성하제는 소장에서 흡수되지 않고
대장 세균에 의해서도 분해되지 않아 수분을 함유할 수 있다.
수분 유지에 의해 장관내 대변부피가 증가하면 대변량이 증가
하고 대변이 부드러워져서 쉽게 배출된다. 하제의 일부는 장
내세균에 의해 대사되어 이산화탄소나 수소와 같은 가스를 형
성한다. 이로 인해 복부 팽만감이나 다량의 방귀를 유발한다.
충분한 양의 물과 함께 복용하는 것이 중요하며 장 협착이나
장 폐쇄 환자에서는 증상을 악화시킬 수 있으므로 사용해서는
안된다. 요약하면, 부피형성하제는 장기간 투약하면서 관찰한 연구
는 없지만 변비의 치료에 효과적이라고 말할 수 있다.

29. Osmolar agents Laxative Usual Adult Dose Onset of Action
Polyethylene glycol
g in 240 mL
liquids
2-4 days
Lactulose
15-30 mL QD or BID
24–48 h
Sorbitol
120 mL of 25%
solution QD
24-48 h
Glycerine
3 g suppository QD
15-60 min
Magnesium sulfate
15 g QD
0.5-3 h
Magnesium citrate
200 mL QD
마그네슘 제제는 삼투성 완하제로서 수산화 마그네슘, 구
연산 마그네슘, 황산 마그네슘 등이 있다. 마그네슘 이온은
장에서 거의 흡수되지 않아서 수분의 저류효과로 장관내압이
증가하여 하제로 작용한다. 과량 복용 시 고마그네슘 혈증을
일으킬 수 있어 신기능 부전 환자와 소아에서는 주의하여 투
여해야 한다.
PEG는 고삼투성 하제로서 장에서 흡수되지 않고 대장 내
에서 높은 삼투압을 유지하여 체내로의 수분의 흡수가 일어나
지 않아 액체 상태로 배변이 된다.
우리나라 소아 변비 환자에서도 PEG를 6개월 이상 투여하
였을 때 심각한 부작용은 관찰되지 않았다.64 우리나라의 임상
의들은 대체적으로 PEG 투여가 변비의 치료에 효과적이라는
데 동의하였다. 요약하면, PEG는 변비 환자에서 안전하게 장기간 투약할
수 있는 효과적인 약제이다.
비흡수성다당류하제는 고삼투성 하제로서 락툴로우스
(lactulose), 락티톨(lactitol), 솔비톨(sorbitol), 글리세린
(glycerine) 등이 있다. 락툴로우스는 갈락토스(galactose)와
프록토스(fructose)의 합성 이당체로서 소장에서 흡수되지 않
고 대장내 세균에 의해 대사되어 삼투효과를 나타낸다.

30. Stimulant laxatives Laxative Usual Adult Dose Onset of Action
Bisacodyl
10-20 mg PO QHS
6-10 h
10 mg suppository QD
15-60 min
Senna
2-4 tablets QHS
6-12 h
자극성하제의 작용 기전은 정확하게 알려져 있지 않지
만 대장 내에서 수분 및 전해질의 흡수를 억제하고 장내에
축적하여 장운동을 촉진하는 것으로 알려져 있다.
일반적인 하제에 반응이 없는 변비 환자에게 단기간 동안
자극성하제를 투여해 볼 수 있다.

31. x
Misconceptions 3
Chronic use of currently available stimulant laxatives is unsafe because they may damage the colon when used chronically.
The basis for the concept that stimulant laxatives can
damage the enteric nervous system and or colonic smooth
muscle is largely derived from uncontrolled observations of
humans and poorly designed studies in animals.
In contrast,
studies that do not report such damage are well done
and numerous. The preponderance of evidence suggests that
chronic use of available stimulant laxatives is not harmful to
the colon, even if they are abused.

32. Bisacodyl Category I drug by the US-FDA Category I
“Safe and effective”

33. x
Misconceptions 4
Stimulant laxatives induce habituation and tolerance or physical dependence and addiction.
There is some evidence that tolerance to stimulant laxatives
occurs in those relatively few patients with severe slow
transit constipation in whom most other laxatives are ineffective
and whose colons are often characterized by loss of
enteric neuronal elements. Although tolerance to laxatives
has not been studied extensively in humans, it seems to be
uncommon in the majority of laxative users.
Because most laxatives are not absorbed and none cross
the blood-brain barrier, there is no pharmacologic basis for
addiction.

34. Better strategy for use of laxatives
Non-stimulant laxatives on a daily basis +
Stimulant laxatives twice or thrice weekly
When patients fail to respond adequately to bulk or osmotic laxatives,
a reasonable regimen is to attempt stimulant laxatives
such as bisacodyl or senna when no spontaneous
bowel movement occurs after 48 hours (thrice weekly) or 72
hours (twice weekly).

35. Probiotics in constipation?

36. Monitoring response to treatment
Spontaneous bowel movement (SBM)
Complete SBM
Bristol stool chart

37. Enterokinetic agents Historical agents Cisapride: withdrawal
Metoclopramide: no effect
Erythromycin: no effect

38. New prokinetic agents Tegaserod Prucalopride Lubiprostone
non-selective serotonin (5-HT4) receptor agonist
Prucalopride
selective, high-affinity 5-HT4 receptor agonist
Lubiprostone
chloride channel activator
Lubiprostone: bicyclic fatty acid  activates chloride channels of the apical membrane of the intestinal epithelial cells  moving water into the gut lumen.

39. Role of Serotonin

40. Serotonin and EC Cells in Constipation
Serotonin stimulates small intestine and colonic motility and accelerates transit1
A study in 10 patients with chronic laxative use demonstrated a reduced number of serotonin immunoreactive cells, P<.052
Reduced number of serotonin cells in slow transit constipation contributes to reduced motility of the colon with consequent constipation2
1Talley , Aliment Pharm Ther 1992; 6: 273
2El-Salhy et al, Scand J Gastroenterol 1990; 10: 1007

41. Serotonin and Motor Activity
Proximal
Distal
Interneurons in the Myenteric Plexus
Movement of gut content
Orad
motor neurons
(contraction)
ACh / SP
Caudad
motor neurons
(relaxation)
VIP / NO
CGRP
Submucosal IPAN
5-HT4 receptor
5-HT1p receptor
. . .
. . .
. . .
5-HT (serotonin)
Enterochromaffin cells in GI tract release 5-HT
Adapted from Grider et al, Gastroenterology 1998; 115: Adapted from Gershon, Rev Gastroenterol Dis 2003; 3: S25

42. How prucalopride works?
5-HT4 수용체에 작용하는 작용제로 장운동을 증가시켜 만성
변비 치료에 효과를 보인다.

43. A placebo-controlled trial of prucalopride for severe chronic constipation
N Engl J Med 2008;358(22):2344–54.

44. Misconceptions 5 ?
Are enterokinetic agents a major advance in treating constipation?
Are enterokinetic agents cost-effective in most constipated patients in the primary care setting?

45. Treatment of choice for pelvic floor dysfunction
Biofeedback
Pelvic floor rehabilitation
Sensory and muscular training
Treatment of choice for pelvic floor dysfunction
바이오피드백은 전기 혹은 기계적 장치를 이용하여 생체내
반응을 인식하게 하는 교육 전략이다.만성 변비 환자에서
바이오피드백 치료는 배변시 골반저 횡문근을 이완하게 훈련
하고 소량의 대변에 의한 직장 팽창을 인식할 수 있게 하며
복압을 효과적으로 상승할 수 있도록 환자를 교육하는 것이 다.
체계적인 분석에 의하면 골반저기능부전 환자에서 바이오
피드백의 치료 효과는 70%정도 된다 치료의 장점으로
는 변비 증상 완화, 삶의 질 향상, 장통과시간의 단축과 하제
의 사용량 감소 등을 가져온다.105,109,110 장기간 추적 연구에서
바이오피드백의 효과는 치료 후 2년까지 지속되었다.

47. Protocol for biofeedback therapy

48. Evidence-based summary for the treatment of constipation

49. Surgical treatment Severe refractory slow-transit constipation
Colonic inertia
Subtotal colectomy with ileorectal anastomosis

50. When to refer for specialist care
Alarm symptoms
Psychological treatment for irritable bowel syndrome
Painful anorectal conditions
anal fissure, haemorrhoids, abscess, or fistula
Obstructed defecation
Paradoxical puborectalis contraction
Solitary rectal ulcer syndrome
Rectocoele
Rectal intussusception and rectal prolapse

51. on chronic constipation
Acute
on chronic constipation

52. SEMS in Acute colonic malignant obstruction

53. Stercoral ulcers

54. Take home messages Basic understanding of pathophysiology
Stepwise approach of laxatives
Biofeedback treatment for pelvic floor dysfunction
Specialist referral for refractory cases

55. Educational web resources
대한소화기학회 (
변비 치료에 관한 임상진료지침 (2011)
Rome Foundation (
British Society of Gastroenterology (
Core (

56. Enjoy your summer vacation!