Lactose intolerance pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
m (Bot: Removing from Primary care)
 
(14 intermediate revisions by 2 users not shown)
Line 1: Line 1:
<div style="-webkit-user-select: none;">
{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
{| class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;"
|-
|-
Line 10: Line 9:
{{CMG}}; {{AE}} {{MA}}
{{CMG}}; {{AE}} {{MA}}
==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
It is thought that lactose intolerance is the result of [[lactose]] [[malabsorption]] caused by low levels of [[Small intestine|small intestinal]] [[lactase]]. [[Lactose]] is metabolized by the [[Intestine|intestinal]] [[lactase]] to [[galactose]] and [[glucose]] in villous [[Enterocyte|enterocytes]]. In the [[Colon (anatomy)|colon]], unabsorbed [[lactose]] is converted to hydrogen and [[short chain fatty acid]]<nowiki/>s such as [[acetate]], [[butyrate]] and [[propionate]] by [[Intestine|intestinal]] [[bacteria]] and creates symtoms of lactose intolerance. Lactose intolerance is inherited in an [[autosomal recessive]] pattern. Acquired primary lactase deficiency is associated with a CC [[genotype]] at -13.9 kb upstream of the [[lactase]] gene. On gross and microscopic pathology, there are no characteristic findings of lactose intolerance.
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Pathophysiology==
==Pathophysiology==


===Pathogenesis===
===Pathogenesis===
*The exact pathogenesis of [disease name] is not fully understood.These symptoms have been attributed to lactose malabsorption, which results from low levels of small intestinal lactase, which may be due to mucosal injury or, much more commonly, reduced genetic expression of the enzyme lactase-phlorizin hydrolase
* [[Lactose]] is a [[disaccharide]] of [[glucose]] and [[galactose]] in ruminant and human milk.  
OR
** Human milk contains ~7% [[lactose]]
* Lactose is a disaccharide of glucose and galactose in ruminant and human milk.[[Lactose intolerance medical therapy#cite note-pmid26404364-3|[3]]]
** Ruminant’s milk contains ~5% [[lactose]]
** Human milk contains ~7% lactose  
** Ruminant’s milk contains ~5% lactose  


*It is thought that lactose intolerance is the result of lactose malabsorption that it is caused by low level of small intestinal lactase ( lactase-phlorizin hydrolase, or LPH''')'''<ref name="pmid26404364">{{cite journal |vauthors=Silanikove N, Leitner G, Merin U |title=The Interrelationships between Lactose Intolerance and the Modern Dairy Industry: Global Perspectives in Evolutional and Historical Backgrounds |journal=Nutrients |volume=7 |issue=9 |pages=7312–31 |year=2015 |pmid=26404364 |pmc=4586535 |doi=10.3390/nu7095340 |url=}}</ref>   
*It is thought that lactose intolerance is the result of [[lactose]] [[malabsorption]] caused by low levels of [[Small intestine|small intestinal]] [[lactase]] ( lactase-phlorizin hydrolase, or LPH''')'''<ref name="pmid26404364">{{cite journal |vauthors=Silanikove N, Leitner G, Merin U |title=The Interrelationships between Lactose Intolerance and the Modern Dairy Industry: Global Perspectives in Evolutional and Historical Backgrounds |journal=Nutrients |volume=7 |issue=9 |pages=7312–31 |year=2015 |pmid=26404364 |pmc=4586535 |doi=10.3390/nu7095340 |url=}}</ref>   
*The most important causes of low level of small intestinal lactase are:
*The most important causes of low level of [[Small intestine|small intestinal]] [[lactase]] are:
**Mucosal injury   
**[[Mucous membrane|Mucosal]] injury   
**Reduced genetic expression of the enzyme lactase-phlorizin hydrolase   
**Reduced genetic expression of the [[enzyme]] lactase-phlorizin hydrolase   
*Lactose is metabolized by intestinal lactase to galactose and glucose in villous enterocytes and then are uptaked by Na+/glucose cotransporter (SGLT1). <ref name="pmid1702075">{{cite journal |vauthors=Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Fiocca R, Finzi G, Cornaggia M, Capella C, Quaroni A |title=Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia |journal=Gastroenterology |volume=100 |issue=2 |pages=359–69 |year=1991 |pmid=1702075 |doi= |url=}}</ref><ref name="pmid8563765">{{cite journal |vauthors=Martín MG, Turk E, Lostao MP, Kerner C, Wright EM |title=Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption |journal=Nat. Genet. |volume=12 |issue=2 |pages=216–20 |year=1996 |pmid=8563765 |doi=10.1038/ng0296-216 |url=}}</ref>     
*[[Lactose]] is metabolized by [[Intestine|intestinal]] [[lactase]] to [[galactose]] and [[glucose]] in the villous [[Enterocyte|enterocytes]] and then uptaken by [[Sodium-glucose transport proteins|Na+/glucose cotransporter]] ([[Sodium-glucose transport proteins|SGLT1]]). <ref name="pmid1702075">{{cite journal |vauthors=Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Fiocca R, Finzi G, Cornaggia M, Capella C, Quaroni A |title=Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia |journal=Gastroenterology |volume=100 |issue=2 |pages=359–69 |year=1991 |pmid=1702075 |doi= |url=}}</ref><ref name="pmid8563765">{{cite journal |vauthors=Martín MG, Turk E, Lostao MP, Kerner C, Wright EM |title=Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption |journal=Nat. Genet. |volume=12 |issue=2 |pages=216–20 |year=1996 |pmid=8563765 |doi=10.1038/ng0296-216 |url=}}</ref>     
*In colon, unabsorbed lactose is converted to hydrogen gas and short chain fatty acids such as acetate, butyrate and propionate by intestinal bacteria and creates symtoms of lactose intolerance.     
*In the [[Colon (anatomy)|colon]], unabsorbed [[lactose]] is converted to hydrogen and [[short chain fatty acid]]<nowiki/>s such as [[acetate]], [[butyrate]] and [[propionate]] by [[Intestine|intestinal]] bacteria and creates symptoms of lactose intolerance.     
*Milk drinkers has greater lactase activity compare with non-drinkers <ref name="pmid1234085">{{cite journal |vauthors=Yoshida Y, Sasaki G, Goto S, Yanagiya S, Takashina K |title=Studies on the etiology of milk intolerance in Japanese adults |journal=Gastroenterol. Jpn. |volume=10 |issue=1 |pages=29–34 |year=1975 |pmid=1234085 |doi= |url=}}</ref>     
*Milk drinkers have greater [[lactase]] activity compared to non-drinkers. <ref name="pmid1234085">{{cite journal |vauthors=Yoshida Y, Sasaki G, Goto S, Yanagiya S, Takashina K |title=Studies on the etiology of milk intolerance in Japanese adults |journal=Gastroenterol. Jpn. |volume=10 |issue=1 |pages=29–34 |year=1975 |pmid=1234085 |doi= |url=}}</ref>     
*The lactase activity was significantly greater in milk drinkers than non-drinkers. And, internationally, the active is higher in those nationalities whose milk consumption is greater. 3. Lactase is an adaptive enzyme and rather easily induced by lactose load feeding in animals. From the data of our own and of the literature, it was further confirmed that environmental factors play a more important role than genetic factors in the etio-pathogenesis of milk intolerance.   
*
*/ is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*it is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*The progression to [disease name] usually involves the [molecular pathway].
*The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Genetics==
==Genetics==
*Lactose intolerance is transmitted in an autosomal recessive pattern.<ref name="pmid11788828">{{cite journal |vauthors=Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I |title=Identification of a variant associated with adult-type hypolactasia |journal=Nat. Genet. |volume=30 |issue=2 |pages=233–7 |year=2002 |pmid=11788828 |doi=10.1038/ng826 |url=}}</ref>
*Lactose intolerance is transmitted in an [[autosomal recessive]] pattern.<ref name="pmid11788828">{{cite journal |vauthors=Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I |title=Identification of a variant associated with adult-type hypolactasia |journal=Nat. Genet. |volume=30 |issue=2 |pages=233–7 |year=2002 |pmid=11788828 |doi=10.1038/ng826 |url=}}</ref>
*Persistence of intestinal lactase until adulthood is inherited as an autosomal-dominant characteristic<ref name="pmid3140651">{{cite journal |vauthors=Scrimshaw NS, Murray EB |title=The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance |journal=Am. J. Clin. Nutr. |volume=48 |issue=4 Suppl |pages=1079–159 |year=1988 |pmid=3140651 |doi= |url=}}</ref>
*Persistence of intestinal [[lactase]] until adulthood is inherited as an [[autosomal dominant]] manner.<ref name="pmid3140651">{{cite journal |vauthors=Scrimshaw NS, Murray EB |title=The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance |journal=Am. J. Clin. Nutr. |volume=48 |issue=4 Suppl |pages=1079–159 |year=1988 |pmid=3140651 |doi= |url=}}</ref>
*Gene involved in the pathogenesis of lactose intolerance include  lactase-phlorizin hydrolase (LPH) gene located on the long arm (q) of chromosome 2 in region 21(2q21). Lactase persistence is strongly related with presence of the T allele of the single nucleotide polymorphisms (SNP ) located at -13.9 kb upstream of the lactase gene. This allele regulates lactase mRNA.<ref name="pmid12692047">{{cite journal |vauthors=Kuokkanen M, Enattah NS, Oksanen A, Savilahti E, Orpana A, Järvelä I |title=Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia |journal=Gut |volume=52 |issue=5 |pages=647–52 |year=2003 |pmid=12692047 |pmc=1773659 |doi= |url=}}</ref><ref name="pmid26550699">{{cite journal |vauthors=Buzás GM |title=[Lactose intolerance: past and present. Part 1] |language=Hungarian |journal=Orv Hetil |volume=156 |issue=38 |pages=1532–9 |year=2015 |pmid=26550699 |doi=10.1556/650.2015.30261 |url=}}</ref>  
*[[Gene|Genes]] involved in the pathogenesis of lactose intolerance include [[polymorphism]] of the [[MCM6]] ( minichromosome maintenance complex component 6), gene located upstream from the gene lactase-phlorizin hydrolase (LPH) on the long arm (q) of [[chromosome]] 2 in region 21 (2q21). Lactase persistence is strongly related with the presence of the T allele of the [[Single nucleotide polymorphism|single nucleotide polymorphisms]] (SNP ) located at -13.9 kb upstream of the [[lactase]] gene. This allele regulates [[lactase]] [[Messenger RNA|mRNA]].<ref name="pmid12692047">{{cite journal |vauthors=Kuokkanen M, Enattah NS, Oksanen A, Savilahti E, Orpana A, Järvelä I |title=Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia |journal=Gut |volume=52 |issue=5 |pages=647–52 |year=2003 |pmid=12692047 |pmc=1773659 |doi= |url=}}</ref><ref name="pmid26550699">{{cite journal |vauthors=Buzás GM |title=[Lactose intolerance: past and present. Part 1] |language=Hungarian |journal=Orv Hetil |volume=156 |issue=38 |pages=1532–9 |year=2015 |pmid=26550699 |doi=10.1556/650.2015.30261 |url=}}</ref>  
*Acquired primary lactase deficiency is associated with a CC genotype at -13.9 kb and lactase persistence is related to TT genotype<ref name="pmid15479673">{{cite journal |vauthors=Rasinperä H, Savilahti E, Enattah NS, Kuokkanen M, Tötterman N, Lindahl H, Järvelä I, Kolho KL |title=A genetic test which can be used to diagnose adult-type hypolactasia in children |journal=Gut |volume=53 |issue=11 |pages=1571–6 |year=2004 |pmid=15479673 |pmc=1774274 |doi=10.1136/gut.2004.040048 |url=}}</ref>  
*Acquired primary lactase deficiency is associated with a CC [[genotype]] at -13.9 kb and lactase persistence is related to TT [[genotype]].<ref name="pmid15479673">{{cite journal |vauthors=Rasinperä H, Savilahti E, Enattah NS, Kuokkanen M, Tötterman N, Lindahl H, Järvelä I, Kolho KL |title=A genetic test which can be used to diagnose adult-type hypolactasia in children |journal=Gut |volume=53 |issue=11 |pages=1571–6 |year=2004 |pmid=15479673 |pmc=1774274 |doi=10.1136/gut.2004.040048 |url=}}</ref>  
*The development of [disease name] is the result of multiple genetic mutations.
 
==Associated Conditions==


==Gross Pathology==
==Gross Pathology==
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072453/
*On gross pathology, there are no characteristic findings for lactose intolerance.


==Microscopic Pathology==
==Microscopic Pathology==
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*On microscopic histopathological analysis, there are no characteristic findings for lactose intolerance.


==References==
==References==
Line 83: Line 43:
{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category: (name of the system)]]
__NOTOC__
{{Lactose intolerance}}
{{CMG}}
== Pathophysiology ==
===Physiology===
Without lactase, the [[lactose]] [[disaccharide]] in many dairy products remains uncleaved and can not be absorbed through the intestinal wall into the bloodstream, so remains in the intestines.  Enteral [[bacterium|bacteria]] adapt to the relative abundance of this undigested sugar and their [[operon]]s quickly switch over to lactose [[metabolism]], which produces copious amounts of gas by [[fermentation (biochemistry)|fermentation]].
This also causes a range of unpleasant abdominal symptoms, including stomach [[cramp]]s, [[bloating]], [[flatulence]] and [[diarrhea]]. As with other unabsorbed sugars ([[mannitol]]), the lactose raises the [[osmotic]] pressure of the [[colon (anatomy)|colon]] contents, preventing the colon from reabsorbing water and hence causing a [[laxative]] effect to add to the excessive gas production.
===Genetics===
The gene is expressed and the enzyme synthesized if at least one of the two genes are present. Only when both gene expressions are affected is lactase enzyme synthesis reduced, which in turn reduces lactose digestion.<ref name="soy">http://www.soynutrition.com/SoyHealth/SoyLactoseIntolerance.aspx Soy Nutrition</ref> Lactose tolerance (lactase persistence) is the [[dominant allele]]. Lactose intolerance is an [[autosomal recessive trait]].
The normal [[mammal]]ian condition is for the young of a species to experience reduced [[lactose]] (milk sugar) production at the end of the [[weaning]] period (a species-specific length of time). In non dairy consuming societies, lactase production usually drops about 90% during the first four years of life, although the exact drop over time varies widely. However, certain human populations have a [[mutation]] on [[chromosome]] 2 which results in a bypass of the common shutdown in lactase production, making it possible for members of these populations to continue consumption of fresh milk and other dairy products throughout their lives.
Pathological lactose intolerance can occur due to [[celiac disease]], which damages the villi in the small intestine that produce lactase. This lactose intolerance is temporary. Lactose intolerance associated with coeliac disease ceases after the patient has been on a [[gluten-free diet]] long enough for the villi to recover.
Certain people who report problems with consuming lactose are not actually lactose intolerant. In a study of 323 Sicilian adults, Carroccio et al. (1998) found only 4% were both lactose intolerant and lactose maldigesters, while 32.2% were lactose maldigesters but did not test as lactose intolerant. However, Burgio et al. (1984) found that 72% of 100 Sicilians were lactose intolerant in their study and 106 of 208 northern Italians (i.e., 51%) were lactose intolerant.
==References==
{{Reflist|2}}
{{WS}}
{{WH}}


[[Category:Gastroenterology]]
[[Category:Gastroenterology]]
[[Category:Endocrinology]]
[[Category:Medicine]]
[[Category:Up-To-Date]]

Latest revision as of 22:28, 29 July 2020

https://https://www.youtube.com/watch?v=_i2cclGYPx0%7C350}}

Lactose Intolerance Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Lactose Intolerance from Other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Lactose intolerance pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Lactose intolerance pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Lactose intolerance pathophysiology

CDC on Lactose intolerance pathophysiology

Lactose intolerance pathophysiology in the news

Blogs on Lactose intolerance pathophysiology

Directions to Hospitals Treating Lactose intolerance

Risk calculators and risk factors for Lactose intolerance pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mahda Alihashemi M.D. [2]

Overview

It is thought that lactose intolerance is the result of lactose malabsorption caused by low levels of small intestinal lactase. Lactose is metabolized by the intestinal lactase to galactose and glucose in villous enterocytes. In the colon, unabsorbed lactose is converted to hydrogen and short chain fatty acids such as acetate, butyrate and propionate by intestinal bacteria and creates symtoms of lactose intolerance. Lactose intolerance is inherited in an autosomal recessive pattern. Acquired primary lactase deficiency is associated with a CC genotype at -13.9 kb upstream of the lactase gene. On gross and microscopic pathology, there are no characteristic findings of lactose intolerance.

Pathophysiology

Pathogenesis

Genetics

  • Lactose intolerance is transmitted in an autosomal recessive pattern.[5]
  • Persistence of intestinal lactase until adulthood is inherited as an autosomal dominant manner.[6]
  • Genes involved in the pathogenesis of lactose intolerance include polymorphism of the MCM6 ( minichromosome maintenance complex component 6), gene located upstream from the gene lactase-phlorizin hydrolase (LPH) on the long arm (q) of chromosome 2 in region 21 (2q21). Lactase persistence is strongly related with the presence of the T allele of the single nucleotide polymorphisms (SNP ) located at -13.9 kb upstream of the lactase gene. This allele regulates lactase mRNA.[7][8]
  • Acquired primary lactase deficiency is associated with a CC genotype at -13.9 kb and lactase persistence is related to TT genotype.[9]

Gross Pathology

  • On gross pathology, there are no characteristic findings for lactose intolerance.

Microscopic Pathology

  • On microscopic histopathological analysis, there are no characteristic findings for lactose intolerance.

References

  1. ↑ Silanikove N, Leitner G, Merin U (2015). "The Interrelationships between Lactose Intolerance and the Modern Dairy Industry: Global Perspectives in Evolutional and Historical Backgrounds". Nutrients. 7 (9): 7312–31. doi:10.3390/nu7095340. PMC 4586535. PMID 26404364.
  2. ↑ Maiuri L, Raia V, Potter J, Swallow D, Ho MW, Fiocca R, Finzi G, Cornaggia M, Capella C, Quaroni A (1991). "Mosaic pattern of lactase expression by villous enterocytes in human adult-type hypolactasia". Gastroenterology. 100 (2): 359–69. PMID 1702075.
  3. ↑ Martín MG, Turk E, Lostao MP, Kerner C, Wright EM (1996). "Defects in Na+/glucose cotransporter (SGLT1) trafficking and function cause glucose-galactose malabsorption". Nat. Genet. 12 (2): 216–20. doi:10.1038/ng0296-216. PMID 8563765.
  4. ↑ Yoshida Y, Sasaki G, Goto S, Yanagiya S, Takashina K (1975). "Studies on the etiology of milk intolerance in Japanese adults". Gastroenterol. Jpn. 10 (1): 29–34. PMID 1234085.
  5. ↑ Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I (2002). "Identification of a variant associated with adult-type hypolactasia". Nat. Genet. 30 (2): 233–7. doi:10.1038/ng826. PMID 11788828.
  6. ↑ Scrimshaw NS, Murray EB (1988). "The acceptability of milk and milk products in populations with a high prevalence of lactose intolerance". Am. J. Clin. Nutr. 48 (4 Suppl): 1079–159. PMID 3140651.
  7. ↑ Kuokkanen M, Enattah NS, Oksanen A, Savilahti E, Orpana A, Järvelä I (2003). "Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia". Gut. 52 (5): 647–52. PMC 1773659. PMID 12692047.
  8. ↑ Buzás GM (2015). "[Lactose intolerance: past and present. Part 1]". Orv Hetil (in Hungarian). 156 (38): 1532–9. doi:10.1556/650.2015.30261. PMID 26550699.
  9. ↑ Rasinperä H, Savilahti E, Enattah NS, Kuokkanen M, Tötterman N, Lindahl H, Järvelä I, Kolho KL (2004). "A genetic test which can be used to diagnose adult-type hypolactasia in children". Gut. 53 (11): 1571–6. doi:10.1136/gut.2004.040048. PMC 1774274. PMID 15479673.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Lactose_intolerance_pathophysiology&oldid=1640077"