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{{Lactose intolerance}}
{{Lactose intolerance}}
{{CMG}}


== Pathophysiology ==
{{CMG}}; {{AE}} {{MA}}
==Overview==
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.


===Genetics===
==Pathophysiology==
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.
===Pathogenesis===
* [[Lactose]] is a [[disaccharide]] of [[glucose]] and [[galactose]] in ruminant and human milk.  
** Human milk contains ~7% [[lactose]]  
** Ruminant’s milk contains ~5% [[lactose]]  


Pathological lactose intolerance can occur due to [[coeliac 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.
*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 intestine|small intestinal]] [[lactase]] are:
**[[Mucous membrane|Mucosal]] injury 
**Reduced genetic expression of the [[enzyme]] lactase-phlorizin hydrolase 
*[[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 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 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>   


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.
==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>
*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|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>
 
==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==
==References==
{{Reflist|2}}


{{Reflist|2}}
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{{WS}}


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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.

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