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__NOTOC__
__NOTOC__
{{Gout}}
{{CMG}} {{AE}} {{Shivam Singla}}
{{CMG}}
[[Image:Home_logo1.png|right|150px|link=https://www.wikidoc.org/index.php/Gout]]
 
==Overview==
==Overview==
Hyperuricemia is considered a multifactorial metabolic disorder in the general population. The levels of uric acid are influenced by the use of drugs, medications, renal impairment, and Alcohol also. The excess of uric acid levels gets deposited in the joints, kidneys, and a lot of tissue leading to clinical manifestations such as tophi, nephrolithiasis along the presence of urate nephropathy. Decreased excretion of uric acid contributes the maximum towards the development of Hyperuricemia. Along with the minimal contribution from other factors like increased production and increased consumption of foods rich in uric acid. The deposits in the joints, skin, and other tissues compromise the function of organs and resulting in the abnormal configuration of joint with funv=ctional limitation along with the presence of clinical signs in the form of pain and swelling.
==Pathophysiology==
In terms of pathophysiological classification, we can categorize gout into 2 main types
1) '''Primary gout''': Mainly hereditary or related to enzymatic abnormalities
2) '''Secondary Gout''': Secondary to other reasons like drugs, renal insufficiency, dietary or related to malignancy[[File:Gout Pathophysiology.png|456x456px|thumb|'''Pathophysiological factors for the development of Gout'''  https://www.pinterest.com/pin/129971139223442993/?nic_v2=1a30H8fPo|alt=]]
The pathophysiology<ref name="pmid23745463">{{cite journal |vauthors=Milas-Ahić J, Prus V, Visević R |title=[Pathophysiology of gout] |journal=Reumatizam |volume=59 |issue=2 |pages=89–92 |date=2012 |pmid=23745463 |doi= |url=}}</ref><ref name="pmid28148582">{{cite journal |vauthors=Abhishek A, Roddy E, Doherty M |title=Gout - a guide for the general and acute physicians |journal=Clin Med (Lond) |volume=17 |issue=1 |pages=54–59 |date=February 2017 |pmid=28148582 |pmc=6297580 |doi=10.7861/clinmedicine.17-1-54 |url=}}</ref>of Gout mainly relates to hyperuricemia. Greater is the degree of hyperuricemia greater is the likelihood of developing Gout<ref name="pmid23895142">{{cite journal |vauthors=Gustafsson D, Unwin R |title=The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality |journal=BMC Nephrol |volume=14 |issue= |pages=164 |date=July 2013 |pmid=23895142 |pmc=3750299 |doi=10.1186/1471-2369-14-164 |url=}}</ref>.
Numerous reasons can lead to the development of an increase in the level of uric acids<ref name="pmid27112094">{{cite journal |vauthors=Dalbeth N, Merriman TR, Stamp LK |title=Gout |journal=Lancet |volume=388 |issue=10055 |pages=2039–2052 |date=October 2016 |pmid=27112094 |doi=10.1016/S0140-6736(16)00346-9 |url=}}</ref><ref name="pmid28233117">{{cite journal |vauthors=Schlee S, Bollheimer LC, Bertsch T, Sieber CC, Härle P |title=Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 1: Epidemiology and pathophysiology |journal=Z Gerontol Geriatr |volume=51 |issue=4 |pages=453–460 |date=June 2018 |pmid=28233117 |doi=10.1007/s00391-017-1197-3 |url=}}</ref>:


Gout occurs when mono-sodium urate crystals form on the articular cartilage of joints, on tendons, and in the surrounding tissues. [[Purine metabolism]] gives rise to uric acid, which is normally excreted in the urine. Uric acid is more likely to form into crystals when there is a [[hyperuricaemia]], although it is 10 times more common without clinical gout than with it<ref>{{cite journal | author=Virsaladze D, Tetradze L, Djavashvili L, Esakia N, Tananashvili D. | title=Levels of uric Acid in serum in patients with metabolic syndrome. | journal=Georgian Med News | year=2007 | volume=146 | pages=34&ndash;7 | id=PMID 17595458}}</ref>
*Enhanced or increased purine uptake.
*Decreased excretion of uric acid
*Increased production of uric acid
*Etiology in a lot of cases with rising uric acid levels is still unknown. <br />


Purines can be generated by the body via breakdown of cells in normal cellular turnover, or can be ingested in purine-rich foods such as seafood. the kidneys are responsible for approximately one-third of uric acid excretion, with the gut responsible for the rest. It may be possible that defects in the kidney that may be genetically determined are responsible for the predisposition of individuals for developing gout.


There are also different racial propensities to develop gout. Gout is high among the peoples of the Pacific Islands, and the Māori of New Zealand, but rare in the Australian aborigine despite the latter's higher mean concentration of serum uric acid.<!--
'''Increased intake'''
  --><ref>{{cite journal | author = Roberts-Thomson R, Roberts-Thomson P | title = Rheumatic disease and the Australian aborigine | journal = Ann Rheum Dis | volume = 58 | issue = 5 | pages = 266&ndasgh;70 | year = 1999 | id = PMID 10225809 | url=http://ard.bmjjournals.com/cgi/content/full/58/5/266}}</ref>  In the United States, gout is twice as prevalent in African American males as it is in Caucasians.<!--
  --><ref>{{cite web | author = Rheumatology Therapeutics Medical Center | title = What Are the Risk Factors for Gout? | url=http://www.arthritisconsult.com/gout.html#risk | accessdate = 2007-01-26}}</ref>


A seasonal link also may exist, with significantly higher incidence of acute gout attacks occurring in the spring.<ref>{{cite web | author =Schlesinger N, Gowin KM, Baker DG, Beutler AM, Hoffman BI, Schumacher HR Jr. | title = Acute gouty arthritis is seasonal. | url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=9489831&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus | accessdate = 2007-09-27}}</ref> <ref>{{cite web | author = Gallerani M, Govoni M, Mucinelli M, Bigoni M, Trotta F, Manfredini R. | title = Seasonal variation in the onset of acute microcrystalline arthritis. | url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=10534553&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstractPlus| accessdate = 2007-09-27}}</ref>
The increased uptake is mainly related to


Hyperuricemia is considered an aspect of [[metabolic syndrome]], although its prominence has been reduced in recent classifications. This explains the increased prevalence of gout among [[obesity|obese]] individuals.  
*Increases intake of purine-rich food substances by the patient such as 
**Asparagus, meat broths, mushrooms, liver, kidney, sweetbreads.
**The increased intake of all of these substances can increase the risk of accumulation of more and more purines ultimately resulting in the excess of uric acid.


Gout is a form of arthritis that affects mostly men between the ages of 40 and 50. The high levels of uric acid in the blood are caused by protein rich foods. Alcohol intake often causes acute attacks of gout and hereditary factors may contribute to the elevation of uric acid. Typically, persons with gout are obese, predisposed to diabetes and hypertension, and at higher risk of heart disease. Gout is more common in affluent societies due to a diet rich in proteins, fat, and alcohol.<ref>{{cite book|author = Robert S. Ivker, D.O. , et al | title = The Complete Self-Care guide to Holistic Medicine | year = 1999 | pages=186&ndash;8 | id = ISBN0-87477-986-J}}</ref> It is known that [[Lead(II) acetate|lead sugar]] was used to sweeten wine, and that chronic [[lead poisoning]] is a cause of gout,<ref>{{cite journal | author=Lin JL, Huang PT. | title=Body lead stores and urate excretion in men with chronic renal disease | journal=J Rheumatol | year=1994 | volume=21 | issue=4 | pages=705&ndash;9 | id=PMID 8035397}}</ref><ref>{{cite journal | author=Shadick NA, Kim R, Weiss S, Liang MH, Sparrow D, Hu H. | title=Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the Normative Aging Study | journal=J Rheumatol | year=2000 | volume=27 | issue=7 | pages=1708&ndash;12 | id=PMID 10914856}}</ref> which condition is then known as '''saturnine gout,''' because of its association with alcohol and excess.<ref>{{cite journal | author=Ball GV. | title=Two epidemics of gout | journal=Bull Hist Med | year=1971 | volume=45 | issue=5 | pages=401&ndash;8 | id=PMID 4947583}}</ref>
*Beer is also particularly rich in guanosine which is a purine nucleotide.


Gout also can develop as co-morbidity of other diseases, including polycythaemia, [[leukaemia]], intake of [[cytotoxic]]s, [[obesity]], [[diabetes]], [[hypertension]], [[renal]] disorders, and [[hemolytic anemia]]. This form of gout is often called secondary gout. [[Diuretic]]s (particularly [[thiazide]] diuretics) have traditionally been blamed for precipitating attacks of gout, but a Dutch case-control study from 2006 appears to cast doubt on this conclusion.<ref>{{cite journal | author = Janssens H, van de Lisdonk E, Janssen M, van den Hoogen H, Verbeek A | title = Gout, not induced by diuretics? A case-control study from primary care | journal = Ann Rheum Dis | volume = 65 | issue = 8 | pages = 1080&ndash;3 | year = 2006 |  id = PMID 16291814 | doi=10.1136/ard.2005.040360}}</ref>
[[File:Gout pathogenesis.png|alt=Numerous factors and conditions responsible for the development of gout|thumb|469x469px|'''Pathophysiology of Gout''' 
https://www.researchgate.net/figure/Key-checkpoints-in-gout-pathogenesis_fig1_44601699]]




'''Increased production'''
The increased production is mainly
*Increase in turn over of cells like in various hematological conditions such as Hemolytic anemia, leukemia, and lymphoma.
*Conditions associated with an increased rate of cell proliferation and cell death.
**Cytotoxic therapy
**Radiation
**Psoriasis<ref name="pmid30317664">{{cite journal |vauthors=Hu SC, Lin CL, Tu HP |title=Association between psoriasis, psoriatic arthritis and gout: a nationwide population-based study |journal=J Eur Acad Dermatol Venereol |volume=33 |issue=3 |pages=560–567 |date=March 2019 |pmid=30317664 |doi=10.1111/jdv.15290 |url=}}</ref>
*Obesity - As the urate production is directly proportional to the body surface area
*Hereditary conditions[[File: Purine catabolism pathway.jpg|thumb|'''Enzymatic Pathway''' resulting in hyperuricemia- De novo synthesis pathway and HGPRT pathway    http://themedicalbiochemistrypage.org/nucleotides-biosynthesis-catabolism/]]
*Enzyme abnormalities
**Overactivity of Phosphoribosyltransferase
**Deficiency of HGPRT
**Absence of HGPRT ( Lesch-Nyhan syndrome)<ref name="pmid18067674">{{cite journal |vauthors=Torres RJ, Puig JG |title=Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome |journal=Orphanet J Rare Dis |volume=2 |issue= |pages=48 |date=December 2007 |pmid=18067674 |pmc=2234399 |doi=10.1186/1750-1172-2-48 |url=}}</ref>
**
'''Decreased/Reduced renal excretion'''
This is the most common cause of hyperuricemia. Various factors responsible for its reduced elimination are:
*Hereditary
*Compromised renal function ( Reduced GFR)
*On Diuretics<ref name="pmid27498351">{{cite journal |vauthors=Ben Salem C, Slim R, Fathallah N, Hmouda H |title=Drug-induced hyperuricaemia and gout |journal=Rheumatology (Oxford) |volume=56 |issue=5 |pages=679–688 |date=May 2017 |pmid=27498351 |doi=10.1093/rheumatology/kew293 |url=}}</ref>
*Alcohol intake<ref name="pmid26082349">{{cite journal |vauthors=Towiwat P, Li ZG |title=The association of vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and gout |journal=Int J Rheum Dis |volume=18 |issue=5 |pages=495–501 |date=June 2015 |pmid=26082349 |doi=10.1111/1756-185X.12622 |url=}}</ref>
**The lactic acid blocks the excretion of urate from the renal tubules. Alcohol induces the purine metabolism in the liver and  increases the formation of lactic acid and
**Alcohol also directly stimulates the synthesis of urate by the liver
*Drugs like cyclosporine that are toxic to the renal tubules leads to the decreased elimination of uric acid and ultimately resulting in the urate retention.
===Gross and Microscopic Pathology===
{| align="center"
|- valign="top"
|[[Image:Gout 0001.jpg|thumb|Kidney: Uric Acid Deposition: Gross, an excellent example of gouty nephropathy with deposits and excavation in pyramids]]
|[[Image:Gout 0002.jpg|thumb|Kidney: Papillary Necrosis: Gross, yellow foci in pyramids, a gout kidney]]
|[[Image: Gout (no birefringence).jpg|thumb|Gout (Needles, no birefringence, monosodium urate)]]
|[[Image: Gout 0003.jpg|thumb|Skin: Tophus: Micro med mag H&E uric acid deposits with giant cells. Easily recognizable as gout or uric acid tophus]]
|
|}
==Sources==
Copyleft images obtained courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA) [http://www.peir.net Images courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology]


==References==
==References==
{{reflist|2}}
{{Reflist|2}}


{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Arthritis]]
[[Category:Rheumatology]]
[[Category:Disease]]

Latest revision as of 23:29, 5 October 2020

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

Overview

Hyperuricemia is considered a multifactorial metabolic disorder in the general population. The levels of uric acid are influenced by the use of drugs, medications, renal impairment, and Alcohol also. The excess of uric acid levels gets deposited in the joints, kidneys, and a lot of tissue leading to clinical manifestations such as tophi, nephrolithiasis along the presence of urate nephropathy. Decreased excretion of uric acid contributes the maximum towards the development of Hyperuricemia. Along with the minimal contribution from other factors like increased production and increased consumption of foods rich in uric acid. The deposits in the joints, skin, and other tissues compromise the function of organs and resulting in the abnormal configuration of joint with funv=ctional limitation along with the presence of clinical signs in the form of pain and swelling.

Pathophysiology

In terms of pathophysiological classification, we can categorize gout into 2 main types

1) Primary gout: Mainly hereditary or related to enzymatic abnormalities

2) Secondary Gout: Secondary to other reasons like drugs, renal insufficiency, dietary or related to malignancy

Pathophysiological factors for the development of Gout https://www.pinterest.com/pin/129971139223442993/?nic_v2=1a30H8fPo


The pathophysiology[1][2]of Gout mainly relates to hyperuricemia. Greater is the degree of hyperuricemia greater is the likelihood of developing Gout[3].

Numerous reasons can lead to the development of an increase in the level of uric acids[4][5]:

  • Enhanced or increased purine uptake.
  • Decreased excretion of uric acid
  • Increased production of uric acid
  • Etiology in a lot of cases with rising uric acid levels is still unknown.


Increased intake

The increased uptake is mainly related to

  • Increases intake of purine-rich food substances by the patient such as
    • Asparagus, meat broths, mushrooms, liver, kidney, sweetbreads.
    • The increased intake of all of these substances can increase the risk of accumulation of more and more purines ultimately resulting in the excess of uric acid.
  • Beer is also particularly rich in guanosine which is a purine nucleotide.
Numerous factors and conditions responsible for the development of gout
Pathophysiology of Gout https://www.researchgate.net/figure/Key-checkpoints-in-gout-pathogenesis_fig1_44601699


Increased production

The increased production is mainly

  • Increase in turn over of cells like in various hematological conditions such as Hemolytic anemia, leukemia, and lymphoma.
  • Conditions associated with an increased rate of cell proliferation and cell death.
    • Cytotoxic therapy
    • Radiation
    • Psoriasis[6]
  • Obesity - As the urate production is directly proportional to the body surface area


Decreased/Reduced renal excretion

This is the most common cause of hyperuricemia. Various factors responsible for its reduced elimination are:

  • Hereditary
  • Compromised renal function ( Reduced GFR)
  • On Diuretics[8]
  • Alcohol intake[9]
    • The lactic acid blocks the excretion of urate from the renal tubules. Alcohol induces the purine metabolism in the liver and increases the formation of lactic acid and
    • Alcohol also directly stimulates the synthesis of urate by the liver
  • Drugs like cyclosporine that are toxic to the renal tubules leads to the decreased elimination of uric acid and ultimately resulting in the urate retention.



Gross and Microscopic Pathology

Kidney: Uric Acid Deposition: Gross, an excellent example of gouty nephropathy with deposits and excavation in pyramids
Kidney: Papillary Necrosis: Gross, yellow foci in pyramids, a gout kidney
Gout (Needles, no birefringence, monosodium urate)
Skin: Tophus: Micro med mag H&E uric acid deposits with giant cells. Easily recognizable as gout or uric acid tophus

Sources

Copyleft images obtained courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA) Images courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology

References

  1. ↑ Milas-Ahić J, Prus V, Visević R (2012). "[Pathophysiology of gout]". Reumatizam. 59 (2): 89–92. PMID 23745463.
  2. ↑ Abhishek A, Roddy E, Doherty M (February 2017). "Gout - a guide for the general and acute physicians". Clin Med (Lond). 17 (1): 54–59. doi:10.7861/clinmedicine.17-1-54. PMC 6297580. PMID 28148582.
  3. ↑ Gustafsson D, Unwin R (July 2013). "The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality". BMC Nephrol. 14: 164. doi:10.1186/1471-2369-14-164. PMC 3750299. PMID 23895142.
  4. ↑ Dalbeth N, Merriman TR, Stamp LK (October 2016). "Gout". Lancet. 388 (10055): 2039–2052. doi:10.1016/S0140-6736(16)00346-9. PMID 27112094.
  5. ↑ Schlee S, Bollheimer LC, Bertsch T, Sieber CC, Härle P (June 2018). "Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 1: Epidemiology and pathophysiology". Z Gerontol Geriatr. 51 (4): 453–460. doi:10.1007/s00391-017-1197-3. PMID 28233117.
  6. ↑ Hu SC, Lin CL, Tu HP (March 2019). "Association between psoriasis, psoriatic arthritis and gout: a nationwide population-based study". J Eur Acad Dermatol Venereol. 33 (3): 560–567. doi:10.1111/jdv.15290. PMID 30317664.
  7. ↑ Torres RJ, Puig JG (December 2007). "Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome". Orphanet J Rare Dis. 2: 48. doi:10.1186/1750-1172-2-48. PMC 2234399. PMID 18067674.
  8. ↑ Ben Salem C, Slim R, Fathallah N, Hmouda H (May 2017). "Drug-induced hyperuricaemia and gout". Rheumatology (Oxford). 56 (5): 679–688. doi:10.1093/rheumatology/kew293. PMID 27498351.
  9. ↑ Towiwat P, Li ZG (June 2015). "The association of vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and gout". Int J Rheum Dis. 18 (5): 495–501. doi:10.1111/1756-185X.12622. PMID 26082349.

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