Gout pathophysiology: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{ | {{CMG}} {{AE}} {{Shivam Singla}} | ||
{{ | [[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>: | |||
*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 /> | |||
'''Increased intake''' | '''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. | |||
[[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" | {| align="center" | ||
|- valign="top" | |- valign="top" | ||
|[[Image:Gout | |[[Image:Gout 0001.jpg|thumb|Kidney: Uric Acid Deposition: Gross, an excellent example of gouty nephropathy with deposits and excavation in pyramids]] | ||
|[[Image:Gout | |[[Image:Gout 0002.jpg|thumb|Kidney: Papillary Necrosis: Gross, yellow foci in pyramids, a gout kidney]] | ||
|[[Image:Gout | |[[Image: Gout (no birefringence).jpg|thumb|Gout (Needles, no birefringence, monosodium urate)]] | ||
|[[Image:Gout | |[[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== | ==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 | 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== | ||
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
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.
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
- Hereditary conditions
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)[7]
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
 |
 |
.jpg) |
 |
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
- ↑ Milas-Ahić J, Prus V, Visević R (2012). "[Pathophysiology of gout]". Reumatizam. 59 (2): 89–92. PMID 23745463.
- ↑ 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.
- ↑ 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.
- ↑ Dalbeth N, Merriman TR, Stamp LK (October 2016). "Gout". Lancet. 388 (10055): 2039–2052. doi:10.1016/S0140-6736(16)00346-9. PMID 27112094.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.