Arthritis urica

Gout

Pánczél Pál dr.

Gout is a metabolic disease, manifested by

• An increase in serum urate concentration• Recurrent attacks of a characteristic type of

arthritis• Deposits of sodium urate monohydrate (tophi),

which occur chiefly in and around the joints of extremities and may lead to joint destruction and severe crippling

• Renal disease involving glomerular, tubular and interstitial tissues and blood vessels and in which hypertension is common

• urolithiasis

History of gout• Gout has been known for at least 2500 years• Hippocrates discovered that gout is the disease of males, its

frequency of occurrence increases with ageing and the symptoms are relived by a copious affusion of cold water. He suggested a drug identical to colhicin (White Hellebore) for the treatment of gout

• Galen described tophi and he attributed gout to debauchery, intemperance and a hereditary trait

• The term gout is derived from the Latin word: gutta. The disease is caused by a noxa, a poison falling drop by drop into the joint

• Clinical description by Thomas Sydenham based on his personal affliction (1683)

• Leeuwenhoek described the crystals in the material prepared from a gouty tophus (1679)

• Scheele discovered uric acid as a component of a kidney stone (1776)

• Garrod discovered the hyperuricaemia of gout: crystallization of uric acid on a linen fiber suspended in acidified serum (1848)

• HGPRT (hypoxanthin-guanin-phosphoribosyl-transferase) deficiency in the background of some cases of gout was discovered in 1967 by Seegmiller and phosphoribosyl-pyrophosphate synthetase over activity that of some cases in 1972 by Sperling .

Prevalence and genetics of gout• 0,13 – 0,37% in Europe and in USA• 10% of adult male Maoris in New Zeeland• Prevalence decreased during world wars• 95% men – 5% women (mainly in the postmenopausal

group)• Family history is positive for gout in 6 – 18% of patients

with the disease.• 25% of all first degree relatives of gouty patients are

hyperuricaemics• Hyperuricaemia is not equal to gout• Hyperuricaemia is correlated with maleness, obesity,

protein intake, social status and education level• Hyperuricaemia is a component of the metabolic

syndrome (hypertriglyceridaemia, insulin resistance, abdominal obesity, hypertension, IHD, hypercoagulability)

In animals urate is converted by uricase to soluble allantoin.

• Human beings are the only exceptions who lack uricase and uric acid is the end-product of purine metabolism.

• Is this a selection benefit?• Has coffee and tea abuse (with high

purine content) also an advantage for the development of brain?

Renal „work up ” of uric acid

6-12excretion

Henle loop40-44distal reabsorption

4

pars recta of proximal tubules

50secretion3

proximal tubules

98-100proximal reabsorption

2

glomeruli100filtration1

localization% of GFR

Uric acid content of the body:

1500 mg (9 mmol)

Catabolism of nucleic acids

Endogenous purinsynthesis

80%

Exogenous purin income20%

de novo purinsynthesis

750 – 900 mg/day

4,5-5,4 mmol/day

renal excretion

70%

gastrointestinal excretion

30%

750 – 900 mg/day4,5-5,4 mmol/day

Pathogenesis and pathology of gout

• The risk of development of gout increases with the degree of hyperuricaemia and with age.

• Solubility of urate in the plasma and body fluids (synovial fluid) is the most important

• The solubility is influenced by pH and temperature: the lower the pH and temperature the higher the risk ofcrystallization of urate (extremities of the body, in kidneys, gouty attacks come at night …)

• Overproduction and/or underexcretion of uric acid causes hyperuricaemia and gout. But the evidences do not support the separation of idiopathic gout into subgroups of metabolic (overproducers) and renal (underexcretors) gout.

• Uric acid can be crystallized in the interstitium of kidneys (interstitial nephritis) and in the urine (kidney stone)

Clinical manifestations of gout• Acute gouty attack by description of Sydenham :

„The victim goes to bed and sleeps in good health. About two o’clock in the morning he is wakened by a severe pain in the greattoe; more rarely in the heel, ankle or instep. This pain is like that of a dislocation, and yet the parts feel as if cold water poured over them. Then follows chills and shivers, and a little fever. The pain, which was at first moderate, becomes more intense. After a time this comes to its height, accommodating itself to the bones and ligaments of the tarsus and metatarsus. Now it is a violent stretching and tearing of the ligament – now it is a gnawing pain and now a pressure and tightening. So exquisite and lively meanwhile is the feeling of the part affected, that it cannot bear the weight of the bedclothes. The night is passed in torture, sleeplessness, turning of the part affected, and perpetual change of posture; the tossing about of the body being worse as the fit comes on. Hence the vain effort, by change of posture, both in the body and limb affected, to obtain an abatement of the pain.”

• Acute gouty arthritis often follows a precipitating event: trauma, surgery, alcohol ingestion, dietary overindulgence, starvation, infection

• Tophaceus gout, chronic gouty arthritis

Secondary gout

• Polycythaemia rubra vera• Other myeloproliferative diseases• Cytotoxic treatment of malignant diseases• Diuretic treatment• Low dose Aspirin treatment (100 mg/day)• Chronic renal failure• Psoriasis, sarcoidosis• Haemolytic anaemias• Lead nephropathy (saturnine gout)

Diagnosis of gout

• Characteristic asymmetric oligoarthritis• Demonstration of monosodium urate dihydrate

crystals in the synovial fluid from an involved joint: needle shaped, negatively birefringent on polarized light

• A rapid response of pain and inflammation to the administration of colhicin (colhicin inhibits macrophages to phagocyte of the needle shaped crystals which would kill them inducing a very acute inflammatory process). The effectiveness of colhicin is specific for gout.

Treatment of gout

Acute gouty attack : colhicin 0,5 mg hourly, maximal dose4-8 mg or gastrointestinal intolerancehigh dose of NSAIDsteroid

Chronic stage :dietallopurinol (inhibits uric acid synthesis)probenecid, sulfinpyrazon, benzbromaron(increase uric acid output in the kidneys)alkalization of urine, increase of fluid intakechronic colhicin treatment 0,5 – 1,0 mg/day)

Fotó: Pánczél Pál

Fotó: Pánczél Pál

Tophi in the subcutaneous tissue, around the joints.

Alcohol

Blood alcohol levels and symptoms

Level mg/dl sporadic chronicdrinkers drinkers

50 Congenial euphoria No observable effect75 Gregarious or garrulous Often no effect100 Incoordination, legally intoxicated M inimal signs125-150 Unrestrained behavior Pleasurable euphoria

Episodic dyscontrol or beg inning dyscontrol

200-250 Alertness lost → Effort required tolethargic maintain emotional and

motor control300-350 Stupor or coma Drowsy and slow>500 Some will die Coma

Treatment of severe tremulousness or delirium tremens

• Attempt control by reassurance and observation

• Treat systemic problems promptly• Treat uncontrollable agitation: control with

diazepam 10 mg iv. give slowly, followed by 5-10 mg iv slowly every 5 minutes to induce calmness. Once calm, maintain with diazepam 5-10 mg iv or more every 1-4 hours

• Continuously supply and balance electrolytes and vitamins, especially thiamine

Major non-neurological complications of alcoholism

• Heart: cardiomyopathy, arrhythmia• Gastrointestinal: gastritis, hepatitis, cirrhosis of the liver,

pancreatitis (acute and chronic), head-neck- esophageal cancer, malabsorption

• Blood: iron and folate deficiency, anaemia, thrombocytopenia, prothrombin deficiency

• Endocrine: male sexual impairment, increased fetal risk• Immune system: increased susceptibility to infection and

impaired healing• Electrolyte disturbances: hypocalcaemia,

hypomagnesaemia, hypophosphataemia, acute water intoxication, alcoholic hyperosmolality, alcoholic ketosis

Major neurological complications of severe alcoholism

• Amblyopia and optic atrophy

• Progressive cerebral degeneration and dementia

• Peripheral neuropathy• Myopathy• Wernicke- Korsakoff disease

• Parenchymatous cerebellar degeneration• Cerebral leukodystrophy (Marchiafava –

Bignami disease)