Zvýšení kyseliny močové - příčiny a rizikové faktory
2-ethylamino-1,3,4-thiadiazole
Glucose-6-phosphatase deficiency - glycogenosis type I - von Gierke disease
- Autosomal recessive disorder
- Within the first 12 months of life
- Symptomatic hypoglycemia
- Hepatomegaly
- Short stature
- Delayed adolescence
- Enlarged kidneys
- Hepatic adenoma
- Hyperuricemia
- Hyperlipidemia
- Increased serum lactate levels [8]
Glykogenóza
[27]Hyperparatyroidismus
- [27]
ABCG2 gene mutations
- ATP-binding cassette (ABC) superfamily G of membrane transporters [18]
- Member 2 gene ABCG2/BCRP
- Locates in a gout-susceptibility locus (MIM 138900)
- On chromosome 4q
- The ABCG2 gene encodes a membrane transporter
- Involved in the trafficking of biologic molecules across cell membranes
- Found to be a xenobiotic transporter
- Role in the multidrug resistance phenotype of a specific human breast cancer (Doyle et al., 1998) [18]
- Multidrug resistance in several cancer cells
- Actively exporting a wide variety of drugs across the plasma membrane [18]
- Anthracycline
- Mitoxantrone
- Doxorubicin
- Daunorubicin
- Rhodamine-123 [18]
- High capacity transporter for uric acid excretion in the
- Kidney,
- Liver
- Gut (summary from Matsuo et al., 2009 and Saison et al., 2012) [18]
- Brain [18]
- Lactating mammary glands
- Major factor in the concentrative transfer of drugs, carcinogens, and dietary toxins to the milk [18]
Stimulace
- Vanadate-sensitive ATPase activity
- Vanadate-dependent adenine nucleotide trapping under nonhydrolytic conditions [18]
- Associated with ABCG2 expression
- Stimulated by compounds known to be transported by this protein [18]
- Only the R482G and R482T mutants showed
- ATPase activity that was stimulated in a drug-dependent manner
- Nucleotide trapping that was stimulated by transported compounds [18]
Inhibice
- Fumitremorgin C
Pokles funkce ABCG2 - disfunkční proteiny
- Genome-wide association studies
- ABCG2 gene relates to serum uric acid levels and gout [17]
- Transporter of nucleotide analogs that are structurally similar to urate
- Urate secretion transporter and a gene causing gout
- Candidate mutations in ABCG2
- Mutation analysis of the ABCG2 gene in 90 Japanese patients with hyperuricemia
- Six non-synonymous mutations
- ATP-dependent urate transport was reduced or eliminated in five variants
- 2/5 variants (Q126X and Q141K) were frequently detected in patients [17]
- Haplotype frequency analysis
- No simultaneous presence of Q126X and Q141K in one haplotype
- Q126X and Q141K are a nonfunctional and half-functional haplotype
- Genotype combinations are divided into four estimated functional groups [17]
- 161 male gout patients and 865 male controls
- All of those who had dysfunctional ABCG2
- Had an increased risk of gout
- Remarkable risk was observed in those with less than 1/4 function
- OR, 25.8; 95% CI, 10.3-64.6; p = 3.39 × 10(-21) [17]
- In 2,150 Japanese individuals
- Frequency of those with dysfunctional ABCG2 was more than 50%
- Combinations of dysfunctional variants of ABCG2
- Major contributing factor in Japanese patients with gout [17]
- ATP-dependent urate transport
- Reduced to 46.7% in cells expressing a Q141K mutation
- Nearly eliminated in cells expressing a Q126X mutation
- Both of these variants significant association with hyperuricemia and gout in 228 Japanese men and 871 controls [17]
- V12M substitution
- Protective effect nonrisk haplotype [17]
- Humans or animals with low or absent ABCG2 activity
- May be at increased risk for developing protoporphyria and diet-dependent phototoxicity
- Abcg2 transports pheophorbide-a
- Occurs in various plant-derived foods [18]
- Homozygous deficient mice
- Novel type of protoporphyria
- Erythrocyte levels of the heme precursor and phototoxin protoporphyrin IX were increased 10-fold
- Structurally related to pheophorbide-a [18]
- Accumulation of heme/porphyrin can lead to collapse of mitochondrial function particularly under low oxygen
- Hypoxia sensitivity of cells was rescued by inhibition of heme biosynthesis
- Chinese population study
- Increase the risk of gout in dominant model
- Rs17731799, OR?=?1.67, 95% CI 1.05-2.66, p?=?0.028
- Rs3114020, OR?=?1.58, 95% CI 1.00-2.51, p?=?0.048
- Decreased the gout risk
- ABCG2 haplotype "GGCTCTC", OR?=?0.46, 95% CI 0.28-0.75, p?=?0.0019 [20]
Tedy vidím, že velmi důležitý transportér a jeho funkce je podníněna ATP. To znamená i to, že stavy, kdy epiteliální buňky ledvin nemají dost ATP, mohou třeba vést k vyšším hladinám k. močové v krvi. Pamatuju si z nefrologie, že nadbytek sodíku ve stravě byl dáván do souvislosti s velkou spotřebou ATP ledvinami na jeho vyloučení. Podaří se mi dohledat souvislost mezi nadměrným solením a vyšší k. močovou ?
Nízké dávky salicylátů
Acidoza
Adenine and hypoxanthine
- Highest uricogenic potential out of all purines
- Especially in comparison with that of guanine and xanthine [17]
Age
- The tendency to develop hyperuricemia increases with age [8]
Ženy
- Gout in women occurs exclusively after menopause
- Women develop gout at an older age than men
- Have twice the prevalence of hypertension, renal insufficiency and exposure to diuretics
- Atypical onset of gout - suspection of inherited enzyme defect or renal disease if before:
- Age 30 in men
- Menopause in women [9]
Akromegálie
- [27]
Aldolase-B deficiency - fructose-1-phosphate aldolase deficiency
- other causes of hyperuricemia
- Combination of overproduction and underexcretion [8]
- Common inherited disorder
- Often resulting in gout
Alkohol
- Accelerated hepatic breakdown of ATP [8]
- Generation of organic acids
- Laktát vzniká ve zvýšené míře
- Compete with urate for tubular secretion v ledvinách [7]
- Inhibuje sekreci kyseliny močové ledvinami [4]
- Lowering the pH of bodily fluids – reduces uric acid solubility and causes its crystallization [17]
- Especially when consumed occasionally in large quantities, is one of the key risk factors for gout attacks [17]
- Snížené vylučování kyseliny močové je později vystřídáno zvýšenou urikosurií [4]
- Significant cause of hyperuricemia
- Increases the plasma concentrations of hypoxanthine and xanthine
- Acceleration of adenine nucleotide degradation [17, 7]
- Increases production of uric acid [17]
- Possible weak inhibitor of xanthine dehydrogenase
Beer
- Additionally contributes purines
- Zbytky kvasinkové DNA aj. nukleotidů
- Promotes dehydration
- Decreases excretion of uric acid by
- Vzácně vede ke cliniké ketoacidoze [7]
- Large quantities of purines in beer
- 500 ml of beer = equivalent of 170 mg of uric acid = corresponds to 71 mg of purines
- 1 mg of purine compounds = equivalent of 2.4 mg of uric acid
Simultaneous consumption of alcohol and fatty products
- Important to avoid
- Synergic action in inducing gout attacks [17]
Zvýšení některých aniontů
- Kompetice o přenašeč tubulární sekrece kyseliny močové [3]
Bartter syndrome
Beryllium
Buněčný rozpad
- Vede ke zvýšenému obratu nukleových kyselin
Při léčbě cytostatiky
- Tumor lysis syndrome
- Produces extreme levels of uric acid
- Mainly leading to renal failure [7]
- Therapy for bulky tumors and no pretreatment with xanthine oxidase inhibitors (allopurinol) or aggressive hydration
- Almost always the plasma uric acid concentration exceeds 20 mg/dL [13]
Rhabdomyolysis
- Acute Renal Failure accompanies diffuse cell injury, as in rhabdomyolysis
- Mean uric acid concentration averages 14 to 15 mg/dL [13]
- Not infrequently exceeds 20 mg/dL [13]
Zvýšený buněčný obrat
- Leukémie aj.
- Lymphoma
- Myeloma [8]
Radioterapie
- Velkého rtg senzitivního tumoru
Ciclosporin
Decreased glomerular filtration
- Při poruchách ledvin
Decreased tubular secretion
- In patients with acidosis
- Diabetic ketoacidosis
- Ethanol or salicylate intoxication
- Starvation ketosis
- The organic acids that accumulate in these conditions
- Compete with urate for tubular secretion [8]
Vrozený defekt enzymů APRT (adeninfosforibozyltransferáza)
- Podílejících se na resyntéze nukleotidů
- Dochází ke sníženému využívání adeninu a guaninu z již odbouraných nukleotidů [27]
Vrozený defekt HGPRT (hypoxantin-guaninfosforibozyltransferáza)
- Podílejících se na resyntéze nukleotidů
- Dochází ke sníženému využívání adeninu a guaninu z již odbouraných nukleotidů [27]
Defekt glukóza-6-fosfatázy
Deficit adenosindeaminasy - Deficit ADA
- Dědičnost AR, X-vázaná
- Hromadění adenosinu a deoxyadenosinu v tělesných tekutinách
- Velmi špatně rozpustné
- Vytváří močové konkrementy
- Velké množství adeninu v plazmě
- Výrazná lymfopenie
- V lymfocytech se hromadí deoxyadenosin a dATP
- Inhibují ribonukleotidreduktázu pro syntézu DNA
- Hypoplázie až absence lymfatické tkáně [2]
- Těžká kombinovaná imunodeficience (SCID - severe combined imunodeficiency disease) [1]
- Kombinovaná imunodeficience (T i B-buněk)
- Příčinou SCID v 15 % [2]
- časté infekce hlavně kůže, respiračního a gastrointestinálního traktu
- Bez léčby umírají do 2 let života
- V pozdějším věku má onemocnění mírnější průběh
- Klinické příznaky hlavně
- Plicní záněty
- Kandidóza
- Chronické vodnaté průjmy
- Neurologické symptomy (poruchy hybnosti a spasticita) [2]
- Aktivita ADA je snížena také v erytrocytech
- Variantní kostní a neurologické odchylky [2]
- Zvýšené vylučování deoxyadenosinu [6]
Terapie
- Transplantace kostní dřeně
- Transfuze ozařovaných erytrocytů
- Podávání ADA modifikované polyetylenglykolem
- Zvýšení poločasu
- Snížení imunogenicity
- úspěšná genová léčba s komplikací leukemie [2]
Deficit adenylosukcinátlyázy
AR dědičnost
- Adenylosukcináza katalyzuje dva kroky v syntéze purinů
- Deficit způsobuje hromadění sukcinylpurinů SAICAR a S-Ado
- Meziproduktů této metabolické dráhy v moči a likvoru [2]
Typ I
- Psychomotorická retardace
- Epilepsie
- Někdy svalová atrofie [2]
Typ II
- Svalová hypotonie
- Mírné opoždění psychomotorického vývoje
- Hypotonie
- Křeče
- Autismus [2]
Léčba
- Doplnit deficit adeninů v tkáních
- Adenin a
- Alopurinol
- Blokuje xanthinoxidázu a tím i degradaci purinů [2]
Deficit B12 a kyseliny listové
- Moje hypotéza
- Pokud porucha syntézy nukleotidů vede k vyššímu odpadu neupotřebených látek
- Pak by tyto deficity mohly vést k vzestupu k. močové - pokud to pak není spíše naopak
- Tak bude zajímavé, co najdu za asociace...
Deficit hypoxanthin-guaninfosforibosyltransferasy
- Genetické onemocnění Lesch-Nyhanův syndrom
- Omezen chod šetřící dráhy
- Zvýšená tvorba urátu (hyperurikemie)
- Zvýšené intracelulární PRPP [1]
Diuretics
Enhanced tubular reabsorption of uric acid
- Distal to the site of secretion
- Responsible for the hyperuricemia observed with
- Diuretic therapy
- Diabetes insipidus [8]
Ethambutol
Excesivní cvičení
Exercise
- Exercise may result in
- Enhanced tissue breakdown
- Decreased renal excretion due to mild volume depletion.
Familial juvenile gouty nephropathy
- Rare autosomal dominant condition
- Progressive renal insufficiency
- Low fractional excretion of urate (typically 4%)
- Kidney biopsy
- Glomerulosclerosis
- Tubulointerstitial disease
- No uric acid deposition [8]
Iron overload
Fructose in the diet
- High dietary intake contributes significantly to hyperuricemia [7]
- In a large study in the United States
- Consumption of 4 or more sugar-sweetened soft drinks per day
- Gave an odds ratio of 1.82 for hyperuricemia [7]
- Studies in the American population, such as the
- Third National Health
- Nutrition Examination Survey
- Demonstrated a direct correlation between uric acid levels and sweetened non-alcoholic beverage
- Irrespective of any other risk factors for hyperuricemia [17]
- Beverages have high fructose content - associated with
- Epidemiologic studies documented a link between
- Lecoultre et al found that
- Fructose-induced hyperuricemia is associated with a decreased renal uric acid excretion [8]
- Increasing purine synthesis
- Increased production of uric acid
- Result of interference
- By a product of fructose metabolism in purine metabolism [7]
- Accentuating degradation of purine nucleotides
- Increasing the conversion of ATP to inosine
- Hence uric acid [7]
- Increasing the synthesis of purine
- Fructose inhibits the excretion of uric acid
- Avoid
- Foods and beverages with high-fructose corn syrup
- Sweetened cereals
- Bakery goods
- Candies etc.
- Limit consumption of naturally sweet fruit juices [16]
Intenzivní tělesná zátěž
- Zvýšené odbourávání ATP [27]
Snížená glomerulární filtrace nebo tubulární sekrece
- Všechny stavy se sníženou glomerulární filtrací
- Všechny stavy spojené s acidózou [27]
Glucose transporter 9 (GLUT9/SLC2A9) higher activity
- uric acid reabsorption [10]
Glycogenoses type I
- Other causes of hyperuricemia
- Combination of overproduction and underexcretion [8]
Glycogenoses types III, IV, and VII
- Can result in hyperuricemia
- From excessive degradation of skeletal muscle ATP [8]
Zpětnovazebný mechanismus + a -
- Vztah zaručuje synthesu téměř stejného množství GMP jako AMP [1]
Dostatek GTP
- Urychlí se přeměna IMP na AMP [1]
Dostatek ATP
- Urychlí se konverse XMP na GMP [1]
Hemoglobinopatie
- Sickle cell disease
- Studies from the 1970s
- Hyperuricemia as a common feature of sickle cell disease in up to 41% of patients
- Center in France during a 2-year period Hyperuricemia was observed in only 9.2% of the patients in the cohort, and none had gout [13]
- Hb SC and CC disease
- Thalassemias [13]
Hemolytické anémie
Lesch-Nyhanův syndrom - úplná deficience HGPRT
- X-vázaná dědičnost
- Téměř kompletní deficit HGPRT (hypoxanthinguaninfosforibosyltransferáza)
- Nejčastější genetické defekty purinového metabolismu
- HGRPT catalyzes the conversion of hypoxanthine to inosinic acid
- PRPP serves as the phosphate donor
- Deficiency of HGPRT results in
- Accumulation of 5-phospho-alpha-d-ribosyl pyrophosphate (PRPP)
- Accelerates purine biosynthesis
- Increase in uric acid production
Klasické formy s naprostým deficitem HGPRT
- Děti se rodí klinicky zdravé
- 1. nadprodukce kyseliny močové
- Růžové krystaly jsou viditelné v plenách, které byly potřísněny močí novorozence [2]
- 2. Později se objevuje
- Zvracení
- Křeče
- Spasticity [8]
- Pomalé nepřetržité pohyby
- Choreoathetosis
- Těžké psychomotorické retardace
- Agresivita [2]
- 3. S přibývajícím věkem
- Automutilační chování
- Sebepoškozování- okusování rtů, prstů, jazyk atd., které nelze ovládat vůlí
- Neurologické příznaky po 3–4 měsících
- Souvisí se sníženou hladinou DOPA dekarboxylázy
- Souvislost mezi HGPRT a DOPA dekarboxylázou není objasněna [2]
- Většinou snížené IQ (50), dysartrie
- Těžká dna už v dětském věku
- urolitiáza až selháním ledvin
- uric acid nephrolithiasis
Léčba
- Alopurinol
- Nízkopurinová dieta
- Zvýšený pitný režim [2]
Prevence
- Možná prenatální diagnostika
- Biopsie choriových klků
- Punkce amniové tekutiny [2]
Částečný deficit enzymu HGPRT šetřící cesty - partial deficiency of HGPRT - Kelley-Seegmiller syndrome
- Hromadění PRPP (fosforibosylpyrofosfátu)
- Není využit HGPRT
- PRPP začne být zvýšeně využíván pro de novo syntézu purinů
- Vede ke zvýšené degradaci purinů
- Vzniku k. močové [2]
- X-linked disorder
- Develop gouty arthritis in the second or third decade of life
- High incidence of uric acid nephrolithiasis
- May have mild neurologic deficits [8]
Hladovění
- Nejen zvýšená syntéza, ale i snížené vylučování díky acidóze [27]
Prevence prochladnutí - horká koupel
- Low temperature is a commonly reported trigger of acute gout
- Day spent standing in cold water
- Followed by an attack of gout the next morning
- Temperature-dependent precipitation of uric acid crystals in tissues
- Keep the hands and feet warm
- Soaking in hot water may be therapeutic
a možná může mírně zvyšovat k. močovou v krvi
Hyperparathyroidism
- V mobilní aplikaci jsem našla i hypoparathyroidismus - šlo o chybu ?
Hypertension
- Hyperuricemia has a higher prevalence (25-40%) in individuals with hypertension
- Associated with increased morbidity in these patients [8]
- Lin et al - study of 837 elderly patients with hypertension
- Followed up over 3.5 years
- Increases in uric acid levels were independently associated with decline in renal function [8]
- A meta-analysis2 of 18 prospective studies including 55?607 subjects
- Hyperuricemia predicted incident hypertension
- 13% higher risk per 1 mg/dL increment in serum uric acid
- Association might vary according to age and sex
- More significant in younger and female [10]
- Liu et al
- Prediction of hyperuricemia was also true for incident prehypertension
- In 15?143 subjects with optimal office blood pressure at baseline
- Subjects with a serum uric acid concentration belonging to the 4-5 quintiles
- Had a 9% and 17% higher risk of incident prehypertension [10]
- Kuwabara et al
- Hyperuricemia played a significant role in the progression from prehypertension to hypertension
- Retrospective cohort study
- Cumulative incidence rate of hypertension was significantly higher in subjects with hyperuricemia
- More in women [10]
- Five-year study period
- Cca 1/4 of the prehypertensive subjects developed hypertension
- Hyperuricemia increased the risk of hypertension by cca 35% [10]
- Hyperuricemia might be a therapeutic target for the prevention of hypertension
- Genetic studies that applied Mendelian randomization approach
- Did not support a causal role of serum uric acid in the development of hypertension [10]
- Meta-analysis5 of genome-wide association studies involving 28?283 individuals
- Genetic urate score estimated from 8 genetic loci
- Was strongly associated with serum urate and gout
- But not with incident hypertension nor blood pressure [10]
- Recent gene knockout studies in mice
- Loss of uricase or intestinal uric acid transporter SLC2A9
- Resulted in hypertension and metabolic disorders [10]
- Experimental studies in rats and cells
- Pathophysiologic process of hyperuricemia-induced hypertension might include
- Initial phase
- Driven by uric acid
- Mediated by oxidative stress, inflammation, endothelial dysfunction
- Activation of the renin–angiotensin–aldosterone system [10]
- Later phase
- Driven by arterial wall hypertrophy [10]
- Renal microvascular changes
- Interstitial inflammation
- No longer dependent on serum uric acid level [10]
Hyperthyroidism
Hypothyroidism
Increased proximal tubular reabsorption of uric acid
- Controlled by URAT1 (uric acid transporter 1)
- Stimulated by
- Organic acids
- Lactate
- Acetoacetate
- Beta-hydroxybutyrate
- Medications
- Niacin
- Pyrazinamide
- Ethambutol
- Cyclosporin
- Chemotherapy
- Reduced extracellular fluid volume [9]
Insulin resistance
- Amelioration of insulin resistance decreases the serum uric acid by:
- Diet
- insulin sensitizing medication
- Elevated uric acid
- Inexpensive tool to suggest the presence of insulin resistance
- Hyperuricemia
- In more than 80% of patients with hypertriglyceridemia [20]
- Diabetes
- Impairs the ability of the kidney to excrete uric acid
- Competition for transport between uric acid and ketones [7]
- Kompetice o přenašeč tubulární sekrece kyseliny močové [3]
- Jedna z možných příčin přechodné elevace k. močové v prvních fázích Metabolic Balance
- Kyselina acetoctová
- Beta-hydroxymáselná [4]
- Furosemide, bumetanide, torsemide, azosemide, ethacrynic acid [15]
- The inverse correlation between hyperuricemia and urine osmolality
- Supposed indirect marker for volume status
- Indirect effect through volume contraction and enhanced proximal sodium and water reabsorption
- Reduced sodium reabsorption in the TAL with elevated urate levels
- Side effects of chronic administration of
- Loop diuretics
- In individuals with Bartter syndrome [13]
- Kompetice o přenašeč tubulární sekrece kyseliny močové [3]
- Acetazolamid,
- Bumetanid,
- Hydrochlorothiazid,
- Cyklosporin,
- Ethambutol,
- Furosemid,
- Metoxyfluran,
- Ester kyseliny nikotinové,
- Pyrazinamid,
- Aspirin (nízké dávky) [27]
- X-vázaná dědičnost
- Téměř kompletní deficit HGPRT (hypoxanthinguaninfosforibosyltransferáza)
- Nejčastější genetické defekty purinového metabolismu
- HGRPT catalyzes the conversion of hypoxanthine to inosinic acid
- PRPP serves as the phosphate donor
- Deficiency of HGPRT results in
- Accumulation of 5-phospho-alpha-d-ribosyl pyrophosphate (PRPP)
- Accelerates purine biosynthesis
- Increase in uric acid production
- Děti se rodí klinicky zdravé
- 1. nadprodukce kyseliny močové
- Růžové krystaly jsou viditelné v plenách, které byly potřísněny močí novorozence [2]
- 2. Později se objevuje
- Zvracení
- Křeče
- Pomalé nepřetržité pohyby
- Těžké psychomotorické retardace
- Agresivita [2]
- 3. S přibývajícím věkem
- Automutilační chování
- Sebepoškozování- okusování rtů, prstů, jazyk atd., které nelze ovládat vůlí
- Neurologické příznaky po 3–4 měsících
- Souvisí se sníženou hladinou DOPA dekarboxylázy
- Souvislost mezi HGPRT a DOPA dekarboxylázou není objasněna [2]
- Většinou snížené IQ (50), dysartrie
- Gout and uric acid nephrolithiasis
- Choreoathetosis
- Spasticity [8]
- Alopurinol
- Nízkopurinová dieta
- Zvýšený pitný režim [2]
- Možná prenatální diagnostika
- Biopsie choriových klků
- Punkce amniové tekutiny [2]
- Při leukémii zaniká mnohem více buněk než normálně
- Degraduje se více purinů
- Konečný produkt kyselina močová [3]
- U novorozenců nebo po terapii leukemie cytostatiky Acidurický infarkt ledviny
- Krystalky kyseliny močové se ukládají v renálních tubulech
- Makroskopicky - rezavě hnědé proužky v papilách [3]
- Hovězí maso
- červená masa
- Vnitřnosti !!!
- Vývary !!!!!
- Hypertension, obesity, insulin resistance, dyslipidemia, and hyperuricemia
- Associated with a decreased fractional excretion of urate by the kidneys
- Encodes a protein that helps to transport uric acid in the kidney
- Several single nucleotide polymorphisms of this gene are known
- Significant correlation with blood uric acid
- Male predominance in a 4:1 ratio of men to women [9]
- Significantly correlated with both impaired kidney function and hyperuricemia
- Causal relationship among these correlations is not known
- In a study of over 2500 people resident in Taiwan
- A blood lead level exceeding 7.5 microg/dL (a small elevation) had odds ratios of
- 1.92 (95% CI: 1.18-3.10) for renal dysfunction
- 2.72 (95% CI: 1.64-4.52) for hyperuricemia [7]
- Chronic
- History may reveal occupational exposure
- Lead smelting
- Battery and paint manufacture
- Consumption of moonshine
- Illegally distilled corn whiskey
- Produced in lead-containing stills [8]
- Exposure to persistent organic pollutants
- Organochlorine pesticides [8]
- Hyperuricemia cosegregating has been shown
- Associated with a mutation in GPATCH8 using exome sequencing [7]
- Poškození ledvinných tubulů [27]
- Elevated uric acid associated with these conditions
- Key clue to the diagnosis
- Because uric acid levels are lower than normal in healthy pregnancies [8]
- Common but minor cause of hyperuricemia
- Diet alone generally is not sufficient to cause hyperuricemia
- Purine content of foods varies
- Foods high in the purines adenine and hypoxanthine
- May be more potent in exacerbating hyperuricemia [7]
- Tedy jídla, které když jí člověk s doutnajícím dnavým zánětem, tak potom ucítí silnější bolest
- Neměl by je tedy moc jíst !!
- Organ meats [15]
- Kidneys, liver, “sweet bread” !!! [9, 15]
- Glandular meats [15]
- Game meats
- Some seafood
- Anchovies, shellfish, sardines and tuna
- Higher in purines than are other types [15]
- Herring
- Scallops [9]
- Mussels
- Bacon
- Codfish
- Trout
- Haddock
- Veal
- Venison
- Turkey
- Overall health benefits of eating fish may outweigh the risks for people with gout [16]
- Moderate portions of fish can be part of a gout diet [16]
- Purine rich
- Also increases uric acid levels by decreasing kidney excretion [9]
- Beer and distilled liquors
- Are associated with an increased risk of gout and recurring attacks [16]
- Bone and meat stocks,
- Broths
- Offal and cold meats
- Canned meat and fish
- Fish from the clupeidae family
- Sardines, sprats, herring
- Some cheeses
- Processed, blue, rennet cheeses,
- High-fat creamy quarks
- Animal fats
- Suet, lard, bacon
- Corn
- Sorrel
- Spinach
- Rhubarb
- Chocolate
- Marinades
- Certain spices
- Pepper, mustard, and root spices [17]
- Alcohol, coffee, black tea, cacao, and hot spices
- Must be eliminated from the diet
- Should not exceed the equivalent of 500 mg of uric acid
- Amount of purine-containing products (substrate) [mg]
- Corresponds to the production of a specific amount of uric acid [in mg]
Laciky řečeno nesníst za den víc, než kolik za 24h vyloučím do moči.
Po podstoupení sběru moči by se dalo vypočítat, kolik to pro koho dělá
- Peas, lentils, spinach, mushroom, cauliflower
- May not affect serum uric acid to desirable extent
- hence purine restricted diet is rarely necessary
- Lze občas jíst - není nutné zcela zakazovat !!!
- Obzvláště pokud se jedná o střídmou odváženou porci dle Metabolic Balance...
- Asparagus [9, 15]
- Spinach [9, 15]
- "Studies have shown that vegetables high in purines, such as asparagus and spinach, don't increase the risk of gout or recurring gout attacks."
- Beef [9, 15]
- Pork [9, 15]
- Lamb [9, 15]
- Bouillon
- Chicken
- Crab
- Duck
- Ham
- Lobster
- Oysters [9]
- Shrimp
- Kidney beans
- Lentils
- Lima beans
- Jako zdroj proteinů se má preferovat:
- "Focus on lean meat and poultry, low-fat dairy and lentils as sources of protein."
- Nevadí, když se tyto potraviny vyskytují v nutričních plánech Metabolic Balance u jedinců s vyšší k. močovou
- Purine-rich vegetables should be eliminated from the diet [17]
- Leguminous plants
- Cabbage
- Brussels sprouts
- Lentils
- Green peas
- White beans [17]
- One of the more common causes of hyperuricemia
- Usual peak uric acid concentration is 9 to 10 mg/dL [13]
- uric acid level does not generally become elevated until the creatinine clearance falls below 20 mL/min
- Unless other contributing factors exist
- Due to a decrease in urate clearance as retained organic acids compete for secretion in the proximal tubule [8]
- Hyperuricemia is commonly observed even with minimal renal insufficiency [8]
- Hyperuricemia is commonly observed even with minimal renal insufficiency [8]
- Contribute to the higher prevalence of hyperuricemia
- Low-dose aspirin as 75?mg/day
- Have been shown to have an impact on serum urate levels
- Taken by more than half of all persons at high risk of cardiovascular events [13]
- Více viz salycilátová dieta
- Urate secretion does appear to correlate with the serum urate concentration
- Small increase in the serum concentration
- Results in a marked increase in urate excretion [8]
- Body to metabolize its own (purine-rich) tissues for energy
- Like a high purine diet
- Increases the amount of purine converted to uric acid
- Starvation also impairs the ability of the kidney to excrete uric acid
- Competition for transport between uric acid and ketones [7]
- Can induce extreme hyperuricemia [7]
- Including some carbohydrate
- Reducing the protein
- Reduces the level [7]
- Thiazide and thiazide-like diuretics
- Hydrochlorothiazide - HCTZ
- Chlorthalidone
- Chlorothiazide
- Indapamide [15]
- Single nucleotide polymorphisms (SNPs) associated with HCTZ-induced elevations in uric acid (UA) and hyperuricaemia
- 5 unique gene regions identified in African Americans
- LUC7L2
- ANKRD17/COX18
- FTO
- PADI4
- PARD3B [13]
- 1 gene region identified in Caucasians
- GRIN3A
- Increases in uric acid levels of up to 1.8 mg/dL following HCTZ therapy
- Homozygous for the above identified risk alleles
- Clinical concern in patients with underlying hyperuricaemia or a history of gout [13]
- Hyperuricemia of this type is a common complication of solid organ transplant [7]
- Calcineurin inhibitors cyclosporine and tacrolimus
- Potent effects on serum urate levels
- Preventing uric acid secretion by transporters in the proximal convoluted tubules of the kidney
- By diminishing glomerular filtration [13]
- Study of renal transplant patients taking
- Prevalence of hyperuricemia was
- 84% in those taking cyclosporine
- 30% in those taking azathioprine [13]
- Fatty meat is one of the best predictors of uric acid levels
- Largely determines the risk of gout [17]
- Treatment of pernicious anemia [10]
- Nejrůznější formy vývarů - asi nejsilnější zdroj purinů vůbec
- Po požití větší porce pacienti udávají bolesti
- Gravy - masová šťáva jako základ omáček
- Také uváděna v lit. jako rizikový faktor
- Sauce often made from the juices of meats that run naturally during cooking
- Thickened with wheat flour or cornstarch for added texture
- Která vede ke zvýšené syntéze purinů
- Nadprodukce i zvýšená exkrece močové kyseliny
- Rare
- Mutated PRPP synthetase enzymes with increased activity
- Zvýšená tvorba PRPP vede ke zvýšené tvorbě purinů de novo
- K jejich zvýšené degradaci cestou kyseliny močové
- Arthritis uratica [2]
- Develop gout when aged 15-30 years
- Have a high incidence of uric acid renal stones [8]
A ketogenic diet
Zvýšení ketolátek
Kličková diuretika
Nicotinic acid
Zvýšená hladina laktátu
Léky
Lesch-Nyhanův syndrom - úplná deficience HGPRT
Klasické formy s naprostým deficitem HGPRT
Léčba
Prevence
Leukémie
Levodopa
Převážně masitá strava
Metabolic syndrome
Gene SLC2A9
Mužské pohlaví
Obesity
Elevated blood lead
Lead intoxication
Organochlorine pesticides
Osteogenesis imperfecta
Otrava Pb, Cd, Be
Paget disease
Polycystic kidney disease
Polycytemia vera
Potassium oxonate
Preeclampsia and eclampsia
Primary antiuricosurics
Psoriasis
Purine-rich diet
All meats but specifically
Beer
Alcohol
Fructose
Názor X
Significantly affect uric acid levels - doporučuje vynechat
Total daily intake of uric acid
Purine rich vegetables
Purine mild content
Zelenina
Maso
Seafood
Lentils and beans
Mushrooms
Doporučení Mayoclinic
Nějaký názor na Research gate
Pyrazinamide
Renal insufficiency
Renal failure acute
Chronic renal failure
Medullary cystic disease
Chronic lead nephropathy
Rybóza-5-fosfát a ATP
Nadbytek Rybosa-5-fosfátu a ATP povede k vyšší syntéze purinů
Takže konzumace fruktozy, inzulínu a málo pohybové aktivity ??
Zvýšená degradace nukleových kyselin při zániku velkého množství buněk
Salicylates
Aspirin ap.
Rostlinné salicyláty
Sarcoidosis
Decreased excretion (underexcretors)
Starvation
Very low calorie diet without carbohydrate
Zmírnění of hyperuricemia
Thiazidy
HCTZ
Transplantace orgánů
Trisomy 21
Tučné maso
Vitamin B12
Vývar
Yeast extract powder
Increased production (overproducers) of uric acid
Zvýšená aktivita PRPP-amidotransferázy
Zvýšená aktivita PRPP syntázy - fosforibosyl-pyrofosfát syntethasy
X-vázaná dědičnost
Zvýšená aktivita fosforibosyldifosfátsyntetázy
