Lec. 1 Uric Acid PDF

Uric acid Uric acid or urate is the end (waste) product of Purine metabolism, Purines are one of the most common chemical compounds on the planet. ‫ والبورينات هي واحدة من أكثر املركبات‬،‫حمض اليوريك أو اليوريا هو املنتج النهائي )النفايات( لعملية التمثيل الغذائي للبورين‬.‫الكيميائية شيوعا على...

Uric acid Uric acid or urate is the end (waste) product of Purine metabolism, Purines are one of the most common chemical compounds on the planet. ‫ والبورينات هي واحدة من أكثر املركبات‬،‫حمض اليوريك أو اليوريا هو املنتج النهائي )النفايات( لعملية التمثيل الغذائي للبورين‬.‫الكيميائية شيوعا على هذا الكوكب‬ Uric acid There are two kinds of purines sources: endogenous and exogenous. Exogenous purines are absorbed by the body through the foods that you eat, whereas, endogenous purines are made directly by the body itself by synthesis from simple precursors or from ingested or degradation of nucleoproteins. Purines, such as adenosine and guanine from the breakdown of ingested nucleic acids or from tissue destruction, are converted into uric acid, primarily in the liver. Note: Adenine and guanine are found in DNA, RNA, ATP, ADP …. etc. 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬ Uric acid is transported in the plasma from the liver to the kidney, where it is filtered by the glomerulus. Reabsorption of 98% to 100% of the uric acid from the glomerular filtrate occurs in the proximal tubules. Small amounts of uric acid are secreted by the distal tubules into the urine. Nearly all of the uric acid in plasma is present as monosodium urate. At the pH of plasma (pH 7), urate is relatively insoluble. Renal excretion accounts for about 70% (two-thirds) of uric acid elimination; the remainder passes into the gut and is degraded by bacterial enzymes to carbon dioxide and ammonia. ‫ في املائة )ثلثي( القضاء على حمض اليوريك؛ ويمر الباقي إلى األمعاء ويتحلل‬70 ‫يمثل اإلفراز الكلوي حوالي‬ ‫بسبب اإلنزيمات البكتيرية إلى ثاني أكسيد الكربون واألمونيا‬ 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬ Healthy adult human body containing about (1.1) gm of uric acid. Uric acid homeostasis is determined by the balance between production, renal excretion and intestinal secretion. The kidney is an important regulator of circulating uric acid levels. Its concentration depends upon the net balance achieved between the rate of synthesis of purines or breakdown of nucleoproteins on one hand and the rate of elimination of uric acid on the other. ‫ الكلى هي منظم مهم‬.‫يتم تحديد توازن حمض اليوريك من خالل التوازن بني اإلنتاج واإلفراز الكلوي واإلفراز املعوي‬ ‫ يعتمد تركيزه على التوازن الصافي الذي تحقق بني معدل تخليق البيورينات أو انهيار‬.‫لتعميم مستويات حمض اليوريك‬ ‫البروتني النووي من ناحية ومعدل القضاء على حمض اليوريك من ناحية أخرى‬ Clinical significance Having some uric acid in the blood is normal. However, if uric acid levels go above or below a healthy range, this can result in health problems. Normal levels: Males (3.5 – 7.0 mg/dl) or (0.21 – 0.42 mmol/L) ‫بالرجال اعلى الن الرجال ذو عضالت بارزة‬ Females (2.6 – 6.0 mg/dl) or (0.15 – 0.36 mmol/L) 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬  Hyperuricemia ‫التخلص‬ Hyperuricemia is an excess of Uric acid in the blood, if the body can’t flush the uric ‫يمكن ان يتراكم‬ acid out through the kidneys, it can build up in the bloodstream and may accumulate ‫او يتم ترسبها‬ ‫حصى‬ in the tissues and make kidney stones (nephrolithiasis), or it’s deposited as needle- ‫كبلورات ع شكل ابرة‬ ‫امللوك‬/ ‫داء النقرس‬ shaped crystals in the joints (gout). These crystals cause severe inflammation and ‫الم شديد‬ intense pain of gout attack. This elevated level is the result of increased production, decreased excretion of uric acid, or a combination of both processes. Note: kidney stone volume ≥ 1.6 mm3 Uric acid stone uric acid crystals (needle shape) 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬  The major causes of Hyperuricemia are: ‫بشكل اساسي‬  Essentially Hyperuricemia (gout). ‫ضعف‬  Impaired renal excretion: Renal failure, drug therapy, alcohol, ketoacidosis ‫زيادة دوران‬  Increased nucleic acids turnover e.g. leukemia, polycythemia  Specific enzyme defect: Deficiency of HGPRT enzyme in lesch-nyhan syndrome. While Hyperuricemia in some cases causes ‫ال توجد أعراض أو مشاكل‬ ‫حالة طويلة‬ no symptoms or problems, a prolonged state of this condition may lead to the development of uric acid crystals, which can be problematic. The two most common conditions that can result from high uric acid levels are gout and kidney disease. Symptoms of Gout include ‫ تشوه‬،‫ تصلب‬،‫ احمرار‬،‫ تورم‬،‫ألم‬ pain, swelling, redness, stiffness, deformity. Uric acid crystals can also be deposited in the kidneys, causing kidney stones to form, Symptoms of kidney stones include: Pain or aching in your lower back, side, abdomen, or groin and also: ‫ألم أو ألم في أسفل الظهر أو الجانب أو البطن أو الفخذ وأيضا‬  Nausea ‫غثيان‬  Increased urge to urinate ‫زيادة الرغبة في التبول‬  Pain when urinating ‫ألم عند التبول‬  Difficulty urinating ‫صعوبة التبول‬  Blood in your urine ‫الدم في البول‬  Foul-smelling or cloudy urine ‫رائحة كريهة أو بول غائم‬ 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬  ‫ألنها مؤوى للبكتيريا‬ Kidney stones can also cause urinary tract infections (UTIs) because they harbor bacteria. Hypouricemia Hypouricemia may be caused by decreased uric acid production, or decreased renal tubular reabsorption due to inherited or acquired disorders. Hypouricemia has been thought of as a biochemical disorder with no clinical significance other than as a marker of underlying disease. ‫يعتقد أن نقص صوديوم الدم هو اضطراب كيميائي حيوي ليس له أهمية سريرية‬ The major causes of Hypouricemia are:.‫سوى عالمة على املرض األساسي‬ ‫التشمع‬ - Liver disease like cirrhosis. - Renal disease that decrease renal tubular reabsorption. - Drugs in large dose like a salicylates. 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬  Foods that contain high levels of purines Measurement of Uric acid Uricase acts on Uric acid to produce Allantoin, carbon dioxide and hydrogen peroxide. Hydrogen peroxide in the presence of peroxidase react with chromogen (amino- antipyrine and dichloro hydrobenzen sulfonate) to yield Quinoneimine, a red coloured complex. The absorbance measured at 520 nm. Uric acid + O2 + H2O Uricase Allantoin + H2O2 + CO2 H2O2 + chromogen peroxidase Quinoneimine + H2O 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬  Blank Standard Test Working reagent (ml) 1 1 1 Standard/R4 (µ) ___ 25 ___ Serum (µ) ___ ___ 25 D.W. (µ) 25 ___ ___ Mix for 5 minutes at 25 ̊Ϲ, Record the absorbance at 520 nm against reagent blank. *color is stabile for 30 minutes. *The concentration of uric acid standard 10 (mg/dL) Calculation 𝐴𝑏𝑠. 𝑇𝑒𝑠𝑡 Results = x standard conc. 𝐴𝑏𝑠. (𝑠𝑡𝑎𝑛𝑑𝑎𝑟𝑑) 2021-2021 /‫ جامعة نينوى‬/‫ كلية الطب‬/‫ خالد محمد خضر‬.‫م‬.‫م‬