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UREA

Biochemistry and Physiology

Catabolism of proteins and nucleic acids results in the formation of urea and ammonia, the so-

called nonprotein nitrogenous compounds. As ammonia has no role in assessing

kidney function, it is discussed in Chapter 32.

Urea [CO!"2#2, $r %& 'a( is the ma)or nitrogen containing metabolic product of protein

catabolism in humans, accounting for more than *+ of the non protein nitrogen eentually

ecreted. /he biosynthesis of urea from amino nitrogen0deried ammonia is carried out

eclusiely by hepatic en1ymes of the urea cycle. 'uring the process of protein catabolism,

amino acid nitrogen is conerted to urea in the lier by the action of so-called urea cycle

en1ymes

igure 2+-#.

$ore than 4& of urea is ecreted through the kidneys, 5ith losses through the gastrointestinaltract and skin accounting for most of the remaining minor fraction. Conse6uently, kidney disease

is associated 5ith accumulation of urea in blood. An increase in serum urea concentration

characteri1es the uremic a1otemic# state. Urea is neither actiely reabsorbed nor secreted by the

tubules but is filtered freely by the glomeruli. 7n a normal kidney, & to *& of the highly

diffusible urea moes passiely out of the renal tubule and into the interstitium, ultimately to re-

enter plasma. /he backdiffusion of urea is also dependent on urine flo5 rate, 5ith less entering

the interstitium in high-flo5 states e.g., pregnancy# and ice ersa. Conse6uently, urea clearance

generally underestimates 89. 7n end-stage renal disease, osmotic diuresis in the remaining

functional nephrons limits the back-diffusion of urea, so that urea clearance approaches inulin

clearance. $easurement of blood and serum urea has been used for many years as an indicator of kidney function.

"o5eer, it is generally accepted that creatinine measurement proides better information in this

respect. :erum and urinary urea measurement may still proide useful clinical information in

particular circumstances, and the measurement of urea in dialysis fluids is 5idely used in

assessing the ade6uacy of renal replacement therapy see Chapter ;#.

Clinical Significance

!umerous etrarenal factors influence the circulating urea concentration, limiting its alue as a

test of kidney function. or eample, plasma urea concentration is increased by a high-protein

diet, increased protein catabolism, reabsorption of blood proteins after gastrointestinalhemorrhage, treatment 5ith cortisol or its synthetic analogs, dehydration, and decreased

perfusion of the kidneys e.g., heart failure#. 7n the prerenal situations already discussed, the

plasma creatinine concentration may be normal. 7n obstructie postrenal conditions e.g.,

malignancy, nephrolithiasis, prostatism#, both serum creatinine and urea concentrations 5ill be

increased, although in these situations, the increase in serum urea is greater than in creatinine

because of increased back-diffusion.


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/hese considerations gie rise to the principal clinical utility of serum urea, 5hich lies in its

measurement in con)unction 5ith that of serum creatinine and subse6uent calculation of the urea

nitrogen-to-creatinine ratio. /his can be used as a crude discriminator bet5een prerenal and

postrenal a1otemia.

or a normal indiidual on a normal diet, the reference interal for the ratio is bet5een


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main source )ack bean meal# to generate ammonium ion, 5hich then is 6uantitated. /his

approach has been used in e6uilibrium, rate, conductimetric, and dry chemistry systems.3


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Other Methods

An improed 7'$: method for serum urea measurement has been listed by FC/@$ as a

reference method.


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urea yang sangat diffusible bergerak pasif keluar dari tubulus gin)al dan ke interstitium, akhirnya

untuk memasukkan kembali plasma. /he backdiffusion urea )uga tergantung pada la)u aliran

urin, dengan kurang memasuki interstitium di negara-negara aliran tinggi misalnya, kehamilan#

dan sebaliknya. Akibatnya, urea cukai umumnya meremehkan 89. Eada penyakit gin)al

stadium akhir, diuresis osmotik dalam nefron fungsional yang tersisa membatasi back-difusi

urea, sehingga i1in urea pendekatan inulin clearance. Eengukuran darah dan serum urea telahdigunakan selama bertahun-tahun sebagai indikator fungsi gin)al.

!amun, secara umum diterima bah5a pengukuran kreatinin memberikan informasi yang lebih

baik dalam hal ini. :erum dan pengukuran urea urin masih dapat memberikan informasi klinis

yang berguna dalam situasi tertentu, dan pengukuran urea dalam cairan dialisis secara luas

digunakan dalam menilai kecukupan terapi pengganti gin)al lihat ?ab ;#.

:ignifikansi klinis

?anyak faktor etrarenal mempengaruhi konsentrasi urea yang beredar, membatasi nilai sebagai

tes fungsi gin)al. $isalnya, konsentrasi plasma urea meningkat dengan diet protein tinggi,

peningkatan katabolisme protein, reabsorpsi protein darah setelah perdarahan gastrointestinal,

pengobatan dengan kortisol atau analog sintetis, dehidrasi, dan penurunan perfusi gin)al

misalnya, gagal )antung#. 'alam situasi prerenal sudah dibahas, konsentrasi kreatinin plasma

mungkin normal. 'alam kondisi postrenal obstruktif misalnya, keganasan, nefrolitiasis,

prostatism#, baik kreatinin serum dan konsentrasi urea akan meningkat, meskipun dalam situasi

ini, peningkatan urea serum lebih besar dari kreatinin karena peningkatan kembali-difusi.

Eertimbangan ini menimbulkan utilitas klinis utama serum urea, yang terletak di pengukurannya

bersamaan dengan itu kreatinin serum dan perhitungan berikutnya dari urea rasio nitrogen-to-

kreatinin. "al ini dapat digunakan sebagai diskriminator mentah antara a1otemia prerenal dan

postrenal.

Untuk indiidu normal pada diet normal, interal referensi untuk rasio adalah antara


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pengganti pada pasien yang menerima nutrisi parenteral. Eada diet protein rata-rata, ekskresi urin

dinyatakan sebagai nitrogen urea adalah

C


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oleh peroksidase C


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7nteral referensi untuk nitrogen serum urea pada orang de5asa yang sehat adalah % sampai 2&

mg = d@ 2,

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