Gastroenterology Unit, Gradenigo Hospital, Turin, Italy.
J Physiol Pharmacol. 2009 Dec;60(4):111-7.
Increased extracellular fluid volume (ECF) characterizes compensated cirrhosis. To identify the mechanisms of fluid retention in cirrhosis through clearance methods, 10 control and 10 preascitic rats with CCl(4)-induced cirrhosis were studied following i.v. loading with 1 ml 5% glucose solution. Glomerular filtration rate and renal plasma flow were evaluated through inulin and para-aminohippurate clearances; water and electrolyte handling was assessed measuring urine and plasma osmolarity, electrolyte excretions, and tubular solute-free water reabsorption (TFWR = osmolar clearance minus urinary output); ECF was assessed through hormonal status determination. After water loading, cirrhotic rats had increased ECF (lower plasma renin activity and aldosterone and higher atrial natriuretic peptide levels, all P<0.03), solute-free water retention (increased TFWR and decreased plasma osmolarity, all P<0.05), reduced absolute and fractional sodium excretions (P<0.05). Cirrhotic rats showed sodium retention in the medullary thick ascending limb of Henle's loop (i.e. increased values of TFWR for any given value of osmolar clearance). Trans-tubular potassium gradient in medullary collecting duct was similar in the two groups (P=0.55), ruling out aldosterone-dependent sodium retention and potassium hyper-secretion. In experimental preascitic cirrhosis NaCl retention in the ascending limb of Henle's loop increases medullary interstitial tonicity leading to vasopressin-independent water back-diffusion in thin descending limb of Henle's loop and collecting duct.
细胞外液容量增加（ECF）是代偿性肝硬化的特征。为了通过清除方法确定肝硬化液体潴留的机制，对 10 只对照大鼠和 10 只 CCl4-诱导肝硬化的预腹水大鼠进行了研究，方法是静脉内输注 1ml 5%葡萄糖溶液。通过菊粉和对氨基马尿酸清除率评估肾小球滤过率和肾血浆流量；通过测量尿和血浆渗透压、电解质排泄以及管腔溶质自由水重吸收（TFWR=渗透压清除率减去尿排量）评估水和电解质处理；通过激素状态测定评估 ECF。水负荷后，肝硬化大鼠的 ECF 增加（较低的血浆肾素活性和醛固酮，较高的心房利钠肽水平，均 P<0.03），溶质自由水潴留（增加的 TFWR 和降低的血浆渗透压，均 P<0.05），绝对和分数钠排泄减少（P<0.05）。肝硬化大鼠在 Henle 袢升支粗段中显示出钠潴留（即 TFWR 值对于任何给定的渗透压清除率值都增加）。两组间髓质集合管中的跨管钾梯度相似（P=0.55），排除了醛固酮依赖性钠潴留和钾过度分泌。在实验性预腹水肝硬化中，Henle 袢升支中的 NaCl 潴留增加了髓质间质的渗透压，导致抗利尿激素非依赖性水在 Henle 袢降支和集合管中的反向扩散。
