Intra- and submembrane particle densities during CO2 stimulation of H+ secretion in turtle bladder.

The apical cell membranes of the H+ secreting, alpha-intercalated cells of turtle urinary bladder (TB) are characterized by studs (cytoplasmic domains of V-adenosinetriphosphatase) on thin-section transmission electron microscopy and by intramembrane particles (spherical units, SPUs) occurring as rod-shaped particles on freeze-fracture electron microscopy. To examine the relationship between studs and SPUs, morphometric studies were carried out on bladders maintained in 5% CO2 and in the absence of exogenous CO2. The stud density per square micrometer of apical membrane was 3,909 +/- 352 (+/-SE) in four TBs (29 alpha-cells) at 5% CO2 and 3,667 +/- 448 (+/-SE) in the paired halves of the same bladders without CO2 (25 alpha-cells). Corresponding densities of SPUs counted on apical membranes of the same bladders (n = 4) were 3,941 +/- 545 in 5% CO2 and 3,599 +/- 511 without CO2. The similarity of the densities of studs and SPUs under both conditions indicates that each SPU within the membrane is matched by one stud projecting into the cytoplasm. The one-for-one relationship between studs and SPUs was preserved over a wide range of transport rates. Addition of CO2 caused only inconsistent increments in the densities of studs and SPUs despite substantial increases in H+ transport rate. Slight variations in spacing of studs were consistent with patterns of distribution of SPUs on fracture surfaces.

Scales of urine acidification: apical membrane-associated particles in turtle bladder.

Since the time of Smith, studies of urinary acidification have shifted their focus to ever smaller scales and have revealed iterative patterns or organization. For this review we focus on the organization of intra- and submembrane particles at the scale of the apical cell membrane of the H+ secreting, alpha intercalated cells. Particles were examined quantitatively by thin section and freeze-fracture (FF) electron microscopy. Ongoing studies in turtle bladder indicate that the density of submembrane particles (studs) per micron 2 is approximately the same as that of spherical units (SPUs) forming linear (rod-shaped) arrays on FF. This one-to-one relationship is observed in the presence or absence of CO2 and suggests that CO2-induced changes in H+ secretion do not involve dissociation of the intramembrane (channel) and cytoplasmic (catalytic) parts of the H-ATPase. Structure-function studies based on density estimates of the particles, morphometry of the H+ secreting cell population, and measurement of H+ transport rate prior to fixation permit functional correlation across scales of study.

Thrombotic thrombocytopenic purpura in pregnancy: successful treatment with plasma exchange. Case report and review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome which presents typically with thrombocytopenia, microangiopathic hemolytic anemia, central nervous system symptoms, fever, and renal abnormalities. The diagnosis of TTP in pregnancy previously carried a poor prognosis and a high fetal mortality when presenting early in gestation. This case report describes the earliest presentation of TTP in pregnancy (6 weeks of gestation) we could identify in the literature treated successfully with a prolonged course of plasma exchange. The differential diagnosis and the pathogenesis of TTP in pregnancy are reviewed. Therapeutic options and data regarding the removal of pregnancy-related hormones by plasma exchange are presented.

Leptospirosis complicated by a Jarisch-Herxheimer reaction and adult respiratory distress syndrome: case report.

Leptospirosis, severe infection due to Leptospira interrogans, is a potentially lethal disease that causes multiple organ failure. In addition to hepatic, renal, and CNS involvement, which are classic complications of leptospirosis, the disease may also be complicated by adult respiratory distress syndrome. Treatment with penicillin may precipitate a severe Jarisch-Herxheimer reaction. The mechanisms of Leptospira-induced toxicity remain obscure. We report a near-fatal case of leptospirosis in a patient who developed a JHR and respiratory failure immediately after initiation of therapy.

Sch-28080 inhibits bafilomycin-sensitive H+ secretion in turtle bladder independently of luminal [K+].

To explore the possible contribution of an H-K-adenosine-triphosphatase (H-K-ATPase) to H+ secretion (JH) in the isolated turtle bladder, we measured electrogenic JH (JeH) as short-circuit current and total JH (JTH) by pH stat titration in the presence of ouabain at different ambient K+ concentration ([K+]) and during luminal addition of a known gastric H-K-ATPase inhibitor, Schering (Sch)-28080. JH was not reduced by decreasing ambient [K+] to undetectable or very low levels (< 0.05 mM by atomic absorption) and luminal BaCl2 addition to further reduce local [K+] at the apical membrane. These K(+)-removal studies indicate that H+ transport is not coupled to countertransport of K+. JTH did not exceed JeH at any point: in K(+)-free solutions JTH was 0.73 +/- 0.05, and JeH was 0.95 +/- 0.08 mumol/h; in standard (3.5 mM) K+ solutions JTH was 0.72 +/- 0.05 and JeH 0.98 +/- 0.06 mumol/h; in high (118 mM) K+ solutions JTH was 0.65 +/- 0.07 and JeH 0.94 +/- 0.08 mumol/h. Sch-28080 caused a rapid inhibition of JH, with similar half-maximal inhibitory concentrations (IC50) in K(+)-free, standard [K+], and high [K+] solutions. Bafilomycin inhibited JeH and JTH with an IC50 of approximately 100 nM. The observed non-potassium-competitive inhibition of JH by Sch-28080 and the bafilomycin sensitivity distinguish the H-ATPase of the turtle bladder from the gastric H-K-ATPase. The rapidity of the inhibition by Sch-28080 suggests that it acts at an accessible luminal site of the ATPase.

Renal malacoplakia with papillary necrosis and renal failure.

Renal parenchymal malacoplakia is a rare cause of renal failure. Patients presenting with renal failure carry a poor prognosis, the majority either dying or requiring chronic dialysis. In this report, we describe an alcoholic man who presented with renal failure due to bilateral renal parenchymal malacoplakia and papillary necrosis. The patient, who initially required dialysis, partially recovered renal function following prolonged antibiotic treatment with a fluoroquinolone antibiotic.

Fractional excretion of urea as a guide to renal dysfunction.

The use of fractional excretion of sodium as a guide to renal perfusion is hampered by the prior use of natriuretic agents. The fractional excretion of urea (FEUr) has been shown to be affected by volume status. We, therefore, determined the value of the FEUr as a guide to renal perfusion. In 6 patients evaluated prospectively and in 87 patients evaluated retrospectively, a low FEUr (less than or equal to 35%) was found to be a sensitive index to renal perfusion, despite the prior administration of furosemide.

Characteristics of apical Cl-HCO3 exchanger of bicarbonate-secreting cells in turtle bladder.

The apical anion exchanger of the beta-carbonic anhydrase (CA) cells differs from the basolateral exchanger of the alpha-cells by reduced sensitivity to disulfonic stilbenes and lack of immunoreactivity with antibodies to erythrocyte band 3 protein. To characterize the exchanger, we examined the effects on electroneutral bicarbonate secretion (JHCO3n) of Cl- replacement by gluconate, Br-, SO4(2-), and NO3- and of inhibition by 1) acetazolamide (ACZ) with and without pretreatment with sodium azide (NaN3), 2) furosemide, and 3) alpha-cyano-4-hydroxycinnamate (CHC). The Cl-dependent JHCO3n was 0.90 +/- 0.09 mumol/h, similar to the ACZ-inhibitable rate of 0.83 +/- 0.08 mumol/h with an apparent Km for Cl near 3.4 mM. Maximal JHCO3n was comparable at luminal pH 6.8 and 4.5. JHCO3n was reduced to approximately 21% in Br-, 13% in SO4(2-), and 7% in NO3- solutions compared with the rates in chloride solutions. ACZ inhibition was not abolished by pretreatment with NaN3. JHCO3n was only slightly inhibited (14%) by furosemide and not inhibited by CHC. In conclusion, the apical exchanger is selective for chloride and relatively resistant to inhibitors. Its dependence on luminal chloride is such that its transport rate is closely regulated by mucosal chloride at concentrations below 20 mM.