Filtration, Diffusion and Molecular Sieving Through Peripheral Capillary Membranes

Pappenheimer, J. R.; Renkin, Eugene M.; Borrero, Luís M.

doi:10.1152/ajplegacy.1951.167.1.13

Cited by 929 publications

(390 citation statements)

References 19 publications

Supporting

Mentioning

374

Contrasting

Unclassified

Order By: Relevance

“…Recent observations made in Karnovsky's laboratory indicate that the slit diaphragm, which continuously spans the space between foot processes, in fact has a highly ordered, isoporous substructure (30). Its central filament and adjacent cross bridges from rectangular pores measuring 50 X 150 ~' The dimensions of these pores are consistent with those calculated from physiological data (31)(32)(33), and suggest that the slit diaphragm may indeed represent the fine filter of the glomerulus.…”

Section: Current Concepts Of Normal Glomerular Filtrationsupporting

confidence: 80%

Altered Functional Properties of the Renal Glomerulus in Autologous Immune Complex Nephritis

Schneeberger

Leber

Karnovsky

et al. 1974

The Journal of Experimental Medicine

View full text Add to dashboard Cite

The present study was undertaken in order to investigate the nature of the glomerular damage in a form of experimental immune complex nephritis. The model of autologous immune complex nephritis (AIC) 1 (Heymann's nephritis) (1) was chosen for several reasons. First, the model bears a remarkable resemblance, in terms of ultrastructural and immunofluorescence features, to an important renal disease in man, membranous glomerulonephritis. Furthermore, the model is highly reproducible. In addition, the basic pathogenetic mechanism has been thoroughly documented (2-4). Briefly, the disease is produced in rats by immunization with homologous kidney preparations, which results in the formation of autoantibodies against a renal antigen, normally found in the brush border of proximal tubules. This antigen is presumed to enter the circulation in small amounts and combine with autoantibody to form complexes which deposit in glomeruli. 2 The complexes are detected as granular deposits of immunoglobulin and complement along the epithelial side of the glomerular basement membrane. The disease, like its human counterpart, is manifested by proteinuria, which is often heavy.Our approach was to use the enzymatic tracers horseradish peroxidase (HRP) (40,000 daltons) and catalase (240,000 daltons), and the electronopaque tracer ferritin (ca. 500,000 daltons) as probe molecules with which to assess the altered functional properties of the glomerular capillary wall. These ultrastructural tracers can be directly visualized, and their location within the glomerular capillary wall can be followed at sequential intervals after intravenous injection. Such protein tracers have been extensively used to identify * This study was supported by U.S. Public Health Service grants no. AM 16392 and AM 13132.1Abbreviations used in this paper: AIC, autologous immune complex; CFA, complete Freund's adjuvant; CL, capillary lumen; DAB, 3,3' diaminobenzidine-tetra-HC1; GBM, glomerniar basement membrane; HRP, horseradish peroxidase; US, urinary space.It is of interest that a related pathogenetic mechanism may operate in man. It has recently been reported that a tubular-derived antigen may be present in the glomerular immune deposits in some cases of human membranous glomerulonephritis (5).

show abstract

Section: Current Concepts Of Normal Glomerular Filtrationsupporting

confidence: 80%

Altered Functional Properties of the Renal Glomerulus in Autologous Immune Complex Nephritis

Schneeberger

Leber

Karnovsky

et al. 1974

The Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…By itself, the apparent d for a heterogeneous membrane is insufficient to provide a complete description of exchange kinetics. Realizing this, Pappenheimer proposed in 1969 (35) that ϳ50% of transcapillary water exchange occurs through a water-only pathway to explain early data on hydraulic conductivity and solute permeability in skeletal muscle measured by his isogravimetric technique (36) and the indicator-dilution work of Alvarez and Yudilevich (3). More recently, Watson (53) and Wolf (54-57) have proposed three pathway pore models for solute exchange in mammalian skeletal muscle, with 41% of steady-state flow through a water-only pathway, 17% through a largepore pathway of radius 28.5 nm, and 42% through a small-pore pathway of radius 4.57 nm.…”

Section: Interpretation Of the Weight Transient Curvementioning

confidence: 99%

Transient transcapillary exchange of water driven by osmotic forces in the heart

Kellen

Bassingthwaighte

2003

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Kellen, Michael R., and James B. Bassingthwaighte. Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285: H1317-H1331, 2003. First published May 8, 2003 10.1152/ ajpheart.00587.2002.-Osmotic transient responses in organ weight after changes in perfusate osmolarity have implied steric hindrance to small-molecule transcapillary exchange, but tracer methods do not. We obtained osmotic weight transient data in isolated, Ringer-perfused rabbit hearts with NaCl, urea, glucose, sucrose, raffinose, inulin, and albumin and analyzed the data with a new anatomically and physicochemically based model accounting for 1) transendothelial water flux, 2) two sizes of porous passages across the capillary wall, 3) axial intracapillary concentration gradients, and 4) water fluxes between myocytes and interstitium. During steady-state conditions ϳ28% of the transcapillary water flux going to form lymph was through the endothelial cell membranes [capillary hydraulic conductivity (Lp) ϭ 1.8 Ϯ 0.6 ϫ 10 Ϫ8 cm ⅐ s Ϫ1 ⅐ mmHg Ϫ1 ], presumably mainly through aquaporin channels. The interendothelial clefts (with Lp ϭ 4.4 Ϯ 1.3 ϫ 10 Ϫ8 cm ⅐ s Ϫ1 ⅐ mmHg Ϫ1 ) account for 67% of the water flux; clefts are so wide (equivalent pore radius was 7 Ϯ 0.2 nm, covering ϳ0.02% of the capillary surface area) that there is no apparent hindrance for molecules as large as raffinose. Infrequent large pores account for the remaining 5% of the flux. During osmotic transients due to 30 mM increases in concentrations of small solutes, the transendothelial water flux was in the opposite direction and almost 800 times as large and was entirely transendothelial because no solute gradient forms across the pores. During albumin transients, gradients persisted for long times because albumin does not permeate small pores; the water fluxes per milliosmolar osmolarity change were 200 times larger than steady-state water flux. The analysis completely reconciles data from osmotic transient, tracer dilution, and lymph sampling techniques. capillary permeability; reflection coefficient; transport modeling; microcirculation; isolated rabbit heart; porous transport THE OSMOTIC WEIGHT TRANSIENT method is one of the few techniques available to measure the reflection coefficient ( ) of small hydrophilic solutes in the vascular beds of whole organs. Using a single-membrane model of events during this experiment, Vargas and Johnson (49) developed a relationship, ϭ J v /(L p S⌬⌸), where L p is capillary hydraulic conductivity, S is surface area, and ⌬⌸ is osmotic perturbation, which relates the volume flux across the capillary wall, J v , to the solute reflection coefficient, , immediately following a step change in perfusate osmolarity. In a whole organ, the total fluid movement across the capillary wall, J v S, is nearly equal to the rate of weight change of the organ; knowledge of the magnitude of ⌬⌸ and L p is all that is needed to estimate . Estimates of using this analysis method and osmotic weight transient measu...

show abstract

“…Although vascular permeability can be assessed by techniques using radiolabeled tracers in vivo and in vitro, the recognition of cellular transport pathways can be achieved only by morphological means. Physiological data have conceptually defined a system of pores on the endothelial wall to account for the vascular permeability for both small solutes and larger circulating proteins (Pappenheimer et al 1951;Pappenheimer 1953;Renkin 1985). Current concepts on the relationship between functional and morphological properties of the microvasculature have assigned the small pore system to the intercellular junctions and the large pore system to the plasmalemmal vesicles (Renkin 1985).…”

mentioning

confidence: 99%

Evidence of a Tubular System for Transendothelial Transport in Arterial Capillaries of the Rete Mirabile

Bendayan

Rasio

1997

J Histochem Cytochem.

View full text Add to dashboard Cite

SUMMARYThe arterial endothelial cells of the rete capillaries of the eel were examined by transmission electron microscopy on thin sections, on freeze-fracture replicas, by scanning electron microscopy, after cytochemical osmium impregnation and perfusion with peroxidase. The study revealed the existence of membrane-bound tubules and vesicles that open at both the luminal and abluminal poles of the cell and at the level of the intercellular space. The tubules are straight or present successive dilations and constrictions. They branch in various directions and intrude deeply into the cell cytoplasm, forming a complex tubular network within the cell. Immunocytochemical techniques were applied on immersion-fixed tissues and on perfusion of the capillaries with albumin and insulin. These demonstrated that the tubular-vesicular system is involved in the transport of circulating proteins. Furthermore, protein A-gold immunocytochemistry has revealed the association of actin with the membranes of this system. On the basis of these results, we suggest that the transendothelial transport of serum proteins takes place by a transcytotic process through a membrane-bound tubular-vesicular system and is equivalent to the large pore system presumed from functional studies. (J Histochem Cytochem 45:1365-1378, 1997)

show abstract

Filtration, Diffusion and Molecular Sieving Through Peripheral Capillary Membranes

Cited by 929 publications

References 19 publications

Altered Functional Properties of the Renal Glomerulus in Autologous Immune Complex Nephritis

Altered Functional Properties of the Renal Glomerulus in Autologous Immune Complex Nephritis

Transient transcapillary exchange of water driven by osmotic forces in the heart

Evidence of a Tubular System for Transendothelial Transport in Arterial Capillaries of the Rete Mirabile

Contact Info

Product

Resources

About