Capillary Type in Spleen Continuous Ainusoidal Fenestrated

Capillary Wall

Thickening of the capillary walls, interstitial tissues, and alveolar membranes produces a barrier at the interface between the capillaries and the alveolar sacs.

From: Paediatric Cardiology (Third Edition) , 2010

Volume 1

C.Charles Michel , in Seldin and Giebisch's The Kidney (Fifth Edition), 2013

Microvascular Ultrastructure

Capillary walls consist of a single layer of flattened endothelial cells, the endothelia, and these cells constitute the barrier between the blood and the ISF. Electron microscopy has revealed that endothelial cells in different tissues are of two distinct types: "continuous" and "fenestrated" ( Figure 9.1). Continuous endothelium is found in microvessels of skin, muscle, lung, and connective tissues. Here, the endothelial cells are joined together by tight junctions to form a continuous layer surrounded by a continuous basement membrane. The plasmalemmal membranes of the continuous endothelia retain their integrity; even in areas where the cells are flattened, reducing their thickness to less than 0.1   μm, the distinct luminal and abluminal membranes are separated by a thin layer of cytoplasm.

Figure 9.1. Diagrams showing the ultrastuctural features of microvascular walls in transverse section: (a) Vessel with continuous endothelium; (b) Vessel with fenestrated endothelium.

The basement membrane (BM) forms a continuous layer around the outside of both vessel types and the luminal surfaces of both endothelia are covered with a negatively charged glycocalyx (SL) (EC: endothelial cell; J: junction; F: fenestration (fenestra); N: endothelial cell nucleus).

Fenestrated endothelium is found in microvessels associated with secretory and absorptive epithelia, e.g., the capillaries of the intestinal mucosae, glomerular, and peri-tubular capillaries of the kidney. The walls of fenestrated microvessels are also made of a single continuous layer of endothelial cells joined by tight junctions and surrounded by a continuous basement membrane, but in these vessels attenuated areas of cells appear to be penetrated by circular openings 40 to 70   nm in diameter. These are the fenestrae (or fenestrations), and in most cases the fenestrations are closed by a thin electron-dense diaphragm, which appears to be arranged as a series of broad spokes with central "hub" ¹⁴ (Figure 9.2).

Figure 9.2. En face view of fenestrated endothelium of peritubular capillary of the kidney in a rapid freeze deep etch preparation.

Scale bar=0.1   μm.

(From ref. [14].)

Covering the luminal surface of endothelial cells is a layer of glycoprotein called the glycocalyx or endocapillary layer (ECL). First identified by Luft in 1966 ⁶⁸ using ruthenium red staining, its importance has only come to be widely appreciated in the past 15 years. Although both continuous and fenestrated endothelia have been found to contain the various inclusions common to most cells (e.g., mitochondria, rough and smooth endoplasmic reticulum) the dominating ultrastructural feature seen in transmission electron micrographs is the large number of small endoplasmic vesicles (Figure 9.3). The majority of vesicles are arranged in fused clusters that communicate with each other and with flask like pits on either the luminal or abluminal surfaces of the cells called the caveolae intracellulares. Chains of fused vesicles forming channels that pass through endothelial cells ¹¹⁹ appear to be relatively rare occurrences in unstimulated endothelium, but are a feature of endothelium activated by certain mediators. ^34,35

Figure 9.3. Electron micrograph of microvascular endothelium of frog.

There are three mitochondria in the central part of the cell and large numbers of plasmalemmel vesicles. Scale bar=0.2 μm.

(Electron micrograph by H.Moffitt.)

The intercellular clefts of continuous endothelia, the fenestrae of fenestrated endothelia, and the small vesicles have all been implicated as pathways through the endothelia as a result of experiments using electron-dense tracers. Controversy surrounded the interpretation of many of these experiments, but progress has been made over the past 20 years as physiological evidence clarified their interpretation. For this reason, the ultrastructural basis of permeability is considered after we have defined the permeability coefficients by considering the principles of passive transport and have discussed their values in different endothelia to different types of molecules.

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Membranous Glomerulonephritis, Secondary

In Diagnostic Pathology: Kidney Diseases (Second Edition), 2016

ANCILLARY TESTS

Immunofluorescence

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Granular capillary wall staining for IgG and kappa and lambda light chains ± complement components

○

IgG1 and IgG2 described in subepithelial deposits of MGN associated with carcinoma

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IgG3 is dominant subclass in membranous lupus nephritis

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Many examples of putative antigen localization in deposits (e.g., carcinoembryonic antigen, bovine serum albumin, enzyme replacement, hepatitis B)

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Caveat that proteins can be trapped nonspecifically in deposits

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Tubular basement membrane Ig deposits common in lupus

Electron Microscopy

•

Subepithelial electron-dense deposits, often stage I

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Mesangial electron-dense deposits

○

Non-PLA2R associated MGN has mesangial deposits in ~ 70% (Cossey)

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MGN 2° with PLA2R deposition has mesangial deposits in ~ 30% (Cossey)

•

Endothelial tubuloreticular inclusions

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In systemic lupus erythematosus or viral infections, such as hepatitis or HIV

•

Bowman capsular electron-dense deposits in lupus

○

Also reported in a few primary MGN cases with substantial clinical follow-up

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Cardiovascular Physiology

George J. Crystal , Paul M. Heerdt , in Pharmacology and Physiology for Anesthesia, 2013

Factors Influencing the Balance Between Capillary Filtration and Absorption

Because the capillary wall is highly permeable to water and to almost all plasma solutes except plasma proteins; it acts like a porous filter through which protein-free plasma moves by bulk flow under the influence of a hydrostatic pressure gradient. Transcapillary filtration is defined as follows:

[5] $\text{Fluid filtration}={\mathrm{C}}_{\mathrm{F}}[({\mathrm{P}}_{\text{cap}}-{\mathrm{P}}_{\text{IF}})-({\Pi }_{\text{cap}}-{\Pi }_{\text{IF}})]$

where C_F = capillary filtration coefficient; P_cap = capillary hydrostatic pressure; P_IF = interstitial fluid hydrostatic pressure; Π_IF = interstitial fluid oncotic pressure; Π_cap = capillary oncotic pressure. P_cap and Π_IF are forces of filtration. P_cap is determined by arterial pressure, venous pressure, and the ratio of postcapillary to precapillary resistance. Elevations of arterial pressure, venous pressure, or venous resistance/arterial resistance produce elevations of P_cap. P_cap is approximately 35 mm Hg at the arterial end of the capillaries and approximately 15 mm Hg at the venous end. Π_I is due to plasma proteins that have passed through the capillary wall and is normally very low compared with P_cap. Thus P_cap is normally the major force for filtration. P_IF and Π_cap are forces favoring absorption. P_IF is determined by the volume of fluid and the distensibility of the interstitial space, and is normally nearly equal to zero. Π_cap is due to plasma proteins (predominantly albumin) and is approximately 25 mm Hg. Π_p is normally the major force for absorption. The direction and magnitude of capillary bulk flow is essentially a function of the ratio of P_cap to Π_cap (Figure 21-14)_. ³³

Filtered fluid that reaches the extravascular spaces is returned to the circulatory system via the lymphatic network. Under normal conditions (see Figure 21-14, A ), filtration dominates at the arterial end of the capillary, and absorption at the venous end because of the gradient of hydrostatic pressure; there is a small net filtration, which is compensated by lymph flow. Edema is a condition of excess accumulation of fluid in the interstitial space and occurs when net filtration exceeds drainage via the lymphatics. Edema can be caused by (1) increased capillary pressure, (2) decreased plasma protein concentration, (3) accumulation of osmotically active substances in the interstitial space, (4) increased capillary permeability, or (5) inadequate lymph flow. Conditions resulting in edema are depicted in Figure 21-14, B-D .

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Pharmaceutical Perspectives of Nonviral Gene Therapy

Ram I. Mahato , ... Alain Rolland , in Advances in Genetics, 1999

A Anatomical and physiological considerations

The blood capillary walls are generally comprised of four layers, namely plasmaendothelial interface, endothelium, basal lamina, and adventia. The endothelium is a monolayer of metabolically active cells, which mediate and monitor the bidirectional exchange of fluid between the plasma and the interstitial fluid. There are several different pathways by which macromolecules can cross the endothelial barrier ( Simionescu, 1983; Taylor and Granger, 1984): (i) through the cytoplasm of endothelial cells themselves; (ii) across the endothelial cell membrane vesicles; (iii) through interendothelial cell junctions; and (iv) through endothelial cell fenestrae. Based on the morphology and continuity of the endothelial layer and the basement membrane, capillary endothelium can be divided into three categories continuous, fenestrated, and discontinuous endothelium.

The continuous capillaries are found in skeletal, cardiac, and smooth muscles, as well as in lung, skin, and subcutaneous and mucous membranes. The endothelial layer of the brain microvasculature is the tightest endothelium, with no fenestrations. This endothelial barrier forms a continuous cellular layer between the blood and brain interstitium, which is impermeable to plasmids. Capillaries with fenestrated endothelia and a continuous basement membrane are generally found in the kidney, small intestine, and salivary glands. Most of these capillaries have diaphragmed fenestrae, which are circular openings of 40–60 nm in diameter. The discontinuous capillaries, also known as sinusoidal capillaries, are common in the liver, spleen, bone marrow, and other organs of the reticuloendothelial system. These capillaries show large interendothelial junction (fenestrations up to 150 nm). Depending on the tissue or organ, the basal membrane in sinusoidal capillaries is either absent (e.g., in liver) or present as a discontinuous membrane (e.g., in spleen and bone marrow) (Venkatachalam and Rennke, 1978). The sinusoids of the liver are lined by highly phagocytic Kupffer cells, and those of the bone marrow by flattened, phagocytic reticuloendothelial cells. In the spleen, the endothelial cells are greatly elongated and contain a large number of pinocytic vesicles (up to 100 nm in diameter).

Due to their large molecular weight (greater than 1000   kDa) and hydrodynamic diameter in aqeuous suspension of 100   nm (Ledley, 1996), plasmids extravasate poorly via continuous capillaries because of tight junctions between the cells. However, plasmids can easily extravasate to sinusoidal capillaries of liver and spleen. Formulating plasmids into unimeric particles of 20–40   nm in diameter may enhance extravasation of plasmids across continuous and fenestrated capillaries.

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Circulatory physiology

Jean-Pierre Barral D.O. (UK), MRO (F) , Alain Croibier D.O., MRO(F) , in Visceral Vascular Manipulations, 2011

Exchanges

Circulation exchanges across the capillary wall occur though different mechanisms. Pores are orifices whose number and dimension vary according to the organ. They afford passage of lipid-insoluble molecules. Flow is limited by size, number of available pores, and blood flow. Lipid-soluble molecules can diffuse across the same capillary wall, which is itself made up largely of lipids. Water movement across the capillary wall is by osmosis, driven by the sum of hydrostatic and osmotic pressures.

Starling's curve (Fig. 2.20) shows that in the initial part of a capillary hydrostatic pressure overcomes osmotic pressure, resulting in filtration, with the result that the fluid moves out of the capillary into the interstitial fluid. In the second part of the capillary, osmotic pressure (derived from blood proteins, particularly albumin) prevails, drawing the water towards the capillary vascular lumen.

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Rheumatoid Arthritis

In Diagnostic Pathology: Kidney Diseases (Second Edition), 2016

Immunofluorescence

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Diffuse or segmental capillary wall deposits identified in MGN with IgG and C3

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Therapy-induced membranous lupus nephritis may have mesangial and capillary wall deposits with "full house" staining

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Mesangial IgM immune deposits often dominant with weaker staining for other Ig and complement components in mesangioproliferative GN related to RA

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Amyloid can be typed by immunofluorescence or immunohistochemistry

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Subtyping of amyloid demonstrates AA protein with no evidence of immunoglobulin light or heavy chains

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Weak nonspecific entrapment of immunoglobulin light and heavy chains should not be misinterpreted as AL amyloid

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No immune complexes in NSAID interstitial nephritis, cyclosporine toxicity, analgesic nephropathy, pauci-immune GN, and minimal change disease

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Volume 2

Kent L. Thornburg , ... George D. Giraud , in Knobil and Neill's Physiology of Reproduction (Fourth Edition), 2015

Glomerular Capillary Permselectivity to Neutral Macromolecules in Human Pregnancy

An estimate of glomerular capillary wall porosity to macromolecules in human pregnancy has been made, utilizing fractional clearance of neutral dextrans spanning a wide size range. This measurement is independent of hydraulic permeability. Neutral dextrans are not restricted in their passage across the glomerular filter by charge or configurational factors, nor are they absorbed or secreted by the renal tubule. Thus they are classically used to assess the glomerular size-selective barrier function. It was a surprise when Lindheimer's group found reduced fractional clearance of dextrans at the lower size ranges during late gestation. ^192,197 This finding points to an altered structure of the glomerular capillary membrane. Their findings could be explained by (1) an increase in molecular movement through a nondiscriminatory "shunt" pathway or (2) an increased range of pore sizes in the late-gestation glomerular capillary wall. ¹⁹⁷

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Hepatitis B Virus

In Diagnostic Pathology: Kidney Diseases (Second Edition), 2016

ANCILLARY TESTS

Immunohistochemistry

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HBcAg stains subepithelial immune complexes along glomerular capillaries

Immunofluorescence

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MGN

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Granular glomerular capillary wall staining for IgG, C3 (variable), and κ and λ

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Mesangial staining also present

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Phospholipase A2 receptor (PLA2R) positive (67%)

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MPGN

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Coarse to granular glomerular capillary wall staining for IgG, C3 (variable), and κ and λ

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Cryoglobulinemic GN

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Coarse to granular glomerular capillary wall staining for IgG &/or IgM, κ and λ

Electron Microscopy

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MGN

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Subepithelial immune deposits

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Mesangial immune deposits

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MPGN

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Subendothelial immune deposits

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Mesangial immune deposits

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Duplication of GBMs

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Subepithelial deposits variably present

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Cryoglobulinemic GN

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Subendothelial immune deposits

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Mesangial immune deposits

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Substructural organization of deposits may be present

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Tubuloreticular inclusions in endothelial cells may be present

•

HBV virions not demonstrable

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Renal Anatomy

Wilhelm Kriz , Marlies Elger , in Comprehensive Clinical Nephrology (Fourth Edition), 2010

Filtration Barrier

Filtration through the glomerular capillary wall occurs along an extracellular pathway including the endothelial pores, the GBM, and the slit diaphragm (see Figs. 1.8 and 1.10). All these components are quite permeable for water; the high permeability for water, small solutes, and ions results from the fact that no cell membranes are interposed. The hydraulic conductance of the individual layers of the filtration barrier is difficult to study. In a mathematical model of glomerular filtration, the hydraulic resistance of the endothelium was predicted to be small, whereas the GBM and filtration slits contribute roughly one half each to the total hydraulic resistance of the capillary wall. ¹⁶

The barrier function of the glomerular capillary wall for macromolecules is selective for size, shape, and charge. ¹³ The charge selectivity of the barrier results from the dense accumulation of negatively charged molecules throughout the entire depth of the filtration barrier, including the surface coat of endothelial cells, and the high content of negatively charged heparan sulfate proteoglycans in the GBM. Polyanionic macromolecules, such as plasma proteins, are repelled by the electronegative shield originating from these dense assemblies of negative charges.

The crucial structure accounting for the size selectivity of the filtration barrier appears to be the slit diaphragm. ¹⁶ Uncharged macromolecules up to an effective radius of 1.8 nm pass freely through the filter. Larger components are more and more restricted (indicated by their fractional clearances, which progressively decrease) and are totally restricted at effective radii of more than 4 nm. Plasma albumin has an effective radius of 3.6 nm; without the repulsion from the negative charge, plasma albumin would pass through the filter in considerable amounts.

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Introduction to Renal Biopsy

Laura Barisoni , ... Lois J. Arend , in Genitourinary Pathology, 2007

ANCILLARY STUDIES

IMMUNOFLUORESCENCE

IF studies show large glomerular capillary wall (pseudolinear pattern) deposits with more granular mesangial deposits positive for IgG, IgM, and C3. In type II MPGN, the deposits are pseudolinear to linear along the capillary walls (ribbon-like) ( Fig. 7-10B).

ELECTRON MICROSCOPY

Glomerular capillaries are obliterated by the presence of double contours, endocapillary proliferation, and mesangial expansion. Electron-dense deposits are present in the subendothelium, mesangium, and occasionally subepithelium (sparse) (Fig. 7-9C). Type II MPGN is characterized by ribbon-like electron-dense deposits substituting for the GBM (Fig. 7-10B).

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