fenestrated capillary

**Definition/Structure:** A type of capillary with a continuous basement membrane and endothelial cells perforated by transcellular pores called fenestrae (~60–80 nm). Most fenestrae are bridged by a thin diaphragm (containing PV1/PLVAP protein). Glomerular capillary fenestrae are the exception and have NO diaphragm.

**Comparison of capillary types (high-yield):** - Continuous: tight junctions, uninterrupted endothelium, complete basement membrane. Found in muscle, skin, lung, CNS (blood-brain barrier, with astrocyte foot processes and pericytes), and the thymic cortex (blood-thymus barrier). Allow passage of small molecules by diffusion and transcytosis. - Fenestrated: pores allow high-volume exchange of fluid and small solutes. Found in the renal glomerulus, peritubular capillaries, intestinal villi (absorption), endocrine glands (pancreatic islets, thyroid, adrenal), exocrine pancreas, ciliary body, and choroid plexus (the blood-CSF barrier is at the choroid epithelium, which has tight junctions). - Sinusoidal (discontinuous): large gaps in the endothelium and an incomplete or absent basement membrane. Found in the liver, spleen, and bone marrow. Allow passage of proteins and cells.

**Renal glomerulus (classic Step 1 point):** The glomerular filtration barrier has three layers: 1. Fenestrated endothelium (size barrier, with a negatively charged glycocalyx). 2. Glomerular basement membrane (GBM), made of type IV collagen, laminin, and heparan sulfate. It provides the charge barrier (negative). 3. Podocyte foot processes with filtration slits, bridged by a slit diaphragm (nephrin, podocin). Loss of the negative charge (for example, in minimal change disease, where the GBM heparan sulfate is lost and podocyte foot processes effaced) causes selective albuminuria, which leads to nephrotic syndrome. Size-selective filtration generally excludes molecules >~70 kDa (albumin is ~69 kDa and is repelled mainly by charge).

**Clinical correlations:** - Because fenestrated endothelium is highly permeable, it is a target in immune-complex and endothelial injury. Examples are thrombotic microangiopathies, such as HUS/TTP, and preeclampsia, where glomerular endotheliosis occurs. - VEGF maintains fenestrations. Anti-VEGF therapy (such as bevacizumab) can cause proteinuria, hypertension, and thrombotic microangiopathy through loss of glomerular endothelial fenestrae. - Fenestrated capillaries in the choroid plexus are leaky, but the blood-CSF barrier is maintained by tight junctions in the choroid plexus epithelium. Circumventricular organs (area postrema, OVLT) also have fenestrated capillaries with no BBB, which lets them sense blood-borne signals (for example, the chemoreceptor trigger zone detects emetogenic toxins).

**Mnemonic:** "Fenestrated = Filtration/absorption/secretion": kidney, gut, and endocrine glands.