Renal 3: Glomerular Filtration

Filtration of plasma, modification of filtrate by tubules

Two major processes in the production of urine

Glomerular filtration

Bulk flow of fluid from the glomerular capillaries into the Bowman’s capsule (Bowman’s space)

Urine formulation begins with this

Bowman’s space

Contiguous (in contact with) the beginning of the renal tubule

Glomerular filtration barrier (GFB)

Highly specialized blood filtration interface

Sieving coefficient (SC)

Ratio of the concentration of a substance in the Bowman’s space and the concentration in capillaries (plasma)

Completely rejected (albumin), completely filtered (water, glucose)

UP/P = 0 —> ___

UP/P = 1 —> ___

Molecular size, charge

The GFB filters based on ___ and ___.

Repelled, enhanced permeability

Mid-sized negative-charged molecules (like proteins!) are ___, and mid-sized positively-charged molecules have ___.

Small anions and cations like electrolytes

Which kinds of molecules pass through the GFB easily?

Plasma proteins and cells; water, small solutes, electrolytes

The GFB slows down the passage of ___ while allowing free passage of ___, ___, and ___.

More

Anions filter with ___ [more or less] difficulty than cations.

Less

The bigger the molecule is, the ___ [more or less] likely it is to be filtered through the GFB.

Thin, large

The GFB is ___ [thick or thin] with a ___ [small or large] surface area.

Fenestrations

Plasma is filtered through ___ (70-90 nm in diameter) = unique to glomerular capillaries

Water, small solutes, small proteins

Three types of molecules that pass through fenestrations of glomerular capillaries

Large molecules, RBCs

Two types of cells/molecules that are kept out of fenestrations of glomerular capillaries

Glycocalyx, anionic

The luminal side of the endothelium of the GFB is coated with a ___ rich in ___ sites that begin to repel based on charge.

Charge, size

The glomerular basement membrane (GBM) is both ___ and ___-selective.

Glomerular basement membrane (GBM)

1. Acellular layer composed of glycosaminoglycans, proteoglycans, and fibrous proteins like laminin and collagen rich in anionic sites

2. Major barrier to proteins; disruption can lead to loss of albumin from blood

Endothelium, glomerular basement membrane (GBM), podocytes

Three functional components of glomerular filtration barrier (GFB)

Podocytes

Specialized visceral epithelial cells of Bowman’s capsule

Foot processes, filtration slits

Podocytes have ___ and small gaps between them called ___.

Filtration-slit diaphragm

1. Thin diaphragm that bridges filtration slit of podocytes

2. Final barrier for the filtrate

3. Composed of clinically important proteins, including nephrin, NEPH-2, and FAT1

4. Widely recognized as the main size-selective filter to keep out macromolecules

Glomerulonephritis

Group of diseases that injure the glomerulus

Hematuria

RBCs in urine

Proteinuria

Protein in urine

Immune complexes, autoimmune reaction

Glomerulonephritis occurs when ___ are filtered out of blood and become trapped within the glomerulus, leading to further ___.

Chronic periodontal disease, heartworm infection, tickborne Lyme disease, cancer

Well-known causes of glomerulonephritis

Alport’s syndrome (in humans), hereditary nephritis

Can be associated with an abnormal GBM that is not due to an immune reaction but a mutation in COL4A5 gene

Glomerulus injury, tubular injury

In general, hematuria, proteinuria, or hypoproteinemia is due to ___, while sodium in urine (sodium-wasting) is due to ___.

Decreased

An increase in creatinine results from ___ [increased or decreased] GFR.

Decrease in GFR, decrease in renal tubule resorption

Causes of increase in BUN

Poststreptococcal glomerulonephritis, Lyme disease

Associated with immune deposits along the GBM

Nephrotic syndrome

Complication in severe cases of glomerulonephritis that can result in extreme urinary protein loss

Disease characterized by heavy proteinuria and hypoalbuminemia. Often ends in renal failure

Hypoalbuminemia (causes generalized edema), heavy proteinuria, abnormal podocyte structure (podocyte detachment)

Clinical signs of nephrotic syndrome

Diabetic nephropathy

Nephrotic syndrome is especially common in patients with ___.

Mutations in slit diaphragm genes (nephrin, NEPH-1, podocin)

What is the breakdown of the GFB associated with in humans?

Hydrostatic, oncotic

Filtration across the glomerular capillary is governed by the sum of ___ and ___ pressures across the capillary membrane.

Ultrafiltration

Filtration using a medium fine enough to retain colloidal particles, viruses, or large molecules

Area, Lp

Components of Kf

Kf

Filtration coefficient of glomerular filtration barrier (GFB)

Rate of filtration per unit of filtration pressure (how much flow per every unit of pressure in mmHg)

Lp

Hydraulic coefficient or conductivity of glomerular filtration barrier (GFB)

Indication of the ease with which water goes across the clefts

Large, higher

Both the surface area of filtration and the Lp tend to be ___. As a result, glomerular capillaries have a Kf that is 100 times ___ than systemic capillaries.

12 mL/min/mmHg

Normal Kf value

Permeability, diabetic nephropathy

___ of the filtration barrier can decline due to the thickening of the glomerular basement membrane during ___.

Hypertension

Reduction of total glomerular surface area due to reduction in total number of functional glomeruli and thus lowered total glom permeability

Kf, GFR

Which values are significantly reduced in nephrotic diseases where the slit diaphragm is injured?