Glomerular Filteration

Basic kidney anatomy diagram

What are the nephrons?

• Hollow tubes - closed at the proximal end, open at the distal end

• Functional uni of the kidneys

• ~1.25 million nephrons per kidney and 3-4mm long

What are the segments of the nephron in order?

Renal corpuscle (glomerulus + Bowman's capsule) → proximal convoluted tubule (PCT) → loop of Henle (descending limb → thin ascending limb → thick ascending limb) → distal convoluted tubule (DCT) → collecting duct

What happens during glomerular filtration?

1. Blood enters glomerulus and sits inside the Bowman’s capsule

2. Plasma filters out of capillaries into Bowman’s space

3. Blood cells and proteins don’t pass into the Bowman’s space but almost everything else does

What substances are normally filtered at the glomerulus?

• Water

• Na⁺ and other ions

• Glucose

• Amino acids

• Urea

• Creatinine

• Other small molecules

What determines whether a substance can pass through the glomerular filtration barrier?

1. Molecular size

• Smaller molecules pass more easily

• Large molecules are restricted

2. Molecular charge

• The filtration barrier is negatively charge → negatively charged proteins are restricted

3. Shape

• The shape of a molecule can affect its ability to pass through the filtration barrier

Therefore, small neutral molecules are filtered most easily, whereas large negatively charged proteins are strongly restricted

What are the three layers of the glomerular filtration barrier?

1. Fenestrated glomerular endothelium

• Contains pores (fenestrations)

• Allows water and small solutes through due to high hydrostatic pressure

• Prevents blood cells from passing

2. Glomerular basement membrane

• Acts as an important physical and charge-selective barrier

• Restricts large molecules and negatively charge proteins as the BM has negatively charged proteoglycans on it

3. Podocytes

• Specialised cells surrounding the glomerular capillaries

• Have extentsions called foot processes

• Gaps between foot processes form filtration slits covered by slit diaphragms

Why are most plasma proteins not filtered?

Most plasma proteins, particularly albumin, are restricted because they:

• Are relatively large

• Are negatively charged

• Are repelled by the negatively charged components of the filtration barrier

Significant protein in the urine (proteinuria) may indicate damage to the glomerular filtration barrier

Why does filtration occur in the glomerulus?

The high hydrostatic pressure due to the wide afferent arteriole and narrower efferent arteriole favour net filtration of plasma into the nephron

What forces govern glomerular filtration?

Starling forces

There are 4 main pressures:

• Forces favouring filtration

  • Glomerular capillary hydrostatic pressure

• Forces opposing filtration

  • Bowman/s capsule hydrostatic pressure

  • Glomerular capillary oncotic pressure

• Bowman’s space oncotic pressure normally has little effect because there’s very little protein the the filtrate

Starling’s forces - pressures on fluid in renal corpuscle (table)

Net filtration favours outward fluid movement (calculation)

What is glomerular capillary hydrostatic pressure?

The pressure of blood within the glomerular capillaries

• It promotes filtration by pushing fluid out of the capillaries and into Bowman's capsule

Relatively high because the glomerulus lies between:

• Afferent arteriole → glomerular capillaries → efferent arteriole

The resistance provided by these arterioles helps maintain high pressure in the glomerulus

What is Bowman's capsule hydrostatic pressure?

The pressure exerted by fluid within Bowman's capsule - it opposes glomerular filtration

If pressure within Bowman's capsule increases, there is less pressure driving fluid from the glomerular capillaries into Bowman's space

• For example, urinary tract obstruction can increase Bowman's capsule pressure and reduce GFR

What is glomerular capillary oncotic pressure?

Caused by plasma proteins within the blood

Proteins attract water and therefore tend to pull water back into the glomerular capillaries

• Therefore, glomerular capillary oncotic pressure opposes filtration

As filtration occurs, proteins become more concentrated in the remaining plasma, causing oncotic pressure to increase along the glomerular capillary

What is Bowman's space oncotic pressure?

Promotes filtration by pulling water into Bowman's space

However, it is normally approximately zero because there is very little protein in Bowman's space

Therefore, it normally has little effect on GFR

Major causes of proteinuria

Protein in the urine due to disruption of the filtration barrier

• Diabetes mellitus - excessive plasma glucose damages filter

• Hypertension - high glomerular hydrostatic pressure damages filter

• Glomerulonephritis - inflammatory damage due to immunological attack

Effects of normal and decreased plasma protein levels on fluid movement across capillaries (diagram)

Excessive proteinuria causes a low level of protein in the plasma which can lead to odema (picture)

Glomerular Filtration Rate

Volume of fluid filtered from the renal glomerular capillaries into the Bowman’s capsule during a certain period of time

Best overall index of renal function

• 125mL/min or 180 L/day

It’s essential that GFR is maintained

Why is glomerular filtration rate clinically important?

GFR provides an indication of kidney filtration function

A reduced GFR can indicate impaired kidney function

GFR is therefore commonly used to:

• Assess renal function

• Detect and monitor chronic kidney disease

• Help determine the severity of kidney impairment

• Guide dosing of some medicines that are eliminated by the kidneys