what is the glomerulus? (4)
- The glomerulus is a network of capillaries located at the beginning of a nephron.
- Blood is filtered across the walls of this capillary network through the glomerular membrane, which yields its filtrate into Bowman’s capsule.
- The filtrate then enters the renal tubule of the nephron.
- The glomerulus receives its blood supply from an afferent arteriole and the glomerular capillaries exit into efferent arterioles.
Three main forces are responsible for enabling glomerular filtration
The rate at which blood is filtered through all of the glomeruli, the measure of the overall renal function, is the glomerular filtration rate (GFR)
glomerular filtration
In order for blood to be filtered, the fluid must pass through three layers that make up the glomerular membrane
three layers that make up the glomerular membrane:
- The glomerular capillary wall
- The basement membrane
- The inner layer of Bowman’s capsule
The glomerular capillary wall (3)
- Like most capillaries, it consists of a single layer of endothelial cells.
- However, it contains many large pores that make it 100 times more permeable to fluids and solutes than regular capillaries.
- The pores are of such size that large plasma proteins cannot pass through, but smaller ones, such as albumin, can.
The basement membrane (3)
- This layer contains no cells and is composed of collagen to provide structural strength, and glycoproteins to help prevent the filtration of small plasma proteins.
- Because the glycoproteins are negatively charged, they help to repel any proteins that do get through the capillary walls.
- Only about 1% of filtered albumin will pass into Bowman’s capsule
The inner layer of Bowman’s capsule
- This layer is composed of podocytes that form narrow filtration slits between them that allow fluid to pass into Bowman’s capsule
forces that regulate glomerular filtration
The forces involved in glomerular filtration are very conceptually similar to the forces involved in bulk flow across any capillary wall
3 forces that regulate glomerular filtration
- Glomerular Capillary Blood Pressure
- Plasma-Colloid Oncotic Pressure
- Bowman’s Capsule Hydrostatic Pressure
Glomerular Capillary Blood Pressure (4)
- This is the pressure exerted by the blood in the glomerular capillaries.
- While regular capillaries have a blood pressure of about 18 mmHg, glomerular capillary pressure is on average 55 mmHg.
- This is due mainly to the afferent arteriole diameter being larger than the diameter of the efferent arterioles, which increases resistance to blood leaving the glomerular capillaries.
- This also prevents glomerular capillary pressure from decreasing along their length, further favouring filtration.
Plasma-Colloid Oncotic Pressure (3)
- The presence of large proteins in the plasma that cannot be filtered produces a oncotic force that resists the movement of water into Bowman’s capsule.
- The plasma-colloid oncotic pressure is about 30 mmHg.
- normally do not vary much and essentially considered constant, buy can change due to pathological conditions.
Bowman’s Capsule Hydrostatic Pressure (3)
- This is the pressure of the fluid in Bowman’s capsule and it also resists the movement of water out of the glomerular capillaries.
- Bowman’s capsule hydrostatic pressure is around 15 mmHg.
- normally do not vary much and essentially considered constant, but can change due to pathological conditions.
equation for net filtration pressure (2)
- net filtration pressure equals the glomerular capillary blood pressure minus the sum of the
plasma-colloid oncotic and Bowman’s capsule hydrostatic pressures - Net Filtration Pressure = 55 mmHg - (30 mmHg + 15 mmHg) = 10 mmHg
glomerular filtration rate (2)
- not only dependent upon filtration pressure, but also the glomerular surface area available and how permeable the membrane is.
- Collectively, these properties are called the filtration coefficient (Kf).
GFR equation
Filtration Coefficient (Kf) x Filtration Pressure = Glomerular Filtration Rate
- In the average male, this value is 125 ml/min, and in females it is 115 ml/min
examples of a pathological condition that leads to changes in GFR (2)
- Someone with a kidney stone that obstructs the ureter will have an increased Bowman’s capsule hydrostatic pressure, again decreasing GFR.
- Someone with severe diarrhea will be dehydrated, as they are losing more fluid than they are taking in. This results in decreased blood pressure due to the decreased plasma volume. There is also an increase in plasma-colloid osmotic pressure that results in a decreased G FR
autoregulation (2)
- Because changes in GFR are directly proportional to glomerular capillary blood pressure, autoregulatory (or intrinsic) mechanisms are in place to prevent sudden swings in GFR.
- This is primarily done by regulating the diameter of the afferent arterioles, such that constricting the afferent arterioles will decrease glomerular capillary blood pressure and dilating the afferent arterioles will increase it.
2 ways that allow autoregulation
- Myogenic Activity
- Tubuloglomerular Feedback (TGF)
myogenic activity (3)
- When an increased pressure stretches the afferent arteriole walls, they automatically constrict to reduce blood flow to the glomerular capillaries and thus prevent an increase in GFR.
- The opposite is also true in that if blood pressure decreases, the afferent arterioles will dilate to increase blood flow and prevent a decrease in GFR.
- constriction of blood vessels = vasoconstriction, and vasodilation = dilation of blood vessels
tubuloglomerular feedback (RGF) (4)
- Specialized tubular cells in the juxtaglomerular apparatus are collectively called the macula densa, which can sense changes in the salt level of the tubular fluid.
- If there is an increased arterial pressure that increases the GFR, more fluid than normal will flow through the distal tubule ( increased salt delivery).
- In response, the macula densa releases ATP, which is degraded to adenosine.
- This adenosine acts on the afferent arterioles to cause constriction and reduce GFR. The opposite is also true
would occur to the glomerular capillary blood pressure, net filtration pressure, and the glomerular filtration rate if there was vasoconstriction in the afferent arteriole?
there would be a decrease in glomerular capillary blood pressure, a decrease in net filtration pressure, and a decrease in glomerular filtration rate
What would occur if there was vasodilation of the afferent arteriole?
there would be an increase in glomerular capillary blood pressure, an increase in net filtration pressure, and an increase in glomerular filtration rate.
sympathetic control of GFR (3)
- Let’s use a haemorrhage as an example (i.e. a sudden loss of blood volume followed by a drop in arterial pressure). This would be sensed by the baroreceptors, which would initiate responses to normalize blood pressure.
- At the level of the kidney, this increased sympathetic activity would constrict the afferent arterioles, which would decrease glomerular capillary pressure, decreasing GFR, and reducing urine production. This is a mechanism by which depleted plasma volumes can be corrected.
the kidneys and cardiac output (5)
- In a healthy person, around 20% of the plasma in the blood enters the kidneys to be filtered.
- So, if the Glomerular Filtration Rate (GFR) is 125 ml/minute, it means the kidneys are receiving 625 ml/minute of blood flow.
- However, only 55% of whole blood is plasma, which can be filtered.
- So, we adjust this to get 1140 ml/minute for renal blood flow.
- Since the total blood pumped by the heart (cardiac output) is about 5000 ml/minute, the kidneys get about 22% of the total blood flow.
