Glomerular filtration Flashcards
What is the nephron?
The fundamental functional unit of the kidney.
Contains:
Afferent and efferent arterioles
Proximal tubule
Distal tubule
Capillary tuft
Glomerulus
Bowmans’ space.
Loop of Henle
Collecting duct
See image
What is the glomerulus?
Blood flows in through the afferent arteriole.
Blood flows out through the efferent arteriole.
A barrier to reduce the amount of flow.
Blood flows from the capillaries into Bowman’s space, and filtrate forms.
The structure is packed in amongst other tubules from other nephron, and its own distal tubule.
What does the glomerulus look like?
Afferent arteriole
Capillary tuft
Proximal tubule
Bowman’s space
Efferent arteriole
See image.
How does filtration in the kidneys occur?
Filtration involves bulk flow, rather than diffusion, due to the speed of fluid through the kidney.
There is a semipermeable membrane that separates the cells and plasma in the capillaries from the filtrate that forms in the Bowman’s space.
It is driven by hydrostatic and osmotic/oncotic pressure.
What is hydrostatic pressure?
Hydrostatic pressure is generated by the heart.
There is a much higher hydrostatic pressure in the glomerular capillaries due to the reduction in diameter, and this drives the fluid out.
What is osmotic pressure?
There is a higher osmotic pressure in the capillaries than the filtrate due to the plasma proteins.
This impedes the flow of filtrate.
Osmotic force increases along the length of the capillaries but equilibrium is not normally achieved, it is oncotic force that has effect.
How does oncotic pressure drive water movement?
The presence of solutes drives water movement.
Oncotic pressure in the plasma is high, because most of the proteins have high concentration per mass but low concentration per moles.
This is important because the proteins cannot cross the membrane.
The higher the solute concentration, the more water movement towards the solutes, and higher oncotic pressure.
What do the graphs of filtration pressure along the glomerular capillary look like?
See graph.
The hydrostatic pressure in the capillary does not change much along the length of the capillary.
As fluid is pushed out, plasma proteins are left behind, which contributes to osmotic pressure.
The osmotic pressure opposes the hydrostatic pressure so slows the water leaving the capillaries.
As fluid flows into Bowman’s space, it creates a hydrostatic pressure in the filtrate, which stops fluid movement back.
What is net perfusion pressure?
The difference between the capillary hydrostatic pressure and the opposing forces.
Capillary hydrostatic pressure - Bowmans’ space hydrostatic pressure, and oncotic pressure in the capillaries.
see graph.
What is filtration pressure along peritubular capillaries?
Once the efferent arteriole leaves hte glomerulus, it enters the portal vein and travels to a second capillary bed surrounding the loop of Henle.
The hydrostatic pressure is much more similar to a systemic capillary, the osmotic pressure is much higher.
What are the glomerular barriers to diffusion?
V = I/R
Current flow = Driving force / resistance
Endothelial cells of the glomerular capillaries, sit on basement membrane.
Glomerular basement membrane
Epithelial cells of Bowman’s capsule.
What are endothelial cells?
Endothelial cells have small holes - fenestrations between them.
Glomerular endothelial cells are very flat.
They stop other cells or platelets passing through the capillary wall.
They have a negatively charged glycocalyx, which creates a charge barrier that is particularly effective for proteins.
What are podocytes?
The epithelial cells of Bowmans’ capsule.
They have foot processes that interlock with neighbouring cells to form slits through which fluid can pass (filtration slits).
What is the basement membrane?
The basement membrane also consists of fixed, negatively charged proteins e.g collagen.
What do the barriers to diffusion look like?
see image
What molecules are allows to be filtered?
The layers of the glomerulus and capillaries allow water to cross, and small molecules. Large molecules are not allows to pass.
Positively charge molecules are more likely to be filtered.
Negatively charged molecules are more likely to be stopped.
See graph.
What is the reason for selective filtration?
Circulating proteins at physiological pH (7.4) are negatively charged.
e.g. albumin net charge is negative, side chains are negatively charged at 7.4.
Don’t want to lose the proteins as useful, so do not cross the barrier to be lost in urine, instead stay in the plasma.
Large molecular weight positively charged molecules should not be in the system, so kidneys have evolved to remove these.
What is bulk flow?
The movement of solutions from an area of high pressure to an area of low pressure.
As the solvent moves it carries any solutes dissolved in it.
What is diffusion?
The movement of a substance from an area of higher concentration to lower concentration as a result of Brownian motion.
Diffusion is too slow in the glomerulus over the great distance, and basement membrane is tortuous, so diffusion cannot work.
What is the filtrate?
Filtrate contains small molecules - solutes (Na+, K+, Mg2+, Ca2+, Cl-, HCO3-, glucose and urea).
There are no proteins, unless they are positively charged and the glomeruli is damaged.
Each nephron filters 30-50nL/min.
The rest of the nephron reabsorbs most of this flow.
The hydrostatic pressure in Bowman’s space helps drive the filtrate along the length of the nephron.
What is filtration fraction?
The proportion of the plasma flow that is filtered by the glomerulus.
Filtration fraction = glomerular flow rate / renal plasma flow.
Around 0.2.
What is the control of glomerular hydrostatic pressure?
Most dynamic control is to control diameter of afferent and efferent arterioles.
Dilate the afferent arteriole (goes into glomerulus).
Contract the efferent arteriole.
In kidneys, have neural and hormonal mechanisms to control it separately.
What happens when you change the diameter of the afferent arteriole?
Vasoconstrict - decreased hydrostatic pressure in capillaries, less glomerular filtration, plasma flow rate to nephron decreases.
Vasodilate - increased hydrostatic pressure, more glomerular filtration, plasma flow rate increases.
What happens when you change the diameter of the efferent arteriole?
Vasoconstrict - increased hydrostatic pressure, more glomerular filtration, decreased plasma flow to the nephron.
Vasodilate - decreased hydrostatic pressure, less glomerular filtratin, increased plasma flow rate to the nephron.
How can GFR be measured?
Glomerular Flow Rate can be measured using substances that are freely filtered, but not secreted or reabsorbed over the length of the tubules.
Can be injected IV - inulin, or produced by the body at a constant rate - creatinine.
How is creatinine measured?
Amount of creatinine in the urine = the concentration of creatinine in the urine x the volume of urine produced.
Rate of creatinine excretion = the amount of creatinine in urine divided by time.
How do you work out how much creatinine is filtered?
Some creatinine is filtered - GFR, the rest goes out at efferent arteriole.
The amount of creatinine filtered = GFR x the concentration of creatinine in Bowman’s space.
How can GFR be calculated using creatinine?
Because creatinine is freely filtered, and not secreted or reabsorbed, the concentration in Bowman’s space is the same as in the plasma.
So the rate at which it is filtered is equal to the rate it is found in the urine.
GFR = concentration of creatinine in the urine divided by the plasma creatinine concentration, x the rate at which urine is produced.
What are empirical estimates of GFR?
Can use a single blood sample rather than 24hr urine collection.
Relies on the fact that the rate of creatinine is constant for a given person, correlated with sex, mass and age.
At equilibrium, the rate of creatinine production = the rate of creatinine loss in the kidney.
So GFR is inversely proportional to plasma creatining concentration.
How does GFR change with age?
With age, nephrons are progessively lost, and GFR falls, which causes creatinine to rise.
So rate of creatinine production falls with age.
What is proteinuria?
Protein in the urine - suggests renal failure, as the glomerulus is the main barrier to protein loss.
When severe it is nephrotic syndrome - the glomerulus is more permeable to plasma proteins.
When there is predominant dysfunction of the glomerulus it is glomerulonephritis.
What is congenital nephrotic syndrome?
Rare genetic disorder involving a component of the glomerular barrier between podocytes.
The component is either the nephrin or the podocin.
The glomerulus is more permeable to plasma proteins, so more protein is found in the urine.
