43) Glomerular Filtration & regulation of renal blood flow

Question 1

What is the renal corpuscle made of?

Answer 1

• A Bowman’s capsule (on the outside) and a glomerulus (on the inside)

Question 2

How does filtration occur?

Answer 2

• Blood flows in from the afferent arteriole and flows through the capillaries
• In the capillaries fluid passes across the membranes as they are being filtered and so enter the urinary space (Bowman’s space)
• The fluid that passes out is called the glomerular fluid or ultrafiltrate which travels down the tubules and into the rest of the nephron
• It then exits into the efferent arterioles

Question 3

What is an adaptation of the epithelium of the Bowman’s capsule?

Answer 3

• The epithelium is invaginated (pushes in) to coat the outer surface of the capillaries (called podocytes)

Question 4

What is glomerular fluid?

Answer 4

• An ultrafiltrate of plasma that passes out of the blood capillaries into the tubules
• They have the same composition as plasma without the proteins

Question 5

What are the key features of glomerular filtrate?

Answer 5

• Small solutes: (e.g. Na+, Cl-, glucose and urea) where concentration of glomerular fluid is the same as concentration in plasma
• Plasma proteins: Concentration of glomerular fluid is close to 0. So urine is routinely tested for proteinuria (protein in the urea) which could be a sign of urinary tract disease or renal disease

Question 6

What drives the ultrafiltration process?

Answer 6

• A net pressure drop across the glomerular membrane drives the ultrafiltration process

Question 7

What are the different Starling forces involved in filtration in the kidneys?

Answer 7

• Pc= Capillary blood pressure (drives fluid from the capillary into the Bowman’s space) and so acts outwards to favour filtration. This force is very large
• (Pi)p = Plasma colloid osmotic pressure (caused by proteins that cannot cross the membranes) and so acts inwards to favour reabsorption. This force is moderately sized
• Pu = Pressure in the Bowman’s space (exerted by the fluid within the space) which acts inwards to favour reabsorption. This force is very tiny

Question 8

What is the overall effect of Starling’s forces?-

Answer 8

• Altogether there is a greater sum of forces of glomerular filtrate pushing into the capillary is less than the force of blood pushing fluid into the Bowman’s space

Question 9

How does fluid passing out of the glomerular capillary affect concentration?

Answer 9

• As the fluid crosses the mmebrane there is a decrease in voluume of the blood whihc has an effect on protein concentration which cannot pass out

Question 10

How does pressure change from afferent arteriole end to efferent arteriole end?

Answer 10

• As we move from afferent to efferent there is a gradual drop in capillary blood pressure and an increase in plasma colloid osmotic pressure

Question 11

What is the net filtration force?

Answer 11

• The difference between the capillary blood pressure and the sum of the forces pushing into the capillary

Question 12

What is the filtered fraction?

Answer 12

• Filtered fraction = GFR/ Plasma flow

- It shows you how much liquid will be absorbed into the glomerular

Question 13

How do Starling’s forces work in the peritubular capillaries?

Answer 13

• In afferent arterioles there is a high pressure and so there is a greater net force acting to excrete fluid into the.
• As the blood enters the glomerulus filtration occurs
• As blood leaves the capillaries the blood pressure decreases which causes the plasma colloid pressure to increase
• In efferent arteriole there is a much lower blood pressure and so as a the net force acting to favour reabsorption of fluid back into the blood.
• Since fluid is entering back into the blood plasma colloid osmotic pressure decreases

Question 14

How does sieving take place in the glomerular membrane?

Answer 14

• In the glomerular membrane there are three levels of sieving that occur
• These layers include the fenestrated capillary, basement membrane and filtration slits in podocytes
• Each layer is increasing in fineness (hence the particles that are able to pass through are smaller)
• Large molecules such as RBCs are kept out by the fenestrated capillary. Slightly smaller molecules can pass through the fenestrated capillary but then are stopped by the basement membranes. Even smaller molecules may pass through the basement membrane but will be stopped by the filtration slits of the podocytes. Small molecules such as water, glucose, urea and NaCl can pass through freely

Question 15

What is a sign of dysfunction in the sieves of the glomerular membrane?

Answer 15

• Proteinuria occurs when proteins leak from the blood vessels into the tubules.
• This can occur when there are damages in the filtration slit or basement membranes

Question 16

What is the Bayliss Myogenic response?

Answer 16

• An increase in perfusion pressure (arteriole blood pressure) will result in an increase in the blood vessel radius.
• This leads to increased blood flow at the capillaries
• Stretching of the arteriole muscle in the afferent arteriole is detected by receptors in the muscle causing it to contract
• This decreases arteriole diameter/radius and increases resistance
• As a result the pressure within the capillary is balanced out

Question 17

What is the equation for blood flow?

Answer 17

F=∆P/R

• F = blood flow
• ∆P = change in pressure
• R = resistance

Question 18

How is mean arterial pressure linked to Glomerular Filtration Rate (GFR)?

Answer 18

• As mean arterial pressure increases GFR also increases

Question 19

What happens to the arteriole at low mean arterial pressure?

Answer 19

• When a low blood pressure enters the arteries it causes the afferent arterioles to be dilated
• As a result in the glomerular capillaries there is a normal pressure being exerted

Question 20

What happens to the arteriole at high mean arterial pressure?

Answer 20

• When a high blood pressure enters the arteries it causes the contraction of the afferent arterioles
• This causes blood pressure within the capillaries to elevate slightly

Question 21

What happens to the GFR when it reaches normal rate?

Answer 21

• When normal GFR is achieved it is held steady as mean arterial pressure increases by the Bayliss Myogenic Response
• This range (in which it operates) is called the autoregulation range

Question 22

What happens when mean arterial pressure increases past the autoregulation range?

Answer 22

• As mean arterial pressure increase past the autoregulation range the afferent blood vessels can no longer contract as they loose the strength to do so
• This means they are gradually forced wider until an increase in arterial pressure causes an increase in GFR

Question 23

What happens when we fail to autoregulate the kidneys?

Answer 23

• Failure of autoregulation in hypotension (e.g. in shock) causes a low amount of fluid crossing the glomerular membrane
• This means a lack of urine is created (called oliguria)

Question 24

How does blood pressure change in different vessels?

Answer 24

• As the blood flows from arteries to arterioles and then to capillaries the pressure starts to fall each time until we reach a safe blood pressure for the kidneys

Question 25

Why is the Bayliss Myogenic Response important?

Answer 25

• If there is an increase in blood pressure in the arteries we would still experience a decrease in pressure as the blood flows into arterioles and capillaries
• It is through the increased contractions (caused by the Bayliss Myogenic Response) that we experience a massive spike in blood pressure at the arterioles
• This means the blood pressure in the capillaries can return back to normal without causing any harm to the body

Question 26

What would happen if there was no Bayliss Myogenic Response?

Answer 26

• If there is an increase in blood pressure in the arteries we would still experience a decrease in pressure as the blood flows into arterioles and capillaries
• However without the Bayliss Myogenic Response there is no increased contractions in the afferent arterioles
• As a result there is no massive spike in arterial pressure hence leading to an increase in capillary pressure which is dangerous and may inflict damage to the body

Question 27

What are the Juxta-glomerular cells?

Answer 27

• Modified smooth muscle cells in the walls of the afferent arterioles close to the glomerulus
• They store inactive pro-renin

Question 28

What are the macula densa?

Answer 28

• Specialised epithelial cells located in the distal convoluted tubules on the surface closest to the arterioles

Question 29

What is the mechanism of tubuloglomerular feedback?

Answer 29

• First there is an increase in blood pressure going into the capillaries of the glomerulus which forces more liquid across the membrane of the glomerulus
• This increases GFR and causes an increase in flow of fluid through the tubules
• As it goes through the distal convoluted tubule it will flow past the macula densa cells
• The macula densa cells will sense the increase in flow and will release paracrine signalling factors which diffuse to the juxtaglomerular cells on the afferent arterioles
• This causes the afferent arterioles to contract and so resistance in the afferent arterioles increases
• Increasing resistance means less blood is able to enter the glomerular capillaries which in turn reduces how much liquid pass into the glomerulus
• Ultimately GFR decreases (hence a negative feedback mechanism)

Question 30

How do macula densa cells detect increased flow?

Answer 30

• Mechanically: This is done via cell surface cilia. The cilia are blown backwards and forwards by the flow of fluid across the surface
• Chemicall: This is done via increased [NaCl]. This is because most physiological causes of increased tubular flow are associated with elevated [NaCl]

Question 31

How do the macula densa cause contraction of afferent arterioles?

Answer 31

• When there is an increase in [NaCl] it will move through a transporter in the macula densa cells
• In response to the increase in [NaCl] the macula densa cells release ATP into mesangial/ lacis cells
• Here the ATP bind to receptors on the cell surface of the juxtaglomerular cells which leads to the contraction of afferent arterioles

Question 32

What happens when there are low levels of NaCl?

Answer 32

• When the macula densa detect low levels of NaCl they will cause the juxtaglomerular cells to activate the Renin-Angiotensin-Aldosterone System (RAAS) route.
• Here it causes the juxtaglomerular cells to secrete more pro-renin which will increase blood pressure

Question 33

What are the extrinsic control of the Glomerular Filtration Rate?

Answer 33

• The renal sympathetic nerves that innervate the kidneys extrinsically control GFR.
• They produce vasoconstriction and is driven by noradrenergic innervation which can reduce GFR by re-setting autoregulation to a lower level.
• This conserves body fluid volume during physical stress.
• This occurs when we are standing upright, heavy exercise or due to haemorrhage or other kinds of clinical shock.
• In shock the sympathetic actions are aided by circulating vasoconstrictor hormones such as adrenaline, angiotensin and vasopressin

Question 34

What do the sympathetic nerves do in the kidneys?

Answer 34

• The sympathetic nerves reset the GFR autoregulation levels to a lower level
• This means less fluid crosses the membrane and so less fluid enters the tubules
• In other words we are retaining more bodily fluid through this method
• So at lower pressures the afferent arteriole will be constricted to provide a lower blood pressure in the capillaries

Question 35

What are the major clinical disorders of the GFR?

Answer 35

• Glomeruli too leaky to plasma proteins: This is normally Nephrotic syndrome cause by, for example, a deficiency in nephrin causing a filtration slits that are improperly formed and so are leaky to protein. This can lead to proteinuria, hypoproteinaemia and oedema. The symptoms respond to steroids
• GFR too low: This is more common and is Chronic glomerulonephritis which is where there is a non-functioning glomeruli. When GFR drop below a certain point we get chronic renal failure

Question 36

How do we treat chronic renal failure?

Answer 36

• Dietary restrictions
• Renal dialysis
• Renal transplant