renal blood flow and glomerular filtration

Question 1

what are the key features of glomerular filtrate ?

Answer 1

• For small solutes, such as NaCl, glucose and urea:
  Concentration in glomerular fluid = concentration in plasma.
• For plasma proteins:
  Concentration in glomerular fluid = almost zero.
  Hence, urine is routinely tested on wards for protein (proteinuria).
  Proteinuria is a sign of renal/urinary tract disease.
• A net pressure drop across the glomerular membrane drives the ultrafiltration process.

Question 2

describe how starling forces drive glomerular filtrate fluid formation

Answer 2

• formation of glomerular filtrate in the kidneys is primarily driven by Starling forces, which are the result of pressure gradients across the walls of the glomerular capillaries. These forces determine the movement of fluid and solutes from the blood into the renal tubules.
• Plasma Colloid Osmotic Pressure (πGC): This is the osmotic pressure exerted by the proteins (mainly albumin) in the blood plasma. These proteins tend to attract water into the capillaries, opposing filtration. The plasma colloid osmotic pressure typically ranges from 25-30 mmHg in humans.
• Bowman’s Capsule Colloid Osmotic Pressure (πBC): Normally, this is negligible because there are very few proteins in the filtrate within the Bowman’s capsule. However, in certain pathologies, this pressure can increase if proteins leak into the capsule, which can further oppose filtration.
• Hydrostatic Pressure (GHP): This is the blood pressure within the glomerular capillaries, which is generated by the heart’s pumping action. The GHP is the main force that pushes fluid and small solutes from the blood into the Bowman’s capsule (the beginning of the nephron), thus initiating the formation of glomerular filtrate. It typically ranges between 45-55 mmHg in humans.

Question 3

what is the glomerular membrane comprised of ?

Answer 3

• Foot processes (pedicel) of an epithelial cell (ep) or ‘podocyte’. Gaps between the processes are called “filtration slits”
• 2, 3, 4. Basal lamina
  (l. rara, l. densa, l. rara)
• Fenestrated endothelium of capillary

Question 4

What is the net filtration rate ?

Answer 4

• The net filtration pressure (NFP) is the overall pressure that determines the direction and rate of fluid movement into the Bowman’s capsule
• If the NFP is positive, filtration occurs, and fluid is pushed out of the glomerular capillaries into the Bowman’s capsule.
• If the NFP is negative or close to zero, filtration is reduced or halted, and reabsorption may occur instead.

Question 5

describe filtration slits in more detail

Answer 5

• Central spine with lateral rungs
• Subdivides filtration slit into pores 4 nm wide.
• Made of proteins - nephrin & podocin
• Deficiency of these proteins causes nephrotic syndrome.
• looks like a train track

Question 6

what is the Bayliss myogenic response ?

Answer 6

• blood vessels in the kidneys can adjust their diameter in response to changes in blood pressure to maintain a relatively constant blood flow.

Increased Blood Pressure:
* When blood pressure rises the afferent arterioles are stretched because the increased pressure forces more blood into the vessels.
The smooth muscle cells in the walls of the afferent arterioles sense this stretching.

Smooth Muscle Contraction:
* The stretch of the smooth muscle cells triggers a response known as myogenic response, which causes the smooth muscle in the afferent arterioles to contract. This contraction reduces the diameter of the blood vessel.
* The contraction helps resist the increase in blood flow and minimizes the increase in glomerular filtration rate (GFR).

Decreased Blood Pressure:
* if blood pressure drops the afferent arterioles are less stretched. In response, the smooth muscle cells relax, causing vasodilation
* This allows more blood to flow into the glomerulus, helping to maintain GFR and proper filtration.

Question 7

describe tubo glomerular feedback

Answer 7

• helps maintain a stable (GFR) and proper kidney function by adjusting the diameter of the afferent arteriole in response to changes in the composition of the fluid flowing through the distal tubule of the nephron.

Sensing Changes in Filtrate Flow:
* The macula densa, a specialized group of cells in the distal convoluted tubule, monitors the flow and composition of the filtrate that passes through the nephron. These cells are sensitive to sodium chloride (NaCl) concentration, which indirectly reflects the flow rate of the filtrate.
* If the flow of filtrate through the distal tubule increases the NaCl concentration in the macula densa will be higher because less time is available for sodium reabsorption.
* if the filtrate flow decreases, the NaCl concentration will be lower.

Response to High NaCl (Increased Flow):
* When the macula densa detects high NaCl concentrations (indicating high filtrate flow), it signals the afferent arteriole to constrict, reducing blood flow into the glomerulus.
* This constriction lowers the glomerular hydrostatic pressure (GHP), thereby decreasing the GFR to normal levels. This helps prevent excessive fluid and solute loss if the filtration rate was too high.

Response to Low NaCl (Decreased Flow):
* When the macula densa detects low NaCl concentrations (indicating low filtrate flow), it signals the afferent arteriole to dilate, increasing blood flow into the glomerulus.
* This increases the glomerular hydrostatic pressure, which raises the GFR to normal levels, ensuring that adequate filtration occurs.

Signaling Pathways:
* The exact signaling pathways that mediate tubuloglomerular feedback involve adenosine and nitric oxide (NO). When the macula densa detects high NaCl, it releases adenosine, which constricts the afferent arteriole. when NaCl levels are low, the macula densa releases signals that promote afferent arteriole dilation, including nitric oxide.

Question 8

how do macula densa cells detect increased flow rate ?

Answer 8

• Mechanically via cell surface cilia
• Chemically via increased [NaCl] *

Question 9

why do macula densa release ATP ?

Answer 9

• triggers contraction of afferent arteriole
• more tubular flow - more ATP released
• more nacl - More ATP released

Question 10

describe the extrinsic control of GFR

Answer 10

• Renal sympathetic nerves (vasoconstriction, noradrenergic) can reduce GFR by re-setting autoregulation to a lower level
• The role is to conserve body fluid volume during physical stress
  This happens in 3 conditions:
  
  • standing upright (orthostasis)
• heavy exercise
• haemorrhage & other forms of clinical shock
• In shock, these sympathetic actions are aided by circulating vasoconstrictor hormones such as adrenaline, angiotensin and vasopressin.

Question 11

what are the 2 major clinical disorders of the GFR ?

Answer 11

• Glomeruli too leaky to plasma protein
• Nephrotic syndrome (eg. Filtration slit disordered by nephrin deficiency)
• Proteinuria
• Hypoproteinaemia
• Oedema
  all 3 above respond well to steroids
• GFR too low (more common)
• Chronic glomerulonephritis  nonfunctioning glomeruli
• When GFR < 30 ml/min, this is chronic renal failure.