GFR and the Glomerulus

Question 1

Describe the histology of the proximal convoluted tubule

Answer 1

• Simple cuboidal epithelium with brush border
• Have villi and microvilli to aid reabsorption
• Mitochondria abundant in epithelial cells to provide energy for active transport

Question 2

Describe the histology of the Loop of Henle

Answer 2

• Simple squamous epithelium
• Thin walls and few mitochondria present as water exits through osmosis
• Mitochondria needed in ascending limb to pump salts into the medulla

Question 3

Describe the histology of the distal convoluted tubule

Answer 3

• Simple cuboidal epithelium with few microvilli
• Has mitochondria to actively transport ions into medulla
• Cells stain paler than proximal convoluted tubule

Question 4

Describe the histology of the collecting duct

Answer 4

• Simple columnar and simple cuboidal epithelium present

- Large lumen with pale staining columnar epithelia

Question 5

Describe the arterial system of the kidney

Answer 5

• Renal artery -> segmental artery -> interlobar artery -> arcuate artery -> interlobular artery
• Interlobular arteries are the source of afferent arterioles for glomerular capillaries

Question 6

Describe cortical nephron type

Answer 6

• Shorter nephron with majority in cortex
• Most nephrons are cortical (70-80%)
• Peritubular arterioles covering most of nephron in random nature

Question 7

Describe juxtamedullary nephron

Answer 7

• Glomerulus sits just above medullary boundary
• Long loop of Henle and penetrates deep into medullary tissue
• Peritubular arterioles run as vasa recta
  - Run straight along loop of Henle

Question 8

Compare cortical and juxtamedullary nephron

Answer 8

• Cortical glomerulus in outer part of cortex while JM glomerulus next to medulla
• Cortical has smaller glomerulus
• Cortical has shorter loop of Henle
• Cortical AA > EA while JM AA = EE
• Cortical EA goes to form peritubular capillary while JM goes to form vasa recta
• Cortical has high renin concentration
• Cortical has rich sympathetic innervation

Question 9

What is the renal corpuscle

Answer 9

Renal corpuscle = glomerulus + Bowman’s capsule

Question 10

What % of blood is filtered in the glomerulus in the nephron types

Answer 10

• Found only in the cortex
• 20% of blood from renal artery is filtered at any one time
• 80% of blood arriving exits via efferent arteriole and thus is unfiltered
• Normal total glomerular filtrate per day = 140-180 L/day
• Amount filtered same in both cortical and juxtamedullary nephrons

Question 11

State the 3 layers of the glomerulus filtration barrier

Answer 11

• Capillary endothelium
• Basement membrane
• Podocyte layer

Question 12

Describe the capillary endothelium barrier

Answer 12

• Permeable and allows water, salts glucose to enter lumen

- Filtrate moves between cells

Question 13

Describe the basement membrane barrier

Answer 13

• Acellular gelatinous layer of collagen/glycoproteins
• Permeable to small proteins
• Glycoproteins repel protein movement (negative charge)
  
  • Clearance decreases with molecular radius
  • For same molecular radius, neutral proteins have better clearance as no repel by glycoproteins
  • Nephrotoxic serum can strip negative charge from anions
    
    • Removing negative charge from the barrier increases the filtration of anions
    • In disease processes, the negative charge on the filtration barrier is lost so that proteins are more readily filtered - proteinuria

Question 14

Describe the forces acting on plasma filtration in the glomerulus

Answer 14

• Hydrostatic pressure in the capillary is main driving force of plasma into Bowman’s capsule
• Hydrostatic pressure in the Bowman’s capsule opposes this
• Oncotic pressure difference between the capillary and tubular lumen is minimal effect
  - No oncotic pressure in capsule as no proteins

Question 15

Explain the myogenic mechanisms of renal autoregulation

Answer 15

• Arterial smooth muscle responds to increases and decreases in vascular wall tension
• Predominantly occurs in arcuate, interlobular and afferent arteriole
• Drop in renal arterial pressure and decrease in GFR cause smooth muscle to relax and dilate AA
  
  • Increases blood flow and hydrostatic pressure
• Increase in renal arterial pressure and increase in GFR cause smooth muscle to contract and constrict AA
  
  • Decreases blood flow and hydrostatic pressure
• A dilated afferent and efferent vessel means no filtration will take place as no gradient

Question 16

What are the sensory detectors of tubuloglomerular feedback

Answer 16

• Acts in response to acute changes in the delivery of fluid and solutes to the juxtoglomerular apparatus (JGA)
• Macula densa cells in the distal convoluted tubule detect changes in sodium and chloride concentration and feedback to glomerulus
  
  • Detect via a concentration-dependent salt uptake through NKCC co-transporter in the apical membrane of MD cells

Question 17

Explain the effects of tubuloglomerular feedback

Answer 17

• Increase in arterial pressure = increase in glomerular capillary pressure = increase RPF = increase GFR
  
  • Increases salt in distal tubule
  • Adenosine is released from JGA to reduce GFR
  • A1 receptors constrict afferent arteriole near the glomerulus
  • A2 receptors dilate efferent arteriole
• Decreases in arterial pressure and thus decrease in GFR:
  
  • Prostaglandins released from JGA act as vasodilator of afferent arteriole

Question 18

How does autonomic nervous system regulate GFR

Answer 18

• Sympathetic nerve fibres innervate afferent and efferent arteriole
  
  • In fight or flight, ischaemia or haemorrhage, renal vessels can be stimulated to cause vasoconstriction which conserves blood volume and cause fall in GFR
• Parasympathetic nervous system release NO for endothelial cells and vasodilation

Question 19

Explain how autoregulation by glomerulotubular balance works

Answer 19

• Autoregulation of GFR prevents significant GFR changes
• Acts as second line of defence behind myogenic and tubuloglomerular feedback
• Always around 67% of sodium is reabsorbed in the PCT where water goes with it
• Thus if GFR increases, then more sodium and thus water is reabsorbed back in the PCT
  
  • Less reliance on DCT and collecting duct to take water out of the nephron as they are less adapted than PCT