2. Structural Basis of Kidney Function

Question 1

What are the functions of the kidneys?

Answer 1

• Production of urine
• Sensitive to body needs e.g. CV
• Endocrine function - signals to rest of body (e.g. renin, erythropoietin, 1,25-OH vitamin D)

Question 2

What are the 5 main steps in the production of urine?

Answer 2

1) Ultrafiltration of blood through glomerulus
2) Selective reabsorption in proximal convoluted tubule
3) Creation of hyperosmotic extracellular fluid by counter-current mechanism in Loop of Henle
4) Adjustment of ion content in distal convoluted tubule
5) Adjustment to concentration of urine in collecting duct as necessary

Question 3

Describe the Renal corpuscle

Answer 3

• Glomerulus + Bowman's capsule
• Glomerulus consists of capillaries with associated podocytes (visceral epithelial cells)
- wrap around capillaries
- long processes
• Fenestrae between processes
- specialised basal lamina
- allows passage of ions and molecules <50,000 molecular weight
• Process is called ultrafiltration

Question 4

Describe the process of selective reabsorption

Answer 4

• Ions, glucose, amino acids, small proteins, water etc. reabsorbed in the proximal convoluted tubule
• Na+ uptake by basolateral Na+ pump (water and anions follow along osmotic & electrochemical gradient)
• Glucose uptake via Na+/glucose co-transporter
• Amino acids via Na+/amino acid co-transporter
• Proteins by endocytosis

Question 5

Describe the structural features of the proximal convoluted tubule

Answer 5

• Large diameter lumen (larger than DCT)
• Cuboidal epithelium sealed with tight junctions
• Brush border at apical surface & basolateral interdigitations
• Aquaporins - mediate transcellular water diffusion
• Prominent mitochondria

Question 6

How is a hyper-osmotic extra-cellular fluid created?

Answer 6

• Achieved by Loop of Henle and vasa recta counter-current mechanisms

1) Na+ and Cl- are actively transported out of ascending limb (but not water due to impermeant tight junctions without aquaporins)
2) This raises concentration in medulla tissue
3) Lower concentration in tissue causes loss of water in descending limb through aquaporins on apical membrane
4) Loss of water concentrates the Na+ and Cl- in the descending limb
5) Higher concentration of descending limb causes Na+ and Cl- to diffuse out at the lower part
6) Hyperosmotic ECF created

Question 7

What happens in the distal convoluted tubule (aka cortical collecting duct)?

Answer 7

Adjustment of ion content of urine
• Cuboidal epithelium with:
- few microvilli
- numerous large mitochondria
- complex lateral membrane interdigitations with Na+ pumps
• Adjusts Na+, K+, H+ and NH4+ (urea) - controlled by aldosterone
• Re-equilibriated luminal fluid- controlled by vasopressin
• Specialisation at macula densa - part of juxtaglomerular apparatus (regulates function of nephorn via renin-angiotensin system)

Question 8

What happens in the medullar collecting duct?

Answer 8

Fine adjustment of urine concentration
• Simple cuboidal epithelium with single cilium per cell and no interdigitations
• Little active pumping - fewer mitochondria
• Contain organelles associated with secretory activity e.g. Golgi
• Aquaporin-2 in apical membrane
- varied by exo/endocytosis mechanism
- controlled by vasopressin
• Aquaporin-3 in basolateral membrane
- transcellular water movement
- not under vasopressin control

Question 9

Outline the mechanism of renin release

Answer 9

• Macula densa of distal convoluted tubule detects [Cl-]
• Juxtaglomerular cells of afferent arteriole sense stretch in arteriole wall
• Secretion of renin