01: Normal Kidney Structure & Function

Question 1

Adult kidney size

Answer 1

10-12cm

Question 2

Functions of kindeys

Answer 2

1. Waste disposal (dz: waste accumulation, uremia)
2. Regulate water/mineral balance (dz: vol overload, hyperkalemia, hyperphosphatemia)
3. Regulate acid/base balance (dz: acidosis)
4. Synthesize erythropoeitin (dz: anemia)
5. Vitamin D3 1-hydroxylation (dz: hypocalcemia, metabolic bone dz)
6. Insulin metabolism (dz: hypoglycemia)

Question 3

Major kidney compartments

Answer 3

1. Glomerulus (affected by immune-mediated dz)
2. Tubules (affected by ischemic or toxic dz)
3. Interstitium (affected by inflammatory dz)
4. Blood vessels (affected by HTN or vasculitis)

Question 4

Cellular components of glomerulus

Answer 4

1. Glomerular endothelial cell
2. Mesangial cell
3. Viseral epithelial cell (podocyte)
4. Parietal epithelial cell

Question 5

Glomerular Filtration

Answer 5

GFR = K x A x (Δ‎P - Δ‎π)

Glom cap. hydrostatic pressure = 40-50 mmHg
Glom cap. oncotic pressure = 15-25 mmHg
Bowman’s space hydrostatic pressure = 10-15 mmHg

EFP = 10-15 mmHg

Question 6

Rete mirable

Answer 6

Peritubular interstitial capillaries in renal cortex allowing for easy reabsorption into capillary bed

Question 7

Mesangial cells

Answer 7

Support the ramifying glomerular capillary network.

Glomerular capillary is not completely encircled by basement membrane, but is open at the mesangial interface.

Contracts in response to angiotensin II, vasopressin, norepinephrine, PAF, PGF2α.

Relaxes in response to ANP, dopamine, PGE2.

Question 8

Glomerular basement membrane (GBM)

Answer 8

1. Lamina rara externa
2. Lamina densa
3. Lamina rara interna

• 320nm in thickness
• Type IV collagen in all three layers
• Laminin in all three layers
• Heparin sulfate in rara layers
• Rara are negative charge sites
• GBM restricts proteins based on size and charge (negatively charged proteins more restricted)

Question 9

Filtration slit diaphragm

Answer 9

• Zipper-like configuration
• Lateral pores highly size restrictive (about the size of albumin; 40 angstroms)
• Nephrin molecules extend into center of slit from adjacent foot processes to form the slit diaphragm; overlapping regions form central bar with lateral pores

Question 10

Proximal tubule

Answer 10

• Bulk transport of water and solutes (isotonic)
• Reabsorbs ~60% of filtered NaCl and water, and ~90% of filtered bicarbonate
• Reabsorbs nutrients such as glucose and amino acids
• Secretes a number of organic anions

Question 11

Loop of Henle

Answer 11

• Descending thin limb highly water permeable
• Ascending limb impermeable to water
• Thick asecnding limb (TALH) reabsorbs 15-25% of filtered NaCl; important for generation of medullary gradient; site of action of loop diuretics (e.g., furosemide)

Question 12

Distal convoluted tubule

Answer 12

• Reabsorbs ~5% of filtered NaCl load
• Site of macula densa which senses NaCl; located in proximity to juxtaglomerular apparatus, responsible for renin release
• DCT is the site of action of thiazide diuretics

Question 13

Role of juxtaglomerular apparatus in BP control

Answer 13

1. **JG cells **activated by a) ↓[NaCl], b) ↓perfusion pressure in afferent arteriole, or c) sympathetic stimulation.
2. JG cells secrete renin, which converts **angiotensinogen **to angiotensin I
3. Angiotensin I converted into angiotensin II
4. Angiotensin II causes a) vasoconstriction, and b) ↑aldosterone –> Na+ retention
5. ↑Blood pressure, which has a feedback loop onto JG cells

Question 14

Cortical collecting duct

Answer 14

• Determines final composition of urine, based on homeostatic needs
• Comprised of principle cells (PC) and intercalated cells (IC)
• PCs can reabsorb last 2-5% of NaCl; site of action of aldosterone, vasopressin, atrial natriuretic peptide (ANP); site of action of K-sparing diuretics
• ICs mediate acid secretion

Question 15

Glomerular Filtration Rate (GFR)

Answer 15

• Measure of kidney function
• Volume of plasma filtered by kidney per unit of time (mL/min or Liters/24hrs)
• nl ~ 90-150 mL/min (200 L/day)
• Estimated by measuring serum creatinine (byproduct of muscle metabolism generated at constant rate and freely filtered without reabsorption)
• Serum creatinine levels are inversely related to kidney function

GFR = (U_[creat] x Volume_24hrs)/P_[creat]

Question 16

Chronic Kidney Disease (CKD)

Answer 16

Diminution of kidney function below normal (↓GFR)

Associated with metabolic abnormalities and increased risk of CV disease

Question 17

End-stage Kidney Disease (ESRD)

Answer 17

Complete loss of kidney function (GFR < 15)

Incompatible with long-term survival; requires dialysis or transplantation.

Top causes: diabetes, hypertension, glomerulonephritis, cystic kidney