Week 1: Glomerular filtration and Regulation of renal blood flow and GFR

Question 1

Apply the starling equation that describes fluid movement across the capillary walls in a form applicable to glomerular capillaries.

Answer 1

GFR=Kf(Pgc-Pbs)-(Ogc-Obs)
Pgc=hydrostatic pressure go glomerular capillary
Pbs=Bowman’s space hydrostatic pressure
Ogc: oncotic pressure of glomerular capillary

Question 2

Discuss how and why each of the variables on the right side of the Starling equation changes as a function of distance along the glomerular capillary

Answer 2

GFR=Kf(Pgc-Pbs)-(Ogc-Obs)

• starling forces favor filtration all along glomerular capillaries
• further along the glomerular capillary, the glomerular capillary oncotic pressure increases, decreasing the pressure driving filtration (from -28 to-35mmHg from afferent to efferent)
• hydrostatic pressure of gc kept high throughout, slight 2mmHg drop

Question 3

How does varying Ra change GFR and RBF?

Answer 3

• Constrict afferent arteriole: decreases GFR, decreases RBF (e.g. to maintain GFR during high bp)
• Constrict efferent arteriole: increases GFR, decreases RBF (e.g. AngII)

Question 4

Differentiate how molecular size and electrical charge on glomerular pores affects filtration of solutes.

Answer 4

• glomerulus is like sieve. Selectivity determined by size and charge
• endothelial cell surface coat contains negatively charged proteoglycans: charge selectivity
• Basement membrane has size and charge selectivity
• slit diaphragms have size selectivity
• clearance: cationic>neutral>anionic
• filtration barrior repel (-) charged macromolecules

Question 5

Summarize the role of nephron-nephrin interaction in setting of the dimensions of the filtration slit.

Answer 5

-Nephrin molecules from opposite foot processes make the slit diaphragm. Disulfide bonds.

Question 6

Explain what is meant by autoregulation of GFR and renal blood flow.

Answer 6

-regulation and maintenance of constant RBF and GFR by control of afferent arteriolar resistance when arterial BP is varied between 90-180mmHg

Question 7

ID the arteriole that mediates auto regulation and the two mechanisms that modulate the resistance of this arteriole to achieve auto regulation.

Answer 7

• The afferent arteriole
  1. Myogenic mechanism: intrinsic property of smooth muscle to contract when stretched
• increased perfusion pressure–> causes afferent arteriolar resistance to increase and diameter of arteriole to decease to normalize flow rate
• decreased perfusion pressure–> Ra decreases and radius increases to normalize flow
  2. Tubuloglomerular feedback: macula densa cells sense transport of NaCl by NaK2Cl transporters in TALH
• if [NaCl] deliver too high, signals sent to constrict afferent arteriole–> decrease GFR
• if [NaCl] deliver too low, signals turned off
• Unrelated: when [NaCl] too low at macular dense, signals sent to increase renin in JG cells.

Question 8

What are factors that affect GFR?

Answer 8

changes in the following:

• Glomerular capillary pressure is a fxn of afferent and efferent arteriolar resistance, blood pressure
• Kf is influenced by SNS, AngII
• Plasma protein concentraiton (Ogc) is due to extra renal changes in protein synthesis.
  1. Sympathetic stimulation: increases Ra and Re, decreases Kf (activated by baroreceptors when bp low)
  2. AngII constrictions both but favors increases Re (when ECF volume low)

Question 9

What are stimuli that increase NaCl at macula densa?

Answer 9

1. increase arterial pressure–>decreased NaCl reabsorption in PT (increased NaCl in tubular lumen)–>stimulates TGF–> decreases GFR and RBF
2. increased GFR (increased perfusion pressure)–>increase NaCl deliver via filtration–> activates TGF–> decreases GFR to control levels
3. anything that decreases NaCl reabsorption in PT or TALH increases volume flow to macular densa–>activates TGF–>reduces GFR