Lecture 3 - Glomerular Filtration and Renal Hemodynamics

Question 1

Mutations in _____ or ______ (two of the proteins that comprise the Slit diaphragms that bridge podocyte slits) are among the most common mutations that cause Glomerular disease.

Answer 1

Nephrin or Podocin

Question 2

Molecules < __Kd or ___nm in diameter are freely filterable. Those that are > ___Kd or ___nm in diameter are not filtered. Molecules that are in between are partially filtered –> what determines if they are more or less filtered?

What is albumin’s charge?

Answer 2

< 7Kd or 4nm

> 70Kd or 8nm

The basement membrane is negatively charged, so negatively charged molecules are less filtered than positively charged or neutral molecules.

Negative

Question 3

Usually, proteins are NOT filtered. What is one exception that indicates muscle damage? What is one that indicates hemolysis?

Answer 3

Myoglobin

Hemoglobin

Question 4

Some small polypeptides CAN be filtered. Specifically, ____, PTH, ____, and ANP are filtered well.

Answer 4

Glucagon

Gastrin

Question 5

_____ __ is a small protein that is FREELY filtered and can be used instead of creatinine to determine presence and severity of kidney disease. It is completely catabolized by renal tubuli, so it can not calculate “clearance” (since it won’t show up in excreted urine.)

Answer 5

Cystatin C

Question 6

Why are small lipid soluble molecules in the blood typically not filtered well?

Answer 6

They tend to bind plasma proteins, especially albumin, and thus remain unfiltered. Think about how this affects clearance of liposoluble drugs.

Question 7

Normal GFR = _____mL/min or about _____L/day.

Answer 7

120mL/min or 175L/day

Question 8

Renal failure is considered GFR < ____mL/min

Answer 8

< 15mL/min

Question 9

______ provides the most accurate estimate of GFR. Keep in mind though creatinine is used, it is not a great indicator if the GFR is in _____ range.

Answer 9

Iothalamate

Normal

Question 10

GFR = Kf x NFP

NFP = ___ - ___ - ___

Answer 10

NFP = Pgc - Pbc - Pi gc

Question 11

Why does NFP decrease along the capillary loop?

Answer 11

Proteins are not filtered, so the Oncotic pressure increases –> decreases NFP.

Question 12

Changes in the hydrostatic or oncotic pressure in the ______ capillaries will affect the efficiency with which reabsorbed material reenters the blood.

Answer 12

Peritubular (or vasa recta)

Question 13

Which causes greater changes in GFR, changes in Afferent or Efferent arteriole?

Answer 13

Afferent

Question 14

Increasing Afferent Arteriole resistance will have what effect on GFR, RPF, and Pgc?

How does this compare to increasing resistance in the Efferent Arteriole?

Answer 14

ALL three will decrease

RPF will decrease as well in this case, but Pgc will greatly increase, and GFR will initially increase, but then it will decrease as RPF reaches lower and lower levels.

Question 15

Autoregulation is a general mechanism by which the _____ Arteriole responds to changes in Arterial pressure –> maintains a relatively constant ______ in the Autoregulatory range (normal BP range). Stretch receptors respond to increase Arterial pressure, causing an influx of _____, which leads to smooth muscle contraction and vasoconstriction.

Answer 15

Afferent Arteriole

GFR

Ca++

Question 16

Tubuloglomerular Feedback (TGF) is another mech by which the _____ Arteriole responds to changes in pressure. If pressure increases, flow increases –> increased flow causes increase NaCl delivery to _____ densa (in DCT) –> sensed by activity of Na+/K+/2Cl- transporter –> constriction of ______ Arteriole –> decreased ____.

Answer 16

Afferent Arteriole

Macula densa

Afferent Arteriole

GFR

Question 17

RAAS and Sympathetic innervation are both examples of _______ (intrinsic or extrinsic?) vasoconstriction.

Answer 17

Extrinsic

Question 18

ANP and Prostaglandins are examples of extrinsic ________.

ANP is secreted from _____ myocytes when _____ increases. It has its effects on BOTH Afferent and Efferent arterioles –> so GFR _____ (increases or decreases?). It also inhibits _____ secretion and decreases ______ reabsorption.

PGE2 and PGI2 are produced in the ______ in response to ________/increased sympathetic activity. They dilate the _____ arteriole more so than the ______. They act to limit the effects of Sympathetic activity and Angiotensin II.

Answer 18

Vasodilators

Atrial myocytes

ECF

GFR Increases

Inhibits Renin secretion

Decreases Na+ reabsorption

Kindey

Angiotensin II

Afferent more so than the Efferent

Question 19

Angiotensin II constricts the ______ Arterioles more so than the ______. Thus, RPF is dereased, GFR remains the same or is slightly increased, and thus FF is _____ (increased or decreased?). This causes an increase in _____ pressure in peritubular capillaries. What effect would this have on Na+ reabsorption?

Keep in mind Angiotensin II also decreases the surface area for filtration, so Kf decreases.

Answer 19

Efferent Arterioles

Afferent

Increased

Oncotic pressure

This would draw water and Na+, so it would increase reabsorption.

Question 20

How do moderate vs maximal Sympathetic nervous system activity affect GFR?

Answer 20

Moderate –> constriction of both afferent and efferent arteriole –> minimal change to GFR

Maximal –> Constriction of Afferent Arteriole favored –> so decreased GFR

Question 21

What happens if NSAIDs are taken when kidney perfusion is Low?

Answer 21

They block prostaglandin synthesis –> decreases vasodilation –> exacerbates decreased perfusion.