Renal Chapter 2: Renal Blood Flow and Glomerular Filtration

Question 1

Describe the blood flow the kidneys receive and where it goes.

Answer 1

receives more than 1L/min …about 20 percent of CO

all blood flows through glomeruli in the cortex
-vast majority continues on via efferent arterioles to peritubular capillaries in the cortex and then into renal venous system

much smaller fraction like 5-10% flows from efferent arterioles down into the medulla.

Question 2

What is normal hematocrit? Plasma?

What is typical renal blood flow (RBF)? What is renal plasma flow (RPF)?

What is typical glomular filtration rate (GFR)?

So of the plasma that enters the glomeruli (provide number), describe how much filters into Bowman’s space. Where does the rest go?

What is filtration fraction?

Answer 2

Normal hematocrit is 45% of blood so 55% is plasma …

typical renal blood flow (RBF) is 1.1 L/min…renal plasma flow (RPF) = 0.55 x 1.1L/min =605mL/min

typical glomular filtration (GFR) rate is about 125mL/min

so of the 605mL of plasma that enters the glomeruli via afferent arterioles, 125mL or 20% filters into Bowman’s space. The rest, 480mL passes via efferent arterioles into peritubular capillaries.

GFR/RPF =filtration fraction
(Bc freely filtered substances are passing into Bowman’s space along with water, about 20% of all freely filtered substances (eg sodium) that enter the kidney also move into Bowman’s space

Question 3

What is the basic equation for flow?

Answer 3

Q= P/R
(R= total vascular resistance...R=8Lviscosity/pi r^4) 
(P= mean pressure in artery supplying the organ minus mean pressure in the vein draining that organ)

Question 4

What makes the vasculature of the cortex unusual?

Answer 4

2 sets of arterioles (afferent and efferent)

2 sets of capillaries (glomerular and peritubular)

Question 5

Describe the hydrostatic pressure in the peritubular/glomerular capillaries. What is the significance of these pressures?

Answer 5

peritubular capillaries are downstream from the efferent arteriole and have lower hydrostatic pressure… t

typica glomerular pressures are near 60mmHg in normal individual, peritubular pressures are closer to 20mmHg

high glomerular pressure is crucial for glomerular filtration whereas the low peritubular capillary pressure is equally crucial for tubular reabsoption of fluid

Question 6

How will a change in arteriolar resistance effect RBF if the change occurs in afferent or efferent arterioles?

Answer 6

A change in arteriolar resistance produces the same effect on RBF regardless of
whether it occurs in the afferent arteriole or efferent arteriole. Because these vessels are in series, a change in either one has the same effect on the total.

When the 2 resistances both change in the same direction, the most common state of affairs, their effects on RBF will be additive. When they change in different directions— one resistance increasing and the other decreasing—they exert opposing effects on
RBF

Question 7

Describe the glomerular filtration barrier (separates blood from urinary space that topologically connects to the outside world via renal tubules, ureter, bladder, and urethra)… describe the route that filtered substances take from the blood through the filtration barrier of a renal corpuscle into Bowman’s space.

Answer 7

3 step process:

• through fenestrae in the glomerular-capillary endothelial layer
• through the basement membrane
• finally through slit diaphragms between podocyte foot processes
  (slit diaphragms essential to prevent excessive leak of plasma protein (albumin))

Question 8

What is selectivity of the barrier to filtered solute based upon?

Describe selection criteria.

Which molecules can/can’t get through?

Answer 8

Selectivity based upon molecular size and electrical charge

no hindrance to movement of molecules with molecular weights less than 7000 Da (all freely filtered when this small)
(includes all small ions, glucose, urea, amino acids, and many hormones)
-electrical charge (negatively charged macromolecules filter to lesser extend and positively charged filter to greater extent than neutral)

completely excludes plasma albumin (66,000 Da) …but extremely small quantities on order of 10mg/L or less (0.02% of concentration of albumin in plasma) can get through

for molecules with molecular weight ranging from 7000 to 70,000 Da, amount filtered becomes progressively smaller as molecule becomes larger.

Question 9

In disease what proteins might appear in the filtrate that doesn’t normally?

Answer 9

certain small proteins not normally present in the plasma appear bc of disease (Hb released from damaged erythrocytes or myoglobin released from damaged muscles)…considerable filtration of these can occur

Question 10

Electrical charge plays a role in determining which molecules can cross the glomerular barrier: negatively charged macromolecules filter to lesser extend and positively charged filter to greater extent than neutral. Why is this?

Answer 10

surfaces of all components of filtration barrier (cell coats of the endothelium, the basement membrane, and the cell coats of podocytes) contain fixed polyanions which repel negatively charged macromolecules during filtration

Because almost all plasma proteins bear net negative
charges, this electrical repulsion plays a very important restrictive role , enhancing that of purely size hindrance.

Certain diseases that cause glomerular capillaries to
become “leaky” to protein do so by eliminating negative charges in the membranes.

the negative charges in the filtration membranes act as a hindrance only to macromolecules, not to mineral ions or low-molecularweight
organic solutes. Thus, chloride and bicarbonate ions, despite their negative charge, are freely filtered.

Question 11

What does a higher GFR rate signify?

Answer 11

higher GFR means greater excretion of salt and water

Question 12

What is the rate of filtration in any of the body’s capillaries, including the glomeruli, determined by?

What is the equation for rate of filtration?

Answer 12

det. by hydraulic permeability of the capillaries, their surface area, and the net filtration pressure (NFP) acting across them

rate of filtration = hydraulic permeability x surface area x NFP

Question 13

How do you calculate the net filtration pressure (NFP) and GFR?

Answer 13

NFP= (PGC- piGC) - (PBC-piBC)

PGC- glomerular capillary hydrostaic pressure
PBC- hydrostatic pressure in Bowman’s capsule
pi BC- oncotic pressure of fluid in Bowman’s capsule
pi GC- oncotic pressure in glomerular capillary plasma

its the algebraic sum of hydrostatic pressures and the osmotic pressures resulting from protein –the oncotic or colloid osmotic pressures, on the 2 sides of the capillary wall

4 pressures to contend with (2 hydrostatic, 2 oncotic pressures) …Starling forces

bc there is normally v little protein in Bowman’s capsule, pi BC can be taken as zero so…
GFR = Kf (PGC-PBC-pi GC)

(Kf is filtration coefficient)

Question 14

Which forces favor filtration and oppose filtration normally?

Answer 14

favor:
glomerular capillary hydraulic pressure

oppose:
hydraulic pressure in Bowman’s capsule
oncotic pressure in glomerular capillary

Question 15

How do hydrostatic and oncotic pressure change along the length of the glomerular capillaries?

How does net filtration pressure change from beginning of glomerular capillaries to the end?

What is the average?

Answer 15

hydraulic pressure changes only slightly along glomeruli bc the very large total cross sectional area of the glomeruli collectively provides only small resistance to flow

oncotic pressure does change a lot… water is moving out of the vascular space and leaving protein behind, thereby raising protein concentration and hence the oncotic pressure of the unfiltered plasma remaining in the glomerular capillaries

mainly bc of this large increase in oncotic pressure, the net filtration pressure decreases from the beginning of glomerular capillaries to the end

(average NFP is 17mmHg) -this is higher than most nonrenal capillary beds

Question 16

What will result from an increase in glomerular surface area (bc of relaxation of glomerular mesangial cells)?

What determinant of GFR is affected and how does GFR change?

Answer 16

Kf affected

increase in GFR

Question 17

What will result if there is an increase in renal arterial pressure?

What determinant of GFR is affected and how does GFR change?

Answer 17

PGC will be affected and GFR will increase

Question 18

What will result if there is a decrease in afferent-arteriolar resistance? (afferent dilation)

What determinant of GFR is affected and how does GFR change?

Answer 18

PGC will be affected

Increase in GFR

Question 19

What will result if there is an increase in intratubular pressure because of obstruction of tubule or extrarenal urinary system?

What determinant of GFR is affected and how does GFR change?

Answer 19

PBC will be affected

GFR will decrease

Question 20

What will result if systemic-plasma oncotic pressure increases?

What determinant of GFR is affected and how does GFR change?

Answer 20

pi GC affected and GFR decreases

systemic plasma oncotic pressure sets pi GC at beginning of glomerular capillaries

Question 21

What will occur if there is a decrease in renal plasma flow?

What determinant of GFR is affected and how does GFR change?

Answer 21

will cause increased rise of pi GC along glomerular capillaries
(pi GC)

decrease in GFR

Question 22

What can cause changes in Kf?

Answer 22

glomerular disease and drugs, variety of chemical messengers which cause contraction of glomerular mesangial cells - that contraction can restrict flow through some of the capillary loops (reducing area available for filtration, thus Kf)
decrease in Kf will lower GFRt

Question 23

How will changes in renal arterial pressure change PGC? Changes in resistance of afferent and efferent arterioles?

What effect will an increase in resistance upstream from glomerulus in afferent arteriole have?

What effect will an increase in resistance downstream from glomerulus in efferent arteriole have? (on PGC and RBF)

Answer 23

a change in renal arterial pressure will cause a change in PGC in same direction

if resistances remain constant, PGC will rise and fall as renal artery pressure rises and falls

changes in resistance of afferent and efferent arterioles have opposite effects on PCG

-increase in resistance upstream from glomerulus in afferent arterioles - lower PGC, lower RBF

increase in resistance downstream from glomerulus in efferent arteriole will increase PGC, decrease RBF

(kink in leaky hose… )

Question 24

What effect will a decrease in afferent resistance (resulting from afferent arteriolar dilation) have on PGC?

What will a decrease in efferent resistance (caused by efferent arteriolar dilation) have on PGC?

What happens when Rafferent and Refferent both increase?

Answer 24

raise PCG (decrease in afferent resistance)

lower PGC (decrease in efferent resistance)

Note: when Rafferent and Refferent both change simulataneously in the same direction (both increase or decrease) they exert opposing effects on PGC, but additive effects on RBF. If they both increase, RBF goes down, PGC same. (when change in different directions they cause additive effects on PGC)

p 41 for explanation and visuals

Question 25

What is the major pathological cause of increased hydraulic pressure in Bowman’s capsule? How is GFR affected?

Answer 25

obstruction anywhere along the tubule or in the external portions of the urinary system (the ureter)

effect of occulusion will be to increase the tubular pressure everywhere proximal to occlusion, all way to Bowman’s capsule.

This decreases GFR.

Question 26

What effect will a decrease in arterial plasma protein concentration (as in liver disease) have on arterial oncotic pressure and GFR?

Answer 26

will lower arterial oncotic pressure and increase GFR

Question 27

Net filtration pressure and filtration decrease along the capillary length. Why? What effect on GFR?

How will a high RPF, all other factors remaining constant, affect piGC and GFR?

Answer 27

pi GC is identical to arterial oncotic pressure only at beginning of GC. pi GC increases along glomerular capillaries as protein-free fluid filters out of the capillary, concentrating the protein left behind

anything that causes steeper rise in pi GC will lower average net filtration pressure and hence, GFR

a high RPF, all other factors remaining constant, will cause πGC to rise less steeply and
reach a final value at the end of the capillaries that is less than normal, which will
increase the GFR.

Question 28

What effect will changes in the GFR/RPF ration have on pi GC?

Answer 28

increase in pi GC directly proportional to filtration fraction… (more volume that is filtered from plasma, the higher is the rise in pi GC.

Question 29

What is filtered load? What is the filtered load for freely filtered substances? (product of what)?

What does high filtered load mean?

Calculate filtered load for Na:
normal plasma concentration is 140mEQ/L. Normal GFR is 125mL/min…

How is filtered load related to increases in plasma concentration and GFR?

Answer 29

filtered load= the amount of substance that is filtered per unit time.
-what is presented to the rest of nephron to handle
(High filtered load means substantial amount of material to be reabsorbed)

for freely filtered substances - filtered load is just the product of GFR and plasma concentration

.14mEq/mL x 125mL/min = 17.5 mEq/min

filtered load rises with increases in plasma concentration and GFR

Question 30

Why is autoregulation important in the kidney?

Answer 30

excretion of salt and water is strongly influenced by GFR

(GFR strongly influenced by renal arterial pressure)

…rise in bp causes incresed excretion of salt/water and fall in bp diminishes excretion

also, vascular pressure in thin walled GC is higher than capillaries elsewhere in body and hypertensive damage ensues if this pressure is too high

Question 31

What is autoregulation in kidney/which factors are auto-regulated?

Draw graph showing autoregulation (BP on horizontal axis, RBF on vertical axis)

What is responsible for the autoregulation mechanism?

Answer 31

GFR and RBF

A rise in driving pressure
is counteracted by a rise in vascular resistance that almost offsets the rise in pressure.
The word “almost” is crucial here. Higher driving pressures do indeed lead
to higher flow but not proportionally

screenshot. or p 44

RBF varies only modestly when mean arterial pressure
changes. This is partly a result of a direct reaction of the vascular smooth
muscle to stretch or relaxation—or the myogenic response—and partly the result of intrarenal signals

Question 32

What are the intrarenal processes that contribute to auto-regulation of kidney? Describe.

Answer 32

called tubuloglomerular feedback

• as filtration rate in an individual nephron increases or decreases, the amount of sodium that escapes reabsorption in the proximal tubule and loop of Henle increases or decreases
• more sodium filtered means more sodium remaining in the lumen of the nephron and more sodium flowing from the thick ascending limb into the distal tubule.
• at division of nephrons is macula densa, a special group of cells in the nephron that passes between afferent and efferent arterioles.
• macula densa senses the amount of sodium and chloride in the lumen (salt detectors)
• changing levels of luminal NaCl is to increase or decrease secretion of transmitter agents into the interstitial space that affect filtration in nearby glomerulus.
• high levels of Na flowing past the macula densa cause a decrease in filtration rate.

(adjusts filtration so that right amount of Na remains in lumen to flow past macula densa) … how? transmitter agents released by salt-sensing macula densa cells produce vasoconstriction of the afferent arteriole, thereby reducing hydrostatic pressure in the GC
(also produce contraction of glomerular mesangial cells, reducing the effective filtration coefficient) both processes reduce effective filtration coefficient

Question 33

A substance X is known to be freely filtered. Therefore, all of the X that enters the
glomerular capillaries is filtered. True or false?

Answer 33

The answer is false. Freely filtered means no restriction or sieving by the
filtration barrier. Because normally about 20% of the plasma volume is
filtered, then about 20% of substance X would be filtered.

Question 34

The concentration of glucose in plasma is 100 mg/dL, and the GFR is 125 mL/min.
How much glucose is filtered per minute?

Answer 34

The answer is 125 mg/min. The amount of any substance filtered per
unit time is given by the product of the GFR and the filterable plasma
concentration of the substance, in this case, 125 mL/min x 100 mg/100
mL (1 dL = 100 mL).

Question 35

The concentration of calcium in Bowman’s capsule is 3 mEq/L, whereas its plasma
concentration is 5 mEq/L. Why are the concentrations different?

Answer 35

Approximately 40% of the calcium in plasma is bound to proteins and so is not filterable.

Question 36

A protein has a molecular weight of 30,000 and a plasma concentration of
100 mg/L. The GFR is 100 L/day. How much of this protein is filtered per day?

Answer 36

If the protein were freely filtered, there would be 100 mg/L x 100 L/
day = 10 g/day. However, no exact value can be calculated from these
data because the molecular weight is high enough so that some “sieving”
would occur. Some would be filtered, but less than 10 g/day.

Question 37

A drug is noted to cause a decrease in GFR. Identify 4 possible actions of the drug
that might decrease GFR.

Answer 37

(1) Constrict glomerular mesangial cells and, hence, reduce Kf .
(2) Lower arterial pressure and, hence, PGC.
(3) Constrict the afferent arteriole and, hence, reduce PGC.
(4) Dilate the efferent arteriole and, hence,
reduce PGC.

Question 38

A drug is noted to cause an increase in GFR with no change in net filtration pressure.
What might the drug be doing?

Answer 38

It might be increasing Kf (ie, changing the hydraulic permeability of the
glomerular membranes or the surface area available for filtration).

Question 39

A person is given a drug that dilates the afferent arteriole and constricts the efferent
arteriole by the same amounts. Assuming no other actions of the drug, what
happens to this person’s GFR, RBF, and filtration fraction?

Answer 39

RBF will show no change because the drug has no effect on total renal vascular resistance. GFR will increase because of a large increase in PGC. Filtration fraction will, therefore, increase. (Now back up and think a bit more about the GFR: Because filtration fraction increases, there
will be a larger than average increase in πGC along the glomeruli, and this will offset some of the GFR-increasing effect of the increased PGC;
therefore, GFR will not increase as much proportionately as the PGC.)

Question 40

A clamp around the renal artery is partially tightened to reduce renal arterial pressure
from a mean of 120 to 80 mm Hg. How much do you predict RBF will change?
A. 33% decrease
B. No change
C. 5–10% decrease
D. 33% increase

Answer 40

The answer is C. Arterial pressure decreases by 33%, but autoregulation
prevents the RBF from decreasing in direct proportion. Autoregulation
is not perfect, so some decrease, but less than 33%, will occur.