8-4 Glomerular Filtration and Renal Blood Flow

Question 1

What is the normal value for GFR?

Answer 1

GFR is remarkably high (c. 125 ml/min, 180 l/day)

Question 2

What 3 physical forces affect GFR?

Answer 2

GFR is product of 3 physical factors:

1. Hydraulic conductivity (Lp) of glomerular membrane
2. Surface area for filtration (c. 2 m2)
   - product of 1 and 2 is ultrafiltration coefficient Kf
3. Capillary ultrafiltration pressure (PUF) - starling forces

Question 3

What is the equation for GFR, considering surface area for filtration and capillary ultrafiltration pressure?

Answer 3

•GFR = Kf · PUF

Question 4

What is Puf?

Answer 4

Difference of 3 pressures:

hydrostatic pressure from GC into bowman’s capsule (large)

oncotic pressure that plasme in GC pulls from bowman’s capsule (med - small)

hydrostatic pressure from bowman’s capsule out into GC (very small)

(no proteins in bowman’s capsule, so oncotic pressure should be nil in there)

Question 5

Glomerular filtration depends on what?

Answer 5

Net filtration pressure:

glomerular hydrostatic pressure, minus

Bowman’s capsule hydrostatic pressure, minus

glomerular oncotic pressure

Question 6

As blood moves across glomerular capillaries, what happens to net filtration pressure? Why is this drop important?

Answer 6

Net filtration pressure drops significantly

• afferent and efferent arterioles are major resistance sites in renal circulation
• hydrostatic pressure drops from ~100 mm Hg at afferent arteriole to ~30 mm Hg in efferent arteriole

Drop in pressure promotes filtration in glomerulus, then reabsorption in peritubular capillaries

Question 7

How can you use net filtration pressure help people who are volume overloaded?

Answer 7

Promote diuresis to promote excretion of fluid

• accomplished by increasing hydrostatic pressure out of Bowman’s

Question 8

In peritubular reabsorption, what are the normal forces of fluid reabsorption?

Answer 8

Water is absorbed back into peritubular capillaries due to increased oncotic pressure in blood, reduced hydrostatic pressure

Question 9

How does decreased blood protein levels or increased interstitial pressure change peritubular reabsorption?

Answer 9

Decreased blood proteins will decrease H2O reabsorption out of PCT

Increased interstitial pressure will also decrease fluid reabsorption

Question 10

How can you alter Kf, or the surface area part of total glomerular filtration rate/GFR?

Answer 10

By mesangial cell contraction

• shortens capillary loops
• lowers Kf
• lowers GFR

Question 11

An altered Puf in GFR rate generally reflects what?

Answer 11

Generally changes in hydrostatic pressure in glomerulus, or Pgc

Question 12

What 3 things determine Pgc?

Answer 12

PGC determined by 3 factors:

–Renal arterial blood pressure
–Afferent arteriolar resistance
–Efferent arteriolar resistance

Question 13

Increasing afferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?

Answer 13

decreased RBF

decreased net ultrafiltration pressure

Question 14

Decreasing afferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?

Answer 14

increased RBF

increased net ultrafiltration pressure

Question 15

Increasing efferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?

Answer 15

decreased rbf

increased net ultrafiltration pressure

Question 16

Decreasing efferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?

Answer 16

Increased RBF

decreased net ultrafiltration pressure

Question 17

How does decreasing Kf change GFR? What are some pathological causes for this?

Answer 17

decreases GFR

• renal disease

DM

HTN

Question 18

How does increasing Pbc change GFR? What are some pathological causes for this?

Answer 18

decreases GFR

urinary tract obstruction - eg kidney stones

Question 19

How does increasing πg change GFR? What are some pathological causes for this?

Answer 19

decreases GFR

decreased renal blood flow/RBF, increased plasma proteins

Question 20

How does decreasing Pg change GFR? What are some pathological causes for this?

Answer 20

Decreasing pressure in glomerulus will decrease GFR

• can be due to decreased arterial pressure
• decreased efferent arteriole pressure due to decreased Ang II (ie taking ACE inhibitors)
• increased afferent arteriole pressure due to increased sympathetic activity, vasoconstrictor hormones (ie NE or endothelin)

Question 21

What are some mechanisms that can cause vasoconstriction?

Answer 21

SNS

Endothelin

Ang II

Myogenic reflex

Question 22

How does the SNS change GFR?

Answer 22

•Sympathetic nervous system activation decreases GFR via constriction of the renal arterioles (afferent>>efferent), decreasing RBF and GFR

Question 23

How do endothelin, Ang II, and the myogenic reflex work?

Answer 23

All cause vasoconstriction

•Endothelin is a peptide hormone (autacoid) released by damaged vascular endothelial cells
•
•Angiotensin II preferentially constricts efferent arterioles
•
•Myogenic reflex (autoregulation)

Question 24

What does SNS stimulation do to cardiac output to kidney? When is this really important?

Answer 24

•Sympathetic nervous system activation diverts the renal fraction to vital organs

–Seems to be most important in reducing GFR during severe, acute disturbances (defense reaction, stress, brain ischemia, hypovolemia, hemorrhage, etc.)

Question 25

What does SNS activation cause?

Answer 25

SNS activation causes: 1.Constriction of afferent arteriole due to release of NE at nerve terminals on afferent arteriole 2.↑ renin secretion by granular cells, which leads to Ang II production •Restores blood pressure (systemic vasoconstriction) •Promotes arteriolar constriction (efferent \> afferent): raises blood pressure, may stabilize GFR at moderate levels of Ang II 3.↑ Na+ reabsorption in PCT, thick ascending limb of LOH, DCT, collecting duct

Question 26

Where do SNS neurons synapse?

Answer 26

•Sympathetic neurons synapse on smooth muscle (causing arteriolar constriction) and granular cells (causing renin secretion) in afferent arterioles

Question 27

Is ang II a circulating hormone or autocoid? Where are receptors for it?

Answer 27

* Ang II is considered a circulating hormone as well as an autacoid * Receptors are present in all blood vessels of the kidneys

Question 28

Which arterioles are affected by Ang II?

Answer 28

•Afferent arterioles appear to be “protected” from the effects of Ang II, while efferent arterioles are highly sensitive to it

Question 29

What does ang II do?

Answer 29

•Aids in maintaining GFR in instances of pressure or volume depletion, helps to increase Na+ and H2O reabsorption –Stimulates aldosterone secretion and the thirst center, prompts you to take in more volume/fluids

Question 30

What is the neurohumoral control of the RAAS system?

Answer 30

SNS stimulation, hypotension, decreased Na+ delivery works on kidney kidney secretes renin renin helps convery angiotensinogen to Ang I Ang I converted to Ang II via ACE Ang II does cardiac and vascular hypertrophy, systemic vasoconstriction, stimulates thirst, increases renal Na+ and fluid retention, and stimulates adrenal cortex to make aldosterone, stimulates pituitary to make ADH Aldosterone and ADH both increase renal Na+ and fluid retention

Question 31

How does endothelial-derived nitric oxide work? What does it do?

Answer 31

Causes vasodilation •Endothelial-Derived Nitric Oxide –Vascular endothelial cells release NO, an important factor involved in normal vasodilation in the kidneys –Appears to be important in allowing the kidneys to excrete normal amounts of Na+ and H2O

Question 32

How do prostaglandins and bradykinin work?

Answer 32

Both cause vasodilation •Prostaglandins and Bradykinin –These are not of major importance in regulating GFR in normal conditions, but are extremely important in regulating the vasoconstriction caused by other mechanisms during situations like volume depletion or after surgery

Question 33

What is autoregulation?

Answer 33

The ability of the kidneys to maintain GFR and renal blood flow at relatively constant rates, despite marked changes in arterial blood pressure. These are instantaneous responses

Question 34

What are 2 mechanisms of autoregulation?

Answer 34

•Myogenic mechanism –Responds to increased systemic arterial pressure –Involves vascular smooth muscle cells – •Tubuloglomerular feedback (TGF) –Responds to increased OR decreased GFR –Involves macula densa cells, juxtaglomerular cells, extraglomerular mesangial cells

Question 35

How does myogenic autoregulation work? What does it do, and protect against?

Answer 35

•Mechanism to maintain constant RBF and GFR •Resistance of blood vessels to stretch when exposed to high arterial pressure •Vascular smooth muscle cells contract in response to stretch via movement of Ca2+ from ECF into cells –Occurs within seconds •May be most important in protecting the kidney from hypertension-induced damage