What is the normal value for GFR?
GFR is remarkably high (c. 125 ml/min, 180 l/day)
What 3 physical forces affect GFR?
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
What is the equation for GFR, considering surface area for filtration and capillary ultrafiltration pressure?
•GFR = Kf · PUF
What is Puf?
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)
Glomerular filtration depends on what?
Net filtration pressure:
glomerular hydrostatic pressure, minus
Bowman's capsule hydrostatic pressure, minus
glomerular oncotic pressure
As blood moves across glomerular capillaries, what happens to net filtration pressure? Why is this drop important?
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
How can you use net filtration pressure help people who are volume overloaded?
Promote diuresis to promote excretion of fluid
- accomplished by increasing hydrostatic pressure out of Bowman's
In peritubular reabsorption, what are the normal forces of fluid reabsorption?
Water is absorbed back into peritubular capillaries due to increased oncotic pressure in blood, reduced hydrostatic pressure
How does decreased blood protein levels or increased interstitial pressure change peritubular reabsorption?
Decreased blood proteins will decrease H2O reabsorption out of PCT
Increased interstitial pressure will also decrease fluid reabsorption
How can you alter Kf, or the surface area part of total glomerular filtration rate/GFR?
By mesangial cell contraction
- shortens capillary loops
- lowers Kf
- lowers GFR
An altered Puf in GFR rate generally reflects what?
Generally changes in hydrostatic pressure in glomerulus, or Pgc
What 3 things determine Pgc?
PGC determined by 3 factors:
–Renal arterial blood pressure
–Afferent arteriolar resistance
–Efferent arteriolar resistance
Increasing afferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?
decreased net ultrafiltration pressure
Decreasing afferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?
increased net ultrafiltration pressure
Increasing efferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?
increased net ultrafiltration pressure
Decreasing efferent arteriole BP causes what changes on RBF and net ultrafiltration pressure?
decreased net ultrafiltration pressure
How does decreasing Kf change GFR? What are some pathological causes for this?
- renal disease
How does increasing Pbc change GFR? What are some pathological causes for this?
urinary tract obstruction - eg kidney stones
How does increasing πg change GFR? What are some pathological causes for this?
decreased renal blood flow/RBF, increased plasma proteins
How does decreasing Pg change GFR? What are some pathological causes for this?
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)
What are some mechanisms that can cause vasoconstriction?
How does the SNS change GFR?
•Sympathetic nervous system activation decreases GFR via constriction of the renal arterioles (afferent>>efferent), decreasing RBF and GFR
How do endothelin, Ang II, and the myogenic reflex work?
All cause vasoconstriction
•Endothelin is a peptide hormone (autacoid) released by damaged vascular endothelial cells
•Angiotensin II preferentially constricts efferent arterioles
•Myogenic reflex (autoregulation)
What does SNS stimulation do to cardiac output to kidney? When is this really important?
•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.)
What does SNS activation cause?
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
Where do SNS neurons synapse?
•Sympathetic neurons synapse on smooth muscle (causing arteriolar constriction) and granular cells (causing renin secretion) in afferent arterioles
Is ang II a circulating hormone or autocoid? Where are receptors for it?
•Ang II is considered a circulating hormone as well as an autacoid
•Receptors are present in all blood vessels of the kidneys
Which arterioles are affected by Ang II?
•Afferent arterioles appear to be “protected” from the effects of Ang II, while efferent arterioles are highly sensitive to it
What does ang II do?
•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
What is the neurohumoral control of the RAAS system?
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
How does endothelial-derived nitric oxide work? What does it do?
•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
How do prostaglandins and bradykinin work?
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
What is autoregulation?
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
What are 2 mechanisms of autoregulation?
–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
How does myogenic autoregulation work? What does it do, and protect against?
•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