Transcript Regulation of Glomerular Filtration

Glomerular Filtration and
Regulation of Glomerular Filtration
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Reference: Principles of Anatomy and Physiology;
Tortora & Derrickson
Chapter 26
Dr. Ebaa M. Alzayadneh, DDS, PhD.
Learning Objectives
• Define Forces in the renal corpuscle that
contribute to net filtration Pressure (equation).
• Understand the consequences of alterations in
these forces on the net filtration pressure.
• Define glomerular filtration rate(GFR), filtration
fraction, renal blood flow and renal plasma flow
and understand how they relate to GFR.
• Describe renal Autoregulation of GFR.
• Describe neural and hormonal regulation of GFR.
Glomerular Filtration Forces
Forces Involved in Glomerular Filtration
Net Filtration Pressure (NFP): This is the
pressure responsible for filtrate
formation.
NFP equals the glomerular hydrostatic
pressure (GBHP) minus the oncotic
pressure of glomerular blood (BCOP) and
capsular hydrostatic pressure (CHP)
NFP = GBHP – BCOP – CHP
NFP = 55 – 30 – 15 = 10
Colloid Osmotic Pressure
Large
molecules
or Proteins
Water moves from areas of low osmolality to
areas of high osmolality
Glomerular Filtration Rate (GFR)
• Filtration Fraction (FF)= Fraction of blood plasma in the afferent
arterioles that becomes filtrate= 16-20%.
• GFR =The volume (ml) of fluid filtered through all the corpuscles
of both kidneys per minute.
• The volume of fluid filtered daily through all the corpuscles of both
kidneys per day = 180 L
• Hence, GFR= 180 L/24hours * (1000 ml/ L)*(1hour/60 min)= 125
ml/min (Males)
• For 125ml/min; renal plasma flow = 625ml/min
FF * PF=GFR, PF= 125/(20%)=625 ml/min
• 55% of blood is plasma, so blood flow = 1140ml/min
55% * BF= PF; BF= 625ml/min/ (55%)=1140 ml/min
• Renal Blood Flow of 1140 ml/min = (22.8 % of 5 liters) is required
to have GFR of 125ml/min.
Clinical Application
• Edema
• Some kidney diseases result in a damage of
the glomerular Capillaries leading to an
increase in their permeability to large
proteins .
• Hence, Bowman’s capsule colloid pressure
will increase significantly leading to drawing
more water from plasma to the capsule (i.e
more filtered fluid).
• Proteins will be lost in the urine causing
deficiency in the blood colloid pressure
which worsens the situation, blood volume
decreases and interstitial fluids increases
causing edema.
Regulation of Glomerular Filtration
• Homeostasis of body fluids requires constant
GFR by kidneys.
• If the GFR is too high, needed substances
cannot be reabsorbed quickly enough and are
lost in the urine.
• If the GFR is too low -everything is
reabsorbed, including wastes that are
normally disposed of.
Regulation of Glomerular Filtration
• GFR is directly related to the pressures that
determine NFP.
• Filtration ceases (become zero) if glomerular
hydrostatic pressure drops to 45 mmHg
NFP = GBHP – BCOP – CHP
0= GBPH-15-30 ; GBPH=45
• However, NFP is increased very little when MAP
rises. GFR is nearly constant if MAP is 80-180
mmHg
Regulation of Glomerular Filtration
• Control of GFR normally result from adjusting
glomerular capillary blood pressure
• 3 mechanisms control the GFR
1. Renal autoregulation (intrinsic system)
2. Neural controls
3. Hormonal mechanism
Effect of afferent and efferent arteriolar
constriction on glomerular pressure
Ra
Re
PG
GFR
Blood
Flow
GFR + Renal
Re
Blood
Flow
Ra
PG
Blood
GFR
GFR +
Blood
Flow
Flow
Renal
Regulation of Glomerular Filtration
• Renal Autoregulation of GFR
– Under normal conditions (MAP =80-180mmHg) renal
autoregulation maintains a nearly constant
glomerular filtration rate
– 2 mechanisms are in operation for autoregulation to
adjust Renal blood flow and Glomerular surface
area:
1. Myogenic mechanism:
– Arterial pressure rises, afferent arteriole stretches
– Vascular smooth muscles contract
– Increased arteriole resistance offsets pressure increase; RBF (&
hence GFR) remain constant.
– Opposite is true, when Arterial pressure drops, afferent
arterioles stretch less and smooth muscles relax.
Renal Autoregulation of
GFR
2. Tubuloglomerular feed
back mechanism:
•
•
•
Feedback loop consists of a flow
rate (increased NaCl in filtrate)
sensing mechanism in macula
densa of juxtaglomerular
apparatus (JGA)
Increased GFR (& RBF) inhibits
release of the vasodilator ; Nitric
Oxide (NO) and stimulates renin
that leads to Ang II
production(vasoconstrictor)
Afferent arterioles constrict
leading to a decreased GFR (&
RBF).
Neural Regulation
• When the sympathetic nervous system is at rest; very low:
– Renal blood vessels are maximally dilated
– Autoregulation mechanisms prevail
• Under stress:
– Norepinephrine is released by the sympathetic nervous system
– Epinephrine is released by the adrenal medulla
– Afferent arterioles(Mainly) constrict (more than efferent) and
filtration is inhibited (GFR drops)
• The sympathetic nervous system also stimulates the reninangiotensin mechanism.
• Sympathetic stimulation causes reduction in urine out put
and permits greater blood flow to other vital organs.
• Under moderate sympathetic stimulation both afferent
and efferent arterioles constricts to same degree so GFR
would not be affected.
Hormonal Regulation
Renin-Angiotensin Mechanism
• A drop in filtration pressure stimulates the
Juxtaglomerular apparatus (JGA) to release renin.
• Renin-Angiotensin Mechanism
• Renin acts on angiotensinogen to release
angiotensin I which is converted to angiotensin II
• Angiotensin II
– Causes mean arterial pressure to rise.
– Stimulates the adrenal cortex to release aldosterone.
– As a result, both systemic and glomerular hydrostatic
pressure rise
Renin secretion regulation
1- Perfusion Pressure
low perfusion in afferent arterioles
stimulates renin secretion while high
perfusion inhibits renin secretion.
Juxtaglomerular
apparatus
Glomeruli
JG cells:
Secretes renin
2-Sympathetic nerve activity
Activation of the sympathetic nerve fibers
in the afferent arterioles increases
renin secretion.
3- NaCl delivery to macula densa:
When NaCl is decreased, Renin
secretion is stimulated and vice versa.
(Tubuloglomerular Feedback)
Macula Densa:
sensor cells
Tubuloglomerular Feedback
Hormonal Regulation
Atrial Natriuritic Peptide ANP
• (ANP) release is stimulated from the atrium
under increased pressure/volume.
ANP causes:
• Vasodilation of the afferent arterioles
• Inhibition of Renin secretion
• Inhibition of aldosterone and ADH secretion