Transcript Renal physiology-226..

Renal Physiology
Dr. Eman El Eter
The Urinary System
• Functions of the urinary system
• Anatomy of the kidney
• Urine formation
– glomerular filtration
– tubular reabsorption
– water conservation
• Urine and renal function tests
Urinary System
• Two kidneys
• Two ureters
• Urethra
Kidney Functions
• Filters blood plasma, eliminates waste, returns useful chemicals to
blood
• Regulates blood volume and pressure
• Regulates osmolarity of body fluids
• Secretes renin, activates angiotensin, aldosterone
– controls BP, electrolyte balance
• Secretes erythropoietin, controls RBC count.
• Formation of the active form of vitamin D
• Regulates acid base balance
• Detoxifies free radicals and drugs
• Gluconeogenesis
Nitrogenous Wastes
• Urea
– proteinsamino acids NH2 removed
forms ammonia, liver converts to urea
• Uric acid
– nucleic acid catabolism
• Creatinine
– creatinine phosphate catabolism
• Renal failure
– azotemia: nitrogenous wastes in blood
– uremia: toxic effects as wastes accumulate
Excretion
• Separation of wastes from body fluids and
eliminating them
– respiratory system: CO2
– integumentary system: water, salts, lactic acid, urea
– digestive system: water, salts, CO2, lipids, bile
pigments, cholesterol
– urinary system: many metabolic wastes, toxins, drugs,
hormones, salts, H+ and water
Anatomy of Kidney
• Renal cortex: outer 1 cm
• Renal medulla: renal columns, pyramids - papilla
• Lobe of kidney: pyramid and it’s overlying cortex
Lobe of Kidney
Nephrons
• Types of nephrons:
• Cortical nephrons (85%)
– short nephron loops
– efferent arterioles branch off
peritubular capillaries
• Juxtamedullary nephrons (15%)
– very long nephron loops, maintain
salt gradient, helps conserve water
– efferent arterioles branch off vasa
recta, blood supply for medulla
Path of Blood Through Kidney
• Renal artery
 interlobar arteries (up renal columns, between lobes)
 arcuate arteries (over pyramids)
 interlobular arteries (up into cortex)
 afferent arterioles
 glomerulus (cluster of capillaries)
 efferent arterioles (near medulla  vasa recta)
 peritubular capillaries
 interlobular veins  arcuate veins  interlobar veins
• Renal vein
• Normal renal blood flow = 1200 ml/min ….1/5th cardiac output.
Blood Supply Diagram
Urine Formation Preview
Glomerular membrane
• 1. Fenestrated endothelium allows passage of
• most elements of plasma, retains formed
elements.
• 2. GBM filters plasma (molecules the size of
• albumin and larger are held back).
• 3. Podocytes secrete GBM, contribute to
• barrier function, provide structural
• reinforcement (pressures up to 40 mm
• mercury)
Glomerular membrane
Glomerular Membrane Diagram
Kidney: glomerular basement
membrane
• Most proteins cannot
pass through GBM
Fibronectin , globulin
and albumin do not
pass .
Molecules of MW
70,000 or less can pass
Albumin does not pass
because it is negatively
charged
• Glucose, ions, water –
pass into ultrafiltrate
Cross-sectional View of the
Glomerular Capillary Wall
Determinants of GFR:
hydrostatic forces
GFR = kf x (P - )
kf = ultrafiltration
coefficient
(hydraulic permeability &
glomerular membrane
surface area)
P = PGC – PPT (hydrostatic pressure
difference between the glomerular
capillary & Bowman’s space)
GFR
 = GC – PT (oncotic pressure difference between the
glomerular capillary & Bowman’s space)
Net Filtration Pressure (NFP)
Glomerular Filtration Rate (GFR)
• Filtrate formed per minute
• Filtration coefficient (Kf) depends on permeability
and surface area of filtration barrier
• GFR = NFP x Kf  125 ml/min or 180 L/day
• GFR = 10 X 12.5 = 125 ml/min
• 99% of filtrate reabsorbed, 1 to 2 L urine excreted
Factors affecting GFR
GFR = Kf x [(PGC – PPT ) – (GC – PT )]
GFR
decreases
by:
PGC
 Renal arterial pressure
 Afferent-arteriolar resistance
 Efferent-arteriolar resistance
PBC
 Intratubular pressure from tubular or
extra-renal urinary system obstruction
GC
 System plasma oncotic pressure
 Renal plasma flow
Intrarenal vasoconstriction is the major mechanism of  GFR
in ARF, and stressed renal microvasculature is more sensitive
to further hypotensive insults.
As vasodilation and vasoconstriction of the afferent and
efferent arterioles alter the blood flow through the
glomerular capillaries, there are corresponding alterations
in the glomerular filtration rate (GFR).
Glomerular Filtration Rate (GFR)
• Defined as: The volume of filtrate produced by both
kidneys per min
– Averages 125 ml/min
– Totals about 180L/day (45 gallons)
• So most filtered water must be reabsorbed or death would ensue
from water lost through urination
•
GFR is directly proportional to the NFP
– Increase GFR leads to an increase in NFP
– Decrease in GFR leads to a decrease in NFP
• Changes in GFR normally result from changes in
glomerular blood pressure (Gcp)
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Why is it important to have
the GFR regulated?
Regulation of GFR
Glomerular Filtration Rate
• If the GFR is too high:
– Fluid flows through tubules too rapidly to be absorbed
– Urine output rises
• Creates threat of dehydration and electrolyte depletion
• If the GFR is too low:
– Fluid flows sluggishly through tubules
– Tubules reabsorb wastes that should be eliminated
– Azotemia develops (high levels of nitrogen-containing
substances in the blood)
• Only way to adjust GFR moment to moment is to
change glomerular blood pressure
Regulation of GFR
• GFR controlled by adjusting glomerular blood
pressure
– Autoregulation
– Sympathetic control
– Hormonal mechanism: renin and angiotensin
Renal Autoregulation
• Renal autoregulation: the ability of nephrons to adjust their own blood
flow and GFR
– IF there were no renal autoregulation and blood pressure (BP)rose
from 100 mmHg to 125 mmHg, urine output would rise from 1.5
L/day to 45 L/day!!
• Two mechanisms used for ‘renal autoregulation’:
– Myogenic Response
• When average BP drops to 70 mm Hg afferent arteriole dilates
• When average BP increases, afferent arterioles constrict
• Allows kidney to maintain a constant GFR over wide range of
BPs
– Tubuloglomerular feedback
• Increased flow of filtrate sensed by macula densa (MD)
• Macula densa signals afferent arterioles to constrict
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Renal Autoregulation of GFR
•  BP  constrict afferent
arteriole, dilate efferent
•  BP  dilate afferent
arteriole, constrict efferent
• Stable for BP range of 80 to
170 mmHg (systolic)
• Cannot compensate for
extreme BP
Negative Feedback Control of GFR
Sympathetic Control of GFR
• When the sympathetic nervous system is at rest:
– 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 constrict and filtration is inhibited
– Note: during fight or flight blood is shunted away from
kidneys
• The sympathetic nervous system also stimulates the reninangiotensin mechanism. This induce vasoconstriction of
efferent arteriole.
Juxtaglomerular Apparatus
- vasomotion
- monitor salinity
Hormonal Control of GFR
-efferent arterioles
Effects of Angiotensin II
Measurement of GFR
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Creatinine clearance
Inulin clearance we inject
More than secreted by renal tubule
Less than absorbed by renal tubule
• Clearance (ml/min)=( U* x V*)/P*
• Next Lecture……..Tubular transport
Tubular Reabsorption and Secretion