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Renal Physiology
Renal Functions:
• Excrete metabolic waste products
• Reabsorb vital nutrients
• Regulate osmolarity:
• Maintain ion balance
extracellular fluid volume (and
• Regulate
thus blood pressure)
Renal Functions:
•
•
•
Regulate blood pH
•
Produce hormones: Reabsorb essential nutrients Excrete excess water, ions and foreign
substances •
•
•
Erythropoietin
Calcitriol (activated vitamin D; essential for Ca++
absorption)
Renin
Renal Function: Produce Urine
• More solutes = darker urine
• Measured in specific gravity or
osmolarity
• Measuring solutes:
• PURE water: 1.000
• Dilute urine: 1.001 • Concentrated urine: 1.035
Urine Characteristics
•
Urine may become
dilute due to:
•
•
Excess drinking,
diuretics, renal failure Urine may become
concentrated due to:
•
Inadequate fluid
intake, fever,
pyelonephritis
Anatomy Review
Abnormal solutes signal problems:
• Glucose • due to excess sugar intake
or diabetes • Proteins • due to physical exertion,
pregnancy,
glomerulonephritis,
hypertension
• Pus • urinary tract infection
• Blood
• bleeding in the urinary tract • Bile pigments • liver disease (hepatitis)
•
Retroperitoneal, below
diaphragm and liver
•
Each one: 160 g; 12 cm x 6
cm (size of a fist)
•
25% of blood flow from heart
goes to renal arteries
5 mm is the limit of stones which can pass on their own
The Nephron:
Vascular Elements
• Vascular elements:
Renal artery !
Afferent arteriole !
Glomerulus !
efferent arteriole !
peritubular capillaries
! venules ! veins
! renal vein
• Notice something
strange here?
The Nephron:
Tubular Elements
• Renal corpuscle
+
• Glomerulus
Bowman's capsule
• Proximal tubule • Loop of Henle • Distal tubule
• Collecting duct
Nephron Processes
Filtration (F)
• Movement of fluid from blood to nephron
lumen
• Once in the lumen, what is it?
• Specific or non-specific?
Where is it?
Filtration
•
What drives filtration?
Filtration
are fenestrated
• These
capillaries
(L: fenestra = window)
is driven by
• Filtration
hydraulic pressure
(about 10 mm Hg) • But is it selective?
If it fits through the holes, it gets filtered!
Rate of Filtration
• Glomerular Filtration Rate (GFR)
= volume
of fluid filtering into Bowman's capsule per
unit time
• = 115 ml/ min in women and 125 ml/ min in
men
• Why does fluid leave the capillary and enter
the capsule? (Here we go again…)
Exchange is now from one tube to another!
Filtration
• SO, if filtration is driven by hydraulic
pressure, does the rate of filtration by the
glomerulus change as hydraulic pressure
changes?
Regulation of GFR
• Extrinsic regulation: ANS
• Intrinsic regulation: Autoregulation
• Intrinsic regulation: Tubuloglomeruler feedback
Autoregulation
Autoregulation
Tubuloglomerular Feedback
Reabsorption (R)
• Returning fluid from the lumen to the blood
• 180L of plasma is filtered, but 99% of that
(178.2L) is reabsorbed
• WHY?
Why do it the
“Hard Way?”
Reabsorption may be:
• Active: Primary, secondary active transport
!
• Passive: diffusion, leak channels, facilitated
diffusion carriers
And how do you know
what kind of transport it is?
• Here we go again...
• Saturation, specificity, competition
Transport Maxima
Glucose transport
• Ex:
saturation • Normal:
• Gluc ≈ 100 mg/dL
• Gluc ≈ 0 mg/dL
blood
urine
!
• Diabetes mellitus:
• Gluc > 300 mg/dL
≈ 300 mg/dL
• Tm
blood
reabsorption
Secretion (S)
• Transporting substances from the blood to
lumen
Excretion (E)
• Urine is very different from the filtrate
entering the nephron
!
• What is enriched? What is removed?
• Depends mostly on membrane transport
systems
Excretion (E)
•
Urine is formed 24/7,
but (thankfully) stored
•
Urinary Bladder •
•
•
Is hollow
Exhibits plasticity
Holds about 500
ml comfortably
Excretion (E)
•
Urethra
•
Internal sphincter: tonic contraction of
smooth muscle
•
External sphincter: skeletal muscle under
control of somatic motor neurons; tonic
stimulation from CNS except during
urination
•
Gender differences...
Seriously...
• How much excretion?
• Obligatory water loss = 400 ml / day
• Maximum? What do you think?
• How is this regulated?
urethral challenges...
Journey Through the Tubules
and TWO BIG QUESTIONS:
How can the kidneys produce urine that is hypertonic to the blood being filtered?
!
Proximal Tubule
• Filtrate is isoosmotic w/ plasma (300 mOsm)
• Na+/K+ pumps • Cl- ions follow Na+ and water follows all
and
!
!
!
How is urine volume / osmolarity regulated as
hydration levels change?
Loop of Henle
• So... is peritubular blood isoosmotic?
• Regulation here?
Loop of Henle
• Reabsorption of 20% of salts and water,
regardless of hydration state • Regulation here?
• Ascending limb:
• Na+ is actively extruded from the
filtrate, Cl- follows passively.
• What about water?
Walls of the ascending
limb are not permeable
to water.
Descending Limb
• Impermeable to salt
• Permeable to water; water moves by
osmosis out of the descending limb in
response to the hypertonic tissue fluid
Descending Limb
• Countercurrent Multiplication Effect
• Effects of Urea
• Contributes to the hypertonicity of tissue
fluid in the medulla.
Show Me
the
Regulation!
Where’s the control?
Other Hormonal Effects