Transcript Physiology 441 - West Virginia University

Physiology 441
The Renal System, Chp. 14
Text: Human Physiology (Sherwood), 6th Ed.
Julie Balch Samora, MPA, MPH
[email protected]
293-3412, Room 3145
Renal Processes 1
Tubular Reabsorption
• All plasma constituents (except proteins)
are filtered through the glomerular
capillaries, including needed nutrients and
electrolytes
• Tubular reabsorption is the discrete
transfer of substances from the tubular
lumen into the peritubular capillaries (to be
returned to the body)
• VERY SELECTIVE PROCESS
Tubular Reabsorption
• Tubules have a high reabsorptive capacity
for substances needed by the body
• Only excess amounts of essential
materials (eg elctrolytes) end up being
excreted in the urine
• Out of the 125 ml/min filtered, ~124 ml/min
are reabsorbed! (178.5/180 L filtered/day
are reabsorbed)
• 99% of filtered water, 100% filtered sugar,
and 99.5% of filtered salt gets reabsorbed
Steps of Transepithelial Transport
A Substance must:
• Cross luminal membrane of tubular cell
• Pass through cytosol from one side of
tubular cell to the other
• Cross the basolateral membrane of the
tubular cell to inter the IF
• Diffuse through the intersitial fluid
• Penetrate the capillary wall to enter the
blood plasma
Tubular
lumen
Tubular
epithelial cell
Interstitial
fluid
Filtrate
Peritubular
capillary
Plasma
Tight
junction
Lateral space
Luminal
membrane
Basolateral
membrane
Capillary
wall
Fig. 14-14, p. 515
Active Reabsorption
• Major substances are reabsorbed via
active transport. These are substances
that are needed by the body (e.g. Na+,
glucose, aa’s, other elctrolytes)
• Sodium reabsorption- 99.5% of filtered
sodium is absorbed
– Proximal tubules (67%)
– Loop of Henle (25%)
– Distal/Collecting tubules (8%)
Sodium Reabsorption
• Na+-K+ ATPase located at the basolateral
membrane of tubular cells.
• Pumps Sodium out of cell into lateral space.
• Keeps tubular cell ICF [Na+] low, creating
concentration gradient for Na+ to diffuse in from
lumen.
• Keeps lateral space [Na+] high creating
concentration gradient for Na+ to diffuse into
blood (against gradient)
Mechanism of Na+ reabsorption
Lumen
Tubular cell
Interstitial fluid
Peritubular
capillary
Diffusion
Na+
channel
Active transport
Basolateral
Na+– K+ ATPase
carrier
Lateral space
Diffusion
Fig. 14-15, p. 516
Control of Na+ Absorption
• Renin-Ang II-Aldo – goal to keep Na+
• If ↓ NaCl, ECF volume, arterial blood
pressure, the JGA secretes renin into
blood
• Ang I Ang II in lung
• Ang II stimulates release of Aldo from
Adrenal Cortex
• Aldo stimulates distal/collecting tubules to
reabsorb sodium, thereby conserving it
Aldosterone
• Only the sodium reabsorbed in the distal
and collecting tubules is subject to
hormonal control
• The amount of this sodium depends on
amt of Aldo secreted
• Without Aldo, can excrete lots of NaCl
daily
• However, maximum Aldo secretion leads
to complete reabsorption of sodium
RAAS
Diuretics
• Drugs/drinks that increase urinary output
• Promote loss of fluid from body
• Function by inhibiting tubular reabsorption
of sodium
• Examples include thiazide, loop and
potassium-sparing diuretics (medicinalused for ↑ BP, CHF, Edema, Diabetes
insipidus), coffee, sodas, and alcohol
Atrial Natriuretic Peptide (ANP)
• Goal to rid body of Sodium
• ANP released from cardiac atria when
senses ↑ECF
• Decreases sodium reabsorption and
increases sodium loss in urine
• Result- decrease sodium load and ECF
volume
• (not nearly as powerful as renin-Ang-Aldo
system!)
Tubular Maximum (TM)
• Represents the maximum amount of a
substance that the tubular cells can
actively transport within a given time
period
• Carriers become saturated
• TM ONLY for active processes
• Sodium only actively reabsorbed
substance w/o transport max
Glucose
• Normally no glucose should be in the urine
• However, DM patients often has glucose
due to TM being overcome
• Amt of substance filtered = plasma
concentration X GFR
• e.g. [plasma glucose] = 100mg/100ml
• Normal GFR = 125 ml/min
• Therefore Filtered Load =
(100mg/100ml)x125ml/min = 125 mg/min
Glucose- 2° active transport
• Energy is not used directly to absorb
glucose, even though it is being
reabsorbed against its concentration
gradient
• Carrier is driven by the sodium
concentration gradient established by the
N +-K+ pump
• TM for glucose carriers is 375 mg glucose/
minute
Glucose Reabsorption
Renal Processes 2
Renal Threshold
• Plasma concentration at which a
substance reaches the TM and 1st starts
appearing in the urine
• Renal threshold for glucose is 300 mg
glucose/100 ml plasma
Phosphate
• Also exhibits a TM – Unlike glucose,
kidneys DIRECTLY contribute to its
regulation because the renal threshold for
phosphate = nml plasma [phosphate]
• Whenever ↑ [plasma phosphate], the
kidneys immediately excrete the excess as
the TM is exceeded
Passive Reabsorption
• All passive reabsorption is ultimately
linked to active sodium reabsorption.
• Includes Cl-, H2O, and urea
• Chloride moves via electrical gradient that
was established by Na+
• Sodium creates an osmotic gradient for
the passive reabsorption of H2O via
osmosis
Urea
• Waste product
• At end of proximal tubule, urea is
concentrated, creating a gradient favoring
entrance into the blood
• However, tubular cell membranes not very
permeable and only ~50% of the filtered
urea is passively reabsorbed
• BUN- measured as a crude assessment of
kidney function
Passive Reabsorption of Urea
at the End of the Proximal
Tubule
No Reabsorption of the other
unwanted substances
• The other waste products are too large or
are not lipid soluble, so even though the
gradient favors their return to the blood,
they do not go.
• Furthermore, there are no carriers to allow
them passage.
• Therefore, they remain in the tubule and
pass into the urine in a highly
concentrated form (e.g. uric acid, sulfate,
nitrates, phenols, etc)
Urea Reabsorption
Renal Processes 2
Tubular Secretion
• Additional mechanism to eliminate certain
substances
• Secretion of H+, NH3, K+, organic anions
and cations
• Acid and ammonia secretion imp. in acidbase balance
• Ammonia is secreted during acidosis in
order to buffer the secreted H+
H+ and NH3 secretion
• Hydrogen and ammonia secretion aid with
acid-base balance
• H+ secretion provides a highly
discriminating mechanism for varying the
amt of H+ excreted in the urine, depending
on the acidity of the body fluids
• NH3 is secreted in pronounced acidosis to
buffer the H+ secreted into the urine
K+ Secretion
• K+ is actively reabsorbed in the proximal
tubule, but is also actively secreted in the
distal tubule.
• Allows fine degree of control over plasma
K+ concentration
• Secretion of K+ is variable and subject to
aldosterone control
• Even slight fluctuations in ECF [K+] can
alter nerve and muscle excitability
Organic anion and cation secretion
• The proximal tubule contains 2 different
carriers for secreting organic ions
• These systems aid in secreting foreign
organic substances
• The liver helps this process by converting
many foreign substances into anionic
metabolites
Process of Secretion
Renal Processes 1
Urine excretion
• The final quantity of urine formed
averages about 1ml/min
• This urine contains a high conc. of waste
products & low or no conc. of substances
needed by the body
• Minimum volume of urine to eliminate
wastes is 500ml/day
Plasma Clearance
• The amount of plasma “cleared” of a
substance
• Plasma clearance for a substance that is
FILTERED, but not REABSORBED or
SECRETED == GFR == 125ml/min
• EXAMPLE = INULIN
INULIN- Filtered, NOT reabsorbed, NOT secreted
Renal Processes 2
Plasma Clearance
• Plasma clearance for a substance that is
FILTERED AND REABSORBED, but NOT
SECRETED < GFR
• EXAMPLE = GLUCOSE, UREA
• Clearance rate can be anywhere from 0 up
to normal clearance (125 ml/min)
depending on amount reabsorbed
Plasma Clearance
• Plasma clearance for a substance that is
FILTERED AND SECRETED > GFR
• EXAMPLE = PAH (Para-aminohippuric acid)
• Not only is the plasma that is filtered
cleared of that substance, but additional
amt cleared from plasma which was not
filtered
• Plasma clearance rate for PAH=RENAL
PLASMA FLOW
Plasma clearance rate for PAH = Renal Plasma Flow
Renal Processes 2