Transcript 21-renal physiology

Renal Physiology- Chapter 27
Basic Mechanisms
of Urine Formation
Filtration, secretion,
reabsorption and
excretion.
How do we determine
these rates?
Master formula
1
Renal Equations (for lab exercise)
For any substance,
The rate of
excretion
= rate of +
filtration
rate of –
secretion
rate of
reabsorption
Other terms that are used to express these ideas:
•For “Rate of excretion” we often use the term “urinary output”
•For “Rate of filtration,”
when referring to filtered fluid, we often use the term GFR
if referring to filtered solute, we use Tubular Load
2
Calculating Tubular Load of a Substance
(any solute, “s”)
 At the glomerulus, fluid and solutes are constantly being
filtered and enter the tubule.
 GFR is the term for the volume of plasma fluid filtered each
minute.
 Once in the tubule, it is “tubular fluid” and no longer plasma,
but not yet urine
 Tubular Load (TLs): the amount of any substance (s)
entering the tubule, each minute.
 TL depends on two things: the plasma concentration and
the rate of filtration of that solute
TL s = Ps x GFR
3
Tubular Filtrate Resembles Plasma
 By far, filtered fluid is mainly NaCl
and water.
 It contains other salts and
electrolytes, amino acids, small
sugars, vitamins and other small
molecules, such as wastes.
 Na+ and Cl- are present in such
large amts; they are over 99%
reabsorbed along the length of the
tubule. (Why? Remember that
plasma volume affects blood
pressure)
 Reabsorption of other solutes, like
amino acids and sugars, is often
linked to the transport of Na+
4
Luminal Membrane
Note: this side contains
microvilli in PCT.
Filtrate arriving from
Bowman’s Capsule
Basolateral
Membranes
Tubular
Cells
Peritubular
Capillaries
Tubular
Lumen
The PCT has an extensively amplified apical membrane called
the brush border and its basolateral membrane is highly
invaginated and contains many mitochondria
5
Transport: Active (primary or
Tubular Reabsorption
secondary)
and Diffusion
 Many different solutes
are reabsorbed by
various transport
methods
 As a result of solute
reabsorption, osmosis
will occur
 As a result, water
movement from the
tubule will affect the
gradients of other solutes
still in the tubule, and if
they are permeable, their
reabsorption.
Figure 27-1;
Guyton and Hall
6
3 modes of net reabsorption
+
Primary
Active
Transport
of
Na
of sodium
Sodium/Potassium
ATPase
Facilitated diffusion/
Secondary active
transport on apical
membrane
Simple diffusion
Bulk flow into
peritubular capillary
Figure 27-2;
Guyton and Hall
7
Mechanisms of Secondary Active
Transport
 Across the luminal membrane:
 Co-transport of
 Na+ Glucose
Na+ Amino Acids.
Na+ H+ Counter-transport
(Exchange)
• Across the basolateral
membranes:
glucose and amino acids
diffuse out to peritubular
capillaries (they are permeable
there) but Na must be actively
transported out of the cell by
Na/K pump.
Figure 27-3;
Guyton and Hall 8
Transport Maximum
Figure 27-4;
Guyton and Hall
 Some substances have a
maximum rate of tubular
transport due to saturation of
carriers, limited ATP, etc.
• Transport Maximum (Tm):
Once the transport maximum is
reached for all nephrons, further
increases in tubular load are not
reabsorbed, but are then
excreted.
• Threshold is the plasma
concentration at which tubular
load just exceeds the transport
maximum (Tm) for reabsorption,
where below threshold all solute
molecules are reabsorbed, and
above threshold, some solutes
are not
 Examples: glucose, amino
acids, phosphate, sulfate
9
=solute
= transporter
5/min
1
2
3
4
5
Transport maximum is
reached when carriers
are saturated.
10
=solute
= transporter
5/min
1
2
3
4
Excretion
5
Saturation is reached, Maximum speed, Tm
11
A patient with uncontrolled diabetes has a
GFR of 90 ml/min, a plasma glucose of 200 mg/dl (2mg/ml), and a
transport max (Tm) shown in the figure. What is the glucose excretion
for this patient?
250
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
Threshold
50
0
50
100
150
200
250
300
350
Filtered Load of Glucose
(mg/min)
Copyright © 2006 by Elsevier, Inc.
12
Answer: Filt Glu = (GFR x PGlu) = (90 x 2) = 180 mg/min
Reabs Glu = T
max = 150 mg/min
Excret Glu =
30 mg/min
250
GFR = 90 ml/min
PGlu = 2 mg/ml
Tmax = 150 mg/min
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
Threshold
50
0
50
100
150
200
250
300
350
Filtered Load of Glucose
Copyright © 2006 by Elsevier, Inc.
(mg/min)
13
Make sure you understand that Reabsorption of
Water and Solutes is Coupled to Na+ Reabsorption
in the PCT
Interstitial
Fluid
K+
- 70 mV
ATP
Na + Tubular
Cells
Na +
ATP
0 mv
Copyright © 2006 by Elsevier, Inc.
K+
Tubular
Lumen
H+
Na +
glucose, amino
acids
Na +
Urea
H20
Na +
Cl-
- 3 mV
14
Changes in Concentration in Proximal Tubule
 Special feature of PCT: is freely
permeable to water
 As a result of solute reabsorption,
osmosis will occur
 Isosmotic reabsorption…what does
that mean? Define. (300mOsm)
 As a result, water movement from the
tubule will affect the gradients of other
solutes still in the tubule, and if they
are permeable, their reabsorption.
 ~100% Glucose and Amino Acids
 67% of Filtered Sodium
 65% of Filtered Water
 What happens to a solute
concentration in the tubule if it is
reabsorbed more than water? or less
than water?
Figure 27-7;
Guyton and Hall
15
Before we move onto the other nephron
segments be mindful of the following:
 The kidneys must be able to excrete
urine that is either hypo-osmotic or
hyper-osmotic with respect to bodily
fluids
 This means that the varying
osmolality requires that solute be
separated from water at some point
along the nephron!
 The loop of Henle, in particular the
thick ascending limb, is the MAJOR
site where solute and water are
separated.
 Thus the excretion of both dilute and
concentrated urine requires normal
function of the loop of Henle
16
LOH- Thin Descending limb
 permeable to water
 AQP-1 water channels
 ??? of filtered water
reabsorbed here
 No active sodium transport
 minimal permeability to
sodium and urea (simple
diffusion
INTO the tubule only 110% of urea)
17
Thick- Ascending limb—Diluting
Segment!!!!
Actively pumps sodium out of tubule to surrounding interstitial fluid
(Na+/K+ ATPase)
Na+/2 Cl-/K+ co-transporter on luminal side
Na+/H+ counter-transport (H+ secretion)
Also, Ca+2, HCO3-, Mg+2, K+, and Na+ paracellularly due to positive
net charge in lumen from backflow of K+
 Impermeable to water
 About ??? of sodium
reabsorption
 Fluid leaving thick
ascending limb is hypoosmotic
18
Sodium
Chloride and
Potassium
Transport in
Thick
Ascending
Loop of Henle
Figure 27-9;
Guyton and Hall
19
Look at properties of cells along tubule:




Cells of tubules are NOT
permeable to water. Water
can’t go in or out.
Cells of tubules actively
reabsorb Na+ and Cl-(out of
tubule and into surrounding
area). Salt is removed but
NOT water.
Interstitial space becomes
highly concentrated!
This makes filtrate more dilute
and osmolality decreases.
400
20
Purpose of the LOH- Counter
Current Multiplier






to create an osmotic gradient deep in
medulla of kidney, not for its own
benefit, but to benefit the collecting
duct that sits adjacent to it.
Creates “salt gradient.”
If Loop is disabled, then collecting
duct adjacent to it cannot give
concentrated urine.
Concentration and volume of urine is
determined by concentration gradient
produced in Loop of Henle and by the
presence of certain hormones.
Urine concentration can then range
from 50 mOsmolal to 1400 mOsmolal.
Let’s write in the osmolalities for the
filtrate in the descending and
ascending tubules
300
300
700
700
1000
1000
12000
21
Factors That Contribute to Buildup of
Solute in Renal Medulla Countercurrent Multiplier
 Active transport of Na+, Cl-,
K+ and other ions from thick
ascending loop of Henle into
medullary interstitium
 Active transport of ions from
medullary collecting ducts into
interstitium
 Passive diffusion of urea from
medullary collecting ducts into
interstitium
 Diffusion of only small
amounts of water into
medullary interstitium– most
absorbed in PCT.
 “sluggish blood”
22
Characteristics of Early and Late Distal
Tubules and Collecting Tubules
• not permeable
to H2O
• not permeable to
urea
Juxtaglomerular apparatus
• permeability
to H2O
depends on hormones
• not permeable to
urea
Figure 27-11; Guyton and Hall
23
DCT- early
 associated with Juxtaglomerular
apparatus (helps in
tubuloglomerular feedback
mechanism for GFR)
 Mesangial cells: smooth muscle like
properties, structural support,
phagocytic activity, secrete
prostaglandins
 Granular cells of the afferent
arteriole- makes renin
 Macula densa of DCTchemoreceptors
 Functionally similar to thick
ascending loop
 Not permeable to water (still
diluting segment) nor urea
 Active reabsorption of Na+, Cl-,
K+, Mg++
 Thiazide diuretics affect Na/Cl cotransporter
24
Late DCT, connecting tubule
Principal cells: what do
they do?
No urea permeability
K+ sparing diuretics work
here
Antagonists to aldosterone
binding sites
Sodium channel blockers
(reduces K+)
Water reabsorption
dependent on hormones
25
Intercalated Cells what do they do?
Intercalated
Cells
Tubular Lumen
H20 (depends on
hormones)
H+
K+
K+
ATP
ATP
Na +
K+
H+
ATP
ATP
ATP
Cl 26
Copyright © 2006 by Elsevier, Inc.
Medullary Collecting Ducts Permeable to urea goes
back to ALOH
 Can reabsorb more water
(ADH dependent)- to be
discussed later!
 important for determining
final urine output
 Can secrete hydrogen
ions.
27
Concentration of Different
Substances in Tubular System
• Concentrations of solutes
depend on relative
reabsorption of the solutes
compared to water.
• if water is reabsorbed to a
greater extent than the
solute, the solute will become
more concentrated in the
tubule (e.g., creatinine,
inulin)
• if water is reabsorbed to a
lesser extent than the solute,
the solute will become less
concentrated in the tubule
(e.g., glucose, amino acids)
Figure 27-14;
Guyton and Hall
28
Peritubular Capillary Net reabsorption forces
Figure 27-15; Guyton and Hall
29
Determinants of Peritubular
Capillary Hydrostatic Pressure
Glomerular
Capillary
Ra
Peritubular
Re Capillary
Arterial
Pressure
Arterial Pressure
Ra
Re
Pc
Pc
Pc
30
We’ve covered filtration and
reabsorption….Now, it’s time for
Tubular Secretion
 First step is simple
diffusion from peritubular
capillaries to interstitial
fluid
 Enter to tubular cell can
be active or passive
 Exit from tubular cell to
lumen can be active or
passive
 Examples: potassium,
hydrogen, organic acids,
organic bases, NH3
H+, K+, NH3
Organic acids
and bases
Secretion = Excretion – Filtration+ reabsorption (0)31