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PHYSIO B 1.2 RENAL PHYSIOLOGY PT. 3 [DR. VILA]

FEU-NRMF INSTITUTE OF MEDICINE
11.10.14 [1MD-D]

Transport Maxima Vs. Renal Threshold

Passive and Active Mechanisms

Renal Threshold: the amount of substance in the plasma

in which it will not be excreted into the urine.

Transport Maxima: capability of the tubules to transport

substances back

The renal threshold for glucose is lower than its

Transport Maxim.
Why? Because different nephrons have different
transport maximums.
The maximum capability of a nephron is 350mg/min
[Ex.] The transport maximum for glucose is 375mg/min.
If filtered load of glucose is about 125mg/min (GFR x
plasma glucose concentration = 125mL/min x 1mg/mL),
glucose will not appear in the urine until plasma glucose
concentration exceeds 300mg/dL.

Figure 27-1. Reabsorption of filtered water and solutes

from the tubular lumen across the tubular epithelial cells,
through the renal interstitium, and back into the blood.

Solutes are transported through the cells

(transcellular path) by passive diffusion or active
transport, or between the cells (paracellular
path) by diffusion.
Water is transported through the cells and
between the tubular cells by osmosis.
Transport of water and solutes from the
interstitial fluid into the peritubular capillaries
occurs by ultrafiltration (bulk flow).
[Guyton, 12th ed.]

Gradient-time Limited
Some substances that are passively
reabsorbed do not demonstrate a transport
maximum because their rate of transport is
determined by the:
electrochemical gradient for diffusion of
substances across the membrane
permeability of the membrane
time that the fluid containing the
substance remains within the tubule

Transport Limitation

Tm Limited (Transport Maxima)

Glucose, SO4, PO4, amino acids, lactate,
malate, Vitamin C
There is a limit to the rate at which the solute
can be transported
The limit is due to the saturation of specific
transport systems involved when the amount of
solute delivered to the tubule exceeds the
capacity of the carrier proteins and specific
enzymes involved in the transport process

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Co-transport
Mechanisms

of

amino

acids

via

Na+

Symport

More substance in urine than what is filtered: substance is

secreted = Excretion Filtration
Basic function of the nephron:
Filtration
Reabsorption
Secretion

Na is freely filtrable through the filtration

membrane
Na+ is most abundant extracellularly
Movement of Na+ into the cell is via passive
transport, specifically simple diffusion
Usually accompanied by glucose, amino acid or
organic ions
More glucose and amino acid intracellularly
Transport of amino acid is via active transport
Together with Na+, they move into the cell via cosymport transport (same direction)
Na+, via passive transport, moves ALONG its
electrochemical gradient.
The energy released is used to drive the amino
acids AGAINST its electrochemical gradient, via
active transport
This is called secondary active transport and it
does not require energy directly from ATP

*Cellular Transport Review*

Secondary Active Transport: one substance moves along
its gradient, one moves against, and does not require
energy directly from ATP
Move same direction: Symport
Move at opposite directions: Counter transport
Primary Active Transport: move solutes against an
electrochemical gradient, with energy from the hydrolysis
of ATP.
Move at opposite directions: Antiport
[Ex.] Na-K ATPase Pump

Estimates of excretion make use of different substances:

Inulin:
Exogenous substance
Freely filtered, neither reabsorbed nor
secreted
May cause allergic reactions to the subject
(which is why Creatinine is used)
Excretion = Filtration

Glucose and amino acids:

100% reabsorbed, provided that it does not
go beyond the renal threshold
Excretion Rate = Zero (0)

PAH:
Freely filtered, partially secreted
Excretion > Filtration

Potassium:
Freely filtered, partially reabsorbed and
secreted
Excretion > Filtration (if excess K+)
Excretion < Filtration (if low K+)
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Sodium:
Freely filtered, partially reabsorbed
Excretion < Filtered

Quantification
QF > QE Reabsorbed
QF < QE Secreted
QF = Qty. Filtered ; QE = Qty. Excreted
Regulation of H2O, Volume and Electrolyte Balance
60% of our body weight (BW) is made up of water.

200mL of water is lost via defecation.

350-500mL of water is lost via skin.
1.5-2.5L of water is lost via kidneys.

Therefore, everyday we lose about 3L of water,

physiologically.
We ingest about 2L of water a day and have 7L of
endogenous fluids inside our body. All in all, 9L of fluid
pass through our GIT.
Out of 9L, only 8.8L is only reabsorbed, leaving 200mL into
our stool.

For a 50kg man, that is 30L of water, of which:

40% intracellular
20% extracellular
15% interstitium
5% intravascular
1-2% transcellular
Blood, on the other hand, is about 6-8% of our body
weight. (Avg: 7%)
For a normal 50kg man, blood is 3.5L
Plasma is 2.5L (5% intravascular)
Intravascular is the first compartment to be affected
during dehydration.
First compartment to lose water
Specifically the plasma
Dec BP, Inc HR
Extravascular fluid contraction to compensate
Every 1 deg Celsius rise in temperature, 1 cup of
water is lost (60-80mL)

Total body weight is affected by:

Obesity: Less H2O
Gender
Males: More muscles (testosterone), less
fats, more H2O
Females: More fats (estrogen), less muscles,
less H2O
Age: Children 70-80% H2O
Children

Male

Female

Thin

80

65

55

Average

70

60

50

Fat

65

55

45

Steady state: Intake = Excretion

Dehydration = Negative water balance
Overhydration = Positive water balance
Movement of water is via:
Osmosis: movement of solvent from a higher
water concentration to a lower water
concentration, via a semi-permeable membrane
driven by osmotic pressure
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Osmolality vs. Osmolarity
Osmolality: osmoles per kilogram
Osmolarity: osmoles per liter of solution
More commonly used
Plasma Sodium Concentration and Osmolarity
The effective plasma (and ECF) osmolarity is determined
by osmoles that act to hold water within the extracellular
space.
Posm = sum of osmolarities of the individual
solutes in plasma
= Most of the plasma osmoles are Na+
salts
with lesser contributions from other
ions,
glucose and urea
Normal = 285-295mOsm/L
Tonicity

The total osmolarity of each of the three

compartments is about 300mOsm/L
The plasma is 1mOsm/L greater than the
interstitial and intracellular fluids, due to the
osmotic effects of plasma proteins.
- Chp 25, Guyton 12th edition

Application:
Increase Fluid Intake
Increase BV
Decrease plasma tonicity
(konti na yung concentration ng solutes sa plasma kasi
dumami yung fluid, kaya decrease tonicity)
Increase BP
Increase RPF
Increase GFR
Increase urine formation
Decrease urine tonicity

Decrease Fluid Intake

Decrease BV
Increase plasma tonicity
(since konti yung fluid intake, mas marami solutes sa
plasma ngayon, kaya increase tonicity)
A. Isotonic soln in which cells do not swell or shrink
B. Cell is placed in a solution with a higher concentration
of impermeable solutes
C. Cell is placed in a solution with a lower concentration of
impermeable solutes
There are certain substances that are freely permeable to
the filtration barrier such as Na+ and Cl-.
Substances that are non-permeable will not be able to
pass through the filter, and will contribute to the
osmolarity of the solution, hence there will be unequal
distribution of solutes/osmoles that are freely permeable.

Decrease BP
Decrease RPF
Decrease GFR
Decrease urine formation
Increase urine tonicity

80% of the total osmolarity of the interstitial fluid

and plasma is due to Na+ and Cl- ions
50% of the total osmolarity of the intracellular
fluid is due to K+ and other intracellular
substances
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Renal Mechanisms for Dilution and Concentrating Urine

slightly permeable to water and urea. Urea is

secreted into the tubules, thus making urine
slightly less hypotonic or isotonic
[Refer to Berne&Levy pg 601-604 or Guyton Chp. 28]

Role of vasa recta: Electrolyte and water

exchange

Fluid in the collecting tubule is called urine

It can no longer be modified, unless acted upon
by hormones such as ADH and aldosterone
Urine is either hypotonic to isotonic
Physiologically, urine should be isotonic to
hypertonic

Fluid in cortex is hypotonic or isotonic

Fluid in the medulla is hypertonic due to the
presence of NaCl and urea in the interstitium.

Fluid entering the descending thin Loop of Henle

from the proximal tubules is isotonic with respect
to plasma. (300mOsm/L)

The descending thin limb is highly permeable to

water, not NaCl
The presence of NaCl and urea in the interstitial
medulla will give the medulla a high osmotic
pressure, therefore attracting fluid into the
interstitium
Since water is reabsorbed, fluid in the descending
limb becomes hypertonic (kasi nawala si water,
at naiwan si NaCl)

The ascending loop of Henle is permeable to

NaCl, but NOT water and urea
NaCl is passively reabsorbed in the thin
ascending limb because concentration of NaCl in
tubular fluid is higher than the interstitial fluid
(passive transport higher conc. to lower conc.)
[Accdg. To Berne and Levy, pg]
Active ion-pumps in the thick ascending limb
trasport NaCl into the medullary intersititium,
reducing its concentration in the tubular fluid.
[Accdg. To Guyton]
Fluid in the ascending limb is now less
concentrated (kasi naabsorb na mga electrolytes)
Fluid leaving the ascending limb is hypotonic with
respect to plasma
The distal tubule and cortical portion of the
collecting duct actively reabsorb NaCl making the
fluid more hypotonic
The medullary portion of the collecting duct is

Countercurrent Multiplier System

1.
Fluid in the loop of Henle and interstitium has an
osmolality equal to plasma (isotonic, 300mOsm/L)
2.
Transport of solute out of the ascending limb into
the interstitium represents the single effect of
separating solute from water.
3.
The osmotic pressure between the descending
limb and interstitium results in passive movement of
water out of the descending limb.
4.
The steps are repeated over and over, with the
net effect of adding more and more solute to the
medulla in excess of water.
5.
The sodium chloride reabsorbed from the
ascending loop of Henle keeps adding to the newly
arrived sodium chloride from the proximal tubules, thus
multiplying its concentration in the medullary
interstitium.
The maximum hypertonicity of the loop of Henle is
1200mOsm/L.
We can dilute urine to as low as 50mOsm/L.
We can concentrate urine to as high as
1200mOsm/L.

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Obligatory urine volume =

600mOsm/ L
1200mOsm / L

= 0.5L/day
Regulation of Water

ADH will act on collecting tubules and collecting ducts via

V2 receptors to cause insertion of aquaporin 2 channels
(water channels) into tubules to cause passive movement
of water into the plasma.
Anti-diuretic Hormone (ADH)
Vasopresin
Produced by the hypothalamus (supraootic
nuclei)
Stored in and secreted by the posterior pituitary
gland

Thirst
Stimuli for thirst:

Stimuli for ADH Secretion:

Greatest factor that will cause release of ADH: Plasma

osmolarity
An increase in 1% plasma osmolarity will cause
ADH release
A decrease in 3-5% BP and BV will also cause ADH
release

An increase in 2-3% plasma osmolarity will cause

thirst sensation
A decrease in 10-15% in blood volume and blood
pressure will cause thirst sensation
ADH secretion comes before thirst sensation.
Thirst center: Anterolateral region of the
hypothalamus where osmoreceptors are located

Application:
Increase ECF plasma osmolarity
Secrete ADH
Increase water reabsorption
Water retained

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Decrease ECF plasma osmolarity

ECF Volume Expansion

Inhibit ADH
Decrease water reabsorption
Urine excreted
ECF Volume Contraction

1.
2.
3.
4.
5.
1.
2.
3.

4.

Increased renal sympathetic nerve activity

Increased secretion of renin, which results in
elevated angiotensin II levels and thus increased
secretion of aldosterone by the adrenal cortex
Inhibition of ANP and BNP secretion by the heart
and urodilatin production by the kidneys
ANP: produced in the right atrium
BNP: produced in the ventricles (hindi brain! Pero
first isolated in the brain)
Urodilatin: secreted by distal and collecting
tubules
Stimulation of ADH secretion by the posterior
pituitary

ADH Secretion Decrease GFR Increase Na+

reabsorption Increase water reabsorption decrease
urine excretion Increase in BV

Decreased activity of the renal sympathetic

nerves
Release of ANP and BNP from the heart and
urodilatin from the kidneys
Inhibition of ADH secretion from the posterior
pituitary and decreased ADH action on the
collecting duct
Decreased renin secretion and thus decreased
production of angiotensin II
Decreased aldosterone secretion, which is caused
by reduced angiotensin II levels, and elevated
natriuretic peptide levels

Signs of ECF Volume Depletion

Decrease Plasma Volume Decrease BP Rapid Pulse
Rate
Sympathetic response
As doctors, we monitor the heart rate, NOT the pulse rate.
Kasi may mga tibok ng puso na hindi dumadating sa
pulses kahit malapit siya sa isa't isa. Hindi lahat ng pagibig dumarating sayo. May ibang pag-ibig na nakakawala.
Nawawala siya along the way, kaya di mo siya
naramdaman. Awtsu!
If decrease in blood volume plasma is not corrected,
interstitial fluid will compensate by going to into the
intravascular compartment.
Therefore, decrease interstitial fluid:
poor skin turgor
dry tongue
sunken eyes
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Signs of ICF Volume Depletion:
1. Intense thirst
2. Disturbance in the functioning of the cells of the
brain (goes mad with thirst)
Edema
Too much hydrostatic pressure or low plasma
protein in blood
Oncotic pressure is low
No attraction of water
It is the excess of fluid within the interstitial
compartment producing visible swelling
Signs:
1.
2.

expanded interstitial space

increase total body Na+

Sources:
Lecture: Dr. Vila
Berne & Levy, 6th edition
Guyton and Hall, 12th edition

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