PHYSIOLOGY – LECTURE

RENAL PHYSIOLOGY II
Trans no. 2 | Shifting No. 3 | Fernando P. Solidum, MD, DPBA, FPSP | February 16, 2021

OUTLINE
I. Body Fluid B. Volume Sensors in
Compartments High Pressure
II. Control of Body Fluid C. Hepatic Sensors
Osmolality D. CNS Sensors
A. Antidiuretic Hormone V. Volume Sensor Signals
B. Osmotic Control A. Renal sympathetic
C. Hemodynamic Nerves
Control B. RAAS
D. ADH Action on C. Atrial Natriuretic
Kidneys Peptide
III. Renal Mechanisms for VI. Control of Na+ Excretion
Dilution and A. During Euvolemia
Concentration of Urine B. During
A. Hyperosmotic Hypervolemia Figure 2. Cations and anions between the ECF and ICF [Solidum, 2021]
Medullary C. During Hypovolemia • Sodium – predominant in ECF is due to the increased activity of
Interstitium VII. Review Questions Na-K ATPase which pumps:
B. Antidiuresis VIII. References → 3 Na ions to the ECF
C. Urea Recycling IX. Appendix → 2 K ions to the ICF
D. Role of the Vasa • Calcium – very large concentration gradient between the two
Recta in Urine compartments which is the reason when calcium are channels
Concentration are open, the calcium ions gush out from the ECF to ICF.
IV. Volume Sensing Systems
→ In nerve conduction, in the presynaptic membrane there is a
A. Volume Sensors in
significant gush or increase in the Ca2+ concentration in the
Low Pressure
ICF
I. BODY FLUID COMPARTMENTS Osmolarity
• Total number of particles in a solution independent of mass,
• Volume of body fluid compartments charge and chemical composition
→ Water = 60% of body weight = 0.6 x body weight • Expressed in mOsm/L of water.
→ Total body water
• Normal osmolarity of ECF and ICF: 280 – 300 mOsm/L
▪ Intracellular fluid - 0.4 x body weight
▪ Extracellular fluid – 0.2 x body weight → 300 mOsm/L for countercurrent mechanism
− Interstitial fluid – ¾ of ECF volume; surrounds the cells Osmolality
in various tissues of the body • Alternative used to express the concentration of dissolved
− Plasma – ¼ of ECF volume (blood volume) particles.
• In a 70-kg individual: • Expressed in mOsm/kg of water.
• Fluid Exchange between Body Fluid Compartments
→ Determined by the hydrostatic pressures: plasma hydrostatic
pressure, interstitial hydrostatic pressure, capillary oncotic
pressure or interstitial oncotic pressure.
→ Two forces
→ Important determinants of fluid movements across capillary
walls
▪ Hydrostatic Pressure
▪ Oncotic Pressure of Plasma Proteins
• Osmotic Pressure Difference between ECF and ICF
→ Moves fluid across cell membranes
→ Descending thin limb: water permeable
▪ If there is no existing concentration or pressure gradient,
even if it is permeable, there will be no water movement
→ No matter how much aquaporins are inserted into the cells of
the collecting duct system, there would still be no water
movement if there is no concentration gradient.
→ Concentration gradient would cause the movement of water
from the tubular fluid to the interstitium.
• Control of Body Osmolality: Urine Concentration and
Figure 1. Body fluid compartments of a 70 Kg man [Solidum, 2021] Dilution
• Ionic composition of the 2 compartments is similar. → Intense dehydration
→ Capillary walls are permeable to ions. ▪ Kidneys are responsible for the maintenance of fluid
→ Difference is due to the permeability of the membrane volume and plasma osmolarity (body fluid osmolarity)
▪ Dependent on the existence of certain factors ▪ Kidneys will try to conserve water by producing less urine
and increases reabsorption of solutes to be brought back
to the plasma.

PHYS – LEC Trans no. 2 | Ang, Canlas, Corsino, Ferido, Genilla, Landicho, Mendoza, S., Moreno, Sarmiento, Soriano, Suelto, Sugon, Tegrado | TH: Babol, Mendoza, M. 1 of 13
 ▪ Increasing solute reabsorption will increase plasma
osmolarity.
▪ Rising of plasma osmolarity will tend to draw in water from
the other compartments (such as the intracellular fluid
compartment).
▪ Drying of skin happens because water is being drawn out
from the cells and is brought back into the circulation.
→ Over hydration
▪ Kidneys needs to maintain a certain amount of blood
volume circulating in the body.
▪ Normal plasma volume: (5 L), anything in excess will be
eliminated by the kidneys.
▪ Increase of water volume in the plasma will decrease
plasma osmolarity.
− Not suitable
− Kidneys are trying to maintain 280-300 mOsm of plasma
osmolarity.
• NOTE: In dilute solutions such as body fluids, osmolality and
osmolarity can be used almost synonymously [Hall, 2016]
Figure 3. Water intake and output [Solidum, 2021]
• Different ways of sourcing water
→ From water, food, water drawn from food metabolically
processed in the gastrointestinal tract system.
▪ Approx. 2,500 mL water per day (INPUT)
Figure 4. Water loss in different conditions [Solidum, 2021]
• Kidney response to different body conditions:
→ Normal Temperature
PHYS - LEC Trans no. 2 | Renal Physiology II
→ Hot Weather
▪ Water loss increases except for urine as the kidney
minimizes water loss by decreasing the amount urine
produced.
→ Prolonged Heavy Exercise
▪ Too much water is lost through sweat.
▪ Kidneys are trying to conserve water by increasing its
reabsorption in the collecting duct system and brings the
fluid back into the circulation.
▪ Better fluid taken is the electrolyte fluid.
• To maintain balance, the body must match water loss and intake.
II. CONTROL OF BODY FLUID OSMOLALITY
A. ANTIDIURETIC HORMONE
• Vasopressin
• Urine volume and osmolality regulator
• Increases water reabsorption [Hall, 2016]
• Increases water permeability of the distal tubule collecting tubule,
and collecting duct epithelia to conserve water
• ADH actions play a key role in controlling the degree of urine
dilution or concentration [Hall, 2016]
• Secreted by the supraoptic and paraventricular nuclei of the
hypothalamus
• 2 Physiologic Regulators
→ Osmotic
→ Hemodynamic
• Hormone released when you are dehydrated (e.g., when you are
stuck in a desert)
• Highly tied up with the mechanism of baroreceptor reflex
→ Remember: baroreceptor reflex decreases in firing in cases of
a decrease in BP or a decrease in blood volume decreases
the blood that being pumped by the LV
→ This decreases the stretch of the walls of the arch of aorta and
carotid sinus, decreasing the firing of the baroceptors
→ Signals are being sent into the NTS and eventually into the
vasomotor center that will activate the SNS
→ Will increase HR and force of contractility and induce
vasoconstriction
Connection of ADH with the Baroreceptors
• Baroreceptors are responsible for maintaining normal blood
pressure
→ Decrease in BP → increase in SNS activation → increase the
force of contraction → increase HR → produce
vasoconstriction → increase CO → increase TPR → increase
BP
→ When there is a decrease in BP, ADH is released
• Signal being received by baroreceptor sent to the NTS is also
being processed in the same area – the vasomotor center
• Aside from being responsible for activating the SNS, vasomotor
center is sending a higher signal to the paraventricular nuclei and
also to the supraoptic neurons
• Paraventricular nuclei and the supraoptic neurons are
responsible for facilitating the release of ADH in the posterior lobe
• Therefore, decrease in baroreceptor firing because of decrease
in BP → activates the releasee of ADH at the same time
• Release of ADH is tied up with the decrease in BP
→ In the same manner, when BP is high in the aortic arch and
carotid sinus → Increased firing rate of the baroreceptors →
Inhibiting the SNS
→ In cases of high BP and increase in blood volume, ADH is
inhibited
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Figure 5. Anatomy of the hypothalamus and the pituitary gland [Solidum, 2021]
B. OSMOTIC CONTROL OF ADH
• Plasma ADH secreted more rapidly when there is decrease in
blood volume/pressure
• Osmoreceptors are sensors for body fluid osmolality located
in the hypothalamus
• ADH is not only responsive to low BP, but also to high
concentration of solutes in the plasma or a decrease in plasma
osmolality
• Sequence: change in body fluid osmolality (specifically an
increase) → stimulation of osmoreceptors (senses the
concentration of solutes in the blood or in the plasma) →
stimulation of SO and PV nuclei → ADH release
C. HEMODYNAMIC CONTROL OF ADH
• When baroreceptors decrease its firing, it activates the
vasomotor center which sends signals to the higher center to
stimulate ADH
• Stimulus: decrease in blood volume and arterial pressure
• Low pressure receptors (volume): left atrium and large pulmonary
vessels
• High pressure receptors (arterial pressure): aortic arch and
carotid sinus
Figure 6. Response of ADH in different conditions [Solidum. 2021]
PHYS - LEC Trans no. 2 | Renal Physiology II
• As plasma osmolarity increases, ADH increases
• Blood volume/pressure decreases (>10%), ADH increases
Figure 7. Plasma ADH concentration in varying blood volume/pressure [Solidum,
2021]
• Plasma ADH secreted more rapidly when there is decrease in
blood volume/pressure
→ Slower rise in plasma ADH when there is an increase in blood
volume/pressure
→ Rapid rise in plasma ADH when there is a decrease in blood
volume/pressure
D. THIRST
• Stimulus: hyperosmolality ([NaCl] & angiotensin II (reduced
volume)
• Increased hyperosmolarity → Increased NaCl concentration →
Activation of RAAS → Release of Angiotesin II → Stimulation of
thirst center (located in anterolateral region of hypothalamus;
subfornical organ and organum vasculosum of lamina terminalis)
• Determinants of thirst satisfaction
→ Plasma Osmolality (back to normal levels)
→ Blood Volume (restored)
→ Arterial Pressure (restored)
NTK:
Patients suffering from massive blood loss present with thirst
because the thirst centers have been activated due to low blood
volume.
BRAIN BREAK (15 MINS.)
Figure . 1-bHie with all the requirements.
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 III. RENAL MECHANISMS FOR DILUTION AND
CONCENTRATION OF URINE
Figure 8. Comparison of Production of Dilute Urine (top) and Concentrated Urine
(bottom)
• Normal blood osmolality: 300 mOsm
• Normal insterstitial osmolality: 300 mOsm
• Vasa recta comes from peritubular capillaries of efferent
arterioles
→ Supplies the loop of Henle and the collecting duct system
• Differences between the two set-up:
→ Water reabsorption in collecting duct for antidiuresis
→ Higher osmolality of medullary interstitium is higher in
antidiuresis (concentration gradient is lower in water diuresis)
A. HYPEROSMOTIC MEDULLARY INTERSTITIUM
• Vital for tubular fluid concentration in the collecting ducts
→ Water reabsorption
• Hyperosmolar medullary interstitium
→ The interstitium must be saturated with solutes.
• To produce a concentrated urine:
→ Hyperosmolar medullary interstitium
→ Increased ADH secretion
• To achieve a hyperosmolar medullary interstitium:
→ Activation of countercurrent multiplication system in the
loop of Henle
→ Activation of urea recycling
B. ANTIDIURESIS (HYPEROSMOTIC URINE)
• Condition wherein the kidneys produce little to no amount of
urine, making it concentrated
• Happens during dehydration as a result of:
→ Decreased fluid intake
→ Increased fluid loss (e.g., intense physical activity)
Requirements in the Production of Hyperosmotic Urine
• Establish Hyperosmolar Medullary Interstitium
→ “Maraming NaCl ang dapat itapon sa medullary interstitium
para maging concentrated ang urine” [Dr. Solidum, 2021]
→ To establish hyperosmolarity, the ff. must be activated:
PHYS - LEC Trans no. 2 | Renal Physiology II
▪ Countercurrent Multiplier – Loop of Henle
▪ Urea Recycling
→ To maintain hyperosmolarity, the ff. must be activated:
▪ Countercurrent Exchanger – Vasa Recta
▪ Recall: Vasa recta is a blood vessel that is an extension
of the efferent arteriole. This is found in juxtamedullary
nephron which has a Loop of Henle that reaches renal
medulla. Its main mechanism for hyperosmolarity is its
slow blood flow.
→ Principal Solutes: Urea & NaCl
• Secrete ADH
Countercurrent Multiplier – Loop of Henle
• Multiplies the osmolarity of medullary interstitium.
• Osmolality of the interstitium is multiplied by increasing the
amount of NaCl that it pumps into the medullary interstitium.
• Given a new nephron that is about to receive its first blood
supply
→ Has not yet received blood from the afferent arteriole and
filtered fluid in the glomerulus
→ Technically, no tubular fluid has passed
→ Osmolarity of the outer cortex and inner medullary must be
equal to normal plasma osmolarity of 300 mOsm.
→ The loop of Henle consists of two parallel limbs with tubular
fluid flowing in opposite directions = countercurrent flow
Please refer to figure 18 in the appendix.
• (1) Blood with normal plasma osmolarity of 300 mOsm will
enter the afferent arteriole.
• (2) Blood will then go towards the glomerulus, increasing the
glomerular capillary hydrostatic pressure as blood flow
increases. This promotes filtration, producing ultrafiltrate with
still the same osmolarity (300 mOsm).
→ Filtration will occur
→ Factor responsible for filtration: glomerular capillary
hydrostatic pressure
→ Filtration of solutes and water in isosmotic fashion
▪ Both solutes and water are being filtered
• (3) Glomerular ultrafiltrate will enter proximal tubule.
Osmolarity of tubular fluid is maintained because even though
there is reabsorption of NaCl and solutes, water is also
reabsorbed isosmotically.
→ K+, HCO3-, amino acids and glucose are not powerful
osmoles unlike NaCl.
→ Ultrafiltrate will then proceed to the proximal tubule and is
now becomes the tubular fluid
• (4) Tubular fluid will then enter the descending thin limb (water
permeable, thus concentrating segment).
→ Osmolarity is still maintained because there is no
concentration gradient. (osmolarity of tubular fluid =
osmolarity of medullary interstitium)
• (5) Tubular fluid will enter the thin ascending limb with still the
same osmolarity.
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• (6) Once the tubular fluid enters the thick ascending limb, its
osmolarity of 300 mOsm will run the activities of transporters
in this region.
→ Na/K ATPase
▪ First to become activated
▪ Generates electrochemical gradient that causes
reabsorption of solutes into medullary interstitium
▪ Electrochemical gradient is created which then activates
the 1Na+/1K+/2Cl- symporter
→ Cl- Channel
▪ Promotes entry of Cl- into medullary interstitium
→ 1Na+/1K+/2Cl- symporter
▪ Pumps solutes from tubular fluid into the cell
Please refer to figure 19 of appendix.
NTK:
Single Effect [Constanzo, 2018]
• As NaCl is reabsorbed out of the ascending limb and
deposited in the surrounding interstitial fluid, water is left
behind in the ascending limb.
• As a result, interstitial fluid osmolarity increases to 400
mOsm/L and the fluid in the ascending limb is diluted to 200
mOsm/L.
• Fluid in the descending limb equilibrates with the interstitial
fluid, and its osmolarity also becomes 400 mOsm/L
Countercurrent Multiplication [Koepen & Stanton, 2017]
• Solute (principally NaCl) is reabsorbed without water from
the ascending limb of Henle’s loop into the surrounding
medullary interstitium.
• This decreases the osmolality in the tubular fluid and raises
the osmolality of the interstitium at this point
• The increased osmolality of the interstitium then causes
water to be reabsorbed from the descending limb of
Henle’s loop, thus increasing the tubular fluid osmolality in
this segment.
• Thus, at any point along the loop of Henle the fluid in the
ascending limb has an osmolality less than fluid in the
adjacent descending limb.
• This osmotic difference was termed the single effect.
• Because of the countercurrent flow of tubular fluid in the
descending and ascending limbs, this single effect could be
multiplied, resulting in an osmotic gradient within the
medullary interstitium, where the tip of the papilla has an
osmolality of 1200 mOsm/kg H2O compared to 300
mOsm/kg H2O at the corticomedullary junction
• (7) Na+ from Na+/K+-ATPase and Cl- from specific Cl- channels
form the NaCl being pumped out towards the medullary
interstitium, increasing the compartment's osmolarity.
→ Osmolarity of the medullary interstitium increases to 400
mOsm
→ Because you are introducing NaCl into the medullary
interstitium because of the activity of the Na-K ATPase
PHYS - LEC Trans no. 2 | Renal Physiology II
• (8) With the increase in osmolarity of medullary interstitium,
there is now a concentration gradient that is able to pull
water from the tubular fluid as it enters the thin descending
limb.
→ Subsequent tubular fluid will have increasing osmolarity as
water is pulled towards the increasingly hyperosmotic
medullary interstitium.
• Steps 6-8 will repeat until osmolarity of medullary interstitium
reaches its maximum at 1200 mOsm.
→ The size of the corticopapillary osmotic gradient depends
on the length of the loop of Henle [Constanzo, 2015]
→ In humans, the osmolarity of the interstitial fluid at the bend
of the loop of Henle is 1200 mOsm/L
→ NTK: In species with longer loops of Henle (e.g. desert
rodents), osmolarity at the bend can be as high as 3000
mOsm/L
ADH Action on the Kidney
• Increases collecting duct permeability to water
• Sequence:
→ ADH binds to V2 receptor on the basolateral membrane of the
cell → increased intracellular cAMP → activates Protein
Kinase A → insertion of water channels (aquaporins) to apical
membrane
→ NOTE: What causes water movement is NOT the presence of
aquaporins but the presence of concentration gradient
Effect of ADH on Urea
• Increases collecting duct permeability to urea
→ Phosphorylation of apical membrane transporter → activation
of urea transporter 1 → Urea inside the cell → activation of
urea transporter 4 in the basolateral membrane
C. UREA RECYCLING
Urea
• Filtered by glomerulus
• Able to pass through filtration barrier
• Reabsorbed and secreted in the nephron by diffusion, either
simple or facilitated, depending on the segment of the nephron
[Constanzo, 2015]
Urea Recycling Cycle
Mechanism as explained by Dr. Solidum; supplementary info from
BRS Physiology:
• An additional mechanism that contributes to the hyperosmotic
renal medulla
Figure 9. Urea Recycling
• Mechanism: (Please see Figure 9)
→ The kidney filters urea in the glomerulus, then:
▪ ½ is reabsorbed in the proximal tubule
− By simple diffusion (First Reabsorption) [Constanzo, 2015]
▪ ½ is delivered to the descending thin limb
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 − The remaining 50% ay iikot; trickles down into the thin
descending limb
→ Urea travels to the thick limb of the loop of Henle, distal tubule,
and cortical collecting tubule where only small amounts of
urea reabsorption normally occur.
▪ Take note: Only sodium, chloride, potassium and
magnesium are absorbed
▪ Urea becomes trapped and accumulates in the thick
ascending limb to collecting ducts (red dashed lines).
→ There is a danger that urea is going to be eliminated into the
urine however, at the distal part of the cortical collecting duct,
there is a transporter that allows urea to be reabsorbed.
→ In the presence of ADH, urea transporters UT-A1 and UT-A3
cause urea reabsorption towards medullary interstitium.
(Second Reabsorption)
▪ When urea is reabsorbed at the end of the collecting duct,
it will meet with sodium.
▪ NaCl and urea shares the equal role in increasing the
osmolarity of the medullary interstitium up to 1200mOsm
(and also the osmolarity values in the thin descending
Figure 10. Urea Recycling.
limb).
Fraction of filtered load that various segments of nephron
→ (*) A moderate share of the urea that moves into the medullary
reabsorb (YELLOW)
interstitium eventually diffuses into the thin loop of Henle and
Fraction of filtered load secreted by TALH
then passes upward through the ascending loop of Henle,
Fraction of filtered load carried away by the vasa recta
distal tubule, and cortical collecting tubule and back down into
(ORANGE)
the medullary collecting duct again.
Fraction of filtered load that remains in the lumen at various
▪ In this way, urea can recirculate through these terminal
sites
parts of the tubular system several times before it is
excreted.
Table 1. Transport and Permeability Properties of Nephron Segments Involved in
→ Take note: Urea recycling is continuous, hence there will Urine Concentration and Dilution [2023A Trans]
be a new batch every single time.
▪ The next 50% of urea enters the circuit, further increasing
its concentration in the medullary interstitium.
▪ Yung 50% na nauna magmimix with a new batch na 50%
thereby making 100% of urea.
▪ Together with the continuing Na/K ATPase pumping out
Na, osmolarity of medullary interstitium INCREASES.
→ Over time, there will be an accumulation of urea in the
medullary interstitium until it reaches 1200 mOsm
▪ 1200 mOsm: Maximum capacity of the nephron for the
reabsorption of water from the descending limb and
collecting duct system with the help of the ADH
▪ Inc. levels of water reabsorption = dec. Urine flow rate →
Inc. urea reabsorption and dec. Urea excretion
D. ROLE OF VASA RECTA IN URINE CONCENTRATION
FYI:
Mechanism as explained in 2023A and 2023B: • Vasa Recta [Berne & Levy, 2017]
1. Kidney filters urea in the glomerulus and reabsorbs about → Extension of efferent arteriole that forms a series of
half in the proximal tubule, with the remaining 50% accompanying vascular loops
travelling down the tubule → Descend into the medulla, where they form capillary networks
2. In juxtamedullary nephrons, the tDLH and the tALH secrete that surround the collecting ducts and ascending limbs of the
urea into the tubule lumen loop of Henle
3. Some urea reabsorption occurs along the TAL up through → Serve important functions in the renal medulla that include:
the CCT. ▪ Conveying oxygen and important metabolic substrates to
4. Finally, the Inner Medullary Collecting Duct (IMCD) support nephron function
reabsorbs urea. The net effect is that the kidney excretes ▪ Delivering substances to the nephron for secretion
less urea into the urine than it filters. Depending on urine ▪ Serving as a pathway for return of reabsorbed water and
flow, the fractional excretion may be as low as ~15% solutes to the circulatory system
(minimal urine flow) or as high as ~65% or more (maximal ▪ Concentrating and diluting urine (urine concentration and
urine flow) dilution)
→ Unlike the Loop of Henle, all segments of the vasa recta are
water and solute permeable
→ Serve as countercurrent exchangers: minimizing the
washout of solutes from the medullary interstitium
→ The ability of the vasa recta to maintain the medullary
interstitial gradient is flow dependent
▪ ↑ in vasa recta blood flow dissipates the medullary gradient
(i.e., washout of osmoles from the medullary interstitium).
▪ ↓ blood flow reduces oxygen delivery to the nephron
segments within the medulla
PHYS - LEC Trans no. 2 | Renal Physiology II 6 of 13
 − There is ↓ salt and solute transport by nephron
segments in the medulla due to reduced blood flow as
this requires ATP and oxygen
− As a result, the medullary interstitial osmotic gradient
cannot be maintained
Figure 11. Vasa Recta as Countercurrent Exchanger
• Main Goal: maintain the hyperosmotic medullary interstitium
by altering its own plasma contents resulting to concentrated
urine production
• Mechanism: (Please see Figure 11)
→ Blood enters and leaves the medulla via the vasa recta at the
boundary of the cortex and renal medulla at 300 mOsm
→ Blood travels down into the deeper portions, still at 300 mOsm
with concentration of the interstitium at 400 mOsm
→ Descending limb: NaCl enters the vessel and water exits →
↑ osmolarity until it equilibrates with the interstitium at 400
mOsm
→ This process repeats as the plasma travels deeper through
the vessel until it increases to 1200 mOsm at the maximum
→ In the ascending limb, osmolarity decreases. As a result, the
vessel now takes in water and NaCl is removed.
→ The process repeats as plasma ascends through the vessel
until it reaches approximately 325 mOsm.
▪ It does not go back to 300mOsm because the role of the
vasa recta is to increase the osmolarity of the plasma to
draw in the water from the other compartments. [Dr. Solidum,
2021]
• The countercurrent multiplier system also works even in normal
conditions
→ This system explains how the kidney produces urine in all
conditions
→ As in the case of water diuresis, there is increased flow in the
vasa recta and osmolarity only reaches up to 600 mOsm as it
washes out the NaCl to return it into the bloodstream
▪ Hence, there is no accumulation of osmolarity in the
medullary interstitium
BRAIN BREAK (15 MINS.)
Figure . when studying renal physio.
PHYS - LEC Trans no. 2 | Renal Physiology II
IV. VOLUME SENSING SYSTEMS
A. VOLUME SENSORS IN LOW PRESSURE
CARDIOPULMONARY CIRCUIT
Baroreceptors
• Kidneys act as a blood pressure monitor
→ 2.4 M nephrons for both kidneys
• Located within the walls of the left and right atria, right ventricle,
and large pulmonary vessels, and they respond to distention
• Ability to regulate blood pressure by releasing Angiotensin II
→ Angiotensin II is a potent vasoconstrictor
→ Can contribute to the increase of total peripheral resistance
• Responds to the “fullness” of the vascular systems.
→ ↓ blood pressure → ↓ firing of baroreceptors → ↑ SNS
stimulation → produces vasoconstriction → ↑ HR and
myocardial contractility
→ High blood pressure →↑ firing of baroreceptors
• Vagus nerve → Solitary tract nuclei of the medulla oblongata
• Modulates sympathetic outflow and ADH release
→ Signal from baroreceptors → afferent fibers of CN IX and X →
nucleus tractus solitarius → brain stem → sympathetic nerve
outflow and ADH secretion
Cardiac Atria
• Releases Atrial Natriuretic peptide (ANP)
→ Synthesized by atrial myocytes from the right atrium
→ Reduces blood pressure
→ Increases NaCl and water excretion
→ Mechanism:
▪ Increased blood volume or venous return → Distention of
atria→ release of ANP → dilation of afferent arterioles and
constriction of efferent arterioles → ↑ glomerular blood flow
→ ↑ GFR → inhibits ADH → ↓ water and NaCl reabsorption
in the collecting ducts → ↑ urine volume → ↓ Blood
pressure
B. VOLUME SENSORS IN HIGH PRESSURE
CARDIOPULMONARY CIRCUIT
Baroreceptors
• Contains baroreceptors present in the arterial side of the
circulatory system such as in the
→ aortic arch
→ carotid sinus
→ afferent arterioles of the kidneys
• Respond to blood pressure (atrial pressure)
• Signals from aortic arch and carotid baroreceptors → afferent
fibers of CN IX and CN X → nucleus tractus solitarius →
→ brainstem → ADH-secreting cells of the supraoptic and
→ paraventricular nuclei → stimulation/inhibition of ADH
•
C. HEPATIC SENSORS
• Located in the liver, which can modulate NaCl excretion though not
as important as vascular sensors
• Different types:
→ Responds to pressure within the hepatic vasculature
(functions similarly as the baroreceptors)
→ Responds to Na concentration of the portal blood entering the
liver.
• Afferent signals are sent to the same area in the brainstem
• Increase pressure in the portal blood Na → decrease in the
sympathetic nerve activity → increase NaCl renal secretion
D. CNS SENSORS
• Sensors are located in the hypothalamus
• Can modulate ECF volume and NaCl secretion
• Modulated by Angiotensin II and ANP
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 • Responds to alteration in the
→ Na+ concentration in blood carried to the brain via the carotid
arteries
→ Increase in the Na+ concentration in the carotid artery or CSF
→ decrease in renal sympathetic activity → increase renal
NaCl secretion
V. VOLUME SENSOR SIGNALS
• ECF volume expansion (increase volume) → increase renal
NaCl and water excretion
• ECF volume contraction (decrease volume) → decrease renal
NaCl and water excretion
• Signals in coupling of volume sensors to kidneys are both neural
and hormonal
Table 2. Signals involved in Control of Renal NaCl and Water Excretion
• Role of Angiotensin II:
1. Increases Filtration Fraction
A. RENAL SYMPATHETIC NERVES
• Sensitive to the changes in pressure
• Effects
→ Constriction of afferent and efferent arterioles by α-adrenergic
receptors → ↓ hydrostatic pressure within glomerular capillary
→ ↓ GFR
→ Decreased in blood pressure → renin secretion mediated by
β-adrenergic receptors → activation of RAAS → ↑ circulating
levels of Angiotensin II and aldosterone → stimulates Na+
reabsorption by nephron
→ α-adrenergic receptor stimulation → ↑ SNS activity → NaCl
reabsorption by the proximal tubules
A. RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
• Juxtaglomerular cells (AKA granular cells)
→ Cells in afferent arterioles
→ Site of synthesis, storage, and release of proteolytic enzyme,
renin
• Determinants of Renin secretion
→ Perfusion pressure
▪ ↓ perfusion pressure → renin release
▪ JG cells in walls of afferent arterioles function as
intrarenal baroreceptors – sensitive to pressure
within the arterioles
▪ Decreased BP in the kidneys (dec. plasma volume)
→ less stretch on JG cells → ↑ renin secretion
→ Sympathetic nerve activity
▪ ↑ sympathetic outflow to afferent arteriole → ↑ renin
secretion
PHYS - LEC Trans no. 2 | Renal Physiology II
→ Delivery of NaCl to Macula Densa
▪ Tubuloglomerular feedback
− ↑ blood flow in the afferent arteriole → ↑ GFR → ↑ NaCl
in the tubular fluid → ↑ NaCl to macula densa → JGA
stimulation → vasoconstriction → GFR and RBF
normalize
− ↑ NaCl to macula densa → ↓ renin secretion
• Calcium paradox
→ Ca+ enters the granular cell → ↑ concentration of the Ca+ in
the smooth muscle → ↓ renin secretion
→ ↓ perfusion pressure → ↓ NaCl to macula densa → ↓ release
of ADP and ATP → ↓ Ca+ concentration in granular cells →
renin is released → ↓ GFR
Angiotensin II
• Stimulation of aldosterone secretion
• Arteriolar vasoconstriction
• Stimulation of ADH secretion and thirst
• Enhancement of NaCl reabsorption by the proximal tubules
→ Vasoconstrict both afferent and efferent arteriole but more on
the efferent arteriole
→ Starling forces
▪ Constricted efferent arteriole → ↑ oncotic pressure, ↓
hydrostatic pressure compared to the peritubular capillaries
→ enhances solute and water reabsorption by the proximal
tubule
→ ↓ BP → ↑ sympathetic flow → ↑ ADH release
→ vasoconstriction of afferent and efferent arterioles
→ More significant effect in efferent arteriole
▪ In afferent arteriole, Angiotensin II →  renal blood flow
▪ In efferent arteriole (more constricted) →  glomerular
capillary hydrostatic pressure →  filtration fraction
caused by:
−  resistance of the blood in efferent arteriole
−  peritubular capillary colloid osmotic pressure caused
by:
o  fluid,  solutes that are not absorbed
−  peritubular capillary hydrostatic pressure
o Kasi nga diba tumaas  filtration fraction natanggalan
mo ng tubig, yung pumupunta sa efferent arteriole,
mababa na yung  hydrostatic pressure kasi
nabawasan na siya [Dr. Solidum, F., 2020]
o So  fluid →  hydrostatic pressure
▪  proximal Na+ reabsorption in proximal tubule → Na+ na
napupunta sa ibang nephron segments, nabawasan na →
 Na+ and H20 excretion
NTK:
From Berne & Levy:
The efferent arteriole is more sensitive than the afferent arteriole
to angiotensin II. Therefore, with low concentrations of
angiotensin II, constriction of the efferent arteriole predominates,
and GFR increases and RBF decreases. However, with high
concentrations of angiotensin II, constriction of both afferent and
efferent arterioles occurs, and GFR and RBF both decrease
Summary of Vasoconstricted Efferent Arteriole:
✓  filtration fraction →  peritubular capillary hydrostatic
pressure &  peritubular capillary colloid osmotic pressure →
 fluid,  solutes →  proximal Na+ reabsorption →  Na+ and
H20 excretion
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 • A steroid hormone produced in the zona glomerulosa of the
adrenal cortex, which stimulates Na+ reabsorption in the
cortical collecting ducts → ↓ NaCl excretion
• Regulates electrolyte excretion and intravascular volume mainly
through its effects on the distal tubules and cortical collecting
ducts of the kidneys in which it acts to increase sodium
reabsorption
• Aldosterone exerts its effects via four mechanisms:
1. Increases amount of Na+-K+ ATPase in the basolateral
membrane
2. Increases expression of Na+ channels in the apical membrane
3. Increases serum-glucocorticoid kinase → increases
expression of Na+ channels
4. Stimulates channel-activating protease that also activates Na+
channels via proteolysis

REMEMBER:
✓ The greater the concentration of aldosterone, the greater the
NaCl reabsorption
✓  aldosterone secretion is due to:
 NaCl reabsorption
 K+ concentration in plasma
↓ NaCl Excretion

C. ATRIAL NATRIURETIC PEPTIDE

• A peptide hormone synthesized and secreted by cells in the
cardiac atria that relaxes vascular smooth muscles
→ Released due to  stretch of the atria as a result from  BV
• Acts on:
→ The renal tubules (several tubular segments) → inhibits
sodium absorption
→ The renal blood vessels →  GFR → sodium excretion
• Trigger
Figure 12. Effects of Vasoconstriction of Efferent Arteriole → Expansion of plasma volume accompanied by  in body Na+
• Actions:
2. Decreases Vasa Recta Blood Flow → Vasodilation of afferent arterioles and vasoconstriction of
• Vasoconstricted efferent arteriole →  vasa recta BF efferent arterioles →  blood flow &  glomerular capillary
▪ Vasa recta has same concentration gradient as the hydrostatic pressure →  in GFR →  and filtered NaCl
interstitium → With angiotensin II, blood flow is  in EA → Inhibition of renin secretion → inhibit RAAS
therefore in the vasa recta as well →  ability to maintain → Inhibition of aldosterone secretion via:
hyperosmotic medullary interstitium →  washing out of ▪ ↓ renin secretion
urea from medullary interstitium →  urea accumulation in ▪ Direct inhibition of aldosterone in glomerulosa cells
medullary interstitium → urea conc. >>  NaCl conc. → → Inhibition of NaCl reabsorption partly due to ↓ aldosterone
gradient produced →  reabsorption of NaCl in the loop of → Inhibition of antidiuretic hormone (ADH)
Henle (thin ascending limb) → NaCl/Urea concentration ▪  BV,  VR → ↓ plasma osmolarity = diluted solutes
equalized →  Na+ and H20 excretion ▪ ADH triggered by  plasma osmolarity & ↓BP/↓BV

Antidiuretic Hormone (Vasopressin)

• The major determinant of the controlled permeability (water
reabsorption) in the cortical and medullary collecting ducts
• In the presence of a high plasma concentration of vasopressin,
the water permeability of the collecting ducts becomes very great.
Therefore, water reabsorption is maximal, and the final urine
volume is small—less than 1 percent of the filtered water.

Figure 13. Role of Angiotensin II.

Aldosterone
• Reabsorption of solutes and water in collecting duct system
• Excretion of K+ in collecting ducts

PHYS - LEC Trans no. 2 | Renal Physiology II 9 of 13

 VI. CONTROL OF SODIUM EXCRETION ▪ Remember that parasympathetic has no effect
▪ Vasodilation is caused by inhibition of parasympathetic
2. Decreased Na+ reabsorption in the proximal tubule
A. DURING EUVOLEMIA
→ Direct stimulation of Angiotensin II
→ Dilation of afferent arterioles
→ Increased hydrostatic pressure in peritubular capillaries
▪ Decreased in Oncotic Pressure
→ Decreased solute reabsorption
3. Decreased Na+ reabsorption in the Collecting Duct
→ There is no RAAS, no Aldosterone, Na+, and water
reabsorption in Collecting Duct is decreased
→ ENaC (epithelial sodium channels) will not be facilitated in
collecting ducts
• Urodilatin (more potent natriuretic than ANP)
→ Hormone stimulated by a rise in blood pressure
→ Inhibits NaCl and water reabsorption across the medullary
portion of the collecting duct

• During volume expansion, there is:

→ Decreased Na+ reabsorption in the proximal tubule
→ Increased delivery of Na+ to the collecting duct
→ Increased Na+ excretion

Figure 14. Segmental Sodium Volume Reabsorption During Euvolemia

• Euvolemia – normal homeostatic condition
→ Goal: Na must be returned back into the system
• Requires precise matching of the amount of NaCl ingested
with the amount excreted from the body
• NaCl is reabsorbed:
→ 67% by proximal tubule
→ 33% by different segments:
▪ 25% by Thick Ascending Limb
▪ 4% by the Distal Tube
▪ 3% by the Cortical Collecting Tube
▪ 1% into the urine Figure 15. Integrative Response to Volume Expansion
• Collecting duct adjusts urinary NaCl excretion to effect Na+
balance
• Regulated by aldosterone
→ ↑ Aldosterone = ↑ Na+ Reabsorption by the Principal cells
→ ↓ Aldosterone = ↓ Na+ Reabsorption by the Principal cells

B. DURING HYPERVOLEMIA
• Occur during over hydration or increased blood volume
• Signals:
→ Decreased renal sympathetic activity
▪ ↑ baroreceptor firing
▪ Vasomotor center not facilitating the activation of SNS
→ Release of ANP due to stretch of Right Atrium
▪ Dilation of the Afferent arteriole
▪ Constriction of the Efferent Arteriole
▪ Increased Venous return Figure 16. Segmental Sodium Reabsorption During Euvolemia and During
→ Inhibition of ADH Volume Expansion
▪ ANP counteracts release of ADH
→ Inhibited Renin secretion C. DURING HYPOVOLEMIA
▪ Inhibition of RAAS
▪ Only triggered by decreased renal perfusion • During ECF volume contraction, the high-pressure and low
→ Decreased Aldosterone secretion pressure vascular volume sensors send signals to the kidneys
• 3 General Responses during volume expansion: that reduce the excretion of NaCl and water.
1. Increased GFR due to decreased activity of SNS • Signals that act on the kidneys include:
→ Vasodilation of afferent arteriole → Increased renal sympathetic nerve activity
→ NOTE: → Increased secretion of renin
PHYS - LEC Trans no. 2 | Renal Physiology II 10 of
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 ▪ 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
→ Stimulation of ADH secretion by the posterior pituitary
• Responses during volume contraction:
1. GFR Decreases
→ Increased renal sympathetic activity
→ Afferent and Efferent Arteriolar Constriction
→ The effect appears to be greater on the afferent than on the
efferent arteriole
→ Decrease in glomerular Hydrostatic pressure
→ Renal plasma flow decreases > GFR ↑ filtration fraction
• 2. Increased Na+ reabsorption by proximal tubule and loop of
Henle
→ Increased sympathetic nerve activity and angiotensin II levels
directly stimulate Na+ reabsorption
→ Constriction of afferent and efferent arterioles
→ ↓ hydrostatic pressure in the peritubular capillaries
→ ↓ hydrostatic pressure in Tubules → ↑ Na+ reabsorption
→ Angiotensin II levels directly stimulate Na+ reabsorption
• 3. Increased Na+ reabsorption in the Collecting duct\
→ Increased sympathetic activity
→ Increased Aldosterone activity
→ Enhance Na+ reabsorption in the thick ascending limb and in
the distal tubule
• During volume contraction, there is:
→ An increased Na+ reabsorption in the proximal tubule
→ Decreased delivery of Na+ to the collecting ducts (collecting
duct reabsorbs virtually all the Na+ it receives)
→ Decreased reabsorption of Na+ in the thick ascending limb
since most of Na+ is already reabsorbed in the PT
→ Decreased Na+ excretion (near zero)
Figure 17. Integrative Response to Volume Contraction
CONGRATS ON FINISHING THIS TRANS!
Figure . Medical Physiology.
PHYS - LEC Trans no. 2 | Renal Physiology II
VII. REVIEW QUESTIONS
1. What is the main goal of vasa recta as countercurrent
exchanger?
a. Establishes hyperosmotic medullary interstitium
b. Maintains hyperosmotic medullary interstitium
c. Serves as a pathway for return of reabsorbed water and solutes
to the circulatory system
2. How is osmolarity affected in the ascending limb of the vasa
recta?
a. It decreases by taking in water and removing NaCl
b. It increases by taking in NaCl and removing water
c. It increases and reaches the maximum 1200 mOsm
3. What is responsible for the secretion of aldosterone?
a. renin
b. angiotensin II
c. ANP
4. An increased NaCl dectected by the Macula Densa would
cause?
a. inhibited release of ADP and ATP
b increased activity of 1Na-1K-2 Cl symporter
c. increased ADH release
5. It is the major determinant of the controlled permeability
(water reabsorption) in the cortical and medullary collecting
ducts.
a. Aldosterone
b. Angiotensin II
c. ANP
d. ADH
6. These are the responses during volume contraction
EXCEPT:
a. GFR Decreases
b. Increased Na+ reabsorption by proximal tubule and loop of Henle
c. Increased Na+ reabsorption in collecting duct
d. Decreased Na+ reabsorption in collecting duct
7.During Urea recycling, urea concentration in the nephron
because there is a/an:
a. Rise in urea levels in the proximal convoluted tubules
b. Fall in urea levels in the medullary collecting ducts
c. Fall in urea levels in the ascending limb of the vasa recta
d. Rise in urea levels in the thin ascending loop of Henle
8.Which of the following nephron segments “traps” urea?
a. Proximal Tubules
b. Thick ascending limb
c. Vasa Recta
d. Descending thin limb
9.The following is true regarding the countercurrent multiplier
a. It increases the osmolarity of the tubular fluid in the TAL and DCT
b. It increases the osmolarity of the medullary interstitium
c. It increases the hydrostatic pressure in the peritubular capillaries
d. It multiplies the solutes pumped by proximal tubules into the
medullary interstitium
10. Which of the following statements is true regarding the
descending limb of vasa recta?
a. The descending limb of the vasa recta is the water losing segment
b. Blood flow in the vasa recta is faster than in the ascending limb
c. Plasma osmolarity in the vasa recta decreases as it goes deep
into the medulla
d. Hydrostatic pressure in the descending limb is decreased
Answer: A. A. B. B. D. D. D. B B. A.
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 VIII. REFERENCES
2023A Trans
2023B Trans
2023D Trans
Constanzo, L. S. (2015). Physiology. (6th ed.). Philadelphia (PA): Lippincott
Williams & Wilkins
Dr. Solidum’s PPT Presentation
Hall, J.E. (2016). Guyton and Hall Textbook of Medical Physiology. 13th ed.
Philadelphia: Elsevier, Inc.
Koeppen, B.M. & Stanton, B.A. (2018). Berne and Levy Physiology. 7th ed.
Philadelphia: Elsevier, Inc

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 IX. APPENDIX

Figure 18. Countercurrent Multiplier Part 1

Figure 19. Countercurrent Multiplier Part 2

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