Catch Up Session

Renal Physiology

Dr. Ratnadeep Saha

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 Addressing
some of your
queries

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 Q. For the absorption in the PCT, why hydrostatic pressure in the Proximal tubule/interstitium is high but low in the
peritubular capillaries and also why is the Oncotic pressure low in peritubular capillaries but high in proximal tubules?

The plasma is filtered through glomerulus and moves down

via PCT. It is a dynamic process and happening
continuously. Fluid and solutes are pushed through
glomerulus, but proteins cannot. So the pressure within
this segment (PCT) will be higher. OP is low or NIL as it has
less proteins (Virtually no proteins in normal state).
In efferent arterioles and in PTC blood HP remains low
as the resistance is offered by the glomeruli. Blood
oncotic pressure remains high as some part of the
fluid (Plasma of blood) is filtered, so protein con.
reaching Peritubular capillary is relatively high.
Q. What is solvent drag?
Net result: REASBSORTION from FILTRATE takes place. Here
fluid is reabsorbed from lumen to interstitial place and then The hugely reabsorbed solvent (mainly water) in
to the peritubular capillary blood (Due to high OP). interstitial places often pushes/ forces/drags solutes
along with it into capillaries---- thus ensures one
Solutes are also reabsorbed into blood down solute gradient way of reabsorption mechanisms
(discussed in other slides in the resource recording)

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Q. For the Na absorption in the late PCT, may I ask why the Na+ cannot flow back from the interstitium to the lumen?
is it because the interstitium has become more negatively charged after the Cl- moves into it?

YES, that’s true

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 A significant portion of Na is reabsorbed in paracellular route in
late segment.

Tubular fluid features in late PCT:

It is different from glomerular filtrate that enters the early PCT.
In early PCT, 100% glucose and amino acids, 70-85% HCO3- and
most phosphates have been reabsorbed along with Na (Mainly
via transcellular transport). So, no glucose & amino acids, and
little HCO3- exist in late PCT.

But, Cl- are in high concentration in late PCT filtrate, because….

1) HCO3- is reabsorbed preferentially in early PCT and

2) Water reabsorption increases [Cl-].
Initially, Cl- moves due to the electrochemical gradient. This makes the lumen more and more positive, which then drives
paracellular movement of Na+. However, these Na ions, whatever entered cannot come back.

Reasons: The luminal side to be more positive in charge. This reduces the electrical gradient for Na. Moreover negativity in
the interstitium (due to available negative molecules) attracts Na and do not allow it to return to lumen again.

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 1. In hypertonic overhydration, how does the osmolarity in the extracellular fluid go up if volume is increasing ? At
the same time as water is moving in from the intracellular space, should it not be going down? (slide 35)

Showing the steps in sequence:

Overhydration state: NaCl>> water

So, ECF concentration gets higher (even

though volume increases) [Your answer]

Water now moves ICF to ECF

ICF vol decreases but osmolarity

increases. ECF osmolarity later
slightly changes [Your answer]
2. Also, we say dehydration and overhydration
relative to what? Is it the intracellular component or
extracellular?
Ans: Relative to ICF mainly.

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Conditions Change in ECF Type of Water Shift Change in ICF
1. Volume dehydration/ 1. Volume
2. Osmolality over-hydration 2. Osmolality
Diarrhoea 1. Decrease Isotonic None 1. No Change
2. No Change dehydration 2. No Change
Addison’s disease 1. Decrease Hypotonic ECF to ICF 1. Increase
(Decreased 2. Decrease dehydration 2. Decrease
aldosterone)
Diabetes insipidus 1. Decrease Hypertonic ICF to ECF 1. Decrease
(Decreased ADH) 2. Increase dehydration 2. Increase
SIADH (Increased 1. Increase Hypotonic ECF to ICF 1. Increase
ADH) 2. Decrease over-hydration 2. Decrease
Isotonic NaCl 1. Increase Isotonic None 1. No Change
infusion 2. No Change over-hydration 2. No Change

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 Q. For the highlighted part,
what does this mean?

Good point:
ECF = Effective circulating volume
not Extracellular fluid volume and
this concept is clinically important.

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 Effective circulatory volume and Na+ balance

Positive Na
Dilute Urine
High Na High Water Increase Increase Suppress ADH Loss of
Absorption Absorption in ECF Blood Baroreceptors & Water and
In ECF in ECF Volume Volume Aldosterone Na in Urine

ECF = Interstitium + Blood Plasma Effective Circulating Volume

Low Na Low Water Decrease Decrease Increase ADH Retention

Absorption Absorption in ECF Blood Baroreceptors & of Water
In ECF in ECF Volume Volume Aldosterone and Na

Concentrated
Negative Na
Urine

Case 3 – Tale of 2 Patients

Describe the concept “effective circulating volume” and be able to predict the effects of positive and negative sodium balance

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Why Effective Circulating Volume (ECV) maintenance is clinically important?
Effective Circulating Volume (ECV) = Portion of extracellular fluid that is actually perfusing tissues and filling
arterial circulation. It is not the same as total body fluid — it depends on arterial pressure, vascular tone, and
plasma volume.

The body has volume sensors that monitor ECV, not total fluid ie: extracellular fluid content

•Carotid sinus & aortic arch → baroreceptors Detect effective perfusion, not just
•Afferent arteriole of the kidney → JG cells (renin release) how much fluid is present in the body.
•Atria → atrial stretch receptors (ANP release)

So conditions like heart failure/ ascites/ cirrhosis, where total fluid is high, the ECV is low.
Sensors respond as if the body is “hypovolemic.” Remember, Sodium regulation is tied directly to perceived ECV

When ECV falls, the body activates:

•RAAS system → ↑ Na⁺ and water reabsorption
•Sympathetic nervous system → renal vasoconstriction Restore arterial filling pressure
•ADH release → water retention
•Reduced ANP → less Na⁺ excretion

But, if the underlying cause of the disease eg: heart failure/ ascites/ cirrhosis, if not treated, vicious cycle continues.
More fluid in ECV ---- more hydrostatic pressure ---- more fluid accumulation in interstitial place.

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 I have doubts regarding this diagram. I understand when urinary flow rate increases, distal K+ secretion will increase, but
what I am not sure about why will distal K+ secretion decrease when ADH levels decrease? If ADH levels are decreased,
less water will be reabsorbed? When less water is reabsorbed, will secretion of distal K+ increase?

ADH affects K+ secretion but its effect has got less impact
on overall potassium excretion
It enhances K secretion
A) by Increase the gradient driven by Na+(Majorly).
B) by Increase permeability of K in apical membrane
(Minor) ---hence more secretion

So, when ADH level decrease, these stimulatory

impacts would be absent-----so will reduce distal K
secretion. But K secretion is altered by Flow rate too.
So, the reduction is counterbalanced by flow rate ----
maintain a constant K+ balance.

Net effect: Distal K secretion will not be perturbed too much

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The effect of increased tubular flow rate is important to preserve
normal potassium excretion during changes in sodium intake:
Explain:
Increased Na intake

Body will need to excrete that extra Na (as it

is in positive Na balance)

How that could be accomplished?

By increasing Na and water excretion in urine

Mechanism: Supress ADH & Aldosterone secretion. Eventually,

body would respond to this by increasing GFR -----increases scope
of extra Na excretion. As ADH is suppressed---water excretes ---
tubular flow would also increase.

This increased tubular flow would enhance K secretion /excretion; Counterbalancing

but normally K secretion is preserved . How? Mechanism Operates

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I have a question ; I don’t understand why inappropriate ADH secretion syndrome has high na+ in urine but water
intoxication has low na+ in urine. It was justified by basically the RAAS inhibition due to hypervolemia [during SIADH]
but why doesn’t water intoxication also inhibit RAAS? why doesn’t it cause the same response as they both cause an
increase in blood volume and pressure initially .

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 Further explanation:
Water toxicity in normal circumstances is rare as there is a precise regulation of the water content happens in the body.
However, excessive water ingestion & water intoxication may occur in the following conditions:

• Exercise (Drinking water after prolonged exercise replete water without correcting electrolyte losses)

• Psychogenic polydipsia (Craving water excessively due to a persistent sensation of thirst)

• Water drinking competitions
So whatever be the conditions, ADH responds accordingly. Since this patient is not having SIADH or ADH related problems,
with excessive ingestion of water within a short period, causes excess water to migrate to the site with increased solute
concentration (owing to diffusion). Thus the amount of intracellular water increases, causing the cells to swell. In the CNS,
the swollen neurons increase the intracranial pressure which leads to the symptoms of confusion, lethargy, headache, and
drowsiness as range of symptoms.

Since ADH acts properly in these patients, ADH secretion diminishes (Compensatory response)--- which enhances
voluminous urine production (ie urine having low Na concentration in it) without inhibiting RAAS. This is mainly because
sudden huge water ingestion dramatically alters the plasma osmolarity which affect ADH secretion (as we know changes in
osmolarity affects ADH secretion).

However in SIADH patients, (it is not that quick) and ADH being excessive already, keeps on reabsorbing water (volume
overload). This reduces RAAS response as compensatory mechanism and makes Na excretion more in urine----
hyponatremia worsens.

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 Can You explain the following:
How the vasa recta helps to maintain the cortico-
papillary gradient

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 Countercurrent Exchanger – Vasa Recta
Peritubular capillaries

Bowman’s
Capsule
Two limbs of VR (blood capillaries) are easily
permeable.
A large amount of fluid and solute exchange
occurs with little net dilution at medulla
Maintaining the Corticopapillary hyperosmotic Vasa Recta
gradient (prevents washing away of solutes
mainly Na & Cl from medulla)

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 Countercurrent Exchanger – Vasa Recta
Vasa Recta
300

Permeable
371 371 371 H2O
to Solutes
450 450 450
Salt & Water
530 530 530
633 633 633 H2O
739 739 739 Gradient
876 Salt would be
876 876 destroyed
1024 1024 1024 H2O
1203 1203 1203
Salt “Washed
Away’
1203
Case 3 – Tale of 2 Patients
Describe the importance of the generation of a hyperosmotic medullary interstitium to urinary concentration / Describe the role of the renal tubules in enabling urinary concentration by reabsorption of salt

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 Water Secreted then Water Reabsorbed
the Solutes Secreted

Countercurrent Exchanger – Vasa Recta

325 300

H2O 371 371 371 H2O

Ascending 450 450 450 Descending
Vessel Salt 530 Salt Vessel
530 530
H2O 633 633 633 H2O Water Secreted
Water
739 739 739 Solutes
Reabsorbed Salt Salt Reabsorbed
876 876 876
Solutes All
H2O 1024 1024 1024 H2O Passively
Secreted
1203 1203 1203
All Salt Salt Blood gets
Passively
viscous
1203 1203
Case 3 – Tale of 2 Patients
Describe the importance of the generation of a hyperosmotic medullary interstitium to urinary concentration / Describe the role of the renal tubules in enabling urinary concentration by reabsorption of salt

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 Countercurrent Exchanger – Vasa Recta (Summary)
Water Secreted then Reabsorbed – passively down Conc. Grad. – exchanging with interstitium
Solutes Reabsorbed the Secreted – passively down Conc. Grad. – exchanging with interstitium

Generally equal amounts of solutes and H20 are secreted as are reabsorbed
– maintaining the Corticopapillary salt gradient of the Interstitium

Only a small amount of solute is lost to the blood

This is dependent upon blood flow – Usually this slow:

Allows time for passive diffusion of solutes and Water

Case 3 – Tale of 2 Patients

Describe the importance of the generation of a hyperosmotic medullary interstitium to urinary concentration / Describe the role of the renal tubules in enabling urinary concentration by reabsorption of salt

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Q. I don’t understand what does it mean by reducing blood flow at vasa recta will decrease salt washout, so that more
salt retain in interstitium and create passive gradient for NaCl reabsorption (this sentence i understand but I’m not sure
about first sentence though).

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Normally the blood flow at the inner medulla is very low. (Mentioned in “urine concentration” class) : Medulla receives
sluggish blood flow (less than 5% of total RBF).
Now imagine, you have a situation, where blood volume in your body has decreased due to some reason. So what would be
body’s compensatory response and how kidney could impart its role?
Besides having several cardiac responses, Na regulation would happen (RAAS activated) and ADH secretion would be seen.
To make ADH role functionally effective, body must create efficient inner medullary gradient so that water can be
reabsorbed and volume could be preserved. RAAS also exert its multiple effects (Na reabsorption etc..). One of them is to
reduce vasa recta blood flow (By angiotensin-II) and thus reducing the potential scopes of urea wash out than normal.
During normal situation, hypertonic medullary environment is not that hypertonic and urea is washed out or is excreted
through urine.

Here, hypovolemia → so you have reduced blood flow to kidney (as most of the blood needs to stay in the main
circulatory system rather than in renal circulation) → reduces circulation blood flow at inner medulla.
Besides, Ang-II → reduce VR blood flow → In combination, these reduce urea washout → help hypertonic
environment → enhance passive reabsorption of water under ADH.

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##/## Join at: vevox.app ID: XXX-XXX-XXX Question slide

Dehydration increases the plasma concentration

of all the following hormones except
Vasopressin
##.##%
Angiotensin II
##.##%
Aldosterone
##.##%
Norepinephrine
##.##%
ANP
##.##%

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##/## Join at: vevox.app ID: XXX-XXX-XXX Results slide

Dehydration increases the plasma concentration

of all the following hormones except
Vasopressin
##.##%
Angiotensin II
##.##%
Aldosterone
##.##%
Norepinephrine
##.##%
ANP
##.##%

RESULTS SLIDE

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 Explanation:
Dehydration reduces water content, so likely to cause hyperosmolarity
& hypovolemia.

So ADH/vasopressin will be released to enhance water reabsorption at

kidney level. Pressure drop also enhances RAAS system to activate
which result in Angitensin II and aldosterone secretion

ANS system also be activated leading to NE release.

Atrial natriuretic peptide should not be released here as it enhance Na

loss and concomitant water content in urine.

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##/## Join at: vevox.app ID: XXX-XXX-XXX Question slide
A marathon runner who sweated a lot for last few hours, at the end of the event
would be subjected to a state of …………………….. dehydration and could develop
………………….. respectively
Hypertonic; Hypernatremia
##.##%
Isotonic ; Hyponatremia
##.##%
Hypotonic; hyponatremia
##.##%
Isotonic; hypernatremia
##.##%
Isotonic; normal Na concentration
##.##%

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##/## Join at: vevox.app ID: XXX-XXX-XXX Results slide
A marathon runner who sweated a lot for last few hours, at the end of the
event would be subjected to a state of …………………….. dehydration and could
develop ………………….. respectively
Hypertonic; Hypernatremia
##.##%
Isotonic ; Hyponatremia
##.##%
Hypotonic; hyponatremia
##.##%
Isotonic; hypernatremia
##.##%
Isotonic; normal Na concentration
##.##%

RESULTS SLIDE

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 Explanation:

In this situation water loss from body is more than the NaCl loss as sweating
itself is generally hypo osmotic in nature which happens in long distance
runners. This develops hypertonic/ hyperosmotic dehydration within the body.

So your body eventually have high Na conc that is you potentially develop
hypernatremia. Both ICF and ECF volume are decreased.
Impact may be seen as follows:

Hyperosmolar ECF=== movement of water out of brain cells===Headache,

agitation, restlessness ==== Needs early treatment.

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##/## Join at: vevox.app ID: XXX-XXX-XXX Question slide

In the presence of vasopressin, the greatest fraction of

filtered water is absorbed in the
Proximal tubule
##.##%
Loop of Henle
##.##%
Distal tubule
##.##%
Cortical collecting duct
##.##%
Medullary collecting duct
##.##%

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##/## Join at: vevox.app ID: XXX-XXX-XXX Results slide

In the presence of vasopressin, the greatest fraction of

filtered water is absorbed in the
Proximal tubule
##.##%
Loop of Henle
##.##%
Distal tubule
##.##%
Cortical collecting duct
##.##%
Medullary collecting duct
##.##%

RESULTS SLIDE

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 Magnitude of fluid absorption along the Nephron
Facultative water
reabsorption

Obligatory water
reabsorption
Nephron
Segment Normal Volume expanded Dehydrated
Proximal tubule 70% 70% 70%

Thin decending Limb 20% 20% 20%

Thin Ascending Limb 0% 0% 0%

Thick Ascending Limb 0% 0% 0%

Distal Tubule 3-5% 4% 5%

Collecting Duct 0-5% ~0 - 4% ~5%

Urine 0.8-1% up to 6% min 0.2%

1.5 l/day ~12 l/day ~0.3 l/day

Obligatory water reabsorption: Water will be reabsorbed as usual irrespective of

bodily condition (PCT + LOH)
Facultative water reabsorption: Water reabsorption or secretion is guided with
respect to fluid volume status of the body. (Mainly at distal kidney ie: DT and CD)

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##/## Join at: vevox.app ID: XXX-XXX-XXX Question slide
A person has developed hypokalemia due to potassium deficient
diet for few weeks. His potassium secretion can be decreased if
there is a likely rise in
Plasma renin
##.##%
Urinary flow rate
##.##%
Tubular Na reabsorption
##.##%
Plasma H+ Ion
##.##%
Plasma HCO3- ion
##.##%

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##/## Join at: vevox.app ID: XXX-XXX-XXX Results slide
A person has developed hypokalemia due to potassium deficient
diet for few weeks. His potassium secretion can be decreased if
there is a likely rise in
Plasma renin
##.##%
Urinary flow rate
##.##%
Tubular Na reabsorption
##.##%
Plasma H+ Ion
##.##%
Plasma HCO3- ion
##.##%

RESULTS SLIDE

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Please
attend few
questions.

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