SSU Lecture 2

RDE SSU 2 Water and Electrolyte Balance

Aims & Content of this lecture• To continue providing you with a refresher

in renal physiology that later lectures covering renal measurement and pathophysiology will build upon.

• The role of antidiuretic hormone (ADH)• The renin-angiotensin-aldosterone system

(RAAS)• Role of the kidney in volume regulation• Control of acid-base balance by the kidneys• Final review of how the renal system

interacts with the cardiovascular and respiratory systems.

ADH also needed to concentrate urine: how does it work?

•Antidiuretic Hormone (ADH)/Arginine Vasopressin (AVP)

•Increases permeability of collecting ducts to H2O by inserting H2O channels (Aquaporins).

•Helps you make small amount of concentrated urine.

•Reabsorption of H2O increase urea conc. in tubule, increasing its recycling effect.•ADH allows rapid, graded control of urine conc. – v. sensitive.•ADH released in response to plasma osmolality and ECF volume – osmoreceptors and baroreceptors.

ADH (aka AVP)• Increased plasma osmolality

stimulates osmoreceptors in the hypothalamus that trigger the release of ADH, which inhibits water excretion.

• Increased osmolality stimulates a second group of osmoreceptors that trigger thirst, which promotes water intake.

• Other factors also trigger ADH release e.g. decreased effective circulating volume, decreased BP, pregnancy, pain, morphine, nausea, congestive heart failure (CHF) (due to reduced ECV).

• CHF may cause such retention of H2O = hyponatremia.

• Hyperaldosteronism = hypernatremia. Due to chronic volume expansion, where osmoreceptors become less sensitive to ADH, reducing ADH inappropriately.

Renin-angiotensin-aldosterone axis

• Principal factor controlling Ang II levels is renin release.

• Decreased circulating volume stimulates renin release via:– Decreased BP

(symp effects on JGA).

– Decreased [NaCl] at macula densa (“NaCl sensor”)

– Decreased renal perfusion pressure (“renal” baroreceptor)

Angiotensin II – important actions

• Stimulation of aldosterone release from adrenal cortex.

• Vasoconstriction of renal and other systemic vessels.

• Enhanced tubuloglomerular feedback – makes macula densa more sensitive.

• Enhance Na-H exchanger and Na channel function to promote Na reabsorption.

• Renal hypertrophy.• Stimulates thirst and ADH release by

acting upon hypothalamus.

Aldosterone• Aldosterone stimulates Na+

reabsorption and K+ excretion by the renal tubule.

• Aldosterone exerts indirect negative feedback on RAAS by increasing ECV and by lowering plasma [K+].

• Really important in conserving Na+ and water, but also really good at preventing massive swings in K+ levels.

Atrial Natriuretic Peptide (ANP)

• ANP promotes natriuresis (loss of sodium).• Atrial myocytes synthesise, store and release ANP

in response to stretch (low P volume sensor).• Major effect is renal vasodilatation. Increased blood

flow = increased GFR.• Thus, more Na+ reaches macula densa.• More Na+ excreted.

• May inhibit actions of renin, and generally opposes effects of angiotensin II.

Feedback systems involved in osmolality control

Comparison of systems controlling effective circulating volume and osmolality

What is sensed?

Effective Circulating Volume

Plasma Osmolality

SensorsCarotid sinus, aortic arch, renal afferent arteriole,

atria

Hypothalamic osmoreceptors

Efferent Pathways

RAAS, Symp NS, ADH, ANP ADH Thirst

EffectorShort term: heart, blood

vesselsLong term: Kidney

KidneyBrain:

drinking behaviour

What is affected?

Short term: Blood pressureLong term: Na+ excretion

Renal water

excretion

Water intake

Control of effective circulating volume

• Feedback control of effective circulating volume.

• A low effective circulating volume triggers 4 parallel effector pathways that act on the kidney.

• Either changes haemodynamics or changes Na+ transport by renal tubule cells.

ECF volume receptors• “Central” vascular sensors

– Low pressure (very important)• Cardiac atria• Pulmonary vasculature

– High pressure (less important)• Carotid sinus• Aortic arch• Juxtaglomerular apparatus (renal afferent arteriole)

• Sensors in the CNS (less important)• Sensors in the liver (less important)

N.B. Regulation of ECF volume = Regulation of body Na+. Thus, regulation of Na+ also dependent upon baroreceptors.

Another vital function of the kidneys: Acid-Base Balance

• Kidneys really important for acid-base balance, along with respiratory system.

• Again, another type of integrative physiology! (are you noticing a theme yet?)

• Important because all biochemical processes must occur within an optimal pH window.

• Prevent ACIDOSIS or ALKALOSIS.• Although the lungs excrete a large amount of

CO2, a potential acid formed by metabolism, the kidneys are crucial for excreting non-volatile acids.

• To maintain acid-base balance, kidney must not only reabsorb virtually all filtered HCO3

-, but must also secrete into the urine the daily production of non-volatile acids.

Sources of H+ gain and loss

• H+ Gain– CO2 in blood (combine with H2O via carbonic anhydrase)– Nonvolatile acids from metabolism (e.g. lactic)– Loss of HCO3

- in diarrhoea or non-gastric GI fluids– Loss of HCO3

- in urine

• H+ Loss– Use of H+ in metabolism of organic anions– Loss of H+ in vomit– Loss of H+ in urine– Hyperventilation (blow off CO2)

• Loss of H+ like gaining HCO3-

• Loss of HCO3- like gaining H+

HCO3- Reabsorption

(main physiological buffer)

• Kidneys alter/replenish H+ by altering plasma [HCO3-].

• HCO3- filtered then practically all reabsorbed under normal conditions.

• Prevents you gradually becoming acidotic because of metabolism. Gains = Losses, means maintain HOMEOSTASIS.

• The secreted H+ combines with filtered HCO3- in tubule to form CO2 and H2O.

Addition of new HCO3- to plasma by

secretion of H+

• When you use up filtered HCO3- in tubule and still have

excess H+ (acidosis), then you must combine H+ with another buffer e.g. HPO4

2-.• Unusual since lots of HCO3

- in tubular fluid!• Gives net gain of HCO3

- to plasma.

• Another way of adding HCO3

- to plasma by metabolising glutamine.

• Takes long time though, so usually only occurs in chronic acidosis e.g. diabetes.

Addition of new HCO3- to plasma by

excretion of ammonium (NH4+)

Normal urine & blood values:

• Urine pH ~ 6.0• Blood pH = 7.4

• Blood [HCO3-] = 24 mM

• Blood PCO2 = 40 mmHg

• Plasma osmolality = 285 mOsm/kg water• Urine osmolality (depends upon hydration

status) = 600 mOsm/kg water (note that this can vary between 50-1200 depending on water intake etc.)

Acid-base disorders

• Remember, these can be either respiratory or metabolic in nature.

• Respiratory ones can be chronic or acute; metabolic ones always chronic.

• Only chronic ones cause marked change in HCO3

-.

• Renal and respiratory systems work together reflexly to compensate for one another.

Final review of renal integration with respiratory and cardiovascular systems

RENAL SYSTEM

CARDIOVASCULAR SYSTEM

RESPIRATORY SYSTEM

Acid-base balance

Gas exchange, ACE

Effective circulating volume

control, ECF osmolality, blood

pressure All of these are constantly changing,

trying to maintain HOMEOSTASIS!

So, why do you need to know this?

• Problems in one system are often only noticed by appearance of problems in another.

• This is because of the integrated nature of these systems – they don’t operate in isolation.

• Means we can sometimes compensate for problems in another system via reflexes, but also means that when disease progresses, lots of problems in several systems can begin to appear.

• If we understand links between systems, we have more targets for drugs and other therapies to correct problems.

• May also target actual cause of problem, rather than just worrying about the symptoms. Scientists think laterally – medics have a tendency just to stay inside their little window of expertise. PY3002 is all about getting you to think independently and laterally.

• These three systems are probably the locations of most of the health-related problems you might encounter in whatever career you follow – regardless of whether you are a sports scientist or a physiologist.