Renal Lecture 4 and 5 Flashcards Preview

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How much of our body weight is water

60% (55% for females)


How is water divided between extracellular fluid and intracellular fluid

1. ECF: 1/3 of water weight, or 0.2 of total body weight
- 3/4 of ECF is interstitial fluid and 1/4 is plasma
2. ICF - 2/3 of water weight or 0.4 of total body weight


How does water transfer between ICF and ECF

Through the cell membrane by osmotic gradient


How does water transfer between interstitial fluid and plasma

Through the capillary wall by osmotic gradient, oncotic pressure, or hydrostatic pressure


Describe the distribution of ion concentration between the ECF and ICF

Na -> much higher ECF
K -> much higher ICF
Ca -> much higher ECF, but very low compared to Na and K
Cl- much higher ECF
HCO3- -> higher ECF, but much lower compared to others
Pi -> much higher ICF
pH -> 7.4 ECF 7.1 ICF


What rapidly changes osmolarity of ECF

eating and drinking, as the ECF is in contact with outside world


What is the osmotic gradient between the two compartments?

0, as there is no net movement (always in equilibrium


Units for osmotic concentration

Units of:
1. osmolarity: mOsm/L
2. osmolality: mOsm/kg H2O


What is more accurate, osmolarity or osmolality?

Osmolality because it is not affected by changes in temperature


Expression for osmotic concentration

no. dissociated particles x concentration of solute = nC


Expression for osmotic pressure

(mmHg)= pi = RTnC


Effective osmotic gradient

= (reflection coefficient) x no. dissociated particles x change in concentration


Effective osmotic pressure gradient

osmotic pressure change = reflection coefficient * RTn(change in C)


Hypotonic cell

Cell swells from added water, decreased osmolarity


Hypertonic cell

Cell shrinks from less water, increased osmolarity


Isotonic cell

Cell is normal, concentration equalized


Water comes into total body water by

Fluids, food, and metabolism (2500 ml/d)


Total body water goes

Insensible losses (skin, lungs) - 700ml/d
Urine - 500-2000ml/d (below 500 is renal failure)
Feces and sweat - 300ml/d


What regulates plasma osmolality?

Changes in water intake (THIRST) - increased H2O intake counteracts hyperosmolality
Changes in water excretion (ADH) - water takin in is retained by kidney (ADH)


Role of hypothalamus in water intake and retention

Increased osmolality can lead to:
1. Thirst osmoreceptor (brain) -> thirst -> h2o intake -> free water -> increased osmalality.
or: increased sodium appetite, cell volume decreases.
2. AVP osmoreceptor -> AVP neurons (PVN and SON) -> AVP -> kidneys -> less H20 excretion -> free water -> increased osmolality



Antidiuretic hormone (ADH), or vasopressin, acts on the kidneys to regulate the volume and osmolality of urine. When plasma ADH levels are low, a large volume of urine is excreted (diuresis), and the urine is dilute.* When plasma levels are high, a small volume of urine is excreted (antidiuresis), and the urine is concentrated.


Where is ADH synthesized

It is synthesized in neuroendocrine cells located within the supraoptic and paraventricular nuclei of the hypothalamus.* The synthesized hormone is packaged in granules that are transported down the axon of the cell and stored in nerve terminals located in the neurohypophysis (posterior pituitary).


ADH set point, or osmotic threshold

The set point of the system is the plasma osmolality value at which ADH secretion begins to increase. Below this set point, virtually no ADH is released. The set point varies among individuals and is genetically determined. In healthy adults, it varies from 275 to 290 mOsm/kg H2O (average, ≈280 to 285 mOsm/kg H2O).


Increased plasma osmolality on pH

Increased stimulation of thirst, increased plasma ADH levels.
Because there are separate cells in the anterior hypothalamus that are exquisitely sensitive to changes in body fluid osmolality and therefore play an important role in regulating the secretion of ADH.* These cells, termed osmoreceptors, appear to behave as osmometers and sense changes in body fluid osmolality by either shrinking or swelling. The osmoreceptors respond only to solutes in plasma that are effective osmoles


Explain how baroreceptors have an effect on ADH release

They act as inhibitors. When activated, baroreceptors send signals to the vasomotor centre to inhibit output.
When there is a decline in baroreceptor activity, (decreased BP and circulating volume) vasomotor centre is activated. Ensures we are not losing water. Sends signal to periphery to central site and stimulates ADH production. This boosts up ECF volume. Once volume is controled, comes back to normal and baroreceptors are inactive.


Do baroreceptors have an effect if there is an overall increase in BP or volume?

No, only act when there is a decrease, and thats when they want high ADH concentration.


Compare effects of hemodrynamics on osmotic threshold

10% decrease in pressure/volume -> Lower and steeper osmotic threshold
10% increase in pressure/volume = edema -> lhigher and more gradual osmotic threshold


Diabetes inspidus

Inadequate release of ADH from the posterior pituitary results in the excretion of large volumes of dilute urine. To compensate for this loss of water, the individual must ingest large volumes of water to maintain constant body fluid osmolality. If the individual is deprived of water, the body fluids will become hyperosmotic. This condition is called central diabetes insipidus. In nephrogenic inspidus, the kidney dpesn't respond well to ADH, such as having no receptors, but has the same diabetes inspidus effect.


Primary action of ADH

The primary action of ADH on the kidneys is to increase the permeability of the collecting duct to water. In addition and importantly, ADH increases the permeability of the medullary portion of the collecting duct to urea. Finally, ADH stimulates reabsorption of NaCl by the thick ascending limb of Henle’s loop, the distal tubule, and the collecting duct.


Mode of primary action of ADH

1. ADH binds to a receptor on the basolateral membrane of the cell. This receptor is termed the V2 receptor
2. Binding to this receptor, which is coupled to adenylyl cyclase via a stimulatory G protein (Gs), increases intracellular levels of cAMP.
3. The rise in intracellular cAMP activates protein kinase A (PKA), which ultimately results in the insertion of vesicles containing aquaporin-2 (AQP2) water channels into the apical membrane of the cell, as well as the synthesis of more AQP2
4. With the removal of ADH, these water channels are reinternalized into the cell, and the apical membrane is once again impermeable to water. This shuttling of water channels into and out of the apical membrane provides a rapid mechanism for controlling permeability of the membrane to water.


Describe the urinary concentrating mechanism

Descending limb:
Outer medulla - NaCL causes H2O to be absorbed
Inner medulla - more H2O absorbed (urea) in interstitial compartment, raising osmolarity.
Ascending limb:
Inner medulla - NaCl diffuses out with gradient.
Outer medulla - Na and Cl ions transported out
Distal tubule:
-ADH makes water leave, more concentrated
-some urea leaves near collecting tubule, and of course more water


Describe the change in interstitial osmolarity from cortex to medullary tip of nephron

Outer medulla =400
Inner medulla=600


What two things happen to continuously reabsorb water?

1. NaCL reabsorbed by ascending limb
2. Urea (water) reabsorption in descending limb and medullary conducting duct


Where does ADH come into play

The late distal tubule, where there is a huge osmotic gradient (low inside, need to take water out)


What happens if you interfere with Na transport in loop of Henle

You interfere with ability to concentrate urine (will be more dilute)


What happens if you interfere with urea production

You interfere with concentating urine.


Summarize the response to dehydration

Deprive of H2O -> Increase plama osmolarity -> stimulates osmoreceptors in anterior hypothalamus...
1. Increrased thirst and drink H2O so decrease in plasma osmolarity
2. Increased ADH secretion from posterior pituitary -> Increased H2O permeability of principal cells in late distal tubule and collecting duct -> Increased H2O reabsorption -> Increased urine osmalarity and decreased urine volume -> decreased plasma osmolarity toward normal


Summarize the response to rehydration

Drink H2O so Decreased plasma osmolarity -> inhibits osmoreceptors in anterior hypothalamus ->
1. Decreased thirst, decreased drinking, increase plasma osmolarity toward normal
2. Decreased ADH secretion from posterior pitiuitary, Decreased H2O permeability of principal cells, Decreased H2O absorption, Decreased urine osmolarity and increase urine volume so that increased plasma osmolarity toward normal occurs


What happens when total body sodium is increased

ECF sodium concentration is increased, and thus ECF osmolarity. Next, 3 things can happen:
1. Increase ICF volume, increase ECF volume 2. Stimulate thirst, water intake, and increase ECF volume
3. Stimulate ADH, reabsorb water, increase ECF volume
The ECF volume increased at a steady state with the steady state of sodium balance at 10 fold the normal sodium intake and secretion.


An example of edema caused by increased venous pressure

Standing, which causes edema in the dependent limbs


An example of edema caused by decreased plasma protein concentration

Decreased synthesis (liver disease)
Decreased intake (protein malnutrition)
Increased excretion (nephrotic syndrome)


An example if edema caused by increased Kf

Inflammation and burn


What types of changes will decrease Na excretion?

Changes in hemodynamics and tubule transport


What will sense a decrease in effective circulating volume?

Baroreceptors, such as in the aortic arch and carotid sinus. Will send signals to the sympathetic division of the ANS and posterior pituiitary.


What will stimulate the proximal tubule to reabsorb sodium?

Angiotensin II and NE


What will the sympathetic division do when tstimulated by baroreceptors?

Stimulate juxtaglomerular apparatus (JGA) to produce renin from its afferent cells and granular cells.


Explain the renin-angiotensin-aldosterone system.

So the kidney secretes renin, which cleaves angiotensinogen from the liver into 2 amino acids called angiotensin I. Angiotensin I encounters a converting enzyme in the lungs to be made into angiotensin II. Angiotensin can act directly on kidney for sodium reabsorption, or go through adrenal cortex to increase aldosterone, which will also increase sodium reabsorption.


What else, besides in terms of aldosterone, can angiotensin II do.

Cause vasoconstriction to increase BP, cause increase AVP in brain to increase H2O reabsorption, and cause thirst to increase H2O intake. All these together with sodium reabsorption will lead to normal effective arterial blood volume.


What will happen to blood pressure if there is too much angiotensin II

Since it causes vasoconstriction (blood vessels), blood pressure would increase.


How does aldosterone work?

Aldosterone stimulates Na reabsorption in the thick ascending limb of Henle's loop, distal tubule and collectinng duct. There is an increase in opened sodium channels and Na/K ATPase channels. It is able to do this my acting on the mineralocorticoid receptor of cells, which stimulates transcription of certain proteins that make up these channels, mitochondrial enzymes, and Na-K pumps.


When BP decreases, how does this affect renin release?

1. Decrease in afferent arteriole pressure to stimulate intrarenal baroreceptors to increase renin release.
2. Decrease in afferent artiole pressure to decrease in glomerular capillary pressure to decreased glomerular filtration rate to decreased tubular flow rate to macula densa cell in the distal tubule to stimulate renin release
3. Systemic barorecptors activate renal sympathetic nerve activity which directly innervates renin release


What has a negative effect on renin release?

Increase AII in blood circulation (feedback, as renin makes AII)


ACE inhibitors

Block the converting enzyme in the lungs that switches AI to AII.


AT1 Receptor Blockers

Block effects of AII and minimizes binding to receptors to minimize vasoconstriction and spike in BP.



Synthesized by myocytes of atria, atrial natriuretic peptide is released when the atria are distended to reduce BP and increase NaCl and water excretion by the kidneys and reduce ECF volume. So, when there is a decrease in ANP release, sodium excretion is inhibited to counteract decreased effective volume.


A decrease in Na excretion

Leads to increased renal Na retention, counteracting decreased effective circulating volume


What are the renal mechanisms of ANP when it is released due to increased effective circulating volume

1. Inhibits renin release, and thus angiotensin II and aldosterone to increase Na and water excretion
2. Stimulates afferent arteriole diameter to increase glomerular filtration rate and increase Na and water excretion
3. Inhibit ADH to inihibit collecting tubule Na and water reabsorption to increase Na and water excretion/


Acts as a powerful vasoconstrictor

Renin-angiotensin, sympathetic nerve activitym vasopressin (ADH), and endothelin. Are antinaturetics. Decrease sodium and water excretion, leads to retention.


Acts as a powerful vasodilator

ANP, nitric oxide, prostaglandins. Are naturetics. Increase sodium and water excretion.


What is a substance that mimics the effects of ANP



Loop diuretics

Inhibit resorption of water and sodium from loop of Henle


Thiazide diuretics

Inhibit Na CL channel in distal tubule Used to treat high BP.


K-Sparing Diuretics

Do not promote secretion of potassium in collecting duct into the urine so that it stays in the principal cell. Thus, more H2O and Na excretion. Weak.