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Hormonal Control of Urine

Production
Long- Term
Regulation of
Blood Pressure
and body fluid
volume,
concentration, and
composition!

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How can we alter osmolality?
How can you make a
fluid more
concentrated?
Solute
Solvent- this changes
volume
How can you make a
fluid more dilute?
Solute
Solvent- this changes
volume
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Hormonal regulation of Osmolarity
(And Blood Volume/Pressure)
ADH-water control
Angiotensin II- solute
and water control
Aldosterone- solute
and water control
Atrial Natriuretic
Peptide (ANPa.k.a
atriopeptin)

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ADH
Made in hypothalamus
and released from
posterior pituitary
Increases water
permeability of principal
cells and collecting ducts
Increases activity of Na+-
K+-2Cl- transporter
Increases urea
permeability of inner
medullary duct

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Collecting Duct- tapping into the water reserve
How much water is left to reabsorb?
Tubular Cells Tubular Lumen
H20 (depends
on ADH)

Aquaporin-3 Aquaporin-2
H20 Aquaporins H20

ADH cAMP More water reabsorbed=


Vesicle concentrated, scant urine
V2 receptor
Less water reabsorbed=
less concentrated,
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copious urine
Copyright2006byElsevier,Inc.
Stimuli for ADH Secretion and Thirst
Increased osmolarity
Decreased blood volume
(cardiopulmonary reflexes)
Decreased blood pressure
(arterial baroreceptors)
Other stimuli:
dryness of mouth
nausea
Fever
Burns
excessive sweating
vomiting, or diarrhea
severe blood loss

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Factors that decrease
ADH and Thirst
Decreased osmolarity
Increased blood volume
(cardiopulmonary reflexes)
Increased blood pressure
(arterial baroreceptors)
Other factors:
alcohol (inhibits ADH!!!)
Gastric distention (inhibits
thirst)
A decrease in ADH means copious
amounts of urine of dilute
concentration Urea 7
Regulation of Sodium and water
Balance: Angio II & Aldosterone
The renin-angiotensin mechanism
triggers the release of aldosterone
This is mediated by the
juxtaglomerular apparatus, which Sympathetic
releases renin in response to: nerve fiber
Sympathetic nervous system
stimulation
Decreased filtrate osmolality
Decreased stretch (due to
decreased blood pressure) Juxtaglomerular
cells
Renin catalyzes (ultimately) the Macula densa
production of angiotensin II, which
prompts aldosterone release

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Renin-Angiotensin- System

Made by Liver
renin
ACE in lungs

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Angiotensin II Increases Na+ and
Water Reabsorption
Stimulates aldosterone release
Directly increases Na+ reabsorption (proximal, loop, and in
principal cells of late distal convoluted tubules)
Constricts efferent arterioles
Helps to maintain GFR and decreases peritubular capillary
hydrostatic pressure
more reabsorption
Ang II Ang II

Na+ Na+
ATP
K+ H+
Interstitial Na+
Fluid Tubular
HCO3-
Lumen
Ang II
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Regulation of Sodium/ Potassium Balance:
Hyperkalemia and
Aldosterone
hypokalemia can:
Disrupt electrical
conduction in the heart
Lead to sudden death
Increased K+ in the ECF
(hyperkalemia) around the
adrenal cortex causes:
Release of
aldosterone leads to
K+ secretion
Potassium controls its
own ECF concentration
via feedback regulation of
aldosterone release

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Late Distal Convoluted Tubule
Principal Cells Tubular Lumen

Na +
Na +
ATP
K+
K+
Cl -

When aldosterone levels are high, all


remaining Na+ is actively reabsorbed (last 8%)
Aldosterone Aldosterone stimulates potassium ion secretion
by principal cells
For each Na+ reabsorbed, a K+ is secreted
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Copyright2006byElsevier,Inc.
Low K+ diet only
Alkalosis!

Normal or high
K+ diet
acidosis

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Conns Cushings
Hyperaldosteronism
Hyperadrenalism-too much
Hypernatremia aldosterone and
Hypokalemia (low glucocorticoids
Hypernatremia
potassium) hypokalemia
Hypertension Hypertension
Increased glucocorticoid
production, resulting in excess
blood sugar levels (resembling
Diabetes Mellitus)
Increased androgen
production, resulting in more
masculinizing signs
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Addisons Disease
Primary adrenal
insufficiency not enough
aldosterone and
glucocorticoids
Hypoaldosteronism
Low blood pressure
Low sodium (hyponatremia)
High potassium
(hyperkalemia)
Mild acidosis
Decreased glucocorticoid
hormones, low blood sugar
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Inhibitors of Aldosterone
and Sodium Reabsorption

Atrial natriuretic peptide (ANP)


Increased Na+ concentration (osmolality)
ACE inhibitors (captopril, benazipril, etc)
Ang II antagonists (losartan, etc.)
decrease aldosterone
directly inhibit Na+ reabsorption of reserve
decrease efferent arteriolar resistance

Natriuresis and Diuresis + Blood Pressure


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Atrial Stretch Reflexes and ANP
Located in the atria of the heart.
Released due to increased ECF
volume (stretch receptors in atria
detect increased chronic venous
return)
ANP
Vasodilation of afferent arterioles
Vasoconstriction of efferent
arterioles
Increased GFR!
directly inhibits Na+ reabsorption
inhibits renin release (and hence,
angio II production) and
aldosterone formation
Reduces ADH release
helps to minimize blood volume
expansion through potent diuretic
and natriuretic effects

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We must separate solute from solvent! Where will
this occur in the nephron?

Formation of a Formation of a Dilute


Concentrated Urine- Urine-diuresis
antidiuresis Continue electrolyte
Continue electrolyte reabsorption
reabsorption Decrease water
Increase water reabsorption
reabsorption
Maximal urine Minimal urine
concentration concentration
= 1200 - 1400 mOsm / L = 50 - 70 mOsm / L
(specific gravity ~ (specific gravity ~
1.030) 1.003)
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Obligatory Water loss-Just how
concentrated can the urine get?
The minimum urine volume in which the excreted solute
can be dissolved and excreted.
Obligatory water loss reflects the fact that:
Kidneys excrete 600-1400 mOsm of solutes to
maintain blood homeostasis
Urine solutes must be flushed out of the body in
water Example:
If the max. urine osmolarity was 1200 mOsm/L,
and a minimum of 600 mOsm of solute must be
excreted each day to maintain electrolyte balance,
the obligatory urine volume is:
600 mOsm/d = 0.5 L/day
1200 mOsm/L 19
Water, water everywhere
Nor any drop to drink
(Coleridges: The Rime of the ancient Mariner)
Depending on the location, seawater
varies from 2000-2400mOsm (8x that of
plasma!)
You are dehydrated from being at sea-
you drink 1L of seawater
(2400mOsmoles!)
Your blood plasma now has a higher
osmolality.
Maximum you can concentrate your
urine ~1200mOsm-dont forget the
600mOsmoles you MUST excrete for
the day!
3000/1200= 2.5L (thats 1. 5L more than
what you drank!)
Hey, Bear, should you really be drinking
that urine?
1200 + 600= 1800/1200= 1.5L! Thats
0.5 L more than what he drank!
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Steps in production of a
HYPER-osmotic urine
How does the
kidney make a
urine more
concentrated
than blood? ADH!

What determines
how
concentrated the
urine will be?
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Figure 28-8;
Guyton and Hall

Osmoreceptor
antidiuretic hormone
(ADH)-Thirst feedback
thirst
mechanism for
regulating extracellular
fluid osmolarity

Osmolality
Plasma volume

/Scant urine and HIGH urine osmolarity 22


With ADH around we create a
scant, concentrated urine

TAL- more solute reabsorption


Principal cells of LDCT and collecting
duct insert AQP2
More urea reabsorption of medullary
duct

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Syndrome of inappropriate ADH
(SIADH)
Circulating levels of ADH
are inappropriately HIGH
Head injury or tumors
(lung)
Urine hyperosmotic
Plasma osmolarity
decreased
Demeclocycline inhibits
ADH activity in kidney

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Production of a
Hypo-osmotic urine
Low levels of ADH
PCT not affected: 67%
of solute and water
reabsorbed
TAL- water not
reabsorbed anyway
EDT- solute reabsorption
continues (diluting)
LDT and collecting
ducts- DO NOT express
AQP2 gene (no water
permeability)

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Diabetes Insipidus-bland urine of high flow
Too little ADH
Polydypsia (high thirst)
Polyuria (high urine output)
Urine osmolality?
Plasma osmolality?
1) Central Diabetes Insipidus head injury
Results from decreased production of ADH by the
CNS
CD, therefore, has poor permeability to water and
leads to diuresis
dDAVP- 1-deamino-8-D-arginine vasopressin
2) Nephrogenic Diabetes Insipidus
Deals with problem of nephron to sense ADH and
malfunctioning ADH receptors in the Collecting Duct
CD, therefore, has poor permeability to water
Give thiazide diuretics

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Lets go through the hormones again, but
with respect to solute maintenance
Sodium salts most abundant in
ECF:
Account for 90-95% of all solutes
in the ECF
Sodium is the only cation
exerting significant osmotic
pressure
Changes in plasma sodium
levels affect:
Plasma volume, blood pressure
ICF and interstitial fluid volumes
Renal acid-base control
mechanisms are coupled to
sodium ion transportreview
how!

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REGULATION OF Na+
BALANCE
Sympathetic nerve activity- more Na+
reabsorption by PCT
R-A-A system: more sodium
reabsorption
Atriopeptin (ANP: Atrial natriuretic
peptide)- increases GFR and
decreased Na+ reabsorption
Starling forces in peritubular capillaries
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SNS can
directly
stimulate Na+
reabsorption in
tubule cells,
too!

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Figure 26.9
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Protein UP

HCT N.C.
Protein down

HCT N.C.

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TYPE EXAMPLE ECF ICF OSMOLARITY HCT PROTEIN

ISO DIARRHEA; BURN DOWN N.C. N.C. UP UP


CONTRACTION

HYPER SWEATING; DIABETES DOWN DOWN UP N.C. UP


CONTRACTION INSIPIDUS; dehydration

HYPO ADRENAL DOWN UP DOWN UP UP


CONTRACTION INSUFFICIENCY
Abuse of diuretics

ISO INFUSION OF UP N.C. N.C. DOWN DOWN


EXPANSION ISOOSMOTIC NACL
HYPER HIGH NACL INTAKE UP DOWN UP DOWN DOWN
EXPANSION Conns ; Cushings
HYPO SIADH UP UP DOWN N.C. DOWN
EXPANSION

Which rows are hypernatremia? Which rows show hyponatremia?


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Hypertension
Primary- unknown cause. Treat the
symptoms-diuretics, ace inhibitors,
calcium channel blockers
Secondary- some other physiological
event triggers the hypertension
Goldblatt: renin released
inappropriately. Leads to cascade
and ultimately increased blood
pressure and hypertrophied heart
muscle (CHF).
Anything that leads to decreased
RBF/ low GFR will lead to renin
release.
Anorexia, blockage in renal
artery, etc.

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DIURESIS-more water flow
Decreasing the amount of solutes
reabsorbed in the tubules
increases the water in the tubule
and thus more urine output
diabetes mellitus (sweet urine of
high flow): unreabsorbed glucose
in tubules causes diuresis and
water loss
Lack of insulin or failure of insulin
to work (hyperglycemia)
High tubular loads and Tm for
glucose is maxed
Polyuria
Glucosuria and ketonuria
Polydipsia (high thirst)

Many types of diuretics to cause


changes in water reabsorption by
altering solute reabsorption
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OSMOTIC DIURETIC-
Mannitol- simple sugar, derived
from mannose.
Is small and freely filtered into
kidney tubules and not harmful to
pt.
Given IV verses eaten
To make it osmotic diuretic, it must
not be reabsorbed. It must then
stay in tubule lumen.
(OBLIGATORY WATER LOSS!)
Water stays in tubule to keep
concentration at 300 mOsmolal.
Water and mannitol is then
excreted.
Mannitol makes pt excrete more
water.
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Diuretics- thick ascending loop
Furosemide, aka
of Henle
Lasix
Inhibits the Na+K+CL-
transporters so the
medullary interstitial gradient
no longer exists
Water remains in the lumen
Very potent
Affects K+ balance, so risk of
hypokalemia (which can
affect RMP of excitable cells
& cause hyperpolarization.

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Diuretics- Early Distal CT
Thiazides
Inhibit Na/Cl
transporters- no salt
reabsorption.
Water stays in lumen

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Diuretics- late DCT (aldosterone inhibitors)
Spironolactone
Decreases numbers of Na/K
pumps on basolateral membranes
so that NaCl reabsorption is blocked.
Results in more salt excreted (&
water follows salt out so more water
is also excreted)
Pros: prevents loss of K+
(potassium sparing diuretic).
Often used in conjunction with
Loop diuretic
Cons: can lead to hyperkalemia and
Anti-androgen effect!! Female
athletes use it to mask steroid use!
Men have gynecomastia.

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Diuretics- late DCT (sodium inhibitors)
Amiloride
Blocks Na+ channels on
luminal membranes so
that less Na+ is able to
enter the tubule from the
lumen in the first place.
Also potassium sparing
used with loop diuretic
Therefore, more is
excreted and water
follows

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