Professional Documents
Culture Documents
Production
Long- Term
Regulation of
Blood Pressure
and body fluid
volume,
concentration, and
composition!
1
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
2
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)
3
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
4
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
6
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
8
Renin-Angiotensin- System
Made by Liver
renin
ACE in lungs
9
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
10
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
11
Late Distal Convoluted Tubule
Principal Cells Tubular Lumen
Na +
Na +
ATP
K+
K+
Cl -
Normal or high
K+ diet
acidosis
13
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
14
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
15
Inhibitors of Aldosterone
and Sodium Reabsorption
17
We must separate solute from solvent! Where will
this occur in the nephron?
What determines
how
concentrated the
urine will be?
21
Figure 28-8;
Guyton and Hall
Osmoreceptor
antidiuretic hormone
(ADH)-Thirst feedback
thirst
mechanism for
regulating extracellular
fluid osmolarity
Osmolality
Plasma volume
23
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
24
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)
25
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
26
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!
27
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
28
29
30
SNS can
directly
stimulate Na+
reabsorption in
tubule cells,
too!
31
Figure 26.9
32
Protein UP
HCT N.C.
Protein down
HCT N.C.
33
TYPE EXAMPLE ECF ICF OSMOLARITY HCT PROTEIN
35
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)
38
Diuretics- Early Distal CT
Thiazides
Inhibit Na/Cl
transporters- no salt
reabsorption.
Water stays in lumen
39
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.
40
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
41