Download AHS renal lecture2_Witney_13

Renal lecture 2
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Regulation of plasma ionic composition
Regulation of plasma osmolarity
Regulation of plasma hydrogen ion concentration
Removal of metabolic waste and foreign substances
• Regulation of salt and water balance
• Anti-diuretic hormone
• Renin- angiotension-aldosterone
Dr Alice Witney
Classification of Body Fluids
Dr Alice Witney
Ionic Composition of the Major
Body-Fluid Compartments
Dr Alice Witney
Concept of Balance
Input+production=
utilization+output
• If there is a positive balance, substances are
entering faster than they are exiting
• If there is a negative balance, substances are
exiting faster than they are entering
Dr Alice Witney
Water Steady State
• Amount Ingested = Amount Eliminated
• Pathological losses
vascular bleeding (H20, Na+)
vomiting (H20, H+)
diarrhea (H20, HCO3-).
Dr Alice Witney
Daily Salt Balance
Dr Alice Witney
Salt Balance
• Very important in regulating ECF volume
• Salt input occurs by ingestion
– Often not well controlled
• Salt balance maintained by outputs in
urine
– Salt also lost in perspiration and in feces
• Kidneys keep salt constant in ECF
– Glomerular filtration rate (GFR)
– Tubular reabsorption of sodium
Dr Alice Witney
Osmolarity
• Hypertonicity
– Cells shrink
– Causes
• Insufficient water intake
• Excessive water loss
• Diabetes insipidus
– Symptoms and effects
• Shrinking of neurons
– Confusion, irritability, delirium, convulsions, coma
• Circulatory disturbances
– Reduction in plasma volume, lowering of blood pressure, circulatory
shock
• Dry skin, sunken eyeballs, dry tongue
Dr Alice Witney
Osmolarity
• Hypotonicity
– Cells swell
– Causes
• Inability to excrete a dilute urine (renal failure)
• when water is rapidly ingested
• When excess water is retained in body due to inappropriate
secretion of vasopressin
– Symptoms and effects
• Swelling of neurons
– Confusion, irritability, lethargy, headache, dizziness, vomiting,
drowsiness, convulsions, coma, death
• Weakness (due to swelling of muscle cells)
• Circulatory disturbances (hypertension and edema)
Dr Alice Witney
Water Reabsorption:
Vasopressin (Anti-Diuretic Hormone; ADH)
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ADH is synthesised within the
Paraventricular Nucleus of the
hypothalamus.
hypothalamus
Paraventricular
nucleus
pituitary
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ADH is stored in the
posterior pituitary.
• ADH exerts a
pressor effect
(i.e., ↑BP)
Dr Alice Witney
Control of Vasopressin/ADH
release
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Left atrial receptors
Monitor pressure of blood flowing through (reflects ECF volume)
Upon detection of major reduction in arterial pressure, receptors
stimulate vasopressin secretion and thirst
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Osmoreceptors
Monitor osmolarity of plasma in CNS and stimulates vasopressin
secretion
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Angiotensin II
Stimulates vasopressin secretion and thirst when renin angiotensinaldosterone mechanism is activated to conserve Na+
Dr Alice Witney
Vasopressin (Anti-Diuretic Hormone; ADH)
hypothalamus
1. Dehydration or salt ingestion
2. ↑ Blood osmolarity
3. Stimulates osmoreceptors
in the hypothalamus
pituitary
↓ BP
5a. Causes vasoconstriction
4. Triggers ADH release
from the pituitary
 ↑ TPR
5b. Promotes water retention by the kidney
Dr Alice Witney
 ↑ BP
 ↑ Blood Volume
Dr Alice Witney
How does ADH work?
(1) ADH binds to receptor on
membrane of principal cell
(2) Activation of a G protein
activates enzyme to catalyse
cAMP
(3) Activates protein kinase A
(4) Stimulates insertion of new
water channels
Dr Alice Witney
DIABETES INSIPIDUS
Kidneys stop conserving water
Thirst
Dehydration
Damage to hypothalamus
Low ADH
Dr Alice Witney
Urine Excretion
• Depending on the body’s state of hydration,
the kidneys secrete urine of varying concentrations.
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Too much water in the ECF establishes a hypotonic ECF.
A water deficit establishes a hypertonic ECF.
• A large, vertical osmotic gradient is
established in the
interstitial fluid of the medulla (from 100 to
1200 mOsm/liter to 1200 mOsm/liter).
This increase follows the hairpin loop of
Henle deeper into the medulla.
• This osmotic gradient exists between the
tubular lumen and the surrounding
interstitial fluid.
Dr Alice Witney
Counter-current Multiplier
Figure 19.7 Pg 542 (3rd Edition Germann & Stanfield)
Dr Alice Witney
18:02:09
Dr Alice Witney
18:02:09
Dr Alice Witney
Na+ Reabsorption
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An active Na+ - K+ ATPase pump
in basolateral membrane is
essential for Na+ reabsorption
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Of total energy spent by kidneys,
80% is used for Na+ transport
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Na+ is not reabsorbed in the
descending limb of the loop of
Henle
Tubule
area
% of Na+
Role of Na+
reabsorbed reabsorption
Proximal
tubule
67%
Plays role in
reabsorbing
glucose, amino
acids, H2O, Cl-,
and urea
Ascending
limb of the
loop of
Henle
25%
Plays critical role
in kidneys’ ability
to produce urine
of varying
concentrations
8%
Variable and
subject to
hormonal
control; plays
role in regulating
ECF volume
Distal and
Water follows reabsorbed sodium collecting
tubules
by osmosis which has a main
effect on blood volume and blood
pressure
Dr Alice Witney
Sodium Reabsorption:
Aldosterone
• Sodium is the primary solute in ECF
• Critical to the function of excitable cells
• Regulation of sodium through reabsorption
• Always actively reabsorbed
Dr Alice Witney
Regulation of Sodium Reabsorption and Balance
• Na+ reabsorption in the proximal tubule is unregulated
Therefore, regulation of GFR can contribute to Na+ regulation
• Na+ reabsorption in the distal tubule is under hormonal control
Aldosterone (increases Na+ reabsorption)
Atrial Natriuretic Peptide (decreases Na+ reabsorption)
Dr Alice Witney
RAAS
• Renin-angiotensin-aldosterone system
• Most import and best known hormonal
system involved in regulating Na+
Dr Alice Witney
Factors Stimulating Renin Release
afferent
arteriole
macula densa
distal
tubule
JG cells (stretch sensitive)
Dr Alice Witney
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RAAS
2,3
4
5
1. Angiotensinogen produced by liver
2. Low BP and High sympathetic
activity stimulate renin secretion
3. Decreased Na+ stimulate renin
4. Angiotensin I produced
5. Angiotensin II produced
Dr Alice Witney
steroid
Aldosterone
distal tubule
adrenal
gland
Na+
K+
adrenal
medulla
adrenal
cortex
Dr Alice Witney
Aldosterone
renin
angiotensin
system
collecting
duct
How does aldosterone work?
Aldosterone:
1a) Stimulates the
opening of sodium
channels and
potassium channels
1b) Stimulates
synthesis and
insertion of
sodium/potassium
pumps
Dr Alice Witney
Roles of Angiotensin II: 4 mechanisms
Increase Blood Pressure
Dr Alice Witney
RAAS
Dr Alice Witney
• At the end of this lecture you should:
• Understand the role of ADH in the control of water
balance/plasma volume and thus blood pressure
• Be familiar with the RAAS
• Understand the role of aldosterone in salt balance
• Know the actions of angiotensin II
Dr Alice Witney
Dr Alice Witney