1. Atrial natriuretic peptide Na+ and H2O reabsorption
Figure Mechanisms and consequences of ANP release.
Stretch of atria
of heart due to BP
Releases
Negative
feedback
Atrial natriuretic peptide
(ANP)
Targets
JG complex
of the kidney
Hypothalamus and
posterior pituitary
Adrenal cortex
Effects
Effects
Renin release*
ADH release
Aldosterone
release
Angiotensin II
Inhibits
Inhibits
Collecting ducts
of kidneys
Vasodilation
Effects
Na+ and H2O reabsorption
Results in
Blood volume
Results in
Blood pressure
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2. Influence of other Hormones
Estrogens:  Na reabs (like aldosterone)
 H2O retention during menstrual cycles and pregnancy
Progesterone:  Na+ reabsn (blocks aldosterone)
Promotes Na+ and H2O loss
Glucocorticoids:  Na+ reabsorption and promote edema
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3. Cardiovascular Baroreceptors
Baroreceptors alert brain of ↑ in BP
Sympathetic NS impulses to kidney decline 
Afferent arterioles dilate 
GFR increases 
Na+ and water output increase 
Reduced blood vol and pressure
© 2013 Pearson Education, Inc.

4. Figure Mechanisms regulating sodium and water balance help maintain blood pressure homeostasis.
Systemic
blood pressure/volume
Stretch in afferent
arterioles
Filtrate NaCl
concentration in ascending
limb of nephron loop
Inhibits baroreceptors
in blood vessels
(+)
(+)
(+)
Granular cells
of kidneys
(+)
Sympathetic
nervous system
Release
(+)
Renin
Systemic arterioles
Catalyzes conversion
Causes
Angiotensinogen
(from liver)
Angiotensin I
Vasoconstriction
Results in
Converting enzyme (in lungs)
Peripheral resistance
(+)
Angiotensin II
Posterior pituitary
(+)
(+)
(+)
Releases
Systemic arterioles
Adrenal cortex
ADH (antidiuretic
hormone)
Causes
Secretes
(+)
Vasoconstriction
Aldosterone
Collecting ducts
of kidneys
Results in
Targets
Causes
Peripheral resistance
Distal kidney tubules
Causes
H2O reabsorption
Na+ (and H2O)
reabsorption
Results in
Blood volume
(+) stimulates
Blood pressure
Renin-angiotensin-aldosterone
Mechanism
Neural regulation (sympathetic
nervous system effects)
ADH release and effects
© 2013 Pearson Education, Inc.

5. pH affects all proteins and biochemical reactions
Acid-base Balance
pH affects all proteins and biochemical reactions
Normal pH of body fluids
Arterial blood: pH 7.4
Venous blood and IF fluid: pH 7.35
ICF: pH 7.0
Alkalosis or alkalemia: arterial pH >7.45
Acidosis or acidemia: arterial pH <7.35
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6. Most H+ produced by metabolism
Acid-base Balance
Most H+ produced by metabolism
Phosphorus-containing protein breakdown releases phosphoric acid into ECF
Lactic acid from anaerobic respiration of glucose
Fatty acids and ketone bodies from fat metabolism
H+ liberated when CO2 converted to HCO3– in blood
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7. Acid-base Balance [H +] regulated by
Chemical buffer systems: rapid; first line
Brain respiratory centers: act within 1–3 min
Renal mechanisms: most potent, but require hrs to d to effect pH changes
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8. Acid-base Balance: Chemical Buffer Systems
Strong acids dissociate completely in water; dramatically affect pH
Weak acids dissociate partially in water; are efficient at preventing pH changes
Strong bases dissociate easily in water; quickly tie up H+
Weak bases accept H+ more slowly
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9. completely into its ions. A weak acid such as H2CO3 does not
Figure Dissociation of strong and weak acids in water.
A strong acid such as
HCI dissociates
completely into its ions.
A weak acid such as
H2CO3 does not
dissociate completely.
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10. Chemical Buffer Systems
Chemical buffer: compounds that act to resist pH changes when acid or base is added
Bind H+ if pH drops; release H+ if pH rises
Bicarbonate buffer system
Only important ECF buffer
2. Phosphate buffer system
3. Protein buffer system
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11. Bicarbonate Buffer System
If strong acid added:
HCO3– ties up H+ and forms H2CO3
HCl + NaHCO3  H2CO3 + NaCl
HCO3– concentration closely regulated by kidneys
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12. Bicarbonate Buffer System
If strong base added
It causes H2CO3 to dissociate and donate H+
H+ ties up the base (e.g. OH–)
NaOH + H2CO3  NaHCO3 + H2O
H2CO3 supply is almost limitless (from CO2 released by respiration) and subject to respiratory controls
© 2013 Pearson Education, Inc.

13. Phosphate Buffer System
Action identical to bicarb buffer
Dihydrogen phosphate (H2PO4–), a weak acid
Monohydrogen phosphate (HPO42–), a weak base
Unimportant in plasma
Effective in urine and ICF, where phosphate concentrations are high
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14. Protein Buffer System
Intracellular proteins are most plentiful and powerful buffers; plasma proteins also important
When pH rises, carboxyl (COOH) groups release H+
When pH falls, NH2 groups bind H+
Hemoglobin functions as intracellular buffer
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15. Physiological Buffering Systems
Respiratory and renal systems
Regulate amount of acid or base in body
Slower than chemical buffer systems
Have more capacity than chemical buffer systems
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16. Respiratory Regulation of H+
Hypercapnia activates medullary chemoreceptors
 Increased respiratory rate and depth
CO2 + H2O  H2CO3  H+ + HCO3–
Rising H+ activates peripheral chemoreceptors
More CO2 removed from blood
[H+ ] reduced
© 2013 Pearson Education, Inc.

17. Respiratory Regulation of H+
Alkalosis depresses respiratory center
Respiratory rate and depth decrease
[H+ ] increases
Respiratory system impairment causes acid-base imbalances
Hypoventilation  respiratory ________
Hyperventilation  respiratory ________
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18. Renal Mechanisms of Acid-Base Balance
Most important renal mechanisms
Conserving (reabsorbing) or generating new HCO3–
Excreting HCO3–
To reabsorb bicarbonate kidney must secrete H+
To excrete excess bicarbonate kidney must retain (not secrete) H+
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19. Primary active transport Secondary active transport
Figure Reabsorption of filtered HCO3– is coupled to H+ secretion.
Slide 1
CO2 combines with water
within the tubule cell, forming
H2CO3. 1
H2CO3 is quickly split, forming H+ and bicarbonate ion (HCO3−). 2
H+ is secreted
into the filtrate. 3a
Nucleus
Filtrate in
tubule
lumen
Peri-
tubular
capillary
PCT cell 3b
For each H+ secreted,
a HCO3− enters the peritubular capillary
blood either via symport with Na+ or via antiport with CI−.
ATPase 3a 3b 4
Secreted H+ combines with HCO3− in the filtrate, forming carbonic acid (H2CO3). HCO3− disappears from the filtrate at the same rate that HCO3− (formed
within the tubule cell) enters the peritubular capillary blood. 2 4
ATPase 5
CA * 1 CA 6
Tight
junction
Primary active transport
Transport protein 6
CO2 diffuses into the tubule
cell, where it triggers further H+
secretion. 5
Secondary active transport
The H2CO3 formed in the filtrate dissociates to release CO2 and H2O. CA
Carbonic anhydrase
Simple diffusion
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20. H2CO3 is quickly split, forming H+ and bicarbonate ion (HCO3−).
Figure New HCO3– is generated via buffering of secreted H+ by HPO42– (monohydrogen phosphate).
Slide 1
CO2 combines with water within the type A intercalated cell, forming H2CO3.
H2CO3 is quickly split, forming H+ and bicarbonate ion (HCO3−). 1 2
H+ is secreted into the filtrate by a H+ ATPase pump. 3a
Nucleus
Filtrate in
tubule
lumen
Tight junction
Peri-
tubular
capillary
For
each H+ secreted, a HCO3− enters
the peritubular capillary blood via an antiport carrier in a HCO3− -CI− exchange process. 3b 1 2 3a 3b
(new)
ATPase 4
Secreted
H+ combines with HPO42−
in the tubular filtrate,
Forming
H2PO4−. 4
Type A
intercalated
cell of collecting duct 5
out in urine
Primary active transport
Transport protein
Secondary active transport
The H2PO4−
is excreted
in the urine. 5
Ion channel
Simple diffusion
Carbonic anhydrase
Facilitated diffusion
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21. the filtrate, taking the place of H+ on a Na+ -H+ antiport carrier. 2a
Figure New HCO3– is generated via glutamine metabolism and NH4+ secretion.
Slide 1
PCT cells metabolize
glutamine to
NH4+and HCO3−. 1
This weak acid NH4+ (ammonium) is secreted into
the filtrate, taking the place of
H+ on a Na+ -H+ antiport carrier. 2a
For each NH4+ secreted,
a bicarbonate ion (HCO3−) enters the peritubular capillary blood via a symport carrier. 2b
Nucleus
Filtrate in
tubule lumen
Peri-
tubular
capillary
PCT tubule cells
Glutamine
Glutamine
Glutamine
Deamination,
oxidation, and
acidification
(+H+) 1 2a 2b
(new) 3
out in urine
ATPase
Tight junction
Primary active transport
Simple diffusion
The NH4+ is excreted in the urine. 3
Secondary active transport
Transport protein
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22. Abnormalities of Acid-Base Balance
All classed as respiratory or metabolic
Respiratory acidosis and alkalosis
Caused by failure of respiratory system to perform pH-balancing role
Single most important indicator is blood PCO2
Metabolic acidosis and alkalosis
All abnormalities not caused by PCO2 levels in blood; indicated by abnormal HCO3– levels
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23. Metabolic Acidosis and Alkalosis
Meta acidosis – low blood pH and HCO3–
Causes
Ingestion of too much alcohol ( acetic acid)
Excessive loss of HCO3– (e.g., persistent diarrhea)
Accumulation of lactic acid (exercise or shock), ketosis in diabetic crisis, starvation, and kidney failure
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24. Metabolic Acidosis and Alkalosis
Meta alkalosis much less common than meta acidosis
Indicated by rising blood pH and HCO3–
Causes; vomiting or intake of excess base (e.g., antacids)
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25. Effects of Acidosis and Alkalosis
Blood pH below 6.8  depression of CNS  coma  death
Blood pH above 7.8  excitation of nervous system  muscle tetany, extreme nervousness, convulsions, death often from respiratory arrest
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26. Respiratory and Renal Compensations
If acid-base imbalance due to malfunction of physiological buffer system, other one tries to compensate
Respiratory attempts to correct metabolic acid-base imbalances
Kidneys attempt to correct respiratory acid-base imbalances
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27. Respiratory Compensation
Changes in respiratory rate and depth
In meta acidosis
High H+ stimulate respiratory
Blood pH below 7.35 and HCO3– level low
As CO2 eliminated, PCO2 falls below normal
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28. Respiratory Compensation
Respiratory comp for meta alkalosis revealed by:
Slow, shallow breathing, allowing CO2 accumulation in blood
High pH (over 7.45), elevated HCO3– levels, PCO2 above 45 mm Hg
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29. Renal Compensation for Respiratory Acid-Base Imbalance
Hypoventilation causes elevated PCO2
Respiratory acidosis
Renal compensation indicated by high PCO2 (causes acidosis) and HCO3– levels (indicates kidneys compensating)
Respiratory alkalosis exhibits low PCO2 and high pH
Renal compensation is indicated by decreasing HCO3– levels
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