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EC questions
• What does ICF stand for?
• a chemical compound that dissociates into
  ions in water is called an______.
• is sodium concentration higher in the ECF or
  ICF?
• a sensation of thirst causes us to:




                                                 1
Describe the major fluid
compartments including intracellular,
extracellular, intravascular and
interstitial.
Total body water
           Volume = 40 L
           60% body weight    Extracellular fluid (ECF)
                              Volume = 15 L
                              20% body weight




Intracellular fluid (ICF)     Interstitial fluid (IF)
Volume = 25 L                 Volume = 12 L
40% body weight               80% of ECF




                                                        Figure 26.1
• Describe the regulation of water intake and
  output
Regulation of Water Intake
• Thirst mechanism is the driving force for
  water intake
• The hypothalamic thirst center
  osmoreceptors are stimulated by
   – Plasma osmolality of 2–3%
   –Angiotensin II or baroreceptor input
   –Dry mouth
   –Substantial decrease in blood volume or
    pressure
Regulation of Water Intake
• Drinking water creates inhibition of the
  thirst center
• Inhibitory feedback signals include
   –Relief of dry mouth
   –Activation of stomach and intestinal
    stretch receptors
• Most of the body’s water is
1. Intracellular
2. Intravascular
3. interstitial




                                7
Regulation of Water Output
• Obligatory water losses
   –Insensible water loss: from lungs, skin,
     Feces
   –Minimum daily sensible water loss of
     500 ml in urine to excrete wastes
• Body water and Na+ content are regulated
  in tandem by mechanisms that maintain
  cardiovascular function and blood
  pressure
Regulation of Water Output: Influence
                of ADH
• Water reabsorption in collecting ducts is
  proportional to ADH release
• ADH dilute urine and volume of body
  fluids
• ADH concentrated urine
• Hypothalamic osmoreceptors trigger or
  inhibit ADH release
• Which of the following would stimulate thirst
  center osmoreceptors?
  1. Plasma osmolality of 2–3%
  2. Angiotensin II or baroreceptor input
  3. Dry mouth
  4. Substantial decrease in blood volume
     or pressure
  5. All of these
                                                  10
• Which of the following is an electrolyte?
  1.   sodium chloride
  2.   Hydrochloric acid
  3.   Sodium hydroxide
  4.   glucose
  5.   1,2, and 3
  6.   All of these
                                              11
• Describe the regulation of the major
  electrolytes- salts, acids and bases
Central Role of Sodium
• Most abundant cation in the ECF
• Sodium salts in the ECF contribute 280 mOsm
  of the total 300 mOsm ECF solute
  concentration
• Na+ leaks into cells and is pumped out against
  its electrochemical gradient
• ECF Na+ concentration remains stable due to
  osmosis
Central Role of Sodium
• Changes in plasma sodium levels affect
  – Plasma volume, blood pressure
  – ICF and IF volumes
• Renal acid-base control mechanisms are
  coupled to sodium ion transport
• No receptors are known that monitor Na+
  levels in body fluids
Regulation of Sodium Balance:
               Aldosterone
• Na+-water balance is linked to blood pressure
  and blood volume control mechanisms
• Na+ reabsorption
  – 65% is reabsorbed in the proximal tubules
  – 25% is reclaimed in the loops of Henle
• Aldosterone      active reabsorption of
  remaining Na+
• Water follows Na+ if ADH is present
Regulation of Sodium Balance:
              Aldosterone
• Renin-angiotensin mechanism is the main
  trigger for aldosterone release
  –Granular cells of JGA secrete renin in
   response to
    • Sympathetic nervous system
      stimulation
    • Filtrate osmolality
    • Stretch (due to blood pressure)
Regulation of Sodium Balance:
              Aldosterone
• Renin catalyzes the production of angiotensin
  II, which prompts aldosterone release from the
  adrenal cortex
• Aldosterone release is also triggered by
  elevated K+ levels in the ECF
• Aldosterone brings about its effects slowly
  (hours to days)
K+ (or Na+) concentration     Renin-angiotensin
     in blood plasma*           mechanism

                            Stimulates

                 Adrenal cortex
    Negative
                            Releases
    feedback
    inhibits
                   Aldosterone

                            Targets

                 Kidney tubules

                            Effects


     Na+ reabsorption             K+ secretion


                            Restores

               Homeostatic plasma
               levels of Na+ and K+


                                                  Figure 26.8
Regulation of Sodium Balance: ANP
• Released by atrial cells in response to stretch
  ( blood pressure)
• Effects
• Decreases blood pressure and blood volume:
  – ADH, renin and aldosterone production
  – Excretion of Na+ and water
  – Promotes vasodilation directly and also by
    decreasing production of angiotensin II
Influence of Other Hormones
• Estrogens: NaCl reabsorption (like
  aldosterone)
  –     H2O retention during menstrual cycles and
      pregnancy
• Progesterone: Na+ reabsorption (blocks
  aldosterone)
  – Promotes Na+ and H2O loss
• The most abundant cation in the ECF is:
1. Sodium
2. Potassium
3. Calcium
4. chloride




                                            21
• Changes in sodium ion concentration effect:
  1.   Blood Plasma volume
  2.   blood pressure
  3.   ICF volume
  4.   IF volume
  5.   All of these




                                                22
Cardiovascular System Baroreceptors

• Baroreceptors alert the brain of increases in
  blood volume and pressure
  – Sympathetic nervous system impulses to the
    kidneys decline
  – Afferent arterioles dilate
  – GFR increases
  – Na+ and water output increase
Regulation of Potassium Balance
• Importance of potassium:
   – Affects RMP in neurons and muscle cells
     (especially cardiac muscle)
      • ECF [K+]      RMP depolarization
       reduced excitability
      • ECF [K+] hyperpolarization and
       nonresponsiveness
Regulation of Potassium Balance
• H+ shift in and out of cells
  – Leads to corresponding shifts in K+ in the opposite
    direction to maintain cation balance
  – Interferes with activity of excitable cells
Regulation of Potassium Balance
• K+ balance is controlled in the cortical
  collecting ducts by changing the amount of
  potassium secreted into filtrate
• High K+ content of ECF favors tubule cell
  secretion of K+
• When K+ levels are low, cells reabsorb some K+
  left in the filtrate
Regulation of Potassium Balance
• Influence of aldosterone
  –Increased K+ in the adrenal cortex
   causes
    • Release of aldosterone
    • Potassium secretion
Regulation of Calcium
• Ca2+ in ECF is important for
  –Neuromuscular excitability
  –Blood clotting
  –Cell membrane permeability
  –Secretory activities
Regulation of Calcium
• Hypocalcemia- excitability and muscle tetany
• Hypercalcemia- Inhibits neurons and muscle
  cells, may cause heart arrhythmias
• Calcium balance is controlled by parathyroid
  hormone (PTH) and calcitonin
Influence of PTH
• Bones are the largest reservoir for Ca2+ and
  phosphates
• PTH promotes increase in calcium levels by
  targeting bones, kidneys, and small intestine
  (indirectly through vitamin D)
Hypocalcemia (low blood Ca2+) stimulates
            parathyroid glands to release PTH.




      Rising Ca2+ in
      blood inhibits
      PTH release.


                                             Bone


                      1 PTH activates
                      osteoclasts: Ca2+
                      and PO43S released
                      into blood.
                         2 PTH increases         Kidney
                         Ca 2+ reabsorption

                         in kidney
                         tubules.
                   3 PTH promotes
                   kidney’s activation of vitamin D,
                   which increases Ca2+ absorption
                   from food.


                                          Intestine

Ca2+ ions
PTH Molecules                                         Bloodstream


                                                                    Figure 16.12
Regulation of Anions
• Cl– is the major anion in the ECF
  – Helps maintain the osmotic pressure of the blood
  – 99% of Cl– is reabsorbed under normal pH
    conditions
• When acidosis occurs, fewer chloride ions are
  reabsorbed
• Other anions have transport maximums and
  excesses are excreted in urine
• Which ion moves in and out of cells to
  maintain cation balance in response to
  hydrogen ion shifts?
1. Sodium
2. Potassium
3. Calcium
4. chloride


                                           33
• Which hormone will increase sodium
  reabsorption?
1. PTH
2. ADH
3. Aldosterone
4. Estrogen
5. Progesterone
6. 3 and 4
                                       34
• Describe buffer systems and their role in
  acid/base balance. what is a buffer?
Acid-Base Balance
• pH affects all functional 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 blood pH >7.45
• Acidosis or acidemia: arterial pH < 7.35
Acid-Base Balance
• Most H+ is produced by metabolism
  –Lactic acid from anaerobic respiration
   of glucose
  –Fatty acids and ketone bodies from fat
   metabolism
  –H+ liberated when CO2 is converted to
   HCO3– in blood
Acid-Base Balance
• Concentration of hydrogen ions is regulated
  sequentially by
   –Chemical buffer systems: rapid; first line
    of defense
   –Brain stem respiratory centers: act within
    1–3 min
   –Renal mechanisms: most potent, but
    require hours to days to effect pH changes
Acid-Base Balance
• Strong acids dissociate completely in water;
  can 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
HCI                         H2CO3




(a) A strong acid such as       (b) A weak acid such as
    HCI dissociates                 H2CO3 does not
    completely into its ions.       dissociate completely.
                                                             Figure 26.11
• Something that resists changes in pH is a
1. Strong acid
2. Electrolyte
3. Buffer
4. hormone




                                              41
• Which of the following dissociates completely
  in water?
1. Strong acid
2. Weak acid
3. Weak base
4. All of these



                                                  42
Bicarbonate Buffer System
• Mixture of H2CO3 (weak acid) and salts of
  HCO3– (e.g., NaHCO3, a weak base)
• Buffers ICF and ECF
• The only important ECF buffer
Bicarbonate Buffer System
• If strong acid is added:
   – HCO3– ties up H+ and forms H2CO3
       • HCl + NaHCO3 H2CO3 + NaCl
   – pH decreases only slightly, unless all
      available HCO3– (alkaline reserve) is used up
   – HCO3– concentration is closely regulated by
      the kidneys
Bicarbonate Buffer System
• If strong base is added
  – It causes H2CO3 to dissociate and donate H+
  – H+ ties up the base (e.g. OH–)
     • NaOH + H2CO3   NaHCO3 + H2O
  – pH rises only slightly
  – H2CO3 supply is almost limitless (from CO2 released
    by respiration) and is subject to respiratory
    controls
Phosphate Buffer System
• Action is nearly identical to the bicarbonate
  buffer
• Components are sodium salts of:
  – Dihydrogen phosphate (H2PO4–), a weak acid
  – Monohydrogen phosphate (HPO42–), a weak base
• Effective buffer in urine and ICF, where
  phosphate concentrations are high
Protein Buffer System
• Intracellular proteins are the
  most plentiful and powerful
  buffers; plasma proteins are also
  important
• Protein molecules are
  amphoteric (can function as
  both a weak acid and a weak
  base)
  – When pH rises, organic acid or
    carboxyl (COOH) groups release H+
  – When pH falls, NH2 groups bind H+
• The most important ECF buffer system is:
1. bicarbonate
2. Phosphate
3. Protein
4. plasma




                                             48
• The phosphate buffer system functions in:
1. ECF
2. ICF
3. Urine
4. 2 and 3
5. All of these



                                              49
Describe the role of the respiratory system in
 acid/base balance.
 Describe the role of the urinary system in
 acid/base balance.
Physiological Buffer Systems
• Respiratory and renal systems
  – Act more slowly than chemical buffer systems
  – Have more capacity than chemical buffer systems
Acid-Base Balance
• Chemical buffers cannot eliminate excess acids
  or bases from the body
  – Lungs eliminate volatile carbonic acid by
    eliminating CO2
  – Kidneys eliminate other fixed metabolic acids
    (phosphoric, uric, and lactic acids and ketones) and
    prevent metabolic acidosis
Respiratory Regulation of H+
• Respiratory system eliminates CO2
• A reversible equilibrium exists in the blood:
  – CO2 + H2O   H2CO3    H+ + HCO3–
• During CO2 unloading the reaction shifts to the
  left (and H+ is incorporated into H2O)
• During CO2 loading the reaction shifts to the
  right (and H+ is buffered by proteins)
54
Respiratory Regulation of H+
• Hypercapnia activates medullary
  chemoreceptors
• Rising plasma H+ activates peripheral
  chemoreceptors- breathing rate increases
   –More CO2 is removed from the blood
   –H+ concentration is reduced
   –CO2 + H2O H2CO3 H+ + HCO3–
Respiratory Regulation of H+
• Alkalosis depresses the respiratory center
  – Respiratory rate and depth decrease
  – H+ concentration increases
• Respiratory system impairment causes acid-
  base imbalances
  – Hypoventilation respiratory acidosis
  – Hyperventilation respiratory alkalosis
  – CO2 + H2O H2CO3 H+ + HCO3–
• The advantage of chemical buffer systems is
1. They have a very high capacity
2. Their effects are long lasting
3. Their effects are rapid
4. All of these




                                                57
2/3 of the body’s fluid is located where?
1. ECF
2. ICF
3. IVF
4. IF




                                            58
Where is the thirst center?
1. mouth
2. hypothalamus
3. cerebellum
4. medulla




                              59
• What hormone regulates water balance
1. Aldosterone
2. PTH
3. ADH
4. Secretin
5. aquaporin



                                         60
• What hormone regulates calcium balance
1. Aldosterone
2. PTH
3. ADH
4. Secretin
5. aquaporin



                                           61
• What hormone regulates sodium balance
1. Aldosterone
2. PTH
3. ADH
4. Secretin
5. aquaporin



                                          62
• How do the lungs eliminate carbonic acid?
1. Excreting it directly
2. Eliminating carbon dioxide
3. They don’t
4. Sending hormones to the kidneys, which
   cause the kidneys to excrete it



                                              63
• The advantage of physiological buffer systems
  is
1. They have a very high capacity
2. Their effects are short term
3. Their effects are instantaneous
4. All of these



                                              64
• Rising plasma H+ concentration will do
  what to breathing rate?
1. Increase
2. Decrease
3. Not change




                                           65
Renal Mechanisms of Acid-Base Balance
• Most important renal mechanisms
   –Conserving (reabsorbing) or generating
    new HCO3–
   –Excreting HCO3–
• Generating or reabsorbing one HCO3– is
  the same as losing one H+
• Excreting one HCO3– is the same as
  gaining one H+
Renal Mechanisms of Acid-Base Balance

• Renal regulation of acid-base balance
  depends on secretion of H+
• H+ secretion occurs in the PCT and in the
  collecting duct:
   –The H+ comes from H2CO3 produced in
    reactions catalyzed by carbonic
    anhydrase inside the renal tubule cells
Peri-
                                     PCT cell                                   tubular
                                                                               capillary


                                                2K+                  2K+
                                                                 ATPase
                                            3Na+                     3Na+
  HCO3– + Na+                                   Cl–                            Cl–


                                                                            HCO3–
                 H+   3a    H+                  HCO3–       3b
  HCO3–
                                      2
                                                                            HCO3–
    4
                           ATPase
                                      H2CO3
        H2CO3                                         Na+                    Na+

        5         *                   1

                                 6
  H2O           CO2                       CO2
                                           +                                  CO2
                                          H2O




Tight junction


                                                                                           68
Reabsorption of Bicarbonate
• Tubule cell luminal membranes are
  impermeable to HCO3–
   – CO2 combines with water in PCT cells,
     forming H2CO3, which dissociates
   – H+ is secreted, and HCO3– is reabsorbed into
     capillary blood
   – Secreted H+ unites with HCO3– to form H2CO3
     in filtrate, which generates CO2 and H2O
• HCO3– disappears from filtrate at the same rate
  that it enters the peritubular capillary blood
Peri-
                                     PCT cell                                    tubular
                                                                                capillary


                                                2K+                   2K+
                                                                  ATPase
                                            3Na+                      3Na+
  HCO3– + Na+                                    Cl–                            Cl–


                                                                             HCO3–
                 H+   3a    H+                   HCO3–       3b
  HCO3–
                                      2
                                                                             HCO3–
    4
                           ATPase
                                      H2CO3
        H2CO3                                          Na+                    Na+

        5         *                   1         CA

                                 6
  H2O           CO2                       CO2
                                           +                                   CO2
                                          H2O




Tight junction


                                                                                            70
Bicarbonate Ion Secretion
• When the body is in alkalosis, renal tubule cells
  – Secrete HCO3–
  – Reclaim H+ and acidify the blood
Abnormalities of Acid-Base Balance
• Respiratory acidosis and alkalosis
• Metabolic acidosis and alkalosis
Respiratory Acidosis and Alkalosis
The most important indicator of respiratory
function is PCO2 level (normally 35–45 mm Hg)
 – PCO2 above 45 mm Hg respiratory acidosis
    • Most common cause of acid-base imbalances
    • Due to decrease in ventilation or gas
      exchange
    • Characterized by falling blood pH and rising
      PCO2
Respiratory Acidosis and Alkalosis
• PCO2 below 35 mm Hg     respiratory
  alkalosis
   –A common result of hyperventilation
    due to stress or pain
Metabolic Acidosis and Alkalosis
• Any pH imbalance not caused by
  abnormal blood CO2 levels
• Indicated by abnormal HCO3– levels
Metabolic Acidosis and Alkalosis
• Causes of metabolic acidosis
  –Ingestion of too much alcohol
    ( acetic acid)
  –Excessive loss of HCO3– (e.g., persistent
    diarrhea)
  –Accumulation of lactic acid, shock, ketosis
    in diabetic crisis, starvation, and kidney
    failure
Metabolic Acidosis and Alkalosis
• Metabolic alkalosis is much less common
  than metabolic acidosis
   –Indicated by rising blood pH and HCO3–
   –Caused by vomiting of the acid contents
    of the stomach or by intake of excess
    base (e.g., antacids)
Effects of Acidosis and Alkalosis
• Blood pH below 7 depression of CNS
  coma death
• Blood pH above 7.8 excitation of
  nervous system muscle tetany, extreme
  nervousness, convulsions, respiratory
  arrest   death
Respiratory and Renal Compensations

• If acid-base imbalance is due to
  malfunction of a physiological buffer
  system, the other one compensates
   –Respiratory system attempts to correct
     metabolic acid-base imbalances
   –Kidneys attempt to correct respiratory
     acid-base imbalances
Respiratory Compensation
In metabolic acidosis
 –Blood pH is below 7.35 and HCO3– level is low
 –High H+ levels stimulate the respiratory
  centers
 –Rate and depth of breathing are increased
 –As CO2 is eliminated by the respiratory
  system, PCO2 falls below normal
Respiratory Compensation
• Respiratory compensation for metabolic
  alkalosis is revealed by:
   –Slow, shallow breathing, allowing CO2
    accumulation in the blood
   –High pH (over 7.45) and elevated HCO3–
    levels
Renal Compensation
• Hypoventilation causes elevated PCO2
• (respiratory acidosis)
   –Renal compensation is indicated by high
    HCO3– levels
• Respiratory alkalosis exhibits low PCO2 and high
  pH
   –Renal compensation is indicated by
    decreasing HCO3– levels
• The respiratory system compensates for
  metabolic acidosis by
1. Increasing breathing rate
2. Decreasing breathing rate


CO2 + H2O H2CO3 H+ + HCO3–


                                           83
• The renal system compensates for respiratory
  acidosis by
1. absorbing or generating bicarbonate
2. Secreting more bicarbonate



CO2 + H2O   H2CO3    H+ + HCO3–

                                                 84

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Ch 26

  • 1. EC questions • What does ICF stand for? • a chemical compound that dissociates into ions in water is called an______. • is sodium concentration higher in the ECF or ICF? • a sensation of thirst causes us to: 1
  • 2. Describe the major fluid compartments including intracellular, extracellular, intravascular and interstitial.
  • 3. Total body water Volume = 40 L 60% body weight Extracellular fluid (ECF) Volume = 15 L 20% body weight Intracellular fluid (ICF) Interstitial fluid (IF) Volume = 25 L Volume = 12 L 40% body weight 80% of ECF Figure 26.1
  • 4. • Describe the regulation of water intake and output
  • 5. Regulation of Water Intake • Thirst mechanism is the driving force for water intake • The hypothalamic thirst center osmoreceptors are stimulated by – Plasma osmolality of 2–3% –Angiotensin II or baroreceptor input –Dry mouth –Substantial decrease in blood volume or pressure
  • 6. Regulation of Water Intake • Drinking water creates inhibition of the thirst center • Inhibitory feedback signals include –Relief of dry mouth –Activation of stomach and intestinal stretch receptors
  • 7. • Most of the body’s water is 1. Intracellular 2. Intravascular 3. interstitial 7
  • 8. Regulation of Water Output • Obligatory water losses –Insensible water loss: from lungs, skin, Feces –Minimum daily sensible water loss of 500 ml in urine to excrete wastes • Body water and Na+ content are regulated in tandem by mechanisms that maintain cardiovascular function and blood pressure
  • 9. Regulation of Water Output: Influence of ADH • Water reabsorption in collecting ducts is proportional to ADH release • ADH dilute urine and volume of body fluids • ADH concentrated urine • Hypothalamic osmoreceptors trigger or inhibit ADH release
  • 10. • Which of the following would stimulate thirst center osmoreceptors? 1. Plasma osmolality of 2–3% 2. Angiotensin II or baroreceptor input 3. Dry mouth 4. Substantial decrease in blood volume or pressure 5. All of these 10
  • 11. • Which of the following is an electrolyte? 1. sodium chloride 2. Hydrochloric acid 3. Sodium hydroxide 4. glucose 5. 1,2, and 3 6. All of these 11
  • 12. • Describe the regulation of the major electrolytes- salts, acids and bases
  • 13. Central Role of Sodium • Most abundant cation in the ECF • Sodium salts in the ECF contribute 280 mOsm of the total 300 mOsm ECF solute concentration • Na+ leaks into cells and is pumped out against its electrochemical gradient • ECF Na+ concentration remains stable due to osmosis
  • 14. Central Role of Sodium • Changes in plasma sodium levels affect – Plasma volume, blood pressure – ICF and IF volumes • Renal acid-base control mechanisms are coupled to sodium ion transport • No receptors are known that monitor Na+ levels in body fluids
  • 15. Regulation of Sodium Balance: Aldosterone • Na+-water balance is linked to blood pressure and blood volume control mechanisms • Na+ reabsorption – 65% is reabsorbed in the proximal tubules – 25% is reclaimed in the loops of Henle • Aldosterone active reabsorption of remaining Na+ • Water follows Na+ if ADH is present
  • 16. Regulation of Sodium Balance: Aldosterone • Renin-angiotensin mechanism is the main trigger for aldosterone release –Granular cells of JGA secrete renin in response to • Sympathetic nervous system stimulation • Filtrate osmolality • Stretch (due to blood pressure)
  • 17. Regulation of Sodium Balance: Aldosterone • Renin catalyzes the production of angiotensin II, which prompts aldosterone release from the adrenal cortex • Aldosterone release is also triggered by elevated K+ levels in the ECF • Aldosterone brings about its effects slowly (hours to days)
  • 18. K+ (or Na+) concentration Renin-angiotensin in blood plasma* mechanism Stimulates Adrenal cortex Negative Releases feedback inhibits Aldosterone Targets Kidney tubules Effects Na+ reabsorption K+ secretion Restores Homeostatic plasma levels of Na+ and K+ Figure 26.8
  • 19. Regulation of Sodium Balance: ANP • Released by atrial cells in response to stretch ( blood pressure) • Effects • Decreases blood pressure and blood volume: – ADH, renin and aldosterone production – Excretion of Na+ and water – Promotes vasodilation directly and also by decreasing production of angiotensin II
  • 20. Influence of Other Hormones • Estrogens: NaCl reabsorption (like aldosterone) – H2O retention during menstrual cycles and pregnancy • Progesterone: Na+ reabsorption (blocks aldosterone) – Promotes Na+ and H2O loss
  • 21. • The most abundant cation in the ECF is: 1. Sodium 2. Potassium 3. Calcium 4. chloride 21
  • 22. • Changes in sodium ion concentration effect: 1. Blood Plasma volume 2. blood pressure 3. ICF volume 4. IF volume 5. All of these 22
  • 23. Cardiovascular System Baroreceptors • Baroreceptors alert the brain of increases in blood volume and pressure – Sympathetic nervous system impulses to the kidneys decline – Afferent arterioles dilate – GFR increases – Na+ and water output increase
  • 24. Regulation of Potassium Balance • Importance of potassium: – Affects RMP in neurons and muscle cells (especially cardiac muscle) • ECF [K+] RMP depolarization reduced excitability • ECF [K+] hyperpolarization and nonresponsiveness
  • 25. Regulation of Potassium Balance • H+ shift in and out of cells – Leads to corresponding shifts in K+ in the opposite direction to maintain cation balance – Interferes with activity of excitable cells
  • 26. Regulation of Potassium Balance • K+ balance is controlled in the cortical collecting ducts by changing the amount of potassium secreted into filtrate • High K+ content of ECF favors tubule cell secretion of K+ • When K+ levels are low, cells reabsorb some K+ left in the filtrate
  • 27. Regulation of Potassium Balance • Influence of aldosterone –Increased K+ in the adrenal cortex causes • Release of aldosterone • Potassium secretion
  • 28. Regulation of Calcium • Ca2+ in ECF is important for –Neuromuscular excitability –Blood clotting –Cell membrane permeability –Secretory activities
  • 29. Regulation of Calcium • Hypocalcemia- excitability and muscle tetany • Hypercalcemia- Inhibits neurons and muscle cells, may cause heart arrhythmias • Calcium balance is controlled by parathyroid hormone (PTH) and calcitonin
  • 30. Influence of PTH • Bones are the largest reservoir for Ca2+ and phosphates • PTH promotes increase in calcium levels by targeting bones, kidneys, and small intestine (indirectly through vitamin D)
  • 31. Hypocalcemia (low blood Ca2+) stimulates parathyroid glands to release PTH. Rising Ca2+ in blood inhibits PTH release. Bone 1 PTH activates osteoclasts: Ca2+ and PO43S released into blood. 2 PTH increases Kidney Ca 2+ reabsorption in kidney tubules. 3 PTH promotes kidney’s activation of vitamin D, which increases Ca2+ absorption from food. Intestine Ca2+ ions PTH Molecules Bloodstream Figure 16.12
  • 32. Regulation of Anions • Cl– is the major anion in the ECF – Helps maintain the osmotic pressure of the blood – 99% of Cl– is reabsorbed under normal pH conditions • When acidosis occurs, fewer chloride ions are reabsorbed • Other anions have transport maximums and excesses are excreted in urine
  • 33. • Which ion moves in and out of cells to maintain cation balance in response to hydrogen ion shifts? 1. Sodium 2. Potassium 3. Calcium 4. chloride 33
  • 34. • Which hormone will increase sodium reabsorption? 1. PTH 2. ADH 3. Aldosterone 4. Estrogen 5. Progesterone 6. 3 and 4 34
  • 35. • Describe buffer systems and their role in acid/base balance. what is a buffer?
  • 36. Acid-Base Balance • pH affects all functional 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 blood pH >7.45 • Acidosis or acidemia: arterial pH < 7.35
  • 37. Acid-Base Balance • Most H+ is produced by metabolism –Lactic acid from anaerobic respiration of glucose –Fatty acids and ketone bodies from fat metabolism –H+ liberated when CO2 is converted to HCO3– in blood
  • 38. Acid-Base Balance • Concentration of hydrogen ions is regulated sequentially by –Chemical buffer systems: rapid; first line of defense –Brain stem respiratory centers: act within 1–3 min –Renal mechanisms: most potent, but require hours to days to effect pH changes
  • 39. Acid-Base Balance • Strong acids dissociate completely in water; can 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
  • 40. HCI H2CO3 (a) A strong acid such as (b) A weak acid such as HCI dissociates H2CO3 does not completely into its ions. dissociate completely. Figure 26.11
  • 41. • Something that resists changes in pH is a 1. Strong acid 2. Electrolyte 3. Buffer 4. hormone 41
  • 42. • Which of the following dissociates completely in water? 1. Strong acid 2. Weak acid 3. Weak base 4. All of these 42
  • 43. Bicarbonate Buffer System • Mixture of H2CO3 (weak acid) and salts of HCO3– (e.g., NaHCO3, a weak base) • Buffers ICF and ECF • The only important ECF buffer
  • 44. Bicarbonate Buffer System • If strong acid is added: – HCO3– ties up H+ and forms H2CO3 • HCl + NaHCO3 H2CO3 + NaCl – pH decreases only slightly, unless all available HCO3– (alkaline reserve) is used up – HCO3– concentration is closely regulated by the kidneys
  • 45. Bicarbonate Buffer System • If strong base is added – It causes H2CO3 to dissociate and donate H+ – H+ ties up the base (e.g. OH–) • NaOH + H2CO3 NaHCO3 + H2O – pH rises only slightly – H2CO3 supply is almost limitless (from CO2 released by respiration) and is subject to respiratory controls
  • 46. Phosphate Buffer System • Action is nearly identical to the bicarbonate buffer • Components are sodium salts of: – Dihydrogen phosphate (H2PO4–), a weak acid – Monohydrogen phosphate (HPO42–), a weak base • Effective buffer in urine and ICF, where phosphate concentrations are high
  • 47. Protein Buffer System • Intracellular proteins are the most plentiful and powerful buffers; plasma proteins are also important • Protein molecules are amphoteric (can function as both a weak acid and a weak base) – When pH rises, organic acid or carboxyl (COOH) groups release H+ – When pH falls, NH2 groups bind H+
  • 48. • The most important ECF buffer system is: 1. bicarbonate 2. Phosphate 3. Protein 4. plasma 48
  • 49. • The phosphate buffer system functions in: 1. ECF 2. ICF 3. Urine 4. 2 and 3 5. All of these 49
  • 50. Describe the role of the respiratory system in acid/base balance. Describe the role of the urinary system in acid/base balance.
  • 51. Physiological Buffer Systems • Respiratory and renal systems – Act more slowly than chemical buffer systems – Have more capacity than chemical buffer systems
  • 52. Acid-Base Balance • Chemical buffers cannot eliminate excess acids or bases from the body – Lungs eliminate volatile carbonic acid by eliminating CO2 – Kidneys eliminate other fixed metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis
  • 53. Respiratory Regulation of H+ • Respiratory system eliminates CO2 • A reversible equilibrium exists in the blood: – CO2 + H2O H2CO3 H+ + HCO3– • During CO2 unloading the reaction shifts to the left (and H+ is incorporated into H2O) • During CO2 loading the reaction shifts to the right (and H+ is buffered by proteins)
  • 54. 54
  • 55. Respiratory Regulation of H+ • Hypercapnia activates medullary chemoreceptors • Rising plasma H+ activates peripheral chemoreceptors- breathing rate increases –More CO2 is removed from the blood –H+ concentration is reduced –CO2 + H2O H2CO3 H+ + HCO3–
  • 56. Respiratory Regulation of H+ • Alkalosis depresses the respiratory center – Respiratory rate and depth decrease – H+ concentration increases • Respiratory system impairment causes acid- base imbalances – Hypoventilation respiratory acidosis – Hyperventilation respiratory alkalosis – CO2 + H2O H2CO3 H+ + HCO3–
  • 57. • The advantage of chemical buffer systems is 1. They have a very high capacity 2. Their effects are long lasting 3. Their effects are rapid 4. All of these 57
  • 58. 2/3 of the body’s fluid is located where? 1. ECF 2. ICF 3. IVF 4. IF 58
  • 59. Where is the thirst center? 1. mouth 2. hypothalamus 3. cerebellum 4. medulla 59
  • 60. • What hormone regulates water balance 1. Aldosterone 2. PTH 3. ADH 4. Secretin 5. aquaporin 60
  • 61. • What hormone regulates calcium balance 1. Aldosterone 2. PTH 3. ADH 4. Secretin 5. aquaporin 61
  • 62. • What hormone regulates sodium balance 1. Aldosterone 2. PTH 3. ADH 4. Secretin 5. aquaporin 62
  • 63. • How do the lungs eliminate carbonic acid? 1. Excreting it directly 2. Eliminating carbon dioxide 3. They don’t 4. Sending hormones to the kidneys, which cause the kidneys to excrete it 63
  • 64. • The advantage of physiological buffer systems is 1. They have a very high capacity 2. Their effects are short term 3. Their effects are instantaneous 4. All of these 64
  • 65. • Rising plasma H+ concentration will do what to breathing rate? 1. Increase 2. Decrease 3. Not change 65
  • 66. Renal Mechanisms of Acid-Base Balance • Most important renal mechanisms –Conserving (reabsorbing) or generating new HCO3– –Excreting HCO3– • Generating or reabsorbing one HCO3– is the same as losing one H+ • Excreting one HCO3– is the same as gaining one H+
  • 67. Renal Mechanisms of Acid-Base Balance • Renal regulation of acid-base balance depends on secretion of H+ • H+ secretion occurs in the PCT and in the collecting duct: –The H+ comes from H2CO3 produced in reactions catalyzed by carbonic anhydrase inside the renal tubule cells
  • 68. Peri- PCT cell tubular capillary 2K+ 2K+ ATPase 3Na+ 3Na+ HCO3– + Na+ Cl– Cl– HCO3– H+ 3a H+ HCO3– 3b HCO3– 2 HCO3– 4 ATPase H2CO3 H2CO3 Na+ Na+ 5 * 1 6 H2O CO2 CO2 + CO2 H2O Tight junction 68
  • 69. Reabsorption of Bicarbonate • Tubule cell luminal membranes are impermeable to HCO3– – CO2 combines with water in PCT cells, forming H2CO3, which dissociates – H+ is secreted, and HCO3– is reabsorbed into capillary blood – Secreted H+ unites with HCO3– to form H2CO3 in filtrate, which generates CO2 and H2O • HCO3– disappears from filtrate at the same rate that it enters the peritubular capillary blood
  • 70. Peri- PCT cell tubular capillary 2K+ 2K+ ATPase 3Na+ 3Na+ HCO3– + Na+ Cl– Cl– HCO3– H+ 3a H+ HCO3– 3b HCO3– 2 HCO3– 4 ATPase H2CO3 H2CO3 Na+ Na+ 5 * 1 CA 6 H2O CO2 CO2 + CO2 H2O Tight junction 70
  • 71. Bicarbonate Ion Secretion • When the body is in alkalosis, renal tubule cells – Secrete HCO3– – Reclaim H+ and acidify the blood
  • 72. Abnormalities of Acid-Base Balance • Respiratory acidosis and alkalosis • Metabolic acidosis and alkalosis
  • 73. Respiratory Acidosis and Alkalosis The most important indicator of respiratory function is PCO2 level (normally 35–45 mm Hg) – PCO2 above 45 mm Hg respiratory acidosis • Most common cause of acid-base imbalances • Due to decrease in ventilation or gas exchange • Characterized by falling blood pH and rising PCO2
  • 74. Respiratory Acidosis and Alkalosis • PCO2 below 35 mm Hg respiratory alkalosis –A common result of hyperventilation due to stress or pain
  • 75. Metabolic Acidosis and Alkalosis • Any pH imbalance not caused by abnormal blood CO2 levels • Indicated by abnormal HCO3– levels
  • 76. Metabolic Acidosis and Alkalosis • Causes of metabolic acidosis –Ingestion of too much alcohol ( acetic acid) –Excessive loss of HCO3– (e.g., persistent diarrhea) –Accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and kidney failure
  • 77. Metabolic Acidosis and Alkalosis • Metabolic alkalosis is much less common than metabolic acidosis –Indicated by rising blood pH and HCO3– –Caused by vomiting of the acid contents of the stomach or by intake of excess base (e.g., antacids)
  • 78. Effects of Acidosis and Alkalosis • Blood pH below 7 depression of CNS coma death • Blood pH above 7.8 excitation of nervous system muscle tetany, extreme nervousness, convulsions, respiratory arrest death
  • 79. Respiratory and Renal Compensations • If acid-base imbalance is due to malfunction of a physiological buffer system, the other one compensates –Respiratory system attempts to correct metabolic acid-base imbalances –Kidneys attempt to correct respiratory acid-base imbalances
  • 80. Respiratory Compensation In metabolic acidosis –Blood pH is below 7.35 and HCO3– level is low –High H+ levels stimulate the respiratory centers –Rate and depth of breathing are increased –As CO2 is eliminated by the respiratory system, PCO2 falls below normal
  • 81. Respiratory Compensation • Respiratory compensation for metabolic alkalosis is revealed by: –Slow, shallow breathing, allowing CO2 accumulation in the blood –High pH (over 7.45) and elevated HCO3– levels
  • 82. Renal Compensation • Hypoventilation causes elevated PCO2 • (respiratory acidosis) –Renal compensation is indicated by high HCO3– levels • Respiratory alkalosis exhibits low PCO2 and high pH –Renal compensation is indicated by decreasing HCO3– levels
  • 83. • The respiratory system compensates for metabolic acidosis by 1. Increasing breathing rate 2. Decreasing breathing rate CO2 + H2O H2CO3 H+ + HCO3– 83
  • 84. • The renal system compensates for respiratory acidosis by 1. absorbing or generating bicarbonate 2. Secreting more bicarbonate CO2 + H2O H2CO3 H+ + HCO3– 84