Chapter 19
Fluid, Electrolyte,
and Acid-base
Balance
Percentages of Solutes in Body Fluids
Solutes
IC fluid
Interstitial fluid
Blood plasma
K+
75
3
3
Na+
6
94
94
Ca++
2
2
2
Proteins
27
traces
10
HCO3-
6
18
16
Chloride
2
77
69
Things to Know about Factors Affecting the
Plasma Composition and Water Balance
Solute and water content in plasma affected by movement of materials into and out of
the body
• Net gain of solutes and water due to the transport of molecules through the GI
wall
• Net loss of solutes and water due to the transport of molecules through the renal
tubular walls
Volume of plasma determined by its water content, affects directly MAP. Increased
volume= increased MAP
Plasma volume affects osmolarity (solute concentration). Increase of plasma water,
decreases osmolarity. Decrease of plasma water, increases osmolarity
Kidneys: control over the volume and composition of plasma by regulating solute and
water composition
• Principal cells: hormonal control of water and electrolyte balance
• Intercalated cells: acid-base balance
Material Exchanges Affecting Plasma Content
Ingestion
Lumen of
digestive
tract
Excretion
Feces
Cells
Absorption
Secretion
(Minimal)
Extracellular
connective tissue
(including bone)
Plasma and
interstitial fluid
(extracellular fluid)
Filtration
Secretion
Reabsorption
Lumen of
renal
tubules
Other losses
Excretion
Sweating,
hemorrhage,
respiration
Urine
The Concept of Water Balance
Output
Input
Input
Output
Output
Input
Increase
No change
Decrease
Balance:
Normovolemia =
normal blood volume
Positive balance:
Hypervolemia =
high blood volume due to positive water balance
Negative balance:
Hypovolemia =
low blood volume due to negative water balance
Continuous
Fluid
Movement
In response of changes in relative
osmolarityà Water moves by osmosis
from hypotonic solution to hypertonic
solution
Fluid intake ànet movement of water
from the blood plasma into the IC
compartment
Dehydrationà net movement of water
from IC compartment into blood plasma
Fluid Balance: Input + production =
utilization + output
Fluid Output (2500mL):
Breathing, sweating,
defecation, cutaneous
transpiration (1000mL)
Urination (1500mL)
Fluid Intake (2500mL):
Preformed water (2300 mL)
Metabolic water (200mL)
Factors Affecting Water Balance: Water intake + metabolically
produced = water output + water used
Cellular
metabolism
0.3 L/day
Ingestion
2.2 L/day
Digestive
tract
Absorption
Feces
2.2 L/day + 0.3 L/day = 2.5 L/day
Filtration
Total body water
42 L/day
Secretion
Excretion
0.1 L/day
Water inputs =
Secretion
Renal
tubules
Reabsorption
Other losses
0.9 L/day
Insensible loss, sweating
Excretion
1.5 L/day
Urine
Water outputs =
0.1 L/day
+ 0.9 L/day
+ 1.5 L/day
= 2.5 L/day
Fluid Output
Obligatory
• Expired air
• Sweat
• Cutaneous transpiration
• Defecation
• Minimum urine production
• Abnormal: vomiting, blood
loss
Regulated
• Hormonal stimulation of
kidney
Decreasing urine output:
Aldosterone
ADH
Angiotensin II
Increasing urine output:
ANP
Osmolarity and the Movement of Water
Osmolarity of body fluids = 300 mOsm (300 milliosmoles of solute per liter of plasma)
Under normal conditions: cell volumes don’t change and ICF and ECF are in osmotic
equilibrium
Water intoxication
•
Kidneys compensate for changes in osmolarity of extracellular fluid by regulating water
reabsorption and adjusting the rate for water excretion
•
•
Water reabsorption is a passive process, based on osmotic gradients. Coupled with
electrolyte (Na+) reabsorption
Water does not get secreted
•
•
PCT: almost 70% of water is reabsorbed, unregulated
DCT and collecting ducts: remaining water is reabsorbed, hormonal regulation
Mechanism of Water Reabsorption in the Proximal Tubule
Peritubular fluid
Tubule
epithelial
cell
Apical
membrane
Basolateral
membrane
Capillary
endothelial cell
Tubular fluid
Plasma
X
Na+
Y
X
X
Na+
K+
Na+
Y
Y
H2 O
Permeating
solute
H2 O
Permeating
solute
Steps for water and urea reabsorption:
Solutes (Na+, X, Y) are actively reabsorbed, increasing the
osmolarity of peritubular fluid and plasma. Creation of osmotic gradient
Water is reabsorbed by osmosis, follows solute reabsorption
Urea (permeating solute) is reabsorbed passively.
Slide 1
Establishment of the Medullary
Osmotic Gradient
Osmotic pressure gradient: Responsible for water
reabsorption by collecting ducts
• near cortexà interstitial fluid osmolarity about 300
mOsm
• near tips of medullary pyramidsà 1400 mOsm
Due to countercurrent multiplier mechanism by loops of
Henle and facilitated diffusion of urea (contributes about
40% to osmolarity of gradient)
Vasa recta prevents the dissipation of osmotic gradient
Medullary Osmotic Gradient
Establishment of Medullary Osmotic Gradient by Countercurrent Multiplier Mechanism
Vasa recta help to maintain
the medullary osmotic
gradient:
The loss of water and gain of
solutes that occurs as the
descending limb goes toward
the tip of the pyramid is
counteracted by the gain in
water and loss of solutes as
the plasma ascends toward
the cortex
Water Reabsorption in DCT and
Collecting Ducts
• 20% water reabsorption by DCT and 10% in
collecting ducts
• Tubular fluid is hypo-osmolar compared to
interstitial fluid
• Epithelial cells are impermeable to water
• Water channels/ aquaporins: type 3 in
basolateral membrane and type 2 in apical
surface activated by AntiDiuretic Hormone
(ADH)
•
A. Water excreted in urine. High volume of low
osmolarity urine
•
B. ADH presence. Water is reabsorbed. Urine isoosmotic to deep layer of medulla. Urine: small
volume and high osmolarity
Clinical Applications:
Intravenous Solutions
0.9% saline solution
• 0.9 g of NaCl to every 100
mL of sterile water
5% dextrose/ D5W
• 5 g of dextrose to every
100L of sterile water
• Standard for fluid
replacement
• Hypertonic solution to
plasma when in holding bag
but when infused à
hypotonic
• Similar osmolarity to plasma
• Supplement for water and
energy
Sodium/Na+
• Principal cation of ECF in the form of NaCl and NaHCO3
• Exerts the greatest osmotic pressure in ECF that drives
water reabsorption
• 135-145 mEq/L
• Daily requirement 1.5 to 2.3 g (0.5 – 20-25g) (3-7 g)
• Determines blood plasma osmolarity and regulates fluid
balance
• Retention of Na+ and waterà increases BV and BP
• Na+ reabsorption in proximal tubules unregulated
• Na+ reabsorption in distal tubules regulated by ADH,
aldosterone, and ANP
• Na+ imbalance: hypernatremia and hyponatremia
Mechanisms of Sodium Reabsorption
in the Renal Tubule
• Freely filtered
• Control of Na+ levels is important in blood pressure and blood volume
• Reabsorbed (70%) in proximal tubules, distal tubules, and collecting
ducts
• No secretion
• Reabsorption regulated by aldosterone and ANP at principal cells of
distal tubules and collecting ducts
In PCT:
• Na+/K+ pump on basolateral membrane drives active reabsorption
• Na+ crosses apical surface: Na+/Glucose/ amino acids cotransport and
Na+/H+ counter-transport
In DCT:
• Na+/K+ pump in basolateral surface
• Na+/ Cl- and HCO3 cotransport and facilitated diffusion through Na+
channels
Na+ Reabsorption in Renal Tubules
Mechanisms of sodium reabsorption in the proximal and distal tubules
Peritubular fluid
Apical
membrane
Proximal tubule
epithelial cell
Capillary
endothelial cell
Basolateral
membrane
Tubular
fluid
Plasma
X
Na+
X
Na+
Na+
H+
Cl–
Sodium reabsorption in the proximal tubule
Na+
K+
Mechanisms of sodium reabsorption in the proximal and distal tubules
Distal tubule
epithelial cell
Cl–
Na+
Na+
Na+
K+
Cl–
K+
Cl–
Na+
Sodium reabsorption in the distal tubule
Cl–
The Effects of Aldosterone
Action: Increases sodium reabsorption and secretion of K+
• Acts on principal cells of distal tubules and collecting ducts
– Increases number of Na+/K+ pumps on basolateral membrane
and open Na+ and K+ channels on apical membrane
• Stimuli for renin release
– Decreased pressure in afferent arteriole
– Renal sympathetic nerve activity
– Decreases in Na+ and Cl– in distal tubule filtrate
Effects of Aldosterone on Principal Cells of the Distal Tubules and Collecting Ducts
Lumen of late distal
tubule or collecting duct
Basolateral
membrane
Peritubular
fluid
Peritubular
capillary
Principal cell
Apical
membrane
Na+
Cytosolic
receptor
Aldosterone
K+
K+
Na+
Na+
Tubular fluid
K+
K+
K+
K+
K+
K+
Na+
Na+
Na+
Na+
Na+
Plasma
Interactions Between Fluid and
Electrolyte Balance
• Physiological response to hemorrhage
– Decrease in blood volume ® decrease in MAP
– Neural control of heart and vasculature
• Baroreceptor reflex
– Hormonal control of blood volume:
o Increase in solute reabsorption increases osmotic gradient
for water reabsorption
• ADH: increases the number of sodium channels in the apical
membrane of principal cells
• Angiotensin II increases ADH secretion
• Renin-angiotensin-aldosterone system (RAAS)
• Atrial natriuretic hormone: decreases ADH secretion
Juxtaglomerular Apparatus
JG / granular cells: enlarged smooth muscle cells in wall of arteriole, granules with renin.
Mechanoreceptors (baroreceptors)
Macula Densa: tall, closely-packed cells in DCT adjacent to the granular JG cells.
Chemoreceptors (NaCl ). Sensor for tubuloglomerular feedback
The Renin-Angiotensin-Aldosterone
System (RAAS)
Decrease in plasma Na+à fall in blood
volumeàGranular/JG cells secrete reninà
Angiotensinogen into angiotensin Ià
Angiotensin-converting enzyme (ACE) converts into
angiotensin IIà Stimulates aldosteroneà
Promotes the reabsorption of Na+ and secretion of
K+ àIncreases blood volume and raises blood
pressure
RAAS System
Mechanisms by which Decreases in MAP Stimulate Renin Release
MAP
Afferent arteriole
pressure
Baroreceptor reflex
Sympathetic activity
GFR
[Na+] and [Cl–]
in distal tubules
Macula densa
Paracrine
secretion
Juxtaglomerular cells
of afferent arteriole
Renin release
Initial stimulus
Physiological response
Result
Slide 1
Mechanisms by which Angiotensin II Increases MAP
Angiotensin II
Systemic arterioles
Vasoconstriction
Adrenal cortex
Posterior pituitary
Hypothalamic neurons
Aldosterone secretion
ADH secretion
Thirst stimulation
Kidneys
Sodium reabsorption
in late distal tubules
and collecting ducts
Extracellular fluid
osmolarity
MAP
Initial stimulus
Physiological response
Result
Water reabsorption
in late distal tubules
and collecting ducts
Plasma volume
Slide 1
Control of Aldosterone
Rise of
K+ in
plasma
Depolarization of
aldosterone–
secreting cells
Low
Na+ in
plasma
Fall in blood
volume àRenin –
AngiotensinAldosterone
system
Atrial Natriuretic Peptide
Secreted by atrial cells in response to distension
of atrial wall
o Increases GFR
• Dilation of afferent arteriole
• Constriction of efferent arteriole
o Decreases Na+ reabsorption by closing Na+
channels in apical membrane
o Inhibition of secretion of ADH, renin, and
aldosterone
o Endogenous diuretic
Atrial Natriuretic Peptide
Increased BV
Decreased BP
Stretch of atria
ANP release
Decreased BV
Decreased
reabsorption of
Na+ and water
Mechanisms by which Secretion of Atrial Natriuretic Peptide Increases Sodium Excretion in
Response to Increased Plasma Volume
Plasma volume
Atria
Atrial wall stretch
ANP secretion
Kidneys
Afferent arteriole
dilation
Efferent arteriole
constriction
Na+ reabsorption
Renin secretion
Glomerular capillary
pressure
GFR
Initial stimulus
Physiological response
Result
Na+ excretion
Aldosterone
Slide 1
Potassium/K+
o Abundant in ICF
o 3.5-5.0 mEq/L
o Control of K+ levels is important in healthy skeletal and cardiac muscle
activity
o Hormonal regulation of K+ in blood plasma by aldosteroneà increases K+
secretion and excretion
o K+ imbalance: the most lethal of electrolyte imbalancesà cardiac or
respiratory arrest
o Distribution:
K+ shifts between ECF and ICF due to concentration in blood plasma,
concentration of H+ in plasma, and insulin (decreases glucose and K+ in
blood)
Renal Handling of Potassium Ions
• Glomerulus: freely filtered
• Proximal tubules: reabsorbed
• Distal tubules and collecting ducts: reabsorbed
and secreted
• K+ secretion in distal tubules and collecting ducts
is regulated
• Aldosterone regulates principal cells
• As K+ increases in plasmaà stimulation of
aldosterone release
Potassium Reabsorption in Renal Tubules
Apical
membrane
Basolateral
membrane
Proximal
tubule
epithelial cell
Lumen of
proximal
tubule
K+
Unknown
mechanism
?
K+
Na+
K+
K+
Tubular fluid
Potassium reabsorption in the proximal tubule
K+
Peritubular
fluid
K+ Secretion
Secretion matches ingestion
DCT and cortical collecting duct
Types:
o Aldosterone-dependent: ingestionà high K+ in
bloodà aldosterone secretionà K+ secretion
o Aldosterone-independent: rise (fall) in blood K+ à
insertion (removal) of K+ channels in collecting duct
Potassium Secretion in Renal Tubules
Apical
membrane
Basolateral
membrane
Principal cell
Lumen of late
distal tubule or
collecting duct
K+
Na+
K+
Tubular fluid
Peritubular
fluid
Potassium secretion in the principal cells of the late distal tubule
and collecting duct
Calcium Balance
• Hypercalcemia: high plasma calcium
• Hypocalcemia: low plasma calcium
Critical function:
– Exocytosis
– Secretion
– Muscle contraction
– Increases contractility of cardiac and smooth
muscle
Routes of Calcium Exchange
Bone
Calcification
(calcitonin)
Ingestion
Digestive
tract
Absorption
(1,25-(OH2)D3)
Resorption
(PTH, 1,25-(OH2)D3)
Plasma
[Ca2+]
Filtration
Reabsorption
(PTH stimulates,
calcitonin
inhibits)
Kidneys
Renal Handling of Calcium
Blood calcium
– Bound to carrier proteins
– Free in plasma
– Ca2+ + protein
Ca-protein
– Free calcium: freely filtered at glomerulus
– 99% of filtered calcium is reabsorbed:
• 70% is reabsorbed in PCT
• 19–20% is reabsorbed in thick ascending limbs of the loops of
Henle. Regulated
• 9–10% is reabsorbed in DCT. Regulated
Hormonal Control of Plasma Calcium
Concentrations: Parathyroid Hormone (PTH)
• Stimulus: decreased Ca2+ in plasma
• Actions
– Increases Ca2+ reabsorption by kidneys
– Stimulates activation of 1,25dihydroxycholecalciferol in kidneys
– Stimulates reabsorption of bone
– Stimulates small increase in calcium absorption
– Overall effect: increased blood calcium
Role of Parathyroid Hormone in Calcium Balance
Slide 1
[Ca2+] in plasma
Parathyroid glands
PTH secretion
Negative
feedback
[PTH] in plasma
Kidneys
Phosphate reabsorption
Ca2+ reabsorption
Calcium excretion
in urine
Bone
1,25-(OH2)D3 activation
Ca2+ resorption
[1,25-(OH2)D3] in plasma
Negative
feedback
Kidneys
Gastrointestinal tract
Ca2+ absorption
Initial stimulus
Physiological response
Result
[Ca2+] in plasma
Hormonal Control of Plasma Calcium
Concentrations: Calcitonin
–Secreted from C cells of thyroid gland
–Release triggered by high plasma [Ca2+]
–Actions at target cells
• Increases bone formation
• Decreases calcium reabsorption by
kidneys
Acid-Base (pH) Balance
Requires the regulation of H+ concentration in body fluids
in order to maintain arterial blood pH= 7.35-7.45
pH < 7.35 = acidosis
pH > 7.45 = alkalosis
H+ concentration altered by:
1. Chemical buffers
2. Respiratory rate
3. Input and output of acids and bases
Compensation for Acid-Base
Disturbances
• Henderson-Hasselbalch equation
pH = 6.1 + log
[HCO3–]
[CO2]
• For pH = 7.4, [HCO3–]/[CO2] = 20:1
• Acidosis: [HCO3–]/[CO2] < 20:1
• Alkalosis: [HCO3–]/[CO2] > 20:1
• Kidneys regulate HCO3–
• Lungs regulate CO2
Inputs and Outputs of Acids to the Blood
Input
Diet
Metabolism
Output
Proteins
Fats
CO2
Lactic acid
Keto acids
H+
Kidneys
CO2
Lungs
Blood
[H+]
pH Balance in the Body
© 2016 Pearson Education,
Inc.
Acid-Base Disturbances
Respiratory Disturbances
Carbon dioxide is a source of acid
CO2 + H2Oà H2CO3 àHCO3– + H+
Normal PCO2 arterial blood = 40 mm Hg
Sources of CO2: metabolism
Output of CO2 through respiratory
system
Hypoventilationà Increased plasma
[CO2] ® Respiratory acidosis
Hyperventilationà Decreased plasma
[CO2] ® Respiratory alkalosis
Metabolic Disturbances
o Metabolic Alkalosis
ü Increased pH
Excessive vomiting
Consumption of alkaline products (baking soda)
Alterations in renal function (increased H+
secretion/ HCO3- reabsorption)
o Metabolic Acidosis
üDecreased pH
High-protein diet
High-fat diet
Heavy exercise
Severe diarrhea (loss of
bicarbonate)
Renal dysfunction (decreased H+
secretion/ HCO3 reabsorption)
Complications with A-B Disturbances
Acidosis
Alkalosis
Denatures proteins
Decreases excitability of
neurons: confusion, coma, and
death
Increases excitability of neuron
Retention of K+
K+ depletion
Cardiac arrhythmias
Vasodilation
Generation of APs in sensory
and motor neurons
Defense Mechanisms Against AcidBase Disturbances
Renal
compensation
Buffering of
hydrogen ions
Respiratory
compensation:
corrects 75% of A-B
disturbances
Adjustments to pH Changes
1. Buffering H+ ions: the quickest defense
ECF buffer: HCO3ICF buffers: phosphate (HPO42– + H+ àH2PO4–) and proteins
2. Respiratory compensation: within minutes
pH decreasesà hyperventilationà decrease of
pCO2àremoval of H+àpH increases
pH increasesà hypoventilationà increase of pCO2à
addition of H+à pH decreases
The Mechanism by which Decreases in Plasma pH Increase Ventilation
Plasma pH ( acidity)
Peripheral chemoreceptors
Detect and respond
Ventilation
Plasma PCO2
Plasma pH
Initial stimulus
Physiological response
Result
Negative
feedback
Adjustments to pH Changes
3. Renal Compensation: hours to days. Regulates hydrogen ions and
bicarbonate in urine
– Proximal tubule
• Bicarbonate reabsorption coupled to hydrogen secretion
– Distal tubule and collecting duct
• Secretion of hydrogen coupled to synthesis of new bicarbonate ions
Low pH (high H+ concentration)à increased reabsorption of HCO3 and
secretion of H+à pH increases
High pH (low H+ concentration)àdecreased HCO3 reabsorption and
secretion of H+à pH decreases
Bicarbonate Reabsorption and Hydrogen Ion Secretion in the PCT
Proximal tubule epithelial cell
H+
H+
H+
+ HCO3–
(secreted) (filtered)
H2CO3
H2O + CO2
Tubular fluid
K+
Na+
H+
CO2 + H2O
H2CO3
CA
CA
HCO3–
Na+
Na+
HCO3–
Cl–
HCO3–
Peritubular
fluid
Bicarbonate synthesis and hydrogen ion secretion by intercalated cells of the distal tubule and
collecting duct.
Intercalated cell
Tubular fluid
Peritubular
fluid
H+
H+
H+ + HPO42–
H2PO4
–
H+
H+
K+
CO2 + H2O
Cl–
H2CO3
CA
HCO3–
Cl–
HCO3–
Adjustments to pH Changes
• Glutamine in renal compensation
–Severe acidosis
Glutamine metabolism
produces new bicarbonate and
secretes hydrogen in the form
of ammonium
Bicarbonate production and hydrogen secretion by glutamine metabolism in the proximal tubule.
Peritubular
fluid
Tubular
fluid
NH4+
Na+
NH3 + H+
NH4+
K+
Glutamine
HCO3–
H+
Na+
Cl–
Na+
Na+
HCO3–
HCO3–
Acidification of the Urine
Compensation for Acid-Base
Disturbances
• Respiratory alkalosis
– Cause:
hyperventilation
– Decreased CO2 ®
decreased H+
– Compensation: renal
• Decreased H+
secretion
• Decreased HCO3–
reabsorption
• Respiratory acidosis
– Cause:
hypoventilation
– Increased CO2 ®
increased H+
– Compensation: renal
• Increased H+
secretion
• Increased HCO3–
reabsorption
Compensation for Acid-Base
Disturbances
• Metabolic acidosis
– Cause: increased H+ independent of CO2
– Compensation: respiratory and renal (unless renal
problem)
– Respiratory compensation
• Increased ventilation ® decreased CO2
– Renal compensation
• Increased H+ secretion
• Increased HCO3– reabsorption
• Increased synthesis of new bicarbonate
Compensation for Acid-Base
Disturbances
• Metabolic alkalosis
– Cause: decreased H+ independent of CO2 (increased
HCO3-)
– Compensation: respiratory and renal (unless renal
problem)
– Respiratory compensation
• Decreased ventilation ® increased CO2
– Renal compensation
• Decreased H+ secretion
• Decreased HCO3– reabsorption
• Decreased synthesis of new bicarbonate
Summary of acid-base disturbances and compensation
Slide 1
Arterial pH
pH < 7.35
OR
pH > 7.45
Acidosis
[HCO3–] < 24 mM
Metabolic acidosis
Respiratory
compensation
PCO2 < 40 mm Hg
OR
Alkalosis
PCO2 > 40 mm Hg
[HCO3–] > 24 mM
Respiratory acidosis
Metabolic alkalosis
Renal
compensation
[HCO3–] > 24 mM
Respiratory
compensation
PCO2 > 40 mm Hg
OR
PCO2 < 40 mm Hg
Respiratory alkalosis
Renal
compensation
[HCO3–] < 24 mM
Relationship between Na+, K+, and H+
• Reabsorption of Na+ stimulates the secretion of K+
and H+
• Low pH stimulates the secretion of H+ and inhibits the
secretion of K+; acidosis can lead to hyperkalemia
• Hyperkalemia stimulates the secretion of K+ and
inhibits secretion of H+; can lead to acidosis
• High pH stimulates the secretion and excretion of
more K+
Reabsorption of Na+ and Secretion of K+,
and H+
Blood Volume Reflex
Low BV
Baroreceptors
and stretch
receptors
Posterior
pituitary: ADH
Increased BV
Decreased water
secretion
Collecting ducts:
increased water
reabsorption
Blood Osmolarity
Low water intake
Elevation of osmolarity
Osmoreceptors in liver
and hypothalamus
Increased water
reabsorption and
constriction of
arteriolesà fluid
reabsorption
Increased secretion of
ADH
Increased thirst and fluid
intake
Decreased water
excretion
Use of Diuretics
• BP control and treatment
of edema
• Increase urine volume,
decreasing blood volume
and interstitial fluid volume