ZOO 3210 Lecture Notes - Lecture 4: Nephron, Inulin, Myoglobin
2 May 2018
School
Department
Course
Professor
Review
1.
Secretion and acid-base balance
2.
Hormonal regulation of kidney function
3.
Learning Outcomes:
Filterability = [substance] in filtrate / [substance] in
plasma
•
= 1 --> solute is filtered
○
< 1.0 --> not easily filtered
○
0 --> not filtered
○
Filterability:
•
Water (MW=18) --> 1.0
○
Sodium (MW=23) --> 1.0
○
Glucose (MW=180) --> 1.0
○
*carbohydrate from plant, used to calculate
GFR
!
Not recognized by mammalian cells
!
No method for reabsorption
!
Inulin (MW=5500) --> 1.0
○
Myoglobin (MW=17,000) --> 0.75
○
Albumin (MW=69,000) --> 0.005
○
Filterability of Substances:
•
Review: Kidney Filterability
Beavers: environment has abundant water,
medulla is thinner, nephrons have short loop of
Henle
○
Kangaroo rats: environment is very dry, medulla
is thicker, nephrons have long loop of Henle
○
Most species (e.g. rabbit) fall in between these
extremes
○
Loop of Henle is a major innovation of terrestrial
animals (mammals, birds ONLY) that allowed the
production of concentrated urine
•
Highly concentrated urine
○
High osmolarity
○
High U:P ratio
○
*maximum urine concentration correlated with
relative thickness of the renal medulla
○
Long loops of Henle produce:
•
Nephrons with long loops of Henle are juxtamedullary
(JM) nephrons, while those with short loops of Henle
are superficial (S) nephrons
•
Review: Loop of Henle
Filtration1.
Reabsorption2.
**Secretion3.
Excretion 4.
Major Functions of Excretory System:
Filtered
○
Re-absorbed
○
Secreted from blood to filtrate
○
Substances in plasma may be:
•
H+
○
HCO3-
○
Na+
○
K+
○
NH4+
○
Organic ions
○
Drugs
○
Toxins
○
Examples of secreted substances:
•
Remember that short-term (minutes to hours)
regulation of CO2 levels in mammals occurs
through variation in ventilation
○
Long term (hours to weeks) compensation for
imbalance of blood [H+] or [HCO3-] levels
occur through kidney via adjustments in
secretion
○
Secretion is linked to acid-base balance
•
[HCO3-] = ~20mM
!
[CO2] = ~1mM
!
Venous blood is slightly acidic
(contains CO2 waste from tissues) ;
pH 7.35
□
Arterial blood is slightly basic ; pH
7.45
□
*note: below 7.4 --> acidic; above 7.4 -->
basic
!
In mammals, when blood pH is 7.4….
○
Increase CO2 --> increase H+ --> decrease
pH
!
[H+] increases from 1 to 2 (100%
increase)
□
(already a large amount of
HCO3-in blood and little
amount of H+ so changes in
CO2 has larger impact on H+
concentration)
!
[HCO3-] increase from 600,000 to
600,001 (0.00017% increase)
□
If [CO2] increases
!
Recall: CO2 + H2O <--> H2CO3 <--> H+ +
HCO3-
○
Therefore: pH = pK + log (20/1) =6.1 + 1.3
= 7.4
!
Recall: pK = pH at which there is an equal
concentration of HCO3-and CO2
!
According to the Henderson-Hasselbach
equation, pH = pK + log([base/[acid])
○
*as temperature decreases, blood pH increases in
ecotherms
○
Normal acid-base balance:
•
pH = 7.1
□
CO2 increases to 2
□
Without compensation:
!
pH = 7.4
□
HCO3 increases to 40 to compensate
for doubling of CO2
□
*compensated by kidney HCO3-
retention
□
With compensation:
!
Respiratory acidosis (caused by hypoventilation)
○
pH = 7.7
□
CO2 decreases to 0.5
□
Without compensation:
!
pH = 7.4
□
HCO3-decreases by 1/2 to 10 to
compensate for CO2 decrease
□
*compensated by kidney HCO3-
secretion
□
With compensation:
!
Respiratory alkalosis (caused by
hyperventilation)
○
The property that is initially altered in respiratory
disturbances of pH is the CO2 partial pressure
•
pH = 7.1
□
HCO3-decreases to 10 mM
□
Without compensation:
!
pH = 7.1
□
CO2 decreases to 0.75 mM while
HCO3-increases to 15 mM
□
*compensated by hyperventilation
and kidney HCO3-retention
□
With compensation:
!
Metabolic acidosis (caused by HCO3-deficit)
○
pH = 7.7
□
HCO3-increases to 40 mM
□
Without compensation:
!
pH = 7.4
□
CO2 increases to 1.25 mM while
HCO3-decreases to 25 mM
□
*compensated by hypoventilation
and kidney HCO3-secretion
□
With compensation:
!
Metabolic alkalosis (caused by HCO3-excess)
○
The property that is initially altered in metabolic
disturbances of pH is the blood [HCO3-]
•
Note: kidneys cannot raise plasma [H+] by
reabsorbing more of the filtered H+ (no
reabsorptive mechanisms for H+)
○
Decrease in plasma [H+] alleviates
initial increase in plasma [H+]
□
--> increases H+ secretion --> increases
H+ excretion
!
Increase in plasma [HCO3-] buffers
initial increase in plasma [H+]
□
--> increases HCO3-conservation -->
decrease HCO3-excretion
!
Increase in plasma [H+] (or [CO2])
○
When the [H+] of the plasma is elevated (blood pH is
low), kidney tubular cells will regulate both H+ and
HCO3-excretion
•
Fish: by the gills
○
Amphibians: by the skin
○
Acid secreting
□
*see slide
□
Na+ is moved into the tubule/duct
from the tubular lumen and into the
blood
□
H+ is moved into the lumen via a
ATPase
□
Note: CO2 + H2O --> HCO3-
+ H+ via carbonic anhydrase
!
From the blood, K+ is exchanged
while CO2 is secreted into the cells
while HCO3-is moved out and into
the blood
□
Cl-also enters the cell from the
blood
□
A-type cells of the kidney:
!
Base secreting
□
+ H2O --> H+ + HCO3-
!
H+ is moved into the blood via
ATPase
!
HCO3-is moved into the
lumen
!
CO2 diffuses into cell from blood
□
Cl-moves in opposite direction from
the lumen into the blood
□
B-type cells of the kidney:
!
Birds and mammals: by the kidney (in distal
tubule and collecting duct)
○
Acid-base balance is achieved by excretion of H+ or
HCO3-
•
Secretion and Acid-base Balance
In thirsty animals (high osmolarity),
osmoreceptor stimulation in the hypothalamus
elicits the secretion of AVP/ADH from the
posterior pituitary into the blood
○
AVP/ADH stimulates the incorporation of
aquaporin channels in the collecting duct,
stimulating the return of water to the ECF by
osmosis
○
Vasopression (AVP) or Anti-diuretic Hormone (ADH)
•
Juxtaglomerular cells in afferent arteriole release
the enzyme renin in response to low blood
pressure
○
Macula densa cells in distal convoluted tubule
release inhibitory substance to prevent renin
release if blood pressure is high
○
Renin stimulates a hormonal cascade that
produces angiotensin II and aldosterone
○
Angiotensin II stimulates arteriole constriction,
thirst, and AVP secretion
○
Aldosterone stimulates Na+ reabsorption which
promotes water retention
○
*see slide for cascade system
○
These cells are stimulated to increase the
expression (mRNA) and synthesis
(protein) of Na+K+ATPase, Na+ channel
and K+ channel
!
Na+ (and Cl-) reabsorption exert an
osmotic "hold" on water
□
More H2O reabsorption results in an
increase in blood pressure
□
Resulting is more Na+ reabsorption
!
Aldosterone is a steroid hormone that binds to
cytoplasmic receptors in the distal tubule and
collecting duct cells
○
Renin-Angiotensin-Aldosterone system
•
Others
•
Hormonal Regulation of Kidney Function
Acid-base Balance
Tuesday,+ March+ 13,+2018
11:23+AM
Review1.
Secretion and acid-base balance2.
Hormonal regulation of kidney function 3.
Learning Outcomes:
Filterability = [substance] in filtrate / [substance] in
plasma
•
= 1 --> solute is filtered
○
< 1.0 --> not easily filtered
○
0 --> not filtered
○
Filterability:
•
Water (MW=18) --> 1.0
○
Sodium (MW=23) --> 1.0
○
Glucose (MW=180) --> 1.0
○
*carbohydrate from plant, used to calculate
GFR
!
Not recognized by mammalian cells
!
No method for reabsorption
!
Inulin (MW=5500) --> 1.0
○
Myoglobin (MW=17,000) --> 0.75
○
Albumin (MW=69,000) --> 0.005
○
Filterability of Substances:
•
Review: Kidney Filterability
Beavers: environment has abundant water,
medulla is thinner, nephrons have short loop of
Henle
○
Kangaroo rats: environment is very dry, medulla
is thicker, nephrons have long loop of Henle
○
Most species (e.g. rabbit) fall in between these
extremes
○
Loop of Henle is a major innovation of terrestrial
animals (mammals, birds ONLY) that allowed the
production of concentrated urine
•
Highly concentrated urine
○
High osmolarity
○
High U:P ratio
○
*maximum urine concentration correlated with
relative thickness of the renal medulla
○
Long loops of Henle produce:
•
Nephrons with long loops of Henle are juxtamedullary
(JM) nephrons, while those with short loops of Henle
are superficial (S) nephrons
•
Review: Loop of Henle
Filtration
1.
Reabsorption
2.
**Secretion
3.
Excretion
4.
Major Functions of Excretory System:
Filtered
○
Re-absorbed
○
Secreted from blood to filtrate
○
Substances in plasma may be:
•
H+
○
HCO3-
○
Na+
○
K+
○
NH4+
○
Organic ions
○
Drugs
○
Toxins
○
Examples of secreted substances:
•
Remember that short-term (minutes to hours)
regulation of CO2 levels in mammals occurs
through variation in ventilation
○
Long term (hours to weeks) compensation for
imbalance of blood [H+] or [HCO3-] levels
occur through kidney via adjustments in
secretion
○
Secretion is linked to acid-base balance
•
[HCO3-] = ~20mM
!
[CO2] = ~1mM
!
Venous blood is slightly acidic
(contains CO2 waste from tissues) ;
pH 7.35
□
Arterial blood is slightly basic ; pH
7.45
□
*note: below 7.4 --> acidic; above 7.4 -->
basic
!
In mammals, when blood pH is 7.4….
○
Increase CO2 --> increase H+ --> decrease
pH
!
[H+] increases from 1 to 2 (100%
increase)
□
(already a large amount of
HCO3-in blood and little
amount of H+ so changes in
CO2 has larger impact on H+
concentration)
!
[HCO3-] increase from 600,000 to
600,001 (0.00017% increase)
□
If [CO2] increases
!
Recall: CO2 + H2O <--> H2CO3 <--> H+ +
HCO3-
○
Therefore: pH = pK + log (20/1) =6.1 + 1.3
= 7.4
!
Recall: pK = pH at which there is an equal
concentration of HCO3-and CO2
!
According to the Henderson-Hasselbach
equation, pH = pK + log([base/[acid])
○
*as temperature decreases, blood pH increases in
ecotherms
○
Normal acid-base balance:
•
pH = 7.1
□
CO2 increases to 2
□
Without compensation:
!
pH = 7.4
□
HCO3 increases to 40 to compensate
for doubling of CO2
□
*compensated by kidney HCO3-
retention
□
With compensation:
!
Respiratory acidosis (caused by hypoventilation)
○
pH = 7.7
□
CO2 decreases to 0.5
□
Without compensation:
!
pH = 7.4
□
HCO3-decreases by 1/2 to 10 to
compensate for CO2 decrease
□
*compensated by kidney HCO3-
secretion
□
With compensation:
!
Respiratory alkalosis (caused by
hyperventilation)
○
The property that is initially altered in respiratory
disturbances of pH is the CO2 partial pressure
•
pH = 7.1
□
HCO3-decreases to 10 mM
□
Without compensation:
!
pH = 7.1
□
CO2 decreases to 0.75 mM while
HCO3-increases to 15 mM
□
*compensated by hyperventilation
and kidney HCO3-retention
□
With compensation:
!
Metabolic acidosis (caused by HCO3-deficit)
○
pH = 7.7
□
HCO3-increases to 40 mM
□
Without compensation:
!
pH = 7.4
□
CO2 increases to 1.25 mM while
HCO3-decreases to 25 mM
□
*compensated by hypoventilation
and kidney HCO3-secretion
□
With compensation:
!
Metabolic alkalosis (caused by HCO3-excess)
○
The property that is initially altered in metabolic
disturbances of pH is the blood [HCO3-]
•
Note: kidneys cannot raise plasma [H+] by
reabsorbing more of the filtered H+ (no
reabsorptive mechanisms for H+)
○
Decrease in plasma [H+] alleviates
initial increase in plasma [H+]
□
--> increases H+ secretion --> increases
H+ excretion
!
Increase in plasma [HCO3-] buffers
initial increase in plasma [H+]
□
--> increases HCO3-conservation -->
decrease HCO3-excretion
!
Increase in plasma [H+] (or [CO2])
○
When the [H+] of the plasma is elevated (blood pH is
low), kidney tubular cells will regulate both H+ and
HCO3-excretion
•
Fish: by the gills
○
Amphibians: by the skin
○
Acid secreting
□
*see slide
□
Na+ is moved into the tubule/duct
from the tubular lumen and into the
blood
□
H+ is moved into the lumen via a
ATPase
□
Note: CO2 + H2O --> HCO3-
+ H+ via carbonic anhydrase
!
From the blood, K+ is exchanged
while CO2 is secreted into the cells
while HCO3-is moved out and into
the blood
□
Cl-also enters the cell from the
blood
□
A-type cells of the kidney:
!
Base secreting
□
+ H2O --> H+ + HCO3-
!
H+ is moved into the blood via
ATPase
!
HCO3-is moved into the
lumen
!
CO2 diffuses into cell from blood
□
Cl-moves in opposite direction from
the lumen into the blood
□
B-type cells of the kidney:
!
Birds and mammals: by the kidney (in distal
tubule and collecting duct)
○
Acid-base balance is achieved by excretion of H+ or
HCO3-
•
Secretion and Acid-base Balance
In thirsty animals (high osmolarity),
osmoreceptor stimulation in the hypothalamus
elicits the secretion of AVP/ADH from the
posterior pituitary into the blood
○
AVP/ADH stimulates the incorporation of
aquaporin channels in the collecting duct,
stimulating the return of water to the ECF by
osmosis
○
Vasopression (AVP) or Anti-diuretic Hormone (ADH)
•
Juxtaglomerular cells in afferent arteriole release
the enzyme renin in response to low blood
pressure
○
Macula densa cells in distal convoluted tubule
release inhibitory substance to prevent renin
release if blood pressure is high
○
Renin stimulates a hormonal cascade that
produces angiotensin II and aldosterone
○
Angiotensin II stimulates arteriole constriction,
thirst, and AVP secretion
○
Aldosterone stimulates Na+ reabsorption which
promotes water retention
○
*see slide for cascade system
○
These cells are stimulated to increase the
expression (mRNA) and synthesis
(protein) of Na+K+ATPase, Na+ channel
and K+ channel
!
Na+ (and Cl-) reabsorption exert an
osmotic "hold" on water
□
More H2O reabsorption results in an
increase in blood pressure
□
Resulting is more Na+ reabsorption
!
Aldosterone is a steroid hormone that binds to
cytoplasmic receptors in the distal tubule and
collecting duct cells
○
Renin-Angiotensin-Aldosterone system
•
Others
•
Hormonal Regulation of Kidney Function
Acid-base Balance
Tuesday,+ March+ 13,+2018 11:23+AM
Document Summary
Filterability = [substance] in filtrate / [substance] in plasma. Loop of henle is a major innovation of terrestrial animals (mammals, birds only) that allowed the production of concentrated urine. Beavers: environment has abundant water, medulla is thinner, nephrons have short loop of. Kangaroo rats: environment is very dry, medulla is thicker, nephrons have long loop of henle. Most species (e. g. rabbit) fall in between these extremes. *maximum urine concentration correlated with relative thickness of the renal medulla. Nephrons with long loops of henle are juxtamedullary (jm) nephrons, while those with short loops of henle are superficial (s) nephrons. Remember that short-term (minutes to hours) regulation of co2 levels in mammals occurs through variation in ventilation. Long term (hours to weeks) compensation for imbalance of blood [h+] or [hco3-] levels occur through kidney via adjustments in secretion. *note: below 7. 4 --> acidic; above 7. 4 --> basic. Venous blood is slightly acidic (contains co2 waste from tissues) ; ph 7. 35.
