Renal Physiology
PART TWO
Renal Clearance
1
Basic Mechanisms of Urine
Formation
Filtration, secretion, reabsorption and
excretion.
How do we determine these rates?
The master equation:
Rate of excretion = filtration +
secretion – reabsorption
2
TERMS
Urinary output is a flow rate; how much
urine are you producing per unit of time,
ml/min
This refers to the amount of urine
dripping into the urinary bladder, not the
amount voided.
3
TERMS
 Rate of filtration is the flow rate of plasma
fluid going into Bowman’s capsule.
 This plasma fluid is called “filtrate”.
 The filtrate is not the same as plasma since
there are no plasma proteins in it (proteins don’t
get through the filtration membrane, not just
because of their size, but also because of their
negative charge).
4
TERMS
 Glomerular Filtration Rate (GFR) is the
amount of fluid going into Bowman’s capsule
per unit of time.
 Normal GFR is 90 - 120 mL/min
 Dissolved in that filtrate are electrolytes,
glucose, and amino acids. We can also calculate
how much of those molecules are entering
Bowman’s capsule.
5
GFR
z Glomerular filtration rate (GFR) can be
calculated by measuring any chemical that
has a steady level in the blood, and is
freely filtered but neither reabsorbed nor
secreted by the kidneys.
6
GFR
z One such substance is creatinine.
z To determine GFR from creatinine, collect urine for 24hours and draw blood before and after the 24-hour
period.
z Then measure the amount of creatinine that was
removed from the blood during that time. Then apply
the results to a formula to determine GFR. You do not
need to do this for this class. On test questions, I will
tell you what the patient’s GFR is.
7
TERMS
 Filtered Load (or Tubular Load) is the amount of a
specific solute (electrolyte, glucose, or amino acid) dissolved
in the fluid that enters Bowman’s capsule. There is an
equation for this, but you have to know two things:
 Patient’s GFR
 Plasma concentration of that solute.
 To determine this, draw blood, place in spectrophotometer.
TL s = Ps x GFR
Filtrate vs. Solute
 If I had a cup and I filled it with 125ml of water,
and then added one packet of Crystal light, how
much fluid entered the cup? 125 ml.
 How much fluid (the filtrate) went into the cup
is the GFR.
 If you know how much solute (Crystal light)
went into the cup, you can calculate the filtered
load.
9
How to calculate Tubular Load
 If we want to know how much glucose was filtered into the
nephron, we need to know that person’s blood plasma glucose
levels, and we would need to calculate their GFR (normal is 90120mL/min).
 Each individual solute will have its own tubular load calculation.
TL glucose = Pglucose x GFR
TL sodium = Psodium x GFR
TL chloride = Pchloride x GFR
Kidney Function and Aging
 With age, our filtration membranes deteriorate, and
we also lose some of our glomeruli.
 With age, the permeability of our kidney
membranes also declines, causing a decline in GFR.
 Thus, we have a decline of urine production,
gradually over our lifetime.
 Some people age better than others with our skin,
some age better with their GFR.
 Older people have to take a lower dosage of
medicines that are excreted in the urine.
11
Solutes Suck!
 Sodium (Na+) is the most numerous of the
solutes in our plasma.
 Remember, if solutes are being reabsorbed,
water will come with it….solutes SUCK water!
 When salt is reabsorbed, water will be
reabsorbed too. When salt is secreted, water is
secreted too.
12
Solutes Suck!
 Some solutes are being reabsorbed, pulling water with
them, but other solutes are not being reabsorbed, so
they stay in the kidney tubules and are trying to keep
water with them.
 If there are more particles being reabsorbed, the water
will mostly be reabsorbed also.
 What will happen to the concentration of the
particles in the tubule that are not being
reabsorbed, while water is leaving? Their
concentration in the tubule will go up.
 Those things that are not reabsorbed will leave the
body.
13
Renal Equations
For any substance,
The rate of
excretion
(Urinary output)
= rate of +
filtration
rate of –
secretion
rate of
reabsorption
(GFR or TL)
Other terms that are used to express these ideas:
•For “Rate of excretion” we often use the term “urinary output”
•For “Rate of filtration,”
when referring to filtered fluid, we often use the term GFR (glomerular
filtration rate)
if referring to filtered solute, we use TL (Tubular Load)
14
Calculating Tubular Load of a Substance
(any solute, “s”)
 At the glomerulus, fluid and solutes (solids that were
dissolved in the fluid) are constantly being filtered and enter
the kidney tubules.
 GFR is the term for the volume of plasma fluid filtered each
minute.
 Once in the tubule, it is “tubular fluid” and no longer plasma,
but not yet urine.
 Tubular Load (TLs): the amount of any substance (s)
entering the tubule, each minute.
 TL depends on two things: the plasma concentration of the
solute and the rate of filtration of that solute
TL s = Ps x GFR
15
Tubular Filtrate Resembles Plasma
 By far, filtered fluid is mainly NaCl and
water.
 But it also contains other salts and
electrolytes, amino acids, small sugars,
vitamins and other small molecules, such
as wastes.
 Na+ and Cl- are present in such large
amounts; they are over 99% reabsorbed
along the length of the tubule. (Why?
We need it to keep our blood pressure
up)
 At a constant GFR, as plasma
concentration of a freely filtered
substance rises, the tubular load of the
substance rises in direct proportion to
plasma concentration
16
Remember the route the fluid takes:
Glomerulus 
Proximal convoluted tubule (PCT) 
Descending limb of LOH 
Ascending limb of LOH 
Convoluted tubule 
Collecting duct
Proximal
convoluted
tubule
Collecting duct
Distal convoluted tubule
Glomerulus
Loop of
Henle
descending
limb
Loop of Henle, thick
ascending limb
Solutes are reabsorbed
into the blood stream
 The next photo is of a Proximal Convoluted Tubule
(PCT), just beyond the glomerulus. The lumen of the
tubule contains the filtrate which leaked out of the
capillaries and into the glomerulus, entered Bowman’s
capsule, and has now arrived in the PCT.
 There are cells (tubular cells) lining the lumen of the
PCT. The cells have proteins that allow some solutes to
diffuse into the cell, and right back out cell, and into the
peritubular capillaries that surround the PCT. In that
way, solutes re-enter the blood stream.
19
Filtrate arriving from
Bowman’s Capsule
Peritubular
Capillaries
Tubular
Cells
Lumen of
PCT
20
Peritubular
capillaries
21
Proximal Convoluted Tubule
PCT
PCT
22
Proximal Convoluted Tubule
 Water will follow the solutes.
 The PCT is the biggest site for reabsorption of
solutes (substances dissolved in water).
 100% of glucose and amino acids are reabsorbed
in the PCT.
 67% of Na and water are reabsorbed here.
 If ADH levels are very high, most of the water will be
reabsorbed in the PCT.
 Water reabsorption along the proximal convoluted tubule
(PCT) occurs by osmosis resulting primarily from
reabsorption of sodium
23
Proximal Convoluted Tubule
 In a state of acidosis, the PCT will secrete H+ ions.
 When the H+ ions are secreted, reabsorption of
bicarbonate ions occurs at the same time.
 H+ ions are also secreted in the DCT, but bicarbonate
cannot be reabsorbed there.
24
Pressures
 Because we drop off a lot of fluid (125 ml of filtrate) into
Bowman’s capsule every minute, the water pressure in
the peritubular capillary beds is low.
 Because proteins cannot get through, the osmotic force
is very high here (proteins are trying to get in, but
cannot).
 In the glomerulus, the forces favor fluid to leave the
glomerulus and enter Bowman’s capsule.
 In the peritubular capillary bed, the forces favor the
fluid to enter the capillary bed.
25
Solutes without
transporters
 There are some solutes that cannot get through
the tubular cell membranes because they have
no protein transporters, so they become more
concentrated in the tubular lumen.
 The concentration increases until they are
forced to diffuse down their concentration
gradient and then they can enter the tubular
cells and be reabsorbed.
 One such solute is chloride (Cl-).
26
Active Transport
Active transport, facilitative transport, and
simple diffusion are all involved in renal
clearance.
It all starts in the membrane of the
tubular cells, which have protein
transporters that allow Na+, K+, glucose,
and other substances to get through. This
is called Active transport (it requires
ATP, so it uses energy).
27
Glucose reabsorption
 Glucose and amino acids leave the tubule and enter the
peritubular capillaries. That is reabsorption.
 When any substance leaves the bloodstream and enters
the lumen of the kidney tubules, it is secretion.
 By adjusting reabsorption and secretion, your body
adjusts its acid-base balance; if too many H+ ions were
kept in the plasma, there is too much acid, and the H+
ions will start to be secreted more.
28
Transport Maximum
 When proteins are shuttling solutes, the rate of this shuttling has a
maximum, called a transport max (Tm).
 If there are more solutes present than can be transported, the
solutes will end up in your urine. There will be a point at which you
can saturate these transporters. For instance, when your blood
glucose levels are elevated because you have a problem making
insulin or responding to insulin, then you will have an increase in
glucose load in Bowman’s capsule. This excess filtered load will
cause a spill of glucose into the urine.
 After the PCT, there are no more glucose transporters to reabsorb
it. 320 mg/ml is the max rate to filter glucose. If you filter 125
mg/ml and reabsorbed 125 mg/ml, how much did you excrete?
None. If you filter 375 mg/ml but reabsorb 320 mg/ml (transport
maximum), 55 mg/ml is excreted
29
Threshold
 Transport maximum is the total transport maximum
throughout all of the nephrons in the kidney. They do
not all have the exact number and type of transporters.
 One single nephron might get to maximum and a tiny
amount of glucose will appear in the urine. As more
nephrons reach their maximum, more glucose will
appear in the urine.
 That appearance of glucose in the urine before you
reach the overall Tm of the kidney is called threshold.
 Threshold is the plasma concentration at which a
substance begins to appear in the urine
30
=solute
= transporter
5/min
1
2
3
4
5
Transport maximum is
reached when carriers
are saturated.
31
=solute
= transporter
5/min
Excretion
1
2
3
4
5
Transport maximum is
reached when carriers
are saturated.
32
Calculate Glucose Excretion
 Step 1: Calculate their filtered load: GFR x
plasma glucose level 90ml/min x 2mg/ml
 Step 2: Determine reabsorption of glucose
(maximum is 150mg/min).
 Step 3: Subtract 150 from 180, and that tells
you their excretion.
 Filtration – reabsorption = Excretion
 Answer: 180 – 150 = 30 mg/min
33
A patient with uncontrolled diabetes has a
GFR of 90 ml/min, a plasma glucose of 2mg/ml, and a transport max
(Tm) shown in the figure. What is the glucose excretion for this patient?
250
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
Threshold
50
0
50
100
150
200
250
300
350
Filtered Load of Glucose
(mg/min)
Copyright © 2006 by Elsevier, Inc.
34
Answer: Filtration (GFR x Pglu) – reabsorption (Tmax) = Excretion
180 – 150 = 30 mg/min
250
GFR = 90 ml/min
PGlu = 2 mg/ml
Tmax = 150 mg/min
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
Threshold
50
0
50
100
150
200
250
300
350
Filtered Load of Glucose
Copyright © 2006 by Elsevier, Inc.
(mg/min)
35
A patient with uncontrolled diabetes has a
GFR of 90 ml/min, a plasma glucose of 2.33mg/ml, and a transport max
(Tm) shown in the figure. What is the glucose excretion for this patient?
250
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
Threshold
50
0
50
100
150
200
250
300
350
Filtered Load of Glucose
(mg/min)
Copyright © 2006 by Elsevier, Inc.
36
Answer: Filtration (GFR x Pglu) – reabsorption (Tmax) = Excretion
210 – 150 = 60 mg/min
250
GFR = 90 ml/min
PGlu = 2.33 mg/ml
Tmax = 150 mg/min
(mg/min)
200
Glucose
a. 0 mg/min
b. 30 mg/min
c. 60 mg/min
d. 90 mg/min
e. 120 mg/min
Transport
Maximum
(150 mg/min)
Reabsorbed
150
100
Excreted
.
Threshold
50
0
50
100
150
200
250
300
350
Filtered Load of Glucose
Copyright © 2006 by Elsevier, Inc.
(mg/min)
37
Urea
 Urea is also reabsorbed in the PCT.
 This happens because its concentration in the tubule is high, so it
diffuses down its concentration gradient, which means it will leave
the tubule and enter the capillaries.
 This is an advantage because it is a particle, and it brings water
with it.
 But urea is a waste product…how will we get rid of it?
 We will reabsorb it now and secrete it again further along in the
nephron. By the time the reabsorbed urea travels in the vasa recta
to the distal convoluted tubule, its concentration is higher in the
bloodstream than it is in the tubule, so it diffuses back out of the
capillaries and into the tubule to be excreted. The DCT is
impermeable to water, so water does not follow it.
38
Salt concentration in the PCT
 As you go along the length of the PCT, the amino acids
and glucose are reabsorbed, in addition to salt and
water.
 The salt concentration in the filtrate stays the same as
the blood plasma salt concentration.
 As we go through the rest of the nephron, the saltiness
will diminish as it becomes more like urine and less like
plasma.
39
Diuretics in the PCT
cause diuresis by reducing net water
reabsorption from the proximal
convoluted tubule
Some diuretics are “Potassium sparing”
because they decrease potassium
excretion
Mannitol: potassium-sparing
Lasix: not potassium-sparing
40
Diuresis in the PCT
 Diuresis means the person is excreting a lot of water.
This is what happens in diabetes mellitus (and insipitus).
It makes the person thirsty, so they drink a lot of water.
 However, that is not why they have diuresis.
 The reason for the diuresis is the large amount
of glucose in the tubule draws water with it,
since glucose is a particle.
 Thus, the large filtered load of glucose has an
osmotic effect on the tubule
41
Summary of PCT functions
Reabsorbs 2/3 of the salt and water
Reabsorbs 100% of glucose and amino acids
Reabsorbs 65% of potassium
Reabsorbs 50% of urea
Regulates pH in the filtrate
Secretes creatinine (waste product after you eat protein)
into the filtrate
42
Now we leave the PCT and
enter the Loop of Henle
 Our kidneys are responsible for adjusting the urinary
output.
 They are responsible for determining if you have a lot of
urine which very dilute, or scant, concentrated urine.
 If you drink a lot of water, it will make your urine dilute
(more water than solutes).
 If you are dehydrated, your urine will be concentrated
(more solutes than water).
 Caffeine and alcohol are dehydrating, so they have the
opposite effect of drinking water. They block antidiuretic
hormone (ADH) too.
43
Before we move onto the Loop of Henle,
be mindful of the following:
 How can you make a solution
more concentrated? Take out
water or add more solute.
 How can you make a solution
less concentrated? Add water or
take out more solute.
 Your kidneys play that game. To do
that, we have to separate solutes
and water. But how do we do that,
since water follows particles? There
are several parts of the nephron that
are impermeable to water.
44
Loop of Henle
Ascending limb
Descending
limb
LOOP OF HENLE:
Descending Limb
 Water is reabsorbed
 Na+ and urea are secreted
 What will your filtrate taste like here?
 We are removing water and adding salt.
46
Keep track of the water:
 20% of water is reabsorbed in the descending limb, and 67% was
reabsorbed in the PCT. That means a total of 87% of our filtered
water has now been reabsorbed. The remaining 13% can be
tapped into if your body needs it. If you are well hydrated, it will go
into the toilet. If you are dehydrated, hormones will be needed
farther along in the nephron in order to reabsorb more water.
 In the PCT, you have reabsorbed 50% of urea. Although it is a
waste product, we use it to create an osmotic gradient to reabsorb
glucose and other good solutes. Now, we want to get rid of the
urea since we are done reabsorbing all the glucose.
 By the time the filtrate is at the tip of the LOH, all of the urea that
had gone back into the blood will be secreted back into the lumen,
plus some more. The descending limb contains 110% of the urea
you initially filtered.
47
LOOP OF HENLE:
Ascending Limb
Impermeable to water, so no water is
reabsorbed or secreted.
Permeable to NaCl and urea:
NaCl (or sodium and chloride separately)
diffuses out of tubule (reabsorbed)
Urea diffuses into tubule (secreted)
48
Saltiness in the LOH
 Now let’s take the LOH together: on the descending limb we have
water leaving and salt entering the lumen.
 On the ascending limb, we have salt leaving, and no more water
leaving the lumen.
 As it goes up the ascending limb, it is becoming more and more
hypo-osmotic (less and less salty). At the top of the ascending limb,
it tastes less salty than blood plasma.
Now we leave the LOH and
enter the distal convoluted
tubule (DCT)
49
Distal convoluted
tubule
Early DCT
Late DCT
Early Distal Convoluted Tubule
(DCT)
 Thiazide diuretics have their effect in the early
distal convoluted tubule.
 A thiazide diuretic is one that blocks sodiumchloride channels, so that sodium cannot be
reabsorbed, so water cannot be reabsorbed.
 This will cause water loss, which will lower blood
pressure.
51
Distal Convoluted Tubule (DCT)
 5% more sodium is reabsorbed
 The DCT activity can be influenced by hormones.
If there are no hormones around, these cells don’t
do anything; whatever is remaining in the lumen
will go into the bladder.
 If there are no hormones, the last 13% of water
and the last 3% of Na goes into the toilet.
 Anti-diuretic hormone (ADH) and aldosterone will
cause more water and salt to be reabsorbed
(raises blood pressure).
52
Distal Convoluted Tubule (DCT)
 Special cells in the DCT, called intercalated cells manage
your acid-base balance, to secrete more H+.
 If you are in a state of acidosis (too much acid in your
blood) because you drank alcohol, your intercalated cells
will secrete more H+ to bring the pH back to normal.
 If you are in a state of alkalosis because you have been
hyperventilating (breathing fast), will the intercalated
cells increase H+ reabsorption or H+ secretion?
 Answer: increase H+ reabsorption.
53
We’ve covered filtration and
reabsorption….Now, it’s time for
Tubular Secretion
Secretion = Excretion – Filtration+ reabsorption
54
Secretion
 Secretion is the opposite of reabsorption. Any time you
see a solute going from the tubular cells and into the
lumen, it is called secretion. Secreted substances end
up in the urinary bladder.
 It happens by active transport. We secrete acids, bases,
phosphates, excess potassium.
 Secretion works this way: solutes diffuse out of the
peritubular capillary bed and into the tubular cells, then
they enter lumen of the convoluted tubule. From there,
they go out the collecting duct, and into the urinary
bladder.
55
Long-Term Dehydration
 Compensations in a dehydrated person who is deprived
of water for 36 hours include the following:
 increased plasma renin
 increased plasma ADH
 decreased concentration of plasma atrial natriuretic
hormone (vasodilator made by the heart; increases
diuresis)
 increased water permeability of the collecting duct
 decreased water permeability in the ascending loop
of Henle
56
Hormones affecting the
kidney
 Renin: released by kidney when blood pressure is too low
 ACE: Pulmonary capillary enzyme that responds to renin. When renin is
elevated, it cleaves angiotensin I into angiotensin 2.
 Angiotensin II: causes blood vessel constriction to increase blood
pressure. It also stimulates the release of aldosterone.
 Aldosterone: Secreted from the zona glomerulosa of the adrenal cortex.
It increases blood pressure by increasing sodium reabsorption. It is
primarily released due to elevated potassium levels.
 ADH: Promotes aquaporin insertion in the cell membranes of the tubules
 Aquaporin is a protein that allows water to pass through the cell
membrane, to be absorbed out of the tubule.
 Atrial natriuretic peptide (ANP): heart hormone that promotes more
diuresis and urine production to lower blood pressure.
 Adenosine: Macula densa use this to molecule to change the radius of the
afferent arteriole.
57
Summary of What’s Going On
Glomerulus
 Capillary hydrostatic pressure is very high here
(about 60mmHg).
Bowman’s capsule
colloid osmotic pressure here is essentially
zero
58
Summary of What’s Going On
PCT
 part of the nephron normally reabsorbs the most water
 Site of sodium-glucose co-transport as well as sodium-amino
acid co-transport
 Even though reabsorption is occurring, tubular fluid is isosmotic
to plasma throughout the length of this region.
 Site of most potassium reabsorption when no aldosterone is
present
 secretes hydrogen, is rich in carbonic anhydrase, and accounts
for most bicarbonate reabsorption
59
Summary of What’s Going On
Descending Limb
allows secretion of sodium and urea and is
permeable to water
These are highly permeable to water, low
permeability to solutes, and are considered
diluting segments.
60
Summary of What’s Going On
LOH
have the maximally hyperosmotic fluid when
ADH levels are high
At the Tip of the LOH
Tubular fluid here is always maximally
hyperosmotic to plasma, and is not hormone
sensitive
61
Summary of What’s Going On
Thick ascending limb
has the Na+/K+/Cl- co-transporter
is sensitive to the diuretic furosemide (lasix).
are impermeable to water, reabsorb solutes,
and are considered diluting segments.
62
Summary of What’s Going On
DCT
Macula densa is found here
is sensitive to sodium channel blockers like
amiloride and aldosterone inhibitors
Site of hormonally regulated potassium
secretion
The intercalated cells of this region secrete
hydrogen, is rich in carbonic anhydrase, and
makes “new” bicarbonate.
63
Summary of What’s Going On
Collecting Duct
have the maximally hyperosmotic fluid when
ADH levels are high
NOTE: Print the following slide and
write notes on what is going in and
what is coming out of each area of
the nephron.
64
Glomerulus
Early Distal convoluted tubule
Bowman’s capsule
Late Distal convoluted tubule
Proximal
convoluted
tubule
Collecting duct
Descending limb
Thick
Ascending
Limb
Vasa
recta
Loop of Henle (tip)
65
Glomerulus
Early Distal convoluted tubule
Bowman’s capsule
Macula densa is found here
is sensitive to sodium channel blockers
like amiloride and aldosterone inhibitors
Site of hormonally regulated potassium
secretion
The intercalated cells of this
region secrete hydrogen,
rich in carbonic anhydrase,
and makes “new” bicarbonate.
Proximal
convoluted
tubule
Descending limb
Late Distal convoluted tubule
allows secretion of sodium
and urea and is permeable to
water
These are highly permeable
to water, low permeability to
solutes, and are considered
diluting segments.
Thick
Ascending
Limb
Collecting duct
have the maximally
hyperosmotic fluid
when ADH levels
are high
Vasa
recta
Loop of Henle (tip)
has the Na+/K+/Cl- cotransporter
is sensitive to the diuretic
furosemide (lasix).
are impermeable to water,
reabsorb solutes, and are
considered diluting segments.
have the maximally hyperosmotic fluid when ADH levels
are high At the tip: Tubular fluid here is always maximally
66
hyperosmotic to plasma, and is not hormone sensitive
Early Distal convoluted tubule
Glomerulus
Capillary hydrostatic pressure is very high here
(about 60mmHg).
Bowman’s capsule
Late Distal convoluted tubule
colloid osmotic pressure
here is essentially zero
Vasa
recta
Proximal
convoluted
tubule
Urea is also reabsorbed in the PCT.
This happens because its
concentration in the tubule is high, so it
diffuses down its concentration
gradient, which means it will leave the
tubule and enter the capillaries.
This is an advantage because it is a
particle, and it brings water with it.
But urea is a waste product…how will
we get rid of it?
We will reabsorb it now and secrete
it again further along in the
nephron. By the time the
reabsorbed urea travels in the vasa
recta to the distal convoluted
tubule, its concentration is higher in
the bloodstream than it is in the tubule,
so it diffuses back out of the capillaries
and into the tubule to be excreted. The
DCT is impermeable to water, so water
does not follow it.
part of the nephron normally
reabsorbs the most water
Site of sodium-glucose cotransport as well as sodium-amino
acid co-transport
Even though reabsorption is
occurring, tubular fluid is isosmotic
to plasma throughout the length of
this region.
Site of most potassium
reabsorption when no aldosterone
is present
secretes hydrogen, is rich in
carbonic anhydrase, and accounts
for most bicarbonate reabsorption
Descending limb
Thick
Ascending
Limb
Loop of Henle (tip)
Collecting duct
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Clinical Correlations
What are the symptoms of severe
dehydration?
1. Disoriented
2. Falls unconscious
3. Measurable loss of weight during
strenuous activity (water loss)
4. Blood pressure drops
68
Clinical Correlations
A marathon runner becomes dehydrated
during a race.
1. What will happen to their weight?
2. What will happen to blood volume?
3. What will happen to blood pressure?
4. What will happen to heart rate?
5. What will happen to their baroreceptors?
6. What will happen to sympathetic outflow?
69
Clinical Correlations
A marathon runner becomes dehydrated
during a race.
1. Weight goes down (water loss)
2. Blood volume decreases (water loss)
3. Blood pressure decreases (volume loss)
4. Heart rate increases (b/c of decreased BP)
5. Baroreceptors decrease firing (low BP)
6. Sympathetic outflow increases (to
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compensate)
Clinical Correlations
A marathon runner becomes dehydrated
during a race.
1. What will happen to their Renal blood
flow (RBF)?
2. What will happen to their tubular load of
sodium?
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Clinical Correlations
A marathon runner becomes dehydrated
during a race.
1. Renal blood flow (RBF) will decrease
The body does not want to lose more water
2. Tubular load of sodium will decrease
Sodium is reabsorbed so water will come with it
72
Clinical Correlations
A marathon runner becomes dehydrated
during a race.
1. What hormones would compensate for
this condition?
These would all be elevated:
Adenosine
Renin
Angiotensin II
Aldosterone
ADH
73
Clinical Correlations
A marathon runner becomes dehydrated
during a race.
1. What will be the urinary output?
Low volume
2. What will be the urine concentration?
High concentration
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Clinical Correlations
A marathon runner becomes dehydrated
during a race and falls unconscious.
1. What type of shock is this?
Hypovolemic shock
2. What is the treatment?
I.V. saline/bicarbonate solution
Giving saline will increase water retention
Giving bicarbonate will reduce acidosis
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Clinical Correlations
A marathon runner becomes dehydrated
during a race and falls unconscious.
1. Why do they have acidosis?
Hypovolemic shock reduces oxygen delivered to
tissues.
Muscles without oxygen start to convert to
anaerobic metabolism to get their ATP. The
waste product of anaerobic metabolism is lactic
acid.
The buildup of lactic acid without the kidney
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excreting it causes metabolic acidosis.
Clinical Correlations
 January 12th, 2007, A 28 year-old mother of three from
Sacramento decides to go on a radio program to compete
in a contest called, “Hold your Wee for a Wii.”
 During this contest, contestants drank great volumes of
plain water. She drank 6 liters in 2 hours (3 liters an hour).
The maximum the kidney can filter is 1 liter an hour.
 After the contest, she called her co-workers to say she
wasn’t coming to work because her head hurt so badly.
 Later she is found dead.
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Clinical Correlations
 Drinking too much water changes the extracellular
osmolality. When the plasma is too dilute (too
much water, too few solutes), water will leave the
bloodstream to enter the tissues, where there are
more solutes (solutes SUCK!).
 Water will enter the tissues (intracellular body fluid
compartment), including the brain.
 The excess water will cause the brain to swell.
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Water moves through
Compartments
 Intracellular water (or other fluid) is the watery substance inside a cell.
 Interstitial water (or other fluid) is the watery substance between cells.
 Extracellular water (or other fluid) is the watery substance that is outside
of cells. Some of it may be interstitial, some may be in the blood, joints,
CSF, etc.
z The concentration of individual solutes (glucose, sodium, potassium,
chloride) is different in intracellular fluid than it is in extracellular or
interstitial fluid, but the total osmolarity (concentration of all the
solutes combined) of the intracellular fluid, extracellular fluid,
and interstitial and is the same.
z Water can move from one compartment to another. It can be drawn out
of the plasma to enter the interstitial compartment first, and then it may
enter the cells.
 Water can also move from the cells to the interstitial compartment, then
into the bloodstream.
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Water/Salt Imbalance
Problems
 Expansion: the body has retained too much water
 Contraction: the body has too little water
 Hypo-osmotic volume
 The water in the body has too much water, too few solutes
 Hyperosmotic volume
 The water in the body has too little water, too many solutes
 Isosmotic volume
 The water in the body has the proper balance of water and solutes.
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Water/Salt Imbalance
Problems
 Hypo-osmotic volume expansion
 Excessive water drinking; plasma osmolality is reduced from too much
water, not enough solutes (hypo-osmotic) and the extracellular fluid
(outside of cells) volume has increased (expansion).
 Hypo-osmotic volume contraction
 Excessive sweating; the person has lost a lot of salt, but has lost some
water, too. They are dehydrated (contraction) and have low salt levels
(hypo-osmotic). The water in the body has low osmolality due to loss of the
salt.
 Hyperosmotic volume expansion
 High salt intake; there is too many solutes, water is retained, so the
overall volume is increased (expansion), but there is a lot of salt, so
osmolality is increased (hyperosmotic).
 Hyperosmotic volume contraction
 Dehydration; the person has lost a lot of water, so overall volume is
decreased (contraction). The salt level has not changed, so that means
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more salt dissolved in less water (hyperosmotic).
Water/Salt Imbalance
Problems
 Isosmotic Volume Contraction
 Diarrhea or burn victim; loss of water and solutes.
Overall water/salt ratio is maintained (isosmotic), but
person loses overall volume (contraction).
 Isosmotic Volume Expansion
 Salt Infusion; person receives an i.v. of normal saline
(isosmotic), and overall volume of body fluid
increases (expansion).
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Water/Salt Imbalance
Problems
 The same number of proteins remains in the blood, but
water may increase or decrease.
 These volume changes therefore affect the protein
concentrations in the blood.
 With more volume (expansion), protein concentrations
decrease. With less volume (contraction), the protein
concentrations increase.
 However, hematocrit is not always affected by blood
volume changes. Small changes in volume affect the
protein concentrations, but may not affect the
hematocrit.
83
Hyperosmotic volume
contraction
Diabetes insipidus
There would be elevated protein
concentration but NO CHANGE in
hematocrit with this condition
84
Hyperosmotic volume
expansion
Conn’s disease would cause this condition
There would be decreased protein
concentration and decreased
hematocrit
85
Hypo-osmotic volume
contraction
Addison’s Disease would cause this
condition
There would be increased protein
concentration and increased
hematocrit
86
Hypo-osmotic volume
expansion
Syndrome of inappropriate ADH
(excessive secretion of ADH) would cause
this condition. Since too much ADH is
present, water is kept in the body.
There would be decreased protein
concentration but NO CHANGE in
hematocrit with this
87
Iso-osmotic volume
expansion
There would be decreased protein
concentration and decreased
hematocrit
Infusion of a 0.9g% saline solution would
cause this condition
In these conditions there would be NO
CHANGE in the intracellular volume
nor osmolality
88
Iso-osmotic volume
contraction
Diarrhea or burns would cause this
condition
In these conditions there would be NO
CHANGE in the intracellular volume
nor osmolality
There would be increased protein
concentration and increased
hematocrit
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Water Imbalance category
Condition
Disorder
Proteins
Hct
Drinking too much water
Low
Normal
or inappropriate ADH
Syndrome
Hypo-osmotic volume expansion
Excess water, low solutes
Hypo-osmotic volume contraction
Loss of water and salt
Addison's disease
High
High
Hyperosmotic volume expansion
High salt intake
Conn's disease
Low
Low
Hyperosmotic volume contraction
Loss of water, normal salt levels
Diabetes insipidis
High
Normal
Isosmotic volume expansion
Increase in normal saline
Normal saline iv
Low
Low
Isosmotic volume contraction
Loss of water and solutes, but water/salt is normal Diarrhea
High
High
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Hypernatremia
(excess sodium in the blood)
 Causes
 Hypovolemic
 Inadequate intake of water, typically in elderly or otherwise
disabled patients who are unable to take in water as their thirst
dictates. This is the most common cause of hypernatremia.
 Euvolemic
 Excessive excretion of water from the kidneys caused by diabetes
insipidus, which involves either inadequate production of ADH or
kidneys not responding to it.
 Hypervolemic
 Intake of a hypertonic fluid such as drinking seawater or receiving
an i.v. of sodium bicarbonate after a vigorous resuscitation. Can
also be caused by mineralocorticoid excess due to a disease state
such as Conn's syndrome or Cushing's Disease
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Hyponatremia
(too little sodium in the blood)
Causes
excessive sweating
persistent diarrhea
overuse of diuretic drugs
92
Hypokalemia
(low potassium in the blood)
 Mild hypokalemia
 Often without symptoms, although it may cause a
small elevation of blood pressure, and can
occasionally provoke cardiac arrhythmias.
 Moderate hypokalemia
 May cause muscular weakness, myalgia (muscle
pain), and muscle cramps
 Severe hypokalemia
 May cause flaccid paralysis and hyporeflexia
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Hypokalemia
(low potassium in the blood)
 Causes
 Inadequate potassium intake (rare)
 Gastrointestinal loss (vomiting or diarrhea)
 Urinary loss
 Thiazide diuretics
 Alkalosis in the blood
 Disease states that cause high aldosterone levels
 Conn’s syndrome (hyperaldosteronism)
 Cushing's syndrome (excess cortisol binds to the
Na+/K+ pumps, so it acts like aldosterone).
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Hyperkalemia
(high potassium in the blood)
 Extreme hyperkalemia is a medical emergency due to the risk of
potentially fatal abnormal heart rhythms (arrhythmia).
 Symptoms include malaise (tired), palpitations and muscle
weakness; mild hyperventilation may indicate a compensatory
response to metabolic acidosis, which is one of the possible causes
of hyperkalemia.
 Often, however, the problem is detected during screening blood
tests for a medical disorder, or it only comes to medical attention
after complications have developed, such as cardiac arrhythmia or
sudden death.
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Hyperglycemia and
Hypoglycemia
 Glucose levels vary before and after meals, and at
various times of day.
 Glucose in fasting adults should be 80 to 110 mg/dl.
 Above 126 mg/dl is hyperglycemia.
 Below 70 mg/dl is hypoglycemia.
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Clinical Correlations
Addison’s Disease
Conn’s Disease
Diabetes Mellitus
Diabetes Insipidus
Cushing’s Disease
Know which of these diseases has
hypernatremia, hypokalemia, hypo or
hyperglycemia, etc.
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Addison’s Disease
Chronic adrenal insufficiency (low
cortisol levels)
Hyponatremia
Hypoglycemia
Hyperkalemia
Possible death at times of extreme stress
Addisonian crisis: low blood pressure  coma
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Conn’s Disease
This is hyperaldosteronism.
The person releases too much
aldosterone, which increases sodium
retention, so water follows, and
hypertension results.
Condition associated primarily with
hypertension and mild hypernatremia and
mild hypokalemia. No diabetogenic
(glucose) problems.
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Diabetes Mellitus
 Condition characterized by polyuria, glucosuria, polydipsia and
ketonuria.
 Polyuria (frequent urination)
 Glucosuria (glucose in urine)
 Polydipsia (thirsty)
 Ketonuria (ketones in the urine)
 When insulin does not pull glucose into the body cells, it stays in
high levels in the blood (hyperglycemia) and spills out in the urine
(glucosuria). The body is starving, so it breaks down fat into fatty
acids for energy, and ketones are the waste product. In small
amounts, they are broken down in the liver, but in large amounts,
they build up in the blood (ketoacidosis: lowers blood pH) and spill
out into the urine (ketonuria). Starvation, fasting, prolonged
vomiting, high protein diets, and low carbohydrate diets also cause
this condition.
100
Diabetes Insipidus
Condition characterized by polyuria and
polydipsia, but not glucosuria.
This is more like a disease of water loss
(ADH is not produced).
101
Cushing’s Disease
 Hypernatremia
 Caused by lack of water in the blood, like
dehydration.
 Hypokalemia (low potassium)
 Hyperglycemia (excess glucose)
 Diabetes mellitus
 Weight gain, particularly of the trunk and face with
sparing of the limbs (central obesity), moon face,
buffalo hump, and sometimes growth of facial hair.
102
K+
Na+
Glucose
Addison's
High
Low
Low
Conn's
Mild low Mild high Normal
Diabetes Mellitus
High
Low
High
Diabetes Insipidus
High
High
High
Cushing's
Low
High
High
BP
Low
High
Other
Possible death at times of extreme stress
Polyuria, glucosuria, polydipsia, ketonuria, ketoacidosis
Polyuria, polydipsia only
Diabetes (Polyuria, glucosuria, polydipsia, ketonuria), central obesity,
moon face, buffalo hump, facial hair in women
103
Tests to assess kidney
function
 BUN (Blood Urea Nitrogen or Urea Nitrogen)
 Creatinine
 BUN/Creatinine Ratio
 Calcium
 Sodium
 Potassium
 Chloride
 CO2
104
Tests to assess kidney
function
BUN (Blood Urea Nitrogen or Urea Nitrogen). This is the
concentration of nitrogen (within urea) in the serum (but not in red
blood cells). A waste product, derived from protein breakdown,
produced in the liver and excreted by way of the kidneys. High values
may mean that the kidneys are not working as well as they should.
BUN is also elevated by blood loss, dehydration, high protein diets
and/or strenuous exercise which may temporarily and artificially raise
levels. A low BUN level may be the result of liver disease, a low protein
diet, pregnancy, or drinking an extreme amount of water.
105
Tests to assess kidney
function
Creatinine. A waste product largely from muscle metabolism
(breakdown). Concentration of creatinine in the blood depends upon
the amount of muscle that you have and the ability of your kidneys
to excrete creatinine. High values, especially with high BUN levels, may
indicate problems with the kidneys. Low values are generally not
considered significant.
BUN/Creatinine Ratio - This ratio is sometimes used or diagnostic
purposes.
106
Tests to assess kidney
function
Calcium. Calcium is one of the most important elements in the body.
The parathyroid glands and the kidneys control the amount of calcium
in the blood. The parathyroid gland is the main regulator of calcium in
the body. Nearly all of the calcium in the body is found in bone
(99%). The remaining 1% is very important for proper clotting, nerve,
and cell and enzyme activity. An elevated calcium level can be due to
medication (such as too much synthetic vitamin D), inherited disorders
of calcium handling in the kidneys, bone disease, or excess parathyroid
gland activity or vitamin D. Low calcium can be due to malnutrition,
drugs and certain metabolic disorders.
107
Tests to assess kidney
function
 Sodium. An electrolyte regulated by the kidneys and adrenal
glands. This element plays an important role in the water/salt
balance in your body.
 Potassium. Potassium is an electrolyte found primarily inside
cells and must be controlled very carefully by the kidneys. Its role
is to maintain water balance inside the cells and to help in the
transmission of nerve impulses. A low potassium level can cause
muscle weakness and heart problems. A high potassium level can
be found in kidney disease or in over ingestion of potassium
supplements.
108
Tests to assess kidney
function
 Chloride. Chloride is an electrolyte regulated by the kidneys and
adrenal glands. Chloride is important to the function of nerves,
muscles, and cells. It is usually associated with a high or low level
of sodium or potassium.
 Some drugs taken by prostate cancer patients such as estrogens
and corticosteriods can cause increased chloride.
 CO2. Co2 levels reflects the acid status of your blood.
Corticosteriods as well as kidney disease can be involved.
109