Chapter 14 - Moorpark College

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Chapter 14 - Kidney
Human Physiology, pages 513-562
I.
II.
Chapter 14 -Introduction
A.
Renal Function - Table 14-1, page 514
1.
Water, sodium, potassium, calcium and H+ regulation
2.
Removal and excretion of metabolic waste products:
creatinine, uric acid, urea
3.
Removal and excretion of foreign substances
4.
Gluconeogenesis
5.
Secretion of two hormones and one enzyme
a)
Erythropoietin
b)
Calciferol
c)
Renin - an enzyme involved in angiotensin secretion
(later)
Structure of the Kidney and Urinary System
A.
Figure 14-1, page 515
1.
Nephron - the functional unit of the kidney (about 1 million in
each), Figure 14-2, page 516
a)
Glomerulus - filtering component
(1)
Has a capillary bed - glomerular capillaries
(2)
Hollow capsule - Bowman's capsule and
space - Figure 14-3, page 517
(3)
Thin filtration barrier between capillaries and
Bowman's capsule - three layers
(a)
Capillary endothelium
(b)
Epithelial lining of Bowman's
capsule
(c)
Noncellular basement membrane
with podocytes (extensions of
epithelial cells through which fluid
moves during filtration)
(d)
Modified smooth muscle cells that
surround the glomerular capillary
loops – mesangial cells
(i)
Not part of the filtration
pathway
b)
Tubule - extends out from Bowman's capsule
(1)
A tube of epithelial cells with different
functions
(2)
Proximal tubule - close to Bowman's
capsule
(3)
Henle's loop - descending and ascending
(4)
Distal tube - farthest portion
(5)
Collecting duct - urine is finally formed here
c)
Path of excretion - Figure 14-4, page 518
(1)
Collecting duct into the renal pelvis
(2)
That leads to ureter
(3)
Empties into the urinary bladder
Chapter 14 - Kidney
Human Physiology, pages 513-562
d)
(4)
Urine eliminated through the urethra
Macula densa and granular cells (juxtaglomerular
cells) of afferent arteriole meet and form
juxtaglomerular apparatus (JGA) - an area of
enzyme secretion and monitoring of plasma - Figure
14-5, page 518
B.
III.
Circulation
1.
Afferent arteriole brings blood to glomerulus for filtration
2.
Unfiltered blood then leaves glomerulus via the efferent
arteriole where it breaks down into the peritubular capillaries
3.
The peritubular capillaries surround the tubules allowing
exchange - VERY IMPORTANT
4.
Blood leaves via the renal vein
5.
This is the Renal Portal System!
Basic Renal Processes
A.
Three basic processes - glomerular filtration, tubular reabsorption
and tubular secretion - Figure 14-6, page 519, Figure 14-7, page
519
Excretion - elimination of urine via kidneys
Defecation - elimination of feces via G.I. tract
Secretion - from cells to surfaces, lumens or into blood
stream
B.
Questions about any given substance
1.
Extent of filterability?
2.
Is it reabsorbed?
3.
Is it secreted?
4.
What role does metabolism by the tubular cells play
regarding the substance and its homeostasis?
C.
Glomerular filtration
1.
Formation of ultrafiltrate
a)
Figure 14-8, page 520
Favoring
filtration:
Blood Pressure
60 mmHg
Bowman's back
pressure
Osmotic gradient
due to absence of
protein in
ultrafiltrate
Net filtration
pressure =
-15 mmHg
Opposing
filtration:
-29 mmHg
16 mmHg
Chapter 14 - Kidney
Human Physiology, pages 513-562
b)
2.
3.
Ultrafiltrate is essentially protein free plasma
containing all the constituents of plasma in the blood
but lacking the protein (or most of it) - important to
understand!
c)
In a healthy person any protein that gets filtered is
reabsorbed by tubule cells
Rate of glomerular filtration (mention inulin)
a)
A 70 kg person filters (from plasma into Bowman's
capsule) 180 liters/day or 45 gallons weighing about
450 lbs
b)
The entire plasma volume is filtered 60 times a day,
i.e. a continuing process
c)
Glomerular filtration rate [GFR] - the volume filtered
per unit time
d)
GFR X plasma concentration of a substance will
determine total amount filtered, filtered load
glucose @ 1 g/l X 180 l/day= 180 g/day
e)
Comparing this figure with the amount appearing in
the urine can indicate whether absorption or
secretion is occurring normally
Balance between renal efferent and afferent arterioles and
PGC
a)
Back pressure effect, etc., Figure 14-9, page 522
Mesangial cells  surround glomerular capillaries
and when they constrict the total surface area for
exchange is reduced and decreases GFR
4.
Total renal plasma flow
a)
About 900 liters/day
b)
The GFR of 180 l/day is 20% of volume
5.
Total renal blood flow
a)
Plasma is 55% of whole blood
b)
Total renal blood flow = 1640 l/day (1.1 l/min)
6.
Kidneys receive 20 to 25% of total cardiac output of 5 l/min
even though their weight is less than 1% of the body weight
Tubular reabsorption, Table 14-2, page 522
1.
Compare values (Per Day)
b)
D.
Substance
Water, l
Sodium, g
Glucose, g
Urea, g
amt filt
180
630
180
54
a)
b)
amt/exc % reabsorbed
1.8
99.0
3.2
99.5
0
100
30
44
Certain substances, under normal conditions, are
reabsorbed completely, others partially
Not all substances are regulated as such, i.e.
glucose - even though it is reabsorbed it is
dependent on the number of carriers
Chapter 14 - Kidney
Human Physiology, pages 513-562
c)
E.
F.
G.
H.
Several substances can exceed the capacity of the
tubule to reabsorb them - more below
d)
Tubular epithelium, Figure 14-10, page 523
2.
Types of reabsorption
a)
Most tubular reabsorption is by mediated transport
mechanisms and/or diffusion
b)
The transport of some is coupled to an active
transport mechanism and is secondary active
transport
(1)
Movement of glucose is usually by facilitated
transported except in kidney tubules where it
is active
(2)
Maximal tubular capacity - Tm, when the
number of carriers are exceeded glucose
can "spill" over into the urine; this holds for
some other organic substances also
c)
Some substances are transformed by the kidney into
polar compounds and these are poorly reabsorbed
by the tubules so they go out in the urine
Reabsorption by diffusion
1.
As tubular-fluid moves through it becomes more
concentrated and materials will diffuse out
2.
Urea is an example
Tubular secretion
a)
This is from peritubular capillaries TO tubular lumen
b)
Two most important substances that are secreted
are potassium and hydrogen ion
c)
Some foreign substances are excreted by tubular
secretion such as penicillin
Metabolism by the tubules
1.
The cells of the tubules are capable of metabolizing or
synthesizing certain substances that can then be secreted
into the tubule
2.
The cells can synthesize ammonia and eliminate it in the
urine
Regulation of membrane channels and transporters
1.
Tubular reabsorption and/or secretion is under control of
regulation of transporter and channel proteins
2.
Regulation is by hormones, neurotransmitters and
paracrine/autocrine agents
Channels also respond to local changes  membrane
potential, mechanical forces and intracellular ion
concentrations
I.
Division of labor in the tubules
1.
Each part of nephron plays a different role in renal function
2.
From Bowman's capsule to the collecting tubules different
regulating forces are responsible for the overall homeostasis
IV.
Concept of Renal Clearance
3.
Chapter 14 - Kidney
Human Physiology, pages 513-562
A.
B.
The volume of plasma from which that substance is completely
cleared by the kidneys per unit time
Clearance of substance S
Us (mg/l) x V(l/hr)
Cs (l/hr)= -------------------Ps (mg/l)
V = urine volume/minute
Us = urine concentration of substance S
Ps = plasma concentration of substance
C.
Inulin  is freely filterable but is neither reabsorbed nor secreted,
Figure 14-11, page 525
300 (mg/l) x 0.1 (l/hr)
CIn (l/hr)= -------------------4 (mg/l)
D.
V.
= 7.5 l/hr
The 7.5 l/hr clearance value for inulin is equal to the GFR since
inulin is not reabsorbed or secreted
E.
4.0 mg/l * 7.5 l/hr = 30 mg/h (total inulin secreted)
Micturition (urination) - Figure 14-12, page 526
A.
Smooth muscle contractions of the ureter-wall propel the urine to
the bladder for storage and eventual elimination or micturition
B.
Walls of smooth muscle are collectively termed the detrusor muscle.
1.
Contraction of the detrusor muscle squeezes on the urine in
the lumen to produce urination.
2.
The detrusor muscle at the base of the bladder is called the
internal urethral sphincter. When the detrusor muscle is
relaxed, the sphincter is closed.
3.
When the detrusor muscle actively contracts, changes in the
muscle's shape pull open the outlet. Beyond the internal
urethral sphincter, skeletal muscle surrounds the urethra.
4.
This is the external urethral sphincter, the contraction of
which can prevent urination even when the detrusor muscle
contracts strongly.
C.
Descending CNS pathways can influence the local spinal reflex
action of micturition
1.
Involuntary: infancy or in persons with spinal-cord damage
a)
Afferent stretch receptor fibers in the bladder wall
stimulate the parasympathetic nerves that stimulate
the detrusor muscle
b)
The filling of the bladder stimulates detrusor muscle
to contract via the parasympathetic effector neurons
c)
The detrusor muscle (in response to filling) becomes
strong enough to pull open the internal urethral
sphincter. Simultaneously, the afferent input from
the stretch receptors inhibits, within the spinal cord,
the somatic motor neurons that were stimulating the
external urethral sphincter to contract.
Chapter 14 - Kidney
Human Physiology, pages 513-562
d)
2.
3.
Both sphincters open and the contraction of the
detrusor muscle is able to produce urination.
Voluntary prevention of micturition, learned response
a)
As the bladder fills, the input from the bladder
stretch receptors causes, via ascending pathways to
the brain, a sensation of bladder fullness and the
urge to urinate.
b)
In response to this, urination can be voluntarily
prevented via descending pathways that stimulate
the motor nerves to the external urethral sphincter
and simultaneously inhibit the parasympathetic
nerves to the detrusor muscle.
c)
The prevention of urination can be overcome once
the bladder exceeds its capacity.
In contrast, urination can be voluntarily initiated, regardless
of the degree of bladder fullness, via the descending
pathways.
SECTION B - REGULATION OF SODIUM, CHLORIDE AND WATER BALANCE
VI.
Total body balance of sodium and water
A.
Table 14-3, page 529 - water balance
Intake:
Drunk
Food
Metabolically
1200 ml
1000 ml
350 ml
TOTAL 2550 ml
Output
Insensible loss
Sweat
Feces
Urine
Total output
B.
900 ml
50 ml
100 ml
1500 ml
2550 ml
Table 14-4, page 529 (sodium chloride per day)
Intake:
Food
Output
Sweat
Feces
Urine
Total output
10.5 g
0.25 g
0.25 g
10.0 g
10.5 g
+
The kidney can regulate wide differences - this deals with Na , Cl
and water balance (kidney can produce from 400 ml to 25 liters a
day of urine!)
VII.
Basic Renal Processes for Sodium and Water
A.
Ninety-nine (99%) of sodium, chloride and water are reabsorbed
1.
Sodium is reabsorbed by primary active transport - Na, KATPase pump, Figure 14-13, page 530
2.
Chloride follows sodium passively and in some cases
actively
C.
Chapter 14 - Kidney
Human Physiology, pages 513-562
3.
B.
C.
D.
E.
VIII.
A.
Water is reabsorbed by diffusion (osmosis) and is dependent
on the transport of Na+ and Cla)
When Na+ is actively transported across the
membrane that creates an osmotic gradient which
water can move down if the membrane is permeable
to water
b)
The tubular cells can have their permeability to
water altered, either increased or decreased
Coupling water reabsorption to sodium reabsorption
1.
Changes osmolarity
2.
Aquaporins  regulated water channels
3.
Figure 14-14, page 530
Antidiuretic hormone - (ADH), also known as vasopressin
1.
Diuretic - anything that increases the output of water, an
antidiuretic prevents water loss
2.
ADH prevent water loss by increasing the tubular
permeability (last nephron section) to water
3.
ADH has little effect on Na+ reabsorption
Crucial aspects
1.
Response to ADH is not all-or-none but can be graded (fine
control over water balance)
2.
There is an obligatory water loss associated with sodium
excretion (or any substance) and this can be large if a large
amount of Na+ must be excreted and greatly effect
extracellular volume
3.
Large volumes of water can be excreted with virtually no Na+
present - important in control of extracellular osmolarity
Urine concentration: The countercurrent multiplier system
1.
Review of osmosis may be required to understand the
following material - Chapter 6
2.
Problem: How does the kidney produce a hyperosmotic
urine?  from 300 mOsmol to 1,400 mOsmol
a)
Daily output of waste is about 600 mOsmol
b)
600 mOsmol/day / 1,400 mOsmol/l = 0.444 l/day
c)
444 ml is the obligatory water loss per day
3.
Figure 14-15, page 532
4.
The key is the increasing hypertonicity of the interstitial fluid
that "draws" out of the collecting ducts and concentrates the
urine
5.
Figure 14-16, page 533
Renal Sodium Regulation
Sodium balance equation, page 534
Na+ excreted = Na+ filtered - Na+ reabsorbed
1.
Major reflex pathways that alter Na+ balance are
a)
Cardiovascular baroreceptors effects on hormone
secretions, next section
Chapter 14 - Kidney
Human Physiology, pages 513-562
B.
C.
b)
Efferent and hormonal pathways to the kidneys
c)
Renal effector sites - arterioles and tubules
2.
Three cases of balance challenge
a)
Drink two liters of distilled water
b)
Drink two liters of Gatorade (balanced salt solution,
i.e. isotonic)
c)
Take six salt tablets, little water
Control of GFR
1.
Constriction of renal arterioles decreases GFR
2.
Dilation of renal arterioles increases GFR
3.
Figure 14-17, page 535 - summary of response to severe
water and salt loss due to diarrhea
Control of sodium reabsorption
1.
While altering the GFR can quickly change the amount of
Na+ excreted for long term control the hormonal control of
reabsorption is more important
2.
Aldosterone and the renin-angiotensin system
a)
Aldosterone - secreted by adrenal cortex, stimulates
Na+ reabsorption
b)
In absence of aldosterone a person can lose 35 g of
salt a day  tell story about boy who ate salt
c)
Renin - specialized cells in the afferent arterioles
synthesize and secrete this enzyme into the blood
(don't confuse with rennin), Figure 14-18, page 536
(1)
Renin secretion can be elicited by
sympathetic input and pressure changes in
the renal arterioles - JGA  intrarenal
baroreceptors
(2)
A complex regulatory mechanism
d)
Angiotensinogen - from liver, is converted into
angiotensin I by the enzyme renin which is then
further converted to angiotensin II by a "converting
enzyme" in lung capillaries
e)
Angiotensin II stimulates cells of the adrenal cortex
to secrete aldosterone
f)
Figure 14-19, page 530 - Effect of plasma volume on
Na+ excretion
3.
Factors other than aldosterone
a)
Renal nerves and angiotensin II also act directly on
the tubules to stimulate sodium ion reabsorption
b)
Atrial natriuretic peptide (ANP), Figure 14-20, page
538
(1)
From atria of heart and inhibits the
reabsorption of Na+
(2)
Increases GFR by acting on renal blood
vessels
Chapter 14 - Kidney
Human Physiology, pages 513-562
(3)
(4)
c)
Also inhibits secretion of renin and
aldosterone
Stimulated by excess sodium and increased
blood pressure or atrial distension
Pressure natriuresis  increase in arterial pressure
inhibits sodium reabsorption and increases sodium
excretion
D.
Conclusion
1.
Na+ balance doesn't vary more than 2%
2.
A balance between osmolarity and volume
IX.
Renal Water Regulation
A.
Person drinking 2 liters of water - no change in total body salt (it
gets diluted)
1.
Must excrete water and keep salt
2.
ADH is inhibited and Na+ is reabsorbed normally - a large
volume of dilute (hypoosmotic) urine is excreted
B.
Baroreceptor control of vasopressin secretion, Figure 14-21, page
539
Decreased extracellular volume  the renin-angiotensin
system causes an increased aldosterone secretion.
a)
Decreased extracellular volume also triggers
increased vasopressin secretion.
b)
Increased vasopressin secretion increases the water
permeability of the collecting ducts, more water is
reabsorbed and less is excreted, and water is
retained.
2.
This reflex is initiated by several baroreceptors in the
cardiovascular system.
a)
The baroreceptors; decrease their rate of firing when
cardiovascular pressures decrease
b)
When blood volume decreases few impulses are
transmitted from the baroreceptors via afferent
neurons and ascending pathways to the
hypothalamus, and the result is increased
vasopressin secretion.
c)
Conversely, increased cardiovascular pressures
cause more firing by the baroreceptors, resulting in a
decrease in vasopressin secretion.
3.
If the plasma vasopressin concentration becomes very high
it, like angiotensin II, causes widespread arteriolar
constriction.
4.
The baroreceptor reflex for vasopressin has a relatively high
threshold - there must be a sizable reduction in
cardiovascular pressures to trigger it. Therefore, this reflex,
compared to the osmoreceptor reflex described next,
generally plays a lesser role under most physiological
circumstances
ADH Secretion and Extracellular Volume
1.
C.
Chapter 14 - Kidney
Human Physiology, pages 513-562
1.
Figure 14-22 page 540 - ADH secretion is decreased when
plasma volume is increased
2.
Osmoreceptors control of ADH secretion
3.
What controls ADH secretion in pure water gains or deficits?
osmoreceptors
4.
Osmoreceptors are located in hypothalamus - an decrease
in osmolarity inhibits ADH
X.
A Summary Example: The Response to Sweating
A.
Figure 14-23, page 541
B.
Understand
XI.
Thirst and Salt Appetite
A.
Thirst is stimulated by both low volume and high plasma osmolarity intake will compensate
1.
Angiotensin can effect thirst directly, (on brain)
2.
Extracellular volume is down and angiotensin causes thirst
which can eventually increase volume if intake is increased
3.
Summary  Figure 14-24, page 542
Salt appetite - questionable in humans
XII.
Potassium Regulation
A.
Closely regulated - effects nerve and muscle, too high is dangerous,
too low is dangerous
1.
Most K+ is found intracellular
2.
Main control is renal
B.
Renal regulation of potassium
1.
Freely filterable at glomerulus
2.
Regulation is primarily by secretion, Figure 14-25, page 543
3.
Aldosterone - increases tubular potassium secretion
a)
Simpler mechanism than for Na+
b)
Adrenal cortex cells respond to the fluid bathing
them, i.e. increased K+ stimulates the cells to
secrete aldosterone which then causes secretion of
excess of K+, Figure 14-26, page 543
4.
Summary - Figure 14-27, page 544
B.
SECTION C - CALCIUM REGULATION
XIII.
Calcium regulation
A.
Important for neuromuscular function
1.
Hypocalcemia - increased excitability of nerve and muscle
and hypocalcemic tetany
2.
Hypercalcemia - cardiac arrhythmias and depressed
muscular ability
B.
Functions of Bone, Table 14-5, page 547
1.
Supports the body and “opposes” gravity
2.
Rigidity for locomotion
3.
Protection of internal organs
4.
Reservoir of calcium
Chapter 14 - Kidney
Human Physiology, pages 513-562
5.
C.
D.
E.
F.
G.
Produces blood cells in marrow
Cross section of bone  Figure 14-28, page 547
Summary of major hormones regulating bone mass, Table 14-6,
page 547
Effector sites for calcium homeostasis - Not regulated like Na+ and
K+ but has three sites listed below
1.
Bone - 99% of the body Ca2+ is in the extracellular matrix
and can be drawn from and deposited to
a)
Hydroxyapatite
b)
Osteoblasts
c)
Osteocytes
d)
Osteoclasts
2.
Gastrointestinal tract - little Ca2+ is absorbed by gut but it
can be increased and decreased as part of regulation
3.
Kidney - Ca2+ filtration and reabsorption occurs to regulate,
phosphorus (PO3-) is intimately involved in Ca2+ regulation
Parathyroid hormone → Figure 14-29, page 548
1.
All three sites above are directly or indirectly subject to
control by this hormone
2.
The regulation of secretion is direct, that is, the secretory
cells of the parathyroid are effected by the Ca 2+
concentration in the extracellular fluid
a)
Low Ca2+ stimulates PTH secretion
b)
Increased Ca2+ inhibits PTH secretion
3.
Four distinct effects in Ca2+ homeostasis
a)
Increases bone demineralization (Ca2+ and PO3-)
b)
Stimulates vitamin D which acts alone to increase
gut Ca2+ absorption
c)
Increases renal tubular Ca2+ reabsorption
d)
Reduces renal tubular PO3- reabsorption, thus
increases PO3- excretion
e)
Summary Figure 14-30, page 549
4.
Importance of phosphorus
a)
Due to equilibrium constant the product of [Ca2+] x
[PO3-] = constant
b)
If PO3- increases that "forces" a deposition of Ca2+
into bone to maintain the product of [Ca2+] x [PO3-]
constant
c)
Since PTH cause both Ca2+ and PO3- to be lost from
bone then the increased PO3- would retard the
process but PTH causes excretion of PO3- which
allows further bone demineralization and increased
plasma [Ca2+]
Vitamin D - calciferol, (a hormone)
1.
This is actually a steroid hormone of which there are about
25 active derivatives
Chapter 14 - Kidney
Human Physiology, pages 513-562
2.
H.
The main role of vitamin D (calciferol) is to stimulate the
absorption of Ca2+ from the gut thus increasing the plasma
Ca2+ level
3.
Pathway of vitamin D activation
a)
Sunlight strikes skin & activates or from dietary
source
b)
Next stop is liver for further transformation
c)
The kidney is the last step which regulates the
amount of circulating hormone, 1,25-(OH)2D3
d)
The level of PTH can act on the kidney, if the Ca2+
level drops PTH causes vitamin D to be increased
which increases absorption and raises plasma Ca2+
concentration
e)
When plasma Ca2+ is "normalized" the extra Ca2+
can be deposited in bone
f)
Lack of vitamin D (no sunlight and from diet) leads to
rickets in children and osteomalacia in adults
g)
Discuss osteoporosis and calcium
4.
Summary - 1,25-(OH)2D3 and PTH action to increase plasma
Ca2+ level, Figure 14-31, page 550
Calcitonin (a hormone)
1.
In thyroid gland, separate from cells that secrete thyroxine
and are directly effected by plasma Ca2+ concentration
2.
Lowers plasma Ca2+ concentration by inhibiting release from
bone
3.
Opposes PTH but plays a minor role in regulation
SECTION C - HYDROGEN-ION REGULATION
XIV.
Hydrogen Ion Regulation
A.
Table 14-7, page 553 - Sources of hydrogen gain or loss
B.
Acids and Buffers
1.
Strong acid ionizes almost completely
2.
HCl H+ + ClWeak acid does not ionize completely
3.
H2CO3  HCO3- + H+
General buffer equation:
pKa is equilibrium constant of acid
pH = pKa + log10
C.
[salt]

[acid]
Generation of hydrogen ions by metabolism in the body
-
1.
H2PO41-  H+ + HPO42-
2.
H2SO4  2H+ + SO42-
Chapter 14 - Kidney
Human Physiology, pages 513-562
CO2 + H2O  H2CO3  HCO3- + H+Organic acids such as
lactic, glutamic etc.
4.
Proteins can ionize
Buffering of hydrogen ions in the body
1.
The concentration of plasma [H+] is 0.00004 mmol/l which is
a pH of 7.4
a)
An increase or decrease of H+ can change the pH if
it were not buffered
b)
Buffers maintain the pH by "picking up" or
"releasing" hydrogen ions
2.
Bicarbonate-carbon dioxide - Figure 14-32, page 555 - pH
and CO2
3.
Reabsorption of carbonate, Figure 14-33, page 556
3.
D.
Figure 14-34, page 556  renal contribution of new
bicarbonate from glutamine (mainly in proximal tubule)
E.
Renal regulation of extracellular hydrogen ion concentration
1.
Buffers do not remove extra H+ but just "bind" them
2.
Hydrogen ion excreted in the urine is almost totally by
tubular secretion
a)
Rather complex
b)
Depends on the ability of tubular cells to synthesize
ammonia
NH3 + H+  NH4+
F.
Renal response to acidosis & alkalosis, Table 14-8, page 557
G.
Classification of disordered hydrogen-ion concentration, Table 14-9,
page 557
1.
Respiratory acidosis or alkalosis
a)
Failure of lungs to eliminate CO2 (acidosis) or
eliminate too much (alkalosis)
b)
Explainable in terms of mass action
2.
Metabolic acidosis or alkalosis
a)
Body producing excess H+- (acidosis)
(1)
Hypoxia or exercise producing lactic acid
(2)
Fasting or diabetes producing ketone bodies
b)
Excessive hydroxyl ions - (alkalosis)
(1)
Bicarbonate loss due to diarrhea
(2)
Loss of HCl in severe vomiting
XV.
Diuretics and Kidney Disease
A.
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4.
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