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REGULATION OF ACIDS,
BASES, &
ELECTROLYTES
Key Topics
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Ventilation as an Acid-Base Controller
Renal Anatomy Review
Starling’s Law of the Capillary
Fluid and Electrolyte balance
Renal Physiology
Kidney as an Acid-Base Controller
Diuretics
Ventilation Control & Regulation
• Volatile acids (i.e. Carbonic Acid) are
removed via the lungs.
• The volume of gas that is removed is
directly related to the alveolar ventilation.
• The amount of alveolar ventilation is
determined by the control and regulation
of ventilation.
Ventilation Control
• Primary respiratory generator is the
inspiratory & expiratory centers in the
medulla.
• These are in turn regulated by:
• The apneustic center
• The pneumotaxic center
• The cerebral cortex – voluntary changes in
ventilation
Ventilation Regulation
• Amount of ventilation is also regulated
through feedback mechanisms.
• Chemoreceptors
• Central and Peripheral
• Reflex Mechanisms
• Hering-Breuer
• J Receptors
Central Chemoreceptors
• Located in the medulla of the CNS
• Not to be confused with the respiratory
centers!
• Chemoreceptors are bathed in CSF that
respond to the pH of the CSF ( H+,
ventilation).
• CSF is relatively impermeable to ions (i.e. HCO3-),
only gases (i.e. PaCO2).
• Known as the blood-brain barrier.
• Slight changes in PaCO2 will yield a change in
ventilation.
• No response to hypoxemia.
Peripheral Chemoreceptors
• Located in arterial system
• Carotid Bodies
• Aortic Bodies
• They respond to the blood passing by them.
• Both respond to:
• PaCO2 /pH: Large increases are needed in PaCO2 or
pH before changes in minute ventilation occur.
• PaO2 : Comes into play with chronic pulmonary
disease (hypoxic drive)
• Dramatic increase in stimulation when PaO2 < 60 mm Hg.
• Baroreceptors: Regulate blood pressure & 2
Ventilation.
Regulation of Ventilation and Blood
Gases in Progressive Pulmonary Disease
Progressive Disease
Normal
Mild
Moderate
Severe
PaO2 (mm Hg)
100
65
55
50
PaCO2
40
40
34
50
Central
Chemoreceptors
++++
++++
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+
Peripheral
Chemoreceptors
+
++
+++
++++
Control
C
C
P
P
(mm Hg)
Reflexes
• Hering-Breuer
• Stretch reflex
• Regulates tidal volume & respiratory rate to minimize work of
breathing.
• Active during overinflation and underinflation.
• Inflation reflex
• Deflation reflex (rapid-shallow breathing)
• J receptors
• Juxtapulmonary capillary receptors
• Interstitial tissue of the A-C membrane
• Respond to thickening of this membrane (? pressure)
• Pulmonary Edema & Pulmonary Fibrosis
• Result in tachypnea & hyperventilation
Renal Anatomy & Physiology
Renal Function
• Three primary functions
• Excretion of nonvolatile waste products
(including nonvolatile acids)
• Regulation of blood volume.
• Regulation of various electrolytes & blood
constituents.
Kidney A & P
• Retroperitoneal
organ.
• Outer cortex; inner
medulla.
• Ureter transports
urine from kidney to
bladder.
Nephron
• Functional unit of
the kidney.
• 1,300,000 per
kidney
• Composed of
• Bowman’s
Capsule
• Proximal
Convoluted
Tubules
• Loop of Henle
• Distal Convoluted
Tubules
• Collecting Tubule
• EGAN
Fluid Compartments
• Total amount of water in 70 kg man = 40 L
• Accounts for 60% of the body’s weight
• Intracellular (within the cells): 25 L
• Red Blood Cell volume: 2 L
• Extracellular (outside the cells): 15 L
• Interstitial (in the spaces between cells): 12 L
• Plasma: 3 L
• 2/3rd of the blood volume is in the cell.
Electrolytes
• Two types of substances found in body
water:
• Non-Electrolytes: Intact uncharged particles
• Urea, Creatinine, Glucose
• Electrolytes: Particles that dissociate and
carry electrical charges
• Cations – Positively charged
• Anions – Negatively charged
Capillary Structure & Function
• Capillaries allow movement of substances (O2,
K+, Glucose) out of the capillary and into the
cell through diffusion and movement of water
by osmosis.
• Capillaries have (basement) membranes with
varying permeability.
• Different organs allow substances of various size to
diffuse across. (lung vs. kidney vs. intestine)
• Some substances never leave the vascular space
under normal conditions (hemoglobin, albumin)
Capillary Structure & Function
• Capillaries are like a leaky hose;
the bulk of the fluid continues along
the hose but some fluid leaks out
due to pressure within the hose.
Fluid Dynamics in the Capillary
• Five factors regulate fluid movement in
and out of the capillary.
• 2 Hydrostatic pressures
• One inside & One outside
• 2 Osmotic (Oncotic) pressures
• One inside & One outside
• The relative permeability of the capillary wall
Hydrostatic Pressure
• HYDROSTATIC PRESSURES PUSH
FLUID OUT.
• Increased capillary (arterial side)
hydrostatic pressure forces fluids out of
the capillary.
• Increased interstitial hydrostatic pressure
forces fluid out of the interstitial space
(into the alveolus in fulminate pulmonary
edema)
Osmotic Pressure
• OSMOTIC PRESSURES PULL FLUID IN.
• Plasma proteins (hemoglobin, albumin)
[aka colloids] that don’t move out of the
vascular space and cross the capillary wall
exert an osmotic (oncotic) pressure within
the vessel and draw fluid (and any
associated soluble waste products) back
into the capillary at the venous end.
• 2 Osmotic pressures (capillary and interstitial)
Starling Forces
• 5th factor is the permeability of the
membrane.
• This phenomenon is known as Starling
forces.
• This movement of fluid allows for:
• Delivery of nutrients to cell
• Waste products to be reabsorbed
• Fluid and Electrolyte Homeostasis both in
peripheral cells and in the kidney.
Net Effect
• Excess fluid left in the tissues can be
caused by:
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Increased Capillary Hydrostatic pressure
Decreased Capillary Osmotic pressure
Decreased Interstitial Hydrostatic pressure
Increased Interstitial Osmotic pressure
Increased Permeability of the capillary wall
Nephron
Bowman’s Capsule
• Located in cortical portion of kidney.
• Beginning of the Proximal Convoluted
Tubule
• Blood enters via afferent arteriole
• Branches into a tuft of capillaries called
the glomerulus.
• The hydrostatic pressure of the capillary
forces fluid out of the capillary and into
Bowman’s capsule.
• Hydrostatic pressure controlled by
contraction and dilation of the arteriole.
Bowman’s Capsule
• 20% of the renal
blood is filtered in the
glomerulus.
• Remainder of the
blood passes out the
glomerulus via the
efferent arteriole and
eventually branches
into the peritubular
capillaries (98-99%)
and vasa recta (12%).
• Fluid from the
Bowman’s capsule
flow into the Proximal
Convoluted Tubule.
Urine Formation
• Three factors are involved in the formation
of urine:
• Glomerular Filtration
• Volume of renal perfusion
• Afferent arteriolar constriction reduces GFR
• Efferent arteriolar constriction increases GFR
• Tubular Reabsorption
• In the peritubular capillaries & vasa recta
• Tubular Secretion
• Exchange of electrolytes as needed
Glomerular Filtration Rate
• Fluid which is filtered by the glomerulus into
Bowman’s capsule is called glomerular filtrate.
It is made up of same substances as are in
plasma with the exception of proteins (albumin,
hemoglobin).
• The amount of glomerular filtrate formed each
minute is called the Glomerular Filtration Rate.
• Average GFR is 125 mL/minute (180 liters/day)
• 15L (entire ECF) every 2 hours!
• 99% of it is reabsorbed; remainder passes out as
urine (1 mL/min)
Proximal Convoluted Tubule
• Glomerular filtrate collects from Bowman’s
capsule into the proximal convoluted tubule.
• Terminal end near medullary border where it
forms the beginning of the Loop of Henle.
• Proximal Convoluted Tubule is surrounded by
the peritubular capillaries, which are protein
“rich” and have a high osmotic pressure.
Proximal Convoluted Tubule
• Reabsorption of:
• Water (65% of glomerular filtrate volume)
• Amino Acids & Glucose (unless there is
an increased plasma level)
• Urine samples are obtained to look for
“spilled” protein and glucose.
• Active reabsorption of Sodium (99% of
Na+ is ultimately reabsorbed.)
• This is continued throughout the Loop of
Henle, Distal Convoluted Tubule & Collecting
Tubule.
NaCl Mechanism
•Active
“pumping”
of Sodium
from
tubule to
peritubular
capillary.
•Chloride
diffuses
with the
Sodium to
maintain
neutrality.
Loop of Henle
• Three components
• Descending limb
• Sharp hairpin turn
• Ascending limb
• 70% of glomeruli are in the cortex with short
Loops of Henle.
• Other 30% are near medulla (juxtamedullary
nephrons) and have long Loops of Henle
surrounded by the vasa recta.
• Medullary interstitial fluid has a greater osmotic
pressure the “longer” the descending loop.
Descending Loop of Henle
• 25% of
glomerular
filtrate enters
the descending
loop.
• High osmotic
pressure
towards the
bottom causes
large
reabsorption of
water (15%)
Ascending Loop of Henle
• Flow is back up towards
cortex (countercurrent
flow).
• This portion of the loop
is impermeable to water
(no water excretion)
• Sodium is actively
pumped into the
interstitial fluid.
• This Sodium is
reabsorbed into the
Descending Loop which
leads to a high level of
Sodium near the bottom
of the Loop that causes
the high osmolarity
(Countercurrent
multiplier)
Distal Tubules & Collecting Duct
• Located in
cortex.
• Additional
10% of water
is reabsorbed.
• Any additional
Sodium is
reabsorbed
(as NaCl)
• Juxtaglomerular
apparatus
Sodium Regulation I & II
• NaCl Mechanism
• As above.
• Primary Active
Transport
• Secondary
reabsorption
through secondary
active secretion of
H+ and K+.
• Used when Cl is
not available.
• Causes Metabolic
Alkalosis
• Loss of H+
Na+ Regulation: Active Secretion
of Potassium
• Occurs when
Hydrogen ions
are scarce
(alkalemia)
• Can lead to
hypokalemia.
Water Reabsorption
• 65% in Proximal Convoluted Tubule
• 25% in Descending Loop of Henle
• 10% in Distal Tubule
Sodium Reabsorption
• As Sodium Chloride via active transport
of Sodium ion (80%).
• As Sodium Bicarbonate (20%) in two
forms:
• With loss of H+ ion in urine and resulting
alkalosis.
• With loss of K+ ion in urine in presence of
existing alkalosis (can’t sacrifice H+)
• This mechanism is also the way the body
controls the level of HCO3-
Renal Failure
• Failure of the kidneys to produce urine,
filter waste products, and regulate fluid
and electrolyte levels.
• Caused by reduced Glomerular Filtration
Rate and manifested by a reduction in
urine formation and an increase in Blood
Urea Nitrogen (BUN) and Creatinine
levels.
• Can be acute (over a few days) or chronic
in nature.
RIFLE Classification of Renal
Failure
• Risk (R) - Increase in serum creatinine level X 1.5 or
decrease in GFR by 25%, or UO <0.5 mL/kg/h for 6
hours
• Injury (I) - Increase in serum creatinine level X 2.0 or
decrease in GFR by 50%, or UO <0.5 mL/kg/h for 12
hours
• Failure (F) - Increase in serum creatinine level X 3.0,
decrease in GFR by 75%, or serum creatinine level >4
mg/dL with acute increase of >0.5 mg/dL; UO <0.3
mL/kg/h for 24 hours, or anuria for 12 hours
• Loss (L) - Persistent ARF, complete loss of kidney
function >4 weeks
• End-stage kidney disease (E) - Loss of kidney function
>3 months
Causes of Renal Failure
• Pre-renal
• Post-renal
• Renal
Pre-Renal Failure
• Normal tubular or glomerular filtration function.
• Reduced GFR is secondary to reduced renal perfusion.
• The most common cause is hypotension, often due to
hypovolemia.
• Evaluate for hemorrhage, vomiting, diarrhea, or reduced fluid
intake in the elderly.
• Less common cause is a pre-renal obstruction (renal
arterial tumor)
• No real damage to kidney itself if treated early.
• Lab results
• Urine osmolarity > 500 mOsm/kg water
• Plasma BUN – creatinine ratio >20
• Urine/Plasma Creatinine ratio > 40
Post-Renal Failure
• Also known as obstructive renal failure as the
problem is with a downstream obstruction.
• Reversible if the source can be identified.
• Causes include
• Ureter obstruction due to kidney stone or cancer.
• Bladder obstruction due to kidney stone, cancer, and
enlarged prostate (most common cause).
• Kidney function returns to normal after correction
of problem.
Renal Failure
• Damage to the nephron which limits its ability to
filter and remove waste material, and its ability to
regulate fluid and electrolytes.
• Causes include:
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Blood vessel disease (e.g. HTN)
Glomerulonephritis
Acute Tubular Necrosis (ATN)
Ischemia from cardiac arrest or a significant reduction
in renal perfusion.
• Lab results
• Urine osmolarity < 500 mOsm/kg water
• Plasma BUN – creatinine ratio < 10-15
• Urine/Plasma Creatinine ratio < 20
Diuretics
Objectives
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After today’s presentation you will:
• Diagram the renin-angiotensin-aldosterone
system.
• Explain how diuretics increase urine
formation by interfering with the NaCI
reabsorption mechanism.
• Explain how diuretics increase urine
formation by interfering with the NaHCO3
reabsorption mechanism.
• State the body’s response to hypotension as
it relates to aldosterone and ADH
Diuretics
• Used to affect the water (and sodium)
level in the body.
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Renal Failure
Heart Failure
Hypertension
Glaucoma ( intraocular pressure)
intracranial pressure (cerebral edema)
Edema
Types of Diuretics
• 5 types
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Carbonic Anhydrase Inhibitors
Osmotic
Thiazides
Loops
Potassium Sparing Diuretics
Web Site on Diuretics
• http://www.thedrugmonitor.com/diuretics.h
tml
Carbonic Anhydrase Inhibitors
• Prevent the reabsorption of water via the
NaHCO3 reaction by inhibiting the
conversion of CO2 into carbonic acid.
• Works in Proximal Tubule.
• Example: Acetazolamide (Diamox)
• Not usually used as a primary diuretic;
used for control of glaucoma.
Osmotic Diuretics
• Osmotic Diuretics: Substances that
pass through glomerular membrane
into filtrate but are not reabsorbed by
peritubular capillaries.
• Mannitol: Elevates osmotic concentration
of tubular fluid, thereby keeping water in
tubules.
• Works in Proximal Tubule and
Descending Loop of Henle.
• Used for Increased Intracranial
Pressure.
Thiazide Diuretics
• Thiazide diuretics work by interfering with
Sodium (mostly as NaCl) reabsorption in the
distal tubule.
• Distal tubule accounts for only 10% of the sodium
reabsorption.
• Not an extremely potent diuretic.
• Examples: Diuril, Hydrodiuril
• Can lead to potassium excretion and
hypokalemia.
Loop Diuretics
• Loop Diuretics: Block active Sodium and
Chloride transport out of the ascending loop.
Diuresis occurs because Sodium stays in
tubule (and water follows) and because
medullary interstitial osmotic pressure
decreases
• Examples:
• Furosemide (Lasix)
• Bumetanide (Bumex)
• Ethacrynic Acid (Edecrin)
• Because they function in the Loop of Henle,
they are more potent diuretics than thiazides.
Potassium Sparing Diuretics
• Prevents sodium reabsorption (via the
NaHCO3 mechanism) in the distal tubule
where Na+ usually exchanges with K+
• If Na+ reabsorption does not occur, K+ is
not excreted into the tubule cells.
• Example:
• Spironolactone (Aldactone)
• Amiloride (Midamor)
• Triamterene (Dyazide, Maxzide)
Fluid Balance
Renin-Angiotensin
ADH
Aldosterone
Juxtaglomerular apparatus and the ReninAngiotension-Aldosterone mechanism & Antidiuretic
Hormone (ADH)
• Reduced BP
• Reduced blood flow
by juxtaglomerular
apparatus
• Renin released by
kidney
• Renin converted to
Angiotension I
• Angiotension I
converted to
Angiotension II
• Vasoconstriction
• Release of Aldosterone
• Sodium Reabsorption
ADH (Vasopressin)
• If blood osmolarity increases
(say when you are in the
desert sweating), ADH is
released from the pituitary
gland (on orders from the
hypothalamus) and water is
retained.
• ADH alters the permeability
of the walls of the collecting
duct, thereby increasing
water reabsorption.
• SIADH (low Na)
• Diabetes Insipidus
• Pituitary doesn’t secrete
ADH