Download Buffer System

Fluid, Electrolyte, and Acid Base Homeostasis
Fluid Compartments
• Body Fluids are separated by semipermeable membranes into various
physiological (functional) compartments
• Two Compartment Model
– Intracellular = Cytoplasmic (inside cells)
– Extracellular (outside cells)
• The Two Compartment Model is useful
clinically for understanding the
distribution of many drugs in the body
Fluid Compartments
• Three Compartment Model
– [1] Intracellular = Cytoplasmic (inside cells)
– [Extracellular compartment is subdivided into:]
– [2] Interstitial = Intercellular = Lymph
(between the cells in the tissues)
– [3] Plasma (fluid portion of the blood)
• The Three Compartment Model is more
useful for understanding physiological
processes
• Other models with more compartments can sometimes be
useful, e.g., consider lymph in the lymph vessels, CSF,
ocular fluids, synovial and serous fluids as separate
compartments
Fluid Compartments
• Total Body Water (TBW)
- 42L, 60% of body
weight
– Intracellular Fluid (ICF) 28L, 67% of TBW
– Extracellular Fluid (ECF) 14L, 33% of TBW
• Interstitial Fluid - 11L, 80%
ECF
• Plasma - 3L, 20% of ECF
Fluid Balance
• Fluid balance
– When in balance,
adequate water is
present and is
distributed among
the various
compartments
according to the
body’s needs
– Many things are
freely exchanged
between fluid
compartments,
especially water
– Fluid movements by:
• bulk flow (i.e., blood
& lymph circulation)
• diffusion & osmosis
– in most regions
Water
• General
– Largest single chemical component of the body:
45-75% of body mass
– Fat (adipose tissue) is essentially water free,
so there is relatively more or less water in the
body depending on % fat composition
– Water is the solvent for most biological
molecules within the body
– Water also participates in a variety of
biochemical reactions, both anabolic and
catabolic
Water
• Water balance
– Sources for 2500
mL - average daily
intake
• Metabolic Water
• Preformed Water
– Ingested Foods
– Ingested Liquids
– Balance achieved
if daily output also
= 2500 mL
• GI tract
• Lungs
• Skin
– evaporation
– perspiration
• Kidneys
Regulating Fluid Intake - Thirst
• Recall the role of the Renin-Angiotensin System
in regulating thirst along with the Autonomic NS
reflexes diagramed below
Regulating Fluid Intake Thirst Quenching
• Wetting the oral mucosa (temporary)
• Stretching of the stomach
• Decreased blood/body fluid osmolarity =
increased hydration (dilution) of the blood
is the most important
Regulation of Fluid Output
• Hormonal control
– AntiDiuretic Hormone (ADH) [neurohypophysis]
– Aldosterone [adrenal cortex]
– Atrial Natriuretic Peptide (ANP) [heart atrial walls]
• Physiologic fluid imbalances
–
–
–
–
–
–
–
Dehydration:  blood pressure,  GFR
Overhydration:  blood pressure,  GFR
Hyperventilation - water loss through lungs
Vomiting & Diarrhea - excessive water loss
Fever - heavy perspiration
Burns - initial fluid loss; may persist in severe burns
Hemorrhage – if blood loss is severe
Concentrations of Solutes
• Non-electrolytes
– molecules formed by only covalent bonds
– do not form charged ions in solution
• Electrolytes
– Molecules formed with some ionic bonds;
– Disassociate into cations (+) & anions (-) in
solutions (acids, bases, salts)
– 4 important physiological functions in the body
• essential minerals in certain biochemical reactions
• control osmosis = control the movement of water
between compartments
• maintain acid-base balance
• conduct electrical currents (depolarization events)
Distribution of H2O & Electrolytes
• Recall Starling’s Law of the Capillaries which
explains fluid and solute movements
Distribution of Electrolytes
Cations and Anions in Body
Fluids
Distribution of Major Electrolytes
• Na+ and CL- predominate in extracellular fluids
(interstitial fluid and plasma) but are very low in
the intracellular fluid (cytoplasm)
• K+ and HPO42- predominate in intracellular fluid
(cytoplasm) but are in very low concentration in
the extracellular fluids (interstitial fluid and
plasma)
• At body fluid pH, proteins [P-] act as anions; total
protein concentration [P-] is relatively high, the
second most important “anion,” in the cytoplasm,
[P-] is intermediate in blood plasma, but [P-] is
very low in the interstitial fluid
Distribution of Minor Electrolytes
• HCO3- is in intermediate concentrations in all
fluids, a bit lower in the intracellular fluid
(cytoplasm); it is an important pH buffer in the
extracellular comparments
• Ca++ is in low concentration in all fluid
compartments, but it must be tightly regulated,
as small shifts in Ca++ concentration in any
compartment have serious effects
• Mg++ is in low concentration in all fluid
compartments, but Mg++ is a bit higher in the
intracellular fluid (cytoplasm), where it is a
component of many cellular enzymes
Electrolyte Balance
• Aldosterone  [Na+] [Cl-] [H2O]  [K+]
• Atrial Natriuretic Peptide (opposite effect)
• Antidiuretic Hormone  [H2O] ( [solutes])
• Parathyroid Hormone  [Ca++]  [HPO4-]
• Calcitonin
(opposite effect)
• Female sex hormones  [H2O]
Electrolytes
• Sodium (Na+) - 136-142 mEq/liter
– Most abundant cation
• major ECF cation (90% of cations present)
• determines osmolarity of ECF
– Regulation
• Aldosterone
• ADH
• ANP
– Homeostatic imbalances
• Hyponatremia - muscle weakness, coma
• Hypernatremia - coma
Electrolytes
• Chloride (Cl-) - 95-103 mEq/liter
– Major ECF anion
• helps balance osmotic potential and electrostatic
equilibrium between fluid compartments
• plasma membranes tend to be leaky to Cl- anions
– Regulation: aldosterone
– Homeostatic imbalances
• Hypochloremia - results in muscle spasms, coma
[usually occurs with hyponatremia] often due to
prolonged vomiting
• elevated sweat chloride diagnostic of Cystic
Fibrosis
Electrolytes
• Potassium (K+)
– Major ICF cation
• intracellular 120-125 mEq/liter
• plasma 3.8-5.0 mEq/liter
– Very important role in resting membrane
potential (RMP) and in action potentials
– Regulation:
• Direct Effect: excretion by kidney tubule
• Aldosterone
– Homeostatic imbalances
• Hypokalemia - vomiting, death
• Hyperkalemia - irritability, cardiac fibrillation,
death
Electrolytes
• Calcium (Ca2+)
– Most abundant ion in body
• plasma 4.6-5.5 mEq/liter
• most stored in bone (98%)
– Regulation:
• Parathyroid Hormone (PTH) -  blood Ca2+
• Calcitonin (CT) -  blood Ca2+
– Homeostatic imbalances:
• Hypocalcemia - muscle cramps, convulsions
• Hypercalcemia - vomiting, cardiovascular symptoms,
coma; prolonged  abnormal calcium deposition, e.g.,
stone formation
Electrolytes
• Phosphate (H2PO4-, HPO42-, PO43-)
– Important ICF anions; plasma 1.7-2.6 mEq/liter
• most (85%) is stored in bone as calcium salts
• also combined with lipids, proteins, carbohydrates, nucleic
acids (DNA and RNA), and high energy phosphate transport
compound
• important acid-base buffer in body fluids
– Regulation - regulated in an inverse relationship with
Ca2+ by PTH and Calcitonin
– Homeostatic imbalances
• Phosphate concentrations shift oppositely from calcium
concentrations and symptoms are usually due to the related
calcium excess or deficit
Electrolytes
• Magnesium (Mg2+)
– 2nd most abundant intracellular electrolyte,
1.3-2.1 mEq/liter in plasma
• more than half is stored in bone, most of the rest
in ICF (cytoplasm)
• important enzyme cofactor; involved in
neuromuscular activity, nerve transmission in CNS,
and myocardial functioning
– Excretion of Mg2+ caused by hypercalcemia,
hypermagnesemia
– Homeostatic imbalance
• Hypomagnesemia - vomiting, cardiac arrhythmias
• Hypermagnesemia - nausea, vomiting
Acid–Base Balance
Terms
• Acid
– Any substance that can yield a hydrogen ion (H+) or
hydronium ion when dissolved in water
– Release of proton or H+
• Base
– Substance that can yield hydroxyl ions (OH-)
– Accept protons or H+
Terms
• pH
– Negative log of the hydrogen ion concentration
– Represents the hydrogen concentration
Acid-Base Imbalances
• Acidosis
– High blood [H+]
– Low blood pH, <7.35
• Alkalosis
– Low blood [H+]
– High blood pH, >7.45
– Note: Normal pH is 7.35-7.45
Terms
• Buffer
– Combination of a weak acid and /or a weak base
and its salt
– What does it do?
• Resists changes in pH
– Effectiveness depends on
• pK of buffering system
• pH of environment in which it is placed
Acid-Base Balance
• Normal metabolism produces H+ (acidity)
• Three Homeostatic mechanisms:
– Buffer systems - instantaneous; temporary
– Exhalation of CO2 - operates within minutes;
cannot completely correct serious imbalances
– Kidney excretion - can completely correct any
imbalance (eventually)
• Buffer Systems
– Consists of a weak acid and the salt of that
acid which functions as a weak base
– Strong acids dissociate more rapidly and easily
than weak acids
Acid–Base Balance
• Buffer System
– Consists of a combination of
• A weak acid
• And the anion released by its dissociation
– The anion functions as a weak base
– In solution, molecules of weak acid exist in
equilibrium with its dissociation products
Acid–Base Balance
• Buffers
– Are dissolved compounds that stabilize pH
• By providing or removing H+
– Weak acids
• Can donate H+
– Weak bases
• Can absorb H+
Acid–Base Balance
•
Three Major Buffer Systems
–
–
Protein buffer systems:
•
Help regulate pH in ECF and ICF
•
Interact extensively with other buffer systems
Carbonic acid–bicarbonate buffer system:
•
–
Most important in ECF
Phosphate buffer system:
•
Buffers pH of ICF and urine
Acid–Base Balance
• Protein Buffer Systems
– Depend on amino acids
– Respond to pH changes by accepting or
releasing H+
– If pH rises
• Carboxyl group of amino acid dissociates
• Acting as weak acid, releasing a hydrogen ion
• Carboxyl group becomes carboxylate ion
Acid–Base Balance
• Protein Buffer Systems
– At normal pH (7.35–7.45)
• Carboxyl groups of most amino acids have already
given up their H+
– If pH drops
• Carboxylate ion and amino group act as weak bases
• Accept H+
• Form carboxyl group and amino ion
Acid–Base Balance
The Role of Amino Acids in Protein Buffer Systems.
Acid–Base Balance
• The Hemoglobin Buffer System
– CO2 diffuses across RBC membrane
• No transport mechanism required
– As carbonic acid dissociates
• Bicarbonate ions diffuse into plasma
• In exchange for chloride ions (chloride shift)
– Hydrogen ions are buffered by hemoglobin
molecules
Acid–Base Balance
• The Hemoglobin Buffer System
– Is the only intracellular buffer system with an
immediate effect on ECF pH
– Helps prevent major changes in pH when
plasma PCO is rising or falling
2
Oxygen Dissociation Curve
Curve B:
Normal curve
Curve A:
Increased
affinity for hgb,
so oxygen
keep close
Curve C:
Decreased
affinity for hgb,
so oxygen
released to
tissues
Bohr Effect
• It all about
oxygen
affinity!
Acid–Base Balance
• Carbonic Acid–Bicarbonate Buffer System
– Carbon Dioxide
• Most body cells constantly generate carbon dioxide
• Most carbon dioxide is converted to carbonic acid, which
dissociates into H+ and a bicarbonate ion
– Is formed by carbonic acid and its dissociation
products
– Prevents changes in pH caused by organic acids and
fixed acids in ECF
Acid–Base Balance
•
Carbonic Acid–Bicarbonate Buffer System
1.
Cannot protect ECF from changes in pH that
result from elevated or depressed levels of CO2
2. Functions only when respiratory system and
respiratory control centers are working normally
3. Ability to buffer acids is limited by availability
of bicarbonate ions
Acid–Base Balance
• Phosphate Buffer System
– Consists of anion H2PO4- (a weak acid)
– Works like the carbonic acid–bicarbonate
buffer system
– Is important in buffering pH of ICF
Acid–Base Balance
• Maintenance of Acid–Base Balance
– Requires balancing H+ gains and losses
– Coordinates actions of buffer systems with
• Respiratory mechanisms
• Renal mechanisms
Acid–Base Balance
•
Respiratory and Renal Mechanisms
–
Support buffer systems by
•
•
•
Secreting or absorbing H+
Controlling excretion of acids and bases
Generating additional buffers
Acid–Base Balance
• Respiratory Compensation
– Is a change in respiratory rate
• That helps stabilize pH of ECF
– Occurs whenever body pH moves outside
normal limits
– Directly affects carbonic acid–bicarbonate
buffer system
Acid–Base Balance
• Respiratory Compensation
– Increasing or decreasing the rate of
respiration alters pH by lowering or raising the
PCO2
– When PCO rises
• pH falls
2
• Addition of CO2 drives buffer system to the right
– When PCO falls
2
• pH rises
• Removal of CO2 drives buffer system to the left
Acid–Base Balance
• Renal Compensation
– Is a change in rates of H+ and HCO3- secretion or
reabsorption by kidneys in response to changes in
plasma pH
– The body normally generates enough organic and
fixed acids each day to add 100 mEq of H+ to ECF
– Kidneys assist lungs by eliminating any CO2 that
• Enters renal tubules during filtration
• Diffuses into tubular fluid en route to renal pelvis
Acid–Base Balance
• Hydrogen Ions
– Are secreted into tubular fluid along
• Proximal convoluted tubule (PCT)
• Distal convoluted tubule (DCT)
Acid–Base Balance
•
Buffers in Urine
–
The ability to eliminate large numbers of
H+ in a normal volume of urine depends on
the presence of buffers in urine:
1. Carbonic acid–bicarbonate buffer system
2. Phosphate buffer system
3. Ammonia buffer system
Acid–Base Balance
• Major Buffers in Urine
– Glomerular filtration provides components of
• Carbonic acid–bicarbonate buffer system
• Phosphate buffer system
– Tubule cells of PCT
• Generate ammonia
Acid–Base Balance
•
Renal Responses to Acidosis
1.
2.
3.
4.
Secretion of H+
Activity of buffers in tubular fluid
Removal of CO2
Reabsorption of NaHCO3
Acid–Base Balance
•
Renal Responses to Alkalosis
1. Rate of secretion at kidneys declines
2. Tubule cells do not reclaim bicarbonates
in tubular fluid
3. Collecting system transports HCO3- into
tubular fluid while releasing strong acid
(HCl) into peritubular fluid
Acid–Base Balance Disturbances
1.
Disorders:
–
–
–
Circulating buffers
Respiratory performance
Renal function
2. Cardiovascular conditions:
–
–
Heart failure
Hypotension
3. Conditions affecting the CNS:
–
Neural damage or disease that affects
respiratory and cardiovascular reflexes
Acid–Base Balance Disturbances
Figure 27–11a Interactions among the Carbonic Acid–Bicarbonate Buffer
System and Compensatory Mechanisms in the Regulation of Plasma
pH.
Acid–Base Balance Disturbances
Figure 27–11b Interactions among the Carbonic Acid–Bicarbonate Buffer
System and Compensatory Mechanisms in the Regulation of Plasma
pH.