Body Fluids & Acid-Base Balance, Buffers
Body Fluids
Body Fluids: Intake vs Output
Daily Intake and Output of Water (ml/day)
Normal
Heavy Exercise
Intake
Fluids ingested
2100
?
From metabolism
200
200
Total intake
2300
?
Output
Insensible-skin
350
350
Insensible-lungs
350
650
Sweat
100
5000
Feces
100
100
Urine
1400
500
Total output
2300
6600
Maintenance of a relatively constant volume and a stable composition of the body fluids is essential for homeostasis.
Despite the continuous exchange of fluid and solutes with the external environment as well as within the different compartments of the body, fluid intake must be matched by equal output from the body to prevent body fluid volumes from increasing or decreasing.
Total Body Fluids
Total Body Water
Intracellular Fluid (ICF): 2/3, 40%, 42 liters
Extracellular Fluid (ECF): 1/3, 20%, 14 liters
In the average 70-kilogram adult human, the total body water is about 60 per cent of the body weight, or about 42 liters.
Total body fluids may vary depending on age, gender, and degree of obesity.
Age: As a person grows older, the percentage of total body weight that is fluid gradually decreases. This is due in part to the fact that aging is usually associated with an increased percentage of the body weight being fat, which decreases the percentage of water in the body.
Gender: Because women normally have more body fat than men, they contain slightly less water than men in proportion to their body weight. Therefore, variations exist on the “average” total body fluid.
Body Fluid Compartments
ICF
ECF
Interstitial Fluid (ISF): 9-10 liters
Plasma: 3 liters
Distributed mainly between two compartments:
Intracellular fluid: Fluid concentrations and composition are similar from one cell to another in living species.
The extracellular fluid is divided:
Interstitial fluid
Blood plasma (non cellular part of blood).
There is exchange of substances through the pores of the capillary membranes between ISF and blood plasma.
These pores are highly permeable to almost all solutes except the proteins.
Therefore composition of ISF and blood plasma are the same except proteins.
There is another small compartment of fluid that is referred to as transcellular fluid.
This compartment includes fluid in the synovial, peritoneal, pericardial, and intraocular spaces, as well as the cerebrospinal fluid(CSF); considered to be a specialized type of extracellular fluid.
In some cases, its composition may differ from that of the plasma or interstitial fluid.
All the transcellular fluids together constitute about 1 to 2 liters.
Electrolytes
Cations (+):
ICF: K+, Mg2+
ECF: Na+
Anions (-):
ICF: Proteins, Organic Phosphates
ECF: Cl-, HCO3-
Plasma Electrolytes (20%): Na+ (145 mmol/L), Cl- (115 mmol/L), HCO3- (24 mmol/L)
Interstitial Fluid Electrolytes (80%): Na+, K+, Ca2+, Cl-, HCO3-
Intracellular Fluid Electrolytes: Na+ (12 mmol/L), K+ (155 mmol/L), Ca2+ (<0.5 mmol/L), Cl- (4 mmol/L), Protein, PO4- (105 mmol/L)
Intracellular fluid contains 2/3 of total body water. Extracellular fluid contains the rest
Composition Body Fluids
Cations
Na+
K+
Ca++
Mg+
Anions
Cl-
HCO_3
PO_4 and organic anions
Protein
Intracellular
Extracellular
Acid – base balance
Basic facts – pH
Regulation of A-B balance
Pathophysiology of clinically important disorders
Acids vs. Bases
Definition: Bronsted-Lowry (1923)
Acid: H^+ donor
Base: H^+ acceptor
Normal A:B ratio ~ 1:20
Strength is defined in terms of the tendency to donate (or accept) the hydrogen ion to (from) the solvent (i.e. water in biological systems)
pH
pH is and indirect measure of [H^+]
Hydrogen ions (i.e. protons) do not exist free in solution but are linked to adjacent water molecules by hydrogen bonds (H_3O^+)
Neutral vs. Normal plasma pH
pH 7.4 (7.36-7.44) ® normal
pH 7.0 ® neutral but fatal!!!
Formula: pH=-log [H^+]
pH 7.40 ~ 40 nM
pH 7.00 ~ 100 nM
pH 7.35 ~ 44 nM
pH 7.45 ~ 36 nM
pH values
Normal pH range for arterial blood: 7.35 - 7.45
Acidosis: pH < 7.35
Alkalosis: pH > 7.45
Survival range: 6.8 - 8.0
pH: Interstitial, Intracellular & Mitochondria
pH of interstitial fluid: Lower than that of blood plasma. It's in intermediate position between the plasma and the site of production of acids within the cells.
Intracellular pH: More acidic than plasma, averaging approximately 7.05. But it is not same in all tissues and differ widely according to the functional activity.
It may be higher in osteoblasts (pH 8.0 or more): optimal activity of the enzyme alkaline phosphatase: similarly, it may be quite low in prostatic cells (pH below < 5.0); optimal activity of the enzyme acid phosphatase.
Mitochondrial pH: More acidic (pH can reach 6.6) than plasma (pH of 7.4) and an intracellular pH 7.0. Mitochondria are therefore considered as small islands of acidity in the relatively alkaline sea of intracellular water
Most enzymes function only with narrow pH ranges
Acid-base balance can also affect electrolytes (Na+, K+, Cl-)
Can also affect hormones
Small changes in pH can produce major disturbances
Acids taken in with foods
Acids produced by metabolism of lipids and proteins
Cellular metabolism produces CO2.
CO2 + H2O \leftrightarrow H2CO3 \leftrightarrow H^+ + HCO_3^-
The body produces more acids than bases
Buffers
A buffer is a system of molecules and ions that acts to prevent changes in H^+ concentration and thus serves to stabilize the pH of a solution.
Blood plasma, for example, the pH is stabilized by the following reversible reaction involving the bicarbonate ion (HCO3^-) and carbonic acid (H2CO_3).
HCO3^- + H^+ \Leftrightarrow H2CO_3
Buffers: Control pH
Extracellular
Carbonic acid/ bicarbonate (H2CO3/ HCO_3^-)
Haemoglobin
Intracellular
Proteins
Phosphoric acid/ hydrogen phosphate (H3PO4/H2PO4^- + HPO_4^{2-})
Henderson-Hasselbalch equation: pH = 6.1 + log([HCO3^-]/0.03 pCO2)
Buffer Systems in Body Fluids
ECF: Carbonic acid-bicarbonate buffer system, Hemoglobin buffer, Amino acid
ICF: Phosphate buffer system, Plasma protein buffers (all proteins)
RBCs only: Protein buffer systems
The Carbonic Acid-Bicarbonate Buffer System
Chief buffers of blood and constitute the so called alkali reserve.
Neutralization of strong and non-volatile acids entering the ECF is achieved by the bicarbonate buffers
H2CO3 thus formed, as it is volatile, is eliminated by diffusion of CO_2 through alveoli of lungs.
Note: Proper lung functioning is important. Hence, bicarbonate buffer system is directly linked up with lungs (respiration).
Alkali reserve: It is represented by the NaHCO_3 concentration in the blood that has not yet combined with strong and non-volatile acid
Phosphate buffer
Major intracellular buffer
H^+ + HPO4^{2-} \leftrightarrow H2PO_4^-
OH^- + H2PO4^- \leftrightarrow H2O + H2PO_4^{2-}
Protein Buffers
Includes hemoglobin, work in blood and ISF
In acidic medium: protein acts as a base, NH2 (Amino group) accepts H^+ ions from the medium forming NH3^+, Proteins become positively charged.
In alkaline medium: Proteins act as an acid. Acidic COOH group dissociates and gives H^+. Proteins become negatively charged (COO-).
Side chains that can buffer H^+ are present on 27 amino acids.
Amino Acid/Protein Buffers
In alkaline medium, amino acid acts as an acid and releases H^+
In acidic medium, amino acid acts as a base and absorbs H^+
Chemical vs Physiological Buffers
First line of defense against pH shift: Chemical buffer system (Bicarbonate, Phosphate, and Protein buffer systems)
Second line of defense against pH shift: Physiological buffers (Respiratory and Renal mechanisms)
Acidosis vs Alkalosis
Acidosis: Increased concentration of H^+, pH drops
Alkalosis: Decreased concentration of H^+, pH rises
Respiratory Mechanisms of Regulation of Blood pH
This is achieved by changing the pCO_2.
The CO_2 diffuses from the cells into the extracellular fluid and reaches the lungs through the blood.
The rate of respiration is controlled by the chemoreceptors in the respiratory center which are sensitive to changes in the pH of blood.
When there is a fall in pH of plasma (acidosis), the respiratory rate is stimulated resulting in hyperventilation. This would eliminate more CO2, thus lowering the H2CO_3 level.
The respiratory system responds to any change in pH immediately, but it cannot proceed to completion.
Renal mechanisms of regulation of blood pH
Kidneys play important roles in regulation of blood pH. Reason why pH of urine being acidic, 6.0. Though the pH of urine may vary from 4.5 to 9.8, depending on the pH status of the blood.
The major renal mechanisms for regulation of pH are:
Excretion of H^+
Reabsorption of bicarbonate
Excretion of titratable acid
Excretion of ammonium NH_4^+
Acid-Base Imbalances
Definitions of Acid-base imbalances are pathologic variations in the partial pressure of arterial carbon dioxide (PaCO2) or serum bicarbonate (HCO3^-) that result in aberrant arterial pH values.
The pH value of 7 indicates neutral.
A pH value of less than 7 denotes acidity.
In contrast, a pH value of greater than 7 indicates a base.
Causes of Acid-Base imbalance
The majority of Acid-base imbalances are caused by:
Infection, disease, or damage to organs (kidneys, lungs, brain) whose proper function is required for acid-base homeostasis
Disease-causing abnormally high generation of metabolic acids to the point that homeostatic systems are overwhelmed
Medical intervention (e.g., mechanical ventilation, some drugs).
Acid-Base Disorders
Respiratory
Abnormal processes which tend to alter pH because of a primary change in pCO_2 levels
Acidosis
Alkalosis
Metabolic
Abnormal processes which tend to alter pH because of a primary change in [HCO_3^-]
Acidosis
Alkalosis
Compensation Mechanism
If underlying problem is metabolic, hyperventilation or hypoventilation can help :respiratory compensation.
If problem is respiratory, renal mechanisms can bring about metabolic compensation.
Respiratory Acidosis
Carbonic acid excess caused by blood levels of CO_2 above 45 mmHg.
Hypercapnia – high levels of CO_2 in blood.
Chronic conditions such as:
Depression of respiratory center in brain that controls breathing rate – drugs or head trauma.
Paralysis of respiratory or chest muscles
Emphysema
Respiratory Alkalosis
Carbonic acid deficit
pCO_2 less than 35 mmHg (hypocapnea)
Most common acid-base imbalance
Primary cause is hyperventilation
Metabolic Acidosis
Bicarbonate deficit - blood concentrations of bicarbonate drop below 22 mEq/L.
Causes:
Loss of bicarbonate through diarrhea or renal dysfunction.
Accumulation of acids (lactic acid or ketones)
Failure of kidneys to excrete H^+.
Metabolic Alkalosis
Bicarbonate excess - concentration in blood is greater than 26 mEq/L.
Causes:
Excess vomiting = loss of stomach acid.
Excessive use of alkaline drugs
Certain diuretics
Endocrine disorders
Heavy ingestion of antacids
Severe dehydration
Diagnosis of Acid-Base Imbalances
Note whether the pH is low (acidosis) or high (alkalosis).
Decide which value, pCO2 or HCO3^-, is outside the normal range and could be the cause of the problem.
If the cause is a change in pCO_2, the problem is respiratory.
If the cause is HCO_3^- the problem is metabolic.
Look at the value that doesn’t correspond to the observed pH change. If it is inside the normal range, there is no compensation occurring. If it is outside the normal range, the body is partially compensating for the problem
Summary of acid base disorders and compensation
Disorder
Primary change
Compensatory mechanism
Timescale for compensation
Metabolic acidosis
Decreased plasma bicarbonate
Hyperventilation (decrease in pCO_2)
Minutes to hours
Metabolic alkalosis
Increased plasma bicarbonate
Hypoventilation (increase in pCO_2)
Minutes to hours
Respiratory acidosis
Increased pCO_2
Elevation in plasma bicarbonate; increase in renal reabsorption of bicarbonate
Days
Respiratory alkalosis
Decreased pCO_2
Reduction in plasma bicarbonate; decrease in renal reabsorption of bicarbonate
Days