Water, pH and dissociation

Lecture 3, Medical Biochemistry

Lecture 3 Outline
Homeostasis The structure and function of water Dissociation of weak acids and weak bases pH and the Henderson-Hasselbalch equation Buffers, biological/physiological examples

HOMEOSTASIS
The dynamic that defines the distribution of water and the maintenance of pH and electrolyte concentrations Water distribution maintained by the kidneys, antidiuretic hormone, hypothalamic thirst response, respiration and perspiration Clinically, need to be aware of water depletion caused by decreased intake (coma, wandering the desert) or increased loss (diarrhea, renal malfunction, overexercise), and excess body water due to increased intake (too much I.V.) or decreased excretion (renal failure)

Structure of H20

From Lehninger, 2nd ed., Ch 4

WATER
Comprises approx 70% of human mass (4560% intracellular, 25% extracellular/blood plasma) dipolar: partial negative charge on oxygen, partial positive charge on hydrogens dipolar nature leads to formation of many low energy hydrogen bonds

Water Solubility / Hydrophilic

From Lehninger, 2nd ed., Ch 4

Hydrophilic/Hydrophobic

From Lehninger, 2nd ed., Ch 4

Hydrophobicity

Hydrophobicity/Micelles
From Lehninger, 2nd ed., Ch 4

Summary of water and pH relationship

Very low dissociation of H2O to H+ or OH The ion product of H2O, Keq X 55.5 M, leads to this: [H+] = [OH-] = 1 X 10-7 M for pure H2O which is a constant in biological systems Therefore, if [H+] > 10-7 M, then [OH-] must be less than 10-7 M, and vice versa. Thus, if the negative logarithm of [H+] is derived ( pH = -log [H+] ), pure water would be pH = 7, acids pH < 7, and bases pH > 7

Dissociation Constant and pH

From Marks, Marks, Smith, Ch 4

Henderson-Hasselbalch Equation

Sample pH problems

Sample pH Problem (cont)

Buffers
Definition: A weak acid plus its conjugate base that cause a solution to resist changes in pH when an acid or base are added

Effectiveness of a buffer is determined by: 1) the pH of the solution, buffers work best within 1 pH unit of their pKa 2) the concentration of the buffer; the more present, the greater the buffering capacity

Physiological Buffers
Carbon Dioxide-Bicarbonate System; a major regulator of blood pH Phosphate System; major regulator of cytosolic pH

[CO2] and [HCO3] are much higher than [PO4] in blood; the reverse is true in the cytosol, [PO4] >>> [HCO3]

Examples - Physiological Buffers

From Marks, Marks, Smith, Ch 4

From Marks, Marks, Smith, Ch 4

From Lehninger, 2nd ed., Ch 4

Blood Bicarbonate and Metabolic Acidosis

The bicarbonate blood buffer in a normal adult maintains the blood pH at about 7.40. If the blood pH drops below 7.35, the condition is referred to as an ACIDOSIS. A prolonged blood pH below 7.0 can lead to death. Clinically for an acidosis, the acid-base parameters (pH, [HCO3- ], [CO2] ) of the patients blood should be monitored. The normal values for these are pH = 7.40; [HCO3- ] = 24 mM; [CO2] = 1.2 mM.

Sample Problem Metabolic Acidosis

The blood values of a patient were pH = 7.03 and [CO2] = 1.1 mM. What is the patients blood [HCO3-] and how much of the normal [HCO3-] has been used in buffering the acid causing the condition?
The pK for [HCO3-]/[CO2] = 6.10

Solution
Substitute into Henderson-Hasselbalch equation: 7.03 = 6.10 + log [HCO3-]/1.1 mM, or 0.93 = log [HCO3-]/1.1 mM The anti-log of 0.93 = 8.5, thus:

8.5 = [HCO3-]/1.1 mM, or [HCO3-] = 9.4 mM

Since normal [HCO3-] equals 24 mM, there was a decrease of 14.6 mmol of [HCO3- per liter of blood in this patient. This would be approaching the point where, if left untreated, the HCO3- buffering capacity would be no longer effective in this patient.