Acids, Bases, Epithelial Transport

Question 1

Describe the law of mass action.

Answer 1

For a given rxn: A + B ↔ C + DIf it is at equilibrium the rate forward equals the rate backwards. And at a given temperature K is a constant.Where K = Keq =[C][D]/[A][B]

Question 2

Define pH and pKa.

Answer 2

pH= -log [H]In chemistry, pH is a measure of the acidity or basicity of a solution.pKa= -logKa.The strength of an acid or base is a measure of its propensity to either donate or accept protons measured as its pKa.

Question 3

Write the Henderson-Hasselbalch (H-H) equation for any given weak acid or base.

Answer 3

At 50% dissociation, pH=pKa

Question 4

What is the relationship between pKa and acidity?

Answer 4

The lower the pKa, the stronger the acid!The higher the pKa, the stronger the base!

Question 5

Define the H-H equation for the bicarbonate buffer system in extracellular fluid and use it to evaluate clinical lab data.

Answer 5

pH = 6.1 + log([HCO3-]mM/ .03*PCO2mmHg)When you get measurements of blood gases, will receive partial pressures in mmHg.

Question 6

Define normal blood pH, [HCO3-] and pCO2.

Answer 6

Blood pH:Arterial: 7.34 - 7.44, Venous: 7.28-7.42[HCO3-]: 24mMpCO2: 40 mmHg, or 40 * .03= 1.2mMRatio of HCO3- to CO2 is 20, gives pH of 7.4 in H-H

Question 7

Use the H-H equation to solve problems of pH changes in defined buffers.i.e. you should be able to determine how many equivalents of acid or base are needed to titrate the ionizable groups(s) of a weak acid or base from a starting pH to a final pH, given its concentration and pKa.

Answer 7

Time for some practice problems!

Question 8

Describe how weak acids and bases work to buffer pH and define the pH range of maximal buffering capacity.

Answer 8

Effective buffering occurs in the range from [A-]/[HA] = 0.1 to 10 or within one pH unit on either side of the pKa.Weak acids and bases interact in a given range to control pH. See bicarbonate buffer in blood.

Question 9

Understand the generic epithelial transport mechanisms for absorbing NaCl and water into the blood.

Answer 9

NaCl: Na+ picked up by the apical membrane (high permeability of apical membrane for Na+) and is transported into the cell, then is pumped out by the Na+/K+ pump out the basolateral membrane. Cl- passively follows the Na+ to equalize the electrical potential.Water follows the influx of NaCl into cells to balance osmolarity.Notice all this is passive (no ATP usage) absorption.

Question 10

Know the basic transport mechanisms by which glucose and amino acids are absorbed into the blood.

Answer 10

Epithelium in GI tract: AA, sugars, and glucose are pumped (secondary active transport) through the apical membrane and diffuse out the basolateral side passively into the blood.AA and sugars are picked up by their target cells by secondary active transport mechanisms.Glucose, as mentioned before, diffuses into the target cell along its gradient (but is phosphorylated in the cell to prevent efflux).

Question 11

Know the major differences between ‘tight’ and ‘leaky’ epithelia.

Answer 11

Tight: more junction proteins, tighter seal between cells. Used particularly in the distal tubules of the kidney.Loose: less junction proteins, looser seal between cells.Tight: fine tuning”– strictly controlled substance transport at lower levels

Question 12

Given two of the following, be able to calculate the third: apical membrane potential, basolateral membrane potential, trans-epithelial potential.

Answer 12

Time for some practice problems!

Question 13

Know the basic process by which some epithelial cells secrete (rather than absorb) fluid.

Answer 13

There’s a chloride-selective channel in the apical membrane in some epithelial cells, cAMP-gated on the inside of the cell to open and allow the efflux of Cl- back out of the apical membrane (which takes Na+ and water with it).Effectively you’re putting watery/serous substance out into the epithelial secretions (mucus, etc).This is the basis for cystic fibrosis: the chloride channel isn’t properly implanted in the cell membrane, and thus no dilution of mucus secretions are possible.This is also the basis for cholera: the cholera toxin gets into the cell and opens the Cl- channel without regulation which leads to a massive efflux of water out the apical membrane into the epithelial system (diarrhea, etc).

Question 14

Which four important substances are never pumped and always move passively down their concentration gradients?

Answer 14

Water, Urea, CO2, O2.

Question 15

Understand the main routes of excretion of metabolic wastes – CO2 and urea, in particular.

Answer 15

CO2, unsurprisingly, is excreted in the alveoli of the lungs.Urea is excreted in the urine after being picked up out of the blood in the kidneys.

Question 16

Concerning hyperkalemia, what does CBIGK mean?

Answer 16

It is an mnemonic for the substances that you treat hyperkalemia with:Calcium, bicarbonate, insulin, glucose, kayexolate.

Question 17

Understand the relative roles of the G.I. tract (minimal) and kidney (extensive) in excreting non-volatile metabolic wastes and regulating ECF composition.

Answer 17

The kidney regulates the ECF composition by adjusting the activity of the transporters that do the reabsorbing.This additional chore arises because the undisciplined GI tract absorbs just about everything presented to it, regardless of the needs of the ECF.

Question 18

What is the main function of the kidney?

Answer 18

The most important function of the kidney is to get rid of these non-volatile (urea, H)metabolic wastes (~500 mM), because no other organ can do it.

Question 19

How does the kidney work, using the I know what I like” method?”

Answer 19

Rather than possessing transporters to pump urea and other exotic non-volatile waste products out of the blood, the kidney takes the exact opposite approach. In essence, it says, “I know what I like.”Consequently, rather than trying selectively to pump waste products out of the plasma, it forms an ultrafiltrate of plasma in the glomerulus, which contains water, salts, sugars, amino acids, and all other beneficial compounds, as well as the non-volatile metabolic waste products. Then, as this plasma ultrafiltrate passes along the renal tubules, the epithelial cells lining the tubules reabsorb (pump back into the blood) the things that it wants to keep (glucose, salts, bicarbonate, etc), allowing the wastes to pass on.It’s incredibly expensive, energetically speaking, to do it this way, requiring a great deal of ATP to drive the reabsorbing pumps.