Acid-Base Balance for Allied Health Majors Using the Henderson-Hasselbach Equation H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - pH = pK + log HCO 3 - pCO 2 ( α ) α =0.03

Acid An acid is a substance that will disassociate a H+ and become more negatively charged (electron acceptor). When hydrogen ions accumulate in a solution, it becomes more acidic ([H+] increases = more acidity). 72 pH HCl H + Cl- Hydronium ions in solution Concentration of hydrogen ions increases, pH drops

Base A base is chemical that will remove hydrogen ions from the solution the base has a negative charge (or extra electrons) to donate to hydrogen ions and thus create a bond with hydrogen 72 pH H + Cl- NaOH Na+ OH - Acids and basis neutralize eachother

72 pH Na+ Cl- H+ OH - H2OH2O A change of 1 pH unit corresponds to a 10-fold change in hydrogen ion concentration

Acids are being created constantly through metabolism Inorganic phosphates (mostly from ATP, etc.) Anaerobic respiration of glucose produces lactic acid Fat metabolism yields organic acids and ketone bodies Carbon dioxide!!!!!

Acids must be buffered, transported away from cells, and eliminated from the body Phosphate: important renal tubular buffer HPO H + H 2 PO 4 Ammonia: important renal tubular buffer NH 3 + H + NH 4 + Proteins: important intracellular and plasma buffers H + + HbHHb Histidine in proteins is particularly good at neutralizing hydrogen ions

Bicarbonate: most important ECF buffer H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - CA From metabolism Hydrogen is buffered by hemoglobin

Buffering is good, but it is a temporary solution. Excess acids and bases must be eliminated from the body H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - CA Lungs eliminate carbon dioxide Kidneys can remove excess non-volatile acids and bases gasaqueous

Excessive Acids and Bases can cause pH changes---denature proteins Normal pH of body fluids is 7.40 Alkalosis or alkalemia – arterial blood pH rises above 7.45 Acidosis or acidemia – arterial pH drops below 7.35 (physiological acidosis) For our class, we will stick to 7.40 as normal! Acidosis: –too much acid –Too little base Alkalosis –Too much base –Too little acid

Compensation for deviation Lungs (only if not a respiratory problem) –If too much acid (low pH)—respiratory system will ventilate more (remove CO 2 ) and this will raise pH back toward set point –If too little acid (high pH)—respiratory will ventilate less (trap CO 2 in body) and this will lower pH back toward set point Kidneys –If too much acid (low pH)—intercalated cells will secrete more acid into tubular lumen and make NEW bicarbonate (more base) and raise pH back to set point. –If too little acid/excessive base (high pH)- proximal convoluted cells will NOT reabsorb filtered bicarbonate (base) and will eliminate it from the body to lower pH back toward normal.

How would your ventilation change if you had excessive acid? [H + ] Alveolar Ventilation pCO 2 H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - This is too high and this means the buffer system swings this way! CO 2 vented out

How would your ventilation change if you had too little acid? [H + ] Alveolar Ventilation pCO 2 H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - This is too low and this means the buffer system swings this way! CO 2 trapped

How can the kidneys control acids and bases? Bicarbonate is filtered and enters nephron at Bowman’s capsule Proximal convoluted tubule –Can reabsorb all bicarbonate (say, when you need it to neutralize excessive acids in body) OR –Can reabsorb some or NONE of the bicarbonate (maybe you have too much base in body and it needs to be eliminated)

How can the kidneys control acids and bases? Acidosis Intercalated cells –Secrete excessive hydrogen –Secreted hydrogen binds to tubular buffers (ammonia and phosphate bases) –Secretion of hydrogen leads to gain of bicarbonate (NEW!) HPO 4 - NH 3

What would happen if the respiratory system had a problem with ventilation? Respiratory Acidosis and Alkalosis P CO2 levels- Normal P CO2 fluctuates between 35 and 45 mmHg Respiratory Acidosis (elevated CO 2 greater than 45mmHg) Depression of respiratory centers via narcotic, drugs, anesthetics CNS disease and depression, trauma (brain damage) Interference with respiratory muscles by disease, drugs, toxins Restrictive, obstructive lung disease (pneumonia, emphysema) Respiratory Alkalosis (less than 35mmHg- lowered CO 2 ) Hyperventilation syndrome/ psychological (fear, pain) Overventilation on mechanical respirator Ascent to high altitudes Fever

What if your metabolism changed? Metabolic acidosis bicarbonate ion levels below normal (22 mEq/L) Metabolic alkalosis bicarbonate ion levels higher (greater than 26mEq/L) Ingestion, infusion or production of more acids (alcohol) Carbonic anhydrase inhibitors (decreased H+ secretion) Salicylate overdose (aspirin) Diarrhea (loss of intestinal HCO 3 - ) Accumulation of lactic acid in severe Diabetic ketoacidosis starvation Excessive loss of fixed acids due to ingestion, infusion, or renal reabsorption of bases Loss of gastric juice during vomiting Intake of stomach antacids (Leisure world syndrome) Diuretic abuse (loss of H+ ions) Severe potassium depletion (increased aldosterone) Steroid therapy (mineralcorticoid excess)

H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - pH = pK + log HCO 3 - pCO 2 ( α ) Acidosis: pH < metabolic: HCO respiratory: pCO 2 Alkalosis: pH > metabolic: HCO respiratory: pCO 2 Mechanisms of Acidosis and Alkalosis α =0.03

Compensation Acidosis (pH<7.40) Alkalosis (pH >7.40) ProblemCompensation Too much acid (High CO 2 ) Too little acid (low CO 2 ) RespiratoryKidneys Too little base (low HCO 3 -) Too much base (high HCO 3 -) MetabolicRespiratory (quick!) Kidneys (long-term)

Analysis of Simple Acid-Base Disorders Figure 30-10; Guyton and Hall Step One: Step 3 Step Two <22>26 <22 <35 >45 Resp and renal compensation

Let’s practice What is the problem?: pH pCO 2 HCO 3 - PCO 2 complete HCO 3 - reabs. + excess tubular H + H + secretion pH Buffers (NH 4 +, NaHPO 4 - ) H + + new HCO 3 - Buffers - H 2 O + CO 2 H 2 CO 3 H + + HCO 3 - What is the correction and which organ system does this?

What is the problem?: pH pCO 2 HCO 3 - P CO 2 H + secretion pH HCO 3 - reabs. + excess tubular HCO 3 - HCO H + excretion Let’s practice What is the correction and which organ system does this?

H + What is the problem?: pH pCO 2 HCO 3 - HCO 3 - complete HCO 3 - reabs. + excess tubular H + pH HCO 3 - filtration + new HCO 3 - Buffers - Buffers (NH 4 +, NaHPO 4 -) What is the respiratory system doing at the same time? Let’s practice What is the correction and which organ system does this?

pH pCO 2 HCO 3 - HCO 3 - pH HCO 3 - filtration HCO 3 - reabs. excess tubular HCO 3 - excretion H + excretion HCO Let’s practice What is the problem?: What is the correction and which organ system does this? What is the respiratory system doing at the same time?

Anion Gap-- protein, phosphate, citrate, sulfate Na+ Cl- Anion gap HCO 3 - Meta. acidosis: too little base More Cl- and anion gap same Diarrhea, renal acidosis Meta. acidosis: too little base More Cl- and anion gap bigger Ketoacidosis, salicylate, lactate Chronic renal failure Na+Cl- Anion gap HCO 3 - Na+ Cl- Anion gap HCO 3 - electroneutrality

Overuse of Diuretics Metabolic Alkalosis K + depletionangiotensin II aldosterone extracell. volume tubular H + secretion HCO 3 reabsorption + new HCO 3 Production Clinical Correlation: Abuse of Diuretics or Conn’s disease Conn’s disease