ACID-BASE BALANCE IN MAMMALS

What is acid-base balance in the organism? 

acid – substance that can donate a proton (H⁺)

base – substance that can accept a proton

buffer – mixture of substances that resist changes in protons (see below)

                                    H⁺ + buffer <-> Hbuffer

Where do acids come from in the organism?

1)     carbon dioxide (CO₂) produced by aerobic metabolism and removed by breathing

2)     acids produced by other metabolic reactions

CO₂ + H₂O <-> H₂CO₃ <-> HCO₃^- + H⁺

So if there is too much CO₂ in the organism, then there is too much acid!

CO₂ levels are controlled by the lungs by breathing.

The major base in the organism is bicarbonate (HCO₃^-) that is controlled by the kidneys.

How does the organism defend against changes in protons or bicarbonate?

1)     buffers – first line of defense (chemical buffers bind to protons)

2)     lungs – second line of defense (increase or decrease breathing quickly)

3)     kidneys – third line of defense (kidneys change rate of proton secretion and/or bicarbonate excretion over 3-4 days)

How does the organism handle bicarbonate?

Proximal tubule cells are impermeable to bicarbonate on the tubule side.

In acid urine, bicarbonate combines with a proton to form carbonic acid that is converted to carbon dioxide and water (enzyme carbonic anhydrase needed)

Thus bicarbonate enters across cell walls in the form of carbon dioxide.

HCO₃^- + H⁺ <-> H₂CO₃ <-> H₂O + CO₂

Inside the cell the carbon dioxide combines with water to make bicarbonate and a proton.

Bicarbonate leaves for the blood side as bicarbonate, while proton either goes into the filtrate or into the blood.

acidosis (pH < 7.35) more protons (or CO₂), less bicarbonate

alkalosis (pH > 7.45) less protons (or CO₂), more bicarbonate

What happens in acidosis (too much H⁺ or carbon dioxide)?

1)     Chemical buffers bind protons.

2)     Organisms immediately increase ventilation to blow off carbon dioxide.

3)     Organisms begin to increase secretion and excretion of protons via the urine thereby decreasing plasma protons.

4)     Organisms reabsorb all filtered bicarbonate from the kidney tubules and add new bicarbonate to the plasma thereby increasing plasma bicarbonate.

What happens in alkalosis (too little H⁺ or carbon dioxide)?

1)       Chemical buffers release protons.

2)       Organisms immediately decrease ventilation to retain carbon dioxide.

3)       Organisms begin to decrease secretion and excretion of protons via the urine thereby increasing plasma protons.

4)       Organisms have incomplete reabsorption of filtered bicarbonate and increased excretion of bicarbonate thereby decreasing plasma bicarbonate.

The kidney compensation for acid-base imbalance is slower than respiratory and takes 3-6 days to bring the organism back into acid-base balance.

Respiratory alkalosis or acidosis means that the cause of the acid-base imbalance is a problem with the lungs.

Metabolic alkalosis or acidosis means that the cause of the acid-base imbalance is a problem with the kidneys.

What other diseases might be related to changes in kidney function?

Diabetes mellitus

Kidney stones – calcium oxalate crystals and proteins form in kidney and lodge in ureter causing PAIN and may obstruct flow of urine

Polycystic kidney disease – cysts develop throughout kidney and affect renal function leading to progressive renal failure (hereditary and very common)

Diabetes insipidus – inadequate secretion or action of vasopressin so collecting ducts not permeable to water and large volume of water lost in urine leading to dehydration

Deficiency of aldosterone -- aldosterone needed in high blood potassium (hyperkalemia) to secrete and excrete potassium or fatal cardiac arrhythmias may result