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pH within the human body varies from pH 1 to 8 depending on the organ and the function. Outside the acceptable range of pH, enzymes lose their ability to function and proteins are denatured. There are several buffering agents in the body that impede any change in pH. Extracellular buffers include bicarbonate and ammonia, whereas proteins and phosphate act as intracellular buffers. Respiratory compensation and renal compensation are 2 ways by which the body can excrete excess molecules to maintain pH. Acid-base imbalances overcoming the buffer system can be compensated in the short term by changing the rate of ventilation, thereby expelling CO₂ and resulting in fewer free hydrogen ions and the pH will rise back to normal. The buffer with a pK_a of 6.1 accounts for 75% of the blood buffer. In response to acidosis or alkalosis, the kidneys secrete or reabsorb hydrogen, bicarbonate, and ammonia. The protein buffer is formed by hemoglobin in the erythrocytes and plasma proteins and is responsible for about 24% of the buffer capacity of the body. Histidine residues in proteins with a pK_a of 6.0 are important. The hydrogen phosphate/dihydrogen phosphate buffer and the ammonia/ammonium buffer are especially important for the urine.

Blood pH is regulated within the narrow range of 7.35–7.45; acidosis is feared. To maintain this physiologic blood pH, the partial pressure of oxygen (pO₂), carbon dioxide (pCO₂), and is carefully regulated by the respiratory and the urinary systems in order to control the acid-base balance (pH) and the buffer capacity [2].

The pH of the surface of barrier organs, which are in close contact with the environment, is different from blood pH but is also tightly regulated. The pH of the healthy lung is neutral, while in cystic fibrosis, the pH is acidic. pH and buffer capacity of the lung are regulated by the exchange of CO₂ with the bicarbonate [3]. Increasing the pH and enhancing the buffer capacity of the lung by adding in a pig model for cystic fibrosis reduces bacterial colonization [4].

In the stomach, the proton pump hydrogen potassium ATPase exchanges K⁺ with H⁺ resulting in a pH 1–1.5 if empty. Anacidity leads to gastrointestinal infections; however, too much acid causes stomach ulcers. Buffers composed of weak acids and their salts exhibit pK_a and pH values not too far away from neutral and therefore, these buffers do not work properly in a very acidic environment.

Urine is slightly acidic in the morning (after fasting), with a pH range of 6.5–7.0, generally becoming more alkaline, with pH = 7.5–8.0 by evening as the body digests food. Vegetarian diet leads to a higher, whereas meat consumption leads to a lower urine pH. Urine contains mostly nitrogen compounds, urea, and creatinine. Urea has a neutral pH, but gets easily hydrolyzed to ammonium cyanate, ammonium, and CO₂, which evaporates and leads to an increase in pH.

Tears of human eyes taken from a yet unopened eye are more acidic in the morning than tears collected later in the day after it comes in contact with the environment (average pH 7.25 vs. 7.45). Tears have a considerable buffer capacity to maintain a healthy eye [5].

The pH of vaginal fluid in reproductive women is 3.8–4.4 and is important to prevent infection. Vaginal microbiota is dominated by Lactobacillus species, which secret enzymes that degrade glycogen to lactic acid keeping the pH acidic [6]. Lactatic acid/sodium lactate buffer has an optimal pH 4.2 and is therefore crucial for maintaining vaginal pH values. Following menopause, the vaginal pH rises and susceptibility to infections increases [7].