major buffer systems in the body

Major chemical buffers in the body

Bicarbonate buffer

A normal adult produces about 300 L of CO₂ daily from metabolism. CO₂ from tissues enters the capillary blood, where it reacts with water to form H₂CO₃, which dissociates instantly to yield H⁺ and HCO₃ ^–.

Blood pH would rapidly fall to lethal levels if the H₂CO₃ formed from CO₂ were allowed to accumulate in the body.

Fortunately, H₂CO₃ produced from metabolic CO₂ is only formed transiently in the transport of CO₂ by the blood and does not normally accumulate. Instead, it is converted to CO₂ and water in the pulmonary capillaries and the CO₂ is expired. As long as CO₂ is expired as fast as it is produced, arterial blood CO₂ tension, H₂CO₃ concentration, and pH do not change.

pK of the HCO₃^-/CO₂ is 6.1.

pH of plasma is 7.4.

 According to Henderson-Hasselbalch equation

7.4 = 6.1 + log [HCO₃^-]/ [CO₂]

1.3= log [HCO₃^-]/ [CO₂]

20= [HCO₃^-]/ [CO₂]

i.e. At pH 7.4, concentration of bicarbonate should be 20 times that of Carbon dioxide.

As described in the previous post, it is the salt portion that neutralizes external acids, so a higher concentration of bicarbonate should suffice. This explains the relative importance of bicarbonate/CO2 buffer over other buffers because most metabolic end products are acidic in nature.

Concentration of HCO3 ^-   in plasma or ECF normally averages 24 mmol/L.  CO₂ is measured from PCO₂ which is about 40 mm Hg and that amounts to 1.2mmol/L of CO₂ (0.03* 40) {The solubility coefficient for CO2 in plasma at 37°C is 0.03 mmol CO2/L per mm Hg PCO2 }.  Although the concentration of dissolved CO2 is lower, metabolism provides a nearly limitless supply. Hence [HCO₃-]/ [CO₂] = 24/1.2=20 supports the theoretical calculations performed above using Henderson-Hasselbalch equation.

The Henderson-Hasselbalch Equation for HCO₃^_/CO₂

_{In aqueous solutions:}

CO₂(d)   +    H₂O      give       H₂CO₃

_(dissolved)

At equilibrium, CO₂(d) is greatly favored; at body temperature,  [CO₂(d)] : [H₂CO₃] is about 400:1 [If [CO₂(d)] is 1.2 mmol/L, then [H₂CO₃] equals 3 μmol/L].

H₂CO₃     instantaneously breaks into H⁺ + HCO₃^-

The Henderson-Hasselbalch Equation for the above equation is:

pH= 3.5 +  log [HCO₃^-]/ [H₂CO₃]

H₂CO₃ is a fairly strong acid (pKa = 3.5). Its low concentration in body fluids lessens its impact on acidity. Because [H₂CO₃] is so low and hard to measure so [CO_2(d)] is used instead.

pH= 3.5 +  log [HCO₃^-]/ [CO_2(d)]/400

pH= 3.5+ log 400 + log [HCO₃^-]/ [CO_2(d)]

pH= 6.1+ log [HCO₃^-]/ [CO_2(d)]

pH= 6.1+ log [HCO₃^-]/ 0.03*pCO₂

pH= 6.1  + log [24]/[1.2]

pH=7.4

Physiological buffers: a brief introduction

Physiological Buffers

A "buffer system," which minimizes pH changes on addition of acid or base, consists of a solution containing a weak acid together with one of its soluble salts e.g. H₂CO₃ and NaHCO₃.

The acid, being weak, is slightly ionized but the soluble salt is ionized to a large extent. The mixture thus provides a reservoir of base (anions) which can combine with added H⁺ (neutralize added acid) and a reservoir of acid (undissociated acid molecules) which can donate hydrogen ions to neutralize added base.

Efficacy of the buffer depends on the pH of the buffer i.e. the concentration of weak acid and base added to constitute the buffer. This relationship is expressed by the Henderson-Hasselbalch equation.

pH= pK+ log [salt]/[acid]

A buffer is most effective when the concentration of its salt and acid are equal. pK of a buffer is that pH at which its salt and acid forms are in equal concentration. Hence a buffer is most effective in a solution the pH of which is equal to the pK of the buffer. The most effective physiological buffers are those whose pK is around 7.4.

In a solution which has various buffer systems then they should be in mutual equilibrium. If the acid:base is known for any one of the buffer systems, the pH of the mixture can be known. This can be described in terms of isohydric principle:

[H⁺] = K1*[acid 1]/[salt 1] = K2*[acid 2]/[salt 2]= K3*[acid 3]/[salt 3]

In plasma, H₂CO₃-NaHCO₃ buffer is the easiest to measure and most important quantitatively. Therefore total CO₂ content of plasma (sum of HCO₃^- and H₂CO₃ + CO₂) can represent the total buffering capacity.

Acids and Bases

Acids and bases

Acid: An "acid" is defined, according to (Lowry and Bronsted), as a substance  which, in solution, tends to liberate hydrogen ions (protons).

These hydrogen ions may

1.   remain as such

2.   may combine with the solvent forming, e.g., hydroxonium ions, H30⁺

3.   may combine with negatively charged ions.

 Base: A “base " is defined as a substance which tends to accept hydrogen ions.

Thus

H⁺ donor ↔ H⁺ + H⁺ acceptor

                                  (Acid)     (Base)

·        Acids, may not always be  undissociated molecules.

·        Bases, may be molecules, though the class includes all anions.

Thus the cation NH₄⁺ liberated from ammonium salts is an acid because it is capable of producing hydrogen ions according to the

equation:

NH₄⁺ ↔ H⁺ + NH₃

                                                (Acid)            (Base)

Similarly the anion HPO₄^-2 is a base because it can accept H⁺ to form H₂PO₄^- and the acid molecule H₃P0₄.

The anions H₂PO₄^- and HPO₄^-2 can also act as acids because they can lose H⁺ to form the base PO₄^-3 (" amphoteric").

Strength of acids

The " strength " of an acid is measured by its tendency to donate hydrogen ions ( by its degree of dissociation)

·        The freely dissociated mineral acids (HCI, etc.) are strong acids; slightly dissociated acids such as carbonic acid are weak.

·        A strong base has a great affinity for hydrogen ions whereas a weak base is a poor acceptor.

·        The anion of a strong acid is a weak base, e.g., Cl-, and the anion of a weak acid is a strong base, e.g., HCO3 -, OH-.

As I was searching literature for a short  and crisp note on acids and bases for the students of medicine, I came across a brilliant paper by 

Frazer and Stewart (J. clin. Path. (1959), 12, 195). I would advise the readers to go through the paper once if time permits. On my part I would definitely strive to elaborate upon all the subtopics explained in the paper and of course all the related material as well. Subsequent posts will lay stress on the physiological buffers and acidosis/ alkalosis.

I wish to have suggestions from the readers in order to improve my blog. Please feel free to ask any doubts related to these topics. As far as the explanation is concerned I think these topics can act as ready-made notes to be covered before each professional examination.

Poorvi

Serum anion gap

Anion Gap

Anion gap (plasma or serum) is an entity which can be calculated from the electrolytes measured in laboratory.

Definition:

“Anion gap is defined as the sum of serum chloride and bicarbonate concentrations subtracted from the serum sodium concentration.”

Normal value:  can vary widely, reflecting both differences in the methods that are used to measure its constituents and substantial interindividual variability. The average serum anion gap in healthy individuals measured varies from 11 ± 2.5   to 15 ±2.5 m eq/l .

Indications: This entity is used mainly for the detection and analysis of acid-base disorders, assessment of quality control in the chemical laboratory, and detection of such disorders as multiple myeloma, bromide intoxication, and lithium intoxication.

Gamblegram:

serum cations=serum anions

The sum of both entities must always be equal. This equivalency is the foundation of the derivation of the serum anion gap.

A graphic display of the ionic environment of the serum (Gamble J, 1950)

Total cations in serum = total anions in serum =155 meq/l

As a routine procedure, only sodium, potassium, chloride, bicarbonate ions are measured. Therefore other remaining cations and anions are called unmeasured cations (UC) and unmeasured anions (UA) respectively.

UC include magnesium (3 meq/l) and calcium (5 meq/l) ions mainly.

UA include proteins (16 meq/l); phosphate (2 meq/l), sulphate (1 meq/l), other miscellaneous anions( 6 meq/l).

Therefore,

Na⁺ + K⁺ + UC = Cl^- + HCO₃^-+ UA……….(i)

By rearranging:

Na⁺ + K⁺  - (Cl^- + HCO₃^-) = UA-UC..........(ii)

Under normal conditions, in a healthy individual, UA> UC (UA=25 meq/l; UC=8 meq/l); therefore, there is anion gap.

The concentration of potassium in the blood usually is relatively small compared with that of sodium, chloride, and bicarbonate;

therefore, many a times when calculating the anion gap potassium ion is omitted as

UA-UC = Na⁺ - (Cl^- + HCO₃^-) …………(iii)

Measured cations (MC)= 147 meq/l

Measured anions (MA) = 130 meq/l

MC-MA = UA-UC

147-130= 25-8

17=17

taken from an indepth review by Kraut and Madias (Clin J Am Soc Nephrol 2: 162–174, 2007).

Deviations in the normal values of serum anion gap would be discussed in some other post.

poem: welcome to holland

Last night, saw a tv program about a disabled child and got to know about this poem.


Welcome To Holland
by
Emily Perl Kingsley

I am often asked to describe the experience of raising a child with a disability - to try to help people who have not shared that unique experience to understand it, to imagine how it would feel. It's like this......

When you're going to have a baby, it's like planning a fabulous vacation trip - to Italy. You buy a bunch of guide books and make your wonderful plans. The Coliseum. The Michelangelo David. The gondolas in Venice. You may learn some handy phrases in Italian. It's all very exciting.

After months of eager anticipation, the day finally arrives. You pack your bags and off you go. Several hours later, the plane lands. The stewardess comes in and says, "Welcome to Holland."

"Holland?!?" you say. "What do you mean Holland?? I signed up for Italy! I'm supposed to be in Italy. All my life I've dreamed of going to Italy."

But there's been a change in the flight plan. They've landed in Holland and there you must stay.

The important thing is that they haven't taken you to a horrible, disgusting, filthy place, full of pestilence, famine and disease. It's just a different place.

So you must go out and buy new guide books. And you must learn a whole new language. And you will meet a whole new group of people you would never have met.

It’s just a different place. It's slower-paced than Italy, less flashy than Italy. But after you've been there for a while and you catch your breath, you look around.... and you begin to notice that Holland has windmills....and Holland has tulips. Holland even has Rembrandts.

But everyone you know is busy coming and going from Italy... and they're all bragging about what a wonderful time they had there. And for the rest of your life, you will say "Yes, that's where I was supposed to go. That's what I had planned."

And the pain of that will never, ever, ever, ever go away... because the loss of that dream is a very very significant loss.

But... if you spend your life mourning the fact that you didn't get to Italy, you may never be free to enjoy the very special, the very lovely things ... about Holland.

* * *

My all time favorite

स्वयं नहीं पीता, औरों को, किन्तु पिला देता हाला,स्वयं नहीं छूता, औरों को, पर पकड़ा देता प्याला,पर उपदेश कुशल बहुतेरों से मैंने यह सीखा है,स्वयं नहीं जाता, औरों को पहुंचा देता मधुशाला।
मैं कायस्थ कुलोदभव मेरे पुरखों ने इतना ढ़ाला,मेरे तन के लोहू में है पचहत्तर प्रतिशत हाला,पुश्तैनी अधिकार मुझे है मदिरालय के आँगन पर,मेरे दादों परदादों के हाथ बिकी थी मधुशाला।
बहुतों के सिर चार दिनों तक चढ़कर उतर गई हाला,बहुतों के हाथों में दो दिन छलक झलक रीता प्याला,पर बढ़ती तासीर सुरा की साथ समय के, इससे हीऔर पुरानी होकर मेरी और नशीली मधुशाला।
पित्र पक्ष में पुत्र उठाना अर्ध्य न कर में, पर प्यालाबैठ कहीं पर जाना, गंगा सागर में भरकर हालाकिसी जगह की मिटटी भीगे, तृप्ति मुझे मिल जाएगीतर्पण अर्पण करना मुझको, पढ़ पढ़ कर के मधुशाला।