Question

Explain the three major ways the body handles potentially developing acidosis (which can be life-threatening, if not dealt with).

Answer 1

There are 2 types of acids
Volatile formed by metabolism of carbohydrates ,proteins and fats
Its is excreted as Co2 from lungs

Non volatile acids ( Fixed acids )
Formed by metabolism of Phospholipid and nucleic acids .
Eg Sulphurica acids ,phosphoric acids and organic acids
Excreted by kidneys .

According To Henderson Hasselbachs equation ,Important determinants of H+ acids are 1 .Bicarbonate ( 22-26 meq/l )
2. Pco2 ( 40 mm hg )

Equation is PH = pka + Log ( Hco3-) / H2Co3
Acidosis may be of metabolic cause if bicarbonate is less in body or Respiratory if excess of Co2 in body .
Normally body main function is to get rid of excess of acids and help in homeostais .

First defence -Chemical buffer system .
Second defence - Respiratory buffer system .
Third defence - Renal buffer .

1)First defence - Chemical buffers
buffering (minutes to hours) - - - Buffers: bicarbonate (HCO3-/H2CO3) most efficient extracellular buffer as concentration of Hco3- maximum in blood .
**PKa of Hco3 - is 6.1 ( weak acids)
Hco3 (-) + H (+) form H2Co3 which dissociates into H20 water and Co2 Carbon dioxide .

**Pka of HpO4 (2-) is 6.8 (weak acid )
Hpo4 (2-) + H(+) forms H2po4 (-) Dihyrogen phosphate .
**When a molecule has got Pka close to physiological Ph it will be effective buffer .

**Intracellular buffer -
Hb (Hb-/HHb), Proteins (P-/HP),
Phosphate buffer .
Hb most important non-carbonic buffer. Buffers H+ 1° through imidazole moieties on histidine residues as well as formation of intracellular HCO3-which diffuses into the ECF

**Protein especially important in buffering of the intracellular compartment.

**Phosphate and ammonium are important urinary buffers

**Cells: exchange of extracellular H+ for intracellular K+

**Bone: exchange of extracellular H+ for Na+ and Ca2+ ions from bone

High acid loads demineralise bone – leads to release of alkaline compounds (CaHPO4 / CaCO3).

2)Second defence -- Respiratory

**Respiratory compensation (hrs → day) - Controls CO2 excretion to restore the [HCO3-]/ PaCO2 ratio.  
It can't directly excrete acid.  
Also Can't compensate completely.

**Mechanism
Decrease in arterial pH detected in chemoreceptors in carotid /aortic bodies cause Stimulation of the medullary respiratory centre cause Hyperventilation and increase in respiratory rate cause excess Co2 washout from lungs and restore the homeostasis .

3)Third defence -- Renal

Altering plasma [HCO3-] to restore [HCO3-]/PaCO2 ratio.

**Regulation of H+ balance by (in this order):
1)Increased reabsorption of HCO3- in renal tubules (80% Proximal Tubule/ 10% ascending limb Loop Henle / 10% Distal tubule/Collecting Duct ) 1:1 H+ excretion:HCO3- reabsorption

* *PCT/LoH/early DCT: Cellular carbonic anhydrase converts CO2 / H2O to H+ / HCO3-. H+ secreted into lumen by Na+/H+ countertransport. HCO3- diffuses into peritubular capillary blood.  

** Late DCT/CD: 1° active secretion H+ via H+ATPase. Passive secretion of Cl-. Controlled by Aldosterone .

2) Excretion of titratable acidity (1° in PCT)
** H+ bound to filtered buffers (1° urine (mono)phosphate – converted to dihydrogen phosphate.

3) Excretion of ammonium – acts as a H+ sink (binds irreversibly). Allows continued secretion of H+ even at maximum acidity - Most metabolic acids excreted as NH4+

*** PCT: glutamine deaminated→ 2xNH4+ + 2xHCO3- (diffuse into blood).

NH4+/Na+ countertransport secretes NH4+ into lumen .

NH3 cannot passively diffuse into lumen as pKA = 9.2.

Most NH4+ is involved in cycling within the medullary interstitium.

*** Most NH4+ produced in PCT is removed from tubular fluid in the medulla leaving only a small amount in the DCT (removed in ascending Loop of Henle).

**"High acid load decrease pH medullary Collecting Duct . The lower urine pH, the more NH4+ transfers from interstitium to lumen. This is regulatory as the amount of NH4+ excreted returns ECF pH toward normal.
So acids are lost in urine in form of ammonium ions .

In this way chemical ,respiratory and renal buffer system handles acids in body .