A  BIRD’S-­‐EYE  VIEW  OF  

HYDROGEN  ION  HOMEOSTASIS    

(ACID  BASE  BALANCE)  

DR.  C.  S.  REX  SARGUNAM,  M.D.  (Ped),  D.C.H.  

Retired  Director  and  Superintendent  

Institute  of  Child  Health  and  Hospital  for  Children,  Egmore,  Chennai,  INDIA    

Pediatric  Consultant,  Department  of  Pediatrics,  St.  Isabel’s  Hospital,  Chennai,  INDIA  and  

Voluntary  Health  Service  Hospital,  Adyar,  Chennai,  INDIA  

President,  Tamilnadu  Health  Development  Association,  Chennai  

 

Under normal circumstances as a result of cellular respiration utilizing oxygen 𝑂! (aerobic metabolism) carbon dioxide is generated (𝐶𝑂!).    𝐶𝑂!      combines with water to form carbonic acid catalyzed by an enzyme, carbonic anhydrase (CA) present in the red blood corpuscles and renal tubular cells. This is a

reversible reaction: 𝐶𝑂! +  𝐻!𝑂!"  𝐻!𝐶𝑂!. Most of the 𝐶𝑂!    is excreted in the lungs. The carbonic acid

may disintegrate into free hydrogen ion (𝐻!) and bicarbonate ion (𝐻𝐶𝑂!!).  This is one of the normal main sources of hydrogen ions (𝐻!). Other than this, hydrogen ions are released directly during the metabolism of amino acids or carbon containing compounds. A net amount of 50 to 100 mM (1mM/kg) of hydrogen ions per day is released from the cells into the ECF and because of the homeostatic mechanisms, the ECF hydrogen ion (𝐻!)  concentration is kept constant, 40 + 5 nM/L (pH 7.4).  

What  is  pH  

pH  is  a  measure  of  𝑯!    ion  concentration.  

Normal  pH  7.4  (range  7.35  to  7.45).  

The  greater  the  𝐻!  ion  concentration  the  lower  is  the  pH.  

e.g.,  pH  6  acidemia.  

The  lower  the  𝐻!    ion  concentration  the  greater  is  the  pH.  

e.g.,  pH  8  alkalemia.  

Under pathological conditions as in circulatory shock and collapse, anaerobic metabolism occurs; that is, cellular metabolism takes place in the absence of oxygen, producing lactic acid. Lactic acid yields free hydrogen ions enormously. Similarly, in severe diabetes mellitus, as glucose is not metabolized acetone, acetoacetic acid and beta-hydroxybutyric acid are formed from fat yielding free hydrogen ions, lowering the pH.

pH is the measure of free hydrogen ion concentration of a solution. pH and hydrogen ion concentration are inversely related. That is, the higher the pH the lower will be the hydrogen ion concentration and vice versa.

Severe acidosis depresses myocardial contractility, sensitizes the heart to arrhythmias, produces arteriolar dilatation, hypotension and predisposes to pulmonary oedema. Severe alkalosis produces tetany and convulsions.  

Henderson  Hasselbalch  Equation  and  Derivation  of  pH

The  law  of  mass  action  states  that  the  rate  of  a  chemical  reaction  is  directly  proportional  to  the    

product  of    𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛  𝑜𝑓  𝑡ℎ𝑒  𝑟𝑒𝑎𝑐𝑡𝑖𝑛𝑔𝑠𝑏𝑠𝑡𝑎𝑛𝑐𝑒𝑠, 𝑎𝑡  𝑎  𝑔𝑖𝑣𝑒𝑛  𝑡𝑒𝑚𝑝𝑒𝑟𝑎𝑡𝑢𝑟𝑒.  

Then, to  remove  the  minus  sign, invert  the  last  term                    

𝑝𝐻   =  𝑝𝐾   +  log    [𝐻𝐶𝑂3−]

[𝐻2𝐶𝑂3]  

𝐶𝑂!  is  inserted  in  the  place  of  𝐻!𝐶𝑂!  

𝑝𝐻   =  𝑝𝐾   +  log    [𝐻𝐶𝑂3−]

[𝐶𝑂2]  

pK  is  6.1.This  is  constant  for  𝐻!𝐶𝑂!:𝐻𝐶𝑂!! buffer state

𝐶𝑂! concentration is derived by multiplying 𝑃𝐶𝑂! by the solubility constant for 𝐶𝑂!  (If 𝑃𝐶𝑂! is expressed in mm Hg the solubility constant of the gas is 0.03 and if the 𝑃𝐶𝑂! is expressed in kilopascal the solubility constant is 0.23.

(𝑅!    and 𝑅! are rates of one forward and backward reaction respectively. 𝐾! and 𝐾! are the rate constants of the forward and backward reactions respectively.

([𝐻!𝐶𝑂!] and [𝐻!] and [𝐻𝐶𝑂!!] denote concentrations of 𝐻!𝐶𝑂!, 𝐻! 𝐻𝐶𝑂!! respectively).

Homeostatic Mechanism to Maintain normal pH

To prevent acidosis or alkalosis, three important control systems are available.  

1. All the body fluids are supplied with acid-base buffer system which acts within a fraction of a second to combine with excess acids or bases to prevent excessive changes in hydrogen ion concentration.

2. If the hydrogen ion concentration is increased considerably, the respiratory centre is stimulated to alter the rate of breathing, and the removal of carbon dioxide from the body fluids is automatically ensured causing the hydrogen ion concentration to return to normal. This readjustment takes place in one to fifteen minutes.

3. When there is a change in hydrogen ion concentration, the kidneys excrete either an acidic or alkaline urine, restoring the pH to normal or near normal: being the most powerful of the acid-base regulating mechanisms, this requires several hours to several days to readjust the hydrogen ion concentration.

The Buffer Mechanisms

Here, certain terminology has to be defined. An acid is a substance which can dissociate to produce hydrogen ions (Protons 𝐻!).

A base is one which can accept hydrogen ions. An alkali is a substance which dissociates to produce hydroxyl ions (𝑂𝐻!).

A strong acid is one which gives rise to greater ionization (formation) of hydrogen ions due to the greater ionization of the acid.  

haemoglobin is normally six times as important as the plasma protein in the total buffering capacity of blood.

Respiratory Regulation of Acid-Base Balance

Blood carries oxygen from the lungs into the tissues and it carries carbon dioxide (𝐶𝑂!) from the tissue to lungs, where 𝐶𝑂! is eliminated. Most of the carbon dioxide combines with water in the presence of carbonic anhydrase enzyme in the RBC to form carbonic acid (𝐻!𝐶𝑂!). They immediately dissociate into hydrogen (𝐻!) and bicarbonate (𝐻𝐶𝑂!!) ions. Most hydrogen ions combine with the haemoglobin in the RBC, because haemoglobin is a powerful acid-baae buffer. Many of the bicarbonate ions diffuse into the plasma while chloride ions diffuse into the RBC.Thus the chloride shift occurs. As much as 70 percent of 𝐶𝑂! in the body is transported like this. In the lungs, the opposite reaction takes place. Chloride ions leave the RBC and bicarbonate ions enter the RBC. Carbonic acid (𝐻𝐶𝑂!)  is formed and 𝐶𝑂! is eliminated in the lungs.

Thus in acidosis there is an increased rate of respiration to eliminate 𝐶𝑂!; and in alkalosis,respiration becomes slower so as to retain 𝐶𝑂!.

Renal Regulation

This is an important and sustained control system in maintaining acid-base balance.  

Bicarbonate  Reclamation  

 The    𝐻𝐶𝑂!!   filtered   in   the   glomeruli   is   completely   titrated   by   the  𝐻!   ion   secreted   into   the   tubules.    𝑁𝑎!ion  which  is  reabsorbed  in  exchange  for  𝐻!  ion  which  is  derived  from  the  dissociation        of  carbonic  acid   formed  by   the   combination  of  𝐶𝑂!   and  𝐻!𝑂  in   the  presence  of   carbonic   anhydrase.   This    𝐶𝑂!   is  from  the   tubular   lumen  after   the  dissociation  of   carbonic  acid   in   the  presence  of   carbonic  anhydrase.  This  is  a  self  perpetuation  cycle  where  there  is  no  loss  of  𝐻!  ion  but  𝐻𝐶𝑂!!  ion  is  reclaimed.  There  is  no  net  gain  of  𝐻𝐶𝑂!!.  This  mechanism  can  not  correct  acidosis,  but  can  maintain  a  steady  buffer  state.  

The  carbonic  anhydrase  enzyme   is  present   in  the  RBC  and  proximal   tubules  of  kidney.  The  reaction  of  𝐶𝑂!   and  𝐻!𝑂   to   form   carbonic   acid   occurs   very   slowly   in   the   distal   tubule   and   in   the   presence   of  carbonic  anhydrase  the  reaction  is  accelerated  5000  times  as  in  the  proximal  tubule.  

The  bicarbonate  ion  is  mainly  reclaimed  in  the  proximal  tubules.  

Bicarbonate  Generation  

As   there   is   a   slight   excess   secretion   of  𝐻!   ion   over   the  𝐻𝐶𝑂!!   ions   filtered,   the   excess  𝐻!   ions   are  secreted  in  two  buffer  forms  as  𝑁𝑎!𝐻!𝑃𝑂!!  and  𝑁𝐻!!𝐶𝑙!.  

The   new   generation   of  𝐻𝐶𝑂!!   occurs   in  more   distal   segments   of   the   nephrons.   (The  mechanisms   for  both  reclamation  and  generation  of  bicarbonates  are  highly  developed,  energy-­‐  

Its  pH  to  7.4  of  the  glomerular  filtrate.  The  titratable  acidity  obviously  measures  only  a  fraction  of  the  acid  secreted  since  it  does  not  measure  the  𝐻!  that  combines  with    𝐻𝐶𝑂!!  or  that  is  buffered  as  𝑁𝐻!𝐶𝑙.  Disodium  monohydrogen  phosphates  (𝑁𝑎!𝐻𝑃𝑂!)   filtered   in  the  glomeruli   is  excreted  as  monosodium  dihydrogen  phosphate  (𝑁𝑎𝐻!𝑃𝑂!)  with  the  absorption  of  sodium  (𝑁𝑎!)  along  with  bicarbonate  𝐻𝐶𝑂!!)  which  is  generated  and  𝐻!  ion  which  is  secreted.  

Ammonia  Buffer  System  

Most  of   the  sodium  chloride   filtered   in   the   renal  glomeruli,   is  absorbed  as   such,  Proximal   tubule  cells  metabolise   glutamine   to  𝑁𝐻!!   and   alpha-­‐ketaglutarate.   The   alpha-­‐ketalutarate   is   metabolized   in   the  proximal   tubule   cell   by   a   process   that   generates  𝐻𝐶𝑂!!.   Thus   each  𝑁𝐻!!   that   appears   in   the   urine  completes  an  overall  process  that  generates  one  𝐻𝐶𝑂!!.  If  each  𝑁𝐻!!  molecule  formed  from  glutamine  is  not  excreted   in   the  urine  but   is   returned   to   the   liver,   the  𝑁𝐻!!   is  metabolized   to  one  𝐻!   and  part  of  urea.   This  𝐻!   thus   balances   the  𝐻𝐶𝑂!!   produced   by   the   kidney   and   no   change   in   acid-­‐base   balance  occurs.  Therefore  the  renal  execration  of  𝑁𝐻!!  is  essential  to  the  process  of  net  𝐻𝐶𝑂!!  generation.  

𝑯!  ion  secretion  in  the  collecting  Tubule  

Aldosterone  Dependent  

Non-­‐Adosterone  Dependent  

1. 𝑃𝑂!  buffer  system  2. 𝑁𝐻!  buffer  system  

Serum  electrolytes  

Blood  pH  (Arterial  Blood  Gas  Analysis)  

Venous  blood-­‐Obtained  without  using   a   tourniquet   from  non-­‐excercising   extremities   provides  pH  and  𝐻𝐶𝑂!!  values  for  assessing  and  following  a  patient  with  acid-­‐base  disorders,  provided  oxygenation  is  not  unquestionably  compromised.  

Metabolic  Acidosis  

The  causative  factor  must  be  corrected  simultaneously  with  the  management  of  metabolic  acidosis.  In  diabetic   ketosis,   the   core   treatment   consists   of   insulin,   intravenous   fluids   with   dextrose,   sodium  bicarbonate  for  acidosis  and  other  supportive  measures.  In  diarhoea  with  severe  dehydration,  child  is  hydrated  along  with  the  correction  of  acidosis  and  in  shock  with  metabolic  acidosis,  shock  is  treated,  perfusion  improved  and  acidosis  corrected.  

In  metabolic  acidosis,  certain  organic  anions  like  lactate,  and  acetate    

are  present.  These  are  called  potential  bicarbonates,  because  the  metabolism  is  reverted  to  normal  by  correction,   for   example:   in   treating   conditions   with   poor   tissue   perfusion   with   intravenous   fluids,  blood   and   other   antishock   measures,   these   potential   bicarbonates   are   converted   into   actual  bicarbonates.  If  this  is  not  considered  and  more  than  required  sodium  bicarbonates  are  administered  mechanically,  one  is  likely  to  over-­‐correct  resulting  in  alkalosis.  

Metabolic  acidosis  is  combated  specifically  by  administrating  sodium  bicarbonate.  It  will  be  rational  to  correct  empirically  

Rather  than  to  follow  the  formula  for  sodium  (Na)  correction,  given  as  follows,  Na  to  be  replaced  =  (Na  125  mEq/l-­‐serum  Na)  x  total  body  water  (in  L/kg).  

This   formula   cannot   be   applied   for   bicarbonate,   because   bicarbonates   can   be   created   or   destroyed  unlike  sodium  which  is  inert  and  can  neither  be  created  nor  destroyed.  Bicarbonates  are  created  when  𝐻!  ions  are  secreted  and  the  urine  is  acidified  or  formed  from  certain  lactate,  and  acetate  ions  and  from  certain   buffer   reactions.   Bicarbonates   are   lost   in   conditions   when   an   alkaline   urine   is   passed   when  intestinal  juice  is  lost.  

The  initial  amount  of  sodium  bicarbonate  given  to  correct  metabolic  acidosis  is  2  to  4  mEq/kg  depending  upon   the   severity,   over   a   period   of   6   to   8   hours.   Bicarbonate   should   not   be   given   by   bolus   infusion  because  it  may  precipitate  cardiac  arrhythmias,  paradoxical  intracellular  acidosis,  overexpansion  of  ECF  and  hyperosmolality.  After  this  period  a  fresh  clinical  assessment  should  be  made  with  acid-­‐base  data,  whether   to  give  next  dose  or  not.   If   it   is   to  be  given,   the  dosage   is  decided  and  given.  This  process   is  continued  till  patient  is  declared  free  of  acidosis.  

Treat  the  Cause  

Acidosis  

𝑵𝒂𝑯𝑪𝑶𝟑   2   mEq/kg   eighth   hourly   by   IV   infusion.   Never   by   bolus.   (In   acute   respiratory   acidosis,  moderate  amount  of  𝑵𝒂𝑯𝑪𝑶𝟑  may  be  given  to  mitigate  acidosis  to  prevent  the  serious  cardiovascular  effects  of  severe  acidosis).  

Alkalosis  

It  occurs  due  to  the  administration  of  excessive  alkalies,  improperly  composed  oral  rehydration  solution,  hypokalemia,  loss  of  chloride  ions  as  in  upper  intestinal  obstruction,  excessive  diuretic  therapy,  etc.  

Metabolic  alkalosis  will  correct  itself  if  sufficient  amount  of  cations  sodium  and  potassium  with  chloride  ions   are   administrated.   As  𝑁𝑎!   is   retained   for   exchange   of   𝐾!     and  𝐻!   ions,  𝑁𝑎!   ion   has   to   be  adequately  supplied  as  NaCl  to  be  absorbed.  Otherwise   in  an  attempt  to  retain  𝑁𝑎!   ion,  there  will  be  increased  regeneration  of  𝐻𝐶𝑂!!  and   increased  secretion  of  𝐻!     ion.   If  𝐾!   ion   is  deficient,  kidney  will  excrete  𝐻!  in  exchange  for  𝑁𝑎!  retention  and  for  each  ion  of  𝐻!  secreted  one  ion  of  𝐻𝐶𝑂!!  is  formed.  

Potassium  deficiency  has  to  be  rectified  by  giving  potassium  chloride,  as  chloride  is  the  main  anion  with  sodium   reabsorbed   in   the   tubules.   If   chloride   id   deficient,   the   sodium   which   would   have   been  reabsorbed  with  chloride  is  instead  reabsorbed  in  exchange  for  potassium  and  hydrogen  thus  alkalosis  is  perpetuated,  along  with  hypokalemia.  

The  above  mentioned  measures  take  some  time  to  correct  metabolic  alkalosis.  At  present,  attempts  are  made  to  treat  metabolic  alkalosis  specifically  when  immediate  partial  correction  is  required  like  prior  to  subjecting   a   patient   to   general   anaesthesis   to   avoid   cardiac   arrhythmia.   Preparations   attempted   are  parenteral  ammonium  chloride  up  to  6mM/kg/day  and  intravenous  arginine  hydrochloride  2-­‐4  mEq/kg  for   a   six   hour   period.   These   measures   are   only   in   an   experimental   stage   and   not   to   be   attempted  clinically.  

Respiratory  alkalosis  occurs  as  a  result  of  overbreathing  due  to  hysterical  conditions,  hyperpyrexia,  high  altitudes,  etc.  This  is  best  treated  by  rebreathing  the  expired  𝐶𝑂!.  

The  ideal  fluid  for  the  management  in  alkalosis  is  normal  saline,  as  sodium  chloride  supplied  will  be  absorbed  as  NaCl  avoiding  further  formation  of  sodium  bicarbonate.  

The  management  of  infantile  hypertropic  pyloric  stenosis  with  hypochloraemic  alkalosis  in  treating  hypovolemia  with  normal  saline  and  allowing  the  kidneys  (if  the  renal  function  is  normal)  to  correct  the  alkalosis.  Potassium  should  be  supplemented  by  oral  or  intravenous  fluids  containing  potassium  not  exceeding  40mEq/L  if  there  is  evidence  of  hypokalemia.  

Acid-­‐Base  Disturbances  Under  Special  Circumstances  Due  to  Change  in  ECF  Volume  

Under  normal  circumstances,  bicarbonate  concentration  is  24  mM/litre  and  carbondioxide  concentration  is  1.2  mM/litre.  The  following  diagrams  on  dilution  acidosis  and  concentration  alkalosis  are  self  explanatory.  

Potassium  

The  normal  serum  potassium  is  3.5  mEq/L  to  5.5  mEq/l.  Hypokalemia  is  present  when  𝐾!  is  less  than  3.5mEq/l  and  hyperkalemia  is  present  when  𝐾!  is  more  than  5.5mEq/l.  The  normal  adult  ingets  1  to  2  mEq  potassium  per  kilogram  of  body  weight.  In  healthy  persons,  about  90  percent  of  the  ingested  potassium  is  absorbed  from  the  gastrointestinal  tract  

into  the  ECF.  The  rest  10  percent  appears  in  the  stools.  98  percent  of  the  body  potassium  enters  the  ICF.  The  plasma  potassium  level  is  low  and  constant  as  it  is  mainly  excreted  in  the  urine  by  the  kidneys.  The  potassium  filtered  at  the    glomerulus  is  reabsorbed  by  the  proximal  tubule  and  is  secreted  into  the  distal  tubule   and   collecting   duct   along   with   hydrogen   ion,   in   exchange   for   sodium   ion,   thus   playing   an  important   role   in   acid-­‐base   homeostasis   in   the   body.   The   potassium   and   hydrogen   ions   compete   for  sodium  reabsorption.  In  hyperkalemia,  excess  potassium  is  secreted  in  preference  to  hydrogen  ion  thus  resulting  in  acidosis.  The  potassium  secretion  also  mainly  depends  on  the  amount  of  sodium  filtered  at  the   glomerulus   and   presented   to   the   distal   segments   for   reabsorption.   In   Addison’s   disease,   the  potassium  excretion   is   impaired.  Sodium  filtration   is   impaired   in  acute  glomerular   failure  eg.:   in  acute  glomerulonephritis,   𝑁𝑎!/𝐾!   exchange   cannot   take   place.   In   both   these   conditions,   plasma   𝐾!   is  increased  resulting  in  hyperkalemia.  

Factors  Producing  Hypokalemia  

1. Alkalosis  

Here  potassium  is  secreted  in  preference  to  hydrogen  for  sodium  reabsorption  in  the  distal  tubule  and  collecting  duct  producing  hypokalemia.  

At  the  cellular  level,  more  of  potassium  enters  the  cells  instead  of  hydrogen  perpetuating  hypokalemia.  

2. Reduction  in  the  total  body  potassium  (TBK)  

For  example:  in  diarrhea.  But  reduction  in  TBK  can  be  associated  with  normokalemia,  eg.:  in  acidosis.  

If   the  KCl   concentration   is  more   than   40  mEq/L,   a   central   vein  may   be   secured   to   avoid   irritation   to  peripheral  veins.  

Severe   hyperkalemia   and   hypokalemia   are   acute   medical   emergencies.   ECG   monitoring   is   a   must.  Intensive  care  management  is  essential.  

Hyperkalemia  

Factors  Producing  Hyperkalemia  

1. In   acidosis,   where   excess   hydrogen   ions   are   secreted   instead   of   potassium   in   exchange   for  sodium   reabsorption   in   the   distal   tubules   and   collecting   ducts   and   at   cellular   level   more   of  hydrogen  ions  enter  competing  for  potassium.  

2. Acute  renal  failure  and  end  stage  renal  failure.  3. Circulatory  collapse  and  shock  with  poor  perfusion.  4. Tissue  necrosis.  5. Ardrenal  cortical  failure.  

Hyperkalemia  can  produce  cardic  arrhythmias  and  death.  

Treatment  

Calcium  gluconate  0.5  ml/kg  of  10%  solution  is  given  intravenously  over  10  to  15  minutes  with  caution.  The   heart   rate   must   be   closely   monitored   with   ECG   during   the   infusion;   a   fall   in   a   rate   of   20  beats/minute  require  stopping  the  infusion  until  the  pulse  returns  to  the  preinfusion  state.  The  onset  of  action  is  within  minutes  and  lasts  for  about  half  an  hour.  Calcium  gluconate  does  not  

5. Peritonial  dialysis.  6. Hemodialysis  

The  last  two  measures  are  used  in  severely  hyperkalemic  patients  as  life  saving  measures.  

𝛽-­‐Andrenergic   agonists,   are   the   new   additions   to   the   armamentarium   for   the   treatment   of   acute  hyperkalemia.  5  microgram/kg  of  Salbutamol,  given  IV  over  15  miunutes,  or  by  nebuilizer  at  2.5-­‐5  mg.  is  very  effective  in  lowering  serum  𝐾!  level  for  up  to  2  to  4  hours.  

Choride  

The  intake  and  absorption  of  chloride  occurs  as  those  of  NaCl  andKCl  absorption  is  through  the  intestinal  route.   Most   of   the   chloride   is   reabsorbed   as   NaCl   and   little   is   excreted   in   the   urine   and   negligible  amount  in  faces  and  sweat.  The  distribution  of  chloride  is  well  illustrated  by  the  following  diagram.  

Chloride   is   the   main   anion   accompanying   the   cation   sodium.   In   the   kidneys   it   is   filtered   as   sodium  chloride   and   99%   of   it   is   reabsorbed   in   the   tubules.   In   the   proximal   tubule   about   65   percent   of   the  sodium   is   actively   absorbed   along   with   the   passive   diffusion   of   chloride.   In   the   diluting   segment  consisting  of  the  ascending  limb  of  the  loop  of  Henle  and  about  half  of  the  proximal  convoluted  portion  of  the  distal  tubule,  chloride  is  actively  absorbed  followed  by  passive  absorption  of  sodium.  In  the  late  distal  tubule  and  collective  duct  sodium  is  actively  reabsorbed  in  exchange  for  potassium  and  hydrogen  ions  which  are  secreted  into  the  urine  in  the  presence  of  aldosterone.  

Hypochloraemic  Alkalosis  

This  condition  may  be  caused  by  infantile  hypertrophic  pyloric  stenosis  or  after  excessive  gastric  suction.  Here  both  𝐻!  and  𝐶𝑙!  ions  are  lost.  This  is  accompanied  by  generation  of  𝐻𝐶𝑂!!  ions  which  are  not  lost.  In  the  proximal  tubule  sodium  is  released  along  with  passive  reabsorption  of  chloride  that  is  available.  A  reduction   in   the   available   chloride   limits   this   isotonic   reabsorption   of   𝑁𝑎𝐶𝑙   and   more   of     𝐻𝐶𝑂!!    formation.  This   results   in  alkalosis  and  hyperkalemia  which   is   corrected  by  administrating  appropriate  amounts  of  normal  saline.  

In  potassium  deficiency  also,  this  should  be  corrected  by  giving  potassium  chloride  than  with  any  other  potassium   salt   because   the   sodium   which   would   have   been   reabsorbed   with   chloride   is   instead  reabsorbed   in   exchange   with   potassium   and   hydrogen   ions   to   preserve   electroneutrality,   producing  hypochloraemic  alkalosis.  

Calcium  

The  normal  plasma  concentration  is  9  to  11  mg/dl.  Total  calcium  exists  in  three  forms:  

1. Ionized  or  free  calcium  (45  to  50  percent).  2. Protein  bound  calcium  (40  percent).  3. Complexes,  eg.:  with  𝑃𝑂!!  in  bones,  𝐻𝐶𝑂!!  and  citrate  (10  to  15  percent).