Approaches to Understanding

Electrolyte and
Acid-Base Physiology

Dr A.Hadi Martakusumah SpPD-KGH

Sub Division of Nephrology and Hypertension
Department of Internal Medicine
Padjadjaran University/Hasan Sadikin General Hospital
Approaches to Understanding Acid-
Base Physiology

 Traditional Approach
 The discussion of acid-base physiology outlined in most
of this lecture is the ‘traditional’ empirical approach.
The concepts and explanations of this approach are still
the most common way that acid-base physiology is
taught and understood by many clinicians to some
extent
 Physico-chemical Approach
 An alternative approach derived from physico-chemical
principles was proposed by Stewart in 1981
 Basic Principles of the Various
Theories of Acids & Bases
Traditional Acid: a substance that has certain
properties (eg sour taste, turns litmus
approach red)

Arrhenius Acid : H + in aqueous solution

Base : OH- in aqueous solution

At neutrality: [H+] = [OH-]
Bronsted-Lowry Acid : H+ donor
Base : H+ acceptor
Conjugate acid-base pairs

Lewis Acid : a potential electron-pair acceptor

Base : a potential electron-pair donor

Usanovich Acid: a substance that donates a cation,

or accepts an anion or an electron
Base: a substance that donates an
anion, or accepts a cation.
 Water
 60-90% of body weight for most life forms
 Essential nutrient to sustain life
 often neglected
 Good solvent
 NaCl
 attraction of ions (Na+ and Cl-) to water > attraction to
each other
 Cohesion
 one water molecule capable of bonding with 4
others
 Water
 Highly reactive
 disassociation of water
 mass of H is small = proton jumping

H+ H+ H+ H+
O- O- OH- + H3O
+
 TBW as % of ECF as % of ICF as %
Age
body weight body weight body weight

Premature 75-80

Newborn 70-75 50 35

1 Year Old 65 25 40-45

Adolescent
60 20 40-45
Male
Adolescent
55 18 40
Female
Adapted from Feld. (1988)
 RULE OF THIRD

Body Weight

1/3 Total Body Water

ICF ECF

1/3 Intravascular
Interstitial
Volume Volume

1/3
8
 THE INTEGRATED VOLUME
RESPONSE
Perubahan Perubahan
hemodinamik keseimbangan
Sistemik garam + air
Respons Tachycardia Haus
Resistensi Retensi air dan
Perifer Natrium oleh
meningkat Ginjal
Onset Menit Jam
Aktifator Katekolamin Katekolamin
Angiotensin ADH
 Penyebab Utama Dehidrasi
 Melalui Ginjal (Renal):  Tidak melalui Ginjal (Extra
 Gangguan hormon Renal )
 Diabetes Insipidus  Perdarahan
 Penyakit Addison  Melalui kulit :
 Gangguan tubulus :  Keringat
 Renal Tubular Acidosis  Luka Bakat
(RTA)  Steven Jhonson’s syndr
 Penyalah gunaan diuretika  Melalui Traktus GI
 Post Obstruksi
 Mual muntah
 PNC
 Diare
 Diuresis Osmotik  Fistula
 DM  NGT
 Pemberian Mannitol
 Terapi Dehidrasi
 Cairan yang diberikan :
 NaCl 0,9 %
 Ringer Laktat
Elektrolit Natrium dan Kalium

Intra Sel Ekstra Sel

+ [Na + ] = 140 meq/L

[Na ] = 20 meq/L

[K + ] = 120 meq/L [K + ] = 4 meq/L

Algoritme pendekatan Pasien dengan Hiponatremia
 Gejala Hiponatremia
 Susunan Saraf Pusat :
 Ringan
 Sakit Kepala
 Apatis
 Lethargy
 Sedang
 Agitasi
 Bingung dan disorientasi
 Psikosis
 Berat
 Sopor sampai Koma
 Pernafasan Cheyne Stoke
 Kematian
 Gejala Hiponatremia
 Saluran Cerna :
 Hilang nafsu makan
 Mual
 Muntah

 Sistim Muskulo Skeletal :

 Kramp
 Refleks tendon menghilang
 Tiga hal yang harus diperhatikan
sebelum melakukan terapi
Hiponatremia
 Apakah penderita menunjukkan gejala
hiponatremia (simptomatik)?
 Sudah berlangsung berapa lama
hiponatremia tersebut ? Akut ? Kronik ?
 Apakah penderita mempunyai faktor resiko
untuk gangguan neurologis ?
 TERAPI HIPONATREMIA
 Kecepatan Terapi harus disesuaikan dengan
kecepatan terjadinya hiponatremia
 Terapi harus agresif pada kasusHiponatremia Akut
 Terapi lebih lambat pada kasus Hiponatremia
Kronik
 Terapi Hiponatremia Akut
(Terjadi < jam)

 Naikkan kadar Na serum sebanyak

2 mmol/L/jam sampai gejala klinis menghilang

 Koreksi sampai kadar Na serum normal

mungkin AMAN tapi biasanya TIDAK PERLU
 Terapi Hiponatremia Kronik
(Terjadi pada kurun > 48 jam)
 Mula mula Naikkan kadar serum sebanyak 10% dari kadar
awal atau 10meq/L dari kadar awal
 Lakukan pemeriksaan neurologis yang ketat .Kecepatan
koreksi diperlambat jika ada perbaikan dalam gejala klinis
 Setiap saat Kecepatan Koreksi tidak boleh melebihi kadar
1,5 meq/L/jam atau kenaikan melebihi 15 meq per hari
 Periksa kadar Na serum dan Urine setiap 2 jam
 Periksa kadar kation urine (UNa + UK) . Kadar ini harus
lebih rendah dari kadar Natrium yang diinfuskan. Untuk
menjaga pengeluaran free water .
 Kalium
 Kadar normal dalam serum 3,5 – 5,5 meq/L
 Asupan normal 50 – 100 meq/hari
 Pengatur kadar kalium serum :
 Shift intra sel
 Ginjal
 Traktus gastro intestinal
 Jumlah K+ Ekstra Sel = 2% dari seluruh K+ total
Hypokalemia without total body K depletion
Hypokalemia with total body k depletion
Treatment of hypokalemia
 Indikasi Pemberian Kalium
Parenteral
 Disritmia
 Paralisis Otot Pernafasan
 Hipokalemia pada penderita Ensefalopati
Hepatik
 Kadar kalium serum sangat rendah < 2 meq/L
Diagnostic approach to Hyperkalemia
Treatment of Hyperkalemia
The Composition of the Human Body

Figure 27.1a
 Strong Ions
 Cations  Anions
 Na+  Cl-
 K+  SO4-
 Ca++  Lactic acid
 Mg++

Disassociate into ions in solution

 pH
 The term pH was coined by the Danish
chemist, Soren Peter Sorensen in 1909 to
refer to the negative log of hydrogen ion
concentration
 the symbol pH meaning ‘potenz’ (power) of
Hydrogen.
 pH = -log [H3O+]
 H3O+ > OH- = acidic
 OH- > H3O+ = basic
 pH = - log10 aH+ (or: aH+ = 10 (-pH) )

where aH+ is activity of H+

Relationship between pH & [H+]
pH [H+]
(nanomoles/l)
6.8 158
6.9 125
7.0 100
7.1 79
7.2 63
7.3 50
7.4 40
7.5 31
7.6 25
7.7 20
7.8 15
Cations and Anions in Body Fluids

Figure 27.2
 Normal

Kation (mEq/L) Anion (mEq/L)

Na+ 140 Cl– 103
K+ 4 HCO 3– 25
Ca + + 5 Protein 16
Mg + + 2 Organic 4
H+ 0.000040 Other 3
(40 nmol/L) Inorganic
 H+ and the Potential
Threat to survival
 The free [H + ] is tiny and must be kept so for
survival
 A very large accumulation of [H + ] may kill
by binding to proteins in cells and changing
their charge ,shape and possibly their function
 Acid-Base Balance
 Each day there is always a net production of
acid by the body’s metabolic processes
 To maintain balance, these acids need to be
excreted.
 The acids produced by the body are classified
as :
 respiratory (or volatile) acids
 metabolic (or fixed) acids.
 Basal Carbon Dioxide Production

 Consider a resting adult with an oxygen

consumption of 250 mls/min and a CO2
production of 200 mls/min (Respiratory
quotient 0.8):
 Daily CO2 production
= 0.2 x 60 x 24 l/day divided by 22.4 l/mole
= 12,857 mmoles/day.
 Metabolic or Fixed Acids
 This term covers all the acids the body produces which
are non-volatile.
 Because they are not excreted by the lungs they are
said to be ‘fixed’ in the body.
 All acids other then H2CO3 are fixed acids.
 These acids are usually referred to by their anion (eg
lactate, phosphate, sulphate, acetoacetate or b-
hydroxybutyrate).
 Net production of fixed acids is about 1 to 1.5 mmoles
of H+ per kilogram per day:
 About 70 to 100 mmoles of H+ per day in an adult.
 This non-volatile acid load is excreted by the kidney
 Dietary acid-base Impact
Nutrient Product [H + ] (mmol/day )
Reactions generating [H + ]
Sulfur-containing amino acid
-Cysteine/cystinine,methionine [H + ] 70
Cathionic amino acids
-Lysine,arginine,histidine [H + ] 140
Organic phosphates HPO42- +[H + ] 30
Reactions removing [H + ]
Anionic amino acid
-Glutamate ,aspartate HCO3- -110
Organic anions eg citrate HCO3- -60
Organic phosphate excretion H2PO42- -30
with [H + ]
NET TOTAL [H + ] to be excreted as NH4+ 40
 Role of the Kidneys
 The lungs are important for excretion of carbon dioxide (the
respiratory acid) and there is a huge amount of this to be excreted: at
least 12,000 to 13,000 mmols/day.
 In contrast the kidneys are responsible for excretion of the fixed acids
and this is also a critical role even though the amounts involved (70-
100 mmols/day) are much smaller.
 The main reason for this renal importance is because there is no other
way to excrete these acids and it should be appreciated that the
amounts involved are still very large when compared to the plasma
[H+] of only 40 nanomoles/litre.
 There is a second extremely important role that the kidneys play in
acid-base balance, namely the reabsorption of the filtered bicarbonate.
 Role of the Kidneys
 In acid-base balance, the kidney is responsible for 2
major activities:
 Reabsorption of filtered bicarbonate: 4,000 to 5,000
mmol/day
 Excretion of the fixed acids (acid anion and associated
H+): about 1 mmol/kg/day.
 Terminology of Acid-Base Disorders
 Acidosis –
 an abnormal process or condition which would lower arterial pH
if there were no secondary changes in response to the primary
aetiological factor.
 Alkalosis –
 an abnormal process or condition which would raise arterial pH
if there were no secondary changes in response to the primary
aetiological factor.
 Simple Disorders
 are those in which there is a single primary aetiological acid-base
disorder.
 Mixed Disorders
 are those in which two or more primary aetiological disorders are
present simultaneously.
 Acidaemia - Arterial pH < 7.36 (ie [H+] > 44 nM )
 Alkalaemia - Arterial pH > 7.44 (ie [H+] < 36 nM )
 The Anion Gap
 Anion gap = [Na+] - [Cl-] - [HCO3-]
 Reference range is 8 to 16 mmol/l.
 An alternative formula which includes K+ is :
 AG = [Na+] + [K+] - [Cl-] - [HCO3-].
 Other Cations
Unmeasured Anions
Other Anions
Proteins (15 mEq/L)
A- Organic Acids (5 mEq/L
Phosphates (2 mEq/L)
HCO3- Sulfates (1mEq/L)
UA = 23 mEq/L
25

Na +
Unmeasured Cations
140 Calcium (5 mEq/L)
Potassium (4.5 mEq/L)
Cl - Magnesium (1.5
mEq/L)

103 UC = 11 mEq/L

 Anion gap = [Na+] - [Cl-] - [HCO3-]

Other Cations When an
Other Anions acid such
A- lactic
L- acid is
Added Anions added
HCO3- The
HCO3-
will fall
Na + and
140 replaced
by
lactate
Cl - anion

103

Metabolic Acidosis with increased anion gap

Other Cations
Other Anions Other Anions
A- A-
A-
L- Added Anions
HCO3-
25
HCO3-

Na +
140

Cl -

103

Normal AG Increased AG
Other Cations Note that
Other Anions with a loss
A- of
HCO3- NaHCO3
HCO3- will
fall but no
new anions
Na + will be
added
140

Cl -

Metabolic Acidosis with normal anion gap

Other Cations

Other Anions Other Anions Other Anions

A- A- A- A-
L- Added Anions HCO3-
HCO3-
25
HCO3-

Na +
140
Cl -
Cl - Cl -

103

Normal AG Increased AG Normal AG

The Basic Relationship between PCO2 and Plasma pH

Figure 27.6
 Mechanisms of pH control
 Buffer system consists of a weak acid and its anion
 Three major buffering systems:
1. Protein buffer system
 Amino acid
 H+ are buffered by hemoglobin buffer system
2. Carbonic acid-bicarbonate
 Buffer changes caused by organic and fixed acids
3. Phosphate
 Buffer pH in the ICF
 Protein buffer system
 If pH climbs, the carboxyl group of amino acid
acts as a weak acid
 If the pH drops, the amino group acts as a weak
base
 Hemoglobin buffer system
 Prevents pH changes when PCO2 is rising or falling
Figure 27.8 Amino Acid Buffers

Figure 27.8
 Carbonic Acid-Bicarbonate
Buffering System
 Carbonic acid-bicarbonate buffer system
 CO2 + H2O  H2CO3  H+ + CO3–
 Has the following limitations:
 Cannot protect the ECF from pH changes due to
increased or depressed CO2 levels
 Only functions when respiratory system and control
centers are working normally
 It is limited by availability of bicarbonate ions
(bicarbonate reserve)
The Carbonic Acid-Bicarbonate Buffer System

Figure 27.9a, b
 Maintenance of acid-base
balance
 Lungs help regulate pH through carbonic acid -
bicarbonate buffer system
 Changing respiratory rates changes PCO2
 Respiratory compensation
 Kidneys help regulate pH through renal
compensation
Kidney tubules and pH Regulation

Figure 27.10a, b
Kidney tubules and pH Regulation

Figure 27.10c
 The Central Role of the Carbonic Acid-
Bicarbonate Buffer System in the Regulation of
Plasma pH

Figure 27.11a
 The Central Role of the Carbonic Acid-
Bicarbonate Buffer System in the Regulation of
Plasma pH

Figure 27.11b
 Rates of correction
 Buffers function almost instantaneously
 Respiratory mechanisms take several minutes
to hours
 Renal mechanisms may take several hours to
days
 Acid-Base Disorders

 Respiratory acid-base disorders

 Result when abnormal respiratory function causes
rise or fall in CO2 in ECF
 Metabolic acid-base disorders
 Generation of organic or fixed acids
 Anything affecting concentration of bicarbonate ions
in ECF
 Respiratory acid-base disorders
 Respiratory acidosis
 Results from excessive levels of CO2 in body fluids
 Respiratory alkalosis
 Relatively rare condition
 Associated with hyperventilation
Respiratory Acid-Base Regulation

Figure 27.12a
Respiratory Acid-Base Regulation

Figure 27.12b
 Metabolic acid-base disorders
 Major causes of metabolic acidosis are:
 Depletion of bicarbonate reserve
 Inability to excrete hydrogen ions at kidneys
 Production of large numbers of fixed / organic acids
 Bicarbonate loss due to chronic diarrhea
 Metabolic alkalosis
 Occurs when HCO3- concentrations become elevated
 Caused by repeated vomiting
The Response to Metabolic Acidosis

Figure 27.13
Metabolic Alkalosis

Figure 27.14
 Detection of acidosis and
alkalosis
 Diagnostic blood tests
 Blood pH
 PCO2
 Bicarbonate levels
 Distinguish between respiratory and metabolic
A Diagnostic Chart for Acid-Base Disorders

Figure 27.15
 Clinical Acid Base Problem Solving
 Langkah Pertama :
 Harus tahu harga normal parameter yang akan digunakan untuk
menganalisis kelainan asam basa :
 a. pH 7.40 atau [H+ ] 40 nmol/L
 Cara merubah pH kedalam [H+ ] :
 Buang angka tujuh dan desimalnya jadi misal pH 7.26 didapat 26
 Kurangi 40 dengan nilai tersebut jadi 40 – 26 = 14
 Tambahkan 40 kedalam harga tersebut : 40 + 14 = 54 nmol/
 b. pCO2 = 40 mm Hg
 c. [HCO3] = 25 mmol/L
 d. Anion gap plasma Na-Cl-[HCO3] = 12 mEq/L jika kadar
albumin normal yaitu 4 gr% . Setiap penurunan albumin 1 gram
% dari harga normal maka kadar AG dikurangi 4
 Clinical Acid Base Problem Solving
Langkah Kedua :
 Apakah ada Lab Error ?

 Cara mengetahuinya adalah masukkan harga PH ,

pCO2 dan [HCO3] kedalam persamaan Henderson di
bawah ini : [H+ ] = pCO2 X 24/ [HCO3]

 Jika penderita tidak demam dan harga [HCO3 ] yang
dihitung dan yang diukur berbeda lebih dari 10% maka
ada lab error .
 Kita harus mengulangi pemeriksaan. Kita tidak ingin
menganalisis hasil AGD berdasarkan hasil
laboratorium yang salah .
 Clinical Acid Base Problem Solving

Langkah Ketiga :
 Tetapkan hasil pH :

 Acidemia jika kurang dari 7.36

 Alkalemia jika lebih dari 7.44

 Clinical Acid Base Problem Solving
Langkah Keempat :
 Tentukan apakah kelainan primernya
respiratorik atau metabolik
 Alkalemia :

 Respiratory Alkalemia jika pCO2 kurang dari 38

 Metabolic Alkalemia jika [HCO3] lebih dari 25

 Acidemia :
 Respiratory Acidemia jika pCO2 lebih dari 44

 Metabolic Acidemia jika [HCO3 ] kurang 25
 Clinical Acid Base Problem Solving
Langkah Kelima :
 Hitung anion gap (AG) serum yaitu :

 Kadar Na serum – ( Cl
 + [HCO ] serum
3
 Jika AG > 10 ada kemungkinan Other
Cation Other
Anion
 metabolic acidemia A-
HCO3-
 Jika AG > 20 dapat dipastikan (25)
ada metabolic acidemia Na+

Jangan lupa factor albumin ! (140)

 Cl-
(103)
 Clinical Acid Base Problem Solving
Langkah Keenam :
 Check derajat kompensasi tubuh :
 Metabolic Acidemia :
 Setiap penurunan pCO2 = 1.3 X penurunan [HCO3]
 Metabolic Alkalemia :
 Setiap kenaikan pCO2 = 0.6 X kenaikan [HCO3]
 Respiratory Acidemia :
 Akut :
 Setiap pCO2 naik 10 mmHg = [HCO3] naik 1 mEq/L
 Kronik :
 Setiap pCO2 naik 10 mmHg = [HCO3] naik 4 mEq/L
 Respiratory Alkalemia :
 Akut :
 Setiap pCO2 turun 10 mmHg = [HCO3] turun 2 mEq/L
 Kronik :
 Setiap pCO2 turun 10 mmHg = [HCO3] turun 5 mEq/L
 Clinical Acid Base Problem Solving

Langkah Ketujuh :

 Determine Delta ratio (Delta gap) =

 (Increase in anion gap / Decrease in
bicarbonate)
Guidelines for Use of the Delta Ratio in Metabolic
Acid-Base Disorders

Delta Ratio Assessment Guideline

< 0.4 Hyperchloraemic normal anion gap acidosis

0.4 - 0.8 Consider combined high AG & normal AG

acidosis Ratio often <1 in acidosis assoc.
with renal failure
1 to 2 Usual for uncomplicated high-AG acidosis
Lactic acidosis: average value 1.6
DKA more likely to have a ratio closer to 1
due to urine ketone loss (esp if patient not
dehydrated)
>2 Suggests pre-existing elevated HCO3 level:
consider a concurrent metabolic alkalosis
or a pre-existing compensated respiratory
 Other parameter to consider
 The Urinary Anion Gap
 The cations normally present in urine are Na+,
K+, NH4+, Ca++ and Mg++.
 The anions normally present are Cl-, HCO3-,
sulphate, phosphate and some organic
anions.
 Only Na+, K+ and Cl- are commonly measured
in urine so the other charged species are the
unmeasured anions (UA) and cations (UC).
 Cl- + UA = Na+ + K+ + UC
 Urinary Anion Gap =
( UA - UC ) = [Na+]+ [K+] - [Cl-]
 Urinary Anion Gap
Clinical Use
 Key Fact: The urinary anion gap can
help to differentiate between GIT and
renal causes of a hyperchloraemic
metabolic acidosis.
 It has been found experimentally
that the Urinary Anion Gap (UAG)
provides a rough index of
urinary ammonium excretion.
 Urinary Anion Gap
Clinical Use
In a patient with a hyperchloraemic
metabolic acidosis:
 A negative UAG suggests GIT loss of
bicarbonate (eg diarrhoea)
 A positive UAG suggests impaired renal
distal acidification (ie renal tubular
acidosis).
 As a memory aid, remember ‘neGUTive’
- negative UAG in bowel causes
 Osmolar Gap
 Osmolar gap = (Measured osmolality) -
(Calculated osmolarity)
 2 [Na+] + Glucose ( mmol/L) + Urea N (mmol/L)
0R
 2 [Na+] + Glucose( mg% /18) + Urea N(mg% /2.8)

 The osmolar gap can be very useful in assisting

diagnosis in metabolic acidosis due to toxic alcohols
& glycols (eg ethylene glycol, methanol).
Common Causes of Metabolic Acidosis
Increased Anion Gap
(Think…”MUDPILES”)
 Methanol intoxication*
 Uremic acidosis (advanced renal failure)
 Diabetic ketoacidosis*
 Paraldehyde intoxication
 Iron overdose
 L-lactic acidosis*
 Ethylene glycol intoxication*
 Salicylate intoxication
 D-lactic acidosis
 Alcoholic ketoacidosis*
*Denotes most common
Common Causes of Metabolic Acidosis
Normal anion gap
 Mild to moderate renal failure*
 Gastrointestinal loss of HCO3- (acute diarrhea)*
 Type I (distal) renal tubular acidosis
 Type II (proximal) renal tubular acidosis
 Dilutional acidosis
 Treatment of diabetic renal tubular acidosis*
 Ketones lost in urine

*Denotes most common

 Common causes of Metabolic
Alkalosis
 Net loss of H+ from the ECF
 G.I. Loss
 Vomiting or nasogastric suctioning
 Chloride losing diarrhea: chronic diarrhea/laxative
abuse
 Renal loss
 Loop or thiazide type diuretics esp. in CHF and
cirrhosis
 Mineralocorticoid excess
 Hyperaldosteronism
 Cushing’s syndrome
 Common causes of Metabolic
Alkalosis
 Retention of HCO3-
 Excess administration of NaHCO3
 Milk-alkali syndrome: antacids, milk, NaHCO3
 Massive (>8 units) blood transfusion (citrate)
 Posthypercapnia metabolic alkalosis (after
correction of chronic respiratory acidosis)
 Mixed acid-base disorders
Two or more simple acid-base disorders coexist

 Metabolic acidosis + Respiratory  Metabolic Acidosis + Respiratory

Acidosis Alkalosis
 pH usually very low  pH may be near normal
 Pa CO2 too high  Pa CO2 too low
 HCO3- too low  HCO3- too low

 Metabolic Alkalosis + Respiratory  Metabolic Alkalosis + Respiratory

Alkalosis Acidosis
 pH usually very high  pH may be near normal
 Pa CO2 too low  Pa CO2 too high
 HCO3- too high  HCO3- too high