PENGATURAN KESEIMBANGAN ASAM

BASA
 Dalam tubuh akibat adanya metabolisme terjadi
perubahan [H+] yang berdampak pada fungsi tubuh 
pengaturan [H+]
 Normal dalam [H+] 0,00000004 mEq/liter
 pH = – log [H+], pH dalam tubuh sekitar 7,4
 pH >> normal = alkalosis
 pH << normal = asidosis
 Ambang homeostatik untuk pH darah: 7.35 – 7.45
pH < 7.35 Acidosis
pH > 7.45 Alkalosis
PENGATURAN KESEIMBANGAN ASAM BASA

 Berdasarkan pH/tingkat keasaman

 Asam:
 pH < 7
 Melepas ion H+
 Kuat-Lemah
 Basa:
 pH >7
 Menerima ion H+
 Kuat-Lemah
 REGULATOR HOMEOSTATIK
[H+] DALAM TUBUH

Bekerja secara sekuensial

1. SISTEM PENYANGGA ASAM –BASA

KIMIAWI CAIRAN TUBUH
(CHEMICAL BUFFER SYSTEM)
2. MEKANISME RESPIRASI (PUSAT
PERNAFASAN)
3. MEKANISME RENAL (GINJAL)
Key Concepts: Buffers

consist of

Weak acid and or Weak base and

its salt its salt
and

resist changes in pH

to

Maintain pH balance

preventing

Acidosis and Alkalosis

SISTEM BUFFER KIMIAWI
 Respon pertama
 Memerlukan waktu < 1 detik
 Fungsi umum: sebagai buffer:
o Menahan perubahan pH yang tiba-tiba
o Secara temporer “mengikat” kelebihan asam
dan basa  melindungi cairan tubuh
 Prinsip: reaksi penggaraman dan pergeseran reaksi
kimia
 NaOH + H2CO3  NaHCO3 + H2O
 CO2 + H2O  H2CO3
Timberlake, Fig 9.6
SISTEM BUFFER KIMIAWI
 Komponen:
o Asam lemah dan garamnya (misalnya H2CO3)
ATAU
o Basa lemah dan garamnya (misalnya NaHCO3)
 Terdiri dari:
 Asam karbonat – Bikarbonat

 Fosfat
 Sistem buffer protein
SISTEM BUFFER
ASAM KARBONAT - BIKARBONAT

Komponen Respirasi Komponen Renal

CO2 + H2O H2CO3 H + + HCO3 –

H2CO3 adalah asam yang bersifat ‘volatile’ (mudah

menguap)  CO2 dihembuskan
SISTEM BUFFER
ASAM KARBONAT - BIKARBONAT
 Komponen:
 H2CO3 : H2O + CO2  H2CO3 (dikatalisis oleh karbonik
anhidrase)
 H2CO3 dalam larutan tubuh akan berionisasi
 H2CO3  H+ + HCO3-
 NaHCO3
 Penambahan asam kuat (HCl) akan disangga oleh
HCO3- yang menyebabkan meningkatnya H2CO3
 CO2 meningkat
 CO2 yang meningkat merangsang SSP untuk
meningkatkan ventilasi paru  frekuensi nafas
meningkat
SISTEM BUFFER
ASAM KARBONAT - BIKARBONAT
 Penambahan basa kuat (NaOH)
 NaOH  Na+ + OH-
 Na+ + H2CO3  NaHCO3
 OH- + H2CO3  HCO3- (tambahan)
 Pada saat bersamaan karena H2CO3 digunakan untuk bereaksi
dengan NaOH  jumlah turun  terjadi pembentukan H2CO3
dari CO2 dan H2O
 Pembentukan H2CO3 dari CO2 dan H2O
menyebabkan kadar CO2 dalam darah turun, efek
kebalikan dengan keadaan CO2 tinggi
 Selain itu penambahan basa kuat meningkatkan
jumlah HCO3-, dikompensasi ginjal
• Sistem
Buffer Asam
Karbonat –
Bikarbonat
Buffer System

~ Paling penting
di ECF (Cairan
ekstra seluler)
• Sistem Buffer
Fosfat

~ Penting di ICF
(Cairan intra
seluler) & urine
SISTEM BUFFER FOSFAT
 Proses sama dengan bikarbonat

 Komponen :
 Na2HPO4 (basa lemah) dan
 NaH2PO4 (asam lemah)
• Sistem Buffer
Protein

~ Penting di ECF
dan ICF

~ Berinteraksi
dengan sistem
buffer yang lain
SISTEM BUFFER PROTEIN
 Berinteraksi dengan sistem buffer lainnya:
 Sistem Buffer Hb
 Sel
darah merah hanya di ICF
 Membantu mencegah pH   ketika pCO2 

CO2 + Hb HbCO2
O2 + HHb HbO2 + H+
 Buffer asam amino ( semua protein)
 Buffer protein protein:
 Lebih lambat daripada buffer kimia lain
 Membuang kelebihan H+ ataupun kelebihan OH-
(tergantung pada pH)
SISTEM BUFFER PROTEIN
 Komponen:
 Gugus karboksil (asam)
 Gugus amino (basa)

 Struktur asam amino (gugus fungsional) pada pH

netral
R

NH2 – C – COOH

H
 Berperan dalam jaringan paru, ketika terjadi
pembentukan ion H+ saat transport CO2
Jika pH  (lebih basa) :  [OH- ] 
Asam amino bekerja seperti asam

R

NH2 – C – COO- + H+

H
Jika pH  (lebih asam) :  [H+ ]  Asam
amino bekerja seperti basa
R

NH3+ – C – COOH

H
MEKANISME RESPIRASI
 Merupakan respon kedua
 Eliminasi CO2/H2CO3 dengan perubahan ventilasi
pulmoner
 Proses reaksi cepat (1-3 menit)
 Melibatkan pusat pernapasan
 Membuang (melepaskan) CO2 & kemudian H2CO3
MEKANISME
 Proses :
RESPIRASI
o Akibat metabolisme sel  CO2 dalam darah
tinggi  transpor ke paru
o Karena enzim karbonik anhidrase terdapat
dalam paru, CO2 + H2O  H2CO3 -  H+ +
HCO3- (Keadaan asam)
 Adanya CO2 tinggi dalam darah  SSP
 Pusat pernafasan  peningkatan frekwensi nafas
 Sebaliknya apabila terjadi alkalosis
MEKANISME RENAL
 Merupakan respon ketiga, tetapi paling potent

 Memerlukan waktu berjam-jam sampai berhari-hari

 Ginjal membuang asam-asam metabolit

 Misalnya asam fosfat, asam urat dan asam laktat;

badan keton
MEKANISME RENAL
 Melalui ekskresi urine dengan mengatur
pengeluaran ion H+ dan reabsorbsi HCO3-
 Proses lama, dan bertahan lama
 CO2 dalam darah difusi ke sel epitel ginjal, karena
adanya karbonik anhidrase :
 CO2 + H2O H2CO3 H+ + HCO3-
 Normal : sekresi ion H+ = dengan laju glomerular
terhadap HCO3-
 Perubahan pH mengaktifkan sistem penyangga
fosfat dan protein dalam sel epitel ginjal  sekresi
ion H+ dan reabsorbsi terhadap HCO3- berubah
 3. ACIDOSIS & ALKALOSIS
Respiratory Acidosis
Of respiratory origin
~ Shallow breathing
~  CO2 exhaled
 CO2 retained
Lung diseases blocking gas diffusion eg pneumonia,
emphysema
 CO2  H+ pH <7.35

Respiratory Alkalosis
Of respiratory origin
~  CO2 exhaled
Hyperventilation
Eg anxiety, hysteria
 CO2  H+  pH > 7.45
Metabolic Acidosis
Not of respiratory origin
~ Renal disease
~ Diarrhoea
~ Starvation
 H+  pH < 7.35

Metabolic Alkalosis
Not of respiratory origin
~ Vomiting
~  Ingestion Bicarb of Soda (NaHCO3)
 H+  pH > 7.45
 Respiratorik
 Akibat penurunan ventilasi pulmoner (pneumonia,
emfisema, obstruksi kronik saluran nafas)
 Dikompensasi oleh ginjal: ekskresi H+ tinggi
 Metabolik
 Akibat asam metabolik tidak dikeluarkan pada
kecepatan yang normal (ketoasidosis pada DM dan
kelaparan, akumulasi asam laktat karena konvulsi,
penyakit ginjal)
 Kompensasi respiratorik : hiperventilasi
 Respiratorik
 Hiperventilasi (cemas, demam, overdosis aspirin dsb)
 Kompensasi :
 Respiratorik (menghisap kembali CO2)
 Ginjal : ekskresi H+ berkurang, reabsorbsi HCO3- berkurang)

 Metabolik
 Kelebihan bikarbonat (muntah berkepanjangan,
disfungsi ginjal, obat diuretik, antasida)
 Kompensasi :
 Respiratorik : ventilasi turun pCO2 dan asam karbonat naik
 Ginjal : ekskresi ion amonium turun, ekskresi Na, K, reabsorbsi
HCO3- turun.
ECF and ICF Buffers
 Major ECF buffers are bicarbonate (HCO3-) and
phosphate (HPO4-)
 Major ICF buffer is hemoglobin
 Oxyhemoglobin releases O2 and takes up CO2 and
combines with H2O to form H2CO3
 Organic phosphates (ATP, AMP, ADP) and proteins
REABSORPTION of Filtered HCO3-
 99.9% of filtered HCO3- is reabsorbed
 Filtered load = GFR (L/day) x plasma bicarb (24mEq/L)
= 4320 mEq/day
 Reabsorbed in proximal convoluted tubule
 1. Na/H+ exchanger
 2. secreted H+ combines with HCO3- and forms H2CO3.
 3. Carbonic anhydrase breaks this down to CO2 and H2O
and they diffuse across membrane
 4. Inside cell, CO2 and H2O goes thru reverse rxn
 5. HCO3- is transported by Na+ cotransport or Cl- exchange.
Example of titratable acid in tubule lumen

HPO4-2 H2PO4-
+ H+
(filtered) (titratable acid
Is excreted)
Acid Base Disorders
(uncompensated responses)
 Metabolic
 Acidosis and alkalosis
 Primary disturbance is HCO3- concentration
 Acidosis = decreased HCO3- (loss results in increased H+)
 Alkalosis = increased HCO3- (loss of H+ and gain of HCO3-)
 Metabolic disturbances do not include changes in arterial CO2 (PaCO2)
 Respiratory
 Acidosis and alkalosis
 Primary disturbance is Pa CO2
 Acidosis = hypoventilation (increased CO2 retention and
decreased ph)
 Alkalosis = hyperventilation (decreased CO2 retention and
increased ph)
Compensation for acidosis or alkalosis

 Metabolic compensation (rapid – minutes)

 Compensation is respiratory
 Acidosis – stimulate chemoreceptors – hyperventilation
– decreased PaCO2
 Alkalosis – inhibits chemoreceptors – hypoventilation –
increased PaCO2
 Respiratory compensation (slow)
 Compensation is renal
 Acidosis – increase H+ secretion – increased HCO3-
reabsorption (days)
 Alkalosis – decreased H+ secretion – incomplete HCO3-
reabsorption – decreased plasma HCO3- (hours)
Diagnosis
 Normal ph 7.35-7.45
 Normal = 7.35 – 7. 45
 [HCO3-] 24 mM, PaCO2 40 mmHg
 Acidosis or alkalosis?
 Look at ph
 Metabolic or respiratory?
 First look at HCO3-, low = metabolic acidosis, up= alkalosis
 Then look at PaCO2, up = acidosis, down = alkalosis
 Compensation?
 Renal or respiratory
Worked example
(compensated metabolic acidosis)
 Arterial blood gases ph = 7.37 (slightly acidic)
 PaCO2 = 32 mmHg, [HCO3-] = 18 mM
 (normal = ph= 7.4, PaCO2 = 40 mmHg, [HCO3- =
24mM]
 Acidosis
 PaCO2 is not up – not respiratory, HCO3- down =
metabolic
 Compensation is respiratory – increased ventilation (to
reduce CO2)
 Has it happened yet? – yes, PaCO2 = 32 mmHg
 Respiratory Acidosis
 Respiratory acidosis is a condition in which a build-up
of carbon dioxide in the blood produces a shift in the
body's pH balance and causes the body's system to
become more acidic
 This condition is brought about by a problem either
involving the lungs and respiratory system or signals
from the brain that control breathing
 There is primary increase in Pco2 with compensatory
increase in HCO3 −; pH usually low but may be near
normal
Respiratory Acidosis
 Carbon dioxide is produced constantly as the body
burns energy
 this CO2 will accumulate rapidly if the lungs do not
adequately dispel it through alveolar ventilation
 Alveolar hypoventilation thus leads to an increased
PaCO2 (called hypercapnia)
 The increase in PaCO2 in turn decreases the
HCO3−/PaCO2 ratio and decreases pH resulting
respiratory acidosis
Types of Respiratory Acidosis
 Acute: In acute respiratory acidosis, the PaCO2 is
elevated above the upper limit of the reference range
(over 6.3 kPa or 47 mm Hg) with an accompanying
acidemia (pH <7.35)
 Acute respiratory acidosis occurs when an abrupt
failure of ventilation occurs
 This failure in ventilation may be caused by
depression of the central respiratory center by
cerebral disease or drugs, inability to ventilate
adequately due to neuromuscular disease (e.g.,
myasthenia gravis, amyotrophic lateral sclerosis,
Guillain-Barré syndrome, muscular dystrophy), or
airway obstruction related to asthma or chronic
obstructive pulmonary disease (COPD) exacerbation
 Types of Respiratory Acidosis
 Chronic: In chronic respiratory acidosis, the PaCO2 is elevated
above the upper limit of the reference range, with a normal
blood pH (7.35 to 7.45) or near-normal pH secondary to renal
compensation and an elevated serum bicarbonate (HCO3− >30
mm Hg)
 Chronic respiratory acidosis may be secondary to many
disorders, including COPD
 Hypoventilation in COPD involves multiple mechanisms,
including decreased responsiveness to hypoxia and
hypercapnia, increased ventilation-perfusion mismatch
leading to increased dead space ventilation, and decreased
diaphragm function secondary to fatigue and hyperinflation
 Chronic respiratory acidosis also may be secondary to obesity
hypoventilation syndrome (i.e., Pickwickian syndrome),
neuromuscular disorders such as amyotrophic lateral sclerosis,
and severe restrictive ventilatory defects as observed in
interstitial fibrosis and thoracic deformities
 Compensation
 Problem: Increase pCO2 and this results in a decrease
blood pH (high H+) [H+] stimulates kidney to generate
and retain bicarbonate respiratory acidosis.is
compensated for by the development of a metabolic
alkalosis
 Compensation is complete ([HCO3] levels out) in 2-4 days
 Final HCO3 can be calculated from the following
equation: HCO3 mmol/L = 0.44 X pCO2 mmHg + 7.6 (+/-
2)
 Limit of compensation is a HCO3 of 45 mmol/L
Alteration of metabolism & function
 Respiratory acidosis is associated with a plasma pH
decrease, arterial PaCO2 increase and often
accompanied by hypoxemia
 The signs and symptoms of respiratory acidosis also
depend on the rapidity of onset of acidosis
 The hypercapnia has some additional impacts on
central nervous system
 On CNS, the manifestations of CNS in respiratory
acidosis are often intermixed with those of oxygen
deficit
Alteration of metabolism & function
 CO2 readily crosses the blood-brain barrier, and
elevated levels of CO2 exert its effects by
producing vasodialation of cerebral blood vessels
and more acid brain fluids resulting in several
complications associated with chronic and acute
acidosis
 Because for HCO3-, to cross the blood brain
barrier is not easy as CO2, the pH values of
cerebrospinal fluid in respiratory acidosis are
usually lower than those of plasma, which means
that the respiratory acidosis usually has more
profound impacts on CNS than the metabolic
acidosis with the same plasma level of pH
Respiratory Alkalosis
 Definition: Respiratory alkalosis is a condition
where the amount of carbon dioxide found in the
blood drops to a level below normal range
 This condition produces a shift in the body's pH
balance and causes the body's system to become
more alkaline (basic)
 This condition is brought on by rapid, deep
breathing called hyperventilation
 There is a primary decrease in Pco2 with or
without compensatory decrease in HCO3 −; pH
high or near normal
Respiratory Alkalosis
 Generally occurs when some stimulus makes a person
hyperventilate
 The increased breathing produces increased alveolar
respiration, expelling CO2 from the circulation
 This alters the dynamic chemical equilibrium of carbon
dioxide in the circulatory system, and the system reacts
according to Le Chatelier's principle
 Circulating hydrogen ions and bicarbonate are shifted through
the carbonic acid (H2CO3) intermediate to make more CO2
via the enzyme carbonic anhydrase
 The net result of this is decreased circulating hydrogen ion
concentration, and thus increased pH (alkalosis)
 There is also a decrease in ionized blood calcium
concentration
Types of Respiratory Alkalosis
 Acute: It occurs rapidly
 During acute respiratory alkalosis, the person may
lose consciousness where the rate of ventilation will
resume to normal
 Chronic: It is a more long-standing condition. For
every 10 mM drop in pCO2 in blood, there is a
corresponding 5 mM of bicarbonate ion drop
 The drop of 5 mM of bicarbonate ion is a
compensation effect which reduces the alkalosis effect
of the drop in pCO2 in blood
 This is termed metabolic compensation
Compensation
 Compensation Problem: decrease pCO2 causing increase
blood pH (low H+)
 Increase pH stimulates the kidney to excrete bicarbonate
respiratory alkalosis is compensated for by the
development of a metabolic acidosis
 If the condition has been present for 7 days or more full
compensation may occur
 Compensation is complete ([HCO3] levels out) in 7-10
days. The limit of compensation is a HCO3 of 12 mmol/L
Alteration of metabolism and function

 The decrease in CO2 content of the blood causes

constriction of cerebral blood vessels
 CO2 crosses the blood-brain barrier rather quickly;
therefore, manifestations of acute respiratory
alkalosis are of sudden onset
 The constrictions of cerebral blood vessels can
cause regional cerebral ischemia in patients with a
pre-existing limitations of cerebral blood flow.
Alteration of metabolism and function

 Alkemia shifts the hemoglobin O2 dissociation

curve to the left, impairing O2 delivery to the
tissue
 An increase in neuromuscular excitability may be
due to decreased free Ca2+ availability, resulting
from increased albumin binding
 Respiratory alkalosis has alteration in
cardiovascular systems as well and also has
frequent hypokalemic consequences