buffers, mechanism, maintenance of body pH and disorders

1. Acid-Base balance

2. Acid Base balance
Acid-base balance refers to the mechanisms the
body uses to keep its fluids close to neutral pH (that
is, neither basic nor acidic) so that the body can
function normally.
Arterial blood pH is normally closely regulated
to between 7.35 and 7.45.

3. acids ？ Any ionic or molecular substance
that can act as a proton donor.
Strong acid ： HCl, H2SO4, H3PO4.
Weak acid ： H2CO3, CH3COOH.
bases ？ Any ionic or molecular substance
that can act as a proton acceptor.
Strong alkali ： NaOH, KOH.
Weak alkali ： NaHCO3, NH3,
CH3COONa.

4. Origin of acids Much more
 Intracellular metabolism
Volatile CO2+H2O=H2CO3 300~400L CO2 (15mol
acids H+)
Lactic acid
Fixed Ketone bodies 50~100 mmol H+
acids Sulfuric acid
Phosphoric acid
Origin of bases less NH3 , sodium citrate, sodium lactate

5. pH
- pH of ECF is between 7.35 and 7.45.
Deviations, outside this range affect
membrane function, alter protein function,
etc.
- You cannot survive with a pH <6.8 or >7.7
- Acidosis- below 7.35
Alkalosis- above 7.45
CNS function deteriorates, coma, cardiac
irregularities, heart failure, peripheral
vasodilation, drop in Bp.

6.  Given that normal body pH is slightly alkaline and that
normal metabolism produces acidic waste products
such as carbonic acid (carbon dioxide reacted with
water) and lactic acid, body pH is constantly
threatened with shifts toward acidity.
 In normal individuals, pH is controlled by two major
and related processes; pH regulation and pH
compensation. Regulation is a function of the buffer
systems of the body in combination with the
respiratory and renal systems, whereas compensation
requires further intervention of the respiratory and/or
renal systems to restore normalcy.

7. Buffer Systems in Body Fluids
Figure 27.7

8. Buffering system
 ECF
Plasma NaHCO3/ H2CO3 NaPr/HPr* Na2HPO4/NaH2PO4
intercellular NaHCO3/ H2CO3 Na2HPO4/NaH2PO4
fluid
 ICF** KPr/HPr K2HPO4/KH2PO4 KHCO3 /H2CO3
organic acids
 RBC KHb/HHb KHbO2/HHbO2 K2HPO4/KH2PO4
KHCO3/ H2CO3
* HPr ： protein ； ** muscle cells 。

9. Major buffer system in the body
Carbonic acid/Bicarbonate(HCO3-/H2CO3) :
The major extracellular buffer ， regulated by lungs
and kidneys ， effective ， determining the pH of
plasma.
Phosphate (HPO42-/H2PO4- ) : Intracellular
Protein (Pr-/HPr) : Plasma/Intracellular
Hemoglobin (Hb-/HHb and HbO2-/HHbO2 ) : RBC
*A buffer system cannot buffer itself.
 fast / no permanence

10. 2) Respiratory control:
Expelling more CO2 through respiration→to
exclude volatile acid.
H+→chemoreceptor → excite respiratory
centre → hyperventilation → exclude volatile acid
Fast / effectively / only excludes
volatile acid

11. PaCO2↑ (40-80 mmHg)→ Blood-brain barrier
permeable to CO2: CO2+H2O↔ H2CO3 ↔ H++HCO3-(in
cerebrospinal fluid, CSF)→ [H+] ↑ → Central
chemoreceptor(beneath the ventral surface of the
medulla oblongata) → Respiratory center ↑ →
Ventilation↑ (Main)

12. 3) Role of kidney (exclusion of
acid with conservation of base)
hydrogen ion secreted
ammonium excreted by renal tubular
cell
bicarbonate reabsorbed
 Effectively ( fixed acid may be
excluded ) / slowly

13. Kidney tubules and pH Regulation
Figure 27.10a,
b

14. Definition of acid-base disorders
An acid base disorder is a change in the
normal value of extracellular pH that may result
when renal or respiratory function is abnormal
or when an acid or base load overwhelms
excretory capacity.

15. PLAY Animation: Relationship Between PCO2 and Plasma pH
Figure 27.6

16. Simple acid-base disorder
1. Metabolic acidosis
1) concept:
primary disturbance [HCO3-] ↓ ; PH .
PaCO2 ↓
2) clasification:
Normal AG
High AG
3) pathogenesis and mechnisms:
(1) lose of bases
(2) gaining acids

17. Metabolic acidosis
Causes:
(1) lose of bases (bicarbonate decreased)
Gastrointestinal losses: diarrhea
Renal losses: proximal renal tubular acidosis and distal
renal tubular acidosis
(2) gaining acids (bicarbonate consumed in buffering)
Lactic acidosis: tissue hypoxia, impaired oxygen utilization, severe liver
dysfunction, and shock
Ketoacidosis: diabetic,hepatic cirrhosis, alcoholic poisoning, or starvation
Renal failure: conservation of acids
Exogenous acid intake: ammonium chloride, salicylate, ethylene
glycol(commonly used in antifreeze), or methanol intoxication

18. 4) Compensation:all regulation system take part in
Compensation
5) Effects:
Effects
(1) Depression of central neural system
a Elevated activities of glutamate decarboxylase
→GABA ↑
b.ATP ↓
(2) Depression of heart and vessel(Ca2+ transport
disorder; hyperkalemia;ATP↓):
cardiac output ↓ ;
cardiac arrhythmias;
peripheral vasodilation.
(3) Skin: warm and flashed
(4) Alteration of skeleton:
decacification, retarding growth and
osteodystrophy

19. Respiratory acidosis
1) Concept:
Concept
Primary change : retention of CO2; pH .
PaCO2↑
2) Classification:
Classification
Acute RAC
Chronic RAC

20. 3) Causes :
Disorder of external respiration -
Overdosage of sedatives, narcotics,etc.
Cerebrovascular accidents.
Cardiopulmonary arrest
Central nervous system trauma, infections
Poliomyelitis
Inhalation of foreign bodies
Chronic obstructive pulmonary disease
Asthma
Pneumonia
Increased CO2 inhalation –

21. 4) Compensation:
Compensation
In acute RAC:
ion exchange across the membrane and
buffering in cell

22. （ somatic cell ）
CO2+H2O
H2CO3
HCO3-
+
H+ H++A- HA
K+ K+

23. In chronic RAC:
excretion of more H+ and ammonia ion
reabsorption of more HCO3- in
kindneys

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

25. 5) Effects:
Effects
(1) Neurological effects:
CO2 narcosis
(2) Cardiovascular effects:
arrhythmias;
pulmonary artery hypertension;
cardiac output decrease.
(3) Inducting of hyerkalemia and hypochloremia
6) principle of treatment:
improve ventilation

26. Metabolic alkalosis
1) Concept:
Concept
Primary disturbance [HCO3-] ↑ ; PH .
PaCO2 ↑
2) Classification:
Chloride – responsive
Chloride – resistant

27. 3) Causes and mechanism:
mechanism
Mechanism:
Mechanism
a. Excessive gain of alkali (bicarbonate)
b. Excessive loss of hydrogen ions,
chloride or potassium ions

28. Causes:
a.Excessive gain of alkali (bicarbonate)
Bicarbonate intake:treatment of MAC
citrate-containing blood transfusions
Parenteral solution containing lactate
b.Excessive loss of hydrogen ions, chloride or
potassium ions
Gastrointestinal H+ loss:vomiting,gastric suction
Renal H+ loss:Aldosteronism,cushing’s syndrome
thiazide
c.Volume contraction
Dehydration
Diuretic therapy

29. 4) Compensation:
Compensation
Blood buffer role
limitation
Respiratory regulation
Ion exchange and H+ out cell to titrate bicarbonate
Renal role: excluding bicarbonate and conserving H +
5) Effects:
Effects
(1) Hypoventilation→ PaCO2 ↑, PaO2 ↓
(2) Agitation of central neural system: GABA↓ → seizures
(3) Increase excitability of the neuromuscle: free [Ca2+] decrease
→ muscle tremors
(4) Mental dysfunction: O2 dissociated curve leftshift → impairing
O2 release → ATP ↓. At 6-8 hs, 2,3-DPG↑ and curve shifts back
towards the right.
(5) Hypokalemia → reduced fibrillation threshold

30. 6) Principle of treatment:
treatment
a. Etiology treatment
b. Administration of KCl. or spironolactone if
K+ and Cl- deficits are present
c, Carbonic anhydrase inhibitor:
acetazolamide

31. Respiratory alkalosis
1) Concept:
Concept
Primary change : H2CO3 ↓ or PaCO2 ↓ ; pH
2) Classification:
Classification
a. Acute RAL
b. Chronic RAL

32. 3) Causes and mechanisms:
mechanisms
Mechanisms: Hyperventilation
Causes:
a. Psychogenic hyperventilation:Hysteria
b. Stimulation of respiratory center:
High altitude hypooxia
Salicylate toxication
Blood ammonia↑(Hepatic
encephalopathy)
Encephalitis
Brain injury
Fever

33. 4) Compensation:
Compensation
In acute RAC:
Ion exchange, H+ out of cell to titrate base in ECF
In chronic RAC:
Decreased excretion of H+ and NH4+
Decreased reabeorption of HCO3-
5) Effects:
Effects
(1) Increased excitability of the nerve and muscle
(2) Mental dysfunction
(3) Hypokalemia,hypochloridemia
6) Principle of treatment:
treatment
a. Decreased ventilation by administration of
sedative.
b. Application of a plastic bag to inspire more

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