Physiology of Acid Base Balance by Dr. ROOMI

7/30/2019 Physiology of Acid Base Balance by Dr. ROOMI

1/70

REGULATION OF ACID BASE

BALANCE:

It means regulation of pH of body fluids.

pH = -log [H+]

pH of arterial blood = 7.4pH of venous blood = 7.35 (because of dissolved CO2)

Why it is important to regulate pH??


2/70

It is important to regulate pH because enzymes

in body need optimal pH & when pH changes,there is marked effect on activity of enzymes.

When pH is >7.45, it is ALKALOSIS When pH is


3/70

Survival range: (very narrow range)

pH of body fluids depend upon BUFFERS inbody fluids.

What is a BUFFER SYSTEM?


4/70


5/70

Buffer system is a solution which minimize or resist change in pH (ITCANNOT PREVENT THE CHANGE!!!)

A buffer system consists of a weak acid & its salt (mostly) or a weakalkali & its salt, e . g,

HCO3- buffer:

salt is NaHCO3 & weak acid is H2CO3

It may be KHCO3salt..but in plasma & ECF main cation is Na+

Another e . g, is

PO4

---

buffer:

salt is Na2HPO4 & acid is NaH2PO4 ACID: Which can donate H+

BASE: Which can accept H+


6/70


7/70

BUFFERS:

1) BLOOD (Plasma & RBCs)

2) IN ISF

3) IN ICF


8/70

BLOOD BUFFERS:

1) HCO3 BUFFER

2) PO4 BUFFER

3) PROTEIN BUFFER

4) Hb BUFFER IN RBCs


9/70


10/70

HCO3 BUFFER IN BLOOD:

It consist of HCO3 (salt) & acid (H2CO3 which isdissolved CO2).

HCO3 means NaHCO3 because Na+ is main cation in

plasma. Ratio = salt/acid = NaHCO3/H2CO3

= 20/1

pka of this buffer system (HCO3) = 6.1

6.1 + log20 = 6.1 + 1.3 = 7.4

pka = -log of dissociation constant of acid


11/70

HENDERSON HASSEL BALCH

EQUATION: pH = pka + log [salt / acid]

pka islog of dissociation constant of acid

HCO3 buffer system:

for HCO3-, pka = 6.1

so 6.1 + log salt or HCO3Acid

= 6.1 + log 24mEq or mM/L

1.2mEq or mM/L

= 6.1 + log 20= 6.1 + 1.3 = 7.4

When ratio between salt & acid is 20, pH will be 7.4.


12/70

PO4 BUFFER IN BLOOD:

SALT= Na2HPO4

ACID= NaH2PO4

Ratio=salt/acid = 4/1

Pka of H3PO4 = 6.8


13/70

PROTEIN BUFFER IN BLOOD:

SALT=Na-Proteinate

ACID=Acid Protein or H-Protein


14/70

Hb BUFFER IN RBCs

Cation in RBCs = K+

For Hb buffer, salt = K-Hemoglobinate

Acid = Acid Hemoglobin=HHb

Hb is very important buffer in blood


15/70

BUFFERS IN ISF:

HCO3

PO4

Weak protein buffer


16/70

BUFFER IN ICF: Main buffer in ICF is protein buffer.

Buffering power of a buffer depends on 2 factors:1) conc. of buffer (quantitative)

2) pka (qualitative)

If conc. is greater, stronger will be the buffer.If pka of buffer is near to pH of blood, stronger will bethat buffer.

If we compare HCO3 & PO4 buffer, quantitatively

powerful is HCO3 buffer.Its conc. is 10x more than PO4 buffer.

Qualitatively, PO4 buffer is more powerful, as 6.8 is closerto 7.4 than 6.1.


17/70

Sources of H+ or acid in the body:

1) OXIDATION OF CARBON CONTAININGCOMPOUNDS:

Gives rise to CO2 (Volatile acid). During exercise production of CO2 increases very

much.

2) FORMATION OF NON VOLATILE OR


18/70

2) FORMATION OF NON-VOLATILE OR

ORGANIC ACIDS DURING

METABOLISM OF CHO, FATS & PROT.

- Most of these acids are further oxidized to form CO2 &H2O, but their level increase in the blood when there isincreased rate of metabolism.

- In hypoxia increased production of these acids. (toprovide energy, rapid metabolism)

- Certain drugs & disorders can increase theirproduction.

- These acids are PYRUVIC ACID, LACTIC ACID, ACETO-ACETIC ACID & BETA HYDROXY BUTYRIC ACID.


19/70

3) FORMATION OF H2SO4:

When S containing compounds (like Cysteine

& Methionine) are oxidized, H2SO4 is

produced.


20/70

4) FORMATION OF H3PO4:

When phospho-esters, phosphatides.

Phospho-proteins & nucleo-proteins are

hydrolyzed in the body.


21/70

4) Small amount of some acids are

INGESTED BY MOUTH:

Like NH4Cl in cough syrup (noshadir)mild

acidosis.


22/70

BUFFERING MECHANISMS IN THE BODY:

(2 TYPES)

1) PHYSICO-CHEMICAL BUFFERING

2) PHYSIOLOGICAL BUFFERING


23/70

PHYSICO-CHEMICAL BUFFERING:

Most immediate buffering. (when an acid or alkali isadded to body fluids, it is the 1st line of defense againstdisturbance of acid base balance.

A) PHYSICO-CHEMICAL BUFFERING OF CO2/VOLATILEACID:

CO2 is transported as HCO3 & in free form. Fromtissues, CO2 RBCs.In RBCs, CO2 + H2O H2CO3H2CO3 (unstable) H + HCO3H ion + Hb HHb (buffered by Hb to formacid-Hb).


24/70

At tissue level, deoxy Hb is available. Deoxy-Hb can bind much more H than oxy-Hb(already acidic).

HCO3 diffuses out into plasma & from plasma,Cl diffuse in to maintain electrical balance.

This is HCO3-Cl SHIFT OR HAMBERGERS SHIFT.


25/70

Some CO2 combine with amino group of Hb

to form CARBAMINO-Hb.

Some CO2 binds with amino group of plasma

proteins to form CARBAMINO-PROTEINS.


26/70

ClHb H

HCO3

H2CO3

CO2 + H20 (CA)

CO2

carbamino-proteinsRBC

carbamino-Hb


27/70

B) PHYSICO-CHEMICAL BUFFERING OF

ORGANIC/NON-VOLATILE ACIDS:

Carried out by various chemical buffers in

body fluids like HCO3 & PO4 buffers.

e.g in body there is production of H3PO4, so

NaHCO3 will buffer it & we get Na2HPO4 +

H2CO3.H3PO4 + NaHCO3 Na2HPO4 + H2CO3.

(strong acid) (salt) (weak acid)


28/70

CONCLUSION:

In case ofvolatile acids buffering:

Hb & plasma proteins play a role.

Incase oforganic/non-volatile acid

buffering:

NaHCO3 is utilized, which must be

replenished & body must get rid of acid

anion/salt & the weak acid; H2CO3.


29/70

ROLE OF PHYSIOLOGICAL BUFFERING:

It is actually to deal with end product of

physico-chemical buffering.

In physiological buffering, there is role of

respiratory system & renal system.


30/70

ROLE OF RESPIRATORY SYSTEM:

It removes CO2 from the body. Also removes dissolved CO2 (i-eH2CO3).

When RBC goes to lung capillaries,blood becomes oxygenated.

O2 enters the RBC. O2 binds with Hb to form oxy-Hb (strong

acid), which cannot hold H). There is reverse HCO3-Cl shift (lung level). From plasma HCO3 move into RBC & Cl move in reverse

direction. CO2 from Carbamino Hb also comes out.

In RBC there is reverse reaction.H + HCO3 H2CO3 CO2 + H2O.CO2 alveoli expired out.


31/70

As a result of physiological buffering, Hb &plasma proteins are again available to bufferCO2 or H.

(RECYCLING)

CO2 is very strong stimulant of respiratorycentre.

Buffering by respiratory system takes minutes tohours.

Buffering power of resp. system is 1 to twicemore powerful, as compared to buffering bychemical buffers in body fluids (HCO3, PO4buffers etc).


32/70

ROLE OF RENAL SYSTEM:

Kidneys regenerate HCO3.

There is reabsorption of Na & Cl ions when

required.

Acid anions or salts are excreted in urine.

There is secretion of H & Ammonia by the

kidney.


33/70


34/70


35/70


36/70

3) METABOLIC ACIDOSIS:

Due to increase H ion production in body, conc

of HCO3 decreases. So salt/acid = HCO3/PCO2

= decreased ratio decreased pH, because of

less HCO3 in arterial blood. So pH decreasesto produce metabolic acidosis.


37/70

CAUSES OF METAB ACIDOSIS:

1) FAILURE TO EXCRETE normally produced metabacids in urine. In chronic renal failure, kidneys cannotexcrete normally produced metab acids.

2) INCREASED PRODUCTION OF METAB/ORGANICACIDS: e.g uncontrolled DM, Severe hypoxia (lacticacidosis).

3) LOSS OF ALKALINE FLUID FROM BODY:e.g Severediarrhoea, intestinal fistula & vomiting of intestinalcontents.


38/70

4) HYPERKALEMIA: In hyperkalemia, body tends to

excrete K ion, instead of H ion. So H ion is conserved

acidosis. (IN HYPERKALEMIA THERE IS ACIDOSIS).

5) CARBONIC ANHYDRASE INHIBITORS: e.gAcetazolamide. H ions are not secreted & no reabs of

HCO3Metabolic acidosis.


39/70

COMPENSATION OF MET ACIDOSIS:

1) Various buffers in body fluids, buffer the excess of Hion,e.g, HCO3 buffer, PO4 buffer & protein buffer.

2) Resp system: Because of increased H ion conc.hyperventillation loss of CO2 less PCO2 Ratio willincrease back to normal & pH will increase back to normal.

*In compensated cases of metab acidosis, there is someresp alkalosis to decrease PCO2 because ofhyperventillation.

3) Renal compensation: Kidney secretes H ion in largeamount. There is increased NH3 secretion. There isincreased HCO3 reabsorption or regeneration. When there

is more HCO3 reabsorption, Cl is lost in urine.


40/70


41/70


42/70


43/70

4) METABOLIC ALKALOSIS:

There is more HCO3 conc. in arterial blood, so ratiobetween salt & acid increases, so pH will increase toproduce metabolic alkalosis.

CAUSES:

1) Ingestion of large amount of alkali ,e.g, ingastritis & peptic ulcer as a treatment.

2) Vomiting of gastric contents, due to loss of acidsfrom stomach in large amounts.

3) Increase of Aldosterone: Increased Na reabswhich is coupled with counter transport of K & alsoH, so when there is increased aldosteronehypokalemia & alkalosis.


44/70


45/70

EFFECTS OF ACIDOSIS & ALKALOSIS

ON BODY:

EFFECT OF ACIDOSIS: When pH decreases

CNS is depressed patient becomes

disoriented, drowsy & comatosed in severe

cases, e.g, diabetic coma of ketoacidosisKussmal breathing (rapid & deep breathing)

with ketotic breath.


46/70

EFFECT OF ALKALOSIS: When ionic calcium

decreases hypocalcemia tetany

(hyperexcitability of nerves) carpopedal &

laryngeal spasm, convulsions, paresthesiasdue to involvement of sensory nerves.


47/70

CLINICAL EVALUATION OF ACID BASE

BALANCE:

-1) MEASUREMENT OF ARTERIAL pH:

(1st parameter) = 7.4

-2) MEASUREMENT OF ARTERIAL PCO2:=

40mmHg-3) MEASUREMENT OF ALKALI RESERVE: (HCO3)

= 24mEq/L

-4) MEASUREMENT OF BUFFER BASE:-5) ANION GAP MEASUREMENT:



48/70


BALANCE:

MEASUREMENT OF BUFFER BASE: It is conc of anion component of buffers in body

fluid. It includes HCO3 conc & conc of protein anions.

Normally buffer base is 48mEq/L.

Out of this, HCO3 is 24 & remaining is Hb (mainlyprotein anions).

We can also evaluate acid base balance by acid basenomograms. It also determines type of acid base

disturbance & its severity.


49/70

ANION GAP MEASUREMENT: It is the

difference between conc of cations other than

Na & conc of anions other than HCO3 & Cl.

ANION GAP MEASUREMENT


50/70

ANION GAP MEASUREMENT:

[ANIONS] = [CATIONS] [MEASURED ANIONS] + [UNMEASURED

ANIONS] = [MEASURED CATIONS] +[UNMEASURED CATIONS]

[Cl-] + [HCO3-] + [UNMEASURED ANIONS]=

[Na+] + [UNMEASURED CATIONS]

[UNMEASURED ANIONS UNMEASURED

CATIONS =

[Na+] [Cl- + HCO3-]


51/70

ANIONS OTHER THAN HCO3 & Cl:

Protein anions, PO4, SO4 & LACTATE.

Difference between these 2 concs is called

ANION GAP. Anion gap is increased, when conc of cations

decreases or anions are increased,e.g,

incresed albumin, SO4,PO4,LACTATE &PYRUVATE.


52/70

ANION GAP IS INCREASED IN:

Metabolic acidosis due to ketoacidosis & lactacidosis like inuncontrolled DM (ketoacidosis) & in severe hypoxia(lactacidosis).

ANION GAP IS NOT INCREASED IN: Hyperchloremic acidosis, which may be due to CA Inhibitors

(acetazolamide) or ingestion of large amount of NH4Cl.


53/70

1) RESPIRATORY ACIDOSIS:

Here PCO2 in arterial blood increases, ratio between salt &acid falls, so pH decreases to produce resp acidosis.

CAUSES: Decreased rate of pulm vent. due to damage to resp

centre or resp centre depression by drugs like morphine ordisease of resp centre. Resp muscle paralysis, airwayobstruction, pulm fibrosis, pneumothorax & pleural effusion.

In resp acidosis, cause is in resp system.


54/70


55/70

COMPENSATORY MECHANISMS: (from outsideresp system)

1) Various non-HCO3 buffers, take up or buffer

H ion to produce HCO3 ion.When there is increased PCO2, there is moreH2CO3. So non-HCO3 buffers will take up Hion from H2CO3 & left behind is HCO3.


56/70

2) Renal compensation: In renal tubules, there is more H ion secretion & more NH3

secretion. More HCO3 reabsorption or regeneration. Moretitrable acidity of urine.

As a result of renal compensation, HCO3 will increase.

Ratio of HCO3/PCO2 conc will increase back to normal pHwill increase back to normal.

In compensated cases of resp acidosis, there is somemetabolic alkalosis because HCO3 is increased.


57/70

2) RESPIRATORY ALKALOSIS:

Here PCO2 in arterial blood decreases. So ratiobetween salt/acid conc is increased, so pH increases resp alkalosis.

CAUSES: Hyper ventilation:

Voluntary

Hysteria / psychoneurosis

Resp centre stimulation in salicylate poisoning &

nikethamide (resp stimulant) At high altitude.


58/70


59/70

COMPENSATION OF RESP ALKALOSIS:

1) By protons donated by various buffers in bodyfluids (some compensation).

2) Main compensation is through kidneys.

In kidney, no H ion secretion, no NH3 secretion,HCO3 is not reabsorbed, it is lost in urine in largeamount. H ions are produced in tubular cells which

are added to ECF. So urine will be highly alkaline.


60/70


61/70


62/70


63/70


64/70


65/70


66/70


67/70


68/70


69/70


70/70

Physiology of Acid Base Balance by Dr. ROOMI

Documents