Acid-Base Balance

and Imbalance

1
 pH Review
• pH = - log [H+]
• Range :- 0 – 14

• If [H+] is high, the solution is acidic; pH < 7

• If [H+] is low, the solution is basic or
alkaline ; pH > 7

2
3
• Acids - H+ / proton donors .
ex- Hcl., H2CO3
• Bases - H+ acceptors /give up OH- in solution.
ex – NaOH , HCO3-
• Acids and bases can be:
– Strong – dissociate completely and rapidly
in solution
• HCl, NaOH
– Weak – dissociate only partially in solution
• Lactic acid, carbonic acid
4
 The Body & pH
• Blood = 7.35 – 7.45
– arterial – 7.4
– venous – 7.35.

• Intra-cellular – varies {slightly acidic}

• Homeostasis of pH is tightly controlled

– < 6.8 or > 7.8 death occurs
5
 Small changes in pH can produce major
disturbances

• Most enzymes function only with in narrow

pH ranges.

• Acid-base imbalance can also affect

electrolytes (Na+, K+, Cl-)

• Can also affect hormones / N.T`s.

6
The body produces more acids
than bases
Acids- produced by metabolism –
 Volatile acids – exhaled via lungs.
 Fixed / non- volatile acids – via kidneys.
1. Cellular metabolism produces CO2.
– CO2 + H20 ↔ H2CO3 - CARBONIC ACID.
– Most common , Volatile acid
2. Non-volatile acids-
- Sulfuric acid , Phosphoric acid - Protein metabolism.
- Lactic acid- Anaerobic metabolism
- Pyruvic acid , keto acids etc. 7
 Production of Bases-
• Very less in body.
– HCO3- - from Lactate/citrate salts of fruit juices.
– NH3 (deamination of A.A)- minor .
– Acetate and biphosphate

• Veg. diet- alkalises

• N.V. diet- acidifies.

8
 Regulatory mechanisms –
pH ???
• These acids – need to be transported to kidneys
/ lungs – via blood .
• But , during this – pH may alter.
• So, this transport and excretion - done by reg.
mechanisms, with out any change in pH -
1. Blood Buffers – 1st line of defence
2. Respiratory mechanism – 2nd line of
defence
[Link] mechanism – 3rd line of defence
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Buffers-
- A mixture of weak acid(HA) and its salt(BA)
with a strong base.
- Resists change in pH .
- Results in a much smaller pH change
- Temporary ↓ H+ .
- Buffer + H+ H buffer
- Take up H+ or release H+ as conditions change.
- (BA) + H+ HA
- HA H+ + BA

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 Buffers -
Buffer Plasma / RBC /
Extra-cellular Intra-cellular

Bicarbonate NaHCO3 / H2CO3 KHCO3 / H2CO3

Phosphate Na2HPO4 / NaH2PO4 K2HPO4 / KH2PO4

Protein Na. protein / [Link]/ [Link]

[Link] K HbO2 / H.HbO2
11
• Buffering capacity depends on –
– Concentration of buffer
– pKa of buffer Vs pH of blood {max. – if pKa
=pH}
Buffer Rel. Buffering pKa Conc.
capacity [Link]/L
Bicarbonate 1 6.3 25

Phosphate 0.3 6.8 1.2

Protein /albumin 8 7.3 7.7

Hemoglobin 40 7.3 53 12
Blood Buffers-
Bicarbonate buffer
 Phosphate buffer
 Protein buffer

Bicarbonate buffer:-
 Sodium Bicarbonate (NaHCO3) and carbonic
acid (H2CO3)
Important buffer in plasma.
 pKa – only 6.3 - why imp. ??????
13
 H2CO3 H+ + HCO3-

By the law of mass action at equil.-

(H+ ) (HCO3-)
• Ka= ------- (1)
H2CO3
Ka=Dissociation constant of H2CO3
(H2CO3)
H+= Ka -------(2)
(HCO3-)
• pH=log 1/H+

HCO3-
• log1/H+ = log1/Ka + log -----(3)
(H2CO3)
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• Log1/Ka = pKa

• pH = pKa + log (HCO3-) --------(4)

(H2CO3)

Henderson – Hasselbalch equation

(Base)
pH = pKa + log
(Acid)

• pH - depends on ratio of conc. of

base to acid of a buffer system.
M/A -
HCl + NaHCO3 H2CO3 + NaCl
NaOH + H2CO3 NaHCO3 + H2O
Good buffer- ?????
HCO3- - 22 -26 [Link]/L- {24}.
- H2CO3 – pCO2 - 40 x 0.03 = 1.2 [Link]/L.
- HCO3- : H2CO3 = 20 : 1 ratio .
- pH = pKa + log (HCO3-)
(H2CO3)
- Substituting values – 7.4 = 6.1 + log 24/1.2
7.4 = 6.1 + log 20{1.3}
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• HCO3- : H2CO3 = 20 : 1 ratio .
– Alkali Reserve

• Blood pH varies with change in

– Conc. of HCO3- or H2CO3 and
Ratio - HCO3- : H2CO3 .

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Phosphate buffer :-
Sodium Dihydrogen Phosphate and Disodium Hydrogen
Phosphate
(NaH2PO4- Na2HPO4 : 4:1)
– Major intracellular buffer
– Imp. Role in renal tubules
{ - high conc. in tubules , low pH of tubules}
– Minor role in plasma
{though pKa – 6.8, but due to low conc.}
– H+ + HPO42- ↔ H2PO4-
– OH- + H2PO4- ↔ H2O + HPO42-
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Organic Phosphate buffer –
In RBC –
• 2,3 BPG – 16% of buffer .
Protein Buffers-
• Plasma proteins, Hemoglobin.
• depends on pKa of ionisable groups of A.A.

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 basic
soln. - +H+

- H+ acidic
soln. -

- R- groups of A.A –
• Imidazole group of Histidine(pK- 6.7)- most effective
group.
Albumin- 16 histidine residues.
- Major plasma protein buffer.
Hb. – 32 histidine residues.
- Major RBC buffer.
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 Buffer systems in
Acid – Base Balance -

• First line of defense –

– with change in H+ , react in fraction of second - ↓
effect .

• Temporary mechanism –
– H+ are not removed but only - ↓ effect

21
 II. Respiratory mechanism:-
• 2nd line of defence
• CO2 from the metabolism –
– CO2 + H20 ↔ H2CO3
• Exhaled by Lungs –
– H2CO3 Carbonic anhydrase CO2 + H2O
– H+ + HCO3- H2CO3 CO2 + H2O

• Respiratory Centre - in Medulla of brain – Controls

Rate of Respiration.
– highly sensitive to changes in the pH of blood .
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• H+ + HCO3- H2CO3 CO2 + H2O
• ↓ in blood pH ↑H+ ↑ H2CO3

- Stimulation of R.C – Hyperventilation (↑rate , depth)

 removes CO2 and ↓H2CO3.
 So - , ratio of HCO3- : H2CO3 ↑ - pH ↑
• H+ ions are eliminated as H2O.

2. ↑ in blood pH -- Depression of R.C – Hypoventilation –

retain CO2 - ↑ H2CO3 -

- so, ratio of HCO3- : H2CO3 ↓ - pH ↓

• Thus , Resp. mechanism regulate –
– removal / retention of CO2 and so - H2CO3
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 H+ + HCO3- H2CO3 CO2 + H2O
↓ in blood pH

↑ H+ ↑ H+ -
R.C stimulation Hyper Ventilation
↑ H2CO3

↑ CO2 removal
↓ H2CO3

↑ HCO3- : H2CO3 ↓ H2CO3

↑ pH
↑ HCO3- : H2CO3

Ventilation rate may ↑ 15x N.

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• Thus, maintains H2CO3 component of HCO3- :
H2CO3 buffer

• Thus, body pH can be adjusted by changing

rate and depth of breathing.
– Powerful, rapid
– but only works with volatile acids
– Doesn’t affect fixed acids like lactic acid
– Short-term process.
– Second line of defense
Generation of HCO3- - Chloride Shift

Erythrocyte
Plasma
CO2 + H2O
CO2
CA
H2CO3
HHb

HCO3- + H+ Hb
HCO3- Cl-
Cl-
Hb. as a BUFFER -
Transport of H+
 Hemoglobin as a buffer -
• Hemoglobin of R.B.C
– major intra-cellular buffer. ( high conc. ,
pKa )

• At Tissues- Hb. binds to H+ ions and transports

CO2 as HCO3- with a minimum change in pH

• Lungs- Hb. combines with O2,

– H+ ions are removed which combine with HCO3- to form
H2CO3 - dissociates to release CO2 to be exhaled
Isohydric transport of
CO2
Transport of co2 from tissues
with out change in pH
 Renal mechanism for pH regulation :-

• Kidneys- play imp. role in regulation of pH

• 3rd line of defense
• Most Effective Regulator of pH
– If kidneys fail, pH balance fails
• Normal urine has a pH around 6 {4.5 to 8}
– Due to non-volatile acids in urine.
– varies with amount of acids excreted in urine.

• kidneys regulate pH by-

– reabsorbing HCO3-
– excreting acids .

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 Renal Regulation of pH :-
• Carbonic anhydrase - Central Role in renal
regulation of pH.
• It occurs by -

– Excretion of H+ via Na+ - H+ exchange

– Excretion of H+ as ammonium ions

– Excretion of H+ as NaH2PO4 – titratable acidity
– Reabsorption of Bicarbonate
 Excretion of H+ ions
• Kidney is the only route through which the H+ can be
eliminated from the body
• effective mechanism to eliminate acids (H+) from
the body with a simultaneous generation of
HCO3- - Alkali Reserve
• H+ excretion occurs – PCT
– is coupled with regeneration of HCO3-

• Carbonic anhydrase – major role

 Excretion of H+ ions via Na+ - H+ exchange -
Renal Tubular Cell
Blood Tubular lumen
Na+
Na+ Na+

HCO3- + H+
HCO3- H+ + B-

H2CO3
CA HB

CO2 + H2O Excreted

• Na+ - H+ exchange - ↑ In acidosis , ↓ alkalosis

 Excretion of titratable acid
• Titratable acidity
– measure of acid/ H+ ions excreted into urine by

kidney

• Titratable acidity
– refers to no. of ml. of N/10 NaOH required to

titrate 1L. of urine to pH 7.4

Excretion of H+ ions as NaH2PO4 :-

Blood Renal Tubular Cell Tubular lumen

Na+ Na+ Na2HPO4

Na+ NaHPO4-2
HCO3- + H+

HCO3- H+
H2CO3
CA NaH2PO4

CO2 + H2O
Excreted
• H+ - secreted into tubular lumen in exchange for Na+.
• This Na+ is obtained from the base- (Na2HPO4)
– combines with H+ to produce the acid, (NaH2PO4)

the major quantity of titratable acid in urine.

• This depends on – phosphate filtered by glomeruli

and pH of urine.
• Acidemia - ↑ phosphate excretion --- ↑ NaH2PO4 excretion

• ↓ GFR (renal disease) - ↓ NaH2PO4 excretion

Excretion of H+ ions as NH4+ :-
Renal Tubular Cell
Blood Glutamine Tubular lumen
NH3 NH3
Glutamine Glutamate glutaminase

Na+ Na+

HCO3- H+
Na +

NH4+
HCO3- + H+
Excreted - NH4Cl ,po4,so4

H2CO3
CA

CO2 + H2O
 Excretion of Ammonium ions -

• The H+ ion combines with NH3 to form (NH4+) ion.

• The renal tubular cells deaminate glutamine to glutamate and
NH3 by the action of enzyme glutaminase
• The NH3,liberated in this reaction, diffuses into the tubular
lumen where it combines with H+ to form NH4+
• Ammonium ions cannot diffuse back into tubular
cells and excreted into urine .
• About 60% of H+ from non-volatile acids – removed as
NH4+ ions.
• Very effective mechanism for excretion of
H+ ions.
• rate of glutamine uptake (from blood)
depends on acid to be excreted .
Acidosis -
• ↑ H+ ↑ glutamine
(10x)uptake ↑ NH3

↑ H+ excretion as (10x)
NH4+

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• CRF – acidosis ????
CRF
Tubular cell damage

↓ glutaminase ↓ Glutamine ----

activity glutamate + NH3

↓ NH3
formation

↑ H+
↓ H+ excretion as NH4+ ions in the blood

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ACIDOSIS
 Reabsorption of bicarbonate :-
Renal Tubular Cell
Blood Tubular lumen
Na+
 Na+ Na+ Plasma
HCO3- + H+
 HCO3- H+
 HCO3-
H2CO3
CA
 H2CO3
 H2O + CO2 CA
 CO2 + H2O


 Reabsorption of Bicarbonate:-

• This mechanism is primarily responsible to

conserve blood HCO3- with simultaneous

excretion of H+ ions.
• HCO3- - freely diffuses from plasma into tubular
lumen- combines with H+, secreted by tubular cells,
to form H2CO3- then cleaved to CO2 and H2O.
• As the CO2 [Link] up in the lumen, it diffuses into the
tubular cells along the concentration gradient.
• In the tubular cell, CO2 again combines with H2O to form
H2CO3 which then dissociates into H+ and HCO3-
• The H+ is secreted into the lumen in exchange for Na+.
• The HCO3- is reabsorbed into plasma in association with Na+.

• Extent of HCO3- reabsorption α extent of Na+

reabsorption.
• For 1 H+ secreted into tubular fluid – 1 Na+ and 1 HCO3-
reabsorbed into blood.
• Kidney reabsorbs all filtered HCO3- at
HCO3- < 25.
• This mechanism helps to maintain the steady
state of HCO3-

• ↑ - acidosis ; ↓- alkalosis

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Renal Regulation of pH -
Blood Renal Tubular Tubular lumen
cell

Na+ Na+
Na2HPO4
HCO3- + H+ -2
NaHPO4
HCO3-
IV I Na+

H2CO3
H+
C.A HCO3-
Glutamine
CO2 + H2O
Glutamine H2CO3
Glutaminase
II
NH3
I
Glutamate + NH3
II
II Na2HPO4 CO2 + H2O
NH4 +

46
 Rates of correction
• Buffers function almost instantaneously
– but temporary , short-lasting.
• Respiratory mechanisms take several minutes to
hours.
– effective , but short-lasting
• Renal mechanisms may take several hours to days
– permanent, highly effective.

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(HCO3- reabsorption)
48
• Acid-base balance – depends on :-
– input – intake + metabolic conversion
– output – excretion + metabolic conversion

• major buffer – bicarbonate buffer

• Resp. , Renal mechanisms maintain
HCO3- : H2CO3 = 20:1

49
50
 Disorders of Acid-Base Balance
• Homeostasis of pH is tightly controlled {7.4}
– < 6.8 or > 8.0 death occurs.
• pH< 7.35- Acidosis
• pH > 7.45 - Alkalosis

52
53
 pH = pKa + log (HCO3-)
(H2CO3)
- Thus, Blood pH - depends on relative conc. of base (HCO3-)
to acid (H2CO3).
 Acidosis- ↓ blood pH < 7.35 .
Metabolic acidosis - due to ↓ in bicarbonate
Respiratory acidosis-Due to ↑ in carbonic acid/pCO2
 Alkalosis- ↑ blood pH > 7.35 .
Metabolic alkalosis-due to an increase in bicarbonate
Respiratory alkalosis-due to a decrease in carbonic
acid/pCO2

54
 Compensation
• The body responds to acid-base imbalance -
compensation
(HCO3 )
-
pH = pKa + log
(H2CO3)
• Acidosis –
– If, due to ↓ HCO3- :- then by ↓ H2CO3 - the ratio can
be normal -20:1.
– If, due to ↑ H2CO3 :- then by ↑ HCO3- - the ratio can
be normal -20:1.
• Alkalosis –
– If, due to ↑ HCO3- :- then by ↑ H2CO3 - the ratio can
be normal -20:1.
– If, due to ↓ H2CO3 :- then by ↓ HCO3- - the ratio can
55
be normal -20:1.
Disorder Primary Compensatory
change mechanism
Met . Acidosis ↓ HCO3- ↓ H2CO3
Hyperventilation

Met . Alkalosis ↑ HCO3- ↑ H2CO3

Hypo ventilation

Resp . Acidosis ↑ H2CO3 ↑ HCO3-

↑ renal HCO3- reabsorption

Resp . Alkalosis ↓ H2CO3 ↓ HCO3-

↓ renal HCO3- reabsorption

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 (HCO3-) HCO3- : H2CO3 = 20 : 1
pH = pKa + log
(H2CO3)
 (HCO3-)
pH = pKa + log
(H2CO3)

58
 (HCO3-)
pH = pKa + log
(H2CO3)
Disorder Primary Compensatory
change mechanism

Met . Acidosis ↓ HCO3- ↓ H2CO3

Hyperventilation
Met . Alkalosis ↑ HCO3- ↑ H2CO3
Hypo ventilation
Resp . Acidosis ↑ H2CO3 ↑ HCO3-
↑ renal HCO3- reabsorption

Resp . ↓ H2CO3 ↓ HCO3-

Alkalosis ↓ renal HCO3-
reabsorption
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 Anion gap :-
• Total Conc. of Cations in plasma = Total Conc. of
Anions in plasma.
• Commonly measured -
– Cations – (Na+ ,K+) – 95% of plasma cations.
– Anions – (Cl-,HCO3-) - 80% of plasma anions.
• Anion gap- Unmeasured anions in plasma.
– {proteins, phosphate, sulfate, org. acids}
• Na+ + K+ = Cl- + HCO3- + A-
– 136 + 4 = 100 + 25 + A-
A- = [Na+ + K+ ] - [Cl- + HCO3- ] = 15 [Link]/L
- 12 – 16 [Link]/L
- Altered anion-gap – seen in acid-base disorders. 60
 Arterial Blood Gas Analysis
• In Acid-base disorders / Respiratory failure – blood
gases measurement helps in RX.
• SAMPLE – Arterial blood from- radial A./ femoral
A.
• By ABG Analyzer.
• Parameters- pO2, pCO2, pH .
– HCO3- - indirectly from Henderson-Hasselbalch
equation.

61
62
 Metabolic Acidosis
• pH < 7.35
– HCO3- < 22mEq/L
• Causes:
– Accumulation of acids (lactic acid or keto-acids)
– Failure of kidneys to excrete H+
– Loss of HCO3- through diarrhea or renal
dysfunction

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Etiology -
• Conditions that increase acids in the blood
• Renal Failure
• DKA
• Starvation
• Lactic acidosis
• Methanol poisoning
KUSMAL
• l/o HCO3-
– Prolonged diarrhea / [Link]
– RTA
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 Symptoms of Metabolic Acidosis –

• Kusmal’s respiration
• Headache, lethargy
• Nausea, vomiting, diarrhea
• Confusion, Coma
• Death.

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Compensation for Metabolic Acidosis -
• HCO3- : H2CO3 should be restored to 20:1.
• Metabolic Acidosis- decrease in HCO3- .

• Compensation - Respiratory mechanism -

by Increased ventilation.
• ↑ CO2 loss - ↓ H2CO3
– Hyper ventilation – short-lived.
• After 3-4 days- Renal mechanism sets
– ↑excretion of H+ ions as NH4+ /Na2HPO4 ions
– ↑ Reabsorption of HCO3-
66
 A. Derangement of acid-base balance in metabolic acidosis.
B. Compensation by reduction of carbonic acid and formation of
additional bicarbonate.
 Lab diagnosis:
ABG Analysis -
• pH < 7.35
• HCO3- < 22 [Link]/L
• Hyperkalemia

Treatment :
 Treat underlying cause
 Monitor ABG, I&O, LOC
 IV lactate solution

68
Excretion of H+/ k+ ions via Na+ - H+ exchange -
Renal Tubular Cell
Blood Tubular lumen
Na+
Na+ Na+

HCO3- + H+
HCO3- H+ + B-

H2CO3
CA HB

CO2 + H2O Excreted

• ↑K+- acidosis ; ↓ k+- alkalosis ??????

70
 Respiratory Acidosis
• pH < 7.35
– ↑ H2CO3 / pCO2 > 45 mm Hg.
• Causes:
– Depression of respiratory center in brain that controls
breathing rate – drugs or head trauma
– Lung diseases-
• Emphysema , COPD
• Adult Respiratory Distress Syndrome
• Pulmonary edema
• Pneumothorax
– chest wall deformities – flail chest , kyphoscoliosis
– Paralysis of respiratory or chest muscles
– Inadequate mechanical ventilation
71
 Signs and Symptoms-

• Breathlessness
• Restlessness
• Lethargy and disorientation
• Tremors, convulsions, coma
• Respiratory rate- rapid
• then gradually depressed

72
 Compensation for Respiratory
Acidosis
• HCO3- : H2CO3 should be restored to 20:1.
• Respiratory Acidosis- increase in H2CO3 .

• Compensation – Renal mechanism - by

– ↑ regeneration of HCO3-
– ↑ excretion of H+ ions as NH4+ ions , H2PO4- ions

73
A. Derangement of acid-base balance in respiratory acidosis. B.
Compensation by formation of additional bicarbonate.
 Lab Diagnosis-
 pH < 7.35
 PaCO2 > 45mm Hg

Treatment -
 Treat underlying cause
 Support ventilation
 Correct electrolyte imbalance
 IV Sodium Bicarb.

75
1
76
 Metabolic Alkalosis
• pH > 7.45 –
– ↑HCO3- > 26 [Link]/L
• Causes:
– Excess vomiting – l/o HCl
ex-pyloric stenosis
– Excessive intake of NaHCO3-
• Heavy ingestion of antacids
• i.v HCO3- therapy
– Certain diuretics
– Endocrine disorders – Cushing`s syndrome.
– Severe dehydration
77
Compensation for Metabolic Alkalosis -
• HCO3- : H2CO3 should be restored to 20:1.
• Metabolic Alkalosis- increase in HCO3- .

• Compensation - Respiratory mechanism - by

decreased ventilation.
• ↓ CO2 loss - ↑ H2CO3
– Hypo ventilation – short-lived.
• After 3-4 days- Renal mechanism sets in-
– ↑excretion of HCO3- ions
– ↓ excretion of H+ as NH4+ ions
78
Symptoms of Metabolic Alkalosis
• Respiration- slow and shallow
• Hyperactive reflexes ; tetany
• Paresthesia, numbness, tingling of extremities
• Dizziness
• Often related to depletion of electrolytes –
hypokalemia
• Atrial tachycardia, Dysrhythmias,

79
 Lab Findings:-
• pH > 7.45
• HCO3- > 26
• Hypokalemia, Hypocalcemia
Treatment :-
• Treat underlying disorder
• Electrolytes- to replace those lost
• IV chloride containing solution

80
81
 Respiratory Alkalosis
• pH > 7.45 - ↓H2CO3 / pCO2 < 35 mm.
• Most common acid-base imbalance

Causes:-
• Primary cause is hyperventilation

82
Causes of Respiratory Alkalosis
• Conditions that Stimulate Respiratory Centre:
– Oxygen deficiency at high altitudes
– Pulmonary disease and C.H.F – caused by hypoxia
– Acute anxiety
– Fever, anaemia
– Hysteria
– Artificial ventilation

83
Compensation of Respiratory Alkalosis
• HCO3- : H2CO3 should be restored to 20:1.
• Respiratory Alkalosis- decrease in H2CO3.
• Renal mechanism –
– ↑ Excretion of HCO3- ions.
– ↓ excretion of H+ ions.

85
A. Derangement of acid-base balance in respiratory alkalosis. B.
Compensation by excretion of bicarbonate
Symptoms of Respiratory Alkalosis -
– Tachypnea
– SOB, chest pain
– Light-headedness, syncope, coma, seizures
– Numbness and tingling of extremities
– tremors, blurred vision
– Weakness, tetany
Lab findings :-
– pH > 7.45
– PCO2 < 35
Treatment :-
• Monitor Vitals and ABG`s
• Treat underlying cause
• Assist client to breathe more slowly
• Sedation
• IV Chloride containing solution – Cl- ions replace lost
bicarbonate ions

88
89
 Mixed Acid-base disorders -
• Presence of 2 /more types simultaneously.
• Both Metabolic {HCO3-} , respiratory{H2CO3} alter.
• Mimic - Due to compensatory mechanisms.
• ∆ - H/o , C/F – very imp.
– lab data – mixed results

90
 Acidosis
• Principal effect of Acidosis – CNS Depression
{↓ in synaptic transmission}
– Generalized weakness
• Deranged CNS function is the greatest threat
• Severe acidosis causes
– Disorientation
– Coma
– Death

91
 Alkalosis
• Alkalosis – Over- excitability of CNS and PNS.
– Numbness
– Light-headedness
• It can cause :
– Nervousness
– muscle spasms or tetany
– Convulsions
– Loss of consciousness
– Death

92
 Disorder -
• Changes –1. pH 2. Pco2 /H2CO3 3. HCO3-
• Causes –
• Symptoms / C/F –
• Compensation –
• Lab data –
• Treatment.

93
Thank U