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Acid Base Balance

Q. 1- What is the normal physiological concentration of Hydrogen ion in body fluids?

A) 40 nEq/L

B) 24 mEq/L

C) 400 mEq/L

D) 7.4 nEq/L

E) 100 mEq/L

Q.2- Which of the following is not a source of hydrogen ion in the body?

A) Ingestion of Citrus fruits

B) High protein diet

C) Ingestion of red meat

D) Starvation

E) Chronic alcohol consumption

Q.3- Which of the following is the most important chemical buffer of the plasma?

A) HCO3 -/H2 CO3

B) HPO42―/H2PO4

C) Organic Phosphate Esters

D) Proteins

E) Hemoglobin

Q.4- A primigravida in labor is breathing rapidly, what you expect out of the following

A) Metabolic Acidosis

B) Metabolic Alkalosis

C) Respiratory Acidosis

D) Respiratory Alkalosis

E) Any of the above.

Q.5- The Henderson-Hasselbalch equation is represented as-

A) pH = pK + log (A-/HA)

B) pH = pK + log (HA/A-)

C) pH = pK – log(A-/HA)

D) pH = pK – log(HA/A-)

E) pH = pK + log(H+/HA)

Q.6- Buffering effect of a buffering solution is optimum at :

A) pH ranges close to pKa± 2 pH units

B) pH = pKa ±3 pH units

C) pH = pKa ±5 pH units

D) pH = pKa

E) None of the above.

Q.7- The pH of extracellular fluid must be maintained between:

A) 6 to 7.4

B) 7 to 7.2

C) 7.35 to 7.45

D) 7.5 to 8

E) 8 to 8.5

Q.8- All are true for renal handling of acids in metabolic acidosis except

A) Hydrogen ion secretion is increased

B) Bicarbonate reabsorption is decreased

C) Urinary acidity is increased

D) Urinary ammonia is increased

E) Renal glutaminase activity is increased

Q.9- Which of the following is most appropriate for a female suffering from Insulin dependent diabetes mellitus with a pH of 7.2, HCO3-17 mmol/L and pCO2-20 mm Hg?

A) High anion gap metabolic Acidosis

B) Metabolic Alkalosis

C) Respiratory Acidosis

D) Respiratory Alkalosis

E) Normal anion gap metabolic acidosis

Q.10-A 50-year-old homeless man was brought to the emergency room in a stuporous state. Below are his lab results, Bicarbonate 10mEq/L (24-26), pH 7.2 (7.35-7.45), PCO2 25mmHg (35-45), Alcohol 40mmol/L (0), Osmolality 370mOsm/L (280-295), Glucose 50mg/dl (60-110) BUN 40mg/dl (5-22). What is the acid-base status?

A) Metabolic acidosis and metabolic alkalosis

B) Metabolic acidosis with partial respiratory compensation

C) Respiratory acidosis and partial metabolic compensation

D) Respiratory acidosis

E) Metabolic alkalosis

Q.11- A 44-year-old man is brought to the emergency room stuporous and obtunded. Serum chemistries are: HCO3 = 42 mEq/L; arterial pH = 7.5; PCO2 = 50mmHg. What is the acid-base status?

A) Metabolic acidosis and metabolic alkalosis

B) Metabolic acidosis with partial respiratory compensation

C) Respiratory acidosis and partial metabolic compensation

D) Respiratory acidosis

E) Metabolic alkalosis

Q.12-The medical student next to you, realizing that there is an examination question on acid base balance, begins nervously hyperventilating and then faints. You make him breathe into a paper bag and he recovers. If you had drawn and analyzed his blood when he fainted you would have expected to see :

A) Decreased pH, decreased pCO2

B) Decreased pH, elevated pCO2

C) Elevated pH, decreased pCO2

D) Elevated pH, elevated pCO2

E) Normal pH, normal pCO2

Q.13- All except one are examples of entoxification:

A) Conversion of methanol to formaldehyde

B) p- methyl amino benzene to p-dimethyl amino azo benzene

C) Conversion of procarcinogens to Ultimate carcinogens

D) Conversion of Aspirin to Acetic acid and Salicylic acid

E) Conversion of Ethyl alcohol to Acetaldehyde.

Q.14- In physiological jaundice of new-born, due to less availability of substrate and immature enzyme system, there is an impaired formation of soluble, non toxic form of bilirubin which is :

A) Bilirubin Sulphate

B) Bilirubin Phosphate

C) Bilirubin diglucuronate

D) Bilirubin Acetate

E) Methylated Bilirubin

15) In  phenylketonuria (a congenital disorder of phenylalanine metabolism that occurs due to deficiency of phenylalanine hydroxylase), there is impaired conversion of phenylalanine to tyrosine. The excess phenylalanine is detoxified and excreted in urine. Which of the following conjugating agents is used for detoxification of phenylalanine?

A) Glutathione

B) Glutamine

C) S-Adenosyl Methionine

D) Active Sulfate (PAPS)

E) D- Glucuronic acid

16) Which of the following is not a cause of secondary dehydration?

A) Excessive sweating

B) Comatose patient

C) Vomiting

D) Diarrhea

E) Congestive heart failure

17) The urinary concentration of sodium chloride (NaCl) ranges between:

A) 2-6 G/litre

B) 4-8 G/litre

C) 5-10 G/litre

D) 6-16 G/litre

E) None of the above

18) The minimum excretory volume to eliminate waste products from the body in dehydration is :

A) 100-200ml

B) 200-400 ml

C) 500-600 ml

D) 1500 ml

E) 600-800 ml

19) Aldosterone acts by promoting:

A) Excretion of Potassium

B) Reabsorption of potassium

C) Reabsorption of sodium

D) Excretion of sodium

E) Reabsorption of sodium and excretion of Potassium

20) Which of the following is not a cause of hypokalemia?

A) Renal tubular acidosis

B) Cushing syndrome

C) GI losses

D) Crush injuries

E) Insulin administration

Key to answers

1)- A, 2)- A, 3)-A, 4)-D, 5)-A, 6)-A, 7)-C, 8)-B, 9)-A, 10)- B, 11)-E, 12)-C, 13)-D, 14)-C, 15)-B, 16)-B, 17)-D, 18)-C, 19)-E, 20)-D.

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Normal Acid-Base Homeostasis and Role of Lungs

Systemic arterial pH is maintained between 7.35 and 7.45 by extracellular and intracellular chemical buffering together with respiratory and renal regulatory mechanisms. The control of arterial CO2 tension (paCO2) by the central nervous system and respiratory systems; and the control of the plasma bicarbonate by the kidneys stabilize the arterial pH by excretion or retention of acid or alkali.

The metabolic (bicarbonate) and respiratory components (carbonic acid) that regulate systemic pH are described by the Henderson-Hassel Balch equation:

pH = 6.1 + log (HCO-3/ H2 CO3)

H2 CO3 = PCO2 (mm Hg) X 0.03

Under most circumstances, CO2 production and excretion are matched, and the usual steady-state paCO2 is maintained at 40 mm Hg. Under excretion of CO2 produces hypercapnia, and over excretion causes hypocapnia. Nevertheless, production and excretion are again matched at a new steady-state paCO2. Therefore, the PaCO2 is regulated primarily by neural respiratory factors and is not subject to regulation by the rate of CO2 production. Hypercapnia is usually the result of hypoventilation rather than of increased CO2 production. Increases or decreases in paCO2 represent derangements of neural respiratory control or are due to compensatory changes in response to a primary alteration in the plasma [HCO3].

In conditions of low plasma [HCO3] due to acidity in the medium (high H+ concentration), medullary chemo receptors  are stimulated with the resultant hyperventilation and elimination of H2CO3(CO2), the ratio of HCO-3/ H2 CO3 is restored back to normal , pH is also restored back to normal.

Reverse occurs in conditions of high plasma bicarbonate concentration (low H +), the medullary chemo receptors are depressed with the resultant hypoventilation and retention of CO2 (H2CO3). The ratio is restored, bringing  pH also back to normal.

 Effect of pCO2

↑pCO2 → ↑Ventilation →Eliminates CO2 → Reduces [H+]  and ↑pH

↓pCO2 → ↓Ventilation → ↑CO2 → ↑ [H+] & ↓ pH

 Doubling the ventilation → ↑pH

 ¼ of normal ventilation → ↓ pH

 Effect of [H+]

– ↑ [H+] → ↑Alveolar Ventilation →↓CO2

– ↓pH (from 7.4-7.0) → ↑Alveolar Ventilation by 4 times normal.

– ↑pH → ↓Alveolar Ventilation

Respiratory Mechanism has effectiveness between 50-75% and  is 1-2 times as great as the buffering power of all other chemical buffers in ECF. The lungs should be healthy for these compensatory changes.  

Role of Kidney in maintaining acid base homeostasis

Acids are added daily to the body fluids. These acids first are buffered by the HCO3 -/H2 CO3 system as follows:

H2 SO4 + 2NaHCO3 «Na2 SO4 + 2H2 CO3 «2H2O +2 CO2

The net result is buffering of a strong acid (H2 SO4) by 2 molecules of HCO3 - and production of a weak acid (H2 CO3), which minimizes the change in pH. The lungs excrete the CO2 produced, and the kidneys replace the consumed HCO3 -, to prevent progressive HCO3 - loss and metabolic acidosis, (principally by H+ secretion in the collecting duct).

To maintain normal pH, the kidneys must perform 2 physiological functions.

The first is to reabsorb all the filtered HCO3 - (any loss of HCO3 - is equal to the addition of an equimolar amount of H+), a function principally of the proximal tubule.

The second is to excrete the daily H+ load (loss of H+ is equal to addition of an equimolar amount of HCO3 -), a function of the collecting duct.

HCO3 - re-absorption

With a serum HCO3 - concentration of 24 mEq/L, the daily glomerular ultra filtrate of 180 L, in a healthy subject, contains 4300 mEq of HCO3 -, all of which has to be reabsorbed. Approximately 90% of the filtered HCO3 - is reabsorbed in the proximal tubule, and the remainder is reabsorbed in the thick ascending limb and the medullary collecting duct (figure-1).

The 3Na+ -2K+ «ATPase (sodium-potassium «adenosine triphosphatase) provides the energy for this process, which maintains a low intracellular Na+ concentration and a relative negative intracellular potential. The low Na+ concentration indirectly provides energy for the apical Na+/H+ exchanger, which transports H+ into the tubular lumen. H+ in the tubular lumen combines with filtered HCO3 - in the following reaction:

HCO3 - + H+ « H2 CO3 « H2 O + CO2

Carbonic Anhydrase (CA IV isoform) present in the brush border of the first 2 segments of the proximal tubule accelerates the dissociation of H2 CO3 into H2O + CO2, which shifts the reaction shown above to the right and keeps the luminal concentration of H+ low. CO2 diffuses into the proximal tubular cell perhaps via the aquaporin-1 water channel, where carbonic anhydrase (CA II isoform) combines CO2 and water to form HCO3 - and H+. The HCO3 - formed intracellularly returns to the pericellular space and then to the circulation via the basolateral Na+/3HCO3 - co transporter.

In essence, the filtered HCO3 - is converted to CO2 in the lumen, which diffuses into the proximal tubular cell and is then converted back to HCO3 - to be returned to the systemic circulation, thus reclaiming the filtered HCO3 -

 Bicarbonate reabsorption

Figure-1- Re-absorption of HCO3-

 Acid excretion

Excretion of the daily acid load (50-100 mEq of H+) occurs principally through H+ secretion by the apical H+ «ATPase in A-type intercalated cells of the collecting duct.

HCO3 - formed intracellularly is returned to the systemic circulation via the basolateral Cl-/HCO3 - exchanger, and H+ enters the tubular lumen via 1 of 2 apical proton pumps, H+ «ATPase or H+ -K+ «ATPase. The secretion of H+ in these segments is influenced by Na+ reabsorption in the adjacent principal cells of the collecting duct. Hydrogen ions secreted by the kidneys can be excreted as free ions but, at the lowest achievable urine pH of 5.0 (equal to free H+ concentration of 10 µEq/L), would require excretion of 5000-10,000 L of urine a day. Urine pH cannot be lowered much below 5.0 because the gradient against which H+ «ATPase has to pump protons (intracellular pH 7.5 to luminal pH 5) becomes too steep. Maximally acidified urine, even with a volume of 3 L, would thus contain a mere 30 µEq of free H+. Instead, more than 99.9% of the H+ load is excreted buffered by the weak bases NH3 or phosphate.

 Titratable acidity

The amount of secreted H+ that is buffered by filtered weak acids is called titratable acidity. Phosphate as HPO4 2- is the main buffer in this system(figure-2) but other urine buffers include uric acid and creatinine.

H2 PO4 «H+ + HPO4 2-

The amount of phosphate filtered is limited and relatively fixed, and only a fraction of the secreted H+ can be buffered by HPO4 2-.

 Phosphate mechanism

Figure-2- showing the buffering of secreted H+ by HPO4-

Ammonia mechanism

A more important urine-buffering system for secreted H+ than phosphate, ammonia (NH3) buffering occurs via the following reaction:

NH3 + H+ «NH4 +

Ammonia is produced in the proximal tubule from the amino acid glutamine, and this reaction is enhanced by an acid load and by hypokalemia. Ammonia is converted to ammonium (NH4 +) by intracellular H+ and is secreted into the proximal tubular lumen by the apical Na+/H+ (NH4 +) antiporter. It can be secreted as such also and can later combine with H+ in the lumen to form NH4+.

 NH4 + is trapped in the lumen and excreted as the Cl salt, and every H+ ion buffered is an HCO3 - gained to the systemic circulation (figure-3)

The kidneys can adjust the amount of NH3 synthesized to meet demand, making this a powerful system to buffer secreted H+ in the urine.

 Ammonia mechanism

Figure –3- showing ammonia mechanism. Glutamine is first converted to glutamate and then to alpha keto glutarate

Renal glutaminase activity is increased in conditions of acidosis, to excrete out the excess acid load  whereas it is decreased in  conditions of alkalosis to conserve acids (H+) to maintain the acid base balance of the body.

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An acid is a substance that can donate hydrogen ions (H+), and a base is a substance that can accept H+ ions, regardless of the substance’s charge.

H2 CO3 (acid) « H+ + HCO3 - (base)

Strong acids are those that are completely ionized in body fluids, and weak acids are those that are incompletely ionized in body fluids.

HCl « H+ + Cl-

Hydrochloric acid (HCl) is considered a strong acid because it is present only in a completely ionized form in the body, whereas H2 CO3 is a weak acid because it is ionized incompletely, and, at equilibrium, all 3 reactants are present in body fluids.

H2 CO3 (acid) « H+ + HCO3 - (base)

In body fluids, the concentration of hydrogen ions ([H+]) is maintained within very narrow limits, with the normal physiologic concentration being 40nEq/L. The concentration of HCO3(24mEq/L) is 600,000 times that of [H+]. The tight regulation of [H+] at this low concentration is crucial for normal cellular activities.

Significance of pH

1) Specific tautomeric forms exist at physiologic pH. This helps in proper hydrogen bonding between the complementary base pairs in the structure of DNA.

2) The solubility and biologic activity of a protein depends upon its 3D structure and that depends upon net charge on protein for the maintenance of hydrogen and ionic interactions. The net charge depends upon the pH of the medium.

3) The movement of ions across the membrane depends upon their net charge as determined by the pH.

4) Ionic state of the nucleic acids, lipids and mucopolysaccharides is also determined by the physiological pH

5) All enzymes function best within an optimum pH range.

6) Nerve conduction and muscle contractions are also pH dependent

7) All metabolic processes are pH dependent.

8) Oxygen and CO2 transport, release or gaseous exchange is pH dependent.

Maintenance of pH is important for proper physiological functioning of cells and tissues. Any changes in pH can alter enzyme activity, cellular uptake, incorporation and use of minerals and metabolites, uptake and release of oxygen, and the formation of biological structural components.

Normal plasma pH = 7.40 (±0.05). The pH range that is compatible with life is from 6.8 to 7.8. The body can comfortably tolerate a shift in pH of about 0.04. Most cells of the body have a pH = 7.0, but RBC’s boast a pH of 7.2. The pH of the body affects its acid-base balance and the pH of blood has the greatest effect.

Sources for pH disturbances

1) Organic acids- The most common sources for pH disturbances are the body’s production of organic acids (acetic, acetoacetate, propionic, butyric, lactic, etc.), which are the major sources of hydrogen ion.

2) Carbonic acid is the chief acid (volatile acid) produced in the body by the metabolic processes in the body. Approximately 300 litres of CO2 are produced and eliminated daily in the body of an adult.

3) Sulphuric acid- it is produced during the oxidation of sulphur-containing amino acids and vitamins.

4) Phosphoric acid- is produced from the metabolism of dietary phosphoproteins, phospholipids, nucleic acids and hydrolysis of phosphoesters.

Mechanism of maintenance of Physiological pH

Under normal conditions, acids and, to a lesser extent, bases are being added constantly to the extracellular fluid compartment but still a physiologic [H+] of 40 nEq/L is maintained and the following 3 processes must take place:

  • Buffering by extracellular and intracellular buffers
  • Alveolar ventilation, which controls PaCO2
  • Renal H+ excretion, which controls plasma [HCO3 -]

Buffers

Buffers are weak acids or bases that are able to minimize changes in pH by taking up or releasing H+. Phosphate is an example of an effective buffer, as in the following reaction:

HPO4 2- + (H+) « H2 PO4 -

Upon addition of an H+ to extracellular fluids, the monohydrogen phosphate binds H+ to form dihydrogen phosphate, minimizing the change in pH. Similarly, when [H+] is decreased, the reaction is shifted to the left. Thus, buffers work as a first-line of defense to blunt the changes in pH that would otherwise result from the constant daily addition of acids and bases to body fluids. With the constant pouring in of H+, the concentration of the monohydrogen phosphate will ultimately diminish and the pH will start falling.

The major Buffer system of the body

(1) HCO3 -/H2 CO3 buffering system HCO/CO2 (bicarbonate/carbon dioxide)

(2) HPO42―/H2PO4 (phosphate),

(3) Organic Phosphate Esters, and

(4) Proteins.

Proteins with side chains that contain more carboxyl terminal groups than amino terminal groups promote an acidic environment. Proteins with side chains that contain more amino terminal groups than carboxyl terminal groups promote an alkaline environment. Protein with side chains containing equal numbers of amino and carboxyl side groups are neutral, not affecting the pH.

Details of Buffers

(1) HCO3 -/H2 CO3 buffering system

In the ECF bicarbonate buffer is the most important buffer. Its function is illustrated by the following reactions:

H2 O + CO2 «H2 CO3 « H+ + HCO3

When an acid load (H+) is added to the body fluids, it results in consumption of HCO3 - by the added H+. Carbonic acid thus formed, in turn, forms water and CO2. CO2 concentration is maintained within a narrow range via the respiratory drive, which eliminates accumulating CO2. The kidneys regenerate the HCO3 - consumed during this reaction.

Put simply, whereas simple buffers rapidly become ineffective as the association of the hydrogen ion and the weak anion of the weak acid reaches equilibrium, the bicarbonate system keeps working because the carbonic acid is removed as CO2. The limit to the effectiveness of the bicarbonate system is the initial concentration of bicarbonate. The acid base status of the patient is assessed by the bicarbonate concentration in the plasma. The association of hydrogen ion with bicarbonate occurs rapidly but the dissociation of H2CO3 to CO2 and H2O is slow. This process is accelerated by the enzyme Carbonic anhydrase, which is present in the erythrocytes and in the kidney whenever this reaction is needed. Buffering at the expense of bicarbonate effectively removes hydrogen ions from ECF. CO2 is removed from the lungs and water assimilates in the ECF without producing any change in p H. The ECF contains a large amount of bicarbonate to the extent of 24 mmol/L, when the H+ concentration increases the bicarbonate concentration comes down since it is used up during the process of buffering.

This reaction continues to move to the left as long as CO2 is constantly eliminated or until HCO3 - is significantly depleted, making less HCO3 - available to bind H+. Since HCO3 - and PaCO2 can be managed independently (kidneys and lungs, respectively) that makes this a very effective buffering system. One of the major factors that make this system very effective is the ability to control PaCO2 by changes in ventilation. As can be noted from this reaction, increased carbon dioxide (CO2) concentration drives the reaction to the right, whereas a decrease in CO2 concentration drives it to the left.

Assessing acid base status

An indication of the acid base status of the patient can be determined by measuring the components of the bicarbonate system.

The Henderson-Hassel Balch equation describes the relationship between blood pH and the components of the H2 CO3 buffering system.  

pH = 6.1 + log (HCO-3/ H2 CO3)

Bicarbonate (HCO3-) is in equilibrium with the metabolic components.

  • Bicarbonate production in the kidney
  • Acid production from endogenous or exogenous sources

Carbonic acid (H2 CO3) is in equilibrium with the respiratory component, as shown by the below equation:

H2 CO3 = PCO2 (mm Hg) X 0.03

Note that changes in pH or [H+] are a result of relative changes in the ratio of PaCO2 to [HCO3 -] rather than to absolute change in either one. In other words, if both PaCO2 and [HCO3 -] change in the same direction, the ratio stays the same and the pH or [H+] remains relatively stable. To diminish the alteration in pH that occurs when either HCO3 - or PaCO2 changes, the body, within certain limits, changes the other variable in the same direction.

2) Phosphate buffer system (Na2HPO4/NaH2PO4)

The phosphate buffer system is directly linked up with kidney.

Upon addition of acid, the H+ is neutralized by the Na2 HPO4 component forming NaH2PO4 that is eliminated through the kidney without any change in pH.

Na2 HPO4 + HCl–>> NaH2PO4 + NaCl

Similarly upon addition of OH-, the acid component reacts to form, Na2 HPO4 that can be eliminated as well through the kidney without any change in pH

NaH2PO4 + Na OH—>> Na2 HPO4 + H2O

In other words Phosphate buffer system works in conjunction with the kidney.

Chemically it is a very good buffer, as pKa is close to Physiological pH, but physiologically due to its less concentration (1.0 mmol/L as compared to bicarbonate 26-28 mmol/L) it is less efficient.

3) Role of Haemoglobin as a buffer

The buffering capacity of Hb is due to the presence of “Imidazole” nitrogen group of Histidine. Oxygenated Hb is a stronger acid than deoxygenated Hb. Acidity of the medium favors delivery of oxygen to the tissues. Alkalinity of the medium favors oxygenation of Hb. Sequence of events that occur in lungs and tissues is as follows;

  • In the lungs

The formation of oxy hemoglobin from deoxy hemoglobin, must release H+, which will react with HCO3- to form H2CO3. Due to the low CO2 tension in the lungs H2CO3, dissociates to form CO2 and H2O . CO2 is then eliminated in the expired air (Figure-1).

 Role of Hb as a buffer in lungs

Figure-1- Role of Hb as a buffer in the lungs.

  • In the tissues

Oxy Hb dissociates to give O2 to the tissues and the deoxy Hb (Reduced Hb) is formed. At the same time CO2 produced as a result of metabolism, is hydrated to for H2CO3, which ionizes to form H+ and HCO3-. Deoxy Hb acts as anion and accepts H+ to form acid reduced Hb (Figure-2)

Role of Hb as a buffer in tissues

Figure-2-  Role of Hb as a buffer at the tissue level.

4) Protein buffer system

Buffering capacity of plasma proteins is much less than Hb. In acidic medium protein acts a base and NH2 group takes up H+ forming NH3+, protein becomes positively charged.

 Reverse occurs in the alkaline medium. Acidic COOH to give H+ that neutralizes the OH- forming H2O. Overall protein becomes negatively charged in the alkaline medium.

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Primary Disorder   Defect   Causes Effect on pH and Ratio of Bicarbonate: Carbonic acid  Compensatory Response
Metabolic Acidosis

HCO3-

Decreased

Gain in H+ or loss of HCO3-

 

(A) High anion gap (Acid gain)

1) Ketoacidosis

  • Diabetes
  • Chronic alcoholism
  • Under nutrition
  • Fasting

2) Lactic Acidosis

  • Shock
  • Primary hypoxia due to lung disorders
  • Seizures

3) Renal Failure

4) Toxins Metabolized to acids

  • Alcohol
  • Methanol (formate)
  • Ethylene glycol (oxalate)
  • Salicylates

B) Normal Anion Gap-Acidosis(Bicarbonate loss- Hyperchloremic acidosis)

1) GI HCO3 loss

  • Colostomy
  • Diarrhea
  • Enteric fistulas
  • Ileostomy

2)Urologic procedures

3) Renal HCO3 loss

  • Tubulointerstitial renal disease
  • Renal tubular acidosis

4) Ingestions

  • Acetazolamide
  • CaCl2
  • Mg sulfate (MgSO4)

 

pH –decreased,

Ratio- decreased

 

Respiratory Mechanism-Respiratory Alkalosis(Hyperventilation)

Pa CO2 Decreased 

Renal mechanisms

1) Increased excretion of H+ ions

2) Decreased excretion of K+ ions in the distal tubules

3) Decreased bicarbonate excretion

4)Increased ammonia formation

5) Increased acid phosphate excretion

 

 

Metabolic Alkalosis

HCO3- Increased

Gain in HCO3-or loss of H+ Chloride-responsive alkalosis

  • Loss of gastric secretions – Vomiting, NG suction
  • Loss of colonic secretions
  • Thiazides and loop diuretics (after discontinuation)
  • Cystic fibrosis( Due to loss of chloride in the sweat)
  • Ingestion of large doses of nonabsorbable antacids

Chloride-resistant alkalosis

  • Primary hyperaldosteronism
  • Cushing syndrome
  • Exogenous mineralocorticoids or glucocorticoids
  • Reno vascular hypertension
  • Renin- or deoxy corticosterone-secreting tumors
  • Current use of thiazides and loop diuretics
  • Hypomagnesaemia(Through Hypokalemia)
  • Milk Alkali Syndrome

 

pH increased,

Ratio increased

Respiratory Mechanism-

Respiratory Acidosis(Hypoventilation)

PaCO2 Increased.

Renal Mechanism

1) Decreased excretion of H+ ions

2) Increased excretion of K+ ions in the distal tubules

3) Increased bicarbonate excretion

4) Decreased ammonia formation

5) Decreased acid Phosphate excretion

 

Respiratory Acidosis

PaCO2

Increased

CO2 Retention A) Central

  • Drugs- Sedatives, Alcohol, General Anesthetic agents
  •  Infections
  • Injuries- head trauma
  • Diseases-  Intracranial tumor
  • Syndromes of sleep-disordered breathing, including the primary alveolar   and obesity-hypoventilation syndromes.

B)Airway obstruction

  • Severe asthma,
  • Anaphylaxis
  • Inhalational burn
  • Toxic injury
  • Laryngeal obstruction
  • End-stage obstructive lung disease.

C) Parenchymatous damage /Inflammation

  • Emphysema
  • Bronchitis
  • Adult Respiratory distress syndrome
  • Pleurisy
  • Barotrauma

D) Neuromuscular

  • Poliomyelitis
  • Kyphoscoliosis
  • Myasthenia gravis
  • Muscular dystrophies

E) Misc.

  • Certain congenital heart diseases
  • Mechanical ventilation
  • Rebreathing from a closed space

 

pH- decreased,

Ratio- decreased

Metabolic Alkalosis

HCO3-Increased.

Renal mechanisms 1) Increased excretion

of H+ ions

2) Decreased bicarbonate excretion

3) Increased ammonia formation

4) Increased acid phosphate excretion

 

Respiratory Alkalosis

PaCO2 Decreased

CO2 Washout A) Central nervous system

  • Pain
  • Hyperventilation syndrome
  • Anxiety
  • Psychosis
  • Fever
  • Cerebrovascular accident
  • Meningitis
  • Encephalitis
  • Tumor
  • Trauma
  • Hypoxia
    • High altitude
    • Severe anemia
    • Right-to-left shunts
  • Drugs
    • Progesterone
    • Methylxanthines
    • Salicylates
    • Catecholamines
    • Nicotine
  • Endocrine
    • Pregnancy
    • Hyperthyroidism
  • Pulmonary
    • Pneumothorax/hemothorax
    • Pneumonia
    • Pulmonary edema
    • Pulmonary embolism
    • Aspiration
    • Interstitial lung disease
    • Asthma
    • Emphysema
    • Chronic bronchitis
  • Miscellaneous
    • Sepsis
    • Hepatic failure
    • Mechanical ventilation
    • Heat exhaustion
    • Recovery phase of metabolic acidosis
    • Congestive heart failure

 

pH –Increased,

Ratio- Increased

Metabolic Acidosis

HCO3-Decreased

Renal Mechanism

1)Decreased excretion of H+ ions

2)Increased bicarbonate excretion

3)Decreased ammonia formation

4)Decreased phosphate excretion

 

 

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Case-1  

A 45 year-old-female suffering from bronchial asthma was brought to emergency in a critical state with extreme difficulty in breathing.

The blood gas analysis revealed the following

pH- 7.3

PCO2- 46 mm Hg

PO2- 55 mm Hg

HCO3- 24meq/L

What is your Interpretation?

Case details-

 Low p H – acidosis

Low PO2 and PCO2 excess signify Primary respiratory problem

HCO3:24 -normal

Thus, the patient is suffering from Acute respiratory acidosis.

Case -2

A 4 day old girl neonate became lethargic and uninterested in breast feeding. Physical examination revealed tachypnea (rapid breathing) with a normal heart beat and breath sounds. Initial blood chemistry values included normal glucose, sodium, potassium, chloride, and bicarbonate (HCO3-) levels.

Blood gas values revealed a pH of 7.53, partial pressure of oxygen (PO2) was normal (103 mm Hg) but PCO2 was 27 mmHg.

What is the probable diagnosis?

Case details-

The baby is suffering from Respiratory Alkalosis

Tachypnea in term infants may be due to brain injuries and metabolic diseases that irritate the respiratory center. The increased respiratory rate removes carbon dioxide from the lung alveoli and lowers blood CO2, forcing a shift in the indicated equilibrium towards left

 CO2 + H2O çè H2CO3 çè H+ + HCO3-

Carbonic acid (H2CO3) can be ignored because negligible amounts are present at physiological pH, leaving the equilibrium

 CO2 + H2O çè H+ + HCO3-

 The leftward shift to replenish exhaled CO2 decreases the hydrogen ion (H+) concentration and increases the pH to produce alkalosis. This respiratory alkalosis is best treated by diminishing the respiratory rate to elevate the blood [CO2], to force the above equilibrium to the right, elevate the [H+], and decrease the pH.

Case study-3

A new-born with tachypnea and cyanosis (bluish color) is found to have a blood pH of 7.1. Serum bicarbonate is measured as 12 mM  while pCO2 is 40 mm Hg.

What is the probable diagnosis?

Case details-

Low p H and low bicarbonate indicate metabolic acidosis. Since p CO2 is normal it can not be compensatory respiratory acidosis ( If the baby had respiratory acidosis, the PCO2 would have  been elevated).This is a hypoxia related metabolic acidosis. Hyperventilation is as a compensation to metabolic acidosis.

This condition can be treated  by administration of oxygen to improve tissue perfusion and decrease metabolic acidosis.

Case study -4

A 60-year-old man was brought to hospital in a very serious condition.  The patient complained of constant vomiting containing several hundred mL of dark brown fluid from the previous two days plus several episodes of melaena. Past history of alcoholism, cirrhosis, portal hypertension and a previous episode of bleeding varices was there.

Arterial Blood Gases revealed-

pH – 7.10

pCO2 – 13.8 mmHg

pO2- 103 mmHg

HCO3- 14.1 mmol/l

Laboratory Investigations

Na+ 131 mmol/l., Cl- 85 mmol/l. K+ 4.2 mmol/l., “total CO2” 5.1, glucose 52mg/dl, urea 38.6mg/dl, creatinine1.24mg/dl, lactate 20.3 mmol/l  Hb 6.2 G%, and WBC- 18 x103/mm3

Case details-

The patient is severely ill with circulatory failure and GI bleeding on a background of known cirrhosis with portal hypertension.

The very low pH indicates a severe acidosis. The combination of a low pCO2 and low bicarbonate indicates either a metabolic acidosis or a compensatory respiratory alkalosis (or both). As this patient has a severe acidosis, so the most probable diagnosis is metabolic acidosis. The anion gap is 31 indicating the presence of a high anion gap disorder. The lactate level of 20.3mmol/l is extremely high and this confirms the diagnosis of a severe lactic acidosis. Hb is very low consistent with the history of bleeding and hypovolemia. Urea and creatinine are elevated (renal failure) but at these levels there would not be retention of anions sufficient to result in a renal acidosis. Hence,

Lactic acidosis can be suspected. The respiratory efforts may be due to the distress or as a consequence of a metabolic acidosis (ie compensatory).

Case study-5

A 56- year -old man who smoked heavily for many years developed worsening cough with purulent sputum and was  admitted to the hospital because of difficulty in breathing. He was drowsy and cyanosed. His arterial blood gas analysis was as follows;

 pH -      7.2

p CO2 – 70 mm Hg

HCO3-   26 mmol/L

P O2-  50 mm Hg

What is the likely diagnosis?

Case details

The patient is suffering from Respiratory acidosis. Difficulty in breathing, cough and purulent sputum signify the underlying lung pathology. Low p H and raised pCO2 indicate respiratory acidosis. Slightly high HCO3- may be due to compensation as a result of increased reabsorption from the kidney. The low pO2 is due to associated hypoxia. The treatment is based on the treating the primary cause.O2 and mechanical ventilation are often needed.

Case study-6

A 5-year old girl displayed increased appetite, increased urinary frequency, and thirst. Her physician suspected new onset diabetes mellitus and confirmed that she had elevated urine glucose and ketones.

Blood gas analysis revealed

pH-7.33

Bicarbonate-12.0 mmol/L

Arterial PCO2- 21

Case details

The patient is suffering from Diabetic ketoacidosis

In the presence of insulin deficiency, a shift to fatty acid oxidation produces the ketones that cause metabolic acidosis. The pH and bicarbonate are low, and there is frequently some respiratory compensation (hyperventilation with deep breaths) to lower the PCO2. A low pH with high PCO2 would have represented respiratory acidosis which is not there in the given case.

Case study-7

A 19-year-old boy was brought to the emergency department with loss of consciousness. Apparently the patient was a homeless found on the street.

Arterial blood gases revealed-

pH –     7.33,

pCo2 – 28 mm Hg,

pO2- 117 mmHg and

HCO3- 14 mmol/L

The blood level of methanol was 0.4 mg/dl.

What is your diagnosis?

Case details-

The patient is suffering from metabolic acidosis as evident from the low p H and low bicarbonate levels. Low p CO2 and high p O2 signify that the patient is in a state of respiratory compensation. Blood methanol level is high, so it might be the case of Methanol poisoning producing metabolic acidosis.

Case study-8

A 66-year-old man had a postoperative cardiac arrest. Past history of hypertension treated with an ACE inhibitor was there. There was no past history of Ischemic heart disease. Following reversal and extubation, myocardial ischemia was noticed on ECG. He was transferred to ICU for overnight monitoring. On arrival in ICU, BP was 90/50, pulse 80/min, respiratory rate was 16/min and S pO2 99%. During handover to ICU staff, he developed ventricular fibrillation which reverted to sinus rhythm with a single 200J counter shock. Soon after, blood gases were obtained from a radial arterial puncture:

Arterial Blood Gases

 pH -7.27

 pCO2 -55.4 mmHg

 pO2- 144 mmHg

 HCO3- 24.3 mmol/l

Biochemistry Results (all in mmol/l): Na+ 138, K+ 4.7, Cl- 103, urea 6.4, creatinine 0.07

What is the probable diagnosis?

Acid-base Diagnosis

1) p H- low , Acidosis is present.

2) p CO2- high, hypoventilation(The residual depressant effect of the Anesthetic agents is considered the most likely cause)

3) Bicarbonate- near normal

4) pO 2- high- This is because the patient is breathing a high inspired oxygen concentration. If the patient had been breathing room air (FIO2 = 0.21), then a depression of alveolar pO2 must have occurred. Most ill patients in hospital breathe supplemental oxygen so it is common for the pO2 to be elevated on blood gas results.

5) An acidemia with the pattern of elevated pCO2 and normal HCO3 is consistent with an acute respiratory acidosis.

6) Anion gapThe anion gap is about 11 which is normal so no evidence of a high anion gap acidosis.

Diagnosis- Acute respiratory acidosis

Cause- Resuscitation from postoperative ventricular fibrillation

Case study -9

A 72-year-old male with diabetes mellitus is evaluated in the emergency room because of lethargy, disorientation, and long, deep breaths (Kussmaul respiration). Initial chemistries on venous blood demonstrate high glucose level of 380 mg/dl (normal up to 120 mg/dl) and pH of 7.3. Bicarbonate 15mM and PCO2 30mmHg, What is the probable diagnosis ?

Case details-

The man is acidotic as defined by pH lower than normal 7.4. His hyperventilation with Kussmaul respiration can be interpreted as compensation by lungs to blow off CO2 to lower PCO2, to increase [HCO3-]/[CO2] ratio, and to raise pH. Thus the patient has metabolic acidosis due to underlying Diabetic ketoacidosis.

Case study-10

A 24 year female with broken ankle was brought to emergency with acute pain.

Blood gas analysis revealed the following

 pH- 7.55

PCO2- 27

PO- 105,  

HCO3- 23

What is the probable diagnosis?

Case details-

 pH:-  7.55 – indicates Alkalosis

PCO2: 27 -low, it is a Primary respiratory disturbance

 PCO2 Deficit = 40-27 = 13

 HCO3 = 23 (Normal)

Interpretation:

It is Respiratory alkalosis due to pain related hyperventilation.

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Q.1- A person was admitted in a coma. Analysis of the arterial blood gave the following values: PCO2 16 mm Hg, HCO3- 5 mmol/l and pH 7.1. What is the underlying acid-base disorder?

a) Metabolic Acidosis

b) Metabolic Alkalosis

c) Respiratory Acidosis

d) Respiratory Alkalosis

Q.2- In a man undergoing surgery, it was necessary to aspirate the contents of the upper gastrointestinal tract. After surgery, the following values were obtained from an arterial blood sample: pH 7.55, PCO2 52 mm Hg and HCO3- 40 mmol/l. What is the underlying disorder?

a) Metabolic Acidosis

b) Metabolic Alkalosis

c) Respiratory Acidosis

d) Respiratory Alkalosis

Q.3- A young woman is found comatose, having taken an unknown number of sleeping pills an unknown time before. An arterial blood sample yields the following values: pH – 6.90, HCO3- 13 meq/liter, PaCO2  68 mmHg. This patient’s acid-base status is most accurately described as

a) Uncompensated metabolic acidosis

b) uncompensated respiratory acidosis

c) simultaneous respiratory and metabolic acidosis

d) respiratory acidosis with partial renal compensation

Q.4- A student is nervous for a big exam and is breathing rapidly, what do you expect out of the following

a) Metabolic Acidosis

b) Metabolic Alkalosis

c) Respiratory Acidosis

d) Respiratory Alkalosis

Q.5- A 45- year-old female with renal failure, missed her dialysis and was feeling sick,  what could be the reason ?

a) Metabolic Acidosis

b) Metabolic Alkalosis

c) Respiratory Acidosis

d) Respiratory Alkalosis

Q.6- An 80-year-old man had a bad cold. After two weeks he said, “It went in to my chest, I am feeling tightness in my chest, I am coughing, suffocated and unable to breathe!” What could be the possible reason?

a) Metabolic Acidosis

b) Metabolic Alkalosis

c) Respiratory Acidosis

d) Respiratory Alkalosis

Q.7- A post operative surgical patient had a naso gastric tube in for three days. The nurse caring for the patient stated that there was much drainage from the tube that is why she felt so sick. What could be the reason?

a) Metabolic Acidosis

b) Metabolic Alkalosis

c) Respiratory Acidosis

d) Respiratory Alkalosis

Q.8- The p H of the body fluids is stabilized by buffer systems. Which of the following compounds is the most effective buffer system at physiological pH ?

a) Bicarbonate buffer

b) Phosphate buffer

c) Protein buffer

d) All of the above

Q.9- Which of the following laboratory results below indicates compensated metabolic alkalosis?

a) Low p CO2, normal bicarbonate and, high pH

b) Low p CO2, low bicarbonate, low pH

c) High p CO2, normal bicarbonate and, low p H

d) High pCO2, high bicarbonate and High pH

Q.10- The greatest buffering capacity at physiological p H would be provided by a protein rich in which of the following amino acids?

a) Lysine

b) Histidine

c) Aspartic acid

d) Leucine

Q.11- Which of the following is most appropriate for a female suffering from Insulin dependent diabetes mellitus with a pH of 7.2, HCO3-17 mmol/L and pCO2-20 mm HG

a) Metabolic Acidosis

b) Metabolic Alkalosis

c) Respiratory Acidosis

d) Respiratory Alkalosis

Q.12- Causes of metabolic alkalosis include all the following except.

a) Mineralocorticoid deficiency.

b) Hypokalemia

c) Thiazide diuretic therapy.

d) Recurrent vomiting.

Q.13- Renal Glutaminase activity is increased in-

a) Metabolic acidosis

b) Respiratory Acidosis

c) Both of the above

d) None of the above

Q.14- Causes of lactic acidosis include all except-

a) Acute Myocardial infarction

b) Hypoxia

c) Circulatory failure

d) Infections

Q.15- Which out of the following conditions will not cause respiratory alkalosis?

a) Fever

b) Anxiety

c) Laryngeal obstruction

d) Salicylate toxicity

Q.16- All are true about metabolic alkalosis except one-

a) Associated with hyperkalemia

b) Associated with decreased ionic calcium concentration

c) Can be caused due to Primary hyperaldosteronism

d) Can be caused due to Renin secreting tumor

Q.17- Choose the incorrect statement out of the following

a) Deoxy hemoglobin is a weak base

b) Oxyhemoglobin is a relatively strong acid

c) The buffering capacity of hemoglobin is lesser than plasma protein

d) The buffering capacity of Hemoglobin is due to histidine residues.

Q.18- Carbonic anhydrase is present at all places except-

a) Gastric parietal cells

b) Red blood cells

c) Renal tubular cells

d) Plasma

Q.19- All are true for renal handling of acids in metabolic acidosis except

a) Hydrogen ion secretion is increased

b) Bicarbonate reabsorption is decreased

c) Urinary acidity is increased

d) Urinary ammonia is increased.

Q.20- Choose the incorrect statement about anion gap out of the following

a) In lactic acidosis anion gap is increased

b) Anion gap is decreased in Hypercalcemia

c) Anion gap is decreased in Lithium toxicity

d) Anion gap is decreased in ketoacidosis.

Q.21- Excessive citrate in transfused blood can cause which of the following abnormalities?

a) Metabolic alkalosis

b) Metabolic acidosis

c) Respiratory alkalosis

d) Respiratory acidosis

 

Answers- 1-a, 2-b, 3-c, 4-d, 5-a, 6-c, 7-b, 8-a, 9-d, 10-b, 11-a, 12-a, 13-c, 14-d, 15-c, 16-a, 17-c, 18-d, 19-b, 20-d, 21-a.

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Q.1- Explain clearly how hyperventilation and hypoventilation affect blood p H ?  Give suitable examples in support of your answer.

Q.2- Explain the role of hemoglobin as a buffer in the maintenance of acid base balance in the body.

Q.3-The maintenance of intracellular pH within narrow limits is essential for life processes. Briefly discuss why this is so and describe the mechanism by which the human body maintains a relatively constant pH despite continuous acid production from cellular metabolism.

Q.4- Name 3 physiological buffer systems, and explain the mode of action of any one of them.

Q.5-A person was brought to the hospital after ingesting a large amount of ammonium chloride. His arterial blood pH was found to be 7.29. Calculate the ratio of [HC03] to [dissolved CO2] in the blood.

Dissolved CO2 + H2« H2CO3 « H+ + HCO3- (pKa = 6.1) How might changes in the pulmonary ventilation help to minimize the fall in pH?

Q.6- Discuss the role of kidneys in the maintenance of acid base balance of the body. Support your answer with flow charts showing the details of the mechanisms.

Q.7- What is anion gap? State all the conditions of variations of anion gap in the body?

Q.8- Calculate the anion gap for a patient who has reported to emergency in a state of shock with following blood reports

p H-    7.2

Pco2-  45 mm Hg

HCO3—12 meq/L

Serum Na 135 meq/L

Cl -          -85 meq/L

Q.9-A 14-year-old girl with cystic fibrosis has complained of an increased cough productive of green sputum over the last week. She also complained of being increasingly short of breath, and she is noticeably wheezing on physical examination. Arterial blood was drawn and sampled, revealing the following values:

pH

7.30

pCO2

50 mm Hg

pO2

55 mm Hg

Hemoglobin – O2 saturation

45 %

[HCO3-]

24 meq / liter

What is the acid base status of the girl? Discuss in detail about the imbalance

How would the kidneys try to compensate for the girl’s acid-base imbalance?

Q.10- A 76-year-old man complained to his wife of severe sub-sternal chest pain that radiated down the inside of his left arm. Shortly afterwards, he collapsed on the living room floor. Paramedics arriving at his house just minutes later found him unresponsive, not breathing, and without a pulse. CPR and electro convulsive shock were required to start his heart beating again. Upon arrival at the Emergency Room, the man started to regain consciousness, complaining of severe shortness of breath (dyspnea) and continued chest pain. On physical examination, his vital signs were as follows:

Systemic blood pressure

85 mm Hg / 50 mm Hg

Heart rate

175 beats / minute

Respiratory rate

32 breaths / minute

Temperature

99.2oF

His breathing was labored, his pulses were rapid and weak everywhere, and his skin was cold and clammy. An ECG was done, revealing significant “Q” waves in most of the leads. Blood testing revealed markedly elevated creatine phosphokinase (CPK) levels of cardiac muscle origin. Arterial blood was sampled and revealed the following:

pH

7.22

pCO2

30 mm Hg

pO2

70 mm Hg

Hemoglobin – O2 saturation     

88 %

[HCO3-]

2 meq / liter

a) What is the diagnosis? What evidence supports your diagnosis?

b) How would you classify his acid-base status? What specifically caused this acid-base disturbance?

c) How has his body started to compensate for this acid-base disturbance?

d) What would his blood pH be if his body had not started compensating for the acid-base disturbance? Show your work.

e) List some other causes of this type of acid-base disturbance.

 

Q.11-An elderly gentleman is in a coma after suffering a severe stroke. He is in the intensive care unit and has been placed on a ventilator. Arterial blood gas measurements from the patient reveal the following:

pH

7.50

pCO2

30 mm Hg

pO2

100 mm Hg

Hemoglobin – O2 saturation      

98%

[HCO3-]

24 meq / liter

a) How would you classify this patient’s acid-base status?

b) How does this patient’s hyperventilation pattern raise the pH of the blood?

c) How might the kidneys respond to this acid-base disturbance?

d) List some other causes of this type of acid-base disturbance.


Q.12-A 28-year-old woman has been sick with the flu for the past week, vomiting several times every day. She is having a difficult time keeping solids and liquids down, and has become severely dehydrated. After fainting at work, she was taken to a walk-in clinic, where an IV was placed to help rehydrate her. Arterial blood was drawn first, revealing the following:

pH

7.50

pCO2

40 mm Hg

pO2

95 mm Hg

Hemoglobin – O2 saturation      

97%

[HCO3-]

32 meq / liter

a) How would you classify her acid-base disturbance?

 b) Why might excessive vomiting cause her particular acid-base disturbance?

 c) How would the kidneys compensate for this acid-base disturbance?

 d) List some other causes of this type of acid-base disturbance.

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