H secretion proximal tubule thick ascending henle
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H + secretion (proximal tubule/thick ascending Henle). Proximal tubule (~80%), thick ascending limb (~15%) of H + secreted. Mechanisms of H + secretion (  intercalated cell).  intercalated cell (~5% of H + secreted). Bicarbonate reabsorption & synthesis.

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H secretion proximal tubule thick ascending henle
H+ secretion (proximal tubule/thick ascending Henle)

Proximal tubule (~80%), thick ascending limb (~15%) of H+ secreted


Mechanisms of h secretion intercalated cell
Mechanisms of H+ secretion ( intercalated cell)

 intercalated cell (~5% of H+ secreted)



Bicarbonate reabsorption synthesis1
Bicarbonate reabsorption & synthesis

if no HCO3- production or utilization:

recycled HCO3- would ensure HCO3- balance

if HCO3- used for buffering:

new HCO3- replaces it


Quantitation of secreted h reabsorbed hco 3
Quantitation of secreted H+ & reabsorbed HCO3-

“Titratable acidity” = excreted H2PO4-& other urinary buffers

“Urinary ammonium” = excreted NH4+


Important principles 1
Important principles 1

H+ secreted = HCO3-reabsorbed

H+ excreted = titratable acidity + urinary NH4+

Most of the H+ secreted is used to “reclaim” filtered HCO3-

Filtered HCO3- is not reabsorbed as such; it is destroyed in tubule and resynthesized in tubular cell

New HCO3-synthesized = H+ excreted = titratable acidity + urinary NH4+


Important principles 2
Important principles 2

Plasma [HCO3-] depends on the rate of renal H+secretion

H+secretion plasma [HCO3-] (metabolic alkalosis)

H+secretion plasma [HCO3-] (metabolic acidosis)

Healthy kidney maintains the constancy of plasma [HCO3-] by maintaining constancy of H+secretion (irrespective of moderate acid or alkaline assaults)


Henderson hasselbalch equation
Henderson Hasselbalch equation

H2O + CO2 H2CO3H+ + HCO3-

Looking at 2nd half of equation:

K (equilibrium constant) = [H+] x [HCO3-]

[H2CO3]

Rearranging and taking negative logs:

pH = pK + log10 [HCO3-]

[H2CO3]

Assuming the 1st half of the equation is at equilibrium:

[H2CO3] = 0.03 x Pa.CO2

Then, the Henderson Hasselbalch equation is:

pH = pK + log10 [HCO3-]

0.03 x Pa.CO2


Why use the bicarbonate buffer system
Why use the bicarbonate buffer system?

Not ideal because:

pK 6.1, and buffers are most effective around their pKs

However:

the body can regulate Pa.CO2 & [HCO3-] independently and thus control pH

lungs regulate Pa.CO2 & kidneys regulate [HCO3-]

regulating pH will alter all buffer systems (isohydric principle)

clinically, we can measure pH & Pa.CO2, & calculate [HCO3-]



Interpreting acid base data drw aim
Interpreting acid base data (DRW AIM)

Normal values:

pH 7.35 – 7.45, Pa.CO2 33 – 44 mm Hg, HCO3- 22 – 28 mEq/L

1. Acidosis or alkalosis?

pH < 7.35 = acidosis, pH > 7.45 = alkalosis

you may have to revise that later, but start with this

“overcompensation” does not occur


Metabolic or respiratory
Metabolic or respiratory?

2a. Is it metabolic acidosis (alkalosis)?

Look at [HCO3-];  metabolic alkalosis,  metabolic acidosis

e.g. pH 7.25, [HCO3-] 14 mEq/L = Yes; metabolic acidosis

e.g. pH 7.25, [HCO3-] 32 mEq/L = No; not metabolic acidosis

2b. Is it respiratory acidosis (alkalosis)?

Look at Pa.CO2;  respiratory acidosis,  respiratory alkalosis

e.g. pH 7.25, Pa.CO2 64 mm Hg = Yes; respiratory acidosis

e.g. pH 7.25, Pa.CO2 26 mm Hg = No; not respiratory acidosis


Respiratory compensation
Respiratory compensation

3. Respiratory compensation (metabolic disorders)

Mechanism:

pH or pH detected by carotid body & aortic arch chemoreceptors,

ventilation rate  Pa.CO2;  ventilation rate  Pa.CO2

Features:

rapid response (minutes); no response suggests respiratory disorder

relatively inadequate because  Pa.CO2 limits response

i.e. metabolic acidosis AVR  Pa.CO2 AVR

Pa.CO2 > 55 mm Hg is respiratory acidosis (too high for compensation)


Metabolic compensation
Metabolic compensation

3. Metabolic compensation (respiratory disorders)

Mechanism:

 Pa.CO2 or  Pa.CO2 causes  or  H+ secretion & HCO3- reabsorption

Features:

buffering is not compensation

[HCO3-] will  by ~1 mEq/L for each 10 mm Hg Pa.CO2 (buffering)

slow response

~ 24 hrs for [HCO3-] (excretion)

days for [HCO3-] (induction of glutaminase II)

very effective (eventually)


Terminology compensation vs mixed condition
Terminology (compensation vs. mixed condition)

pH 7.30, [HCO3-] 14 mEq/L, Pa.CO2 29 mm Hg

is compensated metabolic acidosis, not (mixed) metabolic acidosis and respiratory alkalosis

pH 7.34, [HCO3-] 32 mEq/L, Pa.CO2 62 mm Hg

is compensated respiratory acidosis, not (mixed) respiratory acidosis and metabolic alkalosis

Compensation will disappear when the primary condition is treated; a mixed condition won’t



Anion gap why does it change
Anion gap; why does it change?

The “gap” is [measured cations] - [measured anions]


Significance of the anion gap
Significance of the anion gap

Used for differential diagnosis of metabolic acidosis

Hyperchloremic metabolic acidosis (normal anion gap)

occurs when disorder is HCO3- loss,

e.g. diarrhea, renal tubular acidosis, carbonic anhydrase inhibitors, Addison’s disease

Normochloremic metabolic acidosis (increased anion gap)

occurs when “non HCl” acids accumulate

e.g. lactic acidosis, ketoacidosis, salicylate, methanol (formate), ethylene glycol (glycolate, oxalate), chronic renal failure (sulfate, phosphate, others)


Causes of respiratory acid base disorders
Causes of respiratory acid base disorders

Respiratory acidosis:

opiates, sleep apnea, administration of O2 to a “blue bloater” type of COPD, weakness of respiratory muscles, extreme obesity, pulmonary edema, asthma, pneumonia, pneumothorax

Respiratory alkalosis:

several respiratory diseases (pneumonia, interstitial fibrosis, pulmonary embolus), hyperventilation, liver failure, salicylate overdose, gram negative septicemia, mechanical ventilation


Causes of metabolic acid base disorders
Causes of metabolic acid base disorders

Metabolic acidosis (hyperchloremic, normal anion gap):

diarrhea, carbonic anhydrase inhibitors, aldosterone deficiency, types I & II renal tubular acidosis

Metabolic acidosis (normochloremic, increased anion gap):

diabetic ketoacidosis, lactic acidosis, chronic renal failure, various poisonings (salicylate, methanol, ethylene glycol)

Metabolic alkalosis:

antacid ingestion, vomiting, nasogastric suction, loop or thiazide diuretics, aldosterone excess, vascular volume depletion, potassium depletion


Case f1 acid base condition
Case F1: acid base condition

pH 7.58; Pa.CO2 23 mm Hg; [HCO3-] 21 mEq/L

1. Look at pH (is it acidosis or alkalosis?)

pH = 7.58  alkalosis

2. Look at HCO3- (is it metabolic alkalosis?)

HCO3- = 21 mEq/L (normal 22-30)  not metabolic alkalosis

3. Look at Pa.CO2 (is it respiratory alkalosis?)

Pa.CO2 = 23 mmHg (normal 35-45)  respiratory alkalosis

  • See if appropriate compensation has occurred:

compensation for respiratory alkalosis is HCO3- excretion

HCO3- = 21 mmHg (normal 22-30)

 uncompensated i.e. acute respiratory alkalosis


Case f1 questions
Case F1: questions

Describe her acid base condition

acute respiratory alkalosis

Plausible causes for her acid base condition?

hysterical hyperventilation

Suggest causes of her dizziness

 Pa.CO2 cerebral vasoconstriction

Any evidence for ventilation/perfusion mismatch in pulmonary function?

A-a O2 difference = 123-116 = 7 (i.e. OK)

What is carpopedal spasm, and its possible cause?

pH Ca++ binding to albumin  free [Ca++]  more negative threshold for muscle cell depolarization (Na+ channel sensitivity)  hypocalcemic tetany


Case f2 acid base condition
Case F2: acid base condition

pH 7.29; Pa.CO2 26 mm Hg; [HCO3-] 12 mEq/L

1. Look at pH (is it acidosis or alkalosis?)

pH = 7.29  acidosis

2. Look at HCO3- (is it metabolic acidosis?)

HCO3- = 12 mEq/L (normal 22-30)  metabolic acidosis

3. Look at Pa.CO2 (is it respiratory acidosis?)

Pa.CO2 = 26 mmHg (normal 35-45)  not resp. acidosis

  • See if appropriate compensation has occurred:

compensation for metabolic acidosis is hyperventilation

Pa.CO2 = 26 mmHg (normal 35-45); partial compensation

5. Anion gap = 142 - (100 + 12) = 30 (increased)

i.e. partially compensated normochloremic metabolic acidosis


Case f2 questions
Case F2: questions

Total CO2 (CO2 content)?

CO2 released when venous plasma is acidified

equals [HCO3-] + 0.03 x P.CO2 (units mEq/L)

Describe his acid base condition

partially compensated normochloremic metabolic acidosis (increased anion gap)

Plausible causes for his acid base condition?

normochloremic metabolic acidosis

diabetic ketoacidosis: [glucose] 650 mg/dL

alcoholic ketoacidosis: starvation, GNG, lipolysis

lactic acidosis:  bp  hypoperfusion

Anion gap?

ketoacids (diabetes, alcohol), lactate (shock, hypoxemia)


Case f2 questions1
Case F2: questions

What precautions with his therapy?

Aims:volume repletion, insulin, pH correction

HCO3-, insulin &  osmolality causes K+ to enter cells (next slide)

give supplemental intravenous K+


Regulation of k distribution
Regulation of K+ distribution

Normally, 98% of total body K+ is intracellular


Case f3 acid base condition
Case F3: acid base condition

pH 7.05; Pa.CO2 45 mm Hg; [HCO3-] 12 mEq/L

1. Look at pH (is it acidosis or alkalosis?)

pH = 7.05  acidosis

2. Look at HCO3- (is it metabolic acidosis?)

HCO3- = 12 mEq/L (normal 22-30)  metabolic acidosis

3. Look at Pa.CO2 (is it respiratory acidosis?)

Pa.CO2 = 45 mmHg (normal 35-45)  poss. resp. acidosis

  • See if appropriate compensation has occurred:

compensation for metabolic acidosis is hyperventilation

Pa.CO2 = 45 mmHg (normal 35-45) respiratory acidosis

5. Anion gap = 140 - (116 + 12) = 12 (unchanged)

i.e. mixed hyperchloremic metabolic acidosis (normal anion gap) and respiratory acidosis


Case f3 questions 1
Case F3: questions 1

Describe her original acid base condition

mixed hyperchloremic metabolic acidosis and respiratory acidosis

Plausible causes for her acid base conditions

hyperchloremic metabolic acidosis

possibilities include: diarrhea, carbonic anhydrase (CA) inhibitors, aldosterone deficiency, & renal tubular acidosis (types I & II)

aldosterone deficiency would have  [K+], hers is 1.4 mEq/L;

history rules out diarrhea, CA inhibitors,

 RTA, urine pH 7.0  type 1

respiratory acidosis:

hypokalemia (1.4 mEq/L) decreases excitability of diaphragm


Renal tubular acidosis
Renal tubular acidosis

In general:

proximal/thick ascending limb Na+/H+ exchager function is to destroy (& reabsorb) filtered HCO3-

 intercalated H+ ATPase is to acidify urine  urinary NH4+ & titratable acidity thus synthesizing new HCO3-

Proximal RTA (type 2)

 activity of proximal/thick AL Na+/H+ exchanger

 serum [HCO3-] proximal HCO3- load;  serum [HCO3-] stabilizes

collecting duct H+ ATPase can acidify urine & synthesize “new” HCO3-

urine pH within normal range

Distal RTA (type 1)

 activity of collecting duct H+ ATPase,or back diffusion of H+

inability of synthesize “new” HCO3- by acidifying urine

progressive depletion of serum [HCO3-]

urine pH at alkaline end of range although  body pH


Case f3 questions 2
Case F3: questions 2

Urine pH towards alkaline end of range (pH 4.5-7.5)?

type 1 RTA is failure of collecting duct H+ secretion

(acidifying region; generating new HCO3-)

Increased [HCO3-] in emergency room ( = +13 mEq/L)?

buffering (1 mEq/L per 10 mm Hg Pa.CO2);

 Pa.CO2 = +94 mm Hg, i.e. ~10 mEq/L  [HCO3-]

Role of hypokalemia?

hyperpolarization  muscle weakness (diaphragm)


Case f3 questions 3
Case F3: questions 3

Cause of hypokalemia (1.4 mEq/L)?

“Holy Grail” of collecting duct function (Na+ for K+ and/or H+) next slide

Urinary NH4+ & titratable acidity?

failure to acidify urine & synthesize “new” HCO3-

Kroger’s chemical?

daily NaHCO3 (baking soda) would work

she was given polycitra-K (K citrate & citric acid)

citrate metabolized as citric acid, removing H+

then, OH- + CO2 HCO3-



Case f4 acid base condition
Case F4: acid base condition

pH 7.44; Pa.CO2 65 mm Hg: [HCO3-] 43 mEq/L

1. Look at pH (is it acidosis or alkalosis?)

pH = 7.44 it’s close, but on alkalotic side of normal

2. Look at HCO3- (is it metabolic alkalosis?)

HCO3- = 43 mEq/L (normal 22-30)  metabolic alkalosis

3. Look at Pa.CO2 (is it respiratory alkalosis?)

Pa.CO2 = 65 mmHg (normal 35-45)  not resp. alkalosis

  • See if appropriate compensation has occurred:

compensation for metabolic alkalosis would be

hypoventilation  Pa.CO2

yes, but Pa.CO2 too high for compensation

 respiratory acidosis

i.e. mixed metabolic alkalosis and respiratory acidosis


Case f4 questions
Case F4: questions

Describe his acid base condition

mixed metabolic alkalosis and respiratory acidosis

Plausible causes for his acid base condition?

metabolic alkalosis: diuretic excess, mild hypokalemia

respiratory acidosis: COPD with hypoventilation (CO2 insensitivity; “blue bloater”)

Ventilation perfusion mismatch?

A-a O2 difference = 71-45 = 26 mm Hg (not bad for age 56 & COPD); hypoventilation & V/Q mismatch  hypoxemia

Cause of mild hypokalemia (3.1 mEq/L)?

furosemide is K+ wasting diuretic

Treatment with 100% O2?

hypercapnia; removal of O2 drive


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