9. TYPES OF ACID-BASE DISTURBANCES
Depression of the central
nervous system, as evidenced
by disorientation followed by
coma
Excitability of the nervous
system; muscles may go
into a state of tetany and
convulsions
17. Hypokalemia Metabolic alkalosis
• Hypokalemia results in the shift of hydrogen ions
intracellularly. The resulting intracellular acidosis enhances
bicarbonate re-absorption in the collecting duct
• Hypokalemia stimulates the apical H+/K+ ATPase in the
collecting duct
• Hypokalemia stimulates renal ammonia genesis and alpha-
ketoglutarate is produced, the metabolism of which
generates bicarbonate that is returned to the systemic
circulation
• It leads to impaired chloride ion re-absorption in the distal
nephron. This results in an increase in luminal electro-
negativity, with subsequent enhancement of hydrogen ion
secretion
20. Competitive affinity for MR
Cortisol >> Aldosterone > cortisone
E Na C
ROMK
Na K ATP ase
Depolarize
Na
K
H
Aldosterone
MR: Mineralocorticoid receptor
21.
22. Gastrointestinal H+ loss
Vomiting or NG suction
Antacids in advanced renal failure
Renal H+ loss
Primary mineralocorticoid excess
Post-hypercapnic alkalosis
Hypercalcemia (milk-alkali syndrome)
Intracellular shift of H+
Hypokalemia / Hypomagnesemia
Alkali administration
Excess CPR (Ringer lactate)
Excess transfusion(citrate blood)
Contraction alkalosis (Loss of bicarbonate-poor, chloride-rich extracellular fluid)
Loop or thiazide diuretics
Bartter or Gitelman syndrome
Sweat loss in cystic fibrosis
Villous adenoma(Chronic chloride diarrhea )or factitious diarrhea(Laxative abuse)
∆HCO3- < 2~4 meq/L
23. ROMK - intracellular magnesium
Huang et al: JASN 2007 (University of Texas Medical Center)
• CCT
E Na C
ROMK
Na K ATP ase
UK 5mM CK 143mM
Na
K
Mg
24. Hypokalemia in magnesium deficiency
Huang et al: JASN 2007 (University of Texas Medical Center)
• CCT
E Na C
ROMK
Na K ATP ase
Urine Blood
Na
K
25. Gastrointestinal H+ loss
Vomiting or NG suction
Antacids in advanced renal failure
Renal H+ loss
Primary mineralocorticoid excess
Post-hypercapnic alkalosis
Hypercalcemia (milk-alkali syndrome)
Intracellular shift of H+
Hypokalemia / Hypomagnesemia
Alkali administration
Excess CPR (Ringer lactate)
Excess transfusion(citrate blood)
Contraction alkalosis
(Loss of bicarbonate-poor, chloride-rich extracellular fluid)
Loop or thiazide diuretics
Bartter or Gitelman syndrome
Sweat loss in cystic fibrosis
Chronic chloride diarrhea (AR)
∆HCO3- < 2~4 meq/L
26. Chloride depletion, even without volume
depletion, enhances bicarbonate re-absorption
• In the late thick ascending limb (THAL) and early
distal tubule, specialized cells called the macula
densa are present
• Na+/K+/2Cl- cotransporter in the apical membrane,
which is mainly regulated by chloride ions
• When fewer chloride ions reach this transporter
(eg, chloride depletion), the macula densa signals
the juxtaglomerular apparatus (ie, specialized
cells in the wall of the adjacent afferent arteriole) to
secrete renin, which increases aldosterone
secretion via angiotensin II ( ↑RAA ).
29. Bartter’s syndrome in THAL
NKCC
ROMK
Na K ATP ase
Na/K
K
2Cl
CaSR
Negative
Positive
ClC-Kb
ClC-KB
30. Variants of Bartter’s syndrome
Israel Zelikovic, NDT 18: 1696-1700, 2003
Defective
transporter/protein
Clinical Locus
Type I NKCC2 (TAL) Antenatal 15q
Type II ROMK (TAL/CD) Antenatal 11q
Type III ClC-Kb (TAL,DCT) Classic 1p36
Type IV Barttin (β of CIC-
Ka/CIC-Kb)
BSND
(Deafness)
1p31
AD
Hypercalciuria
CaSR
(PT/TAL/DCT/CD)
Hypocalcemia 3q
37. 11-beta-hydroxysteroid dehydrogenase type 2
(11β-HSD2): cortisolcortisone
allow Aldosterone free access to MR in CCD
E Na C
ROMK
Na K ATP ase
Depolarize
Na
K
H
Aldosterone
MR: Mineralocorticoid receptor
38. 11-beta-hydroxysteroid dehydrogenase
type 2 (11B-HSD2) deficiency
• AR
• Syndrome of apparent mineralocorticoid excess
(AME)
• Hypertension with low renin and low aldosterone,
hypokalemia, and metabolic alkalosis
• Serum cortisol is within the reference range
because the negative feedback of cortisol on
adrenocorticotropic hormone (ACTH) is intact.
• The enzyme may be inhibited by glycyrrhizic acid,
which is found in licorice and chewing tobacco, or
carbenoxolone, which is a synthetic derivative of
glycyrrhizinic acid
44. General Principles of Treatment
↑ Renal bicarbonate excretion ( urine pH>7 )
A reduced effective arterial blood volume (EABV)
Chloride depletion (hypochloremia)
Potassium depletion (hypokalemia) K supply
All exogenous sources of alkali should be
discontinued: Citrate/Ketones/Lactate
Drugs that reduce gastric HCl secretion.
H2 blockers
PPI
NS
45. General Principles of Treatment
Acetazolamide(250-500mg/D) is a carbonic
anhydrase inhibitor that preferentially
inhibits proximal sodium bicarbonate
reabsorption
Potassium-sparing diuretics
NH4Cl ( 100 meq/L/ 20 mL vial)
1-2 vials in 1000 mL of NS