renal tubular acidosis and other causes of normal anion gap metabolic acidosis
TRANSCRIPT
![Page 1: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/1.jpg)
By Dr. Jagjit Khosla
RENAL TUBULAR ACIDOSIS
By Jagjit Khosla
Approach to a patient with Normal Anion Gap Metabolic Acidosis
![Page 2: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/2.jpg)
By Dr. Jagjit Khosla
METABOLIC ACIDOSIS
Definition- Blood pH <7.35 (Acidemia) - [HCO3
-]
- [PaCO2] (1.2 mm Hg fall in [PaCO2] for every 1 meq/L reduction in [HCO3
-])
![Page 3: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/3.jpg)
By Dr. Jagjit Khosla
TYPES OF METABOLIC ACIDOSIS
Metabolic Acidosis
High Anion Gap Normal Anion Gap
![Page 4: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/4.jpg)
By Dr. Jagjit Khosla
ANION GAP
![Page 5: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/5.jpg)
By Dr. Jagjit Khosla
ANION GAPNa+ + Unmeasured cations = Cl- + HCO3
- + Unmeasured anionsOr, Unmeasured anions – Unmeasured cations = Na+ - (Cl- + HCO3
-)
Anion Gap = Na+ - (Cl- + HCO3-)
DefinitionAnion gap is Quantity of anions not balanced by cations- usually due to the NEGATIVELY CHARGED PLASMA PROTEINS as the charges of the other unmeasured cations and anions tend to balance out.
Na
Cl HCO3 UnNormal Anion Gap (10 – 12 mM/L)
Note : - Adjust for Hypoalbuminemia
![Page 6: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/6.jpg)
By Dr. Jagjit Khosla
ANION GAPIf an acid is added to blood
Anion H+ Na+ HCO3-+
Na
Cl HCO3 UnHCO3
![Page 7: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/7.jpg)
By Dr. Jagjit Khosla
ANION GAP
Na
Cl UnHCO3
Cl- Other Anion
Normal Anion gap Metabolic Acidosis(Hyperchloremic)
High Anion gap Metabolic Acidosis
![Page 8: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/8.jpg)
By Dr. Jagjit Khosla
NORMAL ANION GAP METABOLIC ACIDOSIS
![Page 9: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/9.jpg)
By Dr. Jagjit Khosla
NORMAL AG METABOLIC ACIDOSIS
Normal Anion Gap Metabolic
Acidosis
(+) Urine Anion Gap (-) Urine Anion Gap
![Page 10: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/10.jpg)
By Dr. Jagjit Khosla
Cl
URINE ANION GAPUNa+ + UK+ + Unmeasured cations = UCl- + Unmeasured anions
Or, Unmeasured anions – Unmeasured cations = (UNa+ + UK+) - UCl-
Urine Anion Gap (UAG) = (UNa+ + UK+) - UCl-
- NH4+ is the primary unmeasured cation which is not balanced by anions.
- UAG as indirect assay for renal NH4+ excretion
Na K NH4+
![Page 11: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/11.jpg)
By Dr. Jagjit Khosla
URINE ANION GAP
Negative Positive
Increased renal NH4+ excretion
(Response to acidemia)
Failure of Kidneys to secrete NH4
+
![Page 12: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/12.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
GI loss of HCO3IngestionDilutional
Post hypocapnia
1234
Type II RTA5
![Page 13: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/13.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
GI loss of HCO31- Diarrhoea- Intestinal or pancreatic fistula- Ureteral diversion- Villous adenoma
![Page 14: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/14.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
GI loss of HCO31Pancreas
Ileum
Colon
Pancreas
Ileum
Colon
HCO3-
HCO3-
Cl-
HCO3-
Cl-
K+ HCO3-
Normal Diarrhea
Cl-
Flooding the colon with HCO3-
instead of Cl- drives K+ secretion
![Page 15: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/15.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
Cl-
Urea
Ureter
HCO3-
NH4+
Sigmoid ColonUrea-splitting organisms
![Page 16: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/16.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
GI loss of HCO3Ingestion
12
- Acetazolamide- Sevelamer- Cholestyramine- Toluene
![Page 17: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/17.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
GI loss of HCO3IngestionDilutional
123
- Due to rapid infusion of bicarbonate-free iv fluids
![Page 18: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/18.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
GI loss of HCO3IngestionDilutional
Post hypocapnia
1234
- Rapid correction of respiratory alkalosis by renal wasting of HCO3
- leading to transient acidosis
![Page 19: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/19.jpg)
By Dr. Jagjit Khosla
NEGATIVE UAG - CAUSES
GI loss of HCO3IngestionDilutional
Post hypocapnia
1234
Type II RTA5
![Page 20: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/20.jpg)
By Dr. Jagjit Khosla
POSITIVE UAG - CAUSES
Type I RTAType IV RTA
12
![Page 21: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/21.jpg)
By Dr. Jagjit Khosla
RENAL TUBULAR ACIDOSIS
![Page 22: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/22.jpg)
By Dr. Jagjit Khosla
RENAL TUBULAR ACIDOSIS
DefinitionDisorders affecting the overall ability of the renal tubules either to secrete hydrogen ions or to retain bicarbonate ions
Types- Type I (Distal)- Type II (Proximal)- Type IV (Hypoaldosteronism)
![Page 23: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/23.jpg)
By Dr. Jagjit Khosla
RENAL ACID-BASE HOMEOSTASIS
- Proximal Acidification Reabsorption of HCO3
- in Proximal tubule
- Distal Acidification H+ secretion in Collecting tubule
Type II RTA
Type I & Type IV RTA
![Page 24: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/24.jpg)
By Dr. Jagjit Khosla
PROXIMAL ACIDIFICATIONProximal Tubule Cell Tubular Lumen
Na+
H+
H20 CO2
3HCO3-
Na+
CA II
3Na+
2K+
Na+K+ ATPase
H+ HCO3-+
H2CO3
CO2 H2O+
Carbonic Anhydrase IV
+
H+HCO3- +
H2CO3
Na+H+ Exchanger
Na+ HCO3-
Cotransporter
Na+
Blood
![Page 25: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/25.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTAProximal Tubule Cell Tubular Lumen
Na+
H+
H20 CO2
3HCO3-
Na+
CA II
3Na+
2K+ H+ HCO3-+
H2CO3
CO2 H2O+
Carbonic Anhydrase IV
+
H+HCO3- +
H2CO3
Na+H+ Exchanger
Na+ HCO3-
Cotransporter
Na+
1
2
5
6
3
4
Na+K+ ATPase
Blood
![Page 26: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/26.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTA
• Fanconi’s syndrome - Loss of Glucose, Calcium, phosphate, citrate, uric acid, lysozymes, light chain immunoglobins, and amino acids.
• Isolated HCO3 wasting is rarely identified.
Isolated HCO3 wasting
Generalised Proximal tubular
dysfunction
![Page 27: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/27.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTA
Primary disorders• Idiopathic, sporadic• Familial disorders
– Cystinosis– Tyrosinemia– Hereditary fructose intolerance– Galactosemia– Glycogen storage disease(Type I)– Wilson’s disease– Lowe’s syndrome– Carbonic Anhydrase deficiency
Secondary disorders• Multiple myeloma• Drugs
– Tenofovir– Carbonic anhydrase inhibitors– Ifosfamide
• Amyloidosis• Heavy metals poisoning (Lead,
Cadmium, Hg, Cu)• Vitamin D deficiency• Renal transplantation• Paroxysmal nocturnal
hemoglobinuria
![Page 28: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/28.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTA
80% reabsorbed15% reabsorbed
5% excreted
HCO3
HCO3
HCO3
HCO3
100%
![Page 29: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/29.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTA
60% reabsorbed15% reabsorbed
25% excreted
HCO3
HCO3
HCO3
HCO3
100%
Decreased Proximal tubule reabsorption Cl-
K+
![Page 30: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/30.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTAFeatures• U. HCO3- (FeHCO3 > 15%)• U. pH <5.5, • S. [HCO3
-] 12-20• U. Na+
• U. K+ - HypokalemiaMechanism of enhanced K+ excretion- Increased distal Na+ delivery - Sodium wasting induced secondary hyperaldosteronism
![Page 31: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/31.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTAEffect on Potassium excretionWithout alkali therapy
Principal Cell LumenBlood
Na+
K+
Na+ Channel
K+ Channel
3Na+
2K+
Na+K+ ATPase
Na+
-+K+
Aldosterone
![Page 32: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/32.jpg)
By Dr. Jagjit Khosla
TYPE II (PROXIMAL) RTAEffect on Potassium excretionWith alkali therapy
Increased S. [HCO3-]
Increased filtered load above proximal reabsorptive capacity
Increased distal sodium and water delivery
Enhanced distal potassium excretion
Note : Alkali therapy in proximal RTA should be accompanied with potassium to prevent hypokalemia
![Page 33: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/33.jpg)
By Dr. Jagjit Khosla
DISTAL ACIDIFICATION
• Collecting tubule (CT) is the major site of H+ secretion
• Made up of : – Cortical Collecting tubule – H+ secretion coupled with Na+
reabsorption– Medullary Collecting tubule – H+ secretion independent of
Na+ reabsorption
• Alpha-intercalated cells are main cells involved in H+ secretion
![Page 34: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/34.jpg)
By Dr. Jagjit Khosla
DISTAL ACIDIFICATIONAlpha Intercalated cell Lumen
K+
H+
H2CO3
H20CO2 +
HCO3-
CA II
Cl-
H+
Blood
3Na+
2K+
Na+K+ ATPase
H+ ATPase
H+ K+ ATPase
H+
HPO42- NH3
H2PO4- NH4
+
Anion Exchanger
![Page 35: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/35.jpg)
By Dr. Jagjit Khosla
DISTAL ACIDIFICATION
Principal Cell LumenBlood
Na+
K+
Na+ Channel
K+ Channel
3Na+
2K+
Na+K+ ATPase
Na+
-+K+ H+
![Page 36: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/36.jpg)
By Dr. Jagjit Khosla
TYPE I (DISTAL) RTAAlpha Intercalated cell Lumen
K+
H+
H2CO3
H20CO2 +
HCO3-
CA II
Cl-
H+
Blood
3Na+
2K+
Na+K+ ATPase
H+ ATPase
H+ K+ ATPase
H+
HPO42- NH3
H2PO4- NH4
+
Anion Exchanger
1
23
![Page 37: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/37.jpg)
By Dr. Jagjit Khosla
TYPE I (DISTAL) RTA
Principal Cell LumenBlood
Na+
K+
Na+ Channel
K+ Channel
3Na+
2K+
Na+K+ ATPase
Na+
-+K+ H+
4
![Page 38: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/38.jpg)
By Dr. Jagjit Khosla
TYPE I (DISTAL) RTAMechanisms- Defective H+-K+ ATPase (Classic Hypokalemic dRTA)
- Defective H+ ATPase (Normokalemic dRTA)
- Gradient defect (Backleak of secreted H+ e.g. Amphotericin B)
- Voltage depended defect (Hyperkalemic dRTA)
- Abnormal Anion Exchange
![Page 39: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/39.jpg)
By Dr. Jagjit Khosla
TYPE I (DISTAL) RTAEtiology
Primary Idiopathic, Sporadic
Familial Autosomal dominant or recessive
Secondary Sjogren’s syndromeHypercalciuriaRheumatoid ArthritisHyperglobulinemiaIfosfamideAmphotericin BCirrhosisSLESickle Cell AnemiaObstructive UropathyLithiumRenal transplantation
![Page 40: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/40.jpg)
By Dr. Jagjit Khosla
TYPE IV RTAMechanisms- Reduced Aldosterone production
- Aldosterone resistance
![Page 41: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/41.jpg)
By Dr. Jagjit Khosla
TYPE IV RTAEtiology
Decreased aldosterone production
Hyporeninemic hypoaldosteronism- Renal disease, most often diabetic nephropathy- Nonsteroidal anti-inflammatory drugs- Calcineurin inhibitors- Volume expansion, as in acute glomerulonephritisMedications - ACE inhibitors, angiotensin II receptor blockers, and direct renin inhibitorsHeparinPrimary adrenal insufficiencySevere illnessInherited disordersCongenital isolated hypoaldosteronismPseudohypoaldosteronism type 2 (Gordon's syndrome)
![Page 42: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/42.jpg)
By Dr. Jagjit Khosla
TYPE IV RTAEtiology
Aldosterone resistance
Inhibition of the epithelial sodium channel- Potassium-sparing diuretics, such as spironolactone, eplerenone, amiloride, and triamterine- Antibiotics, trimethoprim and pentamidinePseudohypoaldosteronism type 1
![Page 43: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/43.jpg)
By Dr. Jagjit Khosla
![Page 44: Renal tubular acidosis and other causes of Normal anion gap Metabolic acidosis](https://reader035.vdocuments.site/reader035/viewer/2022081723/58e76dec1a28abd6068b4cbf/html5/thumbnails/44.jpg)
By Dr. Jagjit Khosla