ACIDOSIS TUBULAR RENAL : UNA ENTIDAD CLINICA

CASO INTERESANTE JUNIO 2015

Dra. Carmen Guadalupe Melara Dr. Roberto Armando Ticas

IDENTIFICACIÓN

Nombre: D.E.R.M

Edad: 24 años

Sexo: masculino

Domicilio: Ciudad Delgado

Ocupación: Mecánico

Fecha de ingreso: 08 de junio de 2015.

Cx: “ el control”

P a c i e n t e y a c o n o c i d o c o n e l diagnóstico de nefropatía perdedora de sales; que este día asiste a su control en la consulta externa, con exámenes, donde encuentran potasio sérico de 2.38 mEq/L. Al momento se encuentra asintomático, no calambres.

Antecedentes personales:

Nefropatía perdedora de sal desde

mayo de 2015, en controles en este

centro.

No otro antecedente medico.

Apendectomía en 2006 en este centro.

Etilísta ocasional.

No tabaquista

No alergias

EXAMEN FÍSICO Signos vitales: TA: 120/70 mmHg FC: 84 X´ FR: 16 X´ T˚: 37 ˚C

Apariencia general:

Paciente masculino en la tercera

década de la vida, eupneico,

alerta, orientado en las 3 esferas,

colaborador.

Cabeza: normocráneo.

Ojos: pupilas isocóricas, reactivas a la luz

y no a la acomodación. Fondo de ojo no

realizado.

Oídos: conducto auditivo externo

permeable.

Nariz: fosas nasales permebles, no aleteo

nasal.

Boca: mucosas húmedas y de aspecto

sano.

Cuello: simetrico, no adenopatías.

Tórax: simétrico, no uso de músculos

accesorios, no tirajes. Expansión costal

simétrica, frémito táctil presente y normal.

Se percute resonancia, murmullo vesicular

normal. Cardíaco: ritmo regular, no soplos.

Abdomen: plano, blando y depresible;

peristaltismo presente y normal. No

visceromegalia, no masa, no dolor a la

palpación.

Extremidades: normotónicas,

normotroficas. Pulsos perifericos

presentes y normales.

Neurologico: alerta, orientado en las 3

esferas. Fuerza 5/5, ROT 2/4, sensibilidad

4/4. pares craneales sin alteraciones.

Impresión diagnóstica:

•  Nefropatía perdedora de sal.

•  Hipokalemia etiologìa?

Examen general de orina 10/06/2015 Aspecto Limpio Color Amarillo Densidad 1010 pH 7 Esterasa leucocitaria Neg Nitritos Neg Leucocitos 0-2 Hematies 0-2 Bacterias No se observa Sodio en orina 118 Potasio en orina 26

08/06/2015 09/06/2015 10/06/2015 11/06/2015 Glucosa 85 mg/dl 89 mg/dl

87 mg/dl

Creatinina 1.42 mg/dl 1.38 mg/dl

1.39 mg/dl

1.61 mg/dl

Nitrogeno ureico

18.69 mg/dl

17.96 mg/dl

19.04 mg/dl

21.64 mg/dl

Sodio 138.5 mEq/L 140.17 mEq/L

140.67 mEq/L

135.15 mEq/L

Potasio 2.38 mEq/L 2.91 mEq/L 3.61 mEq/L 3.01 mEq/L Cloro 103.45 mEq/

L 98.12 mEq/L

Magnesio 1.07 mEq/L Depuracion creatinina

71 ml/min

INTERCONSULTA NEFROLOGÍA

10/06/2015

Se presenta caso a Dr. Ticas, quien refiere se

puede tratarse de una acidosis tubular renal

( I o II). Paciente con acidosis metabólica ,

pH urinario >7, hipokalemia. Aniòn Gap?

Plan: furosemida 80 mg vo #1, luego evaluar

pH urinario en 1 hora.

11/06/2015

Se realiza interconsulta continuada con

nefrología, quien re-evalúa a paciente y

manifiesta que dado que el pH urinario del

paciente posterior a la administración de

80 mg de furosemida, fue de 8, se trata de

una acidosis tubular renal tipo I. se

recomienda agregar triamterene 100 mg vo

c/12 horas y que se deje cita con Dr. Ticas

el 19/06/2015 en el servicio de Medicina

Interna con electròlitos séricos y urinarios.

OBJECTIVES Physiology of Renal acidification.

Types of RTA and characteristics

Lab diagnosis of RTA

Approach to a patient with RTA

Treatment

The term renal tubular acidosis (RTA) is applied to a group of transport defects in the reabsorption of bicarbonate (HCO3−), the excretion of hydrogen ion (H+), or both

The renal acid-base homeostasis may be broadly divided into two processes: (1) reabsorption of filtered HCO3−, which occurs

fundamentally in the proximal convoluted tubule; and

(2) excretion of fixed acids through the titration of urinary buffers and the excretion of ammonium, which takes place primarily in the distal nephron.

Distal Urinary Acidification Urinary acidification takes place in the distal nephron by three related processes: (1)  reclamation of the small fraction of filtered HCO3−

that escapes reabsorption proximally (10 to 20%); (2)  titration of divalent basic phosphate (HPO4=), which

is converted to the monovalent acid form (H2PO4−) or titrable acid; and

(3) accumulation of ammonia (NH3) intraluminally, which buffers H+ to form nondiffusible ammonium (NH4+).

DISTAL URINARY ACIDIFICATION

The thick ascending limb of Henle’s loop reabsorbs about 15% of the filtered HCO3- load by a mechanism similar to that present in the proximal tubule, i.e., through Na+-H+ apical exchange(NHE3).

H+ SECRETION The collecting tubule (CT) is the major site of H+ secretion and is made up of the medullary collecting duct (MCT) and the cortical collecting duct (CCT).

Alpha and Beta-intercalated cells make up 40% of the lining while Principal cells and collecting tubule cells make up the remainder.

Alpha-Intercalated Cells are thought to be the main cells involved with H+ secretion in the CT.

This is accomplished by an apically placed H+-K+-ATPase and H+-ATPase with a basolateral Cl-/HCO3

- exchanger and the usual basolateral Na+ - K+ ATPase.

Beta-Intercalated Cells in contrast to the above have a luminal Cl-/HCO3

- exchanger and a basolateral H+-ATPase.

They play a role in bicarbonate secretion into the lumen that is later reabsorbed by the CA IV rich luminal membrane of medullary collecting duct.

ALDOSTERONE AND RENAL ACIDIFICATION

Favors H+ and K+ secretion through enhanced sodium transport. Recruits more amiloride sensitive sodium channels in the luminal membrane of the collecting tubule. Enhances H+-ATPase activity in cortical and medullary collecting tubules. Aldosterone also has an effect on NH4+ excretion by increasing NH3 synthesis

TYPES OF RTA

Proximal RTA (type 2) Isolated bicarbonate defect

Fanconi syndrome

Distal RTA (type 1) Classic type

Hyperkalemic distal RTA Hyperkalemic RTA (Type 4)

PROXIMAL RTA Proximal RTA (pRTA) is a disorder leading to HCMA secondary to impaired proximal reabsorption of filtered bicarbonate. Since the proximal tubule is responsible for the reabsorption of 85-90% of filtered HCO3

- a defect at this site leads to delivery of large amounts of bicarbonate to the distal tubule.

.

Isolated defects in PCT function are rarely found. Most patients with a pRTA will have multiple defects in PCT function with subsequent Fanconi Syndrome.

The most common causes of Fanconi syndrome in adults are multiple myeloma and use of acetazolamide. In children, cystinosis is the most common.

pRTA is a self limiting disorder and fall of serum HCO3_ below 12 meq/l is unusual, as the distal acidification mechanisms are intact.. Urine ph become remains acidic(<5.5) mostly but becomes alkaline when bicarbonate losses are corrected. F E H C O 3 i n c r e a s e s ( > 1 5 % ) w i t h administration of alkali for correction of acidosis

CAUSE OF HYOKALEMIA IN TYPE 2 RTA

Ø Metabolic acidosis in and of itself decreases pRT Na+ reabsorption leading to increased distal tubule delivery of Na+ which promotes K+ secretion. Ø The pRTA defect almost inevitably leads to salt wasting, volume depletion and secondary hyperaldosteronism. Ø The rate of kaliuresis is proportional to distal bicarbonate delivery. Because of this alkali therapy tends to exaggerate the hypokalemia.

Pat ien t s w i th pRTA rare ly deve lop nehrosclerosis or nephrolithiasis. This is thought to be secondary to high citrate excretion.

In children, the hypocalcemia as well as the HCMA will lead to growth retardation, rickets, osteomalacia and an abnormal vitamin D metabolism. In adults osteopenia is generally seen.

DISTAL RTA

Distal RTA (dRTA) is a disorder leading to HCMA secondary to impaired distal H+ secretion. It is characterized by inability to lower urine ph maximally(<5.5) under the stimulus of systemic acidemia. The serum HCO3- levels are very low <12 meq/l. It is often associated with hypercalciuria, h y p o c i t r a t u r i a , n e p h r o c a l c i n o s i s , a n d osteomalacia.

The term incomplete distal RTA has been proposed to describe patients with nephrolithiasis but without metabolic acidosis.

Hypocitraturia is the usual underlying cause.

NON SECRETORY DEFECTS CAUSING DISTAL RTA

Gradient defect: backleak of secreted H+ ions. Ex. Amphotericin B

Voltage dependent defect: impaired distal sodium transport ex. Obstructive uropathy, sickle cell disease, CAH, Lithium and amiloride etc.

This form of distal RTA is associated with hyperkalemia(Hyperkalemic distal RTA)

The most common causes in adults are autoimmune disorders, such as Sjögren's syndrome, and other conditions associated with chronic hyperglobulinemia.

In children, type 1 RTA is most often a primary, hereditary condition.

SECRETORY DEFECTS CAUSING DISTAL RTA

A high urinary pH (5.5) is found in the majority of patients with a secretory dRTA. Excretion of ammonium is low as a result of less NH4

+trapping. This leads to a positive urine anion gap. Urine PCO2 does not increase normally after a bicarbonate load reflecting decreased distal hydrogen ion secretion. Serum potassium is reduced in 50% of patients. This is thought to be from increased kaliuresis to offset decreased H+ and H-K-ATPase activity.

LAB DIAGNOSIS OF RTA

RTA should be suspected when metabolic acidosis is accompanied by hyperchloremia and a normal plasma anion gap (Na+ - [Cl- + HCO3-] = 8 to 16 mmol/L) in a patient without evidence of gastrointestinal HCO3- l o s s e s a n d w h o i s n o t t a k i n g acetazolamide or ingesting exogenous acid.

FUNCTIONAL EVALUATION OF PROXIMAL BICARBONATE ABSORPTION

Fractional excretion of bicarbonate Urine ph monitoring during IV administration of sodium bicarbonate.

FEHCO3 is increased in proximal RTA >15% and is low in other forms of RTA.

FUNCTIONAL EVALUATION OF DISTAL URINARY ACIDIFICATION AND POTASSIUM SECRETION

Urine ph

Urine anion gap

Urine osmolal gap

Urine Pco2

TTKG

Urinary citrate

URINE PH

In humans, the minimum urine pH that can be achieved is 4.5 to 5.0. Ideally urine ph should be measured in a fresh morning urine sample. A low urine ph does not ensure normal distal acidification and vice versa. The urine pH must always be evaluated in conjunction with the urinary NH4+ content to assess the distal acidification process adequately . Urine sodium should be known and urine should not be infected.

URINE ANION GAP

Urine AG = Urine (Na + K - Cl). The urine AG has a negative value in most patients with a normal AG metabolic acidosis.

Patients with renal failure, type 1 (distal) renal tubular acidosis (RTA), or hypoaldosteronism (type 4 RTA) are unable to excrete ammonium normally. As a result, the urine AG will have a positive value.

URINE OSMOLAL GAP

When the urine AG is positive and it is unclear whether increased excretion of unmeasured anions is responsible, the urine ammonium concentration can be estimated from calculation of the urine osmolal gap. UOG=Uosm - 2 x ([Na + K]) + [urea nitrogen]/2.8 + [glucose]/18.

UOG of >100 represents intact NH4 secretion.

URINE PCO2

Measure of distal acid secretion. In pRTA, unabsorbed HCO3 reacts with secreted H+ ions to form H2CO3 that dissociate slowly to form CO2 in MCT. Urine-to-blood pCO2 is <20 in pRTA. Urine-to-blood pCO2 is >20 in distal RTA reflecting impaired ammonium secretion.

TTKG

TTKG is a concentration gradient between the tubular fluid at the end of the cortical collecting tubule and the plasma. TTKG = [Urine K ÷ (Urine osmolality / Plasma osmolality)] ÷ Plasma K. Normal value is 8 and above. Value <7 in a hyperkalemic patient indicates hypoaldosteronism. This formula is relatively accurate as long as the urine osmolality exceeds that of the plasma urine sodium concentration is above 25 meq/L

URINE CITRATE

The proximal tubule reabsorbs most (70-90%) of the filtered citrate. Acid-base status plays the most significant role in citrate excretion. Alkalosis enhances citrate excretion, while acidosis decreases it. Citrate excretion is impaired by acidosis, hypokalemia,high–animal protein diet and UTI.

TREATMENT

Proximal RTA A mixture of Na+ and K+ salts, preferably citrate, is preferable.

10 to 15 meq of alkali/kg may be required per day to stay ahead of urinary losses.

Thiazide diuretic may be beneficial if large doses of alkali are ineffective or not well tolerated.

Bicarbonate wasting is negligible in adults who can generally be treated with 1 to 2 meq/kg of sodium citrate (Bicitra) or bicarbonate.

Potassium citrate, alone or with sodium citrate (Polycitra), is indicated for persistent hypokalemia or for calcium stone disease.

For patients with hyperkalemic distal RTA, high-sodium, low-potassium diet plus a thiazide or loop diuretic if necessary.

Distal RTA