Fisiología renal y

homeostasis
hidroelectrolítica
Jorge Sanhueza S., PhD
Introducción

• Homeostasis de electrolítos.

• Homeostásis de desechos metabólicos.

• Aclaramiento (clearence).

• Autorregulación.

• Hormonas: SRAA, EPO, Vit. D.

• Balance acido-base.

• Regulación de la presión arterial.

Bibliografía
in nephrology over the next 10 years.
Clinical course of AKI
The clinical course of AKI — including the
concepts of reversal (both the duration
of kidney dysfunction and the degree of
achieve a >26 µmol/l increase. Moreover,
a 60% increase in serum creatinine that
reverts to baseline 2 days later is staged in
Introducción
the same way as an equivalent increase that
has not yet returned to baseline on day 6.
This is problematic because an increase
without AKI (P < 0.01). Even stage 1 AKI
defined by oliguria alone (that is, >6 h but
<12 h of oliguria and no AKI by creatinine
criteria) was associated with an increased
risk of MAKEs at 6 months (odds ratio
1.76; 95% CI 1.20–2.57; P = 0.004), which

Cardiorenal Brain
syndrome • Altered haemodynamics • Uraemic encephalopathy
• Low cardiac output • Dementia (long term)
• Venous congestion • Stroke (long term)
• Neuro-hormonal activation
• Drugs and contrast media
• Inflammation and cytokine release Heart
• Congestive heart failure
Lung–kidney • Arrhythmia
interactions • Respiratory distress • Ischaemic heart disease
AKI
• Venous congestion
• Pulmonary hypertension
• Hypoxia and hypercapnia Lung
• Inflammation and cytokine release • Acute lung injury
• Altered capillary permeability • Pulmonary oedema
• Increased ventilatory drive

Hepatorenal • Splanchnic vasodilatation

syndrome • Increased abdominal pressure Liver
• Altered intestinal barrier Altered hepatic metabolism
• Inflammation and cytokine release and/or synthesis
• Decrease in circulating volume
• Altered microbiota
• Decreased blood pressure Intestine
• Altered gut microbiota
Sepsis • Uraemic toxin
• Circulating endotoxins accumulation
• Altered immune response
• Inflammation and cytokine release
• Oxidative stress, DAMPS and PAMPS Immune system
• Endothelial damage and capillary leak Systemic inflammation
• Anatomical–functional dissociation

Fig. 5 | Pathogenesis and clinical consequences of various forms of AKI. Various organ crosstalk syndromes are associated with acute kidney injury
(AKI). In each example on the left, an organ failure (for example, heart failure) might lead to AKI, which in turn might further damage the heart, as well as
leading to other pathological conditions (for example, immune dysfunction), as illustrated on the right. The process can be cyclical and sustained over
many days. DAMPs, damage-associated molecular patterns; PAMPs, pathogen-associated molecular patterns. Right panel adapted with permission from
Ronco86, Piccin Nuova Libraria.
reduce GFR, increases the likelihood of
damage to the kidney.
Reversibility of damage and relationship
to functional improvement. Some types
of kidney damage might be reversible (lost
kidney tubule cells can be replaced), whereas
other types of damage might be permanent.
However, in patients with sub-functional
The primary endpoint was AKI within
7 days (15 patients (13.6%) developed AKI)
and the secondary endpoints included
measurement of GFR and RFR at 3 months
and the expression of urinary biomarkers.
Introducción
Pre-operative RFR was significantly reduced
in patients who developed AKI (P < 0.001)
and predicted AKI with an area under the
receiver operating characteristic curve
predictive of AKI, and AKI was associated
with 90-day RFR loss.
Of relevance to the definition of damage
or stress in AKI, in the above cohort,
elevated​urinary​[TIMP2]•[IGFBP7]​
identified patients who went on to
lose RFR even in the absence of AKI.
Therefore, not only did patients with
‘clinical’ AKI lose RFR but so did patients

a Stressors b Insult c Persistent insult d Maladaptive repair

Podocyte

Damaged
podocyte

Hyperfiltration • Endothelial and/or epithelial • Loss of filtering units • Progressive

alterations: proteinuria • Loss of permselectivity nephron loss
• Slight decrease in GFR • Decrease of GFR • CKD
• Loss of renal functional reserve (AKI or AKD Stages 1-2-3)

Na+ Na+
Pump
K+
K+
Tubular • Tubular necrosis and/or Myofibroblast Collagen
epithelial cell • Loss of adhesion molecules apoptosis
• Damage biomarkers • Intraluminal cell exfoliation
• Impaired reabsorption and • Tubular obstruction and Sclerosis and/or
Stress biomarkers mitochondrial function interstitial backflow fibrosis

Fig. 3 | Types and consequences of kidney damage and dysfunction.
The duration and severity of kidney stressors and/or insults determine the
pathological findings — molecular, structural and functional changes —
that are associated with kidney damage and dysfunction throughout the
nephron. In the glomerulus, stressors might induce hyperfiltration, whereas
cellular damage, including podocyte loss, will result in loss of renal func-
tional reserve (RFR) and reduce the glomerular filtration rate (GFR). In the
tubules, the early expression of stress biomarkers might precede damage
to epithelium that compromises tubular reabsorption. Nephron loss and the
development of chronic kidney disease (CKD) might occur following acute
kidney injury (AKI) or acute kidney disease (AKD), owing to severe and/or
sustained insults that aggravate the damage to the kidney and maladaptive
repair that leads to the formation of sclerotic and/or fibrotic lesions.
Examples are not exhaustive or mutually exclusive.
 38 / CHAPTER 3

clearance of certain substances is a method to measure glomerular filtration rate

(GFR). Evaluation of GFR via renal clearance is commonly used clinically as an

Introducción
overall assessment of renal health. Repeated assessments over a period of time can
indicate whether renal function is stable or deteriorating.

CLEARANCE UNITS
The units of renal clearance are often confusing to the first-time reader,
so let us be sure of the meaning. First, the units are volume per time (not
amount of a substance per time). The volume is the volume of plasma
that supplies the amount excreted in a given time. For example, suppose each
liter of plasma contains 10 mg of a substance X, and 1 mg of substance X is
excreted in 1 hour. Then 0.1 L of plasma supplies the 1 mg that is excreted, that
is, the renal clearance is 0.1 L/h. The reader should appreciate that removing all
of a substance from a small volume of plasma is equivalent to removing only
some of it from a larger volume, which is actually the way the kidneys do it. If
all of substance X is removed from 0.1 L in 1 hour, this is equivalent to removing
half of it from 0.2 L, or one quarter of it from 0.4 L, and so on. The clearance is
0.1 L/h in all these cases.
These concepts are illustrated in Figure 3–1. As the kidneys clear a substance,
plasma leaving the kidney in the renal vein has a lower concentration of the sub-
stance than does plasma entering the kidney in the renal artery. This is equivalent
Excreción urinaria= (Filtración glomerular - reabsorción tubular) + secreción tubular activa

Plasma in renal artery Plasma in renal vein

(Excreted in urine)

Plasma in renal artery Plasma in renal vein

(Excreted in urine)
 Vasculatura renal R

a Anatomy of the kidney vasculature b Tissue-dependent e

Arteries and cell heterogeneity
arterioles
Capillaries Tissue A
Efferent arteriole
Glomerular capillaries
Afferent arteriole
Peritubular capillaries

Dimension 2
Interlobular artery Kid
Capillary plexus
Arcuate artery
Ascending vasa recta
Interlobar artery
Descending vasa recta
Segmental artery
Large artery
Tissue C
Dimen
Veins and venules
Large vein c Renal endothelial c
Lymphatics
Interlobar vein Genetic factors
Capsular lymphatics • Cortex–medulla–
Subcapsular lymphatics Arcuate vein glomeruli
Interlobular • Artery–
Interlobular lymphatics capillary–vein
venule and vein
Arcuate lymphatics
Stellate venule
Interlobar lymphatics and vein
Hilar lymphatics

• Different transcrip
• Different metabolic

Kidney fu
Capsule Cortex Medulla Glomerulus Ureter

Fig. 1 | Anatomy and heterogeneity of the kidney vasculature. a | The human kidney contains a hi
 Vasculatura renal
Cells 2021, 10, 1087
Figure 1. Anatomy of the renal vasculature. Blood enters the kidney via the renal artery which
divides dichotomously into segmental arteries and branch progressively into interlobar arteries.
Arcuate arteries, separating the border between the cortex and medulla, giving rise to interlobular
arteries which further diverge to supply the glomeruli. Besides the glomerular capillary network,
the renal microcirculation can be divided into cortical and medullary capillary plexus based on the
anatomical location. Finally, blood flows via the arcuate, interlobar, and segmental veins to exit the
kidney via the renal vein.
The cortical microcirculation is physically separated by the arcuate arteries that give
rise to interlobular arteries that further branch from both sides into several afferent arteri-
oles to supply the glomerular capillary network [14]. The branching occurs at a different
angle depending on the location of the glomeruli within the cortex. Via the afferent arte-
riole, the glomerular capillary network consisting of 6–8 capillary loops is supplied with
blood that exits via the efferent arteriole after being filtered [10]. Glomerular capillaries
(Figure 2a) are formed of a thin, continuous, and mostly flat fenestrated endothelium which
is covered by podocytes. The fenestrated areas can take up to 20–50% of their entire cell
surface [16]. The cortical glomeruli compose 90% of all glomeruli present in the kidney, and
therefore it is not surprising that most of the RBF predominantly flows through [13]. The
remaining 10% of all glomeruli are situated at the cortico-medullary border and are bigger
3 of 22
4 of 22
Figure 2. The renal microvascular network exhibits remarkable heterogeneity on morphological and
functional level. The (a) glomerular capillaries have a fenestrated endothelium and are wrapped
by podocytes. The highly muscularized (b) cortical afferent arteriole is surrounded by pericytes, in
contrast to (c) cortical efferent arteriole which contains less smooth muscle cells and flows into the
(d) peritubular capillaries that are highly surrounded by pericytes. The glomeruli situated close to
the arcuate artery and vein are bigger in size, which is reflected by a larger vessel diameter of (e)
juxtamedullary afferent arteriole and (f) juxtamedullary efferent arteriole. The vascular network of
the medulla is supplied by efferent arterioles, which arise from the juxtamedullary glomeruli forming
a dense capillary plexus and interbundle plexus in the inner stripe of the outer medulla. The (g)
vascular bundle is wrapped by many pericytes and enter deeper into the inner medulla to form the
vasa recta capillaries between the (h) descending vasa recta (DVR) and the fenestrated (i) ascending
vasa recta (AVR).
Filtered blood exits each of the cortical glomeruli via the efferent arteriole to come
together in the dense cortical capillary plexus surrounding the renal tubules [10]. Apart
from the glomerular capillary system, this second capillary compartment is known as the
peritubular capillary system [16]. The peritubular capillaries (Figure 2d) are fenestrated
Arteriola Corteza renal
eferente Glomérulos
superficiales
Arteriola
aferente Vena interlobulillar
Lecho capilar
Arteria
peritubular
interlobulillar FSR= 20-25% GC
Vena Arteria
Glomérulo arqueada arqueada
yuxtamedular FPR?

TFG= 125 ml/min

Asa de Henle Tasa de producción de orina= 1,25 ml/min

Vasos rectos
ascendentes Excreción urinaria= 500-1500 ml/día
Vasos rectos
descendentes

Vena
interlobulillar

Arteria
interlobulillar
RBF = Flujo sanguíneo renal
RPF = Flujo plasmático renal
Hct = hematocrito
Médula renal
(pirámide)

(Ganong, 2012)
 Sites of largest
vascular resistance
100

75

Pressure (mm Hg)

50

25

le

lary
le

l vein

l vein
ry

capil lar
lary

r terio
r terio
l ar te

eru

capil

rena

Rena
Glom

ent a
ent a
Rena

bular

Intra
Effer
Affer

u
Figure 2–2. Blood pressure decreases as blood flows through the renal vascular Perit
network. The largest drops occur in the sites of largest resistance—the afferent and
efferent arterioles. The location of the glomerular capillaries, between the sites of high
resistance, results in their having a much higher pressure than the peritubular capil-
laries. (Reproduced with permission from Kibble J, Halsey CR. The Big Picture: Medical
Physiology. New York: McGraw-Hill; 2009.)

GLOMERULAR FILTRATION
 Review of Renal Physiology 3

Nefrona Glomerular filtrate

Afferent arteriole
Juxtaglomerular apparatus
Macula densa
Distal convoluted tubule

Efferent
arteriole

Cortical
collecting duct

Cortex
Thick ascending
limb of loop
Proximal tubule of Henle

Thin ascending

Medulla
limb of loop
of Henle
Thin descending
limb of loop Outer medullary
of Henle collecting duct

Inner medullary
collecting duct

Papillary
duct

FIGURE 1.1. Anatomy of the nephron. Filtrate forms at the glomerulus and enters the
674 SECCIÓN VII Fisiología renal

sidades, no hay un borde “en cepillo” distintiv

se fusionan para constituir túbulos colectores
dor de 20 mm de longitud y pasan a través d
médula para desembocar en la pelvis del riñón
Túbulo
contorneado distal pirámides medulares. El epitelio de los túbulo
Túbulo Túbulo colector tituido por células principales (células P) y
contorneado proximal
(células I). Las primeras, que son las predom
Glomérulo
relativamente altas y presentan pocos organe
reabsorción de iones sodio y en la de agua estim
sina. Las segundas, las cuales están presenten
también se encuentran en los túbulos distales
Corteza llosidades, vesículas citoplásmicas y mitocond
Nefrona
secreción de ácido y del transporte de bicarbon
gitud total de las nefronas, incluidos los túbu
Médula
de 45 a 65 mm.
externa Las células en los riñones que al parecer
secretora, además de incluir las células granulo
taglomerular, también comprenden algunas e
Asa de Henle, de la médula renal; éstas han recibido el nomb
rama ascendente
gruesa ciales de la médula renal (RMIC, renal medu
Médula son células especializadas similares a fibroblas
interna
de lípido y son el sitio principal de expresión
(COX-2) y la prostaglandina sintasa (PGES).
Asa de Henle, rama noide principal que sintetiza en los riñones y u
descendente delgada
importante de la homeostasis de sodio y agua.
FIGURA 371 Diagrama de una nefrona. Se muestran también las es secretada por RMIC, por la mácula densa
principales características histológicas de las células que constituyen tubos colectores; la prostaciclina
(Ganong,(PGI
2012) ) y otra
2
Relación vascular y tubular
 Filtración
glomerular
 CORPUSCULO RENAL

GLOMERULO

CAPSULA DE BOWMAN

ARTERIOLA
EFERENTE

ARTERIOLA
AFERENTE

ESPACIO CAPSULAR
 Función glomerular

Todos los solutos y moléculas con un peso

molecular menor que el de la albúmina (68 kDa)
y un diámetro hidrodinámico (HD) <5-7 nm
pueden pasar esta barrera.
28 / CHAPTER 2

Bowman’s
space

PBS
PGC
Glomerular
capillary
πGC

TFG= PFN x Kf Forces mmHg

Favoring filtration:
Glomerular capillary blood pressure (PGC) 60
TFG=125 ml/min Opposing filtration:

Fluid pressure in Bowman’s space (PBS) 15

Osmotic force due to protein in plasma (π GC) 29

Net glomerular filtration pressure = PGC – PBS – πGC 16

Figure 2–4. Forces involved in glomerular filtration as described in the te

 1.0

Filtrate/plasma concentration ratio

Inulin
(~ 5000)

0.5

Hemoglobin (68,000)
Albumin (~ 69,000)
0
0 35 70
Molecular weight (thousands)

Positively charged = more filtered

Neutral
Filtration

Molecular size
Negatively charged = less filtered

Figure 2–3. A, As molecular weight (and therefore size) increases, filterability declines,
so that proteins with a molecular weight above 70,000 Da are hardly filtered at all. B, For
any given molecular size, negatively charged molecules are restricted far more than neu-
tral molecules, whereas positively charged molecules are restricted less. (Reproduced
with permission from Kibble J, Halsey CR. The Big Picture: Medical Physiology. New York:
McGraw-Hill; 2009.)
 Resistencia al ujo

TFG= PFN x Kf

TFG=125 ml/min

• GFR = Kf [(Pc-Pb)-(Πc)]
• GFR = Glomerular Filtration Rate (ml/min). Equivalent of Jv in Starling Forces
• Kf = Permeability Constant of glomerular capillaries
• Pc = Glomerular Capillary Hydrostatic Pressure
• Pb = Bowman's Space Hydrostatic Pressure
• Πc = Glomerular Capillary Oncotic Pressure
fl
 Fuerzas que afectan la TFG (Analogía)
PRESIÓN HIDROSTATICA
CAPSULA

PRESIÓN HIDROSTATICA
GLOMERULAR (PRESIÓN
SANGUINEA)
PRESIÓN OSMOTICA
GLOMERULAR
 Tasa de ltrado glomerular
30 / CHAPTER 2

Table 2–2. Summary of direct GFR determinants and factors that influence them

Direct determinants of GFR: Major factors that tend to increase the

GFR = Kf (PGC − PBC − πGC) magnitude of the direct determinant
Kf 1. ↑ Glomerular surface area (because of relaxation
of glomerular mesangial cells)
Result: ↑ GFR
PGC 1. ↑ Renal arterial pressure Afferent-arteriolar
2. ↓ resistance (afferent dilation)
Efferent-arteriolar resistance (efferent constriction)
3. ↑ Result: ↑ GFR
PBC 1. ↑ Intratubular pressure because of obstruction of
tubule or extrarenal urinary system
Result: ↓ GFR
πGC 1. ↑ Systemic-plasma oncotic pressure (sets πGC
2. ↓ at beginning of glomerular capillaries)
Renal plasma flow (causes increased rise
of πGC along glomerular capillaries)
Result: ↓ GFR
GFR, glomerular filtration rate; Kf , filtration coefficient; PGC, glomerular-capillary hydraulic pressure;
PBC, Bowman’s capsule hydraulic pressure; πGC, glomerular-capillary oncotic pressure. A reversal of
all arrows in the table will cause a decrease in the magnitudes of Kf , PGC, PBC, and πGC.

renal disease is not a change in these parameters within individual nephrons, but
rather a decrease in the number of functioning nephrons. This reduces K .
fi
 Coe ciente de ultra ltrado (Kf)

Marcus J. Moeller & Verena Tenten

Nature Reviews Nephrology 9, 266-277 (May 2013)
fi
fi
 ¿Proteinuria?
Rev Méd Chile 2009; 137: 137-177

Tabla 3.1. Definición de Proteinuria y Albuminuria

CATEGORÍA Valor (mg/ 24 h) Valor (mg/ g creatinina)

Excreción de Proteína P/ C
Normal <150 <200
Proteinuria >150 >200
Proteinuria nefrótica >3.500 >3.500
Excreción de Albúmina A/ C
Normal <30 <30
Microalbuminuria 30-300 30-300
Macroalbuminuria >300 >300

P/ C: cuociente proteína-creatinina, A/ C: cuociente albúmina-creatinina.

Esta razón puede subestimar la proteinuria
en pacientes musculosos (alta producción
de creatinina) o sobreestimarla en pacien-
tes delgados y de edad avanzada.
enérgico de la presión arterial, uso de fárma-
cos antiproteinúricos como inhibidores de la
enzima de conversión y/ o antagonistas del
receptor de angiotensina, y otros tratamientos
coadyuvantes.

TRATAMIENTO
Guía 4
 Proteínas
reguladoras de la
interacción celular

• Estas proteínas interactúan con el

citoesqueleto del podocito y participan en la
transmisión de señales intracelulares e
intercelulares.

• Parece ser que el diafragma de filtración,

además de ser un filtro dependiente del
tamaño de las moléculas, también ejerce su
función de acuerdo con la carga eléctrica,
pudiendo así repeler las proteínas y evitando
que este diafragma se tapone

• En respuesta a muchos tipos de agresión, los

podocitos sufren un cambio morfológico
denominado «borramiento» (o fusión) de
procesos podocitarios, que se debe a una
alteración arquitectural del citoesqueleto y la
unión intercelular.

Chih-Kang Chiang & Reiko Inagi

Nature Reviews Nephrology 6, 539-554 (September 2010)
34 / CHAPTER 2 Autorregulación

1.5 150

Glomerular filtration rate (mL/min)

“Autoregulatory range”
Renal blood flow (L/min)

0 0
0 80 180
Renal perfusion pressure (mm Hg)

Figure 2–7. Autoregulation of renal blood flow (RBF) and glomerular filtration rate
 Sistemas de regulación de la TFG

Extrinsecos:

• SRAA.

Intrínsecos:

• Re ejo miogénico.

• Sistema de retroalimentación tubulo-glomerular.

fl
F 438
Sistemas de regulación de la TFG INVITE D RE VIE W

F ig. 5. P ost u la t ed m a cu la den sa sign a l-

in g m ech a n ism s. Nu m ber s in cir cles
r efer t o t h e followin g sequ en ce of even t s.
1 ) F low-depen den t ch a n ges in t u bu la r
flu id com posit ion (osm ola lit y, Na 1, Cl 2,
et c.). 2 ) Mem br a n e a ct iva t ion su ch a s
m em br a n e depola r iza t ion a n d en h a n ced
Na Cl en t r y. 3 ) In t r a cellu la r Ca 21 m obi-
liza t ion . 4 ) In t r a cellu la r even t s: for m a -
t ion a n d r elea se of a r a ch idon ic a cid
(AA) m et a bolit es, for m a t ion a n d m e-
t a bolism of pu r in er gic a gen t s, for m a -
t ion of NO. 5 ) E ffect s of secr et ed a gen t s
on m em br a n e pot en t ia l a n d a ct iva t ion
of Ca 21 ch a n n els in va scu la r sm oot h
m u scle cells. 6 ) Va scu la r con t r a ct ile

Downloaded from http://ajprenal.physiology.org/ by

r espon ses. COX, cyclooxygen a se; TX,
t h r om boxa n e; Ado, a den osin e; P LA2 ,
ph osph olipa se A2 ; R, r ecept or. [Modi-
fied fr om Na va r et a l. (69) a n d in clu des
va r iou s post u la t ed bu t n ot yet pr oven
m ech a n ism s.]-

invited review
im plica t in g t h e im por t a n t r ole of ANG II in t h e TGF In t egrr ecogn
a t in gized
m u tlthiple a t inpa t r arraen crainl eANG r eguIIla ser t orves s a s a ver y
m ech a n ism . Addit ion a lly, it wa s r ecen t ly sh own t h a t im por t a n t m odu la t or of t h e TGF m ech a n ism , it is n ot a
ANG II AT 1 r ecept or s a r e a lso pr esen t in m a cu la denof sa r envia
a lblem icr
ca novadida scut e la
a sr t hdyn e maedia m ics t or. Never t h eless, it is a n
cells (29). Ot h er r ecen t st u dies dem on st r a t in g t h a t essen t ia l per m issive fa ct or in t h a t n or m a l TGF r e-
L. GABRIE L NAVAR 1
t u bu la r flu id ANG II con cen t r a t ion s a r e in t h e n a n om o- spon ses a r e m a r kedly a t t en u a t ed or ca n n ot be elicit ed
Departm en t of Ph ysiology, Tu lan e Un iversity S ch ool of M ed icin e, N ew Orlean s, L ou isian a 70112
la r r a n ge su ggest s t h a t ANG II m a y in t er a ct a t t h e level wh en ANG II is t ot a lly blocked or a bsen t .
of t h e m a cu la den sa cells a s well a s by in flu en cin g Th er e is Ngr
a v aowin
r, L. Gag brieal.ccorIn t egrd
a t infor
g m u tlt h e papr
iple esen
r a cr cela t orofs ofar enva
in e r egu
m icr ova scu la r dyn a m ics. Am . J . Ph ysiol. 274 (R en al Ph ysiol. 43): F 433 –
a l r iet y

a r t er iola r va scu la r sm oot h m u scles dir ect ly (70). H ow- of pa r a cr in e syst

F 444, 1998.—Th emer eshin m at r em
a s been cuenladouden s gr owtsa
h in cells (F ig.a bou
ou r kn owledge
t h e m u lt iple in t er a ct in g m ech a n ism s t h a t r egu la t e r en a l m icr ova scu la r
5).
t On e
 Sistemas de regulación de la TFG Review of Renal Physiology 21

680 SECCIÓN VII Fisiología renal

CUADRO 373 Agentes que producen contracción

o relajación de las células del mesangio
Juxtaglomerular
Contracción Relajación
apparatus

Sensores Endotelinas

Angiotensina II
ANP

Dopamina
Renal sympathetic Vasopresina PGE2
neurons
Noradrenalina cAMP
Renin-producing Factor activador de plaquetas
granular cells
Factor de crecimiento derivado de
Macula le
terio las plaquetas
densa ar
Distal ent Tromboxano A2
r
tubule E ffe PGF2

Aff Leucotrienos C4 y D4
e ren Histamina
ta Extraglomerular FIGU
rt e un ca
mesangial cells PGF2, prostaglandina F2; ANP, péptido natriurético auricular; PGE2, prostaglandi-
PUF , p
rio

na E2; cAMP, monofosfato de adenosina cíclico.

(πT) n
le

(Con a
chlorid
bifurcan las asas capilares tal vez desvía el flujo sanguíneo, alejándo-
lo de algunas de las asas y, en otras partes, las células del mesangio
contraídas se distorsionan y comprimen la luz de los capilares. En el plasm
Bowman’s capsule Bowman’s capsule cuadro 37-3 se enumeran los fármacos que se han utilizado para tanc
afectar las células del mesangio. La angiotensina II constituye un
regulador importante de la contracción del mesangio y en los glomé- espe
rulos existen receptores de angiotensina II. Además, algunas prue- conl
bas indican que las células del mesangio sintetizan renina. hum
Glomerular
mesangial cells PRESIÓN HIDROSTÁTICA Y OSMÓTICA CA
Sistemas de regulación de la TFG
Retroalimentación tubuloglomerular
Respuesta miogénica
 3487-01_Ch01-rev.qxd 3/28/06 10:11 AM Page 20

Afferent arteriole Pgc Efferent arteriole

GFR RPF
26 Renal Pathophysiology: The Essentials
A
tion). Creatinine production can also be influenced by the intake of meat,
which contains creatine, the precursor of creatinine. For example, plasma
creatinine concentration
Afferent arteriole Pgc can fall by as much as 15%
Efferent by switching to a
arteriole
20 Renal Pathophysiology: The Essentials
meat-free diet, without any change in GFR.
The idealized reciprocal relationship between GFR and plasma cre- 110
atinine concentration
GFRis shown
RPF by the solid curve in Figure 1.10. There
are three points to note about this relationship:
B
■ The relationship is valid only in the steady state when plasma creatinine 100
FIGURE 1.7. Relationship between glomerular arteriolar resistance, glomerular filtration Control
concentration is stable. If, for example, GFR suddenly ceases, plasma

GFR (percent control)

rate (GFR), and renal plasma flow (RPF). Constriction of the afferent arteriole increases
creatinine concentration will still be normal for the first few hours be-
renal vascular resistance (thereby reducing RPF) and decreases the intraglomerular pres-
cause there has not been time for nonexcreted creatinine to accumulate. 90
sure and GFR, since less of the arterial pressure is transmitted to the glomerulus (A).
■ The shape of the curve is important, since there is a variable relation
Constriction of the efferent arteriole also lowers RPF but tends to elevate the intra-
between a change in plasma creatinine concentration and the degree
glomerular pressure and GFR (B). Arteriolar dilation has the opposite effects.
80 A antagonist

glomerular filtration. However, 9.0 GFR (and renal plasma flow) are almost 70
constant over a relatively wide range of renal arterial pressures (Fig. 1.8).
This phenomenon, which 8.0 is also present in other capillaries, is called
autoregulation. 7.0
60
70 85 105 125
Plasma creatinine (mg/dL)

Autoregulation in most capillaries is mediated by changes in precap-

illary resistance. In the kidney, 6.0 for example, an increase in afferent arte- Renal artery pressure, mm Hg
riolar tone can, when perfusion pressure rises, prevent the elevation in FIGURE 1.8. Autoregulation of glomerular filtration rate (GFR), expressed as a per-
5.0
pressure from being transmitted to the glomerulus, thereby preventing centage of control values, as the renal artery pressure is reduced from a baseline level
any significant change in Pgc 4.0and GFR. Conversely, GFR can be preserved of 125 mm Hg in dogs. The squares represent control animals in which GFR was main-
by afferent dilation when renal perfusion pressure falls. tained until renal perfusion pressure was markedly reduced. The circles represent ani-
However, the mechanism 3.0 of autoregulation of GFR is more complex. mals given an intrarenal infusion of an angiotensin II antagonist. In this setting, GFR is
Angiotensin II makes an important contribution when renal perfusion less well maintained. Although not shown, autoregulation also applies when renal artery
2.0
pressure falls, a situation in which the renin-angiotensin system is acti- pressure is initially raised.
vated. Angiotensin II preferentially1.0 increases the resistance at the effer-
ent arteriole, thereby preventing the Pgc from declining in the presence of
0
hypotension. 0 20 40 60 80 100 120 140 160 180 pressure is mediated by tubuloglomerular feedback (see next section)
The contribution of angiotensin II to autoregulation GFR (mL/min) can be seen in and the stretch receptors.
Figure 1.8. In normal animals,
FIGURE 1.10. GFR begins
Relationship to glomerular
between true fall onlyfiltration
whenrate there
(GFR;isasameasured
marked reduction in renal
by inulin perfusion
clearance) and plasmapressure;
creatininethis limitation
concentration presumably
in 171 patients with glomeru- QUESTION
Narrowing of the renal arteries (renal artery stenosis) is a rela-
lar disease. The red circles joined by the solid line
is due in part to maximal dilation of the afferent arteriole. In comparison,that would
represent the relationship
exist if creatinine were excreted solely by glomerular filtration; the dotted line represents 3 tively common cause of severe or refractory hypertension, and is
GFR begins to fall at a limit
the upper higher perfusion
of normal for plasma pressure in animals
creatinine concentration pretreated
of 1.4 mg/dL. In the patients
with an angiotensin II antagonist.
(dark circles Even ininGFR
), however, variations this situation,
between however,
120 and 60 mL/min were the
often asso-
usually due to atherosclerotic lesions in older patients. What should happen to
ciated with a plasma creatinine concentration
ability to autoregulate is maintained with the initial reduction in renal that remained well within the normal GFR in a stenotic kidney as blood pressure is lowered with antihypertensive
range due to increased creatinine secretion. The latter becomes saturated at a plasma agents that act independently of angiotensin II? Would the response be different
perfusion pressure. Thisconcentration
creatinine autoregulationabove 1.5atto 2mild
mg/dL;reductions in perfusion
as a result, plasma creatinine concentra-
tion rises as expected with further reductions in GFR. if an angiotensin-converting enzyme inhibitor, which decreases the formation of
angiotensin II, were given?
 Sistema de control
Factores que aumentan la TFG

• Dietas ricas en proteínas.

• Sobrepeso.

Factores que disminuyen la TFG

• Disminución de la presión hidrostática intracapilar

(hipotensión).
• El aumento de la presión coloidosmótica del
plasma (deshidratación).
• Aumento de la presión en el espacio de Bowman
(obstrucción urinaria).
• Disminución del flujo sanguíneo renal (insuficiencia
cardiaca).
• Disminución del coeficiente de ultrafiltración
(enfermedad renal intrínseca).
 •
Secreción tubular de Cr sobreestima Dieta en Enfermedad Renal (MDRD).
VFG Estima la VFG ajustada a superficie
• Requiere recolección de orina, habitual- corporal29. Esta ecuación fue reexpresa-
mente en 24 horas. da en 2005, para usar con creatinina
• Hereda los errores de la creatinina estandarizada, que logra valores 5%
sérica menores de creatinina sérica.

Estimación de la TFG
• Cystatin a C: Inhibidor de proteasa de cis-
teína, es un marcador endógeno producido
por todas las células nucleadas. Fácil de
medir, filtra libremente por el glomérulo, su
producción es estable, no influenciada por
la edad, sexo, dieta, masa muscular, infla-
mación. No tiene aún un rol clínico esta-
27.
ClCr (ml/min) =
blecido UxV/P
c) Estimación de VFG mediante ecuaciones:
• Estas ecuaciones predicen VFG basadas en
U= concentración de creatinina en la orina (mg/dl). la creatinina, pero incluyen variables como
edad, sexo, raza y tamaño corporal, en un
V= volumen minuto de orina (ml/min). intento por superar los errores de la creati-
nina aislada. Son fórmulas matemáticas
P= concentración plasmática de creatinina (mg/dl). derivadas de técnicas de regresión que
modelan la relación observada entre el
nivel sérico del marcador (creatinina) y
VFG medida en una población estudiada 27.
• Las ecuaciones CG y MDRD han sido
evaluadas en poblaciones con nefropatía
diabética y no diabética, en trasplante renal
y donantes de trasplante renal27,30. La co-
rrelación entre VFG medida y estimada es
mejor a medida que la función renal decli-
na. Con función renal normal, las ecuacio-
•
nes tienden a subestimar la función renal.
Las ecuaciones de predicción están teniendo
amplia utilización clínica y epidemiológica 27:
• Han formado la base de la nueva clasifi-
cación de la enfermedad renal crónica
• Se recomienda su uso rutinario en la
detección de la enfermedad renal cróni-
ca, particularmente en el nivel de Aten-
ción Primaria. Esto implica desterrar de
la práctica clínica cotidiana el uso del
clearance de creatinina.

Tabla 6.1. Ecuaciones para estimar función renal (VFGe)

Cockcroft Gault (CG)

VFGe (ml/ min) = (140 - edad) x Peso (kg) x 0,85 (si mujer)/ x (72 x CrS(mg/ dl))

MDRD- 6 variables
VFGe (ml/ min/ 1,73m 2) = 170 x CrS -0,999(mg/ dl) x (edad) - 0,176 x BUN - 0,170 (mg/ dl) x Alb +0,318(g/ dl)
x 0,762 (si mujer) x 1.180 (si afroamericano)

MDRD- 4 variables (abreviada)

VFGe (ml/ min/ 1,73m2) = 186 x CrS-1,154 (mg/ dl) x edad -0,203 x 0,742 (si mujer) x 1,21 (si
afroamericano)

VFGe: velocidad de filtración glomerular estimada, CrS: creatinina sérica, BUN: nitrógeno ureico
plasmático, Alb: albúmina.

SU P L E M E N T O 153
sured (mGFR) after administration of exogenous filtration
logic conditions (Table
51 1) [24]. It
99m decreases with age and is ! "
markersapproximately
such as inulin,halved at the age ofTc-DTPA
Cr-EDTA, 80 years and
(likecertain Relative G FR 2
muscle P-creatinine hasmL=min=1:73
been the routinem marker for a century to es
iodine mass,
contrastsee media
below)(I-CM),
[25]. e.g., iohexol and iothalamate
mate renal function.
¼ Absolute It fulfilsÞ $
G FRðmL=min several requirements for an a
1:73=BSA:
[24, 26]. Requirements
It is not possibleoftoameasure
good filtration marker
GFR directly, arefiltration
since sum-
ceptable GFR marker. Creatinine is not protein bound, free
marizedoccurs
in Box
and expensive,
1. However,inmeasuring
simultaneously
and therefore
urine changes
Estimación de la TFG
millions ofGFR
not suited
in both volume
is labor
nephrons
to evaluatewhen
and composition
intensive
and the primary
renalpassing
func-
filtered, not metabolized by the kidneys and is physiological
inert [28]. However, creatinine is also excreted by tubul
tion inthrough
everydaythe kidney.
routineHowever,
practice.GFR can be GFR
Instead, indirectly
canmea-be Creatinine
sured (mGFR) after administration of exogenous filtration secretion, the significance of which increases with decreasi
Table 1 markers inulin, 51affecting
suchofasconditions
Examples Cr-EDTA, 99m
GFR Tc-DTPA and certain renal function resulting in false, too-low p-creatinine valu
P-creatinine has been the routine marker for a century to esti-
iodine contrast media (I-CM), e.g., iohexol and iothalamate relative to actual renal function.
Parameter Effect onmarker
GFR are sum- mate renal function. It fulfils several requirements for an ac-
[24, 26]. Requirements of a good filtration
ceptable GFR marker. Creatinine is not protein bound, freely
marized in Box 1. However, measuring GFR is labor intensive Table 2 GFR categories according to KDIGO (Kidney Disea
Circadianand
variation Decreases during nights filtered, not
Improving metabolized
Global by the
Outcomes) [1] kidneys and is physiologically
expensive, and therefore not suited to evaluate renal func-
Diabetestion in everyday routine practice.Hyperfiltration early sign inert [28]. However, creatinine is also excreted by tubular
Instead, GFR can be
secretion,
GFR the significance
category GFR (mL/min/1.73 m2)increases
of which Terms with decreasing
Exercise Decreases
Table 1 Examples of conditions affectingIncreases
GFR renal function resulting in false, too-low p-creatinine values
Protein intake G1 ≥90renal function. Normal or high
relative to actual
PregnancyParameter Increases
Effect on GFR G2 60–89 Mildly decreased
Smoking Decreases Table 2 GFR45–59
G3a categories according to KDIGO
Mildly to(Kidney Disease:
moderately decrease
Circadian variation Decreases during nights Improving Global Outcomes) [1]
Extreme overweight Increases G3b 30–44 Moderately to severely decreas
Diabetes Hyperfiltration early sign
Extreme underweight (anorexia) Decreases GFR category GFR
G4 (mL/min/1.73 m2) Terms
15–29 Severely decreased
Exercise Decreases
Analytical imprecision
Protein intake Increase/decrease
Increases G5 <15 Kidney failure
G1 ≥90 Normal or high
Pregnancy Increases G2 60–89 Mildly decreased
Smoking Decreases G3a 45–59 Mildly to moderately decreased
Extreme overweight Increases G3b 30–44 Moderately to severely decreased
Extreme underweight (anorexia) Decreases G4 15–29 Severely decreased
Analytical imprecision Increase/decrease G5 <15 Kidney failure
 Obesity-related glomerulopathy:
clinical and pathologic characteristics
Filtrado Glomerular y obesidad and pathogenesis
REVIEWS
Vivette D. D’Agati1, Avry Chagnac2, Aiko P.J. de Vries3, Moshe Levi4, Esteban Porrini5,
Michal Herman-Edelstein6 and Manuel Praga7
Abstract | The prevalence of obesity-related glomerulopathy is increasing in parallel with 2016
the worldwide obesity epidemic. Glomerular hypertrophy and adaptive focal segmental
glomerulosclerosis define the condition pathologically. The glomerulus enlarges in response to
obesity-induced increases in glomerular filtration rate, renal plasma flow, filtration fraction and
Systemic • High salt diet
tubular sodium reabsorption. Normal insulin/phosphatidylinositol 3-kinase/Akt and mTOR
hypertension • Low
signalling are critical for podocyte hypertrophy nephron
and adaptation. Adipokines and ectopic lipid
Systemic or local number
accumulation in the kidney promote insulin resistance of podocytes and maladaptive responses
Deactivation of • High protein diet
intrarenal actor(s to cope with the mechanical forces of renal hyperfiltration. Although most patients have stable or
tubuloglomerular slowly progressive proteinuria, up to one-third develop progressive renal failure and end-stage
feedback
? renal disease. Renin–angiotensin–aldosterone blockade is effective in the short-term but weight
loss by hypocaloric diet or bariatric surgery has induced more consistent and dramatic
↓ Solute delivery erent ↑ Single nephron ± erent arteriole
antiproteinuric effects and reversal of hyperfiltration. Altered fatty acid and cholesterol
to macula densa arteriole dilation plasma o metabolism are increasingly recognized as key mediators of renal lipid constriction
accumulation,
inflammation, oxidative stress and fibrosis. Newer therapies directed to lipid metabolism,
including SREBP antagonists, PPARα agonists, FXR and TGR5 agonists, and LXR agonists, hold
↑ Glomerular
therapeutic promise. • Ang II
pressure • Aldosterone
Obesity and diabetes mellitus occurring in the context Pathology of ORG
of obesity — known as diabesity — are now leading Biopsy incidence
causes of chronic kidney disease (CKD)1–8. Between 1978 The obesity epidemic has led to an increase in the num-
↑ Filtrate o (singleand 2013, the proportion of overweight and obese adults ber of ↑ Glomerular
renal biopsies performed in obese patients. Early
nep ron ltration rate (BMI ≥25 kg/m2) worldwide increased from 28.8% to capillary
case reports of ORG wall
were limited to autopsy studies13,
36.9% among men, and from 29.8% to 38.0% among which identified an association between extreme obesity
women9. In the USA, the prevalence of obesity (BMI and thetension
development stress
of glomerular hypertrophy (glo-
≥30 kg/m2) among adults aged 20–74 years has more merulomegaly). In 1974, an association between mas-
Shear stress on podocytes than doubled over the past three decades, from 15% to sive obesity and nephrotic-range proteinuria was first
35% in 2011–2012 (REF. 10). This increase occurred in described14. The full spectrum of ORG emerged from
↑ Proximal tubular men and women of all age groups and across diverse detailed Basement
clinical–pathologic studies15–17, and from stud-
ethnicities. Estimates suggest that by 2030 more than ies that contrasted ORG with primary focal segmental
salt reabsorption membrane
Mechanotransduction: 50% of the US population will be obese and either 11at glomerulosclerosis (FSGS)16. The frequency of ORG
↑ Ang II, AT1R, TGF-β and TGF-βR risk of, or experiencing, obesity-related complications , distension
has increased in US, European and Asian cohorts over
resulting in a substantial economic burden12. The obesity the past 30 years15–17. A retrospective study that evalu-
epidemic has led to an increased incidence of obesity- ated native kidney biopsy samples received at Columbia
related glomerulopathy (ORG), a distinct entity featuring University, New York, USA, reported a 10-fold increase
• Ang II Podocyte hypertrophy
Correspondence to proteinuria, glomerulomegaly, progressive glomerulo- in the incidence of ORG from 0.2% in 1986–1990 to
Capillary growth and
• Renal sympathetic V.D.D. vdd1@columbia.edu
anddoi:10.1038/nrneph.2016.75
apoptosis
sclerosis and renal functional decline. Here we review
Mismatch
the pathologic and clinical features of ORG as well as the
2.0% in 1996–2000
glomerulomegaly
2001–2015
(REF. 16), with a further rise to 2.7% in
(V. D’Agati, unpublished data). In this study
nervous system Published online 6 June 2016 pathogenesis and potential therapeutic targets. all ORG biopsies were performed for overt renal disease:
• Insulin
• ↑ Peritubular NATURE REVIEWS | NEPHROLOGY Podocyte detachment VOLUME 12 | AUGUST 2016 | 453
oncotic pressure
• Microvilli
mechanosensing
and transduction Focal segmental glomerulosclerosis—obesity-related glomerulopathy

Figure 2 | Haemodynamic alterations in obesity. Primary dilatation of the afferent arteriole and variable constriction of
the efferent arteriole via activation of angiotensin II (Ang II) and aldosterone contribute to increases in single nephron
plasma flow, glomerular intracapillary hydrostatic pressure, and filtration rate. The major driver of afferent arteriolar
 Reabsorción
tubular y
secreción
tubular activa
 Introducción
125 ml por minuto.

7,5 Litros por hora

¿Por que orinamos

180 Litros 24 horas tan solo 1,5 litros
diarios?
 Introducción

%
SUSTANCIA UNIDADES FILTRADO REABSORBIDO EXCRETADO REABSORBIDO
DEL TOTAL EXCRETADO

Agua 180 178,5 1,5 99,2

l/día

Na+ 25200 25050 150 99,4

mEq/dia

K+ 720 620 100 86,1

mEq/dia

Ca+2 540 530 10 98,2

mEq/dia

HCO3- 4320 4318 2 99,9

mEq/dia

Cl- 18000 17850 150 99,2

mEq/dia

Glucosa 800 800 0 100

mmol/dia

Urea 56 28 28 50
g/dia
 Reabsorción tubular
Hay dos rutas de reabsorción: en la barrera de la célula tubular:
• La ruta Transcelular Membrana luminal y membrana basolateral
• La ruta Paracelular Espacio intercelular lateral
48 / CHAPTER 4

Lumen Interstitium BASIC TRANSPORT MECHANISMS / 49

Apical Peritubular
membrane Interstital capillary
Channel or space Substance A 1
Diffusion
transporter

Me
Trancellular

mb
Uniporter
reabsorption

ran
Substance B 2

e
Basolateral
membrane Symporter
Substance C
Substance D 3
Paracellular
reabsorption Antiporter
Substance E 4
Substance F

Tight junction Basement

Substance G 5 Ion channel
membrane
A

6 Primary active
Substance H
transport

ADP + Pi

ATP

Figure 4–2. Mechanisms of transmembrane solute transport. With the exception of

Tight junction Membrane protein simple diffusion through the lipid bilayer, all transport involves channels and transport-
Plasma membrane
 Proximal
Tubular lumen tubular cell Peritubular capillary
− +

− +
Túbulo Contorneado Proximal
Na+
− +

•
Glucose
Phosphate
3Na+
Epitelio funcional.
Na-K-
ATPase

•
2K+
Na+ 70-75% de reabsorción del ltrado.
H+

• Reabsorción de glucosa y bicarbonato.

K+

Na+

Apical Basolateral
membrane membrane

FIGURE 1.2. General model for transtubular sodium reabsorption and schematic
model of ion transport in the proximal tubule. Filtered sodium enters the cell across the
fi
 Túbulo Contorneado
Proximal, segmento
inicial.

FIG. 12. Cellular mechanism of sodium, potassium, anion, and water transport in proximal convoluted tubules. The
sports re- H1-ATPase. Na1/H1 exchangers constitute a family of

from http://physrev.physiology.org/ by 10.220.33.2 on July 10, 2017

Túbulo Contorneado
Proximal, segmento nal.

on, and water transport in proximal convoluted tubules. The

fi
Transporte de aminoácidos
 BASIC TRANSPORT MECHANISMS / 57

Lumen Interstitium

Peritubular
capillary
ATP
1 Na
2 Na K

5
3 Anions

4 Water

Water, anions

Figure 4–4. Epithelial salt and water reabsorption. See text for explanation of each
individual step. (1) Sodium is actively extruded into the interstitium. (2) Sodium enters
passively from the tubular lumen. (3) Anions follow the sodium (transcellularly and
paracellularly). (4) Water follows the solute (transcellularly and paracellularly). (5) Water
and solutes move by bulk flow into the peritubular capillary.

consequences, the key one being that it keeps the concentration of sodium within
the cell low enough to favor the passive entrance of sodium from lumen to cell in
 712 SECCIÓN VII Fisiología renal
Túbulo Contorneado Proximal:
Balance
Líquido
intersticial
Célula acido-base
del túbulo renal
Luz
tubular
Líquido Célula Luz
712 SECCIÓN VII Fisiología renal intersticial del túbulo renal tubular
+
Na
+
CO2 + H2O Na+ Na+ + HCO3–
Líquido K Luz
Célula del túbulo renal Líquido Célula Luz
intersticial Anhidrasa tubular + H+ + HCO3–
carbónica intersticial del túbulo renal H tubular
+
Na K+ H2CO3 HCO3– HCO3– CO2 + H2O
+
CO2 + H2O Na+ Na+ + HCO3–
K +
Anhidrasa Na + Na–
Na+ H+ H+ +Na
HCO +
3 HPO4
2-

HCO3
–
HCO3
– carbónica
+ +
H H+ +
+
H2CO3 HCO – HCO – H+ +
K HCO3– 3 HCO3– 3 CO2 + H2OH
+
Na + H PO
Na+ Na+ Na+Na
HPO 24
2- –
4
HCO3– HCO3– + H
+
H+ +
FIGURA 391 Secreción de ácido por las células de los túbulos
proximales en el riñón. El hidrogenión (H+) es transportado hacia la luz HCO3– Na+ HCO3– H+ NaH++A–
tubular por un cotransporte bidireccional en intercambio por iones sodio
(Na+). El transporte activo por la Na, K-ATPasa está señalado con las flechas H+ H+
Na+ H2PONH
–
4 4+ A–
en el círculo. Las flechas de rayas indican difusión. CO2, dióxido de carbono;
K+, iones – HCO3– HCO3– NH3 NH3
FIGURA 391potasio; H2O, agua;
Secreción HCOpor
de ácido 3 , bicarbonato; H2los
las células de CO3túbulos
, ácido carbónico.
proximales en el riñón. El hidrogenión (H+) es transportado hacia la luz Na+ Na+ A–
tubular por un cotransporte bidireccional en intercambio por iones sodio
(Na+). Elingresan
transporte activo por
al líquido la Na, K-ATPasa
intersticial está
un ion deseñalado con las
sodio y uno de flbicarbonato
echas H+ H+
en el círculo. –).flechas de rayas indican difusión. CO2, dióxido de carbono;
Las NH4+ A–
(HCO –
HCO3392 HCO3– del NH NH
3
K+, iones potasio; H2O, agua; HCO3–, bicarbonato; H2CO3, ácido carbónico. FIGURA Destino hidrogenión
3 (H3 +) secretado hacia un
La anhidrasa carbónica cataliza la formación de H2CO3; los fár- túbulo en intercambio por iones sodio (Na+). Arriba: reabsorción del
macos que la inhiben deprimen tanto la secreción de ácido por los bicarbonato filtrado a través del dióxido de carbono (CO2). En medio:
túbulos proximales como las reacciones que dependen de la misma. formación del fosfato monobásico (H2PO4–). Abajo: formación de
ingresan al líquido intersticial un ion de sodio y uno de bicarbonato amonio (NH4+). Obsérvese que en cada caso un ion sodio y uno de
Algunas pruebas indican que el hidrogenión es secretado en los
(HCO3–). bicarbonato (HCO3–) entran en el torrente circulatorio por cada
túbulos proximales por otros tipos de bombas, pero los indicios de FIGURA 392 Destino del–hidrogenión (H+) secretado hacia un
La anhidrasa carbónica cataliza la formación de H2CO3; los fár- túbulo hidrogenión secretado. A , anión; NH3, amoniaco;
+ HPO42–, fosfato
en intercambio por iones sodio (Na ). Arriba: reabsorción del
estas bombas adicionales son controvertibles y, en cualquier caso, su dibásico.
macos que la inhiben deprimen tanto la secreción de ácido por los
contribución es pequeña en comparación con el mecanismo debicarbonato filtrado a través del dióxido de– carbono (CO2). En medio:
túbulos proximales como las reacciones que dependen de la misma. formación del fosfato monobásico (H2PO4 ). Abajo: formación de
intercambio de sodio-hidrógeno. Esto contrasta con lo que ocurreamonio (NH +). Obsérvese que en cada caso un ion sodio y uno de
Algunas pruebas indican que el hidrogenión es secretado en los
en los túbulos distales y en los túbulos colectores, donde la secreciónbicarbonato 4
de transporte – pueden secretar corresponde a un pH urinario de casi
(HCO ) entran en el torrente circulatorio
3 por cada
Túbulo Contorneado Proximal:
Balance acido-base
cuando el bicarbonato plasmático se reduce a menos de unos 26 derivados de sulfonamidas se han utilizado en
meq/L, el valor en el cual todo el hidrogenión secretado se está utili- como diuréticos por sus efectos inhibidores en
zando para reabsorber bicarbonato, se dispone de mayor cantidad de drasa carbónica en el riñón.
Túbulo Contorneado Proximal:
Balance acido-base
Filtrado
(durante la expansión mínima hidrogeniones para combinarse con otros aniones a
Bicarbonato filtrado, excretado o reabsorbido

Reabsorbido
y acentuada)
150 Por consiguiente, cuanto más desciende la concentr
bonato plasmático, más ácida se vuelve la orina y tan
contenido de amonio (Recuadro clínico 39-1).
Expansión
100
(μeq/min)

mínima
CONSERVACIÓN
Expansión
acentuada Bicarbonato
DE LA CONCENTRACIÓN
50
Expansión
acentuada
DE HIDROGENIONES

Excretado
Expansión La tradición que envuelve al tema del equilibrio ac
mínima
necesario señalar que el problema central no es “la b
0 dora” o “el catión fijado” o algo parecido, sino simplem
0 10 20 30 40 50 60 vación de la concentración de los hidrogenion
–
Concentración plasmática de HCO3 (meq/L) extracelular. Los mecanismos reguladores de la co
líquido extracelular son muy importantes respecto d
FIGURA 394 Efecto del volumen del líquido extracelular (ECF) cífico, ya que el aparato celular es muy sensible a los
sobre la filtración, la reabsorción y la excreción del bicarbonato
concentración de hidrogeniones. Esta última, que
(HCO3–) en ratas. El patrón de excreción de bicarbonato es similar en el
ser humano; su concentración plasmática normalmente es de unos 24 con el uso de microelectrodos, colorantes fluorescen
meq/L. (Con autorización de Valtin H: Renal Function, 2nd ed. Little, Brown, 1983.) pH y resonancia magnética con fósforo, es diferente
 Túbulo Contorneado Proximal:
CAPÍTULO 39 Acidificación de la orina y excreción de bicarbonato 715
Balance acido-base
ogeniones (H+) Aminoácidos

ión de H+ NH4+ + HCO3– Glucosa H3PO4 + H2SO4 Hígado

mol/L pH *
Urea Glutamina
0.15 0.8
H+ 2–
HPO42– SO4 ECF
3 × 10–5 4.5 HCO3–

1 × 10–7 7.0 Glutamina HCO3– H+

4 × 10–8 7.4 * * Riñón
α-Cetoglutarato
2 × 10–8 7.7
NH4+ H2PO4–
1 × 10–8 8.0
Urea NH4+ H2PO4– SO42– Orina

FIGURA 395 Participación del hígado y los riñones en el control

procesos intracelulares; de las cargas de ácido que produce el metabolismo. Se indican con
concentración de hidro- asterisco los lugares donde ocurre la regulación. ECF, líquido
extracelular; NH4+, amonio; H+, hidrogenión; HCO3–, bicarbonato; H3PO4,
ácido fosfórico; H2SO4, ácido sulfúrico; HPO42–, fosfato dibásico; H2PO4–,
ara expresar las concen-
fosfato monobásico; SO42–, sulfato. (Modificada con autorización de Knepper MA,
, porque éstas son bajas et al: Ammonium, urea, and systemic pH regulation. Am J Physiol 1987;253:F199.)
or consiguiente, el valor
Rol del amonio
Túbulo Contorneado Proximal:
Balance acido-base
fic expression of brush border membrane SGLT2 in early may also have the potential to reduce the glucose toxic
mal tubule and SGLT1 in later sections of the proximal and hyperfiltration observed in the diabetic kidney. Desp
e (1, 14). Much of the evidence for the relative quantita- this new clinical interest in renal glucose handling, surpr

Reabsorción de glucosa
ress for reprint requests and other correspondence: V. Vallon, Depts. of
ne and Pharmacology, Univ. of California San Diego and VA San
Healthcare System, 3350 La Jolla Village Dr., San Diego, CA 92161
: vvallon@ucsd.edu).
ingly little information has been available on the speci
characteristics of human SGLT2 and SGLT1.
The timely study by Hummel and colleagues (5) in this iss
of American Journal of Physiology-Cell Physiology builds
the previous pioneering studies of Wright’s group in the fie

Glucose transport in the kidney. Under normoglycemia, "97% of filtered glucose is reabsorbed via the Na!-glucose cotransporter SGLT2 primarily
ly segments of the proximal tubule. A significant capacity of SGLT1 to reabsorb glucose in later segments of the proximal tubule is unmasked by SGL
on ("40% of filtered glucose under normoglycemia; see numbers in parentheses), on the basis of our previous work (14) and the assumption that ap
glucose uptake in the kidney is primarily mediated by SGLT2 and SGLT1. The glucose transporters GLUT2 and GLUT1 mediate glucose transport acr
solateral membrane. Na!-glucose cotransport is electrogenic, and luminal K! channels serve to stabilize the membrane potential (12, 13): KCN
wn #-subunit and KCNE1/KCNQ1 in early and late proximal tubule, respectively.

http://www.ajpcell.
Reabsorción de glucosa
 Reabsorción de glucosa
RENAL HANDLING
Si se supera el transporte máximo para la glucosa, esta OF ORGANIC SOLUTES / 65
aparece en la orina

Lumen
ATP
Na+
Na+ K+
Glu
Glucose reabsorption

Glu
2Na+
Glu

Rate of
600 filtration

Rate of
Glucose flux
(mg/min)

reabsorption
400

Rate of
200 Tm
excretion

0
0 150 300 450
Plasma glucose
(mg/dL)

Figure 5–1. Glucose handling by the kidney. (Top) Glucose is taken up across the
 Túbulo Contorneado
Proximal

• 70-75% de reabsorción del ltrado.

• Reabsorción de glucosa, bicarbonato

y aminoácidos 100%.
fi
 Secreciones del
Túbulo contorneado proximal

• Desde la sangre al liquido tubular.

• Productos de desecho endogenos, exogenos y toxinas.

• Muchos de ellos no fueron filtrados debido a su unión a proteínas.

• Este proceso esta mediado por transportadores (saturables).

 Organic cations enter across the basolateral membrane via one of several uniport-
ers, members of the OCT family (Organic Cation Transporter) driven energetically
by the negative membrane potential. This raises the cytosolic concentration of the

Secreciones del
cation well above that in the interstitium. The cations then exit into the lumen via
an antiporter that exchanges a proton for the organic cation (Figure 5–2). Because
this antiporter exchanges 2 univalent cations, it is electroneutral and unaffected

Túbulo contorneado proximal by the membrane potential.

Table 5–1. Some organic cations actively secreted by the

proximal tubule

Endogenous substances Drugs

Acetylcholine Atropine
Choline Isoproterenol
Creatinine Cimetidine
Dopamine Meperidine
Epinephrine Morphine
Guanidine Procaine
Histamine Quinine
68 / CHAPTER 5
Serotonin Tetraethyl ammonium
Norepinephrine
Lumen
ATP
Lumen
ATP
RENAL HANDLING OF ORGANIC SOLUTES /
Thiamine
Na+ Na+
K+ K+
Table 5–2. Some organic anions actively secreted by
3Na+ the proximal tubule
H+ C+ αKG
C+ A–
αKG Endogenous substances Drugs
A–
Bile salts Acetazolamide
Fatty acids Chlorothiazide
Cation secretion Anion secretion
Hippurates Ethacrynate
Figure 5–2. Common tubular secretory mechanisms for organic cations and anions. Hydroxybenzoates Furosemide
Secreted cations are taken up by the tubular epithelium via OCTs, driven by the nega-
tive membrane potential and secreted across the apical membrane via antiporters in Oxalate Penicillin
exchange for protons. Secreted anions are taken up across the basolateral membrane
by antiporters in exchange for αKG. They are secreted across the apical membrane by Prostaglandins Probenecid
several different transporters including the multidrug resistant protein MDR-2. Urate Saccharin
Salicylates
Sulfonamides
PROXIMAL SECRETION OF ORGANIC ANIONS
Secreción
tubular
activa
 Desechos Nitrogenados
Urea: Proteínas - aminoácidos - NH2 - removido forma amonio, el hígado lo
convierte a urea

Acido úrico: Catabolismo de los ácidos nucleicos

Creatinina: Catabolismo del fosfato de creatinina

Falla renal

Azotemia: desechos nitrogenados en sangre, exceso de urea creatinina y otros

productos nitrogenados del metabolismo de las proteínas y aminoácidos.
Uremia: efectos tóxicos por acumulación de urea.
Desechos Nitrogenados
 Nitrogeno ureico en la sangre (BUN)

BUN es un subproducto del metabolismo proteico y es producido en el hígado. Se usa para estimar la función
renal. Rango 7-18 mg/dl.

A bajos flujos, el túbulo proximal aumenta la reabsorción de urea, elevando su concentración en mayor grado que
creatinina.

La razón BUN/creatinina puede ayudar a diferenciar la insuficiencia renal de causas prerenal y postrenales de
aquellas de causa renal intrínseca.

Una razón de 10:1 sugiere patología renal intrínseca

una razón > de 20:1 sugiere patología prerenal o postrenal

El BUN puede encontrarse reducido:

Enfermedad hepática, desnutrición,
SIADH, embarazo , 3º trimestre.
BUN

Aumento de BUN:

Insuficiencia renal
Sangramiento gastrointestinal
Alta ingesta proteica

Disminución del BUN:

Falla hepática
Desnutrición
 Asa de Henle

La rama descendente:

Epitelio plano, células con escasas mitocondrias y pliegues membranosos.

Casi inexistencia de transporte activo.

La rama ascendente:

Epitelio cúbico, con abundantes mitocondrias y pliegues membranosos

Transporte activo
Concentración y dilución
de la orina
Asa de Henle, segmento
delgado
 Rama ascendente delgada

• Na+, Cl- transporte pasivo

Liquido peritubular: 600mosm por el Na+ y el Cl- y

600mosm por la urea.

Líquido tubular : 1120 mosm son de NaCl y 80

mosm por la urea.

Por lo tanto aunque las osmolaridades son iguales

habrá un gradiente de concentración para que el NaCl
tubular (1120mosm) salga hacia el espacio peritubular
(600mosm) y por el contrario la urea peritubular
(600mosm) ingrese a la luz del túbulo (80mosm).
88 / CHAPTER 6

Lumen Interstitium

Na Na
Na

2CI ATP
Na
K K
K
K

Cl
K
Cl
H2O

Figure 6–4. Major transport pathways for sodium and chloride in thick ascending limb
of the loop of Henle. The key transporter in the thick ascending limb is the Na-K-2Cl sym-
 110%
5.5

100%
1

50%
1.2

Manejo de la Urea

50%
25

Figure 5–4. Urea handling by the kidney. The arrows indicate that urea is reabsorbed in
the proximal tubule, secreted in the thin portions of the loop of Henle, and reabsorbed
again in the inner medullary collecting ducts. The top halves of boxes indicate the per-
centage of the filtered load remaining in the tubule at a given location, and the bottom
halves indicate tubular concentration relative to plasma. Note that, while the amount
remaining in the collecting duct (and thus excreted) is half the amount filtered, the
concentration is much higher than in plasma because most of the water has been reab-
sorbed. These numbers are highly variable, depending on several factors, particularly the
hydration status.
 Review of Renal Physiology 9

Asa de Henle, segmento

grueso
Tubular lumen Loop of Henle cell Peritubular capillary

Na+
K+ January 2001 Na1-K1-ATPase-DEPENDENT Na1 TRANSPORT IN

2Cl−
two diffusion
3Na+ lumen-positiv
TAL. Howev
Na-K- shunted by th
ATPase pathway; bec
2K+ than for anion
sodium reabs
back flux. Th
K+ ing force for
889). The gen
the selective
nesium, was
to be respons
Cl− With the
highest sodi
ATPase activ
conditions, t
+ − TAL cells per
the intracellu
+ −
constant intr
+ − tight coordin
porters involv
And, indeed,
leads to dram
dling. Thus B
Na+ tion of either
Ca2+ the basolater
Mg2+ tassium chan
TAL also
Tight junction fication and a
FIG. 17. Cellular mechanism of sodium, potassium, and anion trans- an apical V-t
FIGURE 1.3. Schematic model of ion transport in the thick ascending limb of the loop port in thick ascending limbs of Henle’s loop. Arrows indicate net fluxes TAL is prima
of solutes. The names of the currently cloned transporters are men- both NHE-2 a
of Henle. The lumen-positive potential generated by the recycling of potassium promotes tioned into rectangular boxes.
membranes (
Asa de Henle, segmento
grueso
 Review of Renal Physiology 11

Túbulo contorneado
distal

Tubular lumen Distal tubular cell Peritubular capillary

Na+

−
Cl

3Na+
Na-K-
ATPase
2K+

D-dependent
Ca++
Ca-binding protein

Ca-
ATPase

Ca++

1Ca++

3Na+

FIGURE 1.4. Schematic representation of the transport mechanisms involved in

 Túbulo colector
Tubular lumen Collecting tubule cell Peritubular capillary

Na+
+

− 3Na+
Na-K-
− ATPase
−
− 2K+
K+
ALDO Aldosterone
R
cGMP

AQP2 ANP receptor

ATP
Gs
CAMP
Adenyl V2 receptor
cyclase
+ AQP-3, -4
PKA
H2O

Cl– Cl–

Tight junction
Vasopresina (ADH)
 P;9I'6; TB6;:B5F6;: D'<?9E:F?;:

P;EF,7:''I',F.@'I6<
Q*(R.!.LS-.//?'M2 +,(G*(GD34,9: THEF,7:''I',F.@'I6<
Plate 7.18 Potassium Balance I 183 Q*(R.U.%KS& VKW//?'M2
56770)89:1,-./7.;7)<,+1*)::9:1+7%&7*./*)/,+1,-./

Potasio (K+)
+,(
*(

7 Kidneys, Salt, and Water Balance

J6:E,FC.IBE,8: *(
*(
X]'I7?9:O J6:E,FC.6;E,8:
,/6;?.,76<9.:E7KY 7,K.L--.//?'M<,C 45C967,'.N?F8O "CB:F8,':/6, *(
EF,I/,
D76<?969
"( *(

P;9I'6; TB6;:B5F6;: D'<?9E:F?;:

TH7F:E6?;
(
* .75,;;:'9
P;EF,7:''I',F.@'I6<
Q*(R.!.LS-.//?'M2 +,(G*(GD34,9: THEF,7:''I',F.@'I6<
Q*(R.U.%KS &VKW //?'M2 =6770)3.+4,-./71/>73)*+),-./7.;7%&7-/7,?)7@->/)A
2'34 ()*+),-./.XN6E5.,'<?9E:F?;:Y
( +,(
* &)-./0 &1-./0
*(
(
D76<?969 * (
*
"( *(
")$
TH7F:E6?; +,(
(
* .75,;;:'9
! *( *(
&
=6770)3.+4,-./71/>73)*+),-./7.;7% 7-/7,?)7@->/)A
2'34 ()*+),-./.XN6E5.,'<?9E:F?;:Y *( *( *(
&)-./0 &1-./0
*( *(
")$
+,(
$ 4F?H6/,'.EI>I':.7:'' "
! (
* *( 4F6;76B,'.7:''.?@.7?;;:7E6;=
*( *( *( %& EI>I':.,;<.7?'':7E6;=.<I7E
Z6'EF,E:[.L--\
" 2,E:.BF?H6/,'[.7,K.%S\
$ 4F?H6/,'.EI>I':.7:''
4F6;76B,'.7:''.?@.7?;;:7E6;= T,F'C.<69E,'[.7,K.L- & )- \
%& EI>I':.,;<.7?'':7E6;=.<I7E
Z6'EF,E:[.L--\ Z6;,'.IF6;:[.% & )-- \ 0)123.+4,-./.XN6E5?IE.,'<?9E:F?;:Y
2,E:.BF?H6/,'[.7,K.%S\
T,F'C.<69E,'[.7,K.L- & )- \
Z6;,'.IF6;:[.% & )-- \ 0)123.+4,-./.XN6E5?IE.,'<?9E:F?;:Y

2'34 ")$ #'&

2'34 ")$ #'&
"#$%& "#$%&
"#$%& "#$%&
*( *( #DPP
*( *( #DPP
( (
" G* GD34,9: "(G*(GD34,9:
$"& ( #$)
"(
"(
+,(
"( $"& ( #$)
*( (
+,(
"
*(
*( *(
! 35678.,97:;<6;=.'6/>.?@.":;':A9.'??B
*( *(
*(
# 3CB:.D.6;E:F7,',E:<.7:'' ! 35678.,97:;<6;=.'6/>.?@.":;':A9.'??B
*(

# 3CB:.D.6;E:F7,',E:<.7:''
 Plate 7.19 Potassium Balance II 185

4+,,52.&$(%,&62&,211'.&,,78,%'.('&/$),2)#,'9.('&/$)

7 Kidneys, Salt, and Water Balance

%&
4.F*+,.2:
&
&
% )F@,(A+ '( )F@,(A+
9F*/:+B.0+?
C2.0/:.: I@.*/-/P ,<.(Q.0+:
6"9)>/8FB+ 8(2,/-+
'(&)*+(K:/*@,./-
.-)#+-8+L:)8//@
(-0)0.:,(8),FKF8+?)*+:@M
N%&O).-)@8(:B( C80/:,+*/-+
(-0)2+88:
'(&):F@@8=)(-0)R8/J)*(,+
'(&)*+(K:/*@,./- .-)2/88+2,.-5)0F2,
.-)2/88+2,.-5)0F2,

%&):+2*+,./-

*+,,-'.('&/$)0,'11'.&,2)#,#'3(2#2&/$),$1,2"#$%&'($)'
78//0)@*+::F*+ #=@+*A(8+B.(
 ()&&*+"$,-./01-2&-3&/4-,/4"0+5&6"#7&"28&9:#7

7 Kidneys, Salt, and Water Balance

! '((
!"#$

E-B;@&;<
)(
%&#$

F&;<=:@8G-C&B
5=8A=A-B;<@<?=&C8D>;
*(

,789:7&;<
Fosfatos (PO4-), Calcio

H&@BI=?-9;&B
+( (Ca+2) y Magnesio

E->&B=D@-><
%8>;@8B=@&>"<

#( 3 4 #( 5
(Mg+2)
24)5
(63 4 2 5
(

'==,789:7&;<=;@&>9:8@;
./#0&1)"*(+,+"-*4-""
!"##$
;+1-2

/ #
$
,-
.&
,01
M8N>=@<"DB&;-8>
,- %&#$
,789:7&;<
O>9<@;-8>
!"#$

,-=?<A-J-;
KBL&B89-9
1I:<@J&BJ<C-&

%&&%&#$=&>?=!"#$=;@&>9:8@;
;+1-2

!"##$

%&#$

!"#$

"
./#0&1)"*(+,+"-*)2$
(3&45*)'4-2$&26
"&1,*#7*8-2"-9'*"##: 2.&$

%&#$

!"#$
$
%&'()"*(+,+"-
Túbulo colector
Resumen
Resumen
 6()-

D@;;E)0-;5B;*10)56;5B;,)./-0)12
'()*+),-
,)./-0)12
9*/:56)1;*6(<,/*2-
)6():)05/2
F2K<K=>(/2-(L%)('.32G
$(M,7)N>+C'B%&-

34,520-/56-
*60*756)202
$(M>(;3>!7#PN F2K<K=>+B.&%;%)(/-%;2G
&2(@+%&B-.%;

$(M>/?(;;2)
F.;3.&2/->2442/-G
=55>;,)./-0)12
F2K<K=>41&%+2'.32G
38)45/),-

$(M,"7)N,OM>+C'B%&- $(M>/?(;;2)
F3.&2/->2442/-G

$(7)>&2(@+%&B-.%; !"#>&2(@+%&B-.%; 97Q>0%)1'2

Micción
 Regulación
Neuroendocrina de la
función renal
SNA
PERSPECTIVES

↑ Renal sympathetic nerve activity −5.9 mmHg (95% CI −11.3 to −

favour of renal denervation28. In
in the single-centre SYMPLICIT
Renal vasculature Juxtaglomerular granular cells Renal tubular epithelial cells study29, published in mid-2015,
↓ Renal blood o ↑ Renin secretion rate ↑ Renal tubular sodium randomized 71 patients with mo
reabsorption and urinary treatment-resistant hypertension
sodium excretion
denervation or sham control. W
were analysed according to per p
performance of the renal denerv
procedure, the change in 24 h sy
pressure at 6 months was signifi
Glomerulus for the renal denervation compa
sham-controlled group: −8.3 mm
−11.7 to −5.0 mmHg) versus −3
(95% CI −6.8 to −0.2 mmHg; P =

Truth or ‘illusion of truth’?

The unexpected neutral results f
SYMPLICITY HTN-3 have bee
debated30–34. As the largest trial o
denervation to date and the first
a sham design, many believed th
publication of SYMPLICITY HT
signalled the end for renal dener
Figure 1 | Effect of increased efferent renal sympathetic activity on three renal nerve effectors. Others argued that the SYMPLI
Increased renal efferent sympathetic activity leads to an increase in renin secretion
Nature from
Reviews the juxta-
| Cardiology findings were at odds with num
glomerular apparatus, increased renal tubular sodium reabsorption and reduced urinary sodium previous and subsequent studies
excretion, and reduced renal blood flow. These mechanisms increase circulating volume, promote
with the sound pathophysiologi
arteriolar vasoconstriction and increase systemic blood pressure.
the procedure. Several possible r
explain the ‘failure’ of SYMPLIC
compared with other renal interventions, as the primary end point27. Both groups had to demonstrate efficacy have bee
but no significant difference in reduction a significant reduction in blood pressure, (BOX 1), including a placebo effec
 Downloaded from http://physrev.physiology.org/ by 10.220.33.2 on July 10, 2017
FIG. 3. Topology of the main nephron segments and sites of action of hormones controling sodium transport.
Schematical representation of a nephron with its successive portions: 1) glomerulus; PCT, proximal convoluted tubule;
PST, proximal straight tubule; 2) thin descending limb of Henle’s loop; 3) thin ascending limb; MTAL, medullary thick
ascending limb of Henle’s loop; CTAL, cortical thick ascending limb; 4) macula densa; 5) distal convoluted tubule; 6)
connecting duct; CCD, cortical collecting duct; OMCD, outer medullary collecting duct; IMCD, inner medullary collecting
duct. For the three structures analyzed in this review (proximal tubule, thick ascending limb of Henle’s loop, and
collecting duct), we mentioned the main hormones or factors that stimulate (3) and inhibit (?—) sodium reabsorption:
ANG II, angiotensin II (low and high referring to pico- and micromolar concentrations); adr, adrenergic agonists; AVP,
arginine vasopressin; PTH, parathyroid hormone; GC, glucocorticoids; MC, mineralocorticoids; PGE2, prostaglandin E2;
ET, endothelin; ANP/Urod, atrial natriuretic peptide and urodilatin; PAF, platelet-activating factor; BK, bradykinin.
 bonate-dependent and -independent transporters. Acti
tion of Na1-K1-ATPase results from increased affinity
sodium brought about by its PKC phosphorylation
Ser-16 without change in its Vmax.
Finally, a PLA2/arachidonate/cytochrome P-4
monooxygenase pathway downregulates the transp
properties of proximal tubules, mainly through inhibit
Túbulo Contorneado
of Na1-K1-ATPase. This inhibitory pathway may be tr
gered by some types of PKCs and/or in response to m
Proximal, regulación
abolic stress. By inhibiting ATP consumption, it can
hormonal.
considered as a protective mechanism against the dele
rious effects of cellular ischemia.
Phorbol ester-sensitive PKCs are the main mediat
of the stimulatory effects of low concentrations of ANG
and of a-adrenergic agonists, eventhough decreas
cAMP production may also participate to the upregulat
of NHE-3. The cAMP/PKA pathway underlies the stimu
tory effect of b-adrenergic agonists, with the inhibito
effect of cAMP/PKA on H1-HCO2 3 transporters be
likely prevented through functional inhibition of NHE-
by direct interaction with activated b-receptors. Fina
the inhibitory effects of dopamine and PTH are media
in part by the PLA2/arachidonate/cytochrome P-4
monooxygenase pathway (inhibition of Na1-K1-ATPa
and in part through cAMP/PKA pathway (inhibition
H1-HCO2 3 transporters).
In addition, tyrosine kinase phosphorylation of N
1
K -ATPase on Tyr-10 appears as the main mechanism
the stimulatory effect of insulin. In contrast, the stimu
tory effect of glucocorticoids mainly results from tr
scriptional activation of apical transporters.
FIG. 16. Overview of the principal signaling pathways controlling
sodium transport in proximal tubule cells. Arrows indicate the direction
of the signaling cascade and the resulting stimulatory (1) or inhibitory
(2) effect on their targets. AT1, angiotensin II receptor; PTHR, parathor-
V. HORMONAL CONTROL OF SODIUM
mone receptor; a1-adr, a1-adrenergic receptor; a2-adr, a2-adrenergic TRANSPORT IN THE THICK
receptor; b-adr, b-adrenergic receptor. ASCENDING LIMB
AILLE AND ALAIN DOUCET Volume 81

ygous

l2 co-
TPase)
bsorp-
en the
of api-
exit.
icated
ateral
was in-
(377), Control hormonal en el

Downloaded from http://physrev.physiology.org/ by 10.220.33.

apical
trans- asa de Henle
ssium
e con-
loride
eger’s
baso-
ellular
al ion

as not
entry,
steps
n any
FIG. 18. Overview of the principal signaling pathways controlling the
asolat- active sodium transport in cells of the thick ascending limb of Henle’s
ivated loop. Arrows indicate the direction of the signaling cascade and the
resulting stimulatory (1) or inhibitory (2) effect on their targets. PDE,
phosphodiesterase; BK, bradykinin; CT, calcitonin; GL, glucagon.
on of
loride
stim-
enes,

physrev.physiology.org/ by 10.220.33.2 on July 10, 2017

n the
h of
pres-
d for
f the
(252,
an in
met-
ms.
ction
ne or
ntry.
ndog-
onds
n the
ect), Control hormonal en el
the
reas-
conducto colector
cting
vivo
milo-
1 1
-K -
ed in
nt to
622),
Pase
that
of an
dium
ance. FIG. 20. Overview of the principal signaling pathways controlling the

vivo active sodium transport in principal cells of the collecting duct. Arrows
1 indicate the direction of the signaling cascade and the resulting stimu-
/H1 latory (1) or inhibitory (2) effect on their targets. V2, vasopressin V2
dium receptor; MR, mineralocorticoid receptor.
 Plate 7.13 Salt and Water Regulation II 173

/=''56+4.&8'$,&+3$&+02'$2('+26+7+&+02

7 Kidneys, Salt, and Water Balance

56+4.&'.&+;<%<.8
GEH/&"2K-$/0EH/4-+53% 9'3-+&+!.:/-F/GEH D-$3-"%'
IL-3!.!",M/2!&$$*%&M I?&+./%A#%''/-$/@&.%$/2%F!#!.J )%$!)*%$&+/&",!-.%"'!"/00M/$%+&A!"
*%3-$$*&,%M/2!5$%.!#'M/65$"'J
4*#+$,
5$20/()3%6.'&+$
67#.28(32'&%"9
56+4.&'+26+7+&+028
1;(

E%".$&+
&",!-.%"'!"/00
/012+&+3)'4)$,&+02.
E%".$&+%/-'3-'%"'-$' ?@:> P/&@&$%"%''/-F/.*!$'.
:;<=> P/'%%Q!",/@&.%$

-.)'/(0&#&1$%+#/
.%"(2.0#&*0+3).2
9:/"-/6+--2=6$&!"/6&$$!%$
(%$!)*%$&+/)$%''5$%
&"2/4-+53%/'%"'-$' -=? 1CD

9LN>O/-$,&"53/4&'#5+-'53/+&3!"&%/.%$3!"&+!' ?H9O/'56F-$"!#&+/-$,&" ;>?O/;5#+R/.$&#.5'/'-+!.&$!!

>=''?)1<%$&+02'0*'.$%&'7$%$2,)
#$%&'()*+,+& ! ;&</&))%.!.% " #$%&')-,)..
>*!$'.
9'3-+&+!.: 9'3-+&+!.:
 Estímulos para la renina

Hígado

Riñón Sistema renina-

angiotensina-aldosterona
Angiotensinógeno
(453 aa)

02 SECCIÓN VII Fisiología renal

Renina (enzima)

uricular (ANP) y el péptido natriurético

Angiotensina cerebral
I (PBC) por el cora- Angiotensinógeno
(10 aa)
n, lo cual produce natriuresis y diuresis.
Renina
En los estados patológicos, la pérdida de agua del cuerpo (des-
Angiotensina I Bradicinina
dratación) origina decremento moderado del volumen del líqui-
o extracelular, a causa de la pérdida de agua de los compartimientos Enzima convertidora de angiotensina
Angiotensina I
e los líquidos intracelular
Enzima convertidora y extracelular, pero laEnzima
de angiotensina
pérdida de sodio en
convertidora
de angiotensina
Angiotensina II Metabolitos
inactivos
s heces (diarrea),(endotelio)
la orina (acidosis grave e insufi ciencia suprarre-
(endotelio) Diversas Receptores AT1
al) o el sudor (postración por Angiotensina II
el calor) disminuyen notablemente el peptidasas
AIII, AIV, Receptores AT2
olumen del líquido extracelular y, tarde o temprano, se desencade- otras
a choque. Las compensaciones inmediatas en el estado de choque
Angiotensina II Metabolitos
peran principalmente para mantener (8 aa) el volumen intravascular, inactivos
ero también afectan el equilibrio del sodio. En la insuficiencia
prarrenal, la declinación del volumen del líquido extracelular se FIGURA 386 Formación y metabolismo de las angiotensinas
Corteza
ebe no sólo a la pérdida de este ion en la orina, sino también
Aparato a su
suprarrenal presentes en la circulación sanguínea.
cardiovascular Aldosterona
ovimiento hacia las células. Dada la posición clave del sodio en la
omeostasis del volumen, no es de sorprender la evoluciónRiñón de más
Al igual que otras hormonas, la renina es sintetizada como una
e un mecanismo para controlar la secreción de este ion.
preprohormona de gran tamaño. La preprorrenina humana contie-
En el capítulo 37, se revisa la filtración y la resorción
Vasoconstricción de sodio en
Retención
de sal y H2O ne 406 residuos de aminoácidos. La prorrenina que permanece des-
s riñones y los efectos de estos procesos sobre la excreción de dicho
pués de retirar una secuencia guía de 23 residuos de aminoácidos del
n. Cuando disminuye el volumen del líquido extracelular, descien-
amino terminal contiene 383 residuos de aminoácido y, luego de
e la presión arterial, se reduce la presión de los capilares glomeru-
retirar la prosecuencia del amino terminal de la prorrenina, la reni-
res y, por tanto, hay decremento de la tasa de filtración glomerular
Presión arterial
na activa posee 340 residuos de aminoácidos. La prorrenina presen-
GFR), con reducción de la cantidad de sodio filtrado. La resorción
 M.:?C76B26R,C2::-

6/--!"#$#7%#,$(*"#)$#789)*"4

+H=A6CF.:-C8BI K6B8BC,6H.6A8:B >:.?128@1A8:BC:D

921,?1CE:2=?6 -21,?1CE:2=?6C1BF
1BFCG2::FC-.6,,=.6 G2::FC-.6,,=.6

!"#$#

#!$
! " # $ % & ' ( ) !* !! !" !
+B/8:A6B,8B:/6B

*
! " # $ % & ' ( ) !6=
+,- +./ 012 34. 526 78, 9.: 9;6 78, <
+B/8:A6B,8BC5

J:BE6.A8B/
6B@4?6

! " # $ % & ' (

+,- +./ 012 34. 526 78, 9.: 9;6

%#,$(*"#)$#-..

J.1E8B/CD:.C,12A
58,*2%&'7-,$*.
3;8.,A

L6B6.12
E1,:H:B,A.8HA8:B
LMKC1BFCKNM %&'()*"+(#"

K6F=H6FC,12AC1BFCO1A6.C6PH.6A8:B

5BH.61,6FCD2=8FC1BFC,12AC8BA1Q6
Section V FLUID, ELECTROLYTE, AND HEMATOLOGIC HOMEOSTASIS

Renin-angiotensin-aldosterone system
Legend
Sympathetic
Secretion
activity from an organ
+ +
Stimulatory
Kidney Na+ –
signal
Lungs Tubular Na+ Cl– K+ Inhibitory signal
Liver Surface of pulmonary reabsorption and K+ Cl– Reaction
and renal endothelium: + excretion. H O retention
ACE 2 H2O Active transport
Passive
Adrenal gland: + transport
+
+ cortex Aldosterone
Angiotensinogen Angiotensin I Angiotensin II Water and salt
secretion retention. Effective
+
circulating volume
Decrease in Renin increases. Perfusion
renal perfusion + Arteriolar
+ vasoconstriction. of the juxtaglomerular
(juxtaglomerular
apparatus increases.
apparatus) Increase in blood
– pressure
Arteriole
Kidney +
ADH secretion
Pituitary gland:
posterior lobe +
Collecting duct: H2O
H2O absorption

Figure 32-4 Renin-angiotensin-aldosterone system. The renin-angiotensin-aldosterone system regulates blood pressure and fluid balance. When blood volume
is low, juxtaglomerular cells secrete renin into the circulation. Plasma renin then converts angiotensinogen released by the liver to angiotensin I. Angiotensin
I is subsequently converted to angiotensin II by angiotensin converting enzyme (ACE) found in the lungs. Angiotensin II is a potent vasoactive peptide
that causes blood vessels to constrict, resulting in increased blood pressure. Angiotensin II promotes ADH secretion by the posterior pituitary, increasing
water reabsorption by the kidneys, resulting in decreased urinary output. Angiotensin II also stimulates the secretion of the hormone aldosterone from the
adrenal cortex. Aldosterone causes the tubules of the kidneys to increase the reabsorption of sodium and water into the blood. This increases the volume
of fluid in the body, which also increases blood pressure.
 *+,,-'.('&/$)0,'11'.&,2)#,#'3(2#2&/$),$1,2"#$%&'($)'
78//0)@*+::F*+ #=@+*A(8+B.(

H+-.-
C"D#

I++)-+1,)@8(,+

C-5./,+-:.-)GG
! "#$!#
C,*./@+@,.- #" " !
#!

3"$,
4#"1(+2#"5, !"#$%&'($)'
I+2*+,./- !
+/(0

;<=:.2(8 '(&)*+,+-,./-)(-0
(2,.>.,=?
"

%&)+12*+,./-).-3
-.

:,*+::
,#
*'+($

I(8.>(*=)58(-0:
6@.-+@<*.-+ IJ+(,)58(-0:
*'+($,#-1('2##, 4+5*(0(,./- E(88K8(00+*
E8F2F*/-(,./-
.-),<+)8.>+* &
%& '(&
'( %&
612*+,./-

7.8+
%&'$()
9+2+: !"#"$
Vitamina D y Riñón
EPO y Riñón
Fisiología renal y
homeostasis
hidroelectrolítica
Jorge Sanhueza S., PhD