Download Renal Physiology 1

Renal Physiology 1
Dr Derek Scott
[email protected]
See also your renal lectures from
BI25B2. These are still on the
School of Medical Sciences
Website.
Aims & Content of this lecture
• To provide you with a reminder of what
you covered in the dim and distant past at
level 2!
• Brief review of renal anatomy
• Explanation of kidney function
• The 3 basic renal processes
• Processes of filtration at glomerular
capillaries
• Processes of reabsorption at peritubular
capillaries
• Renal handling of Na+, K+, glucose and
amino acids
• The countercurrent multiplier
Renal system – important points
• Kidneys have excellent
blood supply: 0.5%
total body weight but
~20% of CO.
• Kidneys process
plasma portion of blood
by removing
substances from it, and
in a few cases, by
adding substances to it.
• Works with
cardiovascular system
(and others!) in
integrated manner
The functional unit of the kidney:
the nephron
• Total of about 2.5
million in the 2 kidneys.
• Each nephron consists
of 2 functional
components:
– The tubular
component (contains
what will eventually
become urine)
– The vascular
component (blood
supply)
• The mechanisms by
which kidneys perform
their functions depends
upon the relationship
between these two
components.
Glomerulus and Bowman’s capsule
• Glomerular filtrate drains into
Bowman’s space, and then
into proximal convoluted
tubule.
• Endothelium has pores to
allow small molecules through.
• Podocytes have negative
charge. This and the basement
membrane stops proteins
getting through into tubular
fluid.
• Macula densa senses GFR by
[Na+]
• Juxtaglomerular (JG)
apparatus includes JG cells
that secrete renin.
• JGA helps regulate renal blood
flow, GFR and also indirectly,
modulates Na+ balance and
systemic BP
Functions of the kidneys
• Regulation of H2O and inorganic ion balance –
most important function!
• Removal of metabolic waste products from blood
and excretion in urine.
• In kidney disease, build-up of waste serious, but
not a bad as ECF volume and composition
disturbances.
• Removal of foreign chemicals in the blood (e.g.
drugs) and excretion in urine.
• Gluconeogenesis
• Endocrine functions (e.g. renin, erythropoetin,
1,25-dihydroxyvitamin D)
The three basic renal
processes
• Glomerular filtration
• Tubular reabsorption
• Tubular secretion
• GFR is very high:
~180l/day. Lots of
opportunity to precisely
regulate ECF composition
and get rid of unwanted
substances.
• N.B. it is the ECF that is
being regulated, NOT the
urine.
Glomerular filtration
• GFR controlled by
diameters of afferent
and efferent arterioles
• Sympathetic
vasoconstrictor nerves
• ADH and RAAS also
have an effect on GFR.
• Autoregulation
maintains blood supply
and so maintains GFR.
Also prevents high
pressure surges
damaging kidneys.
• Unique system of
upstream and
downstream arterioles.
• Remember: high hydrostatic pressure (PGC) at glomerular
capillaries is due to short, wide afferent arteriole (low R to
flow) and the long, narrow efferent arteriole (high R).
GFR depends on diameters of afferent
and efferent arterioles
Glomerulus
Afferent arteriole
Efferent arteriole
GFR
GFR
Glomerular
filtrate
Aff. Art. dilatation
Prostaglandins,
Kinins,
Dopamine (low
dose), ANP, NO
Eff. Art.
constriction
Angiotensin II
(low dose)
Aff. Art.
constriction
Ang II (high dose),
Noradrenaline (Symp
nerves), Endothelin,
ADH, Prost. Blockade)
Eff. Art. dilatation
Angiotensin II
blockade
Peritubular reabsorption
• Peritubular capillaries
provide nutrients for
tubules and retrieve the
fluid the tubules reabsorb.
• Oncotic P is greater than
hydrostatic P in these
capillaries, so therefore get
reabsorption NOT filtration.
• Must occur since we filter
180l/day, but only excrete
1-2l/day of urine.
• Reabsorb 99% H2O, 100%
glucose, 99.5% Na+ and
50% urea. Most of this
occurs at proximal
convoluted tubule.
Renal transport systems
• Lots of transporter
proteins for different
molecules/ions so they
can be reabsorbed.
• They all have maximum
transport (TM) capacities
where transport
saturates i.e. 10mmol/l
for glucose.
• Over this value, you
excrete the excess in
urine, so can be useful
sign of disease either in
kidneys or other
systems.
• Amino acids also have a
high TM value because
you try and preserve as
much of these useful
nutrients as possible.
Na+ absorption
• Na+ absorbed by active
transport mechanisms, NOT
by TM mechanism. Basolateral
ATPases establish a gradient
across the tubule wall.
• Proximal tubule is very
permeable to Na+, so ions flow
down gradient, across
membranes.
• Microvilli create large surface
area for absorption.
• Electrical gradient created also
draws Cl- across.
• H2O follows Na+ due to
osmotic force.
• Means fluid left in tubule is
concentrated.
Glucose handling
• Glucose
absorption also
relies upon the
Na+ gradient.
• Most reabsorbed
in proximal
tubule.
• At apical
membrane, needs
Na+/glucose
cotransporter
(SGLT)
• Crosses
basolateral
membrane via
glucose
transporters
(GLUT’s), which
do not rely upon
Na+.
Amino acid handling
• Preserve as much of these essential nutrients as possible.
• Can be absorbed by GI tract, products of protein catabolism, or
de novo synthesis of nonessential amino acids.
• TM values lower than that of glucose, so can excrete excess in
urine.
• Amino acid transporters rely upon Na+ gradient at apical
membrane, but a couple of exceptions don’t.
• Exit across basolateral membrane via diffusion , but again,
some exceptions rely on Na+.
K+ handling
• K+ is major cation in cells and
balance is essential for life.
• Small change from 4 to 5.5
mmoles/l = hyperkalaemia =
ventric. fibrillation = death.
• To 3.5 mmoles/l =
hyperpolarise = arrhythmias
and paralysis = death.
• Reabsorb K+ at proximal
tubule.
• Changes in K+ excretion due
to changes in K+ secretion in
distal tubule
• Medullary trapping of K+ helps
to maximise K+ excretion
when K+ intake is high.
K+ handling
• K+ reabsorption along the
proximal tubule is largely
passive and follows the
movement of Na+ and
fluid (in collecting
tubules, may also rely
active transport).
• K+ secretion occurs in
cortical collecting tubule
(principal cells), and
relies upon active
transport of K+ across
basolateral membrane
and passive exit across
apical membrane into
tubular fluid.
Modulation of K+ secretion
Luminal factors
Stimulators
Inhibitors
 Flow rate
 [K+]
 [Na+]
 [Cl-]
 [Cl-]
 [Ca2+]
 [HCO3-]
Ba2+
-ve luminal voltage
Amiloride
Selected Diuretics
Peritubular Factors
Stimulators
Inhibitors
 K+ intake
pH
 [K+]
Adrenaline
pH
Aldosterone
ADH
Countercurrent
Multiplier
•Countercurrent is easy, fluid
flows down the descending limb
and up the ascending limb.
•The critical characteristics of
the loops which make them
countercurrent multipliers are:
•1. The ascending limb of the
loop of Henle actively cotransports Na+ and Cl- ions out
of the tubule lumen into the
interstitium.
The ascending
limb is impermeable to H2O.
•2. The descending limb is
freely permeable to H2O but
relatively impermeable to NaCl.
H2O that moves out of tubule
into intersitium is removed the
blood vessels called vasa recta –
thus gradients maintained and
H2O returned to circulation.
formation of
hyperosmotic
urine
Osmolality of fluid along nephron
• Red = water
restriction
• Blue = high
water intake
• Initial
concentration of
tubular fluid at
loop of Henle,
then finally at
collecting ducts.
Role of urea in concentrating
urine
• Urea very useful in concentrating
urine.
• High protein diet = more urea =
more concentrated urine.
• Kidneys filter, reabsorb and secrete
urea.
• Urea excretion rises with increasing
urinary flow.
Urea recycling
• Urea toxic at high
levels, but can be
useful in small
amounts.
• Urea recycling
causes buildup of
high [urea] in
inner medulla.
• This helps create
the osmotic
gradient at loop of
Henle so H2O can
be reabsorbed.