Transcript Aldosteron

Biochemical aspects
of the kidney function
František Duška
Overview
• Functions of exploded nephron
• Internal environment and the kidneys
– isovolumia
– isoionia
– isohydria
• Excretion of nitrogen waste (urea and
ammonia)
• Kidney as an endocrine and metabolic
organ
Nefron
Glomerular filtration I.
• Blood plasm is strained through a
molecular sieve composed of:
– capillary endothelium
– basal membrane: colagen IV., glycoproteins
– podocyte processes
• Basal membrane is negatively charged,
foreclosing albumin to pass through.
Glomerular filtration
II.
• 20% of flowing plasma is filtered (2 ml/s),
i.e. 160-180 l daily
• Primary urine:
– is identical with plasma, but...
– contains only a small amounts of proteins (α2
and β2 microglobulin, lysozyme) which are
than resorbed in tubules
Proteinuria
• ...means pathological presence of protein in
definitive urine (i.e. > 0.15 g/24 hr.)
• ...is common sign of glomerular impairment:
– mechanical: non-selective proteinuria
– charge loss: albuminuria
• “Tubular proteinuria“: the presence of proteins
normally filtered, which are not resorbed in tubules
• Extrarenal causes: myoglobine, Hb etc..
Tubules sophisticated
analytical laboratory
• Tubules analyse urine and excrete or
save back substances according to
body needs, using:
– tubular resorption (back to plasma)
– tubular secretion
• Many active transporters - huge
energy demands
• Hormonal regulation (ADH,
aldosteron)
Proximal tubule
• …is a site of obligatory (hormoneindependent) resorption of:
– most Na+, Cl-, K+, 70% of water
– all filtered glucose and amino acids
– bicarbonate
• Actively resorbed Na+ is followed by Cl- and
water
• Secondary active transport of Glc and AA
The loop of Henle
• Function:
– resorption of futher 20% of filtrated volume
– creation of hyperosmolar environment in the
kidney medulla
• Counter-current multiplication system
– descending limb is freely permeable for water
– ascending limb has Na+K+2Cl- co-transporter
Distal tubule
• Aldosterone-dependent Na+ resorption
and K +excretion
• Further resorption of 0 - 5% filtered water
• Aldosterone:
– increases Na+ and fluid conserving in the
body
– insreases K+ excretion in the distal tubule
– acts by inducing Na+ K+ ATPase of
bazolateral membrane
Collecting tubule
• …determines definitive urine final
volume and osmolality
• ADH increases tubule wall
permeability for water, thus
concentrating urine
– in the presence of ADH water is
passively moved to hyperosmotic
intersticium
– otherwise urine pass the kidney medulla
Water metabolism obligatory resorption
• From180 l of primary urine daily:
– 60-70% (110-130 l) is resorbed in the
proximal tubule
– 20% (40 l) is resorbed in counter-current
systém of Henle’s loop
– remains 20 l of hypotonic urine
incomming to the distal tubule…
…and here excreted volume is to be
regulated.
Regulation of urine
volume and osmolality
• … 20 - 30 l of hypoosmotic urine daily
come to the distal tubule, where...
• Aldosteron - conserves sodium,
increases kalium excretion (Na+ / K+
exchange)
• ADH - conserves water
• Definitive urine: 0.5 - 24 l daily (normally
1-2 l), 100 - 1400mosm/l, according to
body needs to maintain plasma volume
Disturbancies of urine
volume and osmolality
• Polyuria = > 3 l/24 hours
– osmotic diuresis
– water diuresis
• Oliguria = < 0.5 l/24 hours
• Anuria = < 0.1 l/24 hours
• Izostenuria
Izoionia - ion
concentration stability
• Na+ active transport is a force for
water, glucose and chloride resorption
• K+:
– resorbed in proximal tubule
– excreted in distal tubule (aldosterone)
– antiport with Na+, competition with H+
• Ca2+ and phosphate: PTH and vit. D
The kidney (and lung) is the
most important organ for
maintaining acid-base
balance.
Protecting the internal
environment against acid
overload.
Izohydria I.
proximal tubule
• Bicarbonate
reabsorption
• H+ secretion
• Carboanhydrase
• H+ excretion
depends on pCO2
+
H
secretion into the
distal tubule
• H+ ATPase performs H+ transport
• Aldosteron increases H+ secretion
• H+ in the urine
– reacts with NH3 (glutaminase, GDH)
– reacts with HPO42-
• Urine pH varies between 4.5 - 8.0
Nitrogen-containing
compouds excretion
• Urea:
– is synthesized in liver
– passivly passes th¨rough the membranes
– plays a role in the counter-current mechanism
• Ammonia, an important urine buffer, rises
from glutamine (and glutamate)
• Creatinine comes from muscles, is neither
resorbed nor excreted in tubules. It is thus
useful for glomerular filtration rate calculations.
The kidney as an
endocrine organ
• Renin-angiotensin system, kalikrein-kinin and
prostaglandins have especially an influence on
haemodynamics (see physiology)
• Erytropoetin
• The role in vit. D3 metabolism: final
hydroxylation on the 1 position gives a rise to an
active form of vitamine D: calcitriol (1,25 dihydroxycholecalciferol)
The role in
intermediary
metabolism
• Tubular epithelium is the most active
• Active transports are energized by
lactate, glutamine and FA oxidation
• Most of the pathways ¨need oxygen.
• Important organ of gluconeogenesis
(and ketogenesis?) during starvation
• Glutamine...
Renal failure
• Hyperkalemia
• Urea and creatinine plasma levels rise
• Acidosis (phosphate and sulphate
accumulation)
• Chronic renal impairment: anaemia
(APO), bone disorders (Ca)
• Volume changes
Review
• The kidney is important for maintaining
stability of internal environment (volume, ion
composition and pH)
• …excrete nitrogen from the body.
• … are a source of several hormones
• … are a target organ for several hormones
• … have an influence on ABB, circulation,
bone, intermediary metabolism, erythropoesis
etc...