RENAL PHYSIOLOGY, HOMEOSTASIS OF FLUID · PDF file2017.12.06. 1 RENAL PHYSIOLOGY, HOMEOSTASIS...
Transcript of RENAL PHYSIOLOGY, HOMEOSTASIS OF FLUID · PDF file2017.12.06. 1 RENAL PHYSIOLOGY, HOMEOSTASIS...
2017.12.06.
1
RENAL PHYSIOLOGY,
HOMEOSTASIS OF FLUID COMPARTMENTS (3)
Dr. Attila Nagy
2017
Protein-type reabsorption
Peptides with small molecular weight: carrier
mediated mechanism,
Proteins with large molecular weight are reabsorbed
with pinocytosis (endocytosis),
albumine, hemoglobine
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Urea transport in the nephron
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CO
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ACTIVE TRANSPORT
PASSIVE TRANSPORT
Urea transport in the nephronUrea-cycle
Uric acid
The filtrated uric acid will be totally reabsorbed in the proximal
tubulue.
In the 3. segment of the proximal tubule the uric acid will be secreted.
This secreted amout will then be excreted (approximately 10% of the
filtrated amount).
Gout
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Mechanism of secretion in the proximal tubule
Organic acids and bases
K+ and H+
PAH-secretion, PAHTm,
Uric acid secretion (10 % of the filtrated amount
is excreted)
The filtrated uric acid entirely reabsorbes, the
excreted uric acid originates from the secreted
amount.
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PAH secretion
excreted
secreted
filtrated
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Tubular functions II.Loop of Henle and the distal nephron (Learning objectives: 57)
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The loop of Henle
thin descending limb,
thin ascending limb,
squamous cells, few mitochondria, few microvilli
thick ascending limb (thick segment)
cuboid cells, many mitochondria, no microvilli
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Loop of Henle
(30% isotonic fluid coming from the proximal tubulus)
Function
–Reabsorbs 20% of Na+ and 10%
of water
– lets hypotonic fluid into the distal
one
–Medullary gradient ( 50% NaCl,
50% urea).
Thin descending limb
1. Weakly permeable to solutes
2. Freely permeably to water
3. No active transport.
The osmolarity increases from 300 mosm/kg -to 1200 mosm/kg
in the long-looped nephrons and to 600 mosm/kg in the short
looped nephrons. The increase in the concentration is a
consequence of water reabsorption.
The predominant substance is Na+ és Cl- in the tubular lumen
and urea in the peritubular space.
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Thin ascending limb
1. Impermeable to water,
2. Freely permeable to Na+- and Cl-
3. Moderately permeable to urea.
Na+ and Cl- diffuses into the peritubular space and urea
diffuses into the tubule.
The osmolarity decreases but the volume of the fluid
does not change.
Thick ascending limb
1. No water permeability
2. Actively reabsorbs Na+ and Cl- .
3. Weak urea permeability
The osmolality decreases in the tubular fluid, the
concentration of Na+ and Cl- concentration is lower.
The concentration of urea is unchanged because of the
low water permeability.
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ATPase
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NH4+-Transport in the loop of Henle
The Na+, K+, 2Cl– Symport can resorbe instead of K+
NH4+.
The fluid leaving the loop of Henle is:
1./ hypoosmotic,
2./ high urea concentration,
3./ unchanged volume.
The Na+ reabsorption is similar to that in the proximal
tubule, only the carrier is different on the apical surface.
The outward movement of one Na+ ion is bound to the
entry of 2 Cl- and one K+. (Na+/K+- 2Cl- symport).
Furosemide inhibits this transport.
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CO
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KÜ
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NA
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A
AKTÍV TRANSZPORT
PASSZÍV TRANSZPORT
Urea transport in the nephronUrea-cycle
Proximal tubule: passive transport, 50% of the filtrated amount will be reabsorbed
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The distal nephron
In distal tubulus and collecting duct is the fine adjusting
of composition of urin.
High gradients can be built but the capacity of transport
is low.
It contains different segments and different kinds of
cells.
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Distal nephron
Function:
active Na+ reabsorption,
weak water permeability,
weak urea permeability.
The distal nephron changes the tubular fluid into urine
Histological characteristics
Convoluted tubule
Cuboid cells, no interdigitation,
many mitochondria
no brush border
Collecting duct
cuboid-cylindrical cells.
Few cell organelle
No brush border
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Active Na+ resorption
Distal convoluted tubule
The active Na+ transport is bound to Cl- carrier
(Na+/Cl- symport).
inhibited by thiazid
The osmolality and electrolyte concentration decrease
because of the Na+ reabsorption and low water
and urea permeability. The urea concentration is still
higher. The amount of tubular fluid is unchanged.
The distal tubule cell
Na+ resorption trough a Na+ Cl-- symporter. Cl– leaves the
cell through a K Cl – symporter of the basolteral membrane.
Na+ will be transported out of the cell through
Na+/K+ -ATPase. Accumulated K+ leaves the cell through
K+ chanels.
These cells can Ca2+ also resorbe. Luminale Ca2+
Channels and basolteral Na+/Ca2+ exchanger.
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Transport in the distal tubule cell
Principal (main) cell
In late distal tubulus and in the collecting duct can be found
these cells.
Luminal Na+ und K+- channels
The cells resorbe Na+ and secrete K+
Increased Na+-Resorption
Increased K+-Sekretion und K+-Excretion
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Principal cell
Intercalated cell
Typ A
Intercalated cell
Typ B
Na+ household
Na+ intake
Na+ content of drinks and food between 10 and 600 mmol
Na+ (100-400 mmol/day in general ).
No physiological mechanism of Na+ intake
Na+ loss
Sweat
Stool
Urine (100-400 mmol/day).
Regulation of salt household
Through salt loss.
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Effector mechanisms
1./ GFR
2./ Renin-Angiotensin-Aldosterone system
Adrenal cortex glomerular zone (mineralocorticoid)
Na+ and K+ ion exchange in the distal tubule and
collecting duct
3./ “third factor”
Renin-angiotensin-aldosteron system
A juxtaglomerular apparatus
myoepithel cells of vas afferents,
macula densa in distal tubulus,
mesangial connective tissue,
Renin ( 66500 d)
angiotensinogen (alfa2-globulin, liver),
Angiotensine I (10 amino acid (ACE, angiotensine
converting enzyme)
Angiotensine II (8 amino acid)
Angiotensine III
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JUXTAGLOMERULAR APPARATUS
endfeet of
podocytes
capillary
mesangial cell
podocyte
mesangial cell
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Renin secretion increased by
1. decreased renal blood flow
2. amount and chemical composition of tubular
fluid at macula densa,
3. stimulation of renal sympatethic nerve,
4. extracellular hypovolemia (bleeding)
Renin secretion decreased by:
1. prostaglandines ( PGE2, PGD2, PGI2)
2. atrial natriuretic factor (ANF)
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Control of renin secretion
Angiotensine II effects
1/ Blood pressure
vasoconstrictor (systolic and diastolic RR increases)
2/ Aldosteron
3/ Central effects (hypothalamus)
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Factors increasing aldosterone secretion:
angiotensine II
decreased atrial natriuretic factor,
increased plasma K+,
ACTH,
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Regulation of Aldosterone secretion
Atrial natriuretic factor (ANF)
Right atrium
28 (21 - 73) amino acid (2800-13.000 dalton).
126 amino acid precursor (pro-ANF (atriopeptinogen).
ANF secreted
Increased atrial stretch (hypervolemia)
ADH
adrenalin
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Effects of ANF
1. Vasodilatation
2. increased GFR
(dilatation of the afferent arteriole)
3. inhibition of renin secretion
4. decreased in aldosterone secretion
5. inhibition of ADH
6. natriuresis and water diuresis
decreased cardiac output
Mechanisms of Na+-resorption in the whole nephron
Na/H antiporter
Na/S symporter
Paracellular transport
Na/K/2Cl symporter
Paracellular transport
Na/Cl Symporter
Na channels
Proximal Tubule
(acetazolamide inhibits)
Loop of Henle
(furosemide inhibits)
Distal Nephron
(thiazide inhibits)
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Intercalated cells
Intercalated cells secrete either H+ (Typ A) or
HCO3- (Typ B).
In intercalated cells Typ A can be observed the H+ Sekretion
through H+-ATPase or in K+-deficit through H+/K+
ATPase.
In intercalated cells Typ B HCO3- secretion is through
Cl-/HCO3- antiporter. The accumulated Cl- leaves the cell
through basolateral Cl- channels.
Paracellular Cl- resorption is also possible.
Principal cell
Intercalated cell
Typ A
Intercalated cell
Typ B
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Potassium household
Factors determining K+ content of the body
1. K+ intake and output,
2. distribution of potassium between the intracellular and
extracellular space.
INTAKE OUTPUT
Drinks, food 50-100 mmol/day Sweat, Stool 5-10 mmol/day
Urine 45-90 mmol/day
Sum 50-100 mmol/day 50-100 mmol/day
Distribution of K+ between the intracellular and extracellular fluids
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K+ reabsorption
proximal nephron 1. and 2. segments
thick segment
K+ secretion
proximal tubule 3. segment
thin descending limb
distal tubule
regulation: aldosterone, (insuline)
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secretion
Potassium transport in the loop of Henle
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Potassium transport in the distal tubule cell
Principal cell
(aldosteron effect)
Intercalated cell
Typ A
Intercalated cell
Typ B
Potassium transport in the principal and intercalated cells