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2018.12.03.
1
RENAL PHYSIOLOGY,
HOMEOSTASIS OF FLUID COMPARTMENTS (4)
Dr. Attila Nagy
2018
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.
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2
Principal cell
Intercalated cell
Typ A
Intercalated cell
Typ B
Water household
Water intake 2100-3400 ml/day
Fluid intake 1000-2000 ml/day
Water content of foodstuffs 800-1000 ml/day
Oxidative water 300-400 ml/day
Water output 2100-3400 ml/day
Insensible perspiration 800-1000 ml/day
sensible perspiration, sweating 200 ml/day
Stool 100-200 ml/day
Urine 1000-2000 ml/day
Minimal urine output 500-600 ml/day (650 mosm solute/day).
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• Physiology of thirst
1. dryness of the mouth
2. angiotensin II
3. hypothalamic osmoreceptors
Control of water intake (hyperosmosis and hypovolaemy)
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Control of loss of water
Regulation of vasopressin
(AVP) production
Renin-angiotensin system stimulates Atrial Natriuretic
Hormon inhibits the AVP production.
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Effects of AVP:
-Water reabsorption from the collecting duct through
Aquaporin-2 water chanels (V2/cAMP)
-V1/ITP-Ca2+ vasoconstrictor effect
-V3 receptor in the ACTH producing neurons of the anterior
pituitary gland
The water transport is regulated by the anti-diuretic
hormone (ADH).
The collecting duct is relatively impermeable to
water and urea in the absence of ADH
In the presence of ADH the water permeability of the
whole collecting duct and the urea permeability of its
papillary part is greatly increasing
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In the absence of ADH the osmolality of the fluid that
leaves the collecting duct is 70 mosm/kg (50 mosm/kg
urea and 20 mosm/kg electrolyte).
In the absence of ADH or V2 ADH receptor up to
15% of the filtrated water will be excreted (max. 26 liter/day)
diabetes insipidus.
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ADH secretion
Increased by Inhibited by
1. High osmolarity of the blood 1. low osmolarity
2. Hypovolemia 2. Hypervolemia
(inhibits ANP secretion)
3. Standing 3. Lying in horisontal position
↓ ANP ↓ ↑ ANP ↑
4. venous stasis 4. Alcohol
5. pain, exercise
Osmolality of the tubular fluid
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The concentration and dilution of the urin
Depending on the need of the body the kidney can produce
1. highly concentrated (to 1.200 mOsm/l) or
2. strongly diluted urin (to 70 mOsm/l).
Factors influencing urine concentration:
Length of Henle loops
Percentage of long-looped nephrons compared to
short-looped ones
Urea
Flow through Henle-loop and collecting duct
Blood-flow through vasa recta
Prostaglandines (PGE2, PGD2)
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Concentration and Dilution of Urine
Countercurrent multiplication
Medullary gradient
300 mosm/kg-1200 mosm/kg
Medullary gradient originates from:
Horisontal gradient – Active Na+ reabsorption in the
ascending thick segment of the loop of Henle
Loop diuretics (i.e. Furosemide) abolishes the medullary
gradient
Vertical gradient (countercurrent) - Fluid movement in the
descending and ascending segment of the Henle-loop
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The motor of the concentrating of the urin is the
electrolyt transport in the loop of Henle
The most important function of the loop of Henle is the
bilding of hyperosmolar renal medulla.
The ascending thick segment resorbs actively Na and Cl,
practically without water resorption. These transports
decrease the osmolarity of the tubular fluid and increase the
osmolarity in the renal medulla.
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CO
RT
EX
OU
TE
RZ
ON
EIN
NE
R
ZO
NEM
ED
UL
LA
ACTIVE TRANSPORT
PASSIVE TRANSPORT
Urea transport in the nephronUrea-cycle
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Blood flow in the renal medulla
The hyperosmolarity and the medullar gratient would be
washed out quickly, if the blod flow and the form of blood
wessels would be conventional. The loop form structure of
Vasa Recta prevents the dilution of renal medulla.
Countercurrent system does not allow the quickly transport
of NaCl and urea.
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The concentration of urin will be inhibited through:
- Karboanhydrase inhibitor (Acetazolamide)
- Loop diuretics (Inhibition of Na+,K+,2Cl--symporters)
-Thiazide (Inhibition of Na+/Cl- cotransporter)
- ATII rezeptor antagonists (Losartan)
- Aldosteron antagonistsen (Spironolakton)
- Potassium deficit (inhibits the Na+,K+,2Cl--symporter)
- Hyperkalcaemia (Decreasing the permeability of tight junctions,
Ca2+-receptors inhibiting the Na+,K+,2Cl--symporter)
- Proteipoor nutrition
- Renal inflammation (Dilatation of Vasa recta)
- Increase of blood pressure
- Osmotic diuresis (filtration of no or partial resorbable osmotic active
substances)
- Diabetes insipidus
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Buffer systems in the urine
1. phosphate buffer
2. ammonia buffer
(3. bicarbonate buffer)
Urine pH: 4.0-8.0
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Phosphate buffer
HPO42- : H2PO4
– = 4:1 (pK= 6.8)
if the urin pH is equal to the pH of the arterial
Blood (7.4)
Titratable acidity
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Ammonia buffer
NH4+ ⇔ NH3 + H+ (pK = 9.3)
Glutaminase Glutamate dehydrogenase
Glutamine Glutaminic acid α-ketoglutaric
acid
NH3 NH3
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Solubility of NH3 and NH4+
NH3 rather soluble in lipids and diffuses passively
through membranes, NH4+ is a polar substance and
not able to diffuse through membranes.
The production of ammonia is regulated by the plasma
pH, through glutaminase activation.
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Ammonia transport in the proximal nephron
Passive diffusion in the tubular lumen (NH3)
Active transport Na+/H+ antiporter (NH4+)
Lumen Sejt Vér
Ammonia transport in the thick ascending limb of loop of
Henle. Na+-K+-2Cl- cotransporter reabsorbs NH4+ instead of
K+.
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Ammonia transport in the distal nephron
In principal cells the Na+/K+ pump could transport NH4+ instead of
K+ .
Principal cell
NH3 – NH4+ reaction in the distal tubule is coupled with H+
secretion and new bicarbonate production
PERITUBULAR SPACETUBULAR LUMEN
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Micturition(Learning objective: 58)
Upper urinary tract
- renal calyces
- renal pelvis
- ureter
Lower urinary tract
- urinary bladder
- urethra
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Micturition reflex
Stimulus: stretch (volume of the urine)
Receptor: stretch receptors
Afferents nerves: pelvic n. (parasympathetic)
Ctr: S2-4
Efferents nerves pelvic n. (parasympathetic)
Somatic innervation: pudendal nerve S1
Sympathetic innervation: hypogastric plex.
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sympatheticafferent
parasympathetic
afferent
vegetative
afferent
somato-motor
pelvic nerve
pudendal nerve