RENAL PHYSIOLOGY, HOMEOSTASIS OF FLUID COMPARTMENTS (4) Dr. Attila Nagy 2018 Intercalated cells Intercalated cells secrete either H + (Typ A) or HCO 3- (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 HCO 3- secretion is through Cl - /HCO 3- antiporter. The accumulated Cl - leaves the cell through basolateral Cl - channels. Paracellular Cl - resorption is also possible. 1
Principal cell Intercalated cell Typ A Intercalated cell Typ B Water household Water intake Fluid intake Water content of foodstuffs Oxidative water 2100-3400 ml/day 1000-2000 ml/day 800-1000 ml/day 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). 2
Physiology of thirst 1. dryness of the mouth 2. angiotensin II 3. hypothalamic osmoreceptors Control of water intake (hyperosmosis and hypovolaemy) 3
Regulation of vasopressin (AVP) production Control of loss of water Renin-angiotensin system stimulates Atrial Natriuretic Hormon inhibits the AVP production. 4
Effects of AVP: -Water reabsorption from the collecting duct through Aquaporin-2 water chanels (V2/cAMP) -V1/ITP-Ca 2+ 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 5
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. 6
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 7
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 (PGE 2, PGD 2 ) 8
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 9
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. 10
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Urea transport in the nephron Urea-cycle MEDULLA INNER ZONE OUTER ZONE CORTEX ACTIVE TRANSPORT PASSIVE TRANSPORT 12
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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. 14
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, Ca 2+ -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 15
Buffer systems in the urine 1. phosphate buffer 2. ammonia buffer (3. bicarbonate buffer) Urine ph: 4.0-8.0 16
Phosphate buffer HPO 2-4 : H 2 PO 4 = 4:1 (pk= 6.8) if the urin ph is equal to the ph of the arterial Blood (7.4) Titratable acidity 17
Ammonia buffer NH 4+ NH 3 + H + (pk = 9.3) Glutaminase Glutamate dehydrogenase Glutamine Glutaminic acid α-ketoglutaric acid NH 3 NH 3 18
Solubility of NH 3 and NH + 4 NH 3 rather soluble in lipids and diffuses passively through membranes, NH 4+ is a polar substance and not able to diffuse through membranes. The production of ammonia is regulated by the plasma ph, through glutaminase activation. 19
Ammonia transport in the proximal nephron Passive diffusion in the tubular lumen (NH 3 ) Active transport Na + /H + antiporter (NH 4+ ) Lumen Sejt Vér Ammonia transport in the thick ascending limb of loop of Henle. Na + -K + -2Cl - cotransporter reabsorbs NH 4+ instead of K +. 20
Ammonia transport in the distal nephron In principal cells the Na + /K + pump could transport NH 4+ instead of K +. Principal cell NH 3 NH 4+ reaction in the distal tubule is coupled with H + secretion and new bicarbonate production TUBULAR LUMEN PERITUBULAR SPACE 21
Micturition (Learning objective: 58) Upper urinary tract - renal calyces - renal pelvis - ureter Lower urinary tract - urinary bladder - urethra 22
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. 23
sympathetic afferent parasympath etic afferent vegetative afferent somato-motor pelvic nerve pudendal nerve 24
medial pontine lateral pontine sympathetic Micturition Detrusor contraction sphincter relaxation Retention Detrusor relaxation sphincter contraction Supraspinal regulation: Pontine Mesencephalic Hypothalamic Cortical centers Spinal transection 25