& Fluid Ion Balance
PSL302Y: Lecture 07, by Prof. Lam!
September 27, 2010
Mon., Sept. 27, 2010
Fluid & Ion Balance Kidneys: control urine concentration Aldosterone: Na+ reabsorption Vasopression: H2O reabsorption Atrial natriuretic peptide: Na+ & H2O
Why is maintaining fluid balance is Why is maintaining fluid balance is important for normal cell fxn? important for normal cell function?
intracellular fluid (2/3)
~55% water
Fluid & Ion Balance September 27, 2010
extracellular fluid (1/3) interstitial fluid: plasma
(75%:25% of ECF)
-By affecting [Na+] in cells, influence water flow in and out of cells -Also regulate thru intake and excretion of water from cells
(varies with sex, age)
cell
blood vessel
How are daily water intake and excretion balanced?
Intake + Metabolic = production 0.3 0 3 L/day Output urine (1 5 L/day) (1.5 sweat, breath (0.9 L/day) feces (0.1 L/day)
September 27, 2010
How are daily water intake and excretion balanced?
Fluid & Ion Balance
food, food drink (2.2 L/day)
-Exogenous appearance of water via diet: 2.2L/day -Endogenous appearance of water via metabolic production: 0.3L/day 2 -Disappearance via urine (1.5L/day), via sweat & breath (0.9L/day) and feces (0.1L/day)
Urine flows from nephrons of therenal cortex and medulla into renal pelvis Urine flows from nephrons of renal cortex and medulla into the renal pelvis p
-Renal artery carries blood to kidneys, allowing blood to flow thru cortex -> medulla 3 -Disposed water flows down calyces into renal pelvis, which drains into ureter & bladder -Filtered blood returns to body via renal vein
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PSL302Y: Lecture 07, by Prof. Lam!
Mon., Sept. 27, 2010
The nephron is the functional unitFluid & the kidney of Ion Balance
The nephron is the fxnal unit of the kidney
September 27, 2010
-First site of filtration at glomerulus -Hormonal actions on reabsorption of water and minerals at collecting duct; receptors found here Urine is formed in the nephron by filtration, reabsorption, secretion Urine isAldosterone: role in regulating water - formed in the nephron by filtration, reabsorption,in regulating blood pressure p reabsorption & secretion
Na+
Fluid & Ion Balance September 27, 2010
K+ H2O
Renal juxtaglomerular cellscells secrete an Renal juxtaglomerular secrete "renin", "renin" Renin:involved in controlling aldosterone releasealdosterone release enzyme enzyme involved in controlling
Bowman's capsule Efferent arteriole Macula densa Proximal tubule Juxtaglomerular cells
September 27, Afferent arteriole 2010
Fluid & Ion Balance
September 27, 2010
Glomerulus
Juxtaglomerular cells senses changes in 5 blood pressure, & is responsible for secreting more aldosterone -> Na reabsorption, 6 indirectly promoting water reabsorption = increase blood pressure Aldosterone (acortex, increases in the adrenal steroid synthesized in the adrenal cortex): Na+ reabsorption sodium reabsorption
aldosterone adrenal kidney
Distal tubule
Fluid & Ion Balance
Aldosterone, a steroid synthesized
Aldosterone induces mineralcorticoid receptor translocation to the nucleus p
Aldosterone induces mineralcorticoid receptor translocation to the nucleus
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Once receptor bound by aldosterone, receptor-complex moves to nucleus and affects gene expression, ultimately affecting Na retention
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PSL302Y: Lecture 07, by Prof. Lam!
Mon., Sept. 27, 2010
Aldosterone acts on the distal tubule and collecting duct Aldosterone acts on the distal tube & collecting duct
receptor binding Principal cell lumen pumps interstitial fluid blood transcription protein synthesis protein modification Na+ Na+ reabsorption K+ secretion
channels K+
-This is where the receptors are found -Gene expression = ATPase pumps and Na & K channels -Increases water reabsorption = blood pressure increases
Fluid & IonAldosterone Balance
September 27, synthesis is controlled by negative feedback: - 2010 Simple (K+, osmolarity) mech and complex (renin-angiotensin path) mech
Stimulators: (1) Angiotensin II (complex) (2) High [K+]plasma (simple) Inhibitor (3) High osmolarity (ECF)
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-Affect multiple organs: can regulate aldosterone in multiple ways -Drugs targeting pathway: ACE inhibitor to reduce blood pressure -Juxtaglomerular cells (in kidneys) sense drop in blood pressure -> renin -Angiotensinogen (precursor) secreted from liver into bloodstream -> AI -AI -> II conversion requires enzyme ACE from lungs -AII travels to: hypothalamus (in brain: signals thirst and drinking), blood vessels (vasoconstriction) & adrenal cortex (on top of kidneys: aldosterone secretion -> kidneys = salt & water retention - Overall effect: elevated blood pressure - Discovery: If AII does not reach brain, drinking not stimulated
Renin-AngiotensinAldosterone Pathway
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PSL302Y: Fluid & Ion Balance
Lecture 07, by Prof. Lam!
September 27, 2010
Mon., Sept. 27, 2010
Vasopressin (antidiuretic hormone, ADH) - Synthesized in hypothalamus, secreted from posterior pituitary = H2O reabsorption - Different action from aldosterone (indirect water reabsorption via Na reabsorption): directly affects kidney only at collecting ducts (receptors found here) - Hypothalamus site for hormone secretion b/c it's close to where blood enters brain
Vasopressin H2O reabsorption by inserting water Vasopressin Action: pores into collecting duct cell membranes
- H2O reabsorption by inserting collecting duct cell water pores into collecting duct cell blood membranes bind interstitial -Vasopressin (peptide hormone) fluid binds to receptor on cell membrane, i l signal Fluid & Ion Balance September 27, 20 triggering downstream signaling Fluid & Ioncascade mediated by cAMP Balance September 27, 2010 collecting insert signal duct lumen -Result: favour recruitment of cascade vasopressin aquaporin-2 aquaporin-2 water pores to cell absorb water pores receptor membrane along collecting duct lumen -> water flows thru collecting Silverthorn, fig.20-6, p.648 duct epithelium and back into bloodstream - Nothing to do with ion balance, only water balance Osmolarity is the most potent stimulus for vasopressin release Osmolarity is the most potent stimulus for vasoprssion release 10
MILESTONES IN NEPHROLOGY 2001
14 - Increase in plasma osmolarity -> sense of Plasma thirst introduced -> rapid riseA RAPID AND POTENT NATRIURETIC RESPONSE TO in [vasopressin] Vasopressin (picomol/L) 5 INTRAVENOUS INJECTION OF ATRIAL MYOCARDIAL in blood (which moves to collecting duct to increase water reabsorption) EXTRACT IN RATS
A. J. de Bold, H. B. Borenstein, A. T. Veress, H. Sonnenberg Dept. of Pathology, Queen's University, Kingston, Ont. and 270 290 310 Milestones in Nephrology, 2001 Dept. of Physiology, University of Toronto,Osmolarity (mOs/kg) Plasma Toronto, Ont. A.J. De Bold, H.B. Borenstein,(Received in final form October 21, 1980) A.T.
Veress, H. Sonnenberg; Dept. Of Pathology, Queen's University, Kingston, ON & Dept of Physiology, University of Toronto, ON - X-axis: time, y-axis: change in BP - Hormone(s) found in heart tissue - Gain of fxn expt: infusion of it into normal rat -> BP decrease! - Results: A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats = Hormone AMP (natriuretic peptides) oppose vasopressin & aldosterone action by inhibiting synthesis of aldosterone
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PSL302Y: Lecture 07, by Prof. Lam!
Natriuretic peptides oppose vasopressin, aldosterone - May not have a direct effect on lowering BP but indirectly by opposing hormone action
Hormone
Mon., Sept. 27, 2010
ANP
BNP
CNP
NPR C NPR-C Receptor Second Messenger Cell response
NPR A NPR-A
NPR B NPR-B
GTP
cGMP GTP cGMP
natriuretic t i ti peptide degradation
vasorelaxation l ti vasorelaxation l ti diuresis cell proliferation natriuresis renin, aldosterone, vasopressin
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