Test 2 (Regulation of Sodium and Water Balance) Flashcards
Major Body Fluid Compartments
Main substances exerting Osmotic Pressure in Compartments:
- Cells: K+
- Interstitial Fluid: Na+
- Plasma: Protein (Usually Albumin)
**Values are for young adult male (70kg)
Electrolyte Compositions of ICF and ECF differ
Na+:
- ICF = 12
- ECF = 145
K+:
- ICF = 150
- ECF = 4
Ca++:
- ICF = 0.001
- ECF = 5
Cl-:
- ICF = 5
- ECF = 105
HCO3-:
- ICF = 12
- ECF = 25
Pi:
- ICF = 100
- ECF = 2
pH:
- ICF = 7.1
- ECF = 7.4
Osmotic Eqilibration
- Osmotic Pressure determines the distribution of Body Water
- Initially, ECF and ICF have same solute concentrations
- Withdraw 3 liters pure H2O from ECF: OSMOTIC GRADIENT IS CREATED
OSMOTIC QUILIBRATION:
- H2O diffuses from ICF to ECF to re-establish Osmotic Equilibrium. Note proportional changes in each compartment’s volume (Look at slide8 in Lecture)
Total Body Na+ content determines ECF Volume
- Water and Na balance are regulated INDEPENDENTLY by specific pathways designed to PREVENT LARGE CHANGES IN PLASMA OSMOLARITY
- INCREASE Total Body Na+ Content
- H2O Osmosis from cells, Renal H2O Retention
- INCREASE Extracellular Fluid Volume
**Thus, INCREASED Na+ in the body expands the Extracellular Fluid Volume and effective Circulating Volume: CAN BE COMPENSATORY RESPONSE FOR HYPOVOLEMIA!!!!!!!!
Sodium Balance
- PLASMA Na+ (and therefore Osmolarity) is regulated Primarily by changes in WATER BALANCE
- TOTAL BODY Na+ CONTENT = Dietary Na+ intake - Urinary Na+ Excretion
- Dietary Na+ intake is not regulated in humans; The kidneys control body Na+ content by adjusting Urinary Excretion
- Increased ECF volume activates mechanisms that INCREASE Na+ EXCRETION
- Decreased ECF volume causes Na+ to be CONSERVED!!!!!!!
Reabsorption of filtered Na+ Load
- Bulk of REABSORPTION of filtered Na+ in Proximal tubule, Loop of Henle; ‘Fine Tuning’ of Na+ handling is exerted in the Distal Nephron
Neurohumoral Factors controlling Renal Na+ Handling
Factors that promote Na+ Reabsorption:
1) Activation of Renal Sympathetic Nerves
2) Activation of Renin/ Angiotensin System
3) Secretion of Aldosterone
Factors that promote Na+ Excretion:
- Release of Atrial, Brain Natriuretic peptides (ANP, BNP)
- Release of Urodilatin
- Interregnal Prostaglandins
Sympathetic activity stimulates Na+ Reabsorption, Renin Secretion
1) INCREASE Activity of Renal Sympathetic Nerves
——>
2a) DECREASE GFR
2b) INCREASE Proximal Na and H2O Reabsorption
2c) Direct Stimulation of Granular Cells (Beta Adrenergic Receptors)
——->
3) DECREASE Rate of Fluid Delivery to the Macula Densa
—–>
4) INCREASE Renin Secretion
Factors that promote Renin Secretion
- RENAL SYMPATHETIC STIMUALTION (due to fall in Perfusion Pressure through the Cardiopulmonary BARORECEPTORS): Directly stimulates Renin secretion via B1 receptor activation in the JG apparatus
- Tubuloglomerular Feedback: DECREASE NaCl delivery to MACULA DENSA ——> RENIN Secretion
- Infrarenal Baroreceptor (Wall of afferent Arteriole): Afferent Arteriolar Vasoconstriction —–> INCREASE PRESSURE in Granular Cells ——–> RENIN Secretion
Angiotensin II Stimulates
- Systemic Artfeiorlar Constriciotn
- Renal Artfeiorlar Constriciton: Efferent > Afferent
- Na+ Reabsorption: PCT (via INCREASE Na-H Exchanger Activity) > TAL, CCD
- Thirst
- ADH Secretion from Posterior Pituitary
- Aldosterone Secretion from Adrenal Cortex
Summary- Renal Effects of Angiotensin II
1) Decreased Renal Blood Flow
2) Proportionately INCREASED Efferent Artfeiorlar Resistance —-> INCREASED Glomerular Capillary hydrostatic Pressure —–> Increased Filtration
3) Glomerular Mesangial Cell Contraction —-> DECREASED Glomerular Capillary surface area available for Filtration —-> DECREASED Filtration (offsets above effect)
4) DECREASED Medullary Blood Flow
5) INCREASED Tubular Sodium Reabsorption —> Sodium Retention
Response of Renin/ Angiotensin mechanism to Decreased ECF Volume
- Angiotensin II DECREASED Medullary Blood Flow, INCREASES Renal Vascular Resistance, and INCREASED Aldosterone
- An INCREASE in Renal Vascular Resistance causes a DECREASE in Renal Insterstitial Hydrostatic Pressure
- All three of these cause an INCREASE in Tubular Sodium Reabsorption
- This leads to a DECREASE in Sodium Excretion
Response of Renin/ Angiotensin mechanism to Decreased BP, RBF or release of Catecholamines
- Low Blood Pressure, Low Renal Blood Flow, and Catecholamines ACTIVATE Renin Secretion!!!!
Aldosterones actions in late Distal Convoluted Tubule, Collecting duct (Principle Cells
1) Stimulates Sodium Reabsorption:
- Results in: Lumen-Negative Potential Difference
- Electroneutrality maintained by: Passive Cl- Reabsorption and K+/ H+ Secretion
2) Stimulates Potassium Secretion by Principal Cells of DT/ CCD
3) Stimulates H+ Secretion (INCREASE H= - ATPase activity in Intercalated Cells of CCD) - *What would happen to K and H Excretion in a patient with Hyperaldosteronism?
- Both would INCREASE!!!
***HYPOALDOSTERONISM: Hypokalemic and Alkalotic Patient Presentation!!!!!!
Factors Controlling Aldosterone Secretion
1) INCREASE Plasma Potassium Concentration
2) ICNREASE Plasma ACTH Concentration
3) Volume Depletion
Feedback Control of Aldosterone Secretion
- Increased Renal Arterial mean Pressure and Decreased discharge of Renal Nerves INHIBITS-NEGATIVE FEEDBACK!!!!!!
***This all comes from DECREASED Na+ (and water) Excretion
ANP Increases Na+, H2O Excretion
- ANP Increases GFR: Afferent Arteriolar Dilation, Efferent Artieorlar Constriction
- ANP INHIBITS Na+ Reabsorption in Medullary Collecting Duct
- ANP SUPPRESSES Renin Secretion
- ANP SUPPRESSES Aldosterone Secretion
- ANP is a Systemic Vasodilator
- ANP Suppresses AVP Secretion, Actions
AANP Response to Increased ECF Volume
- INCREASED Extracellular Fluid Volume leads to DECREASED Tubular Sodium Reabsorption
- That then leads to INCREASED SODIUM EXCRETION!!!
Renal Response to Increased Blood Volume
- INCREASED in Circulating Blood Volume
——->
- INCREASED Atrial Stretch
——–>
- DECREASED ADH Secretion, DECREASED Aldosterone Secretion, DECREASED Renal Nerve Discharge, INCREASED Heart Rate
——>
- All of these lead to INCREASED Salt and Water Excretion
——>
- This leads to DECREASED CIRCULATION BLOOD VOLUME!!!!!
Urodilatin: Endogenous Renal Natriuretic Peptide
- SECRETED by DCT, Collecting Duct in response to INCREASED Arterial Pressure and ECF Volume
- Urodilatin SUPPRESSES Na+ and Water Reabsorption by medullary Collecting Duct
- Unlike ANP and BNP, Urodilatin has NO EFFECT on Systemic Circulation
Infrarenal Prostaglandins (Ex: PGE2) INCREASE Na+ EXCRETION
- INCREASE GFR by Dilating Renal Arterioles
- Suppress Na+ Reabsorption in THICK ASCENDING LIMB, Cortical Collecting Duct
- **What effect would this have on the Solute Concentration in the Renal Medullary Tissue?
a) The concentration of solutes will DECREASE and there will be a DECREASED Osmolarity
b) This gets rid of the Gradient to REABSORB Sodium and Water and therefore we won’t be able to Concentrate our Urine
- Net effect: INCREASED Urinary Na+ EXCRETION!!!
Summary- Nephronal NaCl Transport Mechanisms and Regulatory hormones
Percentage of Filtered NaCL Reabsorbed:
1) Proximal Tubule:
- 67%
2) Loop of Henle:
- 25%
3) Distal Tubule:
- 5%
4) Late Distal Tubule and Collecting Duct:
- 3%
Anatomy of AVP Synthesis, Secretion
- HYPOTHALAMUS
Osmoreceptors, Baroreceptors Control AVP Secretion
Two major Stimuli for ADH Release:
1) HYPEROSMOLALITY
2) Volume Depletion
- Hypothalamic Osmoreceptors are MORE IMPORTANT than hepatic Osmoreceptors
