Renal Physiology Intensive Care Training Program Radboud University Medical Centre Nijmegen
Salt and water balance • ECF volume regulated by total body
content of NaCl (sodium is the main osmotic constituent of the ECF)
• Water content of the body is the main
determinant of the osmolality (total body osmoles largely a function of intracellular milieu)
EXTRACELLULAR 40%
♂ 70 kg - TOTAL BODY WATER = 42 liters
INTRACELLULAR 60%
What happens with + increased Na intake?
Compare hypertonic saline for ICP↑ ECF expansion increases amount of urinary sodium
Effective circulating volume • Most probably related to arterial filling • Both low- and high pressure sensors of
which the low pressure sensors are the most important
Effective Circulating Volume
A
B
Renin-Angiotensin-Aldosteron axis
Renin release • Decreased systemic blood pressure
(increased sympathetic outflow to JGA)
• Decreased NaCl concentration at the macula densa
• Decreased renal perfusion pressure sensed in granular cells afferent arterioles
Aldosterone effect
Role of Angiotensin II
Pressure diuresis Independent from 4 pathways
Osmolality control Vasopressin
• Water retention/excretion by the kidneys • Stimulation/inhibition of thirst mechanism
Circumventricular organs = breeching of BBB Subfornical organ
Organum Vasculosum Lamina Terminalis
Location of osmoreceptors
Atrial low-pressure receptors Vagus nerve
•Breakdown of AVP by liver and kidney •Plasma half-life 18 minutes •Liver and kidney failure increases AVP levels
Plasma AVP secretion in response to plasma osmolality
Nerve IX
Vagus nerve -
Non-osmotic stimuli also enhance AVP secretion
AVP and the kidney
200 L 15 L
Non osmotic stimuli of AVP secretion • Reduction in effective circulating volume (Both hypovolemia and CHF)
• Low arterial pressure • Pregnancy • Pain, nausea and medication (morphine) e.g. postoperative
GFR =
[Ux] × V [Px]
Ideal substance
(ml/min)
Glomerular Filtration Rate
•Freely filterable •Neither reabsorbed nor secreted •Not synthesised, broken down or accumulated •Physiologically inert
Creatinine clearance
• Secreted by the tubules • Stems from normal metabolism of creatine phosphate in muscle (relatively constant)
Effect of sudden decrease in GFR
Glomerular ultrafiltration
Glomerular hemodynamics
Decreased GFR in AKI
Pressure profile along the renal vasculature
Renal blood flow Approximately 20% of CO ≈ 1 L Renal plasma flow ≈ 600 mL GFR dependent on RPF
Renal blood flow
Prowle JR. Blood Purif 2009;28:216-225
Effect of afferent and efferent arteriolar constriction
RPF = Clearance of PAH
Peritubular capillaries: deliver oxygen to epithelial cells and fluid uptake
Autoregulation
Both renal myogenic and tubuloglomerular feedback mechanism
Tubuloglomerular feedback mechanism
Volatile acids
[H+] = 40 nmol/l
Total body acid-base balance
Role of kidney in acidbase balance • Reabsorb 4320 mmol of filtered HCO • Excreting 30 mmol H /day as titratable acid 3-
+
(mostly phosphate buffer)
•
Excreting 40 mmol H+/day as NH4+
4320 mEq/day
Proximal tubule
Symporter NBCe I
Type IV
HCO3- reabsorption
Type II
Combination of H+ with urinary buffers HPO42- + H+ ➙ H2PO4-
Quantification by urine titration with alkali to raise pH to that of blood ⅓ of RNAE - mostly phosphate
Titratable acid
Preferable - 2/3 of RNAE
Ammoniagenesis and NH4+ secretion
Urinary Net Charge •
During acidosis UNC (Na+ + K+ - Cl-) should be < 0 reflecting excretion of NH4+
• An value of 0 or positive value is indicative of a defect in NH4+ secretion
Regulation • Respiratory and metabolic acidosis increase proximal H+ secretion and NH3 synthesis
• ECV contraction stimulates renal H
+
secretion bij increasing levels of AG II, aldosterone and sympathetic activity
• • Gluco- and mineralocorticoids stimulate Hypokalemia increases H+ secretion acid secretion