Costanzo | Physiology | Chapter 6 | Renal Physiology | Study Guide
Chapter 6: Renal Physiology Notes
I. Anatomy and Blood Supply
Nephron Types: There are two types: superficial cortical nephrons (short loops of Henle) and juxtamedullary nephrons (long loops of Henle). Juxtamedullary nephrons are essential for the concentration of urine.
Renal Vasculature: The kidneys receive approximately 25% of the cardiac output. Blood enters via the renal artery and eventually reaches the glomerular capillaries where filtration occurs.
II. Body Fluids
60-40-20 Rule: Total body water (TBW) is 60% of body weight, Intracellular Fluid (ICF) is 40%, and Extracellular Fluid (ECF) is 20%.
Fluid Shifts: Water shifts freely between compartments to maintain osmotic equilibrium.
Isosmotic volume contraction (e.g., diarrhea) results in ECF volume loss with no change in osmolarity.
Hyperosmotic volume contraction (e.g., water deprivation) leads to increased osmolarity and water shifting from ICF to ECF.
III. Renal Clearance
Definition: Clearance is the volume of plasma cleared of a substance per unit time.
Glomerular Filtration Rate (GFR): Measured by the clearance of inulin, as it is freely filtered but neither reabsorbed nor secreted.
Renal Plasma Flow (RPF): Measured by the clearance of para-aminohippuric acid (PAH) because it is both filtered and secreted.
IV. Glomerular Filtration
Starling Forces: GFR is determined by the balance of hydrostatic and oncotic pressures. Filtration is favored by glomerular capillary hydrostatic pressure (PGC) and opposed by Bowman’s space hydrostatic pressure (PBS) and glomerular oncotic pressure (πGC).
Filtration Fraction: The ratio of GFR to RPF, normally about 20%.
V. Reabsorption and Secretion
Proximal Tubule: Reabsorbs 67% of filtered Na+ and water (isosmotic reabsorption). It also reabsorbs all filtered glucose and amino acids via Na+-dependent cotransport.
Loop of Henle:
The thick ascending limb reabsorbs 25% of filtered Na+ using the Na+-K+-2Cl− cotransporter. It is impermeable to water, making it the "diluting segment".
Distal Tubule and Collecting Duct: Final site of regulation for Na+, K+, and water. Principal cells reabsorb Na+ and secrete K+, a process stimulated by aldosterone.
VI. Water Balance and Urine Concentration
Corticopapillary Osmotic Gradient: A gradient of osmolarity from the cortex (300 mOsm/L) to the papilla (1200 mOsm/L). It is established by countercurrent multiplication in the loops of Henle and urea recycling in the collecting ducts.
Antidiuretic Hormone (ADH): Increases water permeability in the late distal tubule and collecting duct by inserting aquaporin-2 channels into the luminal membrane.
Free-Water Clearance (CH2O): If CH2O is positive, hyposmotic (dilute) urine is excreted; if negative, hyperosmotic (concentrated) urine is produced.
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Chapter 6 Study Guide
I. Glossary of Key Terms
Aldosterone: A steroid hormone that increases Na+ reabsorption and K+ secretion in principal cells.
Countercurrent Multiplication: An active process in the loop of Henle that establishes the corticopapillary osmotic gradient.
Effective Arterial Blood Volume (EABV): The portion of ECF in the arteries perfusing tissues.
Filtration Equilibrium: The point at the end of the glomerular capillary where net ultrafiltration pressure becomes zero.
Inulin: A fructose polymer used as the gold standard to measure GFR.
Isosmotic Reabsorption: Coupling of solute and water reabsorption such that the osmolarity of tubular fluid remains constant.
Principal Cells: Cells in the late distal tubule and collecting duct responsible for Na+ reabsorption and K+ secretion.
Renin: An enzyme secreted by juxtaglomerular cells that initiates the RAAS pathway to increase blood pressure.
Splay: The region of the glucose titration curve where excretion begins before full saturation (Tm) is reached.
Vasa Recta: Specialized capillaries that maintain the medullary osmotic gradient via countercurrent exchange.
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II. 50 Question-and-Answer Quiz
What percentage of total body water is ICF? 40%.
Which nephrons have long loops of Henle? Juxtamedullary.
What is the formula for renal clearance? Cx=[U]x×V˙/[P]x.
Which substance is used to measure GFR? Inulin.
Which substance measures RPF? PAH.
What is the normal GFR in a healthy adult? 120 mL/min.
How is RBF calculated from RPF? RBF=RPF/(1−Hct).
Which Starling force favors filtration? PGC.
What is the normal filtration fraction? 20%.
Where is 67% of Na+ reabsorbed? Proximal tubule.
What is the Tm for glucose? Approximately 375 mg/min.
Which segment is the "diluting segment"? Thick ascending limb.
Which cotransporter is found in the thick ascending limb? Na+-K+-2Cl−.
What effect does ADH have on water permeability? It increases it.
Which hormone increases Na+ reabsorption in the distal tubule? Aldosterone.
What defines positive Na+ balance? Na+ excretion is less than Na+ intake.
Which cells secrete K+? Principal cells.
Where does PTH inhibit phosphate reabsorption? Proximal tubule.
What is the maximum urine osmolarity in humans? 1200 mOsm/L.
Which process established the medullary gradient? Countercurrent multiplication.
What happens to RBF if afferent arteriolar resistance increases? It decreases.
What happens to GFR if efferent arteriolar resistance increases? It increases.
What is the effect of Na+ volume expansion on Ca2+ reabsorption? It inhibits it.
Which diuretic inhibits the Na+-K+-2Cl− cotransporter? Loop diuretics (e.g., furosemide).
What is the Pk of the phosphate buffer? 6.8.
Which segment is the site of urea recycling? Inner medullary collecting duct.
What is the effect of hyperkalemia on K+ secretion? It increases it.
Which cells reabsorb K+ in the collecting duct? α-intercalated cells.
What is a "glomerular marker"? A substance like inulin that is only filtered.
What does a clearance ratio of 1.0 mean? The substance is handled like inulin.
What is the primary stimulus for ADH secretion? Increased serum osmolarity.
Which receptor does ADH bind to for water reabsorption? V2 receptor.
What is the second messenger for ADH in principal cells? cAMP.
What is the effect of ANP on Na+ excretion? It increases it.
Where is glucose reabsorbed? Early proximal tubule.
What is the renal response to water deprivation? Secretion of ADH and production of hyperosmotic urine.
What condition is characterized by a lack of ADH? Central diabetes insipidus.
Which vessels provide countercurrent exchange? Vasa recta.
What is "titratable acid"? H+ buffered by phosphate in the urine.
How many mEq of fixed H+ are produced daily? Approximately 50 mmol/day.
Which enzyme is needed for NH4+ production? Glutaminase (implied by NH3 synthesis).
What happens to GFR in a person with a ureteral stone? It decreases due to increased PBS.
What is the "single effect"? The function of the thick ascending limb in countercurrent multiplication.
Which ion drives Ca2+ reabsorption in the thick ascending limb? Na+ (via the lumen-positive potential).
What defines CH2O=0? Isosmotic urine is produced.
Which drug blocks Na+ channels in the collecting duct? Amiloride.
What is the effect of angiotensin II on the efferent arteriole? Vasoconstriction.
Which part of the nephron is always impermeable to water? Thick ascending limb.
What is the primary cation in the ECF? Na+.
What is the primary cation in the ICF? K+.
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III. Short Answer Questions
Explain the cellular mechanism of ADH action on the collecting duct.
Answer: ADH binds to V2 receptors on the basolateral membrane of principal cells, activating adenylyl cyclase via a Gs protein to produce cAMP. cAMP activates protein kinase A, which triggers the insertion of aquaporin-2 water channels into the luminal membrane, increasing water permeability.
Describe the concept of "Splay" in the glucose titration curve.
Answer: Splay is the portion of the curve where glucose begins to be excreted in the urine before the plasma concentration reaches the point of full carrier saturation (Tm). It occurs due to the low affinity of the transporters and the heterogeneity of nephrons.
How does the kidney participate in countercurrent multiplication?
Answer: The "single effect" in the thick ascending limb actively transports NaCl into the interstitium while being impermeable to water. This increases interstitial osmolarity, which pulls water out of the descending limb, concentrating the tubular fluid and establishing the corticopapillary gradient.
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IV. Essay Questions
Describe the integrated renal and hormonal response to a high Na+ intake.
Answer: High Na+ intake increases ECF volume and EABV. This triggers: (1) a decrease in sympathetic activity to the kidneys, increasing GFR; (2) an increase in ANP, inhibiting Na+ reabsorption; (3) a decrease in RAAS (lowering aldosterone), further reducing Na+ reabsorption; and (4) a decrease in oncotic pressure in peritubular capillaries, inhibiting proximal reabsorption. Together, these increase Na+ excretion to restore balance.
Compare and contrast the mechanisms of H+ excretion as titratable acid versus NH4+.
Answer: Titratable acid involves H+ secreted by H+-ATPase or Na+-H+ exchange combining with filtered phosphate (HPO4−2) to form H2PO4−. This is limited by the amount of filtered buffer. NH4+ excretion involves the synthesis of NH3 from glutamine; NH3 diffuses into the lumen, combines with H+ to form NH4+, and is "trapped" for excretion. Unlike titratable acid, NH4+ production can be up-regulated during chronic acidosis.
