P: Urinary System 3

Urinary System

Overview

The urinary system plays a critical role in maintaining homeostasis by regulating fluid balance, electrolyte concentrations, and waste excretion. Chapter 17 focuses on renal physiology, including potassium handling, water reabsorption, and measurement of glomerular filtration rate (GFR).

Blood Potassium Concentration (3.5 to 5.0 mEq/L)

Importance of Potassium

• Potassium (K+) is essential for determining the resting membrane potential (RMP) of cells.

• Hypokalemia (low K+ levels): RMP becomes hyperpolarized, making cells farther from threshold and less excitable.

• Hyperkalemia (high K+ levels): RMP becomes less negative, cells are closer to threshold, but excessive depolarization can inactivate Na+ channels, impairing action potentials.

• Symptoms: Muscle weakness, cramps, paralysis, and cardiac arrhythmias.

Reabsorption and Secretion of Potassium

Renal Handling of Potassium

• The ascending limb of the nephron loop requires a specific K+ concentration for its transport mechanisms.

• The endothelium of the descending limb is impermeable to potassium.

• Approximately 65-70% of K+ is reabsorbed before entering the nephron loop.

• Reabsorbed ions can be secreted in the collecting duct.

• Additional info: In chronic kidney disease, the colon can eliminate K+ in the feces.

Reabsorption of NaCl and Water

Proximal Convoluted Tubule (PCT)

• The filtrate is isosmotic with plasma.

• The PCT reabsorbs 65% of filtered Na+, Cl-, and water.

• Active transport of Na+ via Na+/K+ ATPase and passive movement of water and Cl-.

• Filtrate remains isosmotic because salts and water are removed in proportionate amounts.

• Osmolarity: 300 mOsm entering and leaving the PCT.

Nephron Loop (Loop of Henle)

• Creates a corticomedullary gradient for urine concentration.

• Descending limb: Permeable to water, not to salt. Filtrate becomes hyperosmotic.

• Ascending limb: Impermeable to water, permeable to salt. Filtrate becomes hypoosmotic.

• This gradient drives water reabsorption by osmosis in the collecting duct.

Distal Convoluted Tubule (DCT) and Collecting Duct

• Filtrate entering the DCT in the cortex is hypotonic; interstitial fluid in the medulla is hypertonic.

• The collecting duct passes through the salty medulla, losing water by osmosis, concentrating urine.

• Vasa recta: Specialized capillaries in the medulla that trap NaCl in the interstitial fluid, maintaining the gradient.

Effect of ADH in Urine Concentration

Antidiuretic Hormone (ADH) Mechanism

• ADH is produced by the hypothalamus and secreted by the pituitary gland.

• ADH binds to V2 receptors on collecting duct cells.

• This triggers insertion of aquaporin-2 water channels into the apical membrane.

• Water is reabsorbed from the tubular fluid into the hyperosmotic medullary interstitium.

• Effect on urine: Volume decreases, osmolality increases.

Regulation and Feedback

• Low water intake/dehydration stimulates ADH release, increasing water reabsorption.

• High water intake suppresses ADH, decreasing water reabsorption.

• Alcohol suppresses ADH secretion, leading to polyuria and dehydration.

Diabetes Insipidus

Pathophysiology

• Inability to concentrate urine, causing excessive urination (polyuria) and thirst (polydipsia).

• Central Diabetes Insipidus: Low or absent ADH production/release from hypothalamus/posterior pituitary.

• Nephrogenic Diabetes Insipidus: Kidneys do not respond to ADH.

Inulin

Properties and Uses

• Inulin is a fructose polymer produced by plants (e.g., artichoke, onions, garlic).

• Used as a mildly sweetener in foods and beverages.

• Glycemic index is essentially 0; safe for people with diabetes.

Measurement of Glomerular Filtration Rate (GFR)

Renal Clearance of Inulin

• Inulin is freely filtered by the glomerulus, not bound to plasma proteins, not secreted, not reabsorbed, and not metabolized by renal tubules.

• All filtered inulin appears in urine; thus, renal clearance of inulin equals GFR.

• Not routinely used to assess kidney function due to practical limitations.

Equations for GFR Measurement

• Rate of inulin excretion:

$\text{Excretion rate} = V \times U$

Where:

• $V$ = rate of urine formation (mL/min)

• $U$ = inulin concentration in urine (mg/mL)

• Rate of filtration:

$\text{Rate filtered} = \text{GFR} \times P$

Where:

• $P$ = inulin concentration in plasma (mg/mL)

• GFR calculation:

$\text{GFR}_{(mL/min)} = \frac{V_{(mL/min)} \times U_{(mg/mL)}}{P_{(mg/mL)}}$

Worked Example

• IV infusion maintains plasma inulin at 0.4 mg/mL.

• Urine formation rate: 1.2 mL/min.

• Urine inulin concentration: 40 mg/mL.

Calculation	Equation	Result
Rate of inulin excretion	$1.2 \times 40$	48 mg/min
Glomerular filtration rate (GFR)	$\frac{1.2 \times 40}{0.4}$	120 mL/min
Rate of filtration of inulin	$120 \times 0.4$	48 mg/min

Summary Table: Renal Handling of Key Substances

Substance	Filtered?	Reabsorbed?	Secreted?	Used for GFR?
Inulin	Yes	No	No	Yes
Glucose	Yes	Yes	No	No
Creatinine	Yes	No	Yes (slightly)	Sometimes

Additional info: Creatinine clearance is often used clinically as an estimate of GFR, though it slightly overestimates true GFR due to tubular secretion.