Renal Physiology: Kidney Function, Water-Solute Balance, and Acid-Base Regulation

Kidney Structure and Function

Overview of Kidney Anatomy

The kidneys are vital organs responsible for filtering blood, maintaining water and solute balance, and excreting waste products. Each kidney consists of distinct regions and structures that contribute to its function.

• Cortex: The outer region containing glomeruli and most of the nephron tubules.

• Medulla: The inner region with loops of Henle and collecting ducts.

• Renal pelvis: Collects urine before it moves to the ureter.

• Ureter: Transports urine to the bladder.

• Capsule: Protective outer covering.

Example: The nephron, the kidney's functional unit, spans both cortex and medulla, performing filtration, reabsorption, secretion, and excretion.

Nephron Structure and Function

Nephrons are the microscopic functional units of the kidney. Each nephron consists of:

• Bowman's capsule: Site of initial filtration.

• Proximal and distal tubules: Sites of reabsorption and secretion.

• Loop of Henle: Establishes medullary osmotic gradient.

• Collecting duct: Final site for water and solute reabsorption, regulated by hormones.

Renal Processes: Filtration, Reabsorption, Secretion, Excretion

Filtration

Filtration occurs at the glomerulus, where blood plasma is filtered into Bowman's capsule. The filtration barrier consists of capillary endothelium, basement membrane, and podocyte foot processes.

• Filtration fraction: Proportion of plasma filtered by the glomerulus.

• Formula: $\text{Filtration fraction} = \frac{\text{Volume filtered}}{\text{Renal plasma flow}}$

• Filtered load: Amount of a specific substance filtered per unit time.

• Formula: $\text{Filtered load} = \text{GFR} \times \text{Plasma concentration of substance}$

• Example calculation: If 120 mL/min plasma is filtered and substance X is 1 mg/mL, filtered load = 120 mg/min.

Capillary Filtration Forces

Filtration pressure is determined by hydrostatic and osmotic forces:

• Net filtration pressure: $P_{GC} - \pi_{GC} - P_{BC}$

• Hydrostatic pressure (PGC): Drives filtration out of glomerulus.

• Colloid osmotic pressure (πGC): Opposes filtration.

• Capsule fluid pressure (PBC): Opposes filtration.

Glomerular Filtration Rate (GFR)

GFR is the rate at which plasma is filtered by the kidneys, typically about 125 mL/min. GFR is autoregulated over a range of blood pressures to maintain homeostasis.

• Autoregulation: Maintains constant GFR between 80-180 mmHg mean arterial pressure.

• Factors affecting GFR: Filtration pressure, surface area, and permeability.

GFR Regulation

GFR is regulated by changes in afferent and efferent arteriole resistance, and by feedback from the juxtaglomerular apparatus.

• Increased afferent resistance: Decreases GFR.

• Increased efferent resistance: Increases GFR.

• Tubuloglomerular feedback: Macula densa senses flow and signals afferent arteriole to constrict or dilate.

Reabsorption

Reabsorption is the process by which substances are transported from the filtrate back into the blood. Most reabsorption occurs in the proximal tubule.

• Mechanisms: Active transport (e.g., Na+), passive diffusion (e.g., water, urea).

• Water reabsorption: Driven by osmotic gradients.

• Glucose reabsorption: Coupled to Na+ via SGLT transporters; limited by transport maximum (Tm).

Saturation and Renal Threshold

Transporters for substances like glucose can become saturated, leading to excretion in urine when plasma concentration exceeds the renal threshold.

• Transport maximum (Tm): Maximum rate of reabsorption.

• Renal threshold: Plasma concentration at which saturation occurs.

Secretion

Secretion is the active transport of substances from blood into the nephron tubule, often for elimination of drugs, toxins, or excess ions.

• Mechanisms: Direct, secondary, and tertiary active transport (e.g., organic anion transporters).

Excretion

Excretion is the elimination of filtered and secreted substances in urine.

• Formula: $\text{Excretion} = \text{Filtration} - \text{Reabsorption} + \text{Secretion}$

Renal Handling of Key Solutes

Solute	Proximal Tubule	Loop of Henle	Distal Tubule	Collecting Duct
Na+	Reabsorbed	Reabsorbed	Reabsorbed	Reabsorbed (regulated)
K+	Reabsorbed	Reabsorbed	Secreted	Secreted (regulated)
Cl-	Reabsorbed	Reabsorbed	Reabsorbed	Reabsorbed
HCO3-	Reabsorbed	Reabsorbed	Reabsorbed	Reabsorbed
H+	Secreted	Secreted	Secreted	Secreted

Additional info: Table inferred from slide showing renal handling of key solutes.

Hormonal Regulation of Renal Function

Vasopressin (Antidiuretic Hormone, ADH)

Vasopressin regulates water reabsorption in the collecting duct, increasing water permeability and concentrating urine.

• Origin: Hypothalamic neurons, released from posterior pituitary.

• Stimuli for release: Increased plasma osmolarity, decreased blood pressure/volume.

• Target: Renal collecting duct (V2 receptors).

• Action: Increases insertion of aquaporin water channels.

Property	Vasopressin (ADH)
Origin	Hypothalamic neurons, posterior pituitary
Chemical Nature	9-amino acid peptide
Transport	Dissolved in plasma
Half-Life	15 min
Target	Renal collecting duct
Receptor	V2 receptor/cAMP
Action	Increases water reabsorption

Renin-Angiotensin-Aldosterone System (RAAS)

The RAAS regulates sodium reabsorption, blood pressure, and fluid balance.

• Renin: Released by juxtaglomerular cells in response to low blood pressure.

• Angiotensin II: Potent vasoconstrictor, stimulates aldosterone release.

• Aldosterone: Increases Na+ reabsorption and K+ secretion in the distal nephron.

Hormone	Origin	Stimulus	Target	Action
Renin	Juxtaglomerular cells	Low BP, low Na+	Blood/plasma	Converts angiotensinogen to angiotensin I
Angiotensin II	Liver (precursor), activated in blood	Renin release	Blood vessels, adrenal cortex	Vasoconstriction, stimulates aldosterone
Aldosterone	Adrenal cortex	Angiotensin II, high K+	Distal nephron	Increases Na+ reabsorption, K+ secretion

Water and Solute Balance

Water Gain and Loss

Water balance is maintained by matching intake and output. Kidneys play a central role in regulating water loss via urine.

• Water gain: Food/drink (2.2 L/day), metabolism (0.3 L/day).

• Water loss: Skin/lungs (0.9 L/day), urine (1.5 L/day), feces (0.1 L/day).

Renal Regulation of Water and Solute

The kidneys adjust GFR and water reabsorption to conserve or excrete fluid as needed. They cannot restore lost volume, only conserve fluid.

• GFR adjustment: Reduces urine output during dehydration.

• Regulated H2O reabsorption: Controlled by vasopressin.

Countercurrent Exchange and Osmotic Gradient

The loop of Henle establishes a medullary osmotic gradient, allowing for concentration of urine.

• Descending limb: Permeable to water, not solutes.

• Ascending limb: Permeable to solutes, not water.

• Countercurrent exchange: Maintains gradient via vasa recta.

Integrated Water and Solute Balance

Homeostatic mechanisms coordinate renal, cardiovascular, and endocrine responses to maintain osmolarity and volume.

• Volume and osmolarity changes: Trigger thirst, vasopressin, and RAAS activation.

• Example: Drinking water decreases osmolarity, suppresses vasopressin, increases urine output.

Volume	Osmolarity Decrease	Osmolarity No Change	Osmolarity Increase
Increase	Drinking water	Isotonic saline	Hypertonic saline
No change	Sweat loss replaced with water	Normal	Eating salt without water
Decrease	Incomplete dehydration compensation	Hemorrhage	Dehydration (sweat loss, diarrhea)

Acid-Base Balance

H+ Balance and Buffering

The kidneys help regulate plasma pH by excreting H+ and reabsorbing bicarbonate (HCO3-).

• Normal plasma pH: 7.38–7.42

• H+ input: Diet (fatty acids, amino acids), metabolism (CO2, lactic acid).

• Buffers: HCO3-, proteins, phosphates, ammonia.

• H+ output: CO2 (lungs), H+ (kidneys).

Renal Acid-Base Regulation

Nephron cells secrete H+ into urine, buffered by phosphate and ammonia, and reabsorb filtered bicarbonate.

• Acidosis: Increased H+ secretion, increased HCO3- reabsorption.

• Alkalosis: Decreased H+ secretion, decreased HCO3- reabsorption.

Review Questions

• If BP decreases, what happens to angiotensin II production? Angiotensin II production increases to restore blood pressure.

• How would you determine the excretion rate of a substance? Excretion rate = urine concentration × urine flow rate.

• Name the hormone involved in water reabsorption. Vasopressin (ADH).

• Name the hormone involved in sodium reabsorption. Aldosterone.

Urinalysis Lab: Homeostatic Responses to Water Intake

• Short-term response to drinking 500 mL water: Decrease in plasma osmolarity, suppression of vasopressin, increased urine output.

• Long-term response: Renal and hormonal adjustments restore osmolarity and volume to baseline.