Renal System and Nephron (Chapter 1-6)

Renal System Overview

• The kidneys perform glomerular filtration of blood, reabsorb needed substances, excrete waste, and regulate body homeostasis of water, electrolytes, and acid-base balance. They also prevent passage of certain substances (e.g., cells and large proteins) during filtration.
• Clinical relevance: urinalysis reflects renal processing of plasma and helps assess kidney function and urinary tract health.
• Overall architecture: two kidneys, each connected to a ureter; ureters drain into the bladder; urine exits through the urethra. Blood enters kidney via the renal artery and leaves via the renal vein.
• Functional unit: the nephron is the core structure that conducts filtration, reabsorption, and secretion to form urine.
• Subdivisions of the kidney: cortex (outer region) and medulla (inner region).
  • Cortex: contains glomeruli where plasma filtration begins.
  • Medulla: contains the loop of Henle and collecting ducts, important for concentrating urine.
• Urine collection pathway: filtrate forms in the glomerulus, moves into Bowman's capsule, then through the nephron (proximal tubule → loop of Henle → distal tubule → collecting duct) and finally into the renal pelvis before entering the ureter.
• Blood vessels of the nephron: afferent arteriole brings blood into the glomerulus; efferent arteriole carries filtrate-adjusted blood away and gives rise to peritubular capillaries.
• Primary processes: filtration, reabsorption, secretion, and concentration of urine to maintain homeostasis.

Kidney Anatomy and Regions

• Kidneys: two organs responsible for filtering blood and forming urine.
• Ureters: two tubes transporting urine from each kidney to the bladder.
• Bladder: stores urine before it exits through the urethra.
• Cortex vs Medulla:
  • Cortex: outer region; contains glomeruli (sites of initial filtration).
  • Medulla: inner region; contains nephron components (loop of Henle, collecting ducts) involved in concentrating urine.
• Renal pelvis: central collecting region where urine begins to collect before entering the ureter.
• Renal artery/vein: supply blood to and drain filtered blood from the kidney.

Nephron: The Functional Unit

• The nephron performs filtration and reabsorption/secretion along its segments.
• Key components in order:
  • Afferent arteriole: brings blood into the glomerulus.
  • Glomerulus: capillary network where plasma is filtered; surrounded by Bowman's capsule.
  • Bowman's capsule: collects filtrate from the glomerulus.
  • Proximal tubule: major site of reabsorption; returns essential solutes and water to the blood.
  • Loop of Henle: creates osmotic gradient for urine concentration; has descending and ascending limbs with different permeability.
  • Distal convoluted tubule: fine-tuning of urine composition; responsive to hormonal control.
  • Collecting duct: final adjustments; hormonal regulation determines final urine concentration.
• Filtration pathway: blood in the afferent arteriole → glomerulus → Bowman's capsule filtrate → proximal tubule → loop of Henle → distal tubule → collecting duct → renal pelvis → ureter.

Glomerular Filtration Barrier: Three Structural Layers

• Capillary endothelium: fenestrated; relatively permeable to water and small solutes but restricts blood cells.
• Basement membrane: less permeable; provides selective barrier against proteins.
• Podocytes: visceral epithelial cells with slit diaphragms; form final restrictive layer preventing passage of large molecules.
• Outcome: the glomerulus filters plasma but retains cells and most proteins in the blood; filtrate enters Bowman's capsule for further processing.

Tubular Segments: Reabsorption and Secretion Profiles

• Proximal tubule (reabsorption hub):
  • Reabsorbs major components from filtrate back into blood: water,
  • ext{Na}^+, ext{Cl}^-, amino acids, glucose, bicarbonate, and other solutes.
  • Water reabsorption occurs along with solutes to maintain osmotic balance.
• Loop of Henle: descending vs ascending limbs
  • Descending limb: permeable to water; not permeable to Na^+/K^+/Cl^-; water exits to concentrate filtrate.
  • Ascending limb: impermeable to water; actively and passively transports Na^+ and Cl^- out of the filtrate; dilutes filtrate and helps build medullary osmotic gradient.
• Distal convoluted tubule: fine adjustments to urine composition
  • Permeability to water and ions is variable and hormonally regulated.
  • Major regulators: aldosterone and ADH (see sections on hormonal control).
• Collecting duct: final adjustments and urine concentration
  • Regulated by aldosterone and ADH; final determination of water reabsorption and, to a degree, sodium handling.
• Overall: the nephron reabsorbs electrolytes and nutrients while concentrating or diluting urine as needed to maintain homeostasis.

Hormonal Regulation of Sodium and Water Handling

• Renin-Angiotensin-Aldosterone System (RAAS)
  • Juxtaglomerular apparatus (JGA): a collection of cells near the afferent arteriole and distal tubule that releases renin.
  • Triggers for renin release: decreased blood volume, low plasma volume, low blood pressure, and low sodium concentrations.
  • Cascade:
  • Renin (enzyme) is secreted by the JGA and converts angiotensinogen to Angiotensin I (Ang I).
  • Ang I is converted to Angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) primarily in the lungs.
  • Ang II stimulates the adrenal cortex to release aldosterone.
  • Aldosterone acts on the distal tubule and collecting duct to increase Na^+ reabsorption; water follows Na^+, increasing blood volume and pressure.
  • Regulatory outcome: when blood volume/pressure is low, RAAS is activated to raise Na^+, water, and pressure; when volume/pressure is high, renin secretion is inhibited and Na^+ excretion is promoted.
• Antidiuretic Hormone (ADH, vasopressin)
  • Produced in the hypothalamus and released into bloodstream via the posterior pituitary.
  • Arterial pressure sensors monitor blood pressure; high arterial pressure inhibits ADH (negative feedback).
  • Low blood pressure stimulates ADH release.
  • ADH actions:
  • Increases water reabsorption in the collecting ducts, leading to conserved water and more concentrated urine.
  • Does not directly alter Na^+ or Cl^- handling; its primary target is water reabsorption.
  • Net effect: ADH adjusts body water content and urine concentrating ability in response to blood pressure and volume signals.

Integrated Flow: From Blood to Concentrated Urine

• Blood flow and filtration:
  • Afferent arteriole delivers blood to the glomerulus, where filtration forms the filtrate that will become urine.
  • Efferent arteriole carries filtered blood onward; peritubular capillaries participate in reabsorption/secretion along the nephron.
• Tubular processing:
  • Proximal tubule reclaims most of the filtered solutes and water.
  • Loop of Henle establishes and maintains the medullary osmotic gradient essential for urine concentration.
  • Distal tubule and collecting duct perform fine-tuning under hormonal control (aldosterone and ADH).
• Hormonal regulation in action:
  • Low blood volume or low sodium → RAAS activation → increased Na^+ reabsorption and water conservation → increased blood volume.
  • Low blood pressure or dehydration → ADH release → increased water reabsorption → concentrated urine.
  • High volume/pressure → RAAS and ADH activity decrease → increased excretion and dilution of urine.

Key Terms and Concepts to Remember

• Nephron: functional unit of the kidney; filtration, reabsorption, secretion, urine concentration.
• Cortex and Medulla: regional distinction; cortex contains glomeruli; medulla contains loop of Henle and collecting ducts.
• Glomerulus and Bowman's capsule: initial filtration unit; filtration barrier consists of capillary endothelium, basement membrane, and podocytes.
• Afferent vs Efferent arterioles: blood inflow and outflow from the glomerulus.
• Proximal tubule, Loop of Henle (descending/ascending limbs), Distal tubule, Collecting duct: sequential segments of the nephron.
• Renin-Angiotensin-Aldosterone System (RAAS): triggers sodium and water reabsorption to restore blood volume and pressure.
• Aldosterone: mineralocorticoid that increases Na^+ reabsorption in distal tubule and collecting duct; water follows.
• Antidiuretic Hormone (ADH): increases water reabsorption in collecting ducts; concentrates urine; independent of Na^+/Cl^- handling.
• Juxtaglomerular apparatus (JGA): site of renin release in response to hemodynamic cues.

Equations and Conceptual Formulas

• RAAS cascade (simplified):
  • ext{Renin}
    ightarrow ext{Angiotensin I}
    ightarrow ext{Angiotensin II}
    ightarrow ext{Aldosterone release}
    ightarrow ext{Na}^+ ext{ reabsorption}
    ightarrow ext{Water reabsorption}
    ightarrow ext{Increased blood volume}
• Angiotensin II adrenocortical signaling:
  • ext{Ang II}
    ightarrow ext{Adrenal cortex}
    ightarrow ext{Aldosterone release}
• ADH action on water:
  • ext{ADH}
    earrow
    ightarrow ext{Water reabsorption in collecting duct}
    ightarrow ext{Concentrated urine}
• Loop of Henle permeability themes:
  • Descending limb: permeability to water only (not Na^+ or Cl^-);
  • Ascending limb: reabsorption of Na^+ and Cl^- but water is not reabsorbed.

Practical and Real-World Relevance

• Urinalysis relies on understanding where and how substances are filtered and reabsorbed to interpret what normal and abnormal urine composition might indicate about renal function.
• The hormonal control of water and electrolyte balance (RAAS and ADH) is central to managing conditions like dehydration, volume overload, hypertension, and certain kidney diseases.
• The nephron’s segmentation explains why proximal, distal, and collecting duct sites are targeted differently by drugs (e.g., diuretics affecting specific segments).

Quick Reference: What to Focus On for Exams

• Where filtration occurs (glomerulus/Bowman’s capsule) and what barriers prevent passage of cells/proteins.
• The sequence of nephron segments and the primary transport activities in each: proximal reabsorption; Loop of Henle osmotic gradient; distal adjustments; collecting duct regulation.
• Hormonal control: when RAAS is activated vs when it is inhibited; how aldosterone and ADH specifically alter urine composition and volume.
• The general flow of blood through the nephron (afferent/efferent arterioles, glomerulus) and how this relates to filtration pressure and filtration rate.

Connections to Foundational Principles

• Homeostasis: maintaining body fluid volume, composition, and pH through selective filtration, reabsorption, and secretion.
• Osmoregulation: the medullary gradient and looping mechanism enable urine concentration and water conservation.
• Feedback mechanisms: negative feedback in both RAAS (high volume suppresses renin) and ADH (high arterial pressure suppresses ADH).

Ethical, Philosophical, and Practical Implications (as Discussed)

• Practical: understanding renal physiology underpins diagnostics and treatment in medicine (e.g., interpreting urinalysis, managing electrolyte and fluid balance).
• Ethical/philosophical discussions are not explicitly covered in these slides, but sound knowledge of renal function informs medical decision-making about patient consent, treatment choices (e.g., diuretics, volume management), and prioritization of renal protection in disease.