PHAR 3244 – Spring 2026 Systems Pharmacology II
PHAR 3244 – Systems Pharmacology II
Learning Objectives
Describe the anatomy of the kidney and nephron.
Describe the process of glomerular filtration.
Describe the forces and properties that promote or counteract glomerular filtration.
Compare the local and systemic controls of glomerular filtration rate (GFR).
Describe the process of reabsorption.
Describe the transporters that are required for reabsorption.
Describe the process of secretion.
Identify the substances that are secreted.
Describe the mechanisms responsible for the medullary osmotic gradient.
Explain the formation of dilute versus concentrated urine.
Describe the role of the kidney in maintaining pH.
Kidney: Functions
Red Blood Cell Production: Kidneys produce erythropoietin, which stimulates the production of red blood cells in response to hypoxia.
Blood Pressure Regulation: Through regulation of blood volume and vasodilation/vasoconstriction.
Acid-Base Balance: Kidneys manage acid-base balance by excreting hydrogen ions and reabsorbing bicarbonate ions.
Regulation of Fluid and Electrolyte Balance: Balancing levels of sodium, potassium, calcium, phosphate, and fluid.
Vitamin D Production & Bone Health: Converting vitamin D into its active form for calcium absorption.
Filtration of Blood & Waste Excretion: Removing wastes from the blood and excreting urine.
Anatomy of the Kidney
Renal Hilum: Entry and exit point of structures such as blood vessels and ureters.
Renal Cortex: The outer layer of the kidney where nephrons are located.
Renal Medulla: Inner region containing renal pyramids and loops of Henle.
Renal Pelvis: Funnel-shaped structure where urine collects before moving to the ureter.
Main Blood Vessels:
Aorta: Supplies blood to the kidneys via the renal artery.
Renal Artery: Branches into smaller arteries supplying blood throughout the kidney.
Renal Vein: Drains blood away from the kidney to the inferior vena cava.
Nephron: The Functional Unit
Over 1 million nephrons per kidney. Main components include:
Renal Corpuscle: Composed of the glomerulus and Bowman's capsule.
Renal Tubules:
Proximal Convoluted Tubule (PCT)
Loop of Henle (LH)
Distal Convoluted Tubule (DCT)
Collecting Duct (CD)
Types of Nephrons:
Cortical Nephrons: Majority (85%), primarily in cortex.
Juxtamedullary Nephrons: Concentrate urine, extend into medulla.
Nephron Capillary Beds
Peritubular Capillaries: Low-pressure vessels for reabsorption, covering renal tubules.
Vasa Recta: Specialized vessels for juxtamedullary nephrons, assist in concentrating urine.
Glomerulus: High-pressure capillary network for filtration, fed by afferent arterioles.
Glomerular Filtration
Process of Filtration: Passive process driven by hydrostatic pressure, filtering blood plasma through glomerular capillaries.
Filtrate Composition: Similar to blood plasma, minus proteins.
Hydrostatic Pressure (HPgc):
High at 55 mmHg, maintained due to the resistance of arterioles, facilitating fluid movement.
Oncotic Pressure: Protein concentration in blood helps maintain fluid balance.
Net Filtration Pressure (NFP): Influenced by hydrostatic pressure, oncotic pressure, and capsular pressure.
Regulation of Glomerular Filtration Rate (GFR)
Intrinsic Regulation:
Myogenic Mechanism: Afferent arteriole constriction/dilation in response to blood pressure changes.
Tubuloglomerular Feedback: Adjusts GFR based on sodium concentration detected by macula densa.
Extrinsic Regulation:
SNS: Norepinephrine constricts afferent arterioles, decreasing GFR during stress.
Hormonal: Renin-angiotensin-aldosterone system (RAAS) increases blood pressure via vasoconstriction and sodium retention.
Urine Formation Steps
Glomerular Filtration
Tubular Reabsorption
Tubular Secretion
Tubular Reabsorption
Process: Essential nutrients and water are reabsorbed back into the capillaries from the filtrate.
Location of Reabsorption:
PCT: Most reabsorption occurs here (65% Na+, all glucose, amino acids).
Loop of Henle: Descending limb (water reabsorption), ascending limb (solute reabsorption).
DCT: Hormonal regulation; specific ions reabsorbed.
CD: Water reabsorption regulated by ADH; aldosterone influences sodium transport.
Tubular Secretion
Process: Selective transfer of substances from blood in peritubular capillaries into renal tubule.
Common substances secreted include K+, H+, NH4+, creatinine, and organic acids.
Acid-Base Balance
Mechanisms include reabsorption of bicarbonate (HCO3-) and secretion of hydrogen ions (H+).
Carbonic Anhydrase: Critical for bicarbonate reabsorption and pH regulation.
Summary Notes
The kidney has multifaceted roles influencing blood cell production, blood pressure, fluid balance, and urine formation through complex processes of filtration, reabsorption, and secretion. Understanding the detailed anatomy and physiology of renal function is crucial in appreciating its regulatory functions in the context of systemic health.
Filtration in the Glomerulus: Blood enters the kidneys via the renal artery and flows into the glomerulus, where hydrostatic pressure forces water and small solutes from the blood into Bowman's capsule, forming the filtrate. The filtrate is similar to plasma but devoid of proteins.
Proximal Convoluted Tubule (PCT): The filtrate then moves into the PCT, where about 65% of water, all glucose, and most amino acids are reabsorbed back into the blood through active transport and osmosis.
Loop of Henle: Next, it flows into the Loop of Henle, which has two limbs:
Descending Limb: Permeable to water but not to salts, allowing water to be reabsorbed, concentrating the filtrate.
Ascending Limb: Impermeable to water, reabsorbs sodium and chloride ions actively, diluting the filtrate.
Distal Convoluted Tubule (DCT): The filtrate passes into the DCT, where further reabsorption of sodium and secretion of potassium, hydrogen ions, and other substances occurs, influenced by hormonal regulation (e.g., aldosterone).
Collecting Duct (CD): Finally, the filtrate enters the collecting duct, where more water reabsorption takes place, regulated by antidiuretic hormone (ADH). The final concentration and volume of urine are determined here before it drains into the renal pelvis.
Urine Excretion: The urine, composed of waste and unneeded substances, then moves down the ureters to the bladder for storage and expulsion to the external environment.
Describe the anatomy of the kidney and nephron.
The kidney consists of the renal hilum, renal cortex, renal medulla, and renal pelvis. The renal hilum is the entry and exit point for blood vessels and ureters. The renal cortex contains nephrons, while the renal medulla features renal pyramids and loops of Henle.
Nephrons, the functional units of the kidney, comprise:
Renal Corpuscle (glomerulus and Bowman's capsule)
Renal Tubules: Proximal Convoluted Tubule (PCT), Loop of Henle, Distal Convoluted Tubule (DCT), and Collecting Duct (CD).
Describe the process of glomerular filtration.
Glomerular filtration is a passive process driven by hydrostatic pressure, effectively filtering blood plasma through glomerular capillaries into Bowman's capsule. The filtrate's composition is similar to plasma but lacks proteins.
Describe the forces and properties that promote or counteract glomerular filtration.
Hydrostatic pressure (HPgc) is high at 55 mmHg due to arteriolar resistance, driving fluid movement. Oncotic pressure from proteins in the blood counters this, aiming to pull water back into the capillaries.
Net Filtration Pressure (NFP) is determined by the balance of these forces.
Compare the local and systemic controls of glomerular filtration rate (GFR).
Intrinsic Regulation includes:
Myogenic Mechanism: Afferent arteriole response to blood pressure changes.
Tubuloglomerular Feedback: GFR adjustments based on sodium concentration detected by the macula densa.
Extrinsic Regulation involves:
Sympathetic Nervous System (SNS): Norepinephrine constricts afferent arterioles, reducing GFR.
Hormonal control: Renin-angiotensin-aldosterone system (RAAS) increases blood pressure through vasoconstriction and sodium retention.
Describe the process of reabsorption.
Reabsorption is the process by which essential nutrients and water are taken back into the bloodstream from the filtrate, primarily occurring in the PCT, Loop of Henle, DCT, and CD.
Describe the transporters that are required for reabsorption.
Various transporters operate in reabsorption, including sodium-potassium pumps, glucose transporters, and aquaporins, which facilitate solute and water movement across renal tubular cells.
Describe the process of secretion.
Secretion involves the selective transfer of substances from the blood in peritubular capillaries into the renal tubule, allowing for waste removal and acid-base balance adjustments.
Identify the substances that are secreted.
Commonly secreted substances include potassium ions (K+), hydrogen ions (H+), ammonium (NH4+), creatinine, and organic acids.
Describe the mechanisms responsible for the medullary osmotic gradient.
The nephron's Loop of Henle creates a medullary osmotic gradient through counter-current multiplication, allowing the kidney to concentrate urine effectively.
Explain the formation of dilute versus concentrated urine.
Concentrated urine is formed when conditions favor water reabsorption in the CD due to ADH, while dilute urine occurs with low ADH levels, leading to less water reabsorption.
Describe the role of the kidney in maintaining pH.
The kidneys regulate pH by reabsorbing bicarbonate (HCO3-) and secreting hydrogen ions (H+), with carbonic anhydrase playing a key role in this process.