Kidney Introduction: Functions and Structure - MED 204

Introduction to the Kidney

• Renal System Module, Code MED 204
• Lecturers are Prof David Henshall & Dr. Patrick Walsh
• February 2025

Kidney Overview

• Functions of the kidney
• Body fluid composition
• The nephron
• Simple overview of urine formation

Role in Homeostasis

• The kidney is a key organ in homeostasis
• Ensures optimal water levels in the body
• Maintains blood pressure
• Eliminates wastes like urea and toxins through urine
• Activates vitamin D for calcium absorption
• Regulates acid-base balance
• Maintains electrolyte balance for heart rhythm (potassium, sodium, calcium)
• Releases erythropoietin to stimulate red blood cell production in bone marrow

Structure

• Bean-shaped organs located under the ribcage on either side of the spine
• Filters blood, removing wastes and water
• Produces urine
• Urine travels down the ureter to be stored in the bladder
• Kidney are bilateral retroperitoneal organs
• Blood supply comes from the renal artery and vein
• Filtrate forms in Bowman’s capsule within the cortex
• Urine flows from collecting ducts into calyces

Primary Functions

• Regulates volume and composition of extracellular fluid (ECF)
• Eliminates potentially toxic metabolic wastes and foreign compounds

Functions Continued

• Maintains water balance
• Maintains proper plasma volume
• Regulation of blood pressure
• Maintains osmolarity (solute concentration) of body fluids
• Regulates quantity and concentration of extracellular fluid ions (Na+, K+, Cl-, Ca2+, PO43-)
• Maintains acid-base balance, influencing pH

Further Functions

• Excretes waste products from metabolism
• Urea is from amino acid metabolism
• Uric acid is from nucleic acid metabolism
• Excretes foreign compounds like drugs and food additives
• Converts vitamin D to active form in proximal tubule cells, which regulates Calcium
• Produces erythropoietin in the interstitium of cortex/outer medulla, stimulating red blood cell production

Body Fluid Composition

• Water accounts for 60% of body mass
• Intracellular water is 2/3 and extracellular water is 1/3.
• Extracellular fluid is outside cells
• Plasma surrounds blood cells
• Interstitial fluid surrounds tissue cells
• Free exchange of water and solutes occurs between plasma and interstitial fluid, except for proteins (across capillary walls)
• Distribution of fluid depends on hydrostatic and osmotic forces
• Composition changes affect cell physiology

Determinants of Plasma and ECF Osmolarity

• Plasma osmolarity is mainly determined by NaCl content relative to water content in the blood
• Decrease in water increases NaCl concentration, which in turn increases osmolarity
• Increase in water lowers NaCl concentration, which in turn lowers osmolarity
• Kidneys maintain water balance to keep plasma and ECF osmolarity constant

Osmolarity in the Body

• Osmolarity of plasma and ECF is normally maintained at 283 ± 11 mosmol/l
• Food contains salts and water, leading to increase in salt and water levels
• Exercise and other causes like vomiting and diarrhea also lead to changes
• Kidneys offset these changes by excreting appropriate amounts of salt and water

Functional Unit: The Nephron

• The nephron is the functional unit of the kidney
• Approximately 1 to 1.2 million nephrons exist in each kidney
• Each nephron has two sub-parts: the renal corpuscle and the tubular system

Sub-Parts of a Nephron

• Renal Corpuscle
• Tuft of capillaries which is the glomerulus
• Bowman’s capsule
• Tubular System
• Fluid-filled tube formed by a single layer of epithelial cells
• Vascular supply

Tubular Components and Functions

• Bowman’s Capsule collects glomerular filtrate
• Proximal Convoluted Tubule (PCT) absorbs and secretes selected substances
• Loop of Henle establishes an osmotic gradient in the renal medulla
• Ascending and descending loops have different channels/functions
• Distal Convoluted Tubule (DCT) regulates reabsorption of Na+ and water, and also secretes K+ and H+
• Collecting Duct transports fluid into the renal pelvis

Nephron Processes

• Filtration of blood
• Tubular reabsorption
• Tubular secretion

Urine Formation

• Filtration of blood forms tubular filtrate (mainly salt and water)
• Reabsorption returns most of the filtrate back into blood
• Secretion moves certain substances into filtrate
• Salt and water content of filtrate adjusted to match intake

Renal Blood Flow

• The first process in the nephron is ultrafiltration of plasma in the glomerulus, dependent on strong hydrostatic pressure
• Approximately 1.2 L/min of blood flows to the kidneys
• Very high: 1/5 of cardiac output

Blood Supply

• Renal artery subdivides into afferent arterioles, then peritubular capillaries, then recombines to venules and the renal vein
• Renal artery subdivides to form many afferent arterioles, each supplying a nephron
• Glomerular capillaries recombine to leave Bowman's capsule as efferent arterioles
• Efferent arterioles give rise to peritubular capillaries, which invest the tubular system of each nephron
• Peritubular capillaries then recombine to form venules and then the renal vein

Peritubular Capillaries

• Nutritive
• Reabsorptive
• Secretive

Glomerular Filtration

• Plasma from the blood entering the glomerulus is filtered with ~20% entering Bowman’s capsule
• Filtrate then flows through the tubular system, where valuable substances are reabsorbed into peritubular plasma

Filtration Barrier

• All components of plasma pass through the filtration barrier, except cells and proteins
• A small amount of protein passes through but is immediately reabsorbed
• Useful substances and waste pass through

Filtrate Volume

• Approximately 180 liters of filtrate are formed per day
• Entire ECF is “filtered” about 10 times per day
• Approximately 1.5 liters of urine is excreted
• Thus, approximately 178.5 liters of filtrate are reabsorbed each day

Tubular Reabsorption

• Reabsorption is highly selective and variable
• Tubules have high reabsorptive capacity for needed substances
• Little to no reabsorptive capacity for useless/harmful substances, which results in these substances staying in the filtrate
• Of the substances filtered, 99% are reabsorbed
• 99% of water, 100% of glucose, and 99.5% of salt are reabsorbed

Reabsorption Types

• Can be active, meaning energy-requiring, or passive
• Active reabsorption
• One or more steps in transepithelial transport requires energy (ATP) expenditure
• Examples: glucose, amino acids, Na+
• Movement occurs against a gradient
• Passive reabsorption
• Examples: water, chloride ion
• Movement occurs down electrochemical or osmotic gradient

Transepithelial transport steps:

• Substance leaves tubular fluid
• Passes through cytosol of tubular cell
• Crosses basolateral membrane
• Diffuses through interstitial space
• Penetrates capillary wall to enter blood plasma

Reabsorption Specific Substance and Locations

• Proximal tubule
• Sodium: 67%
• Water: 65%
• Loop of Henle
• Sodium: 25%
• Water: 15%
• Distal tubule and collecting tubules
• Sodium: 8%
• Water: 20%

Tubular Secretion

• Transepithelial transport occurs
• Substances are transferred from peritubular capillaries into tubular lumen
• Examples: H+, potassium, organic ions, drugs, food additives, and environmental pollutants

Composition of Urine

• Urine is final product and approximately 1ml/min is formed
• Comprises:
• Water (H2O)
• Urea (formed in liver as end product of protein metabolism)
• Creatinine (waste product of muscles)
• Ions (Na+, K+)
• Phenol
• Slightly acidic with a pH of approximately 6.0
• Osmolarity ranges from 50 - 1200 mOsm, depending on water levels in body

Learning Outcomes

• Explain the main functions of the kidneys
• Describe the basic tubular and vascular system of the nephron
• Explain the three major processes performed by the nephron to produce urine
• Describe body fluid composition
• Define the normal volume and composition of urine