Renal Physiology

• Lecture 12 is about Renal Physiology

Objectives

• Learn the function and anatomy of the kidney.
• Learn about the nephron.
• Learn about filtration.

Function of the Kidney

• Regulation of ECF volume and blood pressure.
• Regulation of osmolarity of blood.
• Regulation of ion balance (electrolytes).
• Homeostasis of pH.
• Excretion of wastes like urea/uric acid.
• Production of hormones like Vitamin D3, erythropoietin, and renin.

Anatomy of the Urinary System

• Kidney
• Ureter
• Urinary bladder
• Urethra

Kidneys

• Kidneys are the site of urine formation.
• Bulk of kidney tissue is made of nephrons.
• Nephrons are hollow tubes modifying water and solutes from blood into urine.
• Blood supplied to kidney via renal arteries are branches of abdominal aorta.
• Blood is carried from kidneys via the renal veins.

Ureter

• Hollow tube called the ureter is where modified fluid leaves the kidney.
• It moves urine into the bladder via peristalsis.

Urinary Bladder

• Left and right Ureters lead to the urinary bladder.
• The detrusor muscle is located inside of it.

Urethra

• Urine is expelled through the urethra.
• Micturition is the process by which urine is excreted.

The Nephron

• The nephron is the functional unit of the kidney.
• The Nephron is the smallest structure that can perform all kidney functions.
• Approximately 1 million nephrons exist.
• The cortex contains all Bowman's capsules and proximal/distal tubules.
• The medulla contains loops of Henle and collecting ducts.

Different Types of Nephrons

• Cortical Nephrons: 85% of kidney nephrons, performing excretory/regulatory functions.
  • They have a short loop of henle which only penetrates outer renal medulla.
• Juxtamedullary Nephrons: 15% of kidney nephrons, concentrating or diluting urea.
  • They have a long loop of henle.

Anatomy of a Nephron

• Glomerulus: Specialized bundle of capillaries.
  • Fluid in capillaries passes directly into the glomerulus.
  • It is involved in selective filtration of blood through tubules within the nephron.
• Bowman's Capsule: Cup-like sack surrounding the glomerulus.
  • Encloses "Bowman's Space", marking the start of proximal convoluted tubule of the Nephron.
• Renal Corpuscle: Glomerulus + Bowman's Capsule.
  • It opens into a tubule.
• Proximal Convoluted Tubule: Segment of nephron between Bowman's Capsule and Loop of Henle.
  • It reabsorbs substances within the filtrate (glucose, Na, AA’s) based on body needs (osmosis).
  • Protein in urine indicates kidney damage as AA’s not being absorbed back into the blood.
• Loop of Henle: Involved primarily in reabsorption.
  • This segment dips down toward medulla of kidney, then back up.
  • Thin and thick segment, impermeable to water.
  • It actively pumps out Na to make medulla salty (hypertonic).
  • This draws out water from filtrate travelling through the nephron.
  • Descending limb is permeable to water, ascending limb actively pumps Na.
• Distal Tubule: Part of nephron between collecting duct and loop of Henle.
  • Reabsorption of ions like Na and Ca occurs here.
  • Waste products/water no longer needed are transferred into the collecting duct.
• Collecting Duct: The last part of the nephron to create the ureter.
  • It collects byproducts/waste from nephrons.
  • Dips back into the medulla (salty part) and is permeable to water.
  • Hormones (ADH) dictate how porous the tube is.
  • More porous = more water leaves
  • ADH = antidiuretic hormone
  • Diuretics make more urine output and dehydration.
  • ADH prevents this by promoting water reabsorption into blood.

Vascular Structures around the Nephron

• Afferent Arteriole: Blood flows into a ball-like network of capillaries (Glomerulus).
• Efferent Arteriole: Blood flows out of the glomerulus.
• Peritubular Capillaries: surrounds the tubule.
  • Also called vasa recta in juxtamedullary nephrons.
• Vasa Recta: peritubular capillaries in juxtamedullary nephrons.
• Renal Venules: vasa recta/peritubular capillaries join with renal venules which are blue.

Juxtaglomerular Apparatus

• The ascending limb of the loop of Henle passes right between the afferent and efferent arterioles.
• Permits flow communication between the structures.
• Facilitates autoregulatory function (e.g., regulation of blood pressure).

Basic Functions of the Kidney

• Filtration: Moving fluid from the blood to the lumen is filtration.

  • Occurs in the renal corpuscle, producing filtrate.

• Reabsorption: Movement of fluid from the lumen back to the peritubular capillaries.

• Secretion: Movement of selected molecules from the blood to the filtrate.

  • It requires various membrane proteins.

• Excretion: Removal of any fluid/substances not reabsorbed into the body.

• The 4 processes of the nephron are: filtration, reabsorption, secretion, excretion

Amount Excreted

• The formula to conceptualize how the kidney handles solutes.
• Amount Excreted = (Amount Filtered - Amount Reabsorbed) + Amount Secreted

Overview of Filtration

• It's the first step in urine formation.
• It's a relatively non-specific process.
• It creates a filtrate that has a similar composition to the plasma except for proteins (water + dissolved solutes).
• Approximately 20% of the plasma moves into Bowman's capsule (filtration fraction).

Filtration Fraction

• 20% of plasma moving through glomerulus is filtered.
• Less than 1% of filtered fluid is eventually excreted.
• Greater than 99% of plasma entering kidney returns to systemic circulation.
• Greater than 19% fluid reabsorbed.
• Less than 1% fluid is excreted to external environment.

Filtration Barriers

• There are 3 in the renal corpuscle.
  • Capillary endothelium
  • Basal lamina
  • Bowman's capsule endothelium

Capillary Endothelium

• Facilitates fenestrations.
  • Large enough for plasma contents to pass.
  • Small enough to stop blood cells.
  • Negatively charged.
  • Proteins are negatively charged, preventing filtration (some proteins are small enough to get through).

Basal Lamina

• It is acellular (does not contain cells)
• Consists of extracellular matrix:
  • Collagen
  • Glycoproteins
• It is located between the capillary and Bowman's capsule endothelial layers.
• Acts like a sieve, preventing entry of proteins in the filtrate.

Bowman's Capsule Endothelium

• It consists of podocytes.
  • These wrap around capillaries and narrow filtration slits.
• Podocytes have negatively charged proteins.
  • Repel proteins in the blood.

What Causes Filtration?

• Capillary pressures influence the filtration process.
• 3 important pressures:
  • Hydrostatic Pressure (PH) - blood in glomerulus: Averages 55 mmHg.
  • Colloid Osmotic Pressure (π) - glomerular capillaries (proteins in fluid): Averages 30 mmHg.
  • Hydrostatic Pressure (Pfluid) - fluid in Bowman's capsule: Averages 15 mmHg.

Glomerular Filtration Rate (GFR)

• It's the volume of fluid that filters into Bowman's capsule per unit time.
• Usually described in mL/min or L/day.
• Average GFR is 125mL/min or 180 L/day.
• Blood volume is 5L, plasma volume is only 3 L
  • Your entire blood plasma volume is filtered by your kidneys 60 times per day!
• GFR is relatively constant because blood flow through the afferent and efferent arterioles can change.

Autoregulation

• The kidney maintains a near-constant GFR at mean arterial pressures of 80–180 mmHg.
• It protects filtration barriers against high pressures.
• Myogenic response maintains a constant GFR.
• Tubuloglomerular Feedback also helps regulate.

Autonomic Nervous System and GFR

• Sympathetic neurons innervate both the afferent and efferent arterioles.
• Alpha-receptors will cause vasoconstriction and reduce GFR.
• Severe hemorrhage leads to lowered blood pressure and kicks in sympathetic nervous system.
• This results in constriction of the afferent arteriole and lowers GFR.