Renal Physiology

Kidney Regulation

• Blood volume (plasma volume) and pressure.

  1. Water concentration and fluid volume.

  2. Inorganic ion composition.

• These two factors keep pressure under homeostatic conditions.

Kidneys Balance

• They help regulate the acid-base balance.

Kidneys Excretion

• Urea, uric acid, creatinine, and bilirubin (breakdown product of Hb).

• Removal of foreign chemicals (i.e. drugs, food addictives, pesticides.

Uric Acid

• Produced from the breakdown of nitrogenous bases.

Creatinine

• Byproduct of muscle metabolism.

Kidneys Synthesis

• Glucose (gluconeogenesis).

Kidneys Secretion

• Acts as a endocrine organ, secreting cytokines or hormones.

• Erythropoietin (EPO) → synthesized in the kidney.

• Renin.

• 1,25-dihydroxy Vitamin D (inactive form).

Fluid Compartments

• Total body water: 42L, around 60% body weight.

• Plasma is 3L, the interstitial fluid is 11L, and the intercellular fluid 28L.

• Functions of the kidneys is to maintain the plasma volume within a narrow range.

Fluid Volume Changes

• Fluid volume can be altered during various health disorders.

• Changes occur through rapid water movement between compartments by osmosis.

Intracellular Fluid (ICF)

• The fluid inside the cell.

Extracellular Fluid (ECF)

• Fluid outside the cell.

• Plasma + interstitial fluid + cerebrospinal fluid.

Plasma

• Non-cellular part of blood, fluid inside blood vessels.

Kidney Regulates ECF

• The ECF is made up of:

  • Plasma.

  • Interstitial fluid.

  • Cerebrospinal fluid.

Dominant Ions in ECF

• Na⁺, HCO₃⁻, Cl⁻.

ICF Dominant in ICF

• K⁺.

Diffusion

• Rate of water diffusion that will affect fluid volume.

• A low and finite degree of H₂O can diffuse through the tissues.

• Aquaporins: water channels.

Osmoles

• 1 osmoles (osm) is equal to 1 mole of solute particles.

Osmolarity

• Number of solutes per unit volume of solution expressed in moles per liter.

• The addition of solute lowers the water concentration.

• Addition of more solute would increase the solute concentration and further reduce the water concentration.

Diffusion

• Is the movement of molecules from one location to another due to their random thermal motion.

• Molecules initially move from a region of higher concentration to lower concentration.

• Over time, solute molecules placed in a solvent evenly distribute themselves.

Diffusional Equilibrium

• Is the result of diffusion.

• Happens over time as solute molecules placed in a solvent evenly distribute themselves.

Osmosis

• Net diffusion of water across a selectively permeable membrane from a region of high water concentration → lower water concentration.

Osmotic Pressure

• The pressure necessary to prevent solvent movement (osmosis).

Reaching Diffusional Equilibrium

• The partition between the compartments is permeable to water and solute.

• After diffusional equilibrium has occurred, movement of water and solutes has equalized their concentrations on both sides.

Reaching Osmosis

• The partition between the compartments is permeable to water only.

• After diffusional equilibrium has occurred, movement of water has equalized solute concentration.

• The opposing pressure required to stop osmosis completely is equal to osmotic pressure.

Tonicity

• Is determined by the concentration of non-penetrating solutes of an extracellular solution relative to the intracellular environment of a cell.

• The solute concentrations may influence changes in cell volume.

Isotonic (Isoosmotic)

• Same osmolarity outside and inside the cell.

Hypertonic (Hyperosmotic)

• Higher osmolarity than inside of the cell.

Hypotonic (Hypoosmotic)

• Lower osmolarity than inside of the cell.

Osmolarity Gradient

• Water flows from osmolarity to higher osmolarity.

• Normal osmolarity inside a cell is about 300mOsm/L.

Non-Penetrating Solutes

• Solutes that cannot easily cross the cell membrane and establish osmotic gradients, thereby influencing cell volume and tonicity.

• They are crucial for maintaining fluid balance.

  • i.e. Na⁺ and K⁺.

Penetrating Solutes

• Solutes that can freely cross cell membranes, meaning they do not establish a sustained osmotic gradient.

• Do not directly influence cell volume or tonicity.

  • i.e. urea.

Changes in Cell Volume

• In a hypertonic solution the cell shrinks.

• In a isotonic solution the cell volume does not change.

• In a hypotonic solution the cell swells.

Absorption

• Movement of solute/water into the blood (plasma).

Filtration

• Movement of solute/water out of blood (plasma).

Plasma Proteins + Movement

• Plasma proteins in the blood create osmotic pressure.

• This draws water into the capillary from the interstitial space.

• Some plasma proteins may escape into the interstitial fluid.

Proteins

• Big molecules that are sometimes charged.

• Due to their size and charge, they cannot move in & out of capillaries easily.

  • Unable to cross capillary walls.

Capillary Hydrostatic Pressure (P_C)

• Pressure exerted on inside of capillary walls by blood.

• Favors fluid movement out of capillary.

Interstitial Fluid Hydrostatic Pressure (P_IF)

• Fluid pressure exerted on the outside of the capillary wall by interstitial fluid.

• Favors fluid movement into capillary; pressure is negligible & does not contribute.

Blood Colloid Osmotic Pressure (π_C)

• Osmotic pressure due to nonpermeating plasma proteins inside the capillaries.

• Favors fluid movement into the capillaries.

Interstitial Fluid Colloid Osmotic Pressure (π_IF)

• Small amount of plasma proteins may leak out of capillaries into interstitial space.

• Favors fluid movement out of capillaries; negligible.

Starling Forces

• Net filtration pressure = P_C + π_IF - P_IF - π_C.

• Govern the movement of fluid across capillary walls, determining whether fluid moves out of the capillary (filtration) or back into it (reabsorption).

Fluid Movement in Capillaries

• At the arterial end, starling forces favour filtration. at the venous end, they favour reabsorption.

• Filtration dominates at the arterial end; reabsorption at the venous end.

• Overall, slightly more fluid is filtered than reabsorbed, with the excess drained by the lymphatic system.

Homeostasis

• Total body balance of any substance; keeping levels constant and maintained.

Urinary System

• The kidneys are retroperitoneal (behind the peritoneum) in location.

• Other structures associated with the urinary system include the ureters, bladder, and urethra.

Ureters

• Drain the formed urine from the kidneys.

• Travel to the bottom of the abdominal cavity and empties into the bladder.

Bladder

• Storage organ or sac.

• Innervated by the ANS.

• Voiding of the bladder is controlled by SNS/PSNS.

• Bladder empties out of the body through the urethra.

Hilum

• Inner concave part of kidneys.

• From the area two tubes emerge; these tubes are called ureters.

Micturition

• The process of releasing the urine outside the body, or urination.

• Bladder emptying with the help of autonomic control.

Kidney Anatomy

• Covered with a capsule-like structure.

• 2 regions:

  • Outer portion: cortex.

  • Inner portion: medulla.

Nephron

• Functional units of the kidney; where the urine is made.

• 1 million nephrons in your kidneys.

• The parts of the nephrons form parts of the cortex and medulla.

• Contains: renal corpuscle and renal tubule.

Renal Corpuscle

• Bulb-like structure; attached to renal corpuscle is a long tube called the renal tubule.

• A cup-like shaped structure with a tuft (loops) of capillaries.

Renal Tubule

• Attached to the renal corpuscle; a long tube.

• Found mostly in the medullary portion.

• Bowman’s capsule + glomerulus.

• The formation of urine occurs through the different segments of the tubule.

Collecting Ducts

• Each nephron has a renal corpuscle and a renal tubule that drains into a collecting duct.

• Multiple nephrons drain into each collecting duct, which then empties the processed contents into the renal pelvis of the kidney.

Glomerulus

• A capillary tuft (loops).

• Sits within the Bowman’s capsule (“cups” it).

Bowman’s Capsule

• Leads into the renal tubule.

Renal Tubule Segments

• Proximal convoluted tubule, Loop of Henle (descending and ascending limbs), distal convoluted tubule, collecting ducts.

Distal Convoluted Tubule

• “Distal” → far away from the renal corpuscle.

• Drains its contents into a main tube called the collecting duct.

• Major homeostatic mechanisms of fine control of water and solute to produce urine.

Proximal Convoluted Tubule

• Proximal = close to the renal corpuscle.

• Twisted.

• Reabsorbs most of the water and non-waste plasma solutes.

• Major site of solute secretion except K⁺.

Loop of Henle

• Divided into descending limb and ascending limb.

• Ascending limb has thick and thin segments.

• Creates osmotic gradients that reabsorb large amounts of ions and smaller amounts of water.

Podocytes

• The outer wall of the Bowman’s capsule is made of epithelial cells.

• Flat cells continue on to form the tubules.

• Cells in contact with the glomerular capillaries, called podocytes (podo = foot, cyte = cell), have foot-like processes.

Renal Corpuscle Filtering

• Blood is brought in by the afferent arteriole and conducted towards the renal corpuscle.

• The blood goes through several twists + turns.

• Blood exits the renal corpuscle through the efferent arteriole.

Tubule Cell Variations

• The cells forming the tubule are modified in structure.

• As they approach the Bowman’s capsule, they slightly change in structure and function.

• All are epithelial cells, but their type varies depending on the tubule segment.

Afferent

• Conducted toward; blood is brought in by the afferent arteriole and conducted towards the renal corpuscle.

Efferent

• Conducted away from; blood is being taken away from the renal corpuscle by the efferent arteriole.

Stage 1 - Renal Corpuscle Development Beginning

• When the kidneys are forming fetal life.

• A nephron will develop first as a blind-ended tube; there is no opening.

• Tube is lined by a layer of epithelial cells sitting on a basement membrane.

Stage 2(1) - Renal Corpuscle Development Formation

• A growing tuft of capillaries penetrates the expanded end of the tubules.

• The tubule invaginates, bringing capillaries closer to the epithelial cell layer.

• The basal lamina becomes trapped between the endothelial cells of the capillaries and the epithelial layer.

Stage 2(2) - Renal Corpuscle Development Structure

• The epithelial layer differentiates into parietal (outer) and visceral (inner) layers.

• The epithelial cells form a cup, and the tuft of capillaries forms the glomerulus.

Stage 3 - Renal Corpuscle Development Final

• The outer layer does not fuse with the inner layer - there is a space between them.

• Parietal layer eventually flattened to become wall of Bowman’s capsule; visceral layer becomes podocyte cell layer.

BC Parietal Layer

• The outer layer of epithelial cells which forms the outer wall of the Bowman’s capsule.

BC Visceral Layer

• The layer closest to the glomerular capillaries; these cells are the podocytes.

Glomerulus Functional Significance

• The site where blood undergoes first filtration.

Interlocked Podocytes

• Podocytes are arranged around the external surface of the glomerular capillaries.

  • The foot processes of one podocyte, which are cytoplasmic projections, interlock with those of another podocyte.

• Between the interlocking foot processes of the podocytes are filtration slits.

Renal Corpuscle Capillaries

Blood is brought in through the afferent arteriole and flows through the capillaries of the glomerulus.

• Capillaries are fenestrated.

Glomerular Capillary Layers

• The glomerular capillary has three layers: the endothelial layer, the basement membrane, and the podocytes.

Endothelial Layer + Basement Membrane

• The capillary endothelial cell layer is fenestrated to allow filtration.

• The endothelial cells sit on a basement membrane, a gel-like mesh composed of collagen proteins and glycoproteins.

Filtration Slits

• Podocytes are located outside the basement membrane, with filtration slits through which fluid moves.

• Foot projections wrap around the capillaries, leaving slits between them.

• Multiple foot processes increase the surface area for filtration.

Basement Membrane

• Gel-like mesh structure.

• Composed to collagen proteins and glycoproteins.

• Meshwork of collagen + other proteins which are negatively charged.

  • Prevents protein passage.

• Filtration layer.

Multiple Foot Processes

• Magnifies surface area for filtration.

Filtration Membrane

• Capillary membrane.

• Basement membrane.

• Podocyte.

Two Types of Nephrons

• The renal corpuscle is in the cortex for both.

• One type of nephron (cortical) has their glomeruli in the outer cortex.

• The other type (juxtamedullary) has their glomeruli closer to the medulla.

Cortical Nephrons

• Make up 85% of all nephrons, with the renal corpuscle always in the cortex.

• The collecting duct, distal convoluted tubule, and proximal tubule are mostly in the cortex, while loop portions may slightly dip into the medulla.

Juxtamedullary Nephrons

• Juxta = close to; these nephrons sit closer to the medulla area.

• Renal corpuscles sit in the cortex but are closer to the medullary area.

• The loop of Henle and the ascending limb are found in the renal medulla.

• 15% of all nephrons.

Cortical Nephrons Function

• Preforms the 3 basic functions.

  • Filtration, reabsorption, and secretion.

Juxtamedullary Nephrons Function

• Perform the three basic functions and regulate urine concentration.

• Create osmotic gradients in the interstitial space outside the Loop of Henle.

  • Regulate water volume and urine concentration.

• Kidneys retain fluid when dehydrated and produce more urine when not dehydrated.

Blood Supply Kidney

• Highly vascular organs.

• They receive ~20% of the total cardiac output.

• Blood enters through the renal artery via the hilum, a curved concave area, and begins branching.

• The renal artery subdivides into arteries and arterioles; afferent arterioles bring blood to the nephrons.

Afferent Arteriole

• Branches off from the renal artery and diverges into the capillaries of the glomerulus.

• Arteriole that brings blood into the glomerular capillary network.

• Blood travels through the Bowman’s capsule in the glomerulus or glomerular capillaries.

Efferent Arteriole

• Blood exits the glomerulus through the efferent arteriole.

  • Efferent arteriole branches around to form a set of capillaries called the peritubular capillary network.

Types of Capillaries

1. Glomerular.

2. Peritubular.

3. Vasa Recta.

Peritubular Capillaries

• Efferent arteriole branches around to form a set of capillaries.

• Found around the proximal convoluted tubules.

• Fuse together to form the renal vein.

Vasa Recta

• Capillaries that are found mostly associated with juxtamedullary nephrons in the medullary portion of the kidney.

  • Both the loop of Henle and this are important in forming the osmotic gradient.

Filter Load

• How much slower the nephrons are getting each time the filtration process is occurring.

Glomerular Filtration

• Fluid in the blood is filtered across the capillaries of the glomerulus and into Bowman’s space.

• Blood is brought to the kidneys by the renal artery → enters the glomeruli through the afferent arterioles and is filtered.

Tubular Reabsorption

• The movement of a substance from inside the tubule into the blood.

  • Glucose is reabsorbed by the body as it is very important as an energy source.

Tubular Secretion

• Movement of nonfiltered substances from the capillaries into the tubular lumen.

• Waste products that did not undergo filtration can be removed from the blood by tubular secretion.

Urinary Excretion

• Blood is filtered at the glomeruli; substances are added/secreted to the tubules.

• While other substances are reabsorbed urine containing unwanted products is excreted from our body.

Lumen Entry & Exit

• Lumen entry via filtration and secretion.

• Lumen exit via reabsorption and excretion.

• Amount excreted = the amount filtered + amount secreted - amount reabsorbed.

Filtration Layers

• Layers that substances move across from the lumen of the glomerular capillaries into Bowman’s space:

  1. Capillary endothelial layer.

  2. Basement membrane.

  3. Podocytes with filtration slits.

Podocytes with Filtration Slits

• Foot processes of the podocytes interdigitate and form filtration slits.

• Slits remain covered with fine semiporous membranes.

• Semiporous membranes are made up of proteins such as nephrins and podocins.

• A filtration layer.

Capillary Endothelial Layer

• Fenestrations (pores) in the capillary endothelium are not large enough to allow proteins to pass through.

• Pores have negative charges that do not allow negatively charged proteins to pass through.

• Filtration layer.

Holding Back Proteins

• Large proteins or albumin are held back because:

  • Pore sizes are not large enough.

  • Pores and BM have negative charges and repel negatively charged proteins.

  • Podocytes have slits.