Kidney Function and Filtration

Renal Structure Review

• The primary function of the kidney is to maintain overall homeostasis.
• The renal cortex and renal medulla are key structures of the kidney.
• The renal corpuscle contains the glomerulus and Bowman's capsule.

Basic Renal Processes Review

• Glomerular filtration involves the movement of blood to tubule.
• Tubular secretion involves the movement of blood to tubule.
• Tubular reabsorption involves the movement of tubule to blood.
• All three processes do not apply to all substances.
• The amount excreted equals the amount filtered, plus the amount secreted, minus the amount reabsorbed.

Glomerular Filtration Review

• Glomerular filtration is the movement of blood to tubule.
• Glomerular filtration depends on net filtration.
• Net filtration is the sum of the flow towards Bowman's capsule and flow towards the glomerular capillary.
• Filtration is normally positive at about 20%.
• Glomerular filtration is subject to physiological regulation.

Today's Lecture Topics

• Tubular Reabsorption
• Tubular Secretion
• Measurement of Kidney Function (GFR)

Lecture Objectives

• Define tubular reabsorption, its two mechanisms, and examples.
• Define transport maximum (Tmax).
• Define tubular secretion and give an example.
• Define the function of the tubular segments.
• Define GFR and how to measure it.

Tubular Reabsorption

• Tubular reabsorption is the movement from tubule to peritubular capillaries.
• Functions to recover "important" substances.
• Primarily regulated by channels.

Tubular Reabsorption Pathway

• Substances pass from the tubular lumen through or between epithelial cells into the interstitial fluid.
• Movement occurs from the interstitial fluid into the peritubular capillary by diffusion.
• Tubule-to-interstitial fluid movement can occur by diffusion or mediated transport.

Mechanisms of Tubular Reabsorption: Diffusion

• Diffusion involves movement down a concentration gradient.
• Diffusion does not require energy.
• Substances move into the interstitial fluid along their concentration gradient, primarily through tight junctions.
• Diffusion is a common mechanism for lipid-soluble substances.

Mechanisms of Tubular Reabsorption: Mediated Transport

• Mediated transport involves movement against a gradient.
• Mediated transport requires active transport and energy.
• Transcellular transport means a substance is transported across the luminal and basolateral cell membranes.
• Ultimately, the products move from the interstitial fluid to blood.
• Mediated transport requires energy, via primary or secondary active transport.

Mediated Transport – Primary Active Transport Example

• Sodium reabsorption is often coupled to potassium secretion.
• Na⁺ moves "downhill" passively across the luminal membrane into the cell by facilitated diffusion through a channel.
• Na+/K+-ATPase actively transports Na+ "uphill” across the basolateral membrane, which is primary active transport.

Mediated Transport – Secondary Active Transport Example

• Glucose is cotransported across the luminal membrane uphill and is coupled to Na+ transport downhill, which is secondary active transport.
• Glucose diffuses across the basolateral membrane by facilitated diffusion.
• Glucose reabsorption is often coupled to Na+ reabsorption.

Concept: Transport Maximum (Tmax)

• Mediated transport requires transporters.
• Transport maximum (Tmax) is the maximum amount of material that can be transported per unit time.
• Maximum transport occurs when binding sites on transport proteins are saturated.

Tubular Reabsorption: Transport Maximum Examples

• Active Transport: Glucose
• Normally, at normal blood glucose levels, Tmax is not exceeded, and all glucose is reabsorbed, so there is no glucose in urine.
• In disease, at high blood glucose levels, filtered glucose exceeds Tmax of the transporter, causing glucose in urine.
• Water-Soluble Vitamins
• Riboflavin (Vitamin B2)

Tubular Secretion

• Tubular secretion is the movement of substances from peritubular capillaries into the tubular lumen.
• Tubular secretion follows a transcellular pathway.
• Functions to excrete substances faster than filtered at the glomerular capillaries, for example, removal of waste.

Mechanism of Tubular Secretion Example

• Potassium (K+)
• K+ enters interstitial fluid by diffusion.
• K+ is transported "uphill" into the cell across the basolateral membrane by primary active transport.
• K+ moves "downhill" into the tubule by facilitated diffusion.
• Potassium secretion is often coupled to sodium reabsorption.
• The result is more K+ excreted than filtered.

Summary: Renal Handling of Substances

• How the kidney handles a substance is determined by three basic renal processes:
• Glomerular filtration is the movement of blood to tubule.
• Tubular secretion is the movement of blood to tubule.
• Tubular reabsorption is the movement of tubule to blood.
• Not all three processes apply to all substances.
• All three processes are not equal.
• The three processes are under physiological control.
• For a given substance, the amount excreted equals the amount filtered plus the amount secreted minus the amount reabsorbed.

Function of Various Parts of Tubules

• Tubular regions process substances differently because of differences in channel numbers.
• The proximal tubule reabsorbs most of the filtered water and non-waste solutes and is a major site of solute reabsorption.
• The loop of Henle establishes the medullary osmotic gradient.
• Distal segments which are the distal tubule and collecting ducts, provide fine tuning for most substances.
• Most homeostatic controls operate in the distal segments.
• Physiological fine tuning is determined by membrane protein (channel) concentration.
• Concentration of membrane proteins is regulated by hormones and paracrine/autocrine factors.
• The amount excreted equals the amount filtered plus the amount secreted minus the amount reabsorbed.

Measuring Renal Function

• There are three basic renal processes: glomerular filtration, tubular secretion, and tubular reabsorption.
• Glomerular filtration is the movement from blood to tubule.
• Tubular secretion is the movement from blood to tubule.
• Tubular reabsorption is the movement from tubule to blood.
• The amount excreted equals the amount filtered plus the amount secreted minus the amount reabsorbed.
• What goes in must come out.

Renal Function: Glomerular Filtration

• Glomerular filtration is the movement from blood to tubule.
• Both liquid and substances are filtered at the Glomerulus, and we can measure both.
• Glomerular Filtration Rate (GFR) is the amount of fluid filtered.
• Filtered Load is the amount of a substance filtered.
• Filtered Load and GFR are indicators of Glomerular Function, so monitoring them is important.

Renal Function: Glomerular Filtration Rate (GFR)

• GFR is the volume of fluid filtered from the glomeruli into Bowman's space per unit time.
• To measure GFR: A substance "S" is filtered, not reabsorbed, and not secreted.
• The amount of substance "S" filtered equals the amount of "S" excreted.
• Calculated as: GFR = (Urine Volume * Urine Concentration) / Plasma Concentration
• Urine volume is per unit time.

Measuring Glomerular Filtration Rate

• GFR = (Urine Volume x Urine Concentration) / Plasma Concentration
• Measurement requires collecting a blood sample and urine sample.
• Substance “S” should not reabsorb or secrete so GFR can function.

Measuring Glomerular Filtration Rate: Substance S

• Use Inulin or Creatinine
• Inulin is readily filtered, not reabsorbed or secreted, and is not naturally occurring in the body, so it needs to be infused.
• Creatinine is naturally occurring in the body, is a muscle breakdown product, and is only an approximate measure of GFR because some secretion does occur.

Magnitude of GFR in Relation to Plasma Volume

• Normal GFR in normal functioning kidneys is 125 ml/min.
• Each minute, 125 ml of plasma is filtered from blood into kidney tubules.
• Typical values: GFR = 125 ml/min or 180 L/day, total plasma volume = 3 L.
• The entire plasma volume is filtered 60 times per day.