URINE FORMATION BY URINE FORMATION BY THE KIDNEYSTHE KIDNEYS

1.1. GLOMERULAR FILTRATION, GLOMERULAR FILTRATION, RENAL BLOOD FLOW RENAL BLOOD FLOW

ANDTHEIR CONTROLANDTHEIR CONTROL■ Multiple Functions of the Kidneys Multiple Functions of the Kidneys

Excretion of metabolic waste products Excretion of metabolic waste products and foreign chemicalsand foreign chemicals

Regulation of water and electrolyte Regulation of water and electrolyte balancesbalances

Regulation of body fluid osmolality and Regulation of body fluid osmolality and electrolyte concentrationselectrolyte concentrations

Regulation of arterial pressureRegulation of arterial pressure

Regulation of acid-based balanceRegulation of acid-based balance

Secretion, metabolism, and excretion of Secretion, metabolism, and excretion of hormoneshormones

Physiologic Anatomy of Physiologic Anatomy of the Kidneysthe Kidneys

General Organization of the kidneys and Urinary General Organization of the kidneys and Urinary TractTract

Renal Blood SupplyRenal Blood Supply

Blood Flow to the kidneysBlood Flow to the kidneys

22% of Cardiac Output or 1100 ml/min.22% of Cardiac Output or 1100 ml/min.

The Nephron and Functional Unit The Nephron and Functional Unit of the Kidneyof the Kidney

Each kidney in humans contains Each kidney in humans contains about 1 million nephronsabout 1 million nephrons

after age 40 functioning nephrons decreases after age 40 functioning nephrons decreases 10% every 10 years10% every 10 years

at age 80, 40% fewer functioning nephrons at age 80, 40% fewer functioning nephrons than age 40than age 40

Regional Differences in Nephron Regional Differences in Nephron Structure-Cortical and Juxtam edullary Structure-Cortical and Juxtam edullary

NephronNephron

■ Cortical Nephron - have glomeruli Cortical Nephron - have glomeruli located in located in the outer cortex and have a the outer cortex and have a short loops of short loops of Henle that penetrates Henle that penetrates into the medulla.into the medulla.

■ Juxtamedullay Nephron - 20 to 30% Juxtamedullay Nephron - 20 to 30% have have glomeruli thatlie dip in the glomeruli thatlie dip in the renal cortex renal cortex near the medulla near the medulla and have long loops of and have long loops of Henle that dip Henle that dip deeply into the medulladeeply into the medulla

Urine Formation Results Urine Formation Results fromfrom

A. Glomerular FiltrationA. Glomerular Filtration

B. Tubular ReabsorptionB. Tubular Reabsorption

C. Tubular SecretionC. Tubular Secretion

Expressed mathematically as:Expressed mathematically as:Urinary excretion rate = Filtration rate - Urinary excretion rate = Filtration rate - Reabsorption Reabsorption rate + rate +

Secretion rateSecretion rate

Real Real Handling of Handling of

4 4 HypotheticaHypothetica

l l SubstancesSubstances

A. Substances freely filtered but not reabsorbedA. Substances freely filtered but not reabsorbed- - waste products waste products in the body such as in the body such as CreatinineCreatinine

B. Substances freely filtered but is also partly B. Substances freely filtered but is also partly reabsorbed from the tubules back into the blood.reabsorbed from the tubules back into the blood.

- - typical for many Electrolytes typical for many Electrolytes of the bodyof the bodyCalculated as Calculated as Filtration rate minus Reabsorption rateFiltration rate minus Reabsorption rate

C. Substances is freely filtered at the glomerular capillaries but is C. Substances is freely filtered at the glomerular capillaries but is not excreted into the urine - all filtered substances as reabsorbed not excreted into the urine - all filtered substances as reabsorbed from the tubules back into the blood.from the tubules back into the blood.

- - Nutritional substances in the blood such as Nutritional substances in the blood such as Amino AcidsAmino Acids and and GlucoseGlucose

D. Substances freely filtered at the glomerular capillaries and is D. Substances freely filtered at the glomerular capillaries and is not reabsorbed. Additional quantities of this substances are not reabsorbed. Additional quantities of this substances are secreted from the peripheral capillary blood into the renal tubules secreted from the peripheral capillary blood into the renal tubules - - Organic Acid and BasesOrganic Acid and BasesExcretion rate = Filtration rate plus Tubular secretion rateExcretion rate = Filtration rate plus Tubular secretion rate

Filtration, Reabsorption and Secretion of Different Substances

- tubular reabsorption is more important than tubular secretion in formation of urine

- Secretion play important role in determining the amounts of potassium and hydrogen ions.

Glomerular Filtration - The first Step in Urine FormationComposition of the Glomerular Filtrate

- protein free and devoid of cellular elements including red blood cells

- calcium and fatty acids not freely filtered because they are bound to plasma proteins

GFR = 125 ml/min or 180 L/dayFiltration Fraction = GFR/Renal plasma flow

Glomerular Capillary Membrane

Major Layers:Major Layers:1. Endothelium of the capillary2. Layer of endothelial cells (podocytes)

- Filterability of Solutes is inversely Related to their size

- Negatively Charge Large Molecules are Filtered Less Easily Than Positively Charged Molecules of Equal Membrane Size

Determinants of the GFR1. The sum of the hydrostatic and colloid osmotic forces across the glomerular membrane which gives the net filtration pressure2. The glomerular capillary filtration coefficient, Kf.

GFR= Kf x Net filtration pressure = Kf x (PG - PB - “G+ “B)

PG is glomerular hydrostatic pressurePB is hydrostatic pressure in Bowman’s capsule“G is colloid osmotic pressure of the glomerular capillary plasma proteins“B is colloid osmotic pressure of the Bowman’s capsule

Page 318 - Forces Page 318 - Forces Favoring Filtration and Favoring Filtration and

Forces opposing FiltrationForces opposing Filtration

Increased Glomerular Capillary Filtration Coefficient Increases GFR

Kf = GFR/filtration pressure

= 125 ml/min/10mmHg

Increased Bowman’s Capsule Increased Bowman’s Capsule Hydrostatic Pressure Decreases Hydrostatic Pressure Decreases GFRGFR

Increases Glomerular Capillary Colloid Osmotic Pressure Increases GFR

Determined by:

1. Arterial pressure

2. Afferent arteriolar resistance

3. Efferent arteriolar resistance

Physiologic Control of Glomerular Physiologic Control of Glomerular Filtration and Blood FlowFiltration and Blood Flow

1. Sympathetic nervous system Activation Decreases 1. Sympathetic nervous system Activation Decreases GFRGFR

2. Hormonal and Autocoid Control of Renal 2. Hormonal and Autocoid Control of Renal CirculationCirculation

Role of Role of TubuloglomerulTubuloglomerular Feedback in ar Feedback in Autoregulation Autoregulation

og GFRog GFR

Other Factors that Increases Other Factors that Increases Renal Blood Flow and GFRRenal Blood Flow and GFR

- High Protein Intake- High Protein Intake- Increased Blood Glucose- Increased Blood Glucose