Copyright © 2010 Pearson Education, Inc. Figure 25.1 Esophagus (cut) Inferior vena cava Adrenal gland Hepatic veins (cut) Renal artery Renal hilum Renal vein Iliac crest Kidney Ureter Urinary bladder Urethra Aorta Rectum (cut) Uterus (part of female reproductive system) Urinary System Organs

Copyright © 2010 Pearson Education, Inc. Table 19-1 Kidney Function

Copyright © 2010 Pearson Education, Inc. Figure 19-1j Bowman’s capsule Distal tubule Proximal tubule Collecting duct Ascending limb Descending limb Loop of Henle (j) Parts of a nephron Descending limb of loop begins Ascending limb of loop ends To bladder The nephron Renal corpuscle Renal tubules Collecting system To Minor calyx

Copyright © 2010 Pearson Education, Inc. Nephron Anatomy Figure 25.5a

Copyright © 2010 Pearson Education, Inc. The Blood Supply to the Kidneys Figure 26.5a, b

Copyright © 2010 Pearson Education, Inc. Arcuate A. Cortical radiate A. Afferent arteriole Glomerulus

Copyright © 2010 Pearson Education, Inc. Glomerulus – site of blood filtration Several small arterioles exit from the cortical radiate arteriole – afferent arterioles Each afferent arteriole folds to create a “little ball”– the glomerulus The blood from the glumerulus is carried out by efferent arteriole The capillaries in the glomerulus are found between 2 arteries the efferent arteriole enters into a regular capillary bed – peritubular capillaries

Copyright © 2010 Pearson Education, Inc. Nephron’s parts - the tubules – reabsorption and secretion The renal tubule is the location of filtrate processing into urine It is consists of Proximal convoluted tubule (PCT) Loop of Henle Distal convoluted tubule (DCT)

Copyright © 2010 Pearson Education, Inc.

Mechanisms of Urine Formation The kidneys filter the body’s entire plasma volume 60 times each day The filtrate: Contains all plasma components except protein Loses water, nutrients, and essential ions to become urine The urine contains metabolic wastes and unneeded substances

Copyright © 2010 Pearson Education, Inc. Glumerular Filtration The fluid that is forced out of capillaries into the Bowman’s space is called glumerular filtrate Similar to blood plasma without the proteins Tubular reabsorption and secretion The fluid in the tubules is called tubular fluid Differs from the filtrate because substances are moving in and out the tubules Water conservation Occur in the collecting duct The fluid is called urine Basic processes of urine formation

Copyright © 2010 Pearson Education, Inc. Figure 19-3 – + = Efferent arteriole Afferent arteriole Glomerulus Bowman’s capsule Peritubular capillaries To renal vein To bladder and external environment amount of solute excreted Amount filtered Amount reabsorbed Amount secreted Tubule Kidney Function The urinary excretion of substance depends on its filtration, reabsorption, and secretion

Copyright © 2010 Pearson Education, Inc. Glomerular filtration membrane Fluid from capillaries need to pass through 3 barriers to get to the capsular space: Fenestrated endothelium of capillaries with pores that allow the passage of relatively large molecules but not blood cells (pores size – nm) In addition, endothelial cells have negatively charged glycoproteins on their surface that “deny” entrance of negatively charged molecules Basement membrane – negatively charged proteins that do not allow the passage of large and negatively charged molecules (stop molecules >8nm)

Copyright © 2010 Pearson Education, Inc. Glomerular filtration membrane Filtration slits – form by the pedicles of the podocyes that create filtration slits (slit size 6-9nm). Filtrate on basis of size and negative charge Water and some solutes pass from blood plasma in the glomerulus capillaries to the capsular space of the nephrone Molecules smaller than 3 nm in diameter (water, sodium, glucose, amino acids, nitrogen wastes) pass freely from blood into capsule

Copyright © 2010 Pearson Education, Inc.

 Most molecules smaller than 3 nm can pass freely. That includes water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes and vitamins

Copyright © 2010 Pearson Education, Inc. Glomerular Filtration Filtration is a passive process in which hydrostatic pressure forces fluid and solutes through a membrane The glomerulus is more efficient than other capillary beds because: Large surface area of the filtration membrane filtration membrane is more permeable Glomerular blood pressure is higher because Arterioles are high-resistance vessels Afferent arterioles have larger diameters than efferent arterioles Higher BP results in higher net filtration pressure

Copyright © 2010 Pearson Education, Inc. Glomerular filtration depends on pressures Filtration depends on the balance between hydrostatic pressure and colloid osmotic pressure on both sides of the capillary wall Blood hydrostatic pressure (BHP) is much higher in the glomerulus (60 mmHg as compared to 10-15) Hydrostatic pressure in the capsular space is about 18 mm Hg (compared to about 0 in the interstitial fluid). This is a result of continuous filtration and the presence of fluid in the space. The colloid osmotic pressure (COP) of the blood is about the same as elsewhere – 32 mm Hg The glomerular filtrate is almost protein-free and has no significant COP

Copyright © 2010 Pearson Education, Inc. Glomerular filtration Total forces in the renal corpuscle: Forces that work to move fluid from capillaries into capsular space: Glomerular capillaries hydrostatic pressure (GHP) – mm Hg Forces that work to move fluid out of capsular space to capillaries: Blood colloid osmotic pressure (BCOP) – 32 mm Hg Capsular space hydrostatic pressure (CsHP) – 18 mm Hg 60 out – 18 in – 32 in = 10 mmHg net filtration pressure

Copyright © 2010 Pearson Education, Inc.

Glomerular filtration rate (GFR) Amount of filtrate produced by the two kidneys each minute (~125 ml) Factors that control GFR: Total surface area available for filtration Filtration membrane permeability Net filtration pressure (NFP) GFR is usually measured over 24 hr and it is about 180 L/day for males and 150 L/day in females

Copyright © 2010 Pearson Education, Inc. Regulation of Glomerular Filtration rate 2 types of mechanisms control the GFR Renal autoregulation (intrinsic system) Tubuloglomerular feedback mechanism Myogenic mechanism Extrinsic mechanisms Neural controls (extrinsic system) Hormonal mechanism (the renin-angiotensin system)

Copyright © 2010 Pearson Education, Inc. Intrinsic Controls - autoregulation Renal autoregulation is the ability of the nephron to adjust the blood flow and GFR without external control Under normal conditions, renal autoregulation maintains a nearly constant glomerular filtration rate Autoregulation involves two types of control Flow-dependent tubuloglomerular feedback – senses changes in the juxtaglomerular apparatus Myogenic – responds to changes in pressure in the renal blood vessels

Copyright © 2010 Pearson Education, Inc. Tubuluglomerular feedback mechanism The juxtaglomerular apparatus (JGA) monitors the fluid entering the DCT and adjusts the GFR Components of the JGA: The granular/juxtaglumerular (JG) cells – enlarged smooth muscle cells in the afferent arteriole. They respond to the cells of the macula densa to dilate or constrict the arterioles Act as mechanoreceptors that sense blood pressure Can release renin when BP decrease The macula densa is a patch of ET at the start of the DCT (in some books it said to be in loop of Henle) directly across from the JG cell Sense NaCl concentration in the tubular fluid

Copyright © 2010 Pearson Education, Inc. Autoregulation control of GFR If GFR rises, flow of tubular fluid increases and rate of NaCl reabsorption decreases. The macula densa sense the change and stimulate the contraction of JG cells This results in constriction of the afferent arteriole thus reducing GFR

Copyright © 2010 Pearson Education, Inc. Intrinsic Controls: Myogenic Mechanism The myogenic mechanism – base on the tendency of smooth muscle to contract when stretches  BP  constriction of afferent arterioles Helps maintain normal GFR Protects glomeruli from damaging high BP  BP  dilation of afferent arterioles Helps maintain normal GFR

Copyright © 2010 Pearson Education, Inc. Figure 19-7 Filtration Autoregulation of glomerular filtration rate takes place over a wide range of blood pressures

Copyright © 2010 Pearson Education, Inc. Extrinsic Controls – neural control When the sympathetic nervous system is at rest: Renal blood vessels are maximally dilated Autoregulation mechanisms is controlling Under stress: Norepinephrine is released by the sympathetic nervous system Epinephrine is released by the adrenal medulla Afferent arterioles constrict and filtration is inhibited The sympathetic nervous system also stimulates the renin- angiotensin mechanism

Copyright © 2010 Pearson Education, Inc. Renin-Angiotensin Mechanism – hormonal control A reduction in afferent arteriole pressure triggers the JG cells release renin Renin acts on angiotensinogen to release angiotensin I Angiotensin I is converted to angiotensin II Angiotensin II: Causes mean arterial pressure to rise Stimulates the adrenal cortex to release aldosterone As a result, both systemic and glomerular hydrostatic pressure rise

Copyright © 2010 Pearson Education, Inc. Extrinsic Controls: Renin-Angiotensin Mechanism Triggered when the granular cells of the JGA release renin angiotensinogen (a plasma globulin) resin  angiotensin I angiotensin converting enzyme (ACE)  angiotensin II

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc. Renal tubules function - Reabsorption and secretion Conversion of the glomerular filtrate to urine involves the removal and addition of chemicals by tubular reabsorption and secretion Reabsorption – from tubules back to the blood stream Secretion – from blood stream to tubules (not part of filtration) Cells of the PCT reabsorb 60-70% of the filtrate volume

Copyright © 2010 Pearson Education, Inc. Normal Rates of Filtration and Reabsorption

Copyright © 2010 Pearson Education, Inc. Reabsorption Figure 19-11, steps 1–4 Na + is reabsorbed by active transport. Electrochemical gradient drives anion reabsorption. Water moves by osmosis, following solute reabsorption. Concentrations of other solutes increase as fluid volume in lumen decreases. Permeable solutes are reabsorbed by diffusion. Na + Anions H2OH2O K +, Ca 2+, urea Tubular epithelium Extracellular fluid Tubule lumen Filtrate is similar to interstitial fluid

Copyright © 2010 Pearson Education, Inc. Non-reabsorbed Substances Substances are not reabsorbed if they: Lack carriers Are not lipid soluble Are too large to pass through membrane pores

Copyright © 2010 Pearson Education, Inc. Nonreabsorbed Substances A transport maximum (T m ): Reflects the number of carriers in the renal tubules available Exists for nearly every substance that is actively reabsorbed When the carriers are saturated, excess of that substance is excreted

Copyright © 2010 Pearson Education, Inc. Transport maximum (T m ) and the Renal Threshold If nutrient concentrations rise in tubular fluid: Reabsorption rates increase until carrier proteins are saturated Concentration higher than transport maximum: Exceeds reabsorptive abilities of nephron Some material will remain in the tubular fluid and appear in the urine Determines the renal threshold

Copyright © 2010 Pearson Education, Inc. Glucose Renal Curve

Copyright © 2010 Pearson Education, Inc. The loop of Henle - Regulation of Urine Concentration and Volume Osmolality The number of solute particles dissolved in 1L of water Reflects the solution’s ability to cause osmosis Body fluids are measured in milliosmols (mOsm) The kidneys keep the solute load of body fluids constant at about 300 mOsm This is accomplished by the countercurrent mechanism

Copyright © 2010 Pearson Education, Inc. The loop of Henle and countercurrent multiplication Countercurrent multiplication – exchange occurs between fluids moving in different directions; the effect of the exchange increased as the fluid movement continues Between the close ascending and descending limbs of loop Difference in permeability in two arms: Thin descending is permeable to water and almost not to solutes Thick ascending relatively impermeable to both but contains active transport mechanism that pump sodium and chloride ions from tubular fluid to peritubular fluid of the medulla

Copyright © 2010 Pearson Education, Inc. Countercurrent multiplication Sodium and chloride are pumped out of the thick ascending limb into the peritubular fluid by co-transport carriers (Na + -K + /2Cl - transporter) That elevates the osmotic concentration in the peritubular fluid around the thin descending limb The result is flow of water out of the thin descending limb into the peritubular fluid and increased concentration of solutes in the thin limb The arrival of highly concentrated solution in the thick limb accelerate the reabsorption of sodium and chloride ions

Copyright © 2010 Pearson Education, Inc. Figure 26.13b Countercurrent Multiplication and Concentration of Urine

Copyright © 2010 Pearson Education, Inc. The countercurrent multiplication: Creates osmotic gradient in medulla Facilitates reabsorption of water and solutes before the DCT Permits passive reabsorption of water from tubular fluid in the collecting system

Copyright © 2010 Pearson Education, Inc. Osmotic gradient The kidney has an osmotic gradient from cortex to medulla The outer layer of the kidney is isotonic with the blood: ~300 milliosmoles/liter The innermost layer (medulla) is very hypertonic: ~1200 milliosmoles/liter

Copyright © 2010 Pearson Education, Inc. Solutes and water reabsorbed in the medulla need to be returned into circulation. Blood enters the vasa recta with osmotic concentration of ~300 mOsm/l Blood descending in the medulla gradually increases in osmotic concentration because of solute reabsorption (plasma proteins limit osmotic flow out of the blood) Blood flowing toward the cortex gradually decreases in osmotic concentration mainly because of water flowing into capillaries Function of the vasa recta

Copyright © 2010 Pearson Education, Inc. Loop of Henle: Countercurrent Mechanism Figure 25.14

Copyright © 2010 Pearson Education, Inc. DCT performs final adjustment of urine by active secretion or reabsorption Tubular cells actively reabsorb Na + and Cl -. In the distal part of the DCT reabsorption of sodium ions in exchange to another cation (usually K+) The ion pumps and Na+ channels are regulated by aldosterone The DCT is a primary site of calcium ions reabsorption (regulated by PTH and calcitriol) Reabsorption and secretion at the DCT

Copyright © 2010 Pearson Education, Inc. Water reabsorption Regulating Water and Solute Loss in the Collecting System By aldosterone Controls sodium ion pumps Actions are opposed by natriuretic peptides By ADH Controls permeability to water Is suppressed by natriuretic peptides

Copyright © 2010 Pearson Education, Inc. Water reabsorption and urine concentration Through control of water reabsorption Water is reabsorbed by osmosis in: Proximal convoluted tubule Descending limb of nephron loop 1%–2% of water in original filtrate is recovered During sodium ion reabsorption In distal convoluted tubule and collecting system

Copyright © 2010 Pearson Education, Inc. Water reabsorption and urine concentration Obligatory Water Reabsorption Is water movement that cannot be prevented Usually recovers 85% of filtrate produced Facultative Water Reabsorption Controls volume of water reabsorbed along DCT and collecting system 15% of filtrate volume (27 liters/day) Segments are relatively impermeable to water Except in presence of ADH

Copyright © 2010 Pearson Education, Inc. Copyright © The McGraw-Hill Companies, Inc.

Copyright © 2010 Pearson Education, Inc. ADH and urine volume and concentration The permeability of the wall of the collecting duct varies under the influence of antidiuretic hormone (ADH). ADH is released by the posterior pituitary in response to increased osmotic pressure (decreased water or increased solutes in blood). When ADH reaches the kidney, it increases the permeability of the epithelial linings of the distal convoluted tubule and collecting duct to water, and water moves rapidly out of these segments, eventually into the blood, by osmosis (water is reabsorbed). Consequently, urine volume falls, and urine concentrates soluble wastes and other substances in minimal water. Concentrated urine minimizes loss of body fluids when dehydration is likely. If the osmotic pressure of the blood decreases, ADH is not released and water stays in the collecting duct, leaves as part of the urine.

Copyright © 2010 Pearson Education, Inc. ADH and urine volume and concentration The Hypothalamus Continuously secretes low levels of ADH DCT and collecting system are always permeable to water At normal ADH levels Collecting system reabsorbs 16.8 liters/day (9.3% of filtrate)

Copyright © 2010 Pearson Education, Inc. Aldosterone and urine concentration Aldosterone is a steroid secreted by the adrenal cortex It is secreted when blood sodium falls or if blood potassium rises It is also secreted if BP drops (indirectly through the release of renin-angiotensin II that promotes aldosterone secretion) Aldosterone secreted – increased tubular reabsorption of Na + in exchange for secretion of K + ions – water follow Net effect is that the body retains NaCl and water and urine volume reduced The retention of salt and water help to maintain blood pressure and volume

Copyright © 2010 Pearson Education, Inc. Atrial natriuretic peptide (ANP) and urine volume Secreted from the atrial myocardium in response to high BP Has 4 actions that result in the excretion of more salt and water in the urine: Dilate afferent arteriole and constricts efferent – increase GFR (more blood flow and higher GHP) Antagonized angiotensin-aldosterone mechanism by inhibiting both renin and aldosterone secretion Inhibits ADH Inhibits NaCl reabsorption by the collecting ducts

Copyright © 2010 Pearson Education, Inc.

A Summary of Renal Function Figure 26.16b