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Chapter 26 Urinary System

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1 Chapter 26 Urinary System
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2 Organs of the Urinary System
Kidneys (2) Ureters (2) Urinary bladder (1) Urethra (1)

3 Functions of the Kidney
Filters blood plasma-removes waste products, toxins, H+, drugs, hormones, water, urea Produces urine Regulate blood volume and pressure through secretions of: Enzyme renin controls blood pressure and electrolyte balance Hormone erythropoietin stimulates production of RBC cells Regulate the osmolarity of the body fluids Collaborate with lungs to regulate/buffer PCO2 and acid-base balance (pH) - loss of hydrogen ions and bicarbonate ions in urine Regulates plasma ion concentrations Sodium, potassium, and chloride ions controlling urine loss Calcium ion levels through synthesis of calcitriol-Vitamin D helps to regulate calcium homeostasis Gluconeogenesis from amino acids in extreme starvation 3

4 NITROGENOUS WASTES Proteins amino acids  NH2 removed  forms ammonia  liver converts to urea
UREA formation (50% of waste products) Uric acid- product of nucleic acid catabolism (DNA purines =adenine/guanine); “gout” Blood urea NITROGEN (BUN) – expression of the level of nitrogenous waste in the blood normal concentration of blood urea is 10 – 20 mg/dl azotemia – elevated BUN indicates renal INSUFFICIENCY acute - result of dehydration or shock Creatinine 0.6 to 1.2 mg/dL product of creatine phosphate catabolism in muscle cells. Little-to-no tubular reabsorption of creatinine. This means it should be eliminated in the urine. If kidney filtering deficient, creatinine blood levels rise (10mg/dl); used to determine inadequate kidney function Uremia – severe toxicity of nitrogenous waste –indicates RENAL FAILURE Requires hemodialysis or organ transplant Waste products are dissolved in bloodstream and eliminated only while dissolved in urine. Subsequent water loss

5 Gout

6 KIDNEYS 3 layers of CT tissue:
Renal fascia: dense, fibrous outer layer binds kidney to abdominal wall Perirenal fat capsule: thick layer of adipose tissue cushions/holds in place Renal/fibrous capsule: layer of collagen fibers encloses the kidney. On top of kidney

7 Anatomy of the Kidney Cortex: outer layer of the kidney
Medulla: middle layer composed pyramids and renal columns. Pyramids: collecting ducts/ loops of Henle, lower portion of the nephrons. Renal columns –extension of cortex Renal sinus: internal cavity within kidney; stabilizes positions of ureter, renal blood vessels, and nerves The papilla of each pyramid projects into the calyx. Calyces collect the urine released from the papillae and allow it to drain into an enlarged collection minor calyx – drains papilla major calyces – drains minor calyx renal pelvis -connected to ureter, which drains kidney Lobe of the kidney = 1 pyramid and overlying cortex; produces urine Hilum - entry for renal artery and renal nerves; exit for renal vein and ureter

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9 Blood supply Kidneys are highly vascular necessary for its function; receives 20%–25% of total cardiac output Path of blood through the kidney: renal artery  segmental arteries  interlobar arteries  arcuate arteries  cortical radiate arteries (interlobular artery)  afferent arterioles  glomerular capillaries  efferent arterioles  peritubular capillaries and vasa recta  venules  cortical radiate veins (interlobular vein)  arcuate veins  interlobar veins  renal vein  inferior vena cava (Interlobular veins) (Interlobular artery)

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12 Renal Nerves Innervate kidneys and ureters Enter each kidney at hilum
Follow tributaries of renal arteries to individual nephrons Sympathetic Innervation Adjusts RATE of urine formation By changing blood flow and blood pressure at nephron Stimulates release of enzyme RENIN Which restricts loss of water and salt in urine (aldosterone formation) by stimulating reabsorption at nephron Renal Nerves

13 The Nephron Functional unit of the kidney Renal corpuscle
Glomerular capsule (Bowman’s capsule) Capillary network (glomerulus) Renal tubule Begins at renal corpuscle Located in cortex Proximal convoluted tubule (PCT) Loop of Henle Extends partially into medulla Distal convoluted tubule (DCT)

14 Blood Access to the Nephron
The nephron receives blood from the afferent arteriole. The afferent arteriole supplies the glomerulus From the glomerulus blood flows into the efferent arteriole. The efferent arteriole flows into more capillaries, the peritubular capillaries, and, in juxtamedullary nephrons, the vasa recta. Peritubular capillaries and vasa recta lead to the venous drainage of the kidney.

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16 Renal Corpuscle Bowman’s capsule and glomerulus.
Filtration unit of the nephron - produces protein-free solution (filtrate) similar to blood plasma BP forces water and dissolved solutes out of glomerular capillaries into capsular space The outer (parietal) layer of Bowman's capsule consists of simple squamous epithelial cells with tight junctions and serves to contain the filtrate in the capsular space. The visceral epithelium of the Bowman's capsule consists of large cells called podocytes with complex processes or “feet” (pedicels) that wrap around specialized dense layer of glomerular capillaries to produce openings called filtration slits. The glomerulus is a condensed mass of capillaries which allows substances to escape by filtration. Glomerular capillaries are fenestrated in order to allow filtration.

17 pedicels

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19 http://histology-group28. wikispaces

20 Tubular Portion of the Nephron
Tubular Cells form the tubular portion of the nephron Absorb organic nutrients, ions, water, and plasma proteins FROM the tubular fluid RELEASES them into peritubular fluid (INTERSTITIAL FLUID around renal tubule) Three (3) Functions of the Renal Tubule Reabsorb useful organic nutrients that enter filtrate and RETURN them to blood Reabsorb more than 90% of water in filtrate RETURNS to blood Secrete waste products into the filtrate that failed to enter renal corpuscle through filtration at glomerulus Lumen

21 PCT / Descending and Ascending Loops
Cells of the tubular portion of the nephron are critical to its function: PROXIMAL CONVOLUTED TUBULE: simple cuboidal epithelial cells with numerous microvilli (for absorption); opposite afferent and efferent arterioles Reabsorption of organic nutrients Active and passive reabsorption of ions Reabsorption of water Secretion Descending thin portion of Loop of Henle: simple squamous cells without microvilli freely permeable TO WATER but not to solutes (Na+); water movement out helps concentrate tubular fluid Ascending thick portion of Loop of Henle: simple cuboidal cells with very few microvilli (impermeable to water but permeable to Na+). Electrolyte pumps (Na+/K+ Pumps) move Na+ and Cl- ions out of tubular fluid

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25 Distal convoluted tubule (DCT)
Simple cuboidal cells called principal cells (hormonally regulated) Active secretion of ions, acids, drugs, toxins Selective reabsorption of Na+, Cl-, Ca2+ ions from tubular fluid; mediated by hormone ALDOSTERONE Selective reabsorption of water; concentrates tubular fluid The Juxtaglomerular Complex (JGC) An endocrine structure (hormonal) that secretes hormone erythropoietin and the ENZYME renin. Formed by 3 types of cells Macula densa- epithelial cells of DCT, Increase/decrease GFR by dilating or constricting the afferent arteriole Stimulates JG cells to release renin Juxtaglomerular cells (granular) (JG) - modified smooth muscle cells primarily in the walls of the afferent arteriole; synthesize, store, and secrete the enzyme renin Mesangial cells specialized smooth muscle cells inside/outside glomerulus – regulate blood flow and blood pressure; produce prostaglandins for local hormonal regulation to control blood flow

26 Mesangial produce prostaglandins to regulate blood flow locally.

27 http://classes. midlandstech. edu/carterp/Courses/bio211/chap25/Slide9

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29 Macula Densa Cells JG Cells

30 The distal convoluted tubule (DCT) opens into the collecting system made of simple cuboidal cells
Multiple nephrons drain into a nearby collecting duct; NOT PART OF THE NEPHRON Several collecting ducts: Converge into a larger papillary duct that empties into a minor calyx carrying tubular fluid to renal pelvis Adjusts fluid composition Determines final osmotic concentration and volume of urine Reabsorbs Na+, bicarbonate, and urea Secretes hydrogen or bicarbonate ions to control body fluid pH Aldosterone controls Na+ pumps and channels in collecting duct reducing loss of Na+ in urine ADH controls permeability to water (aquaporins) Collecting duct

31 Types of Nephrons Cortical nephrons 85% of all nephrons
short nephron loops efferent arterioles branch into peritubular capillaries around PCT and DCT Juxtamedullary nephrons 15% of all nephrons very long nephron loops, maintain salinity gradient in the medulla and helps conserve water efferent arterioles branch into vasa recta around long nephron loop

32 Ureter, Urinary Bladder, Micturition Reflex
From the collecting ducts urine passes through the papillary ducts, the minor calyces, the major calyces, and the renal pelvis. The ureters are connected to the renal pelvis and carry urine to the urinary bladder. Urine is stored in the urinary bladder Micturition (urination) occurs when sphincters of the urethra open to allow urine to flow out of the body.

33 Ureters Ureters are connected to the renal pelvis of the kidneys.
Urine travels to the urinary bladder through the ureters by peristalsis. Ureters retroperitoneal, attached to posterior abdominal wall; penetrate posterior wall of the urinary bladder Ureteral openings are slit-like rather than rounded Shape of ureters helps prevent backflow of urine when urinary bladder contracts Outer layer made of fibrous connective tissue. Ureters have TWO layers of smooth muscle (muscularis) in their wall: a longitudinal layer (outermost) and a circular layer (innermost). The lining of the ureters is made of transitional epithelium which allows them to stretch and reduce back pressure on the kidney. Lumen very narrow easily obscured or injured by kidney stones.

34 http://high-blood-pressure-symptoms. com/wp-content/uploads/2011/12/17
Ureters

35 Urinary Bladder Hollow muscular and elastic organ stores urine.in lower pelvic cavity. 3 layers: the mucosa, the detrusor muscle, the adventitia The mucosa comprised of transitional epithelium supported by a lamina propria. Transitional epithelium can be stretched Epithelial cells secrete mucus which coat against the acidity of urine. Numerous rugae allow bladder to expand and return to its original shape. The detrusor muscle made of two layers of longitudinal smooth muscle (outer and inner layers), and a middle circular layer. Can spasm during infection The internal urethral sphincter (involuntary) is part of the detrusor muscle. The external urethral sphincter (voluntary) is part of the urogenital diaphragm The fibrous adventitia covers the bladder and is attached to the visceral peritoneum. Opening of the two ureters and urethra mark a smooth surfaced triangular area called the TRIGONE on the bladder floor. Common site of bladder infections.

36 Urinary Bladder Common site of infection

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38 Urethra The urethra is a tubular organ that allows drainage of the urinary bladder. In females it is a short tubule. Its external orifice is located within the vulva. In males the urethra is subdivided into 3 regions: prostatic, membranous, and spongy regions. Near the bladder the male and female urethra is lined with transitional epithelium and near the external urethral orifice it is stratified squamous. The longer male urethra has pseudostratified columnar epithelium in its center. Small mucous cells of the urethral mucosa secrete mucous to protect the urethral lining from acidic urine.

39 Male and Female Urethra

40 Micturition Reflex Micturition is urination
Urine pressure stimulates receptors in the bladder wall: triggers a parasympathetic reflex causing detrusor muscle contractions and relaxation of the internal urethral sphincter. The internal urethral sphincter (involuntary) is part of the detrusor muscle. The need to urinate cannot be repressed but the delivery of urine can be delayed by the external urethral sphincter. This sphincter is made of skeletal muscle fibers from the urogenital diaphragm. It is voluntary. When conditions are appropriate, additional parasympathetic stimuli result in micturition and voluntary stimuli relax the external sphincter. Involves the pons as well as the amygdala and cerebrum. If the need to urinate arises and is inconvenient, stretch receptors will fatigue and stop firing. Continued tension in the bladder will resume firing with increased frequency.

41 Urinary Incontinence- Children
Absence of control of urination: Normal in children less than 3 years old Abnormal in teenagers and adults Newborns void frequently bladder is small kidneys cannot concentrate urine until 2 mos of age. Voluntary control of the urinary sphincters depends on nervous system development complete bladder control even during the night does not usually occur before 4 years of age. Children may be trained to develop control of the external urethral sphincter.

42 Urinary Incontinence- Adults
Adults may experience various disorders ranging from paralysis, stress, traumatic injury etc… Polyuria (excessive urine production) due to uncontrolled diabetes mellitus Caffeine or cola beverages also stimulate the bladder. Urinary retention may occur in males with an enlarged prostate gland which compresses the urethra and restricts urine flow Stress incontinence- laughing coughing Neurological- spinal cord injury Kidney function declines with age due to: nephrons decrease in size and number the bladder also shrinks and loses tone, resulting in frequent urination reduced sensitivity to ADH inability to retain fluid

43 Urinary Tract Infection (UTI)
The urinary tract is the body’s drainage system for removing wastes and extra water. The urinary tract includes two kidneys, to ureters, a bladder, and a urethra. cystitis – infection of the urinary bladder especially common in females due to short urethra frequently triggered by sexual intercourse can spread up the ureter causing pyelitis pyelitis – infection of the renal pelvis from blood borne agents such as bacteria. Can also arise from cystitis. pyelonephritis – infection that reaches the cortex and the nephrons. ie: kidney infection Generally results from blood-borne bacteria or virus Escherichia coli (e-coli) is often the bacteria associated with infection 23-43

44 Disorders Kidney stones form in renal pelvis
hard granule of calcium phosphate, calcium oxalate, uric acid, or a magnesium salt Renal insufficiency – where kidneys cannot maintain homeostasis due to extensive destruction of their nephrons 75% of nephrons are lost urine output (GFR) of 30 mL/hr is insufficient (normal mL/hr) to maintain homeostasis Causes: hypertension, diabetes, chronic kidney infections, trauma (blow to the back) prolonged ischemia and hypoxia, poisons, CAN SURVIVE WITH ONLY 1/3 OF ONE KIDNEY!! Uremia- 90% loss of kidney function Nephrons can regenerate restoring kidney function following short-term injury.

45 http://cardiologydoc. files. wordpress
When the force of blood flow is high, blood vessels stretch so blood flows more easily. Eventually, this stretching SCARS and WEAKENS blood vessels throughout the body, including those in the kidneys. Ruptured vessels can also produce clot formations further diminishing blood filtration.

46 Disorders Diabetes mellitus : Approximately1/3 of people with diabetes are susceptible to chronic kidney disease. The filtering units of the kidney are filled with tiny blood vessels. over time, high sugar levels in the blood can cause these vessels to become narrow and clogged. Without enough blood, the kidneys become damaged and albumin (plasma protein) passes through these filters and ends up in the urine. Nephrotic syndrome is a nonspecific kidney disorder. It is characterized by an increase in permeability of the capillary walls of the glomerulus leading to the presence of high levels of protein passing from the blood into the urine (proteinuria at least 3.5 grams per day per 1.73m2 body surface area). As the condition worsens, scarred tissue (Focal segmental glomerulosclerosis (FSGS) gradually replaces healthy kidney tissue. accounts for about 1/6th of the cases of nephrotic syndrome glomerulosclerosis is a hardening of the glomerulus. It is a general term to describe scarring of the kidneys' tiny blood vessels.

47 Protein Loss due to Nephrotic Syndrome and Diabetes
Focal segmental glomerulosclerosis Kidney vessels rupture allowing release of proteins into tubular solution

48 Hemodialysis Peritoneal Dialysis
Treatment for loss of kidney function Hemodialysis is the artificial clearing of blood wastes. Blood pumped from radial artery to a dialysis fluid. As blood flows thru semipermeable cellophane tube excess fluid, urea, K+ and other waste products are removed via diffusion. Glucose, electrolytes and drugs can be added to dialysate. In peritoneal dialysis wastes and water are removed from the blood using the peritoneal membrane of the peritoneum. Not as efficient; increased risk of infection Good Animation:

49 Urine Formation Three processes of urine formation:
Goal of urine production is to maintain homeostasis by regulating volume and composition of blood including excretion of metabolic waste products Three processes of urine formation: Glomerular Filtration Tubular reabsorption Tubular secretion

50 Mechanism of Urine Formation Glomerular Filtration
Each day the kidneys process about 200 quarts of blood to sift out approximately 2 quarts of waste products and extra water. Filtration is the passive process which produces a protein -free solution known as filtrate similar to blood plasma. Filtrate moving through tubules is called tubular fluid. Filtration averages 125 ml/min for the two kidneys. This amounts to about 180 liters/d males; 150 L/d females. Urination accounts for an average of 1500 ml per day (1.5 L/d; approximately 1% of the filtrate); 99% of the filtrate must be reabsorbed into the blood. Small molecules (water, electrolytes, urea, uric acid, glucose, amino acids, bicarbonate, toxins, drugs, H+, creatinine) pass from the blood through the capillaries of the glomerulus into the capsular space of the Bowman’s capsule. Fluids and solids are forced through porous 3-layered filtration membrane by HYDROSTATIC PRESSURE. Large protein molecules and blood cells do not move out of the blood into Bowman's capsule.

51 Filtration Membrane 3 layers lie between blood and the interior wall of glomerulus capsule. Fenestrated capillary endothelium-prevents release of blood cells Basement membrane Visceral membrane on glomerulus-podocytes/pedicels/ /filtration slits 1000x more permeable to water and solutes than other capillaries. Kidney infections / trauma can damage filtration membrane allowing proteins and blood cells to escape into filtrate and be released into the urine.

52 Filtration Pressure Force that produces filtration is the result of the interaction of three forces: Glomerular blood hydrostatic pressure (GBHP) force fluids and solute molecules out of the glomerulus capillaries. Pressure is higher here than any other capillaries due to large afferent arteriole inlet to capsule; smaller efferent outlet Capsular hydrostatic pressure (CsHP) opposes GBHP. Blood colloid osmotic pressure (BCOP) is the pull exerted on capsular fluid by glomerular blood proteins. It opposes filtration GBHP. Tends to draw water out of filtrate and back into plasma Net filtration pressure is the average pressure forcing water and dissolved materials out of glomerular capillaries Into capsular spaces GBHP – CHP – BCOP = NFP In a normal kidney NFP is usually positive.

53 Net Filtration Pressure (NFP)

54 http://humanphysiology2011. wikispaces

55 Glomerular Filtration Rate
GFR amount of filtrate kidneys produce each minute; highly regulated RATE TOO HIGH - fluid is moving too fast; unable to REABSORB water and solutes or remove waste/undesirable substances- can result in dehydration. RATE TOO LOW- fluid is moving too slow; can reabsorb waste products into blood that should be eliminated in the urine; azotemia may occur Creatinine Clearance Test used to estimate GFR measures level of waste product in the blood and urine. Creatinine formed from creatine phosphate metabolism used to produce ATP; taken out of blood by kidneys and passed to urine. *** Only way to adjust GFR from moment to moment is to change the glomerulus blood pressure. Three mechanisms work together to maintain a constant GFR renal autoregulation neural regulation hormonal regulation

56 GFR Regulation: Renal Autoregulation
Maintains adequate GFR by changing diameters of the nephron efferent arterioles, afferent arterioles, and gomerular capillaries. Uses 2 mechanisms: Myogenic mechanism –makes adjustment to kidney flow affected by systemic blood pressure Responds to changes in pressure in the renal blood vessels. Systemic Blood Pressure is ELEVATED when vessels are constricted. Constriction is also seen in the afferent arterioles of the kidney which RESTRICTS blood flow to the glomerulus This REDUCTION in blood flow TRIGGERS the myogenic mechanism to COMPENSATE by: Dilating afferent arteriole- less resistance flow will increase Constricting efferent arterioles - slows blood down as it leaves the glomerulus -- Systemic Blood Pressure DROPS blood flow increases. The RISE in blood flow triggers the myogenic mechanism to: Stretch the walls of afferent arterioles stimulates smooth muscle cells to contract Constriction of afferent arterioles produces more resistance decreasing glomerular blood flow

57 GFR Regulation Renal Autoregulation
Juxtaglomerular Complex (JGC): found at the end of nephron loop. Two types of cells are in close proximity of each other. Macula densa - specialized cells located in the DCT Cause intense vasoconstriction of the afferent arteriole in response to RAPIDLY FLOWING FILTRATE and/or changes in osmolarity (solute concentrations particularly Na+ and Cl-) This will HINDERS blood flow, SLOWS the glomerular filtration rate allowing more time for filtrate processing. Promotes vasodilation of the afferent arteriole when the filtrate is flowing slowly or there is low osmolarity This INCREASES the glomerular filtration rate, preventing reabsorption of harmful substances. Stimulates the juxtaglomerular cells secretion of renin which increases the release of aldosterone. Juxtaglomerular cells - enlarged smooth muscle cells of the afferent arteriole. Macula densa (DCT) stimulate the JG cells to 1) DILATE OR CONSTRICT the arterioles 2) to release RENIN. renin is also released via the nervous system when stimulated by sympathetic nervous system

58 http://classes. midlandstech. edu/carterp/Courses/bio211/chap25/Slide9

59 GFR Regulation Nervous/Hormonal Regulation
Changes in blood pressure; blood volume; osmotic concentration of tubular fluid near macula densa ACTIVATES hormonal regulation. Process involves the action of Sympathetic renal Nerves (SNS) to activate the Renin Angiotensin Aldosterone System (RAAS) mechanism: SNS causes release of the “ENZYME” Renin by juxtaglomerular cells. Renin converts angiotensinogen (BLOOD PLASMA GLOBULIN “PROTEIN”) made in the LIVER, to the PEPTIDE angiotensin I. “Peptide” Angiotensin I converted to the “HORMONE” angiotensin II by Enzyme (angiotensin converting enzyme – ACE) produced in the LUNGS/KIDNEYS Angiotensin II causes constriction of the EFFERENT arteriole increasing glomerular hydrostatic pressure, and increasing GFR. Angiotensin II also stimulates adrenal glands to release aldosterone. Aldosterone controls Na+ pumps and channels in both the DCT and Collecting duct reducing loss of Na+ in urine. Sodium conservation is associated with potassium loss.

60 Renin stimulated by Sympathetic Nervous System
Renin stimulated by JG cells Plasma protein –made in liver (Enzyme from JG cells) Renin stimulated by Sympathetic Nervous System Peptide (ACE) Hormone – from lungs and liver Efferent arteriole in the heart ventricles

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62 GFR Regulation Nervous/Hormonal Regulation
Natriuretic Peptides Atrial natriuretic peptide (ANP) is released by atria chamber of the heart in response to the stretching of heart walls due to increased blood volume or pressure Brain natriuretic peptide (BNP) is released by ventricles Triggers “dilation” of AFFERENT arterioles and “constriction” of EFFERENT arterioles Elevates glomerular pressures and INCREASES GFR

63 Autoregulation Hormonal and nervous regulation
Arterial Pressure Glomerular Hydrostatic Pressure GFR Autoregulation Macula Densa NaCl Vessel Diameter Juxtaglomerular Cells Hormonal and nervous regulation Renin - Aldosterone system; vessel diameter ANP

64 Urine Formation Three processes of urine formation
Glomerular Filtration Tubular reabsorption Tubular secretion

65 http://humanphysiology2011. wikispaces. com/file/view/filtration

66 2. Tubular Reabsorption (TR) Proximal Convoluted Tubule (PCT)
Reabsorption (back into the blood from the nephron tubules) is a 2- step process that begins with active or passive removal of substances and tubule fluid into the renal interstitium (connective tissue surrounding nephrons) transport of these substances from the interstitium into the bloodstream. TR reclaims water, NaCl, glucose, K+, P, Ca2+, Mg, vitamins, lactate, urea, uric acid, and amino acids. 65% of glomerular filtrate reabsorbed and returned to the blood and interstitial fluid via (PCT). Almost 100% of glucose / 90% of bicarbonate and H2O, 65% Na+, K+ / 50% Cl- / 85% P 40%-60% of urea also reabsorbed. Paracellular reabsorption proceeds via diffusion between cells – solvent drag Transcellular reabsorption result of primary and secondary active transport through the bottom of the cells Transcellular absorption increases due to water channels called aquaporins in the plasma membrane – controlled by ADH

67 Proximal Convoluted Tubules
Reabsorption Proximal Convoluted Tubules

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69 Reabsorption of PCT Two types of transport proteins channels Symports simultaneously bind Na+ and other solutes such as glucose (SGLT). Antiports pull Na+ into cell while pumping H+ out of the cell into the tubular fluid. Water moves through water channels=aquaporins

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71 Transport Maximum Some nutrients such as sodium, glucose, lactate, and amino acids require transport proteins (ex: SGLT) to move nutrients out of the PCT. It is essential nutrients such as glucose and amino acids are completely reabsorbed from the PCT. Some transport proteins channels require ATP (Na+K+Pump); others are passive Transport maximum (Tm) is the maximum rate of absorption reached when transporters (ex: symports, antiports) are saturated or FULL. If the quantity of nutrients exceed the transport capacity of the cells, the excess nutrients are NOT REABSORBED AND PASS INTO URINE. Renal threshold is the plasma concentration at which a specific compound or ion begins to appear in urine. When blood glucose levels are very high such as in diabetes mellitus, a large amount of glucose passes into the filtrate.

72 PCT Na+ Role in Reabsorption
Sodium ions are ESSENTIAL FOR REABSORPTION. They creates osmotic and electrical gradient that drives absorption of water and other solutes. REMEMBER: osmolarity is the measurement of solutes per liter of solution. Na+ / K+ ATPase pumps prevent the accumulation of Na+ in tubule epithelial cells and sends it to the renal interstitium Reabsorption of salt and other solutes increases the osmolarity of the interstitium, and lowers the osmolarity of the tubular cells. Water follows the solutes into interstitium by osmosis. 65% of H2O reabsorption occurs from the PCT. The remaining filtrate contains water, urea, sodium and other electrolytes that will be reabsorbed along the tubules.

73 Higher NaCl concentration in tubule moves to a lower concentration
Water follows Na+ concentrating fluid that remain in tubule as it reaches CT Higher the interstitium osmolarity more water leaves the descending loop The more water that leaves the tubules, the higher the salt content or osmolarity of the “TUBULAR” FLUID Higher NaCl concentration in tubule moves to a lower concentration

74 Loop of Henle: Countercurrent Multiplier
The ability of kidney to concentrate urine depends on salinity gradient in renal medulla. The countercurrent multiplier is a mechanism that creates a concentration gradient between the loop of Henle and the blood (vasa recta) 4x as salty in the renal medulla than the cortex Nephron loop acts as countercurrent multiplier multiplier - the two loops increase or multiply the osmotic gradient between tubular fluid and interstitial space by continually recaptures salt and returns it to extracellular fluid of medulla effectively “multiplying the salinity or salt content of the medulla”. countercurrent - fluid flowing in opposite directions in adjacent tubules of nephron loop amplifies the effect of transport from one limb on transport from the other limb. Ions leave via the Na-K-Cl symports and the Na-H antiports Fluid flowing downward in descending limb passes through environment of increasing osmolarity Cells of the descending limb are impermeable to NaCl but very permeable to water H2O passes from tubule into extracellular fluid leaving salt behind the filtrate becomes more and more concentrated. Animation: 23-74 74

75 Animation Countercurrent multiplier:
1) 2)

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78 Countercurrent Multiplier
Fluid flowing upward in ascending limb impermeable to water Na+, K+, and Cl- moved by active transport pumps into extracellular fluid increases osmolarity of the surrounding interstitium of renal medulla tubular fluid becomes hypotonic (low volume of solutes) due to loss of solutes Vasa recta – capillary branching off efferent arteriole in medulla provides blood supply to medulla BUT does not remove NaCl and urea from medullary extracellular fluid This mechanism allows vasa recta capillaries to deliver nutrients and oxygen to kidney cells and pick up waste products and CO2 without disrupting the osmolarity gradient of the medulla.

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80 H20 Reabsorption Distal Convoluted Tubules
Tubular fluid at DCT arrives with high osmotic concentration. Rate of ion transport across thick ascending limb is dependent on the ion’s concentration in tubular fluid. Tubular cells at the DCT actively transport Na+ and Cl– out of tubular fluid Water reabsorption in the DCT is regulated by hormones: ADH, aldosterone, Atrial natriuretic peptide (ANP) Aldosterone controls Na+ pumps and channels reducing loss of Na+ in urine ADH allows water to be reabsorbed from DCT and collecting duct and not lost in urine. The water is reabsorbed by osmosis driven by medullary hypertonicity (high volume of solutes) Stimulates synthesis of aquaporins in plasma membrane of tubules. Serve as water channels allowing more release of fluid from tubules. Overhydration causes low blood osmolarity which slows the release of ADH -- dilute urine is produced. ADH deficiency causes the production of a large amount of dilute urine, a condition called diabetes insipidus.

81 Distal Convoluted Tubules
Reabsorption Distal Convoluted Tubules

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83 Collecting Duct Regulation of water and solute loss in the Collecting Duct is controlled by aldosterone and ADH. Aldosterone increases the number of Na+/K+ pumps that allow increased sodium reabsorption and potassium secretion. Na+ is reabsorbed into the blood, K+ is secreted in urine Stimulates thirst; triggers release of ADH Stimulates reabsorption of water in distal portion of DCT and CD collecting system Exposure to ADH determines final urine concentration Final adjustments in volume and osmotic concentration of tubular fluid occurs in DCT and Collecting duct UREA is a waste product of protein metabolism that is passively reabsorbed from the nephron contributing to interstitial fluid hypertonicity (high volume of solutes) Overall, MORE urea passes into urine than is reabsorbed causing a net loss of urea from the body; remains concentrated in the CD Recycling of urea: lower end of CD permeable to urea continually cycled from CD to the nephron loop and back

84 Urine Formation Three processes of urine formation
Glomerular Filtration Tubular reabsorption Tubular secretion

85 3. Tubular Secretion Secretion is the release of substances INTO THE FILTRATE BACK FROM THE BLOOD by active transport. Substances will be excreted in the urine. Accomplished by tubular cells. The substances secreted into the filtrate are mainly derived from the blood in the peritubular capillaries. Occurs concurrently with reabsorption It occurs in the proximal convoluted tubule, the distal convoluted tubule, and the collecting duct.

86 Purposes of Secretion 1) Eliminate remaining toxins and drugs not already filtered these substances flow from the peritubular capillaries (out of the blood) directly into the tubules of the nephron and are passed into urine. 2) Establish electrolyte balance. Reabsorption of Na+ causes an imbalance of electrical charges; the secretion of positively charged ions such as K+ corrects this imbalance Negatively charged ions such as Cl- will either be secreted or will diffuse down their electrochemical gradient. Bicarbonate ions are always retained by blood because they act as buffers.

87 Purposes of Secretion 3) Acid / base balance. Achieved by managing Hydrogen ions (H+) and Bicarbonate ions (HCO3-): Hydrogen ions produced by carbon dioxide (CO2) and water combining to form carbonic acid (H2CO3) carbonic acid dissociates into Bicarbonate ion and Hydrogen ion (H+). CO2 + H2O H2CO HCO3- + H+ Bicarbonate ions are retained as a buffer and exchanged for chloride = the chloride shift. Hydrogen ions can be secreted during moderately acidic conditions. Severe acidic conditions H+ combines with the amino group from specific amino acids. The resulting ammonium ions, NH4+ are secreted. During extreme acidity H+ can also combine with phosphate groups to form phosphoric acid which is secreted.

88 Animations Good overview of kidney and nephron (6+mins) Good Summary (3+mins) Good animation urine formation Good overview of urine production animation

89 89

90 Glomerulus- produces filtrate similar to blood plasma w/o proteins
PCT reabsorbs 65% of glomerular filtrate and returns it to peritubular capillaries Nephron loop reabsorbs another 25% of filtrate DCT reabsorbs Na+, Cl- and water under hormonal control, especially aldosterone and ANP The tubules extract drugs, wastes, some solutes from the blood ; secrete them into the tubular fluid DCT completes the process of determining the chemical composition of urine Collecting duct conserves water; releases urine

91 Love your Kidneys!


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