The Urinary System

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2. Describe the major functions of the kidneys.

1. Filter blood to remove metabolic wastes which are then eliminated when urine exits the body. 2. Regulate fluid and electrolyte balance by regulating osmolarity (blood solute concentration) by either conserving or eliminating water and electrolytes. 3. Regulate acid-base balance and blood pH by conserving or eliminating hydrogen ions (H+) and bicarbonate ions (HCO3-). 4. Directly influence blood pressure by controlling blood volume and by secreting an enzyme that influences blood volume and peripheral vascular resistance. 5. Regulate red blood cell production (erythropoiesis) by releasing hormone erythropoietin. 6. Vital to many other metabolic functions including: detoxifying substances in blood, activating vitamin D, and making new glucose (gluconeogenesis).

7. List the 3 major processes in urine formation and provide the overall function of each process and where each occurs in the nephron and collecting system.

1. GLOMERULAR FILTRATION - initial process of nephrons to filter blood. Functions to selectively filter blood in glomerular capillary membranes. 2. TUBULAR REABSORPTION - mostly occurs in proximal tubule and nephron loop but may occur along entire length of tube. (To modify the filtrate as it flows through the tubules). Functions to modify the filtrate as it flows through tubules by reclaiming or reabsorbing substances such as water, glucose, amino acids, and electrolytes from tubular fluid to return them into circulating blood. 3. TUBULAR SECRETION - may occur along entire tubule. Functions to add substances into filtrate from peritubular capillaries for excretion from body. Helps maintain electrolyte and acid-base homeostasis;removes toxins from blood that did not enter tubular fluid by filtration. (Following the above, urine is formed. Urine filtration)

7. List the 3 major processes in urine formation and provide the overall function of each process and where each occurs in the nephron and collecting system.

1. GLOMERULAR FILTRATION: initial process of nephrons which is to filter blood (based on size; large proteins not filtered). Functions to selectively filter the blood in the glomerular capillary membranes. 2. TUBULAR REABSORPTION: mostly occurs in proximal tubule and nephron loop but may occur along entire length of tube. Modifies the filtrate as it flows through the tubules by reclaiming or reabsorbing substances such as water, glucose, amino acids, and electrolytes from tubular fluid to return them into circulating blood. 3. TUBULAR SECRETION: may occur along entire tubule, some subst. secreted more from 1 region than another. Functions to add substances into filtrate from peritubular capillaries for excretion from body. Helps maintain electrolyte and acid-base homeostasis; removes toxins from blood that did not enter tubular fluid by filtration. 4. URINE FORMATION

15. Describe obligatory and facultative water reabsorption.

85% of water reabsorption is OBLIGATORY. Obligatory water loss occurs in the proximal tubule. 15% of water can be adjusted according to the needs of the body: FACULTATIVE water reabsorption. Occurs in the late distal tubule and the cortical collecting duct. Regulated by hormone stimulation: Aldosterone, Antidiuretic (ADH), and atrial natriuretic peptide. It determines the final urine concentration.

11. Describe autoregulation of GFR and include an explanation of the myogenic and tubuloglomerular feedback mechanisms.

AUTOREGULATION - internal kidney mechanisms that work together to maintain GFR within normal range. Two negative feedback processes: 1. MYOGENIC MECHANISM - restores GFR by changing vessel diameter INCREASED systemic blood pressure stretches afferent arteriole increasing GFR; triggers smooth muscle (turns down the faucet) CONSTRICTION of afferent arteriole, reducing blood flow through glomerulus and returning GFR back to normal. DECREASED systemic blood pressure stretches afferent arteriole LESS, reducing GFR; triggers smooth muscle RELAXATION, increasing blood flow through glomerulus, causing an increase in GFR back toward normal range. (Turns up the faucet) Mechanism works best for SBP changes b/t 80-180 mm Hg to rapidly restore. GFR back to normal. 2. TUBULOGLOMERULAR FEEDBACK - involves macula densa of distal renal tubule; controls pressure in glomerulus in response to NaCl concentration of filtrate. Controls GFR by changing vessel diameter. As GFR increases, volume of filtrate flowing through renal tubule increases, and more sodium and chloride ions are absorbed into macula densa. Macula densa responds to increases in NACl concentration by releasing chemicals that cause afferent arteriole to constrict. MD signals JG cell causing reduction in release of hormones, renin and Angiotensin II, when reduced allow efferent arteriole to dilate causing a decrease in GFR toward normal. Decreases in GFR reduces sodium and chloride ions absorbed by MD, which triggers dilation of afferent arteriole and constriction of efferent arteriole, which increase GHP to restore GFR.

6. Compare and contrast cortical and juxtamedullary nephrons.

CORTICAL NEPHRONS make up about 80% of nephrons in kidneys. Renal corpuscles are found in outer renal cortex. Have short nephron loops that barely enter renal medulla, if at all. Peritubular capillaries supply blood to loops of cortical nephrons indirectly by exchanging materials through interstitial fluid. JUXTAMEDULLARY NEPHRONS much less common than cortical nephrons. 1. Renal corpuscles found near boundary b/t renal cortex and medulla 2. Have long nephron loops that travel deep within renal medulla 3. Cortical portion of nephron is surrounded by peritubular capillary branches from neighboring cortical nephrons. 4. Nephron loop is surrounded by a ladder-like network of capillaries called the vasa recta 5. Both capillary types drain into interlobular veins 6. Unique capillary structural arrangement allows juxtamedullary nephrons to control volumes and concentration of urine

6. Compare and contrast cortical and juxtamedullary nephrons.

CORTICAL nephrons make up 80% of nephrons in kidneys. Renal corpuscles are found in outer renal cortex, have short nephron loops that barely enter renal medulla if at all; peritubular capillaries supply blood to loops of cortical nephrons indirectly by exchanging materials through interstitial fluid. JUXTAMEDULLARY nephrons much less common. Renal corpuscles found near boundary b/t renal cortex and medulla. Have long nephron loops that travel deep within renal medulla. Cortical portion of nephron is surrounded by peritubular capillary branches from neighboring cortical nephrons. Nephron loop is surrounded by vasa recta. Both capillary types drain into interlobular veins. Unique capillary structural arrangement allows juxtamedullary nephrons to control volume and concentration of urine.

3. Describe the external coverings of the kidney.

Each kidney is held in place and protected by 3 external layers of connective tissue. Retroperitoneal. 1. Renal Fascia - dense irregular connective tissue. Anchors each kidney to peritoneum and musculature of posterior abdominal wall 2. Adipose capsule - thickest layer. Wedges each kidney in place and shields them from physical shock. 3. Renal capsule - think layer of dense irregular connective tissue. Covers exterior of each kidney. Protects it from infection and physical trauma.

8. Describe the structure of the filtration membrane. Include which substances can and cannot pass the filtration membrane.

Filtration membrane consists of 3 layers: collectively creates a barrier. 1. FENESTRATED GLOMERULAR CAPILLARY ENDOTHELIAL CELLS: large pores b/t endothelial cells; make them leaky. 70-100 nm. Still prevents lg subs. like blood cells, platelets, lg proteins from exiting capillary blood flow 2. BASAL LAMINA: thin layer of extracellular matrix gel. Collagen fibers form a meshwork that acts like a sieve to prevent subs. greater than 8 nm from entering; blocks entry of most plasma proteins; Negatively charged collagen fibers also repel negatively charged plasma proteins regardless of their size. 3. PODOCYTES: finest sieve of 3 layers; allows subs smaller than 6-7 nm. to pass into capsular space. Pedicels form filtration slits by wrapping themselves around glomerular capillary endothelial cells. ALBUMIN that reaches this layer is effectively prevented from entering capsular space. PORE SIZE determines comp. of fluid and solutes that pass into caps. space as filtrate. Water and small solutes like GLUCOSE, AMINO ACIDS, and VERY SMALL PROTEINS pass through filt. mem. easily. NITROGENOUS WASTES readily filtered: UREA and AMMONIUM IONS from protein metabolism. CREATININE produced by enzyme creatine kinase in muscle. URIC ACID: product of nucleic acid metabolism.

9. Define the glomerular filtration rate (GFR) and state its average value.

GFR is amount of filtrate formed by both kidneys in one minute. Kidneys filter 180 liters per day. Average value is 125 ml/min. 3 liters 60x day.

12. Describe how each of the following functions in the extrinsic control of GFR: renin-angiotensin-aldosterone system, natriuretic peptides, and sympathetic activity.

Hormonal Effects on GFR are part of a larger system that involves regulation of systemic blood pressure and includes angiotensin-II and natriuretic peptides. Hormonal mechanisms are 1. Sympathetic Nervous System activated; decreased GFR; decreased systemic blood pressure. RAAS responds. Main effects are: Vasoconstriction of efferent arteriole (clogs the drain) Systemic vasoconstriction Reabsorption of sodium ions from the filtrate in the proximal tubule Release of aldosterone Reabsorption of water. EFFECTS: INCREASE of GFR 2. Increased systemic blood pressure causes ATRIAL NATRIURETIC PEPTIDE to respond. Main effects: Vasodilation of afferent arteriole Vasoconstriction of efferent arteriole (turns up the faucet and clogs the drain) Decreased reabsorption of sodium ions Increased water loss EFFECTS: INCREASE of GFR 3. NEURAL REGULATION OF GFR involves sympathetic nervous system of and its hormone norepinephrine as it works to constrict all vessels and decrease GFR. EFFECTS are to constrict all blood vessels including efferent and afferent arterioles.Stimulates RAAS. Effects: DECREASE GFR.

5a. Describe the juxtaglomerular apparatus and the collecting system. Trace the pathway of filtrate flow through these tubules.

JGA found at transition point between ascending limb of nephron loop and distal tubule. Macula Densa is a group of cells in contact with modified smooth muscle cells (JG cells) found in walls of both Afferent and Efferent Arteriole. JGA regulates blood pressure and glomerular filtration rate. The Collecting System is a series of functionally and structurally distinct tubules; they further modify filtrate before it exits kidney. FLOW: A. Filtrate from several distal tubules enters cortical collecting duct B. Cortical collecting duct becomes medullary collecting duct as it enter renal medulla C. Several medullary collecting ducts merge to form a papillary duct D. Once filtrate enters papillary duct, it is known as urine, not filtrate E. Urine exits papillary duct at papilla of renal pyramid into a minor calyx.

18.Describe the 2 mechanisms for the production of concentrated urine. Include an explanation of the countercurrent mechanism.

Kidneys effectively conserve water by producing very concentrated urine using 2 mechanisms (reaching nearly 1200 osmolarity): 1. Release of ADH turns on facultative water reabsorption 2. Creation and maintenance of medullary osmotic gradient. Countercurrent mechanism creates and maintains medullary osmotic gradient by exchanging materials in opposite directions b/t filtrate and interstitial fluids. CM involves 3 factors: 1. CC multiplier system in nephron loops of juxtamedullary nephrons. (NaCl pumped into fluid) 2. Recycling of urea in medullary collecting ducts adds to gradient. 3. CC exchanger in vasa recta allows the inner medulla to be perfused while maintaining the medullary interstitial gradient.

4. Trace the path of blood through the kidneys.

Left and right renal arteries are branches of abdominal aorta. Kidneys receive about 1/4 total cardiac output or about 1200 ml of blood per minute. 1. Renal Artery 2. Segmental Artery 3. Interlobar Artery 4. Arcuate Artery 5. Interlobular Artery 6. Afferent Arteriole 7. Glomerulus 8. Efferent Arteriole 9. Peritubular Capillaries 10. Interlobular Vein 11. Arcuate Vein 12. Interlobar Vein 13. Renal Vein

16. Briefly describe the medullary collecting system.

Medullary collecting system is the last chance for regulation of fluid, electrolyte, and acid-base balance before filtrate becomes urine. Cells of this system have the following properties: 1. Impermeable to water in absence of ADH 2. Permeable to urea; allows urea to be reabsorbed passively into interstitial fluid. 3. Local intercalated cells secrete hydrogen ions into filtrate against a steep concentration gradient, increasing H+ concentration in filtrate by as much as 900 times.

22.Define micturition and briefly describe the micturition reflex and micturition center.

Micturition - urination or voiding; discharge of urine from urinary bladder to outside of body. • Micturition reflex - reflex arc mediated by parasympathetic nervous system when urine fills bladder and stretches walls: Stretch receptors send a signal to sacral region of the spinal cord via sensory afferent fibers Parasympathetic efferent fibers stimulate detrusor muscle to contract and internal urethral sphincter to relax; allows for micturition • Micturition center - found in pons (central nervous system); given time and training makes micturition a voluntary process. 1) Urine fills bladder and stretches its wall. 2) Stretch receptors send signal via sensory afferent fibers to sacral portion of spinal cord. 3) PS efferent fibers stim. detrusor muscle to contract and the internal urethral sphincter to relax, causing micturation. 4) Interneurons in spinal cord communicate "full bladder" signal to micturition center in pons. 5) If micturition appropriate, cerebral cortex allows urethral sphincter to relax, and urine is voided.

5. Describe the structure and function of the nephron to include all parts of the renal corpuscle and the renal tubule.

Most of the kidney functions occur at the nephrons. Nephrons filter blood and modify filtered fluid as it passes through renal tubules. Nephons' 2 main divisions: 1) RENAL CORPUSCLE is responsible for filtering blood. Composed of 2 parts: Glomerulus (group of looping fenestrated capillaries, leaky, permeable) 2) GLOMERULAR CAPSULE - double-layered outer sheath of epithelial tissue. A) Outer parietal extension of renal tubule made of simple squamous epithelium. B) Inner visceral layer made of modified epithelial cells called podocytes. Extensions called foot processes , or pedicels, surround glomerular capillaries to form filtration slits. C) Capsular space, hollow region b/t parietal and visceral layers; continuous with entrance of Rena tubule lumen. Podocytes and fenestrated glomerular capillaries form a complex membrane that filters blood flowing through glomerulus. Filtered fluid (filtrate) exits glomerular capillaries into capsular space, then enters lumen of renal tubule. RENAL TUBULE - newly formed filtrate enters renal tubule where it can be further modified. 3 regions: 1. Proximal tubule - simple cuboidal epithelial cells with microvilli, project to form brush border, increases surface area. 2. Nephron Loop - dip into renal medulla. Consists of descending and ascending limb. 3. Distal tubule - has both straight and convoluted sections - last segment of renal tubule that filtrate passes through, simple cuboidal epith, w/o brush border.

10. Describe the hydrostatic and colloid osmotic forces that favor and oppose filtration in the renal corpuscle.

NFP (net filtration pressure) at the glomerulus is determined by 3 driving forces: 1. GLOMERULAR HYDROSTATIC PRESSURE (GHP): determined mostly by systemic blood pressure; about 50 mm Hg, which is higher than average capillary bed hydrostatic pressure (17-35 mm Hg); favors filtration of substances through filtration membrane into capsular space. 2. GLOMERULAR COLLOID OSMOTIC PRESSURE (GCOP): similar to COP, created mostly by albumin; only slightly higher (30 mm Hg) than typical capillary bed; opposes filtration by pulling water back into glomerular capillaries. 3. CAPSULAR HYDROSTATIC PRESSURE (CHP): Generated as capsular space rapidly fills with new filtrate (10 mg Hg) as fluid can only move so quickly into renal tubule which opposes filtration. NFP is combo of these 3 forces: NFP = GHP - (GCOP) + (CHP) NFP favors filtration as GHP is greater than sum of forces that oppose filtration (GCOP + CHP)

17. Describe the production of dilute urine.

Osmolarity of filtrate changes through different regions of nephron until urine is formed. 1. Filtrate that exits blood and enters nephron has same osmolarity of blood: Iso-osmotic (equal to osmolarity in plasma). 2. Descending limb of the nephron loop (permeable to water) concentrates filtrate. 3. Ascending limb of loop and distal tubule (permeable to salts) dilutes filtrate. 4. In absence of ADH, solutes reabsorbed while water remains in filtrate further diluting filtrate. 5. Creates dilute, or HYPOTONIC, urine.

14. Explain which substances are reabsorbed and secreted in each tubular segment and the collecting duct.

Reabsorbed in Proximal Tubule: -65% of water in filtrate -100% glucose, amino acids, other organic solutes -90% bicarbonate ions -65% or more of Sodium, Potassium, Calcium, Chloride, Magnesium Reabsorbed in thin descending limb: 20% water in filtrate Reabsorbed in thick ascending limb: 25% Sodium and Chloride Reabsorbed in distal tubule and collecting duct: -Most of remaining water -Nearly of of remaining Sodium, Chloride, Calcium -Bicarbonate ions SECRETED in Proximal Tubule: -Hydrogen Ions -Nitrogenous wastes such as uric acid -some drugs SECRETED from distal tubule and collecting duct: Potassium and Hydrogen (regulated by hormones) *Late distal tubule and collecting ducts have hormone receptors that regulate water, electrolyte, and acid-base balance.

20. Define renal clearance and explain how it is used to measure GFR. Explain the relationship of creatinine and inulin to GFR.

Renal clearance is measurement of rate at which kidneys remove a substance from blood. Can be used to estimate glomerular filtration rate Both measured in milliliters of plasma per minute For a substance to provide an accurate measure of renal clearance and GFR, substance should be completely filtered and neither reabsorbed nor secreted. • Renal clearance and GFR can also be estimated by measuring: Creatinine - waste product of muscle cell metabolism o Blood levels of creatinine are elevated when kidneys are impaired; clearance of creatinine is therefore decreased; not totally accurate (5-50% in urine arrived via secretion, not filtration) Inulin- complex carbohydrate found in plants such as garlic and artichokes; neither secreted or absorbed; must be injected o More accurate assessment of GFR

13. Define tubular reabsorption and secretion. Explain the two routes for moving substances in the rental tubule.

Tubular reabsorption: substances must pass from filtrate in lumen of tubule across or b/t tubule cells, into interstitial fluid, and finally across or between endothelial cells of the peritubular capillaries to re-enter blood. Tubular secretion: substances move in opposite direction. Two routes across epithelia: Paracellular: pass BETWEEN adjacent tubules; tight junctions b/t tubule cells are just leaky enough to allow some substances (small ions and water) to move passively between them, particularly in proximal tubule. Transcellular: (glucose and amino acids) substances too large to move b/t cells or where concentration gradient opposes their movement must move through tubule cells. Reabsorbed substances first crosses apical membrane of tubule cell (faces tubule lumen), then travels through cytosol, and finally exits cell through basolateral membrane (faces interstitial fluid). Substances reabsorbed and secreted by each tubular segment and the collecting duct.

1. List and describe the organs of the urinary system.

Urinary system (organs of excretion) is composed of a pair of kidneys and urinary tract. The kidneys filter blood to remove metabolic waste products and modify existing fluid. Urinary tract consists of 2 ureters, bladder to store urine, and urethra to allow urine to exit the body.

21. Describe the functions of the ureters, urinary bladder, and the urethra.

Urinary tract consists of two ureters, urinary bladder, and urethra. Ureters are muscular tubes that undergo peristalsis to propel urine towards the bladder empties into bladder. Urinary bladder functions to store urine until elimination. o Holds 700-800 ml of urine in males and slightly less in females. Urethra - last segment of urinary tract, drains urine from urinary bladder to outside of body.

19. Describe normal urine composition.

Water, sodium, potassium, chloride, Hydrogen Ions, Phosphates, Sulfates, Metabolic wastes such as urea, creatinine, ammonia, and uric acid. Also small amounts of bicarbonate, calcium, and magnesium may also be present. Urinalysis is used to analyze urine composition as a diagnostic tool for detecting disease: Urine color is Formed by a yellow pigment, urochrome; breakdown product of hemoglobin. Darker urine is more concentrated; has less water. Lighter urine is less concentrated; has more water. -Despite color, urine should be translucent (light is able to pass through); cloudy urine may be a sign of infection or that too much protein is present. -Freshly voided urine should have a mild odor; strong odor may be caused by diseases, infections, or by ingesting certain foods. Normal pH of urine is slightly acidic at 6.0; ranges from 4.5-8.0


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