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   Functions of urinary system Anatomy of kidney Urine formation glomerular filtration  tubular reabsorption  tubular secretion    Urine and renal function tests Urine storage and elimination  Is the passive transport of WATER across a selectively permeable membrane Two kidneys Two ureters One urethra 23-3  Filters blood plasma    returns useful substances to blood eliminates waste Regulates osmolarity of body fluids, blood volume, BP  acid base balance   Secretes    renin and erythropoietin Detoxifies free radicals and drugs Gluconeogenesis  Urea (most abundant)    Uric acid   nucleic acid catabolism Creatinine   proteinsamino acids NH2 removed forms ammonia liver converts to urea creatine phosphate catabolism Renal failure   azotemia is defined as BUN, nitrogenous wastes in blood uremia is a term used more loosely = toxic effects of  nitrogenous wastes  Separation of wastes from body fluids and eliminating them; by four systems     Lungs: CO2 Skin: water, salts, lactic acid, urea Digestive: water, salts, CO2, lipids, bile pigments, cholesterol Urinary: many metabolic wastes, toxins, drugs, hormones, salts, H+ and water 23-6  Position, weight and size retroperitoneal, level of T12 to L3  about 160 g each  about size of a bar of soap (12x6x3 cm)   Shape   lateral surface - convex; medial - concave Connective tissue coverings renal fascia: binds to abdominal wall  adipose capsule: cushions kidney  renal capsule: encloses kidney like cellophane wrap  23-7    Renal cortex: outer 1 cm Renal medulla: renal columns, pyramids - papilla Lobe of kidney: pyramid and it’s overlying cortex 23-8   Notice where the nephron sits Where is the glomerulus?  Nephrons connect to collecting ducts - Glomerulus (vascular) - Bowman’s Capsule (collecting)  Renal artery  interlobar arteries (up renal columns, between lobes)  arcuate arteries (over pyramids)  interlobular arteries (up into cortex)  afferent arterioles  glomerulus (cluster of capillaries)  efferent arterioles (near medulla  vasa recta)  peritubular capillaries  interlobular veins  arcuate veins  interlobar veins  Renal vein 23-11 The glomerulus is a portal system no segmental veins 23-12  Proximal convoluted tubule (PCT)   Nephron loop - U shaped; descending and ascending limbs    longest, most coiled, simple cuboidal with brush border thick segment (simple cuboidal) initial part of descending limb and part or all of ascending limb, active transport of salts thin segment (simple squamous) very water permeable Distal convoluted tubule (DCT) – typo on pg 901  cuboidal, minimal microvilli Arcuate artery and vein Interlobular artery and vein  Collecting duct   several DCT’s join Flow of glomerular filtrate:  glomerular capsule  PCT  nephron loop  DCT  collecting duct  papillary duct  minor calyx  major calyx  renal pelvis  ureter  urinary bladder  urethra Arcuate Arcuate artery artery and and vein vein Interlobar artery Interlobular andand veinvein artery 23-14   True proportions of nephron loops to convoluted tubules shown Cortical nephrons (85%)    short nephron loops efferent arterioles branch off peritubular capillaries Juxtamedullary nephrons (15%)  very long nephron loops, maintain salt gradient, helps conserve water Arcuate artery and vein Interlobular artery and23-15 vein  Peritubular capillaries shown only on right 23-16 23-18  Fenestrated endothelium   70-90nm pores exclude blood cells Basement membrane proteoglycan gel, negative charge excludes molecules > 8nm  blood plasma 7% protein, glomerular filtrate 0.03%   Filtration slits  podocyte arms have pedicels with negatively charged filtration slits, allow particles < 3nm to pass 23-19     GFR = mls of filtrate formed per minute filtration coefficient (Kf) depends on permeability and surface area of filtration barrier Blood hydrostatic pressure is higher than usual capillaries 99% of filtrate reabsorbed, 1 to 2 L urine excreted 23-20     GFR = mls of filtrate formed per minute filtration coefficient (Kf) depends on permeability and surface area of filtration barrier Blood hydrostatic pressure is higher than usual capillaries 99% of filtrate reabsorbed, 1 to 2 L urine excreted 23-21      Hypertension ruptures glomerular capillaries Leads to scarring of glomeruli Scarred glomeruli have decreased permeability thus decreased GFR Nitrogenous wastes accumulate Kidney failure     Inappropriate increase in GFR, urine output rises can result in dehydration and electrolyte depletion If disease GFR  wastes are not efficiently excreted (azotemia possible) If MAP rose from 100 to 125 mmHg then, in the absence of control mechanisms, urine output would rise to 45 liters/day GFR controlled by adjusting glomerular blood pressure 1. 2. 3. Autoregulation Sympathetic control Hormonal mechanisms: renin and angiotensin 23-23  Juxtaglomerular Cells  dilate or constrict arterioles  secrete renin  Mesangial Cells  Mysterious function  Gap junctions  Macula Densa Cells  monitors salinity  inhibit renin release 23-24  Myogenic mechanism    BP  stretches afferent arteriole  afferent arteriole constricts  restores GFR Tubuloglomerular feedback  Macula densa on DCT monitors tubular fluid for high salt and signals juxtaglomerular cells (smooth muscle, surrounds afferent arteriole) to constrict afferent arteriole to  GFR 23-25     If BP  constrict afferent arteriole and dilate efferent to bring GFR back to normal If BP   dilate afferent arteriole and constrict efferent Stable for BP range of 80 to 170 mmHg (systolic) Cannot compensate for extreme hypertension   Strenuous exercise or acute conditions (circulatory shock) stimulate afferent arterioles to constrict through both innervation and epinephrine effect This results in  GFR and  urine production, redirecting blood flow to heart, brain and skeletal muscles 23-27   JG cells secrete renin when blood pressure drops Renin is an enzyme that acts in the production of angiotensin II 23-29      Azotemia Uremia Glycosuria Pyuria Glomerulonephritis      Urinary incontinence Renal failure Oliguria Proteinuria UTI - cystitis 23-31   There is about 180 liters of glomerular filtrate each day! The renal tubules act to maximize retention of water and Na+ while maximizing elimination of wastes   Blood has unusually high COP here, and BHP is only 8 mm Hg (or lower when constricted by angiotensin II); this favors reabsorption Water absorbed by osmosis and carries other solutes with it (solvent drag) 23-33   Reabsorbs 65% of GF to peritubular capillaries Great length, prominent microvilli and abundant mitochondria for active transport  Reabsorbs greater variety of chemicals than other parts of nephron   transcellular route - through epithelial cells of PCT paracellular route - between epithelial cells of PCT  Transport maximum    when transport proteins of cell membrane are saturated blood glucose > 220 mg/dL some remains in urine (glycosuria) Solvent drag  Waste removal   Acid-base balance   urea, uric acid, bile salts, ammonia, catecholamines, many drugs secretion of hydrogen and bicarbonate ions regulates pH of body fluids Primary function of nephron loop    Arcuate artery and vein Interlobar artery Arcuate artery and vein and vein water conservation generates salinity gradient, allows DCT to concentrate urine also involved in electrolyte reabsorption 23-37  Principal cells (more abundant) – receptors for hormones   involved in salt/water balance Intercalated cells (lots of mitochondria)   involved in acid/base balance K+ in, H+ out  Action affected by hormones      ADH Atrial Natriuretic Peptide Aldosterone Parathyroid Effect of ADH      dehydration stimulates hypothalamus hypothalamus stimulates posterior pituitary posterior pituitary releases ADH ADH  water reabsorption  urine volume Atrial natriuretic peptide (ANP)     atria secrete ANP in response to high blood pressure has four actions: 1. dilates afferent arteriole, constricts efferent arteriole -  GFR 2. inhibits renin/angiotensin/aldosterone pathway 3. inhibits secretion and action of ADH 4. inhibits NaCl reabsorption Promotes Na+ and water excretion,  urine volume,  blood volume and BP 23-40  Aldosterone effects  BP  renin release  angiotensin II formation  angiotensin II stimulates adrenal cortex  adrenal cortex secretes aldosterone   promotes Na+ reabsorption  promotes water reabsorption   urine volume  maintains BP  Effect of PTH     calcium reabsorption in DCT -  blood Ca2+  phosphate excretion in PCT,  new bone formation stimulates kidney production of calcitriol 23-42   Osmolarity is 4x as concentrated deep in medulla Medullary portion of CD is more permeable to water than to NaCl  Producing hypotonic urine    NaCl reabsorbed by cortical collecting ducts (CD’s) water remains in urine Producing hypertonic urine     dehydration   ADH   aquaporin channels,  CD’s water permeability more water is reabsorbed urine is more concentrated is possible only because of the countercurrent multiplier   Recaptures NaCl and returns it to renal medulla Descending limb    The thick segment of the ascending limb      reabsorbs water but not salt concentrates tubular fluid reabsorbs Na+, K+, and Clmaintains high osmolarity of renal medulla impermeable to water tubular fluid becomes hypotonic Recycling of urea: collecting duct-medulla  urea accounts for 40% of high osmolarity of medulla  Descending capillaries water diffuses out of blood  NaCl diffuses into blood   Formed by vasa recta   provide blood supply to medulla do not remove NaCl from medulla  Ascending capillaries water diffuses into blood  NaCl diffuses out of blood      Some species of E. coli live harmlessly in your GI tract A few types of bacteria, usually E. coli strain O157:H7, cause food poisoning and are nephrotoxic Shiga toxin enters the bloodstream, attaches to renal endothelium and initiates an inflammatory reaction leading to acute renal failure (ARF) The toxin also initiates destruction of RBCs and platelets  Appearance  almost colorless to deep amber; yellow color due to urochrome, from breakdown of hemoglobin (RBC’s) Odor - as it stands bacteria degrade urea to ammonia  Specific gravity    density of urine ranges from 1.001 -1.028 Osmolarity - (blood - 300 mOsm/L) ranges from 50 mOsm/L to 1,200 mOsm/L in dehydrated person   pH - range: 4.5 - 8.2, usually 6.0 Chemical composition: 95% water, 5% solutes  urea, NaCl, KCl, creatinine, uric acid Normal urine does not contain glucose     Normal volume - 1 to 2 L/day Polyuria > 2L/day Oliguria < 500 mL/day Anuria - 0 to 100 mL/day   Chronic polyuria of metabolic origin With hyperglycemia and glycosuria diabetes mellitus I and II, insulin hyposecretion/insensitivity  gestational diabetes, 1 to 3% of pregnancies   ADH hyposecretion  diabetes insipidus; CD  water reabsorption  Effects    Uses    urine output  blood volume hypertension and congestive heart failure Mechanisms of action  GFR   tubular reabsorption    Renal clearance: volume of plasma cleared of a waste in 1 minute Determine renal clearance (C) by assessing blood and urine samples: C = UV/P U (waste concentration in urine)  V (rate of urine output)  P (waste concentration in plasma)    Determine GFR: inulin is neither reabsorbed or secreted so its GFR = renal clearance GFR = UV/P Clinical GFR estimated from creatinine excretion  Ureters (about 25 cm or 10 inches long)  from renal pelvis passes dorsal to bladder and enters it from below, with a small flap of mucosa that acts as a valve into bladder  3 layers  adventitia - CT  muscularis - 2 layers of smooth muscle with 3rd layer in lower ureter  urine enters, it stretches and contracts in peristaltic wave  mucosa - transitional epithelium  lumen very narrow, easily obstructed   Located in pelvic cavity, posterior to pubic symphysis 3 layers       parietal peritoneum, superiorly; fibrous adventitia rest muscularis: detrusor muscle, 3 layers of smooth muscle mucosa: transitional epithelium Trigone: openings of ureters and urethra, triangular rugae: relaxed bladder wrinkled, highly distensible capacity: moderately full - 500 ml, max. - 800 ml   3 to 4 cm long External urethral orifice   between vaginal orifice and clitoris Internal urethral sphincter detrusor muscle thickened, smooth muscle  involuntary control   External urethral sphincter skeletal muscle  voluntary control     much longer than the female urethra Internal urethral sphincter External urethral sphincter 3 regions prostatic urethra during orgasm receives semen membranous urethra passes through pelvic cavity spongy (penile) urethra 200 ml urine in bladder, stretch receptors send signal to sacral spinal cord Signals ascend to     Signals descend to    further inhibit sympathetic neurons stimulate parasympathetic neurons Result  urinary bladder contraction  relaxation of internal urethral sphincter External urethral sphincter - corticospinal tracts to sacral spinal cord inhibit somatic neurons - relaxes   inhibitory synapses on sympathetic neurons micturition center (integrates info from amygdala, cortex)