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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)