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  1. Urinary Part Two

  2. Urine Formation • 3 Processes • Glomerular Filtration • Glomerular filtrate • Tubular Reabsorption • Tubular fluid • Tubular Secretion • Tubular fluid Figure 15.4

  3. Glomerular Filtration • Nonselective, passive process • Fluid from blood passes into glomerular capsule = glomerular filtrate – blood plasma w/o blood proteins • Blood cells and proteins too large, when found in urine indication problem with glomerular filtration • If blood pressure normal, filtrate made, in blood pressure drops, no movement out of blood Figure 15.5

  4. Filtration Membrane • Plasma from capillaries of glomerulus to capsular space – pass thru 3 barriers • Fenestrated endothelium – capillaries are honeycombed, larger pores • Basement membrane of capillary – proteoglycan layer, size and charge (-) • Filtration slits – podocytes octopi w/pedicels

  5. Glomerular Filtration Rate (GFR) • Filtrate formed/min by both kidneys • Men 180L/day • Women 150L/day • 50-60X blood plasma so what’s going on? • Reabsorb 99% of filtrate as forming urine

  6. Regulation of Glomerular Filtration • GFR regulated • Too fast or too slow? • Have to change the glomerular pressure – 3 homeostatic mechanisms • Renal autoregulation • Sympathetic Control • Renin-Angiotensin

  7. Regulation of GFR- Renal Autoregulation • Nephrons adjust own blood flow and GFR with hormonal or nervous control • Limited – doesn’t work at extremes! • Even as Mean Arterial Pressure (MAP) varies, filtrate production remains consistent • Helps ensure stable fluid and electrolyte balance • Two mechanisms • Myogenic Mechanism • Tubuloglomerular feedback

  8. Myogenic Mechanism • Stabilizing GFR with smooth muscle contraction • Arterial BP rises, stretches afferent arteriole • SM constrictions prevents blood flow into glomerulus from changing much • Arterial BP drops, SM relaxes, consistent blood flow • Consistent blood flow, consistent filtrate!

  9. Tubuloglomerular Feedback • Jusxtaglomerular apparatus (JGA) monitors fluid entering DCT and adjust GFR • 3 components • Juxtaglomerular (JG) cells – SM found in afferent arteriole, some efferent. Stimulated by macula densa to constrict or relax. Also release renin • Macula densa – dense epithelial cells at start of DCT • Mesangial cells – connected to JG and macula densa cells via gap junctions and may communicate

  10. Regulation of GFR - Sympathetic Control • Sympathetic nerves innervate the renal BV • Stress and exercise – sympathetic nervous and epinephrine from adrenal gland cause constriction of afferent arterioles • Less GFR, less urine • Redirects blood to heart, brain, skeletal muscles

  11. Regulation of GFR – Renin - Angiotensin • When BP drops, sympathetic system stimulates juxtaglomerular cells to secrete renin. • Renin cleaves angiotesinogen (plasma protein) into angiotensin I. • In lung and kidneys, Angiotensin-converting exzyme (ACE) cleaves angiotensin I into angiontensin II (hormone)

  12. Functions of Angiotensin II • Stimulates vasoconstriction – incr. MAP • Constrict afferent and efferent arteriole – reduce GFR • Stimulates secretion of ADH, promotes water absorption • Stimulates secretion of aldosterone, promotes sodium and water retention • Stimulates sense of thirst, incr. water intake

  13. Tubular Reabsorption • In addition to waste, nutrients also in filtrate • H2O, glucose, a.a., ions • Reclaim from filtrate • PCT – tubule cells are “transporters”, take up from filtrate and pass out into extracellular space -> peritubular capillary blood • Some passive, some use carriers, are no carriers for substances body doesn’t need • Nitrogenous Waste Products – high concentrations in urine – urea, uric acid, creatinine • Ions absorbed or not depends on blood Figure 15.5

  14. PCT – Tubular Reabsorption • Reabsorbs 60% of filtrate, removes some waste from blood and secretes into tubules • Remember microvilli! • Cells have lots of mitochondria for ATP. PCT 6% of your resting ATP and calorie consumption • Two routes for reabsorption by PCT • Trancellular route • Paracellular route

  15. How does Sodium move? • Sodium is key to everything! • Creates osmotic and electrical gradient that drives movement of everything else. • Both transcellular and paracellular • More concentrated in tubule than cell, movement into epithelial cell by facilitated diffusion • First half of PCT – • moved by symport with glucose, AA, P, etc • H+ generated in cell from CO2-> bicarbonate rxn, Na-H antiport, Na in, H out • Second half PCT – [Cl] high, antiport Na and Cl

  16. More Sodium • Sodium only moves because of gradient • With all sodium going into cell, what happens to gradient? • Na-K pumps on basement and lateral membranes into ECF • Secondary active transport – some solutes transported with Na, and they rely on gradient which is powered by Na-K pump

  17. Chloride • Paracellular and transcellular • Cl- follows Na+ • Water reabsorption concentrates Cl and creates gradient in lower half of PCT • Some antiports

  18. Bicarbonate • Urine is bicarbonate free • Not reabsorb by nephron • Cells produce own bicarbonate molecules which diffuse into ECF picked up by blood

  19. Electrolytes and Glucose • K, Mg, Pi diffuse thru paracellular route with water • Most Ca is later but some via paracellular route • Sulfates and nitrates are waste, not reabsorbed • Glucose cotransported with Na = sodium-glucose transport proteins

  20. Water • Kidneys reduce 180L of filtrate to 1-2L of urine each day • Water reabsorption imp • 2/3 of water absorption by PCT • Water follows solutes via paracellular and transcellular routes (aquaporins) • PCT water absorbed at constant rate, regulated by hormones in other tubule areas

  21. Peritubular Capillaries • Reabsorption from ECF into peritubular capillaries by osmosis and solvent drag (movement of water drags solvents) • High interstitial fluid pressue • Low hydrostatic pressure in peritubular capillaries • High colloid pressure

  22. Tubular Secretion – PCT and Loop • From BV into tubule • Waste removal – urea, uric acid, bile acids, ammonia, catecholamines, creatinine, drugs, toxins • Acid-base balance – H and bicarbonate ions regulates pH

  23. Nephron Loop • Generate salinity gradient allows collecting duct to [urine] and conserve water • Reabsorbs 25% of Na, K, Cl and 15% of water. • Thick segment – cells bind 1Na, 1K, and 2Cl from tubular fluid and contransport into cytoplasm • K re-enters cell via Na-K pump, NaCl remains in tissue fluid of medulla • Water cannot enter thick segment, filtrate dilute as enters DCT

  24. DCT and Collecting Duct • Still contains 20% of water from glomerular filtrate – still doing reabsorption • Hormonal regulation!!! – aldosterone, atrial natruiretic peptide, ADH, and PTH • Two types of cells • Principal cells – more abundant, receptors for hormones, salt and water balance • Intercalated cells – lots of mitochondria, reabsorb K, secrete H, acid-base balance

  25. Aldosterone • Salt retaining hormone • Secreted by adrenal cortex • Drop in blood Na or incr in K stimulates release directly • Drop in BP – stimulates renin->angiotensin II-> stimulates release of aldosterone • Causes DCT and cortical part of collecting duct to reabsorb more Na (Cl and water follow) • Secrete more K • Urine volume is reduced, contains more K and less NaCl

  26. Atrial Natriuretic Peptide • Secreted by atrial myocardium in response to high BP • 4 actions to excrete salt and water in urine • Dilates afferent arteriole and constricts efferent, incr GFR • Antagonizes angiotensin-aldosterone mechanism, inhibits secretion of aldosterone and renin • Inhibits secretion of ADH and action on kidney • Inhibits NaCl reabsorption by collecting duct

  27. ADH • Secreted by Post Pituitary in response to dehydration and rising blood osmolarity • Makes collecting ducts more permeable to water

  28. PTH • Promotes Ca reabsorption by ascending loop of Henle and DCT • Also inhibits reabsorption of P by PCT • Prevents P from binding to Ca

  29. Collecting duct • Starts in cortex, multiple nephrons • In medulla, reabsorbs water and concentrates urine • Osmolarity of ECF is 4x as high in deep medulla than in cortex • Medullary part is more permeable to water than to NaCl • As pass thru CD, water leaves thru osmosis, NaCl and wastes remain

  30. Urine • Yellow color – urochrome, pigment form destroyed Hb, pale vs. darker, diet • Sterile when formed • pH is slightly acidic pH=6.0 • Diet can change, protein, wheat, or vegetarian • Some diseases or food can change smell • Substances not common in urine = glucose, blood proteins, RBCs, Hb, WBC, bile

  31. Abnormal Urinary Constituents

  32. Urinary Diseases • Urinary Retention – unable to expel urine • After surgery – anesthesia • Hyperplasia of prostate gland • May require catheter to avoid damage • Incontinence – unable to control external sphincter. • Ages 2 and younger • Sound sleepers • Emotional problems, pressure (pregnancy), Nervous system (stroke, spinal cord damage)

  33. Polycystic Kidneys • Congenital abnormality • Degenerative disease • Enlarged kidneys, blisters contain urine • Sac obstruct urine drainage • Can prevent infection, but renal failure inevitable.