Ch 19: The Kidneys

1. Ch 19: The Kidneys Functional unit of kidneys: ?? 4 basic processes of urinary system: Filtration Reabsorption Secretion Excretion

2. Functions of Kidneys Homeostatic regulation of • H2O & solute concentration • ECF volume • osmolarity, ion concentration • pH(acid-base balance) • Excretion of wastes & foreign substances • Hormone and enzyme production etc. Further functions

3. Four Processes of Urinary System • Filtration, Reabsorption, Secretion, Excretion • Related by equation: E = F - R + S 180 L / day filtered, >99% reabsorbed, 1.5 L / day excreted Figs 19-2/3

4. Peritubular capillaries Distal tubule Efferent arteriole S R Glomerulus F R S Afferent arteriole Proximal tubule Bowman’s capsule R S R R Loop of Henle KEY F = Filtration: blood to lumen To renal vein = Reabsorption: lumen to blood R Collecting duct = Secretion: blood to lumen S E = Excretion: lumen to external environment E To bladder and external environment

6. 1) Filtration = Movement of fluid from blood to lumen of nephron (rel. nonspecific process) Once in lumen – consider it outside body Composition of filtrate? Fig 19-4

7. Filtration: Passage across 3 Barriers • Capillary endothelium • Basal lamina (= BM) • Bowman’s capsule epithelium (visceral layer) Some small molecules (Ca2+, low m.w. fatty acids) bind to plasma proteins  ? Fig 19-4

9. Cause of Filtration Three types of pressures are at work: • Hydrostatic pressure in capillaries (see exchange in tissues) • Osm. Pin caps > Osm. P in Bowman’s capsule • Hydrostatic fluid P from presence of fluid in Bowman’s capsule Net (?) driving pressure: ~ 10 mmHg Fig 19-6

10. Filtration Pressure Net driving pressure = ?

11. Glomerular Filtration Rate = GFR Describes filtration efficiency: Amount of fluid filtered per unit of time Average GFR ? influenced by • Net filtration pressure • Available surface area Fig 19-5

13. GFR closely regulated to remain constant over range of BPs (80 - 180 mm Hg) Goal is to control blood flow though afferent and efferent arterioles – via • Reflex regulation  NS & Hormones (e.g.: angiotensin II and prostaglandins) • Autoregulation  (myogenic & tubuloglomerular feedback)

14. Autoregulation via Tubuloglomerular Feedback GFR  Macula densa cells: release paracrines juxtaglomerular cells (smooth muscle fibers from afferent arteriole): contract GFR  Fig 19-10

15. Distal tubule Efferent arteriole Glomerulus Bowman’s capsule GFR increases. 1 Proximal tubule Macula densa 2 Flow through tubule increases. 4 1 5 3 Flow past macula densa increases. Afferent arteriole Granular cells 3 2 2 4 Paracrine diffuses from macula densa to afferent arteriole. 5 Afferent arteriole constricts. Resistance in afferent arteriole increases. Collecting duct Hydrostatic pressure in glomerulus decreases. Loop of Henle GFR decreases.

16. Tubular Reabsorption Highly selective Amount of filtrate / day? and variable Urine production / day? % reabsorbed? Mostly transepithelial transport (examples: Sodium and glucose) Reabsorption may be active (Na+, glucose) or passive (urea) Fig 19-5 Figs 19-11(!!!) and 13

17. 1 Na+ is reabsorbed by active transport. Filtrate is similar to interstitial fluid. 2 Electrochemical gradient drives anion reabsorption. Na+ 1 2 Anions 3 Water moves by osmosis, following solute reabsorption. 3 H2O Concentrations of other solutes increase as fluid volume in lumen decreases. Permeable solutes are reabsorbed by diffusion. 4 4 K+, Ca2+, urea Tubular epithelium Extracellular fluid Tubule lumen

18. Saturation of Renal Transport Same 3 characteristics as discussed in mediatedtransport Transport maximum determined by • Saturation  Renal Threshold • Specificity • Competition Fig 19-14 Example: Glucose (Fig 19-15)

19. Secretion 2nd route of entry into tubules for selected molecules Mostly transepithelial transport (analogous to reabsorption). Depends mostly on membrane transport systems (usually 2o active transport) Provides mechanism for rapid removal of substances (most important for H+, K+, foreign organic ions and drugs such as penicillin etc.)

20. Excretion = Urine Output Excretion of excess ions, H2O, toxins, "foreign molecules“ "nitrogenous waste“ (NH4+ , urea) Depends on F, R, S (formula ?) Direct measurement of F, R, S impossible  infer from blood & urine analysis Kidneys clean or “clear” plasma of certain substances For any substance: Clearance = plasma volume completely cleared of that substance per minute

21. Clinical Importance of GFR and Clearance GFR is indicator for overall kidney function Clearance→ non-invasive way to measure GFR (inulin and creatinine) Substance is filtered and reabsorbed but not secreted  clearance rate < GFR Substance is filtered and secreted but not reabsorbed  clearance rate > GFR

22. Micturition Reflex Spinal cord integration: 2 simultaneous efferent signals In infant just simple spinal reflex Later: learned reflex under conscious control from higher brain centers Various subconscious factors affect reflex Fig 19-18

23. 1 2 3 Stretch receptors fire. Parasympathetic neurons fire. Motor neurons stop firing. Smooth muscle contracts. Internal sphincter passively pulled open. External sphincter relaxes. (b) Micturition Higher CNS input may facilitate or inhibit reflex. Stretch receptors Sensory neuron 1 Parasympathetic neuron 2 3 + – Motor neuron Tonic discharge inhibited Internal sphincter 2 3 External sphincter

24. Renal Failure & Artificial Kidney Hemodialysis: 3/week 4-8h/session Symptoms when < 25% functional nephrons due to: • Kidney infections • Chemical poisoning (lead, paint-thinner) etc.

25. Alternative: CAPD Continuous Ambulatory Peritoneal Dialysis

26. The End