Ch 17 Physiology of the Kidneys

Transcription

1 Ch 17 Physiology of the Kidneys Review Anatomy on your own

2 SLOs List and describe the 4 major functions of the kidneys. List and explain the 4 processes of the urinary system. Diagram the filtration barriers a H 2 O molecule will pass as it travels from the blood into the nephron and illustrate the anatomical structures and mechanisms by which filtration can be controlled. Define GFR and give the average value for GFR. Describe the hydrostatic and osmotic pressures that contribute to glomerular filtration and indicate the direction of fluid movement favored by the net pressure. Diagram how GFR can be influenced by: variable resistance in afferent and efferent renal arterioles. myogenic and tubuloglomerular autoregulatory mechanisms. hormonal control and neural control. Describe active and secondary active transport and passive reabsorption mechanisms used by the kidney to accomplish reabsorption of Na + and glucose. Create a generalized graph of the reabsorption of glucose in order to demonstrate how protein-mediated renal transport can reach saturation. Mark on the graph where transport maximum and renal threshold occur. Explain the connection between GFR and Clearance rate and explain clinical significance of the clearance Apply the equation E = F R + S to analyze renal handling of a substance. Diagram the involuntary micturition reflex and incorporate the voluntary control influence exerted by higher brain centers.

3 17.1 FUNCTION OF THE KIDNEYS Kidneys function in H 2 O & solute concentration homeostasis ECF volume ( BP) osmolarity, electrolyte concentration ph homeostasis (acid-base balance) Excretion of wastes & foreign substances Hormone and enzyme production Functional unit?

4 Four Processes of Urinary System 1. Filtration 2. Reabsorption 3. Secretion 4. Excretion Related by equation: E = F - R + S 180 L / day filtered, >99% reabsorbed, 1.5 L / day excreted Fig 19-4

5 17.2 GLOMERULAR FILTRATION = Movement of fluid from blood to lumen of nephron (rel. nonspecific process) Capillaries are Once in lumen: Considered outside body Composition of filtrate?

6 Glomerular Ultrafiltrate: Passage Across 3 Barriers Some small molecules (Ca 2+, low m.w. fatty acids) bind to plasma proteins? Compare to Fig 17-9

7 3 Types of Pressures Influence Filtration 1. Hydrostatic pressure in capillaries 2. Colloid osmotic pressure 3. Hydrostatic pressure in Bowman s capsule Net driving pressure?

8 Glomerular Filtration Rate = GFR Describes filtration efficiency: Amount of fluid filtered per unit of time Average GFR? Fig Total blood volume is filtered every 40 minutes Most must be reabsorbed immediately

9 GFR Closely Regulated to remain constant over wide range of MAPs ( mm Hg) Goal is to control blood flow through afferent and efferent arterioles RBF? P H? GFR? vasodilation

10 GFR Regulation either via 1. Renal Autoregulation myogenic tubuloglomerular feedback 2.Reflex regulation NS Hormones (e.g.: angiotensin II and prostaglandins)

11 17.3 TUBULAR REABSORPTION H 2 O reabsorption via osmosis (PCT and CD Electrolyte reabsorption highly selective and variable Mostly transepithelial transport (examples: Na + and glucose) Reabsorption may be active (Na +, glucose) or passive (urea)

12 Na + Reabsorption in Proximal Tubule

13 PCT and LOH Reabsorption 65% of salt and water reabsorbed in PCT An additional 20% reabsorbed in LOH Happens continuously and is unregulated Final 15% of water ( 27 L) absorbed in CD under hormonal control Fluid entering loop of Henle is isotonic to extracellular fluids

14 Countercurrent Multiplier not covered!

15 Fig Reabsorption in LOH

16 Renal Medulla Creates Concentrated Urine Body fluid osmolarity :? Urine osmolarity can vary from 50 to 1200 mosm. Reabsorption of varying amounts of H 2 O and Na + established by LOH and CD How is H 2 O absorbed? Only by due to the high medullary interstitial osmolarity Key player: ADH =, or

17 Collecting Duct: Effect of ADH Released from? when? Controls water permeability of last section of DCT and all of CD Regulates aquaporin channels How? ADH regulated via 1. ECF osmolarity 2. BP and BV

18 ADH Stimulation of Aquaporin Channels Fig 17-19

19 Clinical Application Diabetes insipidus A. Neurogenic / Central: B. Nephrogenic: C. Also: Dipsogenic and gestational Desmopressin for A and C Nocturnal enuresis

20 Review: Concentrated vs. Dilute Urine In presence of ADH: Insertion of H 2 O pores At maximal H 2 O permeability: Net H 2 O movement stops at equilibrium Maximum osmolarity of urine? No ADH: DCT & CD impermeable to H 2 O Osmolarity can plunge to ~ 50 mosm

21 ADH No ADH

22 17.4 RENAL PLASMA CLEARANCE Kidneys must also remove excess ions and wastes from the blood Renal Clearance GFR begins this process Reabsorption returns some substances to blood (decreases renal clearance) Secretion moves substances from peritubular capillaries into tubules (increases renal clearance) Fig 17.21

23 Clinical Importance of GFR and Clearance GFR is indicator for overall kidney function Clearance non-invasive way to measure/estimate GFR (creatinine and inulin) If substance is filtered and reabsorbed but not secreted clearance rate > or?< GFR If substance is filtered and secreted but not reabsorbed clearance rate > or?< GFR Inulin used as markers of glomerular filtration rate because it is filtered but not reabsorbed or secreted Easier to use Creatinine

24 Mechanism of Reabsorption in the PCT Complete reabsorption in PCT via 1. 2 active transport with sodium = 2. facilitated diffusion = 3. simple diffusion Fig 17.24

25 Reabsorption of Glucose Na + linked Glucose Reabsorption in Proximal Tubule

26 Characteristics of Renal Transport As in all mediated transport Transport maximum determined by 1. Specificity 2. Competition 3. Saturation Renal threshold, determines transport maximum.

27 Saturation of Mediated Transport Fig 19-9 Copyright 2010 Pearson Education, Inc.

28 Glucose Handling by the Nephron Fig Copyright 2010 Pearson Education, Inc.

29 Glycosuria Diabetes mellitus Untreated DM high blood glucose levels Similarities and differences to diabetes insipidus? Osmotic Diuresis Polyuria and polydipsia

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

31 Excretion = Urine Output Excretion of H 2 O, excess ions, nitrogenous waste, toxins, and other foreign molecules 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

32 Micturition Reflex Spinal cord integration: 2 simultaneous efferent signals Infant: Simple spinal reflex Later: Learned reflex under conscious control from higher brain centers Various subconscious factors affect reflex Fig 19-14

33 17.5 RENAL CONTROL OF ACID-BASE BALANCE Kidneys maintain blood ph by reabsorbing bicarbonate and secreting H +. Normal urine ph? Fig 17.29

34 Acid Base Balance Normal blood ph? Enzymes & NS very sensitive to ph changes Kidneys have K + /H + antiporter Importance of hyperkalemia and hypokalemia Acidosis vs. alkalosis Fig 20-14

35 Acidosis Respiratory acidosis due to alveolar hypoventilation accumulation of Possible causes: Respiratory depression, increased airway resistance ( ), impaired gas exchange (,,, ) Metabolic acidosis due to gain of fixed acid or loss of bicarbonate Possible causes: lactic acidosis, ketoacidosis, diarrhea Buffer capabilities exceeded once ph change appears in plasma. Options for compensation?

36 3 Mechanisms to Deal with ph Changes Buffers 1 st defense, immediate response Ventilation 2 nd line of defense, can handle ~ 75% of most ph disturbances Renal regulation of H + & HCO 3 - final defense, slow but very effective

37 Renal Compensation for Acidosis Reabsorption of HCO 3 - and Secretion of H + Compare to Fig 17.29

38 Alkalosis much rarer Respiratory alkalosis due to alveolar hyperventilation in the absence of increased metabolic CO 2 production Possible causes: Anxiety with hysterical hyperventilation, excessive artificial ventilation, aspirin toxicity, fever, high altitude Compensation? Metabolic alkalosis due to loss of H + ions or shift of H + into the intracellular space. Possible causes: Vomiting or nasogastric (NG) suction; antacid overdose Compensation?

39 Renal Failure & Artificial Kidney Symptoms when < 25% functional nephrons Hemodialysis: 3/week 4-8h/session Causes 1. Chronic: Diabetes, HBP 2. Acute: 1. Kidney infections 2. Chemical poisoning (lead, paint-thinner) etc.

40 Alternative: Continuous Ambulatory Peritoneal Dialysis CAPD