Kidney Physiology 1 Functions of the Kidneys Regulate

Kidney Physiology 1

Functions of the Kidneys • • • Regulate plasma ionic composition Regulate plasma volume Regulate plasma osmolarity Regulate plasma p. H Remove metabolic waste products and foreign substances from plasma 2

Other Functions of the Kidneys • Secretes erythropoietin • Secretes renin • Activate vitamin D 3 to calcitriol for Ca+2 uptake from GI tract • Gluconeogenesis 3

Bowman’s capsule Proximal tubule Descending limb of loop begins Distal tubule Ascending limb of loop ends Collecting duct Descending limb (j) Parts of a nephron Ascending limb Loop of Henle To bladder 4 Figure 19 -1 j

Kidney Function • Filtration, reabsorption, secretion, and excretion Distal tubule Peritubular capillaries Efferent arteriole Glomerulus Afferent arteriole Bowman’s capsule Proximal tubule KEY = Filtration: blood to lumen = Reabsorption: lumen to blood Loop of Henle Collecting duct To renal vein = Secretion: blood to lumen = Excretion: lumen to external environment To bladder and external environment 5 Figure 19 -2

Kidney Function 6 Table 19 -1

The Filtration Fraction Efferent arteriole 80% Afferent arteriole 1 Plasma volume entering afferent arteriole = 100% Peritubular capillaries 2 20% of volume filters. Bowman’s capsule 4 >99% of plasma entering kidney returns to systemic circulation. 3 >19% of fluid is reabsorbed. 5 <1% of volume is excreted to external environment. Remainder of nephron Glomerulus 7 Figure 19 -4

The Renal Corpuscle Foot process of podocyte Pores in endothelium Filtration slit Basal lamina Capillary lumen Filtered material Lumen of Bowman’s capsule (d) Filtered substances pass through endothelial pores and filtration slits. 8 Figure 19 -5 d

Filtration What gets filtered out at glomerulus? – Water – Glucose – Ions/ Electrolytes (Na, Cl, K, Ca, Mg, P) – Amino acids – Bicarbonate, protons – Wastes (creatinine, urea) What doesn’t get filtered out at the glomerulus? 9

• Factors governing filtration rate at the capillary bed are: – Net filtration pressure – Total membrane surface area available for filtration (sympathetic control) – Filtration membrane permeability (podocytes) 10

Net Filtration Pressure 11

Glomerular Filtration Rate (GFR) • Measurement of functional capacity of the kidney • Dependent on difference in pressures between capillaries and Bowman’s space • Net filtration pressure drives glomerular filtration rate • High pressure= high filt. rate 12

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Regulation of Glomerular Filtration • Goal= regulate GFR • If the GFR is too high: – Needed substances cannot be reabsorbed quickly enough and are lost in the urine • If the GFR is too low: – Everything is reabsorbed, including wastes that are normally disposed of 14

GFR Regulation • Myogenic response – Similar to autoregulation in other systemic arterioles • Tubuloglomerular feedback – Involves Na+, K+, Cl- • Hormones and autonomic neurons (NE/Epi) – By changing resistance in arterioles – By altering the filtration coefficient 15

Myogenic Autoregulation • Goal is to keep GFR constant! BP aff. const GFR BP GFR aff. dial GFR 16

Tubuloglomerular Mechanism • Involve macula densa cells in the DCT • MD cells are sensitive to [Na+] 17

Tubuloglomerular Feedback Tubuloglomerular 1 GFR increases. Mechanism +] is high in DCT • If 2[Na Flow through tubule increases. GFR is too fast aff. 3 Flow past macula densa increases. art. constricts • If [Na+] is low in DCT 4 Paracrine from macula to afferent arteriole GFRdensa is too slow aff. art. vasodilates 5 Glomerulus Efferent arteriole Bowman’s capsule Macula densa 4 1 5 Granular cells Afferent arteriole 2 3 Proximal tubule Afferent arteriole constricts. Resistance in afferent arteriole increases. Collecting duct Hydrostatic pressure in glomerulus decreases. GFR decreases. Distal tubule Loop of Henle

ANS & Hormonal Regulation of GFR Sympathetic NS (NE, Epi) vasoconstricts afferent arteriole Angiotensin II vasoconstricts afferent arteroile 19

Hormonal Regulation(RAAS) Renin-Angiotensin-Aldosterone System: Renin is released from juxtaglomerular apparatus when: • Aff. art. MAP drops (JG cells don’t stretch as much) • Macula densa cells sense low plasma osmolarity or low [Na+] • Sympathetic NS input What does renin do? 20

Renin-Angiotensin-Aldosterone System RAAS animation

JG Apparatus Animation • http: //www. wisconline. com/objects/ap 2204. swf 22

Glomerular Filtration Rate (GFR) Can Be Estimated Creatinine clearance rate= volume of blood plasma that is cleared of creatinine/ time • Creatine is secreted as well but that can be blocked by the drug cimetidine • Used in conjunction with blood urea nitrogen(BUN) when chronic kidney disease is suspected Also use inulin excretion in the urine 23

Reabsorption, Secretion, and Excretion…. 24

Fluid and Electrolyte Homeostasis Na+ and water ECF volume and osmolarity K+ Cardiac and muscle function Ca 2+ Exocytosis, muscle contractions, and other functions H+ and HCO 3 – Body must maintain mass balance p. H balance Excretion routes: kidney and lungs 25

Reabsorption, Secretion, Excretion

Sodium reabsorption in the proximal tubule -active transport Filtrate is similar to interstitial fluid. Na+ reabsorbed 1 Na+ enters cell through membrane proteins, moving down its electrochemical gradient. 2 Na+ is pumped out the basolateral side of cell by the Na+-K+-ATPase. [Na+] high [Na+] low 1 Na+ Tubule lumen Proximal tubule cell 2 ATP [Na+] high K+ Interstitial fluid KEY = Membrane protein ATP = Active transporter

Glucose Reabsorption – Freely filtered at glomerulus – Normally 100% actively reabsorbed in proximal tubule – Normally, no glucose appears in urine 28

Glucose Reabsorption – Carrier proteins for glucose reabsorption • Apical membrane: secondary active transport • Basolateral membrane: facilitated diffusion 29 Figure 18. 15

Glucose Renal Curve 30 Figure 18. 16

Reabsorption, Secretion, Excretion 32

Cells in Late Distal Tubule and Collecting Duct That Regulate Balance – Principal cells • Water • Electrolytes – Intercalated cell • Acid-base 33

Distal Tubule Sodium Reabsorption Coupled to the secretion of K+ and H+ 34 Figure 19. 13 b

Effects of Aldosterone on Sodium Reabsorption – Aldosterone increases sodium reabsorption – Steroid hormone – Secreted from adrenal cortex – Acts on principal cells of distal tubules and collecting ducts • Increases number of Na+/K+ pumps on basolateral membrane • Increases number of open Na+ and K+ channels on apical membrane 35

Potassium Balance • Regulatory mechanisms keep plasma potassium in narrow range – Aldosterone plays a critical role • Hypokalemia – Muscle weakness and failure of respiratory muscles and the heart • Hyperkalemia – Can lead to cardiac arrhythmias • Causes include kidney disease, diarrhea, and diuretics 36

Effects of Aldosterone 37 Figure 19. 14

Reabsorption, Secretion, Excretion 38

Acid-Base Balance – Normal p. H of arterial blood = 7. 35– 7. 45 • p. H < 7. 35 = acidosis • p. H > 7. 45 = alkalosis – Complications with acid-base disturbance • • • Conformation change in protein structure Changes in excitability of neurons Changes in potassium balance Cardiac arrhythmias Vasodilation 39

Inputs and Outputs of Acid 40 Figure 19. 23

Renal Handling of Hydrogen and Bicarbonate Ions – Proximal tubule • Bicarbonate reabsorption coupled to hydrogen ion secretion – Distal tubule and collecting duct • Secretion of hydrogen ions coupled to synthesis of new bicarbonate ions 41

Bicarbonate Reabsorption 42 Figure 19. 25

Hydrogen Ion Secretion 43 Figure 19. 26

Urine Concentration Osmolarity changes as filtrate flows through the nephron (from 300 m. Osm/L to 100 m. Osm/L) Distal tubule Proximal tubule 1 Isosmotic fluid leaving the proximal tubule becomes progressively more concentrated in the descending limb. 300 m. Os. M 300 CORTEX 100 MEDULLA 1 3 2 600 m. Os. M Only water reabsorbed Ions reabsorbed but no water Permeability to water and solutes is regulated by hormones. Variable reabsorption of water and solutes 900 m. Os. M 2 Removal of solute in the thick ascending limb creates hyposmotic fluid. 3 Hormones control distal nephron permeability to water and solutes. 4 Urine osmolarity depends on reabsorption in the collecting duct. Loop of Henle 1200 m. Os. M Collecting duct 4 50– 1200 m. Os. M urine excreted 44 Figure 20 -4

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Countercurrent exchange in the medulla of the kidney 46

Countercurrent Exchange Animation • http: //www. colorado. edu/intphys/Class/IPHY 3430 -200/countercurrent_ct. html 47

Water Reabsorption in Collecting Duct No ADH 48 Figure 20 -5 b

with ADH 49 Figure 20 -5 a

Antidiuretic Hormone

Effects of ADH on Principal Cells 51 Figure 19. 10

Regulation of Blood Pressure Figure 21– 13 Short-Term and Long-Term Cardiovascular Responses

Micturition • The storage of urine and the micturition reflex Higher CNS input Relaxed (filling) state Bladder (smooth muscle) Internal sphincter (smooth muscle) passively contracted External sphincter (skeletal muscle) stays contracted Tonic discharge (a) Bladder at rest 53 Figure 19 -18 a

Micturition Stretch receptors Sensory neuron 1 Parasympathetic neuron 2 Higher CNS input may facilitate or inhibit reflex 3 2 Parasympathetic neurons fire. Motor neurons stop firing. Motor neuron Internal sphincter External sphincter 3 1 Stretch receptors fire. 2 Tonic discharge inhibited 3 Smooth muscle contracts. Internal sphincter passively pulled open. External sphincter relaxes. (b) Micturition 54 Figure 19 -18 b

Micturition Stretch receptors 1 Sensory neuron 1 Stretch receptors fire. Internal sphincter External sphincter (b) Micturition 55 Figure 19 -18 b, step 1

Micturition Stretch receptors 1 Sensory neuron Parasympathetic neuron 2 Higher CNS input may facilitate or inhibit reflex 1 Stretch receptors fire. 2 Parasympathetic neurons fire. Motor neurons stop firing. Motor neuron 2 Internal sphincter External sphincter Tonic discharge inhibited (b) Micturition 56 Figure 19 -18 b, steps 1– 2

Micturition Stretch receptors Sensory neuron 1 Parasympathetic neuron 2 Higher CNS input may facilitate or inhibit reflex 3 2 Parasympathetic neurons fire. Motor neurons stop firing. Motor neuron Internal sphincter External sphincter 3 1 Stretch receptors fire. 2 Tonic discharge inhibited 3 Smooth muscle contracts. Internal sphincter passively pulled open. External sphincter relaxes. (b) Micturition 57 Figure 19 -18 b, steps 1– 3