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Lecture 7

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BIOL 370
Dinu Nesan

Lecture 7: The Kidney - Transporter expression in epithelial cells controls solute uptake & deposition - Length of the loop is directly related to urine concentration - Single effect based on active NaCl transport - Countercurrent multiplication is a key to producing concentrated urine - Endocrine regulation of urine formation - Internal organ with multiple cell types “tubule” that maintains ion & water balance - Vertebrate kidney (6 roles in homeostasis) o Ion balance: Na o Osmotic balance: Urine volume o Blood pressure: Long term regulator o pH balance: w/ Respiratory system [H vs. HCO3] o Excretion of metabolic wastes & toxins o Hormone production: Renin that controls BP & Erythropoietin that regulates RBC synthesis - Mammalian kidney (Filtration  Reabsorption  Secretion  Excretion) o Outer cortex + Inner medulla o Kidney  Ureter  Urinary bladder  Urethra o Functional unit of the kidney: Nephron  Renal tubule: 1 layer of transport epithelium with specific transport functions @ different segments  Associated vasculature “blood vessels”: Glomerulus surrounded by Bowman’s capsule & capillary beds that surrounds the renal tubule o Cortical Nephrons: Loop of Henle is located predominately @ outer cortex  Peritubular capillaries are efferent arterioles that drains the cortical nephrons o Juxtamedullary Nephrons: Loop of Henle is located deep into the inner medulla  Vasa recta are efferent arterioles that drains the juxtaglometular nephrons - Function of the Kidney o Urine formation  Primary urine (introduced into the kidney via ultrafiltration)  Definitive urine (solution before elimination)  Ultrafiltration: Pressure driven mass flow o Filtration of blood at the glomerulus  Water & small solutes crosses the glomerular wall through filtration slits  Blood cells & large macromolecules are not filtered/retained  Fenestrated glomerular capillaries are lined with podocytes (with pedicles)  Mesangial cells in-between capillaries with podocytes to control blood pressure & filtration within glomerulus, they can initiate contraction to restrict blood flow  Glomerular Filtration Rate (GFR): The amount of filtrate production per minute @ glomerulus  Determined by balance of pressures across the glomerular wall (3) o Glomerular capillary hydrostatic pressure (60mm Hg) o Bowman’s capsule hydrostatic pressure (15mm Hg) o Oncotic pressure (30mm Hg): Osmotic pressure due to protein in blood  GFR = 15mm Hg  Intrinsic Regulation of GFR (3)  Myogenic regulation: Autocrine regulated, constriction/dilation of afferent arteriole o ↑GFR  ↑ Filtration pressure  ↑Capillary pressure  ↑ Afferent arteriolar pressure  Arteriole SM stretches  ↑ Constriction of afferent tubule ↓ GFR  Tubuloglomerular feedback @ Juxtaglomerular apparatus o Macula densa cells in the distal tubule can signal Juxtaglomerular cells in the afferent arteriole to control the diameter of the afferent arteriole o ↑ GFR  ↑ Filtration pressure  ↑ Capillary pressure  ↑ Flow @ macula densa of distal tubule  Chemical signal release  ↑ Constriction of afferent tubule  ↓ Capillary pressure  Mesangial control: Changes in filtration apparatus to alter the permeability of the glomerulus  Extrinsic Regulation of GFR (3 hormones)  Vasopressin: Antidiuretic to ↓ Loss of H2O  Renin-Angiotensin Aldosterone pathway: Increases Salt retention, ↓ H O2loss  Atrial Natriuretic peptide: Increases GFR  Filtrate flows from the Bowman’s capsule into the proximal tubule o Reabsorption where specific molecules in the filtrate are removed back to the blood  Most water & salt is reabsorbed using transport proteins & energy  Renal threshold: The rate of reabsorption is limited by the # of transporters o Concentration of specific solute can overwhelm re-absorptive capacity  Most reabsorption, and some secretion takes place at the proximal tubule +  Na cotransporter with inorganic or organic molecules  Water then follows by osmosis  Major driving force: Na /K ATPase @ basolateral membrane (Primary transporter)  E.g. Glucose reabsorption via secondary active transport o Basolateral Na /K ATPase pumps out Na (favorable inward Na gradient) @ apical sid+ + + o Apical: Na /Glucose cotransporter (Secondary transporter) & Na /H exchanger brings Na & glucose into the cells o Basolateral: Glucose permease allows glucose to cross via facilitated diffusion o Secretion of specific molecules into the filtrate  Molecules that are secreted include K , NH4, H , pharmaceuticles etc.  Loop of Henle: Descending (H 2 reabsorption) & Ascending (Solute reabsorption)  Descending limb: Permeable to water (aquaporin) o Water is reabsorbed & primary urine becomes more concentrated o 300mOsM  1200mOsM o H 2 enters from the apical side via osmosis  Ascending limb: Impermeable to water (no aquaporin) o Ion are reabsorbed & primary urine becomes dilute o Apical NKCC, K secreted @ apical side + + - + - + o Basolateral Na /K ATPase excretes Na, Cl/K cotransporter excretes Cl & K , Cl channel excretes Cl- o 1200 mOsM  100 mOsM  Distal tubule: Reabsorption completed  Hormone mediated regulation of solutes & water uptake, alters the level & activities of transport proteins o Adrenal gland cortex: mineralocorticoid o Hypothalamic-pituitary: vasopressin o Parathyroid: Parathyroid hormone  Apical: Na+-Cl- cotransporter takes both in, Na+ is excreted @ basolateral side via Na+/K+ ATPase & Cl- leaves @ basolateral side via Cl- channels, K+ is secreted  Ca2+ enters distal through Ca2+ channels, exits @ basolateral via Na+/Ca2+ exchanger & Ca2+ ATPase  Important site for H2O recovery via aquaporin expression  Collecting duct: Drains multiple nephrons & carries urine to renal pelvis  Principal cells: K+ secretion & Na+ reabsorption “Aldosterone responsive”  Intercalated cells: H+/HCO3- secretion “Acid-base balance” o H2O + CO2  Carbonic anhydrase  H+ & HCO3- o Apical H+/Na+ exchanger that excretes H+ & imports Na+ o Basolateral Na+/K+ ATPase excretes Na+ & imports K+  Whether K+ is excreted r reabsorbed depends on K+ homeostasis o Excretion of urine from the body  Urethra: 2x spincters of Smooth muscles  Spinal cord reflex arc controls the opening & closing of sphincters & this can be influenced by voluntary controls - Countercurrent Multiplier @ Loop of Henle o
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