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Renal Physiology

Renal Physiology. The kidneys 5 functions Regulation of body fluid volume Regulation of Osmolarity & Ion Balance Regulation of pH Excretion of Wastes Synthesis of Hormones. Kidney Anatomy. Blood enter/leaves via Renal artery/vein. Urine leaves via Ureter. Nephron.

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Renal Physiology

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  1. Renal Physiology • The kidneys 5 functions • Regulation of body fluid volume • Regulation of Osmolarity & Ion Balance • Regulation of pH • Excretion of Wastes • Synthesis of Hormones

  2. Kidney Anatomy Blood enter/leaves via Renal artery/vein Urine leaves via Ureter

  3. Nephron

  4. Nephron: 4 ways substances move Blood Filtrate Urine

  5. Filtration Bowman’s Capsule Efferent Arteriole Podocyte Glomerulus Proximal tubule Glomerular capillary Afferent Arteriole ~ 20% PLASMA entering Glomerulus enter NEPHRON by BULK FLOW!

  6. What is filtered? VIDEO Filtrate in Nephron contains Plasma (ions, waters, small molecules) It SHOULD NOT contain large proteins or blood cells (they can’t fit through Pores/Slits)

  7. How much is filtered? Normal: 125 ml/Min = 180 L/day = Glomerular Filtration Rate Your plasma is filtered 60 times per day! Blood flow to kidney MUST be HIGH

  8. Control of Filtration Rate Local mechanisms alter the diameter of the afferent arteriole Bowman’s Capsule Efferent Arteriole Podocyte Macula Densa (Ascending LOH) Glomerulus Proximal tubule Glomerular capillary Afferent Arteriole Macula Densa releases local control chemicals (ATP, ADP, NO)

  9. Control of Filtration Rate Sympathetic ANS: vasoconstriction of afferent & efferent arterioles REDUCED FLOW, decreased Filt. Rate Hormones: Angiotensin II > vasoconstriction > decreased Filt. Rate Prostaglandins > vasodilation > increased Filt. Rate Angiotensin II & Prostoglandins also affect the size of the filtration slits!

  10. Reabsorption: What is reabsorbed? 99% of molecules entering renal tubule are reabsorbed into peritubular capillaries! Na+, K+, Ca2+, Glucose, Water, Cl-, Urea, small proteins

  11. ReabsorptionActive Transport ofNa+ DRIVES REABSORPTION!!!!!!!Everything else is DIFFUSION (electrical or concentration gradient) Na+ reabsorbed by Active Transport! Na+ Electrical Gradient Anions (-) reabsorbed Na+ hypertonic Anions Osmotic gradient (high ISF) Water reabsorbed Water High Renal Tubule Conc. Other molecule diffuse down conc. gradients Ca2+ K+ Urea Renal Tubule ISF

  12. Glucose Reabsorption 100% of Glucose is reabsorbed @ normal blood glucose levels Diabetes mellitus > elevated blood glucose >> glucosuria

  13. Secretion FROM Peritubular Capillary TO Renal Tubule Organic molecules (too big for Filtration), K+, H+ are key molecules SECRETED

  14. Penicillin (Antibiotic)Secretion Penicillin is filtered & secreted @ 4 hours: plasma conc. of penicillin = 0 100% of Penicillin is EXCRETED by 4 hours

  15. Excretion 180 L/Day - 178.5 L/Day + 0 = 1.5 L/Day Water 200 mg/min - 200 mg /min + 0 = 0 mg/min Glucose

  16. Fluid and Electrolyte Balance Why does your body maintain fluids and electrolytes in a balanced state? Na+ & Water determine blood volume and pressure K+ is essential for resting membrane potential in excitable cells H+ and HCO3-are key in maintaining pH Ca2+ is a key signaling ion Integrative, multisystem task; kidney, cardiovascular, respiratory, neural

  17. Water Homeostasis 8 – 8oz waters 9 oz from food Living in DRY Places can INCREASE Diarrheacan INCREASE You body maintains water homeostasis, PRIMARILY, by altering urine volume!

  18. WaterReabsorption Important: Water reabsorption in the LOH is ALWAYS on (unless drugs are present) Your body ONLY alters water reabsorption in the distal tubule & collecting duct!

  19. Variable Water Reabsorption Vasopressin (ADH) & Aquaporins Vasopressin (ADH) & Aquaporins Antidiuretic Hormone (ADH) = Vasopressin Antidiuresis = little concentrated urine Diuresis = lotsa dilute urine

  20. What drives ADH release? • Blood Osmolarity • High OSM > Increase ADH • Low OSM > Decrease ADH • 2) Blood Volume • 3) Blood Pressure • Low BP> Increase ADH • High BP> Decrease ADH

  21. Na+ balance is intimately tied to blood pressure and volume homeostasis! Sodium Homeostasis 25% of Adult Americans are Hypertensive Hypertension = Leading Cause of Cardiovascular Death! Excess SALT Intake is Major contributing Factor Americans consume : 3.5 - 8 grams per day NAS recommended: 2 grams per day

  22. Effect of ingested Sodium on Kidney Function ASSUME: Each day you consume 2 grams of salt This could increase you blood osmolarity to 307 mosm/L Cardiovascular Atrial natriuretic peptide (ANP) Aldosterone Pathway Renal = Renin-Angiotensin-Aldosterone Pathway

  23. Sodium Reabsoption is variable ONLY in the distal tubule and collecting duct Aldosterone: Adrenal hormone that regulates Na+ reabsorption Aldosterone : more Na-K ATPase pumps more K+ and Na+ channels

  24. Aldosterone Release controlled by Osmolarity Adrenal Cortex Reduce Aldosterone Synthesis Sodium Excretion Aldosterone Release is also controlled by Blood pressure Renin-Angiotensin-Aldosterone Pathway

  25. constantlyproduces Angiotensinogenin the plasma Liver produce Low Blood Pressure Renin Kidney ANG I in plasma contains ACE(enzyme) Blood vesselendothelium ANG II inplasma Sympathetic Activation Heart Vasculature Adrenal Cortex Hypothalamus ADH Synthesis Vasoconstrict Aldosterone Synthesis Thirst enhances Water Reabsorption Sodium Reabsorption Increase Blood Volume Increase Blood Pressure

  26. Aldosterone Release controlled by Osmolarity Adrenal Cortex Reduce Aldosterone Synthesis Sodium Excretion Aldosterone Release is also controlled by Blood pressure Renin-Angiotensin-Aldosterone Pathway

  27. constantlyproduces Angiotensinogenin the plasma Liver ACE inhibitor drug for HYPERTENSION High Blood Pressure produce Renin Kidney ANG I in plasma contains ACE(enzyme) Blood vesselendothelium ANG II inplasma Sympathetic Activation Heart Vasculature Adrenal Cortex Hypothalamus Reduce ADH Synthesis Vasodilation Reduce Aldosterone Synthesis Thirst enhances Water Excretion Sodium Excretion Reduce Blood Volume Lower Blood Pressure

  28. Adrenal Cortex Reduce Aldosterone Synthesis Cardiovascular Reduce ANG II Sodium Excretion

  29. Atrial Natiuretic Peptide (ANP) BP Blood Volume Atrial Stretch ANP secretion Increase GFR Decreased ADH Decreased Sympathetic Decreased Renin Decreased Aldosterone Increase Water Excretion Increase Na+ Excretion Lower Blood Volume Lower Blood Pressure

  30. General Pathways for Sodium, Blood Volume, and Blood Pressure Homeostasis Adrenal Cortex Increase ANP Decrease Symp. Reduce Aldosterone Synthesis Reduce ANG II Sodium Excretion

  31. pH Review More H+ ions Few H+ ions

  32. Acid-Base Homeostasis: pH pH is affected by the concentration of H+ Your body maintains pH at 7.38-7.43, precisely! Low pH = acidosis (reduced CNS function) High pH = alkalosis…hyperexcitable membranes (diaphragm arrest!)

  33. Where do acids (H+ ions) come from? H+ is always being produced ….so… H+ always needs to be excreted

  34. 3 mechanisms of pH homeostasis • Buffering systems • Lungs • Kidneys – 25% 75% Loss of any mechanism can lead to ACIDOSIS > lowered blood pH

  35. The buffer of H+ is HCO3- CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- Law of Mass Action CO2 + H2O H2CO3 H+ + HCO3- H+ combines with HCO3- to BUFFER the effect of increase H+ CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- More CO2 & H2O are produced by buffering action HCO3- is used up HCO3- is 600,000 x more concentrated than H+ in blood

  36. Respiratory Regulation of pH CO2 + H2O ← H2CO3 ← H+ + HCO3- Carotid & Aortic chemoreceptors Brainstem chemoreceptors Increased Ventilation Rate and Volume CO2 + H2O → H2CO3 → H+ + HCO3-

  37. Renal Regulation of pH- 25% Filtered HCO3- cannot be directly reabsorbed Most Filtered H+ is not directly excreted • Reabsorbtion of HCO3- ; indirect excretion of H+ Always ON Hydrogen Phosphate Ion HPO42- H+ HCO3- H+ HCO3- HCO3- ATPase REABSORBTION H2CO3 H2CO3 C.A. C.A. H2O + CO2 H2O + CO2 REABSORBTION Amino Acids NH3 HCO3- HCO3- H2PO4- Phosporic Acid NH4+ Ammonium Ion Peritubular Capillaries PROXIMAL Renal Tubule Nephron Cell Renal ISF

  38. Skeletal System: Functions • Support • Movement • Calcium Homeostasis!

  39. Parathyroid Gland Ca2+ receptors are linked to G-protiens that control the release of PTH (parathyroid hormone)!

  40. Calcium Homeostasis • Ca2+ Receptors in Parathyroid gland monitor blood Ca2+ levels • If Ca2+ Low – PTH released • Bone breaks down releasing Ca2+ • Kidney reabsorbs Ca2+ • Intestines uptake more Ca2+ • If Ca2+ High – PTH syn. inhibited • Bone building, incorporating Ca2+ • Kidney does not reabsorb Ca2+ • Intestines do not uptake Ca2+ Bone accounts for 99% of the calcium reserves in your body!

  41. Osteoporosis Osteoporosis is linked to long-term low dietary intake of Ca2+ Bone Loss > Bone Building… so that Ca2+ levels are maintained Ca2+ is a key ion everywhere!!!! Women are more susceptible than men….lower bone mass & menopausal estrogen decrease

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