RENAL PHYSIOLOGY. Physiology Unit 4

Transcription

1 RENAL PHYSIOLOGY Physiology Unit 4

2 Renal Functions Primary Function is to regulate the chemistry of plasma through urine formation Additional Functions Regulate concentration of waste products Regulate mineral balance Regulates body water balance Regulate blood pressure (MAP) Regulate plasma ph Produce and secrete hormones

3 Renal Tubular Membrane Transport 1. Filtration Blood to renal tubules Out of your blood Non specific/bulk Flow 2. Reabsorption Renal tubules to blood Into your blood 3. Secretion Blood to renal tubules Out of your blood Highly specific 4. Excretion Urine

4 Glomerular Filtration Rate (GFR) Filtration of Plasma GFR = Volume of filtrate produced by both kidneys per minute GFR rates 115 ml/min in women (166 L/day) 125 ml/min in men (180 L/day) 7.5 L/hour about 45 gallons/day Entire plasma volume (3L) is filtered over 60 times a day! Factors that determine GFR Permeability of the filter - fixed Surface area for filtration - fixed Net filtration pressure (NFP) **can be regulated**

5 Renal Corpuscle The Filter Renal corpuscle is the filter The permeability of the filter determined by the size of pore and electrical charge Ultrafiltration is the result of a pore size that is 0.01 microns Electrical charge Negatively charged surface of podocytes prevents movement of proteins Filtrate is protein-free and acellular

6 Renal Corpuscle The Filter Starling forces in the glomerulus favor filtration NFP = 16mmHg Higher than peripheral NFP of 10mmHg Ultrafiltration is driven by a high hydrostatic pressure in the glomerulus that is created by the differences in the diameter of the afferent and efferent arteriole The high hydrostatic pressure forces small molecules through the filter into the nephron Water, urea, uric acid, creatinine, amino acids, minerals (ions)

7 Renal Net Filtration Pressure NFP is a factor that determines GFR NFP is subject to physiological control Regulation of the afferent and efferent arterioles Cause changes in vessel diameter Vasoconstriction/Vasodilation can change NFP NFP = GFR NFP = GFR

8 Nephrons Cortical Nephrons LOH extends just slightly into the renal medulla Peritubular capillaries receive products of reabsorption Primary function is reabsorption Juxtamedullary Nephrons LOH extends deep into the renal medulla Vasa recta follow the LOH and receive H 2 0 from collecting ducts Primary function is water reclamation

9 Na + Reabsorption Cortical Nephrons tube blood driven by the Na + /K + /ATPase pump The majority of reabsorption occurs at the PCT The Na + /K + /ATPase pump establishes and maintains a low [Na + ] inside the tubular cells The movement of Na + is used to move other molecules out of the lumen of the tube and into the tubular cells Cotransport/Countertransport H +, glucose, amino acids Mineral Balance

10 Glucose Reabsorption Cortical Nephrons Average Blood Sugar Level The amount of glucose in plasma 125 mg/dl Range is 100 mg/dl (fasting) 140 mg/dl (2 hours post-meal) Renal Threshold of Glucose (RTG) Concentration 125 mg of glucose per deciliter of filtrate in PCT Threshold of filtered glucose is >180 mg/dl If RTG is exceeded, the result is glucosuria (glucose in the urine) Causes dehydration (called osmotic diuresis) Usually caused by diabetes mellitus..how?? Carrier Mediated Transport of Glucose Can Become Saturated Rate Glucose reabsorption happens in the proximal convoluted tubules SGLT-1/SGLT-2 transporters are found on the apical of the renal tubular cells The transport maximum of glucose is 325 mg/min (this is a rate) 100% of glucose filtered 100% of glucose reabsorbed 1dL=100mL Mineral Balance

11 Glucose Reabsorption Mineral Balance Apical surface Basolateral surface Proximal Convoluted Tubule

12 H 2 O Reabsorption Cortical Nephrons Water Balance About 65% of H 2 O is reabsorbed at the PCT The Na + /K + /ATPase pump establishes and maintains a low [Na + ] inside the tubular cells The movement of Na + is used to move H 2 O out of the lumen of the tube and into the tubular cells Water continues to chase the salt into the peritubular capillaries

13 Juxtamedullary Nephrons Water Balance

14 Regulation of Water Balance Water Balance Amount of of filtrate produced 180 L/day 180 L of water moved out of your blood to form filtrate 99% of water is reabsorbed Average urine output 1.8 L/day Obligatory water loss 0.5 L/day How do you get water to move back into your blood?

15 Antidiuretic Hormone (ADH) The regulation of water balance Water Balance ADH is the primary regulator of body water balance ADH is released from the posterior pituitary ADH causes the insertion of aquaporins in the collecting ducts Without aquaporins, the CD is impermeable to H 2 O

16 Antidiuretic Hormone (ADH) The regulation of water balance Water Balance The stimulus for secretion of ADH is plasma osmolarity Monitored by osmoreceptors in the hypothalamus Plasma osmolarity below threshold Osmoreceptors are not activated ADH secretion is suppressed Plasma osmolarity above threshold Osmoreceptors stimulate neurons to secrete ADH Another stimulus for secretion of ADH is a decrease in blood volume

17 Countercurrent Multiplier System Juxtamedullary Loop of Henle and Vasa Recta Water Balance Descending limb Impermeable to NaCl Permeable to H 2 O Ascending limb Permeable to NaCl Impermeable to H 2 O Creates a hyperosmotic gradient in the IF of the medulla of the kidney Hyperosmotic gradient promotes H 2 O reclamation from filtrate H 2 O moves from the CD through aquaporins into the Vasa Recta

18 Regulation of Blood Pressure Blood Pressure One of the functions of the kidneys is to regulate BP Regulating BP - regulates MAP The kidneys regulate BP is by adjusting blood volume Blood volume is adjusted by reabsorption and excretion of Na + at the DCT How do you get water to move to adjust blood volume?

19 Water Chases the Salt The reabsorption/excretion of Na + will adjust BP Blood Pressure Reabsorption of Na + will increase blood pressure Na + reabsorption H 2 O reabsorption blood volume blood pressure A response to decreased BP Excretion of Na + will decrease blood pressure Na + reabsorption H 2 O reabsorption blood volume blood pressure A response to increased BP

20 Sensory Receptors Provide sensory feedback to regulate BP Blood Pressure Macula Densa Patch of cells in the DCT where the ALOH meets the DCT Chemoreceptors Sensitive to a drop in [Na + ] Juxtaglomerular (JG) Cells Secretory cells surround the afferent arteriole (secrete an enzyme) Baroreceptors Sensitive to a drop in BP

21 Regulation of Blood Pressure RAAS - Renin-Angiotensin Aldosterone System Blood Pressure Activation of RAAS increases BP Renin (angiotensinogenase) Cleaves Angiotensinogen to Angiotensin I Angiotensin I is converted to Angiotensin II by ACE ACE: angiotensin converting enzyme Angiotensin II Strong vasoconstrictor (increases BP) Stimulates Aldosterone production Aldosterone Increases blood volume (increases BP) 1. Causes vasoconstriction (angiotensin II) 2. Increases blood volume (aldosterone) What would an ACE inhibitor do to BP?

22 Regulation of Blood Pressure Renin (RAAS) Blood Pressure Renin is an enzyme that converts angiotensinogen to angiotensin I (in plasma) Renin is secreted by JG cells in response to: Decrease in NFP Detected by JG cells Decreased [Na + ] in DCT Detected by the macula densa Sympathetic activation

23 Regulation of Blood Pressure Angiotensin II (RAAS) Blood Pressure Angiotensinogen Produced by the liver Renin converts to Angiotensin I In plasma Angiotensin I ACE converts to Angiotensin II In the lungs Pulmonary endothelial cells Produced in the lungs to prevent pulmonary vasoconstriction Also because the half life is 16 seconds Angiotensin II Causes vasoconstriction Increases BP Stimulates secretion of Aldosterone Increases BP Stimulates thirst Increases BP Stimulates the production of ADH from the posterior pituitary Increases BP

24 Regulation of Blood Pressure Aldosterone (RAAS) Blood Pressure Region of Adrenal Cortex Zona Glomerulosa Zona Fasciculata Zona Reticularis Hormones Released Mineral Corticoids Glucocorticoids Androgens Example Aldosterone Cortisol DHEA Aldosterone stimulates Na + reabsorption in the DCT and CD

25 Regulation of Blood Pressure Aldosterone (RAAS) Blood Pressure Stimuli for Aldosterone: Serum potassium levels Increased plasma [K+] Angiotensin II Acidosis Increased ACTH Stretch receptors in the atria Response to decreased stretch

26 Regulation of Blood Pressure Aldosterone (RAAS) Blood Pressure Na + reabsorption 90% reabsorbed in PCT Without Aldosterone Total Na + reabsorption is 98% 8% Na + reabsorbed in DCT 2% Na + excreted in urine With Aldosterone Total Na + reabsorption is 100% K + is excreted

27 Regulation of Blood Pressure Atrial Natriuretic Peptide (ANP) Blood Pressure Atrial Natriuretic Peptide (ANP) Produced by atrial myocardial cells Stimulus for ANP: Atrial stretch - high blood volume Increased sympathetic activation Vasoconstriction Exercise The Response to ANP Reduces Na + reabsorption in the DCT and CD Causes natriuresis Increases renal Na + excretion Causes diuresis Decreases blood volume Decreases secretion of renin Decreases TPR vasodilation

28 Regulation of Blood Pressure Atrial Natriuretic Peptide (ANP) Blood Pressure Vasodilates afferent arteriole Decreases GFR Na + reabsorption Decreases Na + permeability in the DCT and CD Na + reabsorption Inhibits aldosterone secretion Na + reabsorption

29 Regulation of Acid-Base Balance Acid/Base Balance Kidneys maintain plasma ph Acid is produced by cellular metabolism H + production increases Increased metabolism Dietary intake of acidic foods Renal regulation of ph 100% reabsorption of filtered HCO 3 - Using hydrogen phosphate as an additional buffer Addition of new HCO 3 - Excretion of NH 4 Daily H + production 100 mmol/day Un-buffered urine Excreting 1-2L of urine only eliminates 1mmol/day of H + Does not match the production of acid Buffered urine HCO 3- is the primary buffer in urine

30 Regulation of Acid-Base Balance 100% Reabsorption of HCO 3 - Acid/Base Balance 100% reabsorption of filtered HCO 3 - PCT, LOH, cortical CD The bicarbonate that is filtered acts as a buffer to accept hydrogen ions Renal tubular cells have carbonic anhydrase HCO 3- production matches HCO 3 - excretion Results in 100% reabsorption This reaction is ongoing

31 Regulation of Acid-Base Balance Addition of New HCO 3 - Acid/Base Balance Increased metabolism produces more acid more buffer is needed Filtered hydrogen phosphate is used as an additional buffer in urine Bicarbonate reaction in the renal tubular cells: New HCO 3 - is produced Secretion of H + HPO 4 2- combines with H + to form H 2 PO 4 - Dihydrogen phosphate is excreted

32 Regulation of Acid-Base Balance Addition of New HCO 3- AND Excretion of NH 4 Acid/Base Balance Renal ammoniagenesis (PCT) Renal NH 4+ excretion is derived from intrarenal production not from NH 4 + filtration Renal metabolism of glutamine produces: HCO 3 - Addition of new HCO 3 - NH 4 + Excreted Promotes H + excretion