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Chunling Jiang MD, Ph.D Professor of Physiology

Physiology. Chunling Jiang MD, Ph.D Professor of Physiology. chapter 8. The formation and excretion of urine. Major Functions of the kidneys. 1. Regulation of body fluid osmolality and volume 2. Regulation of electrolyte balance 3. Regulation of acid-base balance

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Chunling Jiang MD, Ph.D Professor of Physiology

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  1. Physiology Chunling Jiang MD, Ph.D Professor of Physiology

  2. chapter 8 The formation and excretion of urine

  3. Major Functions of the kidneys 1. Regulation of body fluid osmolality and volume 2. Regulation of electrolyte balance 3. Regulation of acid-base balance 4. Excretion of metabolic products and foreign substances 5. Production and secretion of hormones

  4.  Renin  Prostaglandins  kinins  1,25-dihydroxyvitamin D3  erythropoietin

  5. Formation of Urine Three steps: • Glomerular Filtration • Reabsorption of renal tubule and collecting duct • Secretion of renal tubule and collecting duct

  6. §1 Functional anatomy of the kidneys and renal blood flow

  7. 1. Nephron 1) structure (Fig.1)Glomerulus Renal corpuscle Renal capsule nephron Proximal tubule Renal tubule Thin segment of Henle’s loop Distal tubule

  8. proximal convoluted tubule Proximal tubule think descending limb of Henle’s loop thin descending limb Thin segment of Henle’s loop thin ascending limb think ascending limb of Henle’s loop Distal tubule distal convoluted tubule

  9. 2) classification (Fig.2) ----- two types Cortical nephron = superficial nephron Juxtamedullary nephron

  10. 2. Juxtaglomerular apparatus (Fig.2) (1) macula densa distal convoluted tubular epithelium modified histologically near the trigonum side (2) extraglomerular mesangial cells (3) granular cells ------ renin specialized myoepithelial cells in the media of afferent arteriole close to the glomerulus

  11. 3. Renal blood flow and its regulation • 1) normal value: 1200 ml/min 25% of the cardiac output The blood flow to the two kidneys is equal to about 25% of the cardiac output in resting persons. However, the kidneys constitute less than 0.5% of the total body weight.

  12. 2) Distribution cortex ------ 90% medulla ------ 8~10% Blood flow within the kidney is not distributed uniformly. It is much higher in the renal cortex than in the medulla. Cortical blood flow is 90% and the medullary blood flow is 8~10% of the total renal blood flow.

  13. 3) Autoregulation A. Experiment The kidneys, like most other organs , regulate their blood flow by adjusting the vascular resistance in response to change in arterial pressure . As illustrated in Figure 3 , this adjustment in resistance is so precise that blood flow remains relatively constant as arterial blood pressure changes between 90 and 180 mm Hg . GFR is also regulated over the same range of arterial pressure

  14. B. Concept: With a perfusing arterial pressure in the range of 80 ~ 180 mmHg, the renal blood flow does not vary in the denervated, isolated or intact kidneys. This indicates that the renal circulation is selfcontrolled or autoregulated.

  15. C. mechanism • Myogenic hypothesis • Tubuloglomerular feedback

  16. myogenic hypothesis

  17. Stretch stimuli to afferent arterioles Arterial perfusion pressure constrict resistance RBF remains relatively constant

  18. Mechanism 2 (Fig. 4) The second mechanism responsible for autoregulation of GFR and RBF, the flow-dependent mechanism, is known as tubuloglomerular feedback (Figure 4). This mechanism involves a feedback loop in which the flow of tubular fluid (or some other factor, such as the rate of NaCl reabsorption, which increases in direct proportion to flow is sensed by the macula densa of the juxtaglomerular apparatus (JGA) and converted into a signal that affects afferent arteriolar resistance and thus GFR.

  19. When GFR increases and causes the flow of tubular fluid at the macula densa to rise, the JGA send a signal that causes vasoconstriction to return RBF and GFR to normal levels . In contrast, when GFR and tubular flow past the macula densa decrease, the JGA sends a signal causing RBF and GFR mainly by changing the resistance of the afferent arteriole, but the mediator for this effect is controversial.

  20. Mediator:  NaCl  Adenosine  ATP

  21. 4. Neural control Standingexerciseemotional excitement Renal sympathetic nerve Constriction of renalblood vessels RBF

  22. 5. Humoral control Ad , NE RBFAⅡ , AVP(vasoconstrictor agents)prostaglandins atrial natriuretic peptide brady kinin RBF nitric oxide (NO)(vasodilator agents)

  23. §2 Glomerular Filtration

  24. 1. Glomerular filtration Glomerular filtration (Ultrafiltration) (Fig.5)  concept highly permeable to water and small molecules impermeable to macromolecules  Exp . 1 determinants of ultrafiltrate composition

  25.  Two important terms (1) Glomerular filtration rate (2) Glomerular filtration fraction

  26. （1） Glomerular filtration rate (GFR) 1.concept The quantity of glomerular filtrate formed per minuite by both kidneys GFR=Kf · PufKf =coefficient of filtration Puf =Effective filtration pressure (= net filtration pressure) 2. normal value: 125 ml/min 3. Significance sustain the formation of urine 4. Measurement Inulin clearance

  27. （2）Glomerular filtration fraction (FF) 1.concept the filtration rate as percentage of the total renal plasma flow that passes through both kidneys. FF=GFR= 125 = 19% RPF 660 2. normal value 19% 3. Significance ? be filtered

  28.  Filtration barrier 1. Permeability of glomerular membrane capillary endothelium basement membrane filtration slits of the podocytes (Fig.6)

  29. 2.Two features: (1) Molecule size selectivity Effective radius ＜ 1.8nm -------- filtered freely Effective radius ＞3.6nm -------- filtered impermeable 1.8nm ＜ Effective radius ＜3.6nm -------- filtered partially MW=10,000 MW= 70,000

  30. (2) Molecular electrical charge selectivity negatively charged glycoproteins → impede the passage of charged plasma substance such as plasma albumin.

  31. （4）Effective filtration pressure 1) concept EFP = PGC - (PBC +  GC) PGC--- -Glomerular Capillary Pressure PBC----Hydrostatic pressure in the Bow-man’s capsule  GC ----Colloid osmotic pressure in the capillary blood 2) significance (Fig. 4 ) In monkey arterial side =? What is the function? venule side =? What is the function?

  32. Fig. 4 The effective filtration pressure

  33. （5）Factors influencing GFR 1) EFP 2) RPF 3) Filtration membrane

  34. 1) EFP autoregulation BP 80~180 mmHg PGC and GFR constant BP 70 mmHg  PGC  EFP  GFR  BP 40 ~ 50 mmHg  PGC   EFP   GFR =0 no urine is excreted PGC

  35. ② GC GC EFP GFR   UV  a) Pathlogical condition: nephropathy syndrome  large amount of urine with protein (Proteinuria) b) Experimental condition: intravenous infusion of a large volume of saline  plasma protein concentration  GC 20 ml NS into rabbit vein one time  UV?

  36. ③ PBC PBC  EFP   GFR   UV  obstruction of the urinary tract by urinary stone

  37. 2) RBF RBF GFR Why? RBF GFR Question 1: How will  GC change when glomerular plasma is filtered across the filtration membrane. 3) Filtration membrane nephritis

  38. §2 Reabsorption of renal tubule and collecting duct

  39. 1. Sodium reabsorption 1) Site: 2) Mechanism: proximal tubule First step: from to tubular lumen tubular epithelium passive down concentration gradient down electrical gradient

  40. Second step : From to tubular epithelium peritubular capillary Active Sodium pump

  41. 2. Glucose reabsorption Completed reabsorbed 1) Site: proximal tubule (proximal convoluted tubule) Completed reabsorbed 2) Mechanism: active process (secondary) carrier cotransport facilitated by the presence of sodium (Fig. 9 ) (Fig. 10 )

  42. The value of plasma glucose concentration glucose in urine Normal range 80 ~ 120 mg/100ml (-) Increase 160 ~ 180 mg/100ml (+) (180 ~ 200 mg/100ml) This value is called the renal glucose threshold Further increase urine glucose >300 mg/100ml glucose reabsorption attains a maximal constant rate Tubular reabsorption of glucose (Tm or TmG) normal value: male : 375 mg/(min•1.73m2) female: 300 mg/(min •1.73m2)

  43. 3. chloride reabsorption 1) Site: renal tubule 99% reabsorbed 2) Mechanism: TAL ---------------- active mechanism:Na+/K+ - 2Cl- active cotransport other tubule ------- passive

  44. 4. water reabsorption 1) Site: renal tubule 99% reabsorbed 2) Mechanism: collecting duct --------- regulated by ADH other tubule --------- move passively

  45. §4 Secretion of renal tubule and collecting duct 1. secretion of K+ 2. Secretion of H+ 3. Secretion of NH3

  46. 1. secretion of K+ 1)Site ---- DCT CT 2)Mechanism: (Fig.11) K+ secretion is closely correlated to Na+ reabsorption ------passive process Na+ Na+ Na+ K+ k+ Tubular lumen cell blood

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