GFR and its Clinical Importance - Renal function
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GFR and its Clinical Importance - Renal function

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Clinical Importance of GFR : Renal System

Clinical Importance of GFR : Renal System

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GFR and its Clinical Importance - Renal function GFR and its Clinical Importance - Renal function Presentation Transcript

  • Dr Manish Chandra Prabhakar MGIMS Sewagram
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •       1- Regulation of plasma ionic composition 2- Regulation of plasma volume 3- Regulation of plasma osmolarity 4- Regulation of plasma hydrogen ion concentration (pH) 5- Removal of metabolic wastes and foreign substances 6- Secondary endocrine organ
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  • Figure 18.1
  • Figure 18.5
  • Figure 18.6
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •    1- Glomerular filtration – in renal capsule 2- Reabsorption – in renal tubules 3- Secretion – in renal tubules
  •     Plasma is filtered through fenestrated epithelium About 180 liters of plasma are filtered per day  filtrate Filtrate = plasma - proteins About 2 liters of urine produced per day
  •      Glomerular capillary hydrostatic pressure  due to blood hydrostatic pressure against capillary wall (BHP) Glomerular osmotic pressure due to the presence of solutes (proteins) in the blood (BOP) Bowman’s capsule hydrostatic pressure  pressure of filtrate against Bowman’s capsule wall (CHP) Bowman’s capsule osmotic pressure  due to the pressure of solutes in the filtrate (COP) Net filtration rate  fluid moves from the glomerulus into the capsule
  •   The glomerular filtration rate (GFR) = volume of plasma filtered per unit of time = 125 ml/min  180 liters per day Filtration fraction = GFR/renal plasma flow = 20%
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •     Glucose, amino-acid, sodium will be pumped out of the tubules, by active transport (ATP needed) Chloride will follow sodium into the peritubular space (accumulation of positive charges draws chloride out) Water will move into the peritubular space because of osmosis Some compounds present in high concentration in the filtrate but low in the blood can move through diffusion
  •  The transporter for glucose on the basolateral membrane has a limited capacity to carry glucose back into the blood. If blood glucose rises above 180 mg/dl, some of the glucose fails to be reabsorbed and remains in the urine  glucosuria
  •     70% of sodium and water are reabsorbed in PCT Reabsorption is not regulated Amino-acids, glucose should be 100% reabsorbed at the end of the PCT The filtrate, at the end of the PCT should be isoosmolar to the filtrate at the beginning
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •  Characteristics of Loop of Henle: -- Descending tubule: permeable to water has no sodium pumps -- Ascending loop: thick epithelium is impermeable to water but has many sodium pumps -- Na+, Cl- and K+ are pumped out into the interstitial fluid  Clfollows (electrochemical gradient)  water follows by osmosis = counter-current multiplier -- formation of an osmotic gradient in the renal medulla which is important for water reabsorption in the CT
  • Figure 19.7 (1 of 6)
  • Figure 18.4
  •    Additional filtrate is reabsorbed The filtrate is concentrated as it travels through the loop but returns to a concentration similar to the other end. Reabsorption in this segment is also (like PCT) not regulated
  •   The longer the loop, the more concentrated the filtrate and the medullary IF become Importance: the collecting tubule runs through the hyperosmotic medulla  more ability to reabsorb H2O Desert animals have long nephron Loop  More H2O is reabsorbed
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •  DCT and CT tubular walls are different from the PCT and Loop of Henle wall: -- DCT and CT walls have tight junctions and the membrane is impermeable to water -- the cell membrane has receptors able to bind and respond to various hormones: ADH, ANP and aldosterone -- The binding of hormones will modify the membrane permeability to water and ions
  • ADH is low  no binding to receptors  H2O is not reabsorbed back into the blood H2O remains in the renal tubule  high urine volume ADH is released by post. Pituitary Binds to receptors in CT channels open  H2O moves into the IF and blood  low urine volume
  •  The neurosecretory neurons for ADH (in the hypothalamus) are located near the center monitoring blood osmotic pressure  if BOP ↑ ADH secretion and release ↑  water reabsorption ↑  blood is diluted  BOP↓ (typical homeostatic regulation)   If BOP ↓  ADH secretion and release ↓  H2O reabsorption ↓  BOP ↑  urine volume ↑ Lack of ADH? Symptoms?
  •      Hypernatremia causes water retention and high blood pressure Hyponatremia  hypotension Because sodium is tightly linked to BP, BP is regulating sodium movement in the tubules Recall that BP directly affects GFR  GFR is sensed by the macula densa of the Juxtaglomerular Apparatus (JGA) If too low, the juxtaglomerular cells of the JGA secrete renin into the blood
  •   As a result, aldosterone will be secreted by the adrenal cortex  promotes sodium reabsorption in the DCT and CT. Another hormone, Atrial Natriuretic Peptide or ANP promotes sodium dumping by the DCT and CT.
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •    Secretion: Selective transport of molecules from the peritubular fluid to the lumen of the renal tubules Excretion: Molecules are dumped outside the tubules Example of excreted waste products: urea, excess K+, H+, Ca++
  •  Carbonic anhydrase inhibitors:  Osmotic diuretics:  Thiazide diuretics  Loop diuretics:  K+ sparring diuretics:
  • Site of Action Mechanisms of Action Predictable Side Effects Proximal tubule Thin descending limb Distal tubule Collecting ducts - impedes water reabsorption and indirectly impedes Na+ reabsorption by blocking the convective movement of Na+ - volume contraction often with increased serum osmolality Diuretic Osmotic diuretic (e.g., mannitol)  Carbonic anhydrase inhibitors Proximal tubule - impedes HCO3-, H+, Na+ reabsorption - HCO3- loss, .: acidosis Loop diuretics (eg. furosemide) TAL - blocks Cl-, Na+ and K+ reabsorption (via Na+/K+/2Clpump) - increased K+ losses, because of increased Na+ delivery with increased aldosterone Thiazides Early distal tubule - blocks Cl- reabsorption, creating intraluminal negative charge which impedes Na+ reabsorption Aldosterone bockers Late distal tubule Early collecting ducts - blocks Na+/K+ antiports, impeding Na+ reabsorption and K+ secretion (K+ sparing effect) - increased K+ losses, because of increased Na+ delivery with increased aldosterone - increased plasma [K+]
  •    GFR: important value for estimating the kidney function. Calculated by using molecules which are filtered but not secreted nor reabsorbed. P X GFR = U X V        P = plasma concentration of A, in mg/mL GFR = glomerular filtration rate of plasma, in mL/min U = urine concentration of A, in mg/mL V = rate of urine production in, in mL/min Solving the equation for GFR will give: GFR = (U X V)/P GFR = (U X V)/P
  •    Best molecule to use: inulin but not occurring naturally in the body Second best: creatinine Urea: cannot be used since it is both secreted and reabsorbed (why is it so?)
  •      Functions Anatomy Urine formation: - Filtration - Reabsorption - Proximal Convoluted Tubule (PCT) - Loop of Henle - Distal Convoluted Tubule (DCT) - Secretion Regulation of GFR Micturition
  •    GFR needs to be constant (p. 519, Fig. 18.10) Changes in BHP will affect GFR strongly BHP is a function of SBP GFR regulation: - to increase GFR: **vasoconstrict efferent vessel ** vasodilate afferent vessel
  •   Vasoconstriction of the efferent vessel is under the control of: --Epinephrine/Norepinephrine from the ANS -- Angiotensin II from the reninangiotensin system Vasodilation of the afferent vessel is under the control of: - paracrines secreted by the macula densa  stimulate vasodilation of neighboring vessel  - myogenic reflex (automatic constriction of smooth muscles lining the wall when the artery is stretched by increased pressure 
  •        Functions Anatomy Renal exchange processes Regional specialization of renal tubules Excretion Regulation of GFR Micturition
  •      Controlled by the sacral parasympathetic NS Stretch sensors in the bladder wall send impulses to the sacral spine  reflex opening of the urethral smooth muscle Impulses also sent to the cortex to notify the brain of the need to urinate  if the moment is OK, the person will go to the bathroom (hopefully!), and will open the skeletal (voluntary) muscle of the urethral sphincter  the person will be able to urinate
  •    What will happen to a person who has suffered a spinal cord injury to T10? Which kind of problem(s) will (s)he have? Why can’t baby control urination? What type of “problem” do they have? What about older people who dribble urine? What causes that? Figure 18.21
  •    Billy is stuck on a raft in the middle of the ocean, without food or water. In order to get a few extra hours of life and a chance to be found ( a boat), should Billy drink some sea-water or his own urine? Justify your answer.
  •     Water intake: - drink - food - catabolism Overall, intake should equal output Urine output should be less than water intake (drinks) Urine is constantly formed at a minimum rate of about 2030 ml/h  Water output - urine - feces - anabolism - respiration
  •    1- Martha is a patient in a nursing home. She is 84 year-old, senile and weak. She is bed bound and does not feed herself anymore. She has a urinary catheter and you noticed, at the beginning of your shift that the bag had a small amount of dark yellow urine. I&O (intake and output): intake 650 cc and output 250 cc. What do you think? - are the numbers balanced? - if not, what could be wrong?    2- Henrietta is Martha's roommate, also in not very good shape. She has been on IV fluid receiving 100ml/h. I&O 900ml. Her urine output is 250 ml (she has a catheter). What do you think? - are the numbers balanced? - if not, what could be wrong?