Renal Physiology - Physiology

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Functions of the Kidney

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Biology

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1

Functions of the Kidney

Regulation of fluid and electrolyte balance Regulation of plasma osmolarity Removal of metabolic wastes, toxins, drugs Endocrine functions (Renin & Erythropoietin) Metabolism Ensuring long-term acid-base balance

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Two major classes of Nephrons

Cortical (superficial, located in cortex) - 80% Juxtamedullary (deep) - 20%

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Renal corpuscle

Comprised of Glomerulus and Glomerular (Bowman's) capsule

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Glomerular (Bowman's) Capsule

Consist of Capsular outer layer, visceral layer (podocytes), Bowman's space (separates two layers)

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Filtration membrane

Fenestrated endothelium of glomerular capillaries, Basement membrane (negatively charged), and foot processes of podocytes (w/ filtration slits)

*No macromolecules, ONLY H2O, glucose, AAs, nitrogenous wasters, solutes smaller than plasma proteins pass (NO blood cells pass)

<p>Fenestrated endothelium of glomerular capillaries, Basement membrane (negatively charged), and foot processes of podocytes (w/ filtration slits)</p><p>*No macromolecules, ONLY H2O, glucose, AAs, nitrogenous wasters, solutes smaller than plasma proteins pass (NO blood cells pass)</p>
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Glomerulus

specialized for filtration

afferent arteriole --> glomerulus --> efferent arteriole

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Peritubular capillaries (cortical nephron)

Low-pressure capillaries adapted for absorption of H2O and solutes; cling to adjacent renal tubules in cortex

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Vasa recta (Juxtamedullary nephron)

Long (thin-walled) vessels parallel to long nephron loops of juxtamedullary nephrons

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9

Jutaglomerular Apparatus (JGA)

one per nephron Has three cell populations:

  • Macula densa

  • Granular cells

  • Extraglomerular mesangial cells

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Macula densa

Epithelial cells of DCT (near renal corpuscle) Function as chemoreceptors

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Granular cells

Granules contain Renin Function as mechanoreceptors (sense blood press. in afferent arteriole)

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Extraglomerular mesangial cells

B/w afferent & efferent arterioles May pass signals b/w macula densa & granular cells

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13

Glomerular Filtration Rate (GFR)

Volume of plasma that is filtered across the glomerular per unit time

  • The amt of filtrate kidneys produce each minute (average: 125 mL/min)

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Two Major Forces of GFR

  • Hydrostatic pressure (forces fluids & solutes thru filtration membrane)

  • Oncotic pressure

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15

Outward pressures promoting filtrate formation

Hydrostatic pressure in glomerular capillaries (HP (GC)) = glomerular blood pressure (55 mm Hg)

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Inward forces stopping filtrate formation

  1. Hydrostatic pressure capsular space (HP (BS)) - 15 mmHg

  2. Colloid oncotic pressure in capillaries (OP (GC)) - 30 mmHg

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Net Filtration Pressure (NFP)

Sum of forces, pressure responsible for filtrate formation Main factor controlling glomerular filtration rate

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Net Filtration Pressure Equation

NFP = (HPgc - HPbs) - (onocGC - onocBS) NFP = outward pressures - inward pressures NFP = (55 - 15) - (30 - 0) = 40 - 30 = 10 mm Hg (onocBS is negligible)

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19

GFR is directly proportional to...

  1. NFP

  2. Total surface area available for filtration

  3. Filtration membrane permeability

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20

Mechanisms of Urine Formation

Three renal processes: Tubular absorption Tubular secretion Glomerular filtration

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Renal Clearance

Cx = Ux * V/ Px

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Cx = C inulin

Filtered, but not Reabsorbed or Secreted

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Cx < C inulin

Filtered and Reasbored Ex: Na+, Cl-, HCO3-, phosphate, urea, glucose, and amino acids

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Cx > C inulin

Filtered and Secreted Ex: para-aminohippuric acid (PAH), creatinine, urea, NH4+, and morphine

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Cx < or > C inulin

Filtered, Reabsorbed and Secreted Ex: H+ and HCO3-

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26

Renal Plasma Flow (RPF)

RBF - (1 - HCT)

Normal adult male: RBF = ~1L/min, HCT = ~40% Ex: Renal Handling of PAH (effective RPF)

<p>RBF - (1 - HCT)</p><p>Normal adult male: RBF = ~1L/min, HCT = ~40% Ex: Renal Handling of PAH (effective RPF)</p>
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27

Constriction of Afferent arteriole

Decrease RPF Decrease HP (Glomerular Cap) --> Decrease GFR

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Constriction of Efferent arteriole

Decrease RPF Increase HP (Glomerular Cap) --> Increase GFR

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Control of GFR

  1. Autoregulation (local level) intrinsic

  2. Hormonal regulation (by kidneys)

  3. Autonomic regulation (sympathetic division)

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Renal autoregulation

Two types:

  1. Myogenic mechanism

  2. Tubuloglomerular feedback mechanism

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Countercurrent multiplier

interaction of filtrate flow in descending/ascending limbs of nephron loops of juxtamedullary nephrons --> creates gradient

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Countercurrent exchanger

blood flow in descending/ascending limbs of vasa recta --> maintains gradient

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Thin descending limb

Permeable to water, impermeable to solutes

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Thick ascending limb

Impermeable to water

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Medullary osmotic gradient

Concentration gradient created in peritubular fluid of medulla

  • Na+, K+, 2 Cl- moves out of ascending limb (via Na+-K+/2Cl- transporter) into interstital fluid and then water diffuses out of descending limb --> raising osmolality of intersititial fluid (to max 1200 mL/min)

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Vasa recta - Countercurrent exhcanger

  • Highly permeable to water and solutes

a. Descending limb: water out, NaCl in --> at bottom of loop reaches 1200

b. Ascending limb: water in, NaCl out --> ends @ 325 (slightly higher than 300 start)

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Urea Recycling

Cortical and outer medullary collecting ducts: ADH increases water permeability but NOT urea permeability --> water is absorbed but urea remains --> urea increase

Inner medullary collecting ducts: ADH increases water permeability & facilitated diffusion of urea (UT1) --> helps maintain gradient

<p>Cortical and outer medullary collecting ducts: ADH increases water permeability but NOT urea permeability --&gt; water is absorbed but urea remains --&gt; urea increase</p><p>Inner medullary collecting ducts: ADH increases water permeability &amp; facilitated diffusion of urea (UT1) --&gt; helps maintain gradient</p>
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Anitidiuretic hormone (ADH)

Prevents excessive water loss in the urine and increases water absorption

*Targets kidney's collecting ducts

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Aldosterone

Determines rate of Na+ reabsorption and K+ loss in kidneys

  • secreted in response to rising K+ or falling Na+

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Atrial natriuretic peptide (ANP)

Released by atrial cells in heart due to stretch (inc BP)

  • Effects: Decreases in blood pressure and volume a. Decreased ADH, renin and aldosterone production b. Inc excretion of Na+ and H2O c. Promotes vasodilation directly and dec of angiotensin II

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Alkalosis

arterial pH > 7.45

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Acidosis

arterial pH < 7.35

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Net gain of H+

Hyperventilation (Increase in CO2, slow breathing) Diarrhea (loss of HCO3-) Cell and protein metabolism Ingestion of acid containing food

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Net loss of H+

Hyperventilation (decrease in CO2) Vomiting Urinary acid excretion

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HH equation

pH = Kidney / Lung = [HCO3-] / P(CO2)

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Blood pH rises (alkaline)

Bicarbonate ions are excreted --> H+ ions retained by kidney tubules

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Blood pH falls (acidic)

Bicarbonate ions are reabsorbed --> H+ ions are secreted

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48

Respiratory acidosis w/ renal compensation

Indicated by: LOW pH HIGH P(CO2) (= cause of acidosis) and bicarbonate levels (compensation)

Kidneys reabsorb more bicarbonate --> create new bicarbonate and secrete more H+

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49

Respiratory alkalosis w/ renal compensation

Indicated by: HIGH pH LOW P(CO2) Decreasing HCO3- levels

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50

Two mechanisms to generate bicarbonate ions

  1. Excretion of buffered H+

  2. Excretion of NH4+ (glutamine)

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