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RENAL PHYSIOLOGY (2 SOLUTE REABSORPTION (Distal tubule segments…

- - - - regulate systemic blood pressure & RBC production
    - - Glomerulus
        
        blood filtration site
        
        a network of capillaries
        
        retain cellular components & medium-to-high-molecular-weight proteins within the vasculature
        
        extruding glomerular filtrate nearly identical to plasma in its electrolyte & water composition
        
        glomerular filter rate (GFR)
        
        renal function parameter
        
        mL/min/kg
        
        glomerular tuft
        
        encased within Bowman's capsule
        
        area between is Bowman's space
        
        site of collection of glomerular filtrate
        
        funneled directly into first segment of proximal tubule
        
        the structure is important in determining rate & selectivity of glomerular filtration
        
        wall of capillaries
        
        3 layers:
        
        1) capillary endothelium
        
        single layer of cells with cytoplasmic extensions
        
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        2) basement membrane
        
        acellular
        
        arranged in 3 layers named according to their density with respect to alectron beam & their relative position
        
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        3) visceral epithelium
        
        a layer of podocytes
        
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        creates barrier to the forces favouring & opposing filtration of blood
        
        forces favouring
        
        movement of water and solutes across glomerular capillary wall
        
        hydrostatic pressure of blood within capillary and oncotic pressure of fluid within Bowman's space (ultrafiltrate)
        
        forces opposing
        
        plasma oncotic pressure within glomerular capillary & hydrostatic pressure in Bowman's space
      - renal tubule segments
        
        site where filtered substances are absorbed from tubule fluid & secretion of plasma components into tubule fluid
      - renal cortex
        
        nephron merge into collecting duct segments
        
        traverse kidney and empties into renal pelvis
  - - - mean net filtration pressure (Pf)
        
        permeability of filtration barrier
        
        determined by structural & chemical characteristics of glomerular capillary wall
        
        selectively permeable
        
        size
        
        all cellular components & plasma proteins the size of albumin molecules /larger retained within bloodstream
        
        water & solutes are freely filtered
        
        net electrical charge
        
        cationic more freely filtered
        
        shape & deformability
        
        long, flexible molecules
        
        neutral dextran
        
        surface area available for filtration
        
        product: ultrafiltration coefficient (KUF)
    - - systemic factors
        
        renal modulation of systemic blood pressure & intravascular volume
        
        renin-angiotensin-aldosterone system
        
        renin:
        
        release is stimulated by a decrease in renal perfusion pressure
        
        caused by systemic hypotension
        
        catalyzes transformation of angiotensinogen produced by liver to angiotensin I
        
        then converted to angiotensin II by angiotensin-converting enzyme (ACE)
        
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        release is suppressed by the improved renal perfusion & elevated plasma angiotensin II
        
        creates negative-feedback system
        
        mediated primarily through humoral factors
      - intrinsic factors
        
        renal blood flow, glomerular capillary pressure, KUF
        
        mediated by 2 autoregulatory systems
        
        control resistance to flow in afferent & efferent artterioles
        
        myogenic reflex
        
        glomerular arterioles respond to changes in arteriolar wall tension
        
        immediate afferent arteriolar constriction after an increase in arteriolar wall tension & arteriolar dilation after a decrease in arteriolar wall tension
        
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        tubuloglomerular feedback
        
        increase in NaCl concentration in tubule fluid at macula densa causes signaling cascade in macula densa cells
        
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    - - determining plasma clearance rate of a substance
        
        = rate of elimination of a substance divided by its plasma concentration
        
        net clearance rate of a substance = (rates of flltration + secretion) - rate of absorption of the substance
        
        inulin as substance for measurement of clearance
        
        freely filtered by glomerulus but is neither reabsorbed nor secreted by renal tubule cells
        
        not produced by the body
        
        rate of its disappearance from blood after intravascular injection related to GFR
        
        creatinine
        
        byproduct of muscle metabolism
        
        similar to inulin
        
        Ccreatinine = Ucreatinine V / Pcreatinine
- - - - % of filtered substance that is excreted in urine
      - net result of tubular reabsorption & secretion of filtered substance
      - FEx = Ux/Px + Ucreatine/Pcreatine
    - - FRx = 1- FEx
  - - - active transport, Na+-K+ ATPase pump
      - bicarbonate HCO3-
        
        indirectly driven by Na+ gradient
        
        transcellular
      - Cl-
        
        indirectly powered by Na+,K+-ATPase pump
        
        paracelullar & transcellular
      - K+ & Ca2+
        
        paracellular
      - filtered peptides & low-molecular-weight proteins
    - - facilitate movement of tubule fluid components into blood
        
        2 pathways
        
        transcellular pathway
        
        cross the apical plasma membrane
        
        discharge across basolateral plasma membrane into interstitial fluid on the blood side of cell
        
        paracelullar pathway
        
        from tubule fluid across zonula occludens
        
        passive diffusion or by solvent drag
        
        enter lateral intercellular space
      - aid movement of water & solute
        
        driven by Starling's forces
    - - endogenous waste products
        
        bile salts
        
        oxalate
        
        urate
        
        creatine
        
        Prostaglandin
      - exogenous drugs / toxins
        
        antibiotics
        
        diuretics
        
        analgesic morphine
        
        potent herbicide paraquat
      - basis of urine testing
        
        hormones & foreign substances as reflection of blood levels that may be only temporarily elevated
  - - - Na+ is actively reabsorbed through basolateral Na+, K+ -ATPase pump
        
        creating electrochemical gradient across apical plasma membrane
        
        drives Na+, K+, Cl- enter cell from luminal fluid through Na+, K+, 2Cl- co-transporter
        
        Cl- diffuses down its concentration gradient
        
        K+ leaves cell through both apical & basolateral K+ channel
    - - NaCl co-transporter
    - - cation-selective paracelullar pathway
    - - Na+ channel in apical plasma membrane
    - - hypotonic tubule fluid
      - diluting segments
        
        fluid volume regulation
        
        allow kidney excrete excess water without salt
        
        prevent water overload & plasma hypotonicity
    - - hormones:
        
        aldosterone
        
        acts on connecting segment cells & principal cells
        
        enhance Na+ reabsorption
        
        enhances water reabsorption to correct perceived volume depletion
        
        stimulated by hyperkalemia (elevated plasma K+ level)
        
        enhance K+ secretion
        
        angiotensin II
        
        directly enhances Na reabsorption in proximal tubule, thick ascending limb of Henle's loop , collecting duct
        
        antidiuretic hormone
        (vasopressin)
        
        release when volume depleted, dehydrated / hypotensive
        
        enhances salt reabsorption from thick ascending limb & collecting duct
        
        endothelin
        
        peptide hormone produce in kidney
        
        in collecting duct & thick ascending limb
        
        acts on specific receptors
        
        increases renal NaCl & water excretion
        
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        atrial natriuretic peptide
        
        produced in cardiac atria
        
        enhances Na+ excretion in distal tubules & collecting duct
        
        by inhibiting aldosterone release & vasopressin effects in collecting duct
        
        parathyroid hormone (PTH)
        
        stimulated by hypocalcemia (low plasma Ca2+ level)
        
        affects bone, intestines & kidneys to raise plasma Ca2+ level
        
        increase apical uptake of Ca2+ in cortical thick ascending limb, dct & connecting segment
        
        by increasing activity of apical Ca2+ channel
        
        in dct, Cl- increases at basolateral plasma membrane
        
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        inhibits inorganic phosphate reabsorption in proximal tubule
        
        internalization of NaPi-2
        
        vitamin D3
        
        converted to active form in proximal tubule, stimulated by PTH
        
        receptors are located predominantly in dct & connecting segment
        
        increases cellular content of Ca2+ binding protein
        
        contributes to enhanced Ca2+ reabsorption
        
        increase expression of NaPi-2 in proximal tubule
        
        enhances phosphate reabsorption
        
        calcitonin
        
        reduces serum Ca2+ concentration
        
        by stimulating Ca2+ deposition in bone
        
        enhances renal Ca2+ reabsorption in thick ascending limb, dct & connecting segment
  - - - intercalated cell
        
        remainder of cortical & outer medullary collecting duct cells
        
        reabsorb potassium
      - principal cell
        
        initial collecting duct
        
        cortical collecting duct
        
        outer medullary collecting duct
        
        reabsorbs NaCl
        
        Na+ is actively reabsorbed through basolateral Na+, K+ -ATPase pump
        
        creating electrochemical gradient across apical plasma membrane
        
        lumen-negative electrical potential drives Cl- absorption through paracellular pathway
        
        K+ is pumped actively from intracellular fluid into cell
        
        intracellular K+ concentration increase
        
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- - - - produce urine that has 7-8 times the osmolality of plasma
    - - hypotonic urine is produced
    - - (1) generation of hypertonic medullary interstitium
        
        allow excretion of concentrated urine
        
        produced & maintained primarily by
        
        reabsorption of osmotically active substances by tubules in medulla
        
        removal of water from medulla interstitium by vasa recta
      - (2) dilution of tubule fluid by thick ascending limb & dct
        
        allows excretion of dilute urine
      - (3) variability in water permeability of collecting duct in response to ADH
        
        determines final urine concentration
    - - superficial
        
        short loops of Henle
        
        extend only into inner stripe of outer medulla
      - juxtamedullary
        
        long loops of Henle
        
        extend deep into inner medulla
        
        particularly responsible for kidney's ability to concentrate urine at much higher level than osmolality of plasma
  - - - active transport
        
        Na+, K+ -ATPase pump in basolateral plasma membrane
        
        transports Na+ from cell into interstitial fluid
        
        drives carrier-mediated secondary active transport & passive uptake of solutes & water
      - passive diffusion
        
        Na+ & other solutes are removed from tubule fluid
        
        creates slight gradient favoring movement of water into cells & intercellular spaces
        
        apical brush border & complex basolateral plasma membrane in proximal tubule
        
        create large surface area for reabsorption
        
        highly permeable to water
        
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