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Renal Physiology - Coggle Diagram

- - - - water movement carries along solute
  - - - via
        
        Transcellular pathway
        
        lumen to cell to interstial fluid
        
        passing cell from apical plasma membrane to cytoplasm to basolateral plasma membrane
        
        Paracellular pathway
        
        lumen to intercellular space via tight junction to interstitium
        
        either via passive diffusion or solvent drag
      - then from interstitium to bloodstream via peritubular capillaries
        
        using starling law (net movement created from opposing hydrostatic prssure and oncotic pressure) where peritubular capillaries that originate from efferent arteriole has low hydrostatic pressure and high oncotic pressure
        
        favours fluid and solute uptake from interstitium into blood stream
      - Solutes
        
        Na
        
        Intracellularly
        
        Down gradient, Na moves through apical p.m. via cotransporter
        
        chemical gradient created by Na-K-ATPase (or Na-K pump) on basolateral membrane
        
        Paracellularly
        
        follows Cl that moves paracellularly due to electrostatic attraction
        
        Cl
        
        Intracellularly
        
        electrical gradient created from Na-K pump favours Cl movement into cell via cotransporter
        
        absorption of other solutes left Cl in the tubule lumen and creates gradient for Cl to enter cells
        
        Paracellularly
        
        via passive diffusion as tight junction is highly permeable to Cl
        
        HCO3-
        
        enters as H20 and CO2 via apical carbonic anhydrase
        
        H provided by Na-H antiporter where Na enters cells, H exits
        
        cytoplasmic carbonic anhydrase hydrolyzes the components back to HCO3-
        
        HCO3 exits basolateral p.m via
        
        Na-HCO3 cotransporter
        
        Na-dependent HCO3-/Cl antiporter
        
        Ca
        
        via solvent drag through paracellular pathway
        
        65% are reabsorbed here
        
        K
        
        passive diffusion via paracellular pathway
        
        Low molecular weight proteins such as insulin, glucagon, PTH
        
        via endocytosis
        
        other solutes such as glucose, phosphate, sulfate, citrate and amino acids
        
        move via secondary active transport
        
        Peptides
        
        broken down by peptidase on apical p.m.
        
        reabsorbed via Na cotransporter
        
        short chain peptides via H cotransporter
    - - Solutes
        
        Endogenous organic ions or exogenous drugs or toxins
        
        poorly filtered by glomerular filtration due to being protein bound, must be secreted for elimination
        
        provides basis for urine testing
        
        p-aminohippurate is used to estimate renal plasma flow
        
        tubular antiobiotics secretion to determine effective antibiotics to treat UTI
  - - - maintain hypertonic medullary interstitium
        
        thin ascending for Na reabsorption
        
        thin descending for water reabsorption
  - - - mainly for reabsorption of Na (and Cl secondarily) via active transport
        
        Solutes
        
        Na
        
        Basolateral Na-K pump creates electrochemical gradient
        
        Na enters apical via NA-K-Cl co transporter in TAL
        
        inhibited by loop diuretics such furosemide and bemetanide
        
        Na exits basolateral to interstitial fluid via this pump
        
        moves down chemical gradient via apical NaCl cotransporter in DCT
        
        Cl
        
        exits via ClC-K channel aka barttin Cl channel driven by electrical gradient in DCT
        
        Barttin is inhibited by thiazide diuretics
        
        exits basolateral p.m. via Cl channels in TAL
        
        both have tall epithelium, and abundance mitochondria to support active transport
    - - K
        
        secreted into lumen via apical K channel
    - - purpose for urine dilution
  - - - Reabsorb NaCl
        
        Collecting Duct is composed of two main types of cells
        
        Intercalated cells
        
        Have apical ENaC or epithelial Na Channel
        
        thus primarily for NaCl reabsorption driven by gradient created by Na-K pump
        
        account for 2/3 of the cells in superficial part of duct (initial CD, cortical CD, outer medullary CD)
        
        Principal cells
        
        have Cl/HCO3- exchanger aka pendrin
        
        mediates luminal Cl uptakes
        
        also enhances ENaC activity of intercalated cells, thus NaCl reabsorption
      - K secretion
        
        K has high intracellular concentration thanks to Na-K pump
        
        K is secreted via apical ROMK and BK
        
        occurs due to 2 reasons
        
        apical ROMK more permeable than basolateral ROMK
        
        negatively charge lumen electrical potential that favors K secretion
      - Can also reabsorb K
        
        reabsorbed via active transport of H-K pump found abundant in intercalated cells
        
        when body needs K
        
        Increased activity of H-K pump
        
        Increased expression of H-K pump in the collecting duct
        
        ROMK and BK activity is inhibited
  - - - Enhances Na reabsorption by binding to angiotensin 1 type receptors
        
        increases Na transport upon activation
      - activation of angiotensin type 2 receptors increases Na secretion
    - - Enhance Na reabsorption and K secretion via increase Na-K pump activity
    - - released upon volume depletion, hypotension or dehydration
        
        enhance salt reabsorption from both TAL and CD via increased NKCC2 (Na-K-Cl cotransporter)
        
        increased activity of ENaC in CD
    - - increases renal and water excretion by inhibiting Na reuptake by inhibiting apical Na channels in TAL and CD
    - - also increases renal and water excretion by binding to ET-B receptors
        
        inhibits Na-K pump amongst other Na channels
    - - inhibits aldosterone and renin release and increases renal Na excretion
    - - reduce phosphate reabsorption by reducing the apical Na coupled phosphate transporter
    - - increases Ca reabsorption
- - - - network of capillaries
        
        wall consists of 3 layers:
        
        capillary endothelium
        
        basement membrane
        
        visceral epithelium
  - - - Cellular components and medium to high molecular weight proteins doesn't pass the glomerulus
      - the rests are called glomerular filtrate
        
        Glomerular filtration rate (GFR)
        
        Determined by:
        
        mean net filtration pressure
        
        affected by capillary hydrostatic pressure vs capillary oncotic pressure
        
        permeability of the filtration barrier
        
        selective permeabilty determined by:
        
        Molecurlar radius of substances
        
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        Net electrical charge of a molecule
        
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        Shape and deformability of molecule
        
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        surface area available for filtration
        
        mesangial cells contration reduces surface area
        
        regulated by:
        
        Renal factor
        
        Renal to system to renal
        
        Renin-Angiotensin-Aldosterone System
        
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        Intrarenal
        
        Myogenic reflex
        
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        Tubuloglomerular Feedback (TGF) involve in single nephron
        
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        Endothelium
        
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        Systemic factor
        
        On blood volume
        
        Angiotensin II, Aldosterone and Vasopressin, all increase water and solute reabsorption
        
        Atrial natriuretic peptides (produced in cardiac atria) - causes natriuesis (sodium wasting) and diueresis (water wasting), thus reducing blood volume
        
        On vessel tone
        
        Vasopressin and catecholamines (adrenaline, noradrenaline) causes systemic vasoconstriction, increase BP
        
        Beta adrenergic stimulation can activate renin-angiotensin system
        
        Alpha adrenergic stimulation can cause renal vasoconstriction
        
        Vasoconstrictors may cause contraction of mesangial cells
        
        measured by:
        
        in clinical settings, using creatinine as they are freely filtered and not reabsorbed and secreted (at least not in dog) into the urine enabling accurate measurement
        
        Ccreatinine = (UcreatinineV)/Pcreatinine
        
        C is plasma clearance
        
        U is urine concentration
        
        V is volume of urine collected of period of time
        
        P is plasma concentration
        
        GFR are expressed on basis of body weight or body surface area
- - - - Generation of a hypertonic medullary interstitium which allows excretion of concentrated urine
        
        maintained by:
        
        the reabsorption of osmotically active substances by tubules in the medulla
        
        via Countercurrent mechanism of loop of Henle
        
        Basically because of nature of permeability of the thin limbs (water permeable at descending, Na permeable at ascending) and their arrangement (parallel to each other) interstitial osmolality is increased without much effort
        
        at descending thin limbs, it is permeable to water but not to Na at least at outer medullary part, and due to hypertonic interstitial fluid contributed by thick ascending limb actively reabsorbing Na water moves out into the interstitium.
        
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        the removal of water from the medullary interstitium by the vasa recta
        
        via Countercurrent Exchange in the Vasa Recta
        
        Vasa recta are permeable to water, salts, and urea
        
        Vasa recta entering the medulla has high oncotic pressure, so water can get into the capillary lumen
        
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      - Dilution of the tubule fluid by the thick ascending limb and the distal convoluted tubule, which allows excretion of dilute urine
        
        TAL and DCT actively reabsorb Na which drives Cl reabsorption, but these segments are impermeable to water so tubule fluid became dilute
      - variability in the water permeability of the collecting duct in response to antidiuretic hormone (ADH, vasopressin), which determines the final urine concentration
        
        During water overload
        
        ADH is absent so CD is impermeable to water, tubule fluid remains hypotonic
        
        If ADH is absent, AQP is located in cytoplasmic vesicles in principal cells and IMCD cells
        
        During dehydration, hypotension or volume depletion
        
        ADH is released from neurohypophysis
        
        If ADH is present, APQ2 inserts into apical p.m. of the said cells and allow water to pass through
        
        AQP3 and AQP4 exists on basolateral p.m. regardless of ADH thus allows movement of water from cells to interstitium
        
        CD is now permeable to water, as it travels down the inner medulla, tubular fluid equilibrates with the interstitium by movement of water out of the tubule producing highly concentrated urine
        
        ADH also contributes to urea reabsorption, thus contributing to medullary hypertonicity
        
        triggered by rise in plasma osmolality as little as 3-5 mOsm/kg
  - - - Concetrations of osmolytes varies depending of diuretic states of animals
        
        , increased during periods of urine concentration when medullary interstitial osmolality is maximised
        
        decreased during diuresis when medullary interstitial osmolality decreases