define & differentiate between osmolarity ecf

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    DEFINE & DIFFERENTIATE BETWEEN

    OSMOLARITY, ECF/ICF, TONICITY,

    PHYSIOLOGY OF FLUID & ELECTROLYTEBALANCE

    R U I

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    DAILY INTAKE OF WATER2 major sources:

    2100ml/day

    200ml/day

    Varies on individual, climate, habits & level of physical activity

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    DAILY LOSS OF BODY WATER

    Insensible water loss

    Water evaporation from the respiratory tract

    300-400ml/day

    In respiratory tract, air vapour pressure- 47 mm Hg

    Inspired air vapour pressure less than 47 mm Hg

    Cold weather nearly 0

    Diffusion through the skin (independently of sweating) 300-400ml/day

    Minimized by the cholesterol-filled cornified layer of the skin

    Layer denuded (extensive burns) 3-5 L/day

    Sweat 100ml/day2L/hour

    Water loss in faeces 100ml/day

    Water loss by the kidneys 0.5L 20L/day

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    REVISION:

    Osmosis: the net diffusion of water across a selectively

    permeable membrane from a region of high water

    concentration to one that has a lower water concentration.

    * Plasma membrane is selectively permeable

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    OSMOLES

    the total number of particles in a solution

    1 osmole = 1 mole (6.02 X 1023)

    Refers to the number of osmotically active particles in a solution rather than to

    the molar concentration

    NaCl Na+ & Cl-

    1 mole/L = 2 osm/L

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    OSMOLARITY

    the osmolal concentration of a solution when express as osmoles per liter

    Osmolality- osmoles per kg

    Total osmolarity of 3 compartments = 300mOsm/L

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    ISOSMOTIC, HYPEROSMOTIC, HYPO-OSMOTIC

    Isosmotic solutions with the same Osm

    Hyperosmotic- solution with higher Osm than

    another

    Hypo-osmotic- solution with lower Osm than theanother

    Osm [water]

    Osm [water]

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    OSMOTIC EQUILIBRIUM:

    Large osmotic pressure can develop across the cell membrane with relatively small

    changes in the concentration of solutes in the ECF

    For each mOsm concentration gradient of an impermeant solute, about 19.3mm Hg

    osmotic pressure is exerted across the cell membranre

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    OSMOLARITY & OSMOTIC PRESSURE

    Osmolarity (Osm): sum of all solutes in a given volume (moles per liter)

    Osmotic pressure (Posm): force generated by osmosis

    Measure of the tendency to take on water by osmosis

    For an isosmotic solution to be isotonic, the membrane must be equally permeable or

    equally impermeable to all solutes

    All isotonic solutions are isosmotic

    Not all isosmotic solutions are isotonic

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    TONICITY

    Isotonic

    Water concentration in the ICF & ECF is equal

    Neither shrinks nor swells

    0.9% solution ofNaCl (9g/L)

    5% solution of glucose (50g/L)

    Hypotonic:

    Water concentration in the ECF is higher than ICF

    Water diffuse into cells dilutingICF Cells swell

    Hypertonic:

    Water concentration in the ICF is higher than ECF

    Water diffuse out of the cells concentratingICF

    Cells shrink

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    PHYSIOLOGY

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    Extracellular fluidvolume

    Cardiac output

    Effective arterial bloodvolume

    Arterial underfilling

    Unloading of high-pressure volume receptors

    Stimulation of sympatheticnervous system

    Nonosmotic ADH release Activation ofRAAS

    peripheral and renal arterial vascular resistance and Na+ & H2O retention

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    Everything

    - protein

    65% of

    filtered load

    of H20, Na &

    > Cl

    20% of the filtered water

    25% of

    the

    filtered

    loads

    ofNa,

    Cl & K

    5% of the

    filtered

    NaCl

    Principle &intercalated

    cells

    >10%

    of

    filtered

    water

    & Na

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    PROXIMAL TUBULAR REABSORPTION

    65% of the filtered load of sodium & water and a slightly lower percentage of filtered chloride

    are reabsorbed

    Due to the highly metabolic epithelial cells with large number ofmitochondria and brush

    border on the luminal side of the membrane which is also loaded with protein carrier

    molecules (co-transport of sodium & glucose/amino acid, counter transport of sodium &

    hydrogen), as well as an extensive labyrinth of intercellular and basal channels (increase

    surface area)

    Proximal tubule is also important for secretion of organic acids and bases such as bile salts,oxalate, urate and catecholamines

    Filtration + secretion absorption

    Para-aminohippuric acid (PAH)

    Secreted so rapid that the average person can clear 90% of PAH from the plasma

    PAH clearance can be used to estimate the renal plasma flow

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    LOOP OF HENLE: THIN DESCENDING SEGMENT

    no brush borders, few mitochondria, minimal levels of metabolic activity

    Highly permeable to water

    Moderately permeable to most solutes including urea & sodium

    Function: to allow simple diffusion of substances through its wall

    Almost 20% of the filtered water is reabsorbed here

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    LOOP OF HENLE: THIN ASCENDING SEGMENTno brush borders, few mitochondria, minimal levels of metabolic activity

    Impermeable to water

    Lower reabsorptive capacity

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    LOOP OF HENLE: THICK ASCENDING SEGMENT

    Thick epithelial cells with high metabolic activity and are capable ofactive reabsorption ofsodium, chloride, and potassium

    Almost 25% of the filtered loads of sodium, chloride and potassium are reabsorbed here

    Sodium-potassium pump in the basolateral membraneimportant component

    The reabsorption of other solutes is closely linked with the reabsorptive capability of the

    sodium potassium pump, which maintains a low intracellular sodium concentration which

    provide a concentration gradient for movement of sodium from the tubular fluid into the cell Also has sodium-hydrogen counter transport mechanism in its luminal membrane

    Referred as the diluting segments

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    DISTAL TUBULE1st portion forms the macula densa, a group of closely packed

    epithelial cells that is part ofthe juxtaglomerular complex &

    provides feedback control of GFR and blood flow in this same

    nephron.

    The next portion of the distal tubule is highly convoluted

    avidly reabsorbs most of the ions but is impermeable to water &

    urea)

    5% of the filtered load of sodium chloride is reabsorbed in the

    early distal tubule

    sodium-chloride co-transporter moves sodium chloride from the

    tubular lumen into the cellsodium-potassium pump transport sodium out of the cell across

    the basolateral membrane

    chloride diffuses out of the cell into the renal interstitial fluid

    through chloride channels in the basolateral membrane

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    Late distal tubule and cortical collecting tubule

    Second half of the distal tubule and the subsequent cortical collecting tubule have similar

    functional characteristics

    They are composed of 2 distinct cell type:

    Principle cells

    Reabsorb sodium and water from the lumen and secrete potassium ion into the lumen

    (sodium potassium pump in basolateral membrane which lowers down sodium

    concentration in the cell, hence diffusion of sodium ions across the luminal membrane)

    Intercalated cells Reabsorbed potassium ions and secrete hydrogen ions into the tubular lumen

    Hydrogen ATPase transporter

    Hydrogen is generated by the action of carbonic anhydrase on water and carbon dioxide

    to form carbonic acid, which then dissociates into hydrogen ions and bicarbonate ions

    For each hydrogen ion secreted into the tubular lumen, a bicarbonate ion becomes

    available for reabsorption across the basolateral membranePermeability is controlled by the concentration ofADH

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    MEDULLARY COLLECTING DUCT

    Reabsorb less than 10% of the filtered water and sodium

    Final site for processing urine

    Epithelial cells are nearly cuboidal in shape with smooth surfaces andrelatively few mitochondria

    Permeability is controlled by the concentration ofADH High level ofADH, water is avidly reabsorb into the medullary

    interstitium, thereby reducing the urine volume and concentratingmost of the solutes in the urine

    Medullary collecting duct is permeable to urea and there are specialurea transporters that facilitate urea diffusion across the luminaland basolateral membranes.

    Some urea is reabsorbed into the medullary interstitium, helping to

    raise the osmolarityMedullary collecting duct is capable of secreting hydrogen ions against

    a large concentration gradient, as also occur in cortical collectingtubule. Thus regulating the acid-base balance

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    GLOMERULOTUBULAR BALANCE

    intrinsic ability of the tubules to increase their reabsorption rate in response to increased

    tubular load

    can occur independently of hormones and can be demonstrated in completely isolated

    kidneys or even in completely isolated proximal tubular segments

    helps to prevent overloading of the distal tubular segments when GFR increases

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    REGULATION OF PERITUBULAR CAPILLARY

    PHYSICAL FORCES2 determinants of peritubular capillary reabsorption that are directly influenced by

    renal hemodynamic changes are the hydrostatic and colloid osmotic pressures of

    the peritubular capillaries.

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    PERITUBULAR CAPILLARY HYDROSTATIC

    PRESSURE

    influenced by the arterial pressure and resistance of the afferent and efferent

    arterioles.

    increase in arterial pressure tend to raise peritubular capillary hydrostatic pressure

    and decrease reabsorption rate

    increase in resistance of either the afferent or the efferent arterioles reduces

    peritubular capillary hydrostatic pressure and tends to increase reabsorption rate

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    COLLOID OSMOTIC PRESSURE OF

    PERITUBULAR CAPILLARY IS DETERMINED BY:

    the systemic plasma colloid osmotic pressure

    increasing the plasma protein concentration of systemic blood tends to raise peritubular

    capillary colloid osmotic pressure, thereby increasing reabsorption

    the filtration fraction

    the higher the filtration fraction, the greater the fraction of plasma filtered through the

    glomerulus and more concentrated the protein becomes in the plasma.

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    Changes in peritubular capillary physical forces influence tubular reabsorption by changing

    the physical forces in the renal interstitium surrounding the tubules.

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    URINE CONCENTRATION

    Established by LOH, CD and

    vasa rectap reabsorption

    of varying amounts of H2Oand Na+

    Key player: ADH (= Vasopressin)

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    URINE CONCENTRATION, CONTD

    Often expressed in osmolaritymM/L or osmolality mM/kg

    Blood: 300 mOsm

    Filtrate in Bowmans Capsule: 300

    mOsm Bottom of LOH: 1200 mOsm

    Urine: 50-1200 mOsm

    Regulated by ADH (vasopressin)

    Osmoreceptors in hypothalamus

    BP and blood volume, too

    Fig. 20-4

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    EFFECT OF ADH

    Controls Urine concentration via

    regulation of water reabsorption

    from the filtrate in the collecting

    ductOsmoreceptors in hypothalamus

    ADH caused by:

    Na+ and/or osmolality in the ECF

    H2O deprivation

    renal blood flow

    Hi [ADH] Lo [ADH]

    Fig 20-5

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    EFFECT OF ADH, CONTD

    ADHReceptors in CD cells

    Luminal CM is generally

    impermeable toH2O

    Aquaporins (rememberCh. 5) oncellmembranesofCD are variably

    active, dependenton ADH

    Membrane Recycling via

    exocytosisofAQP2

    AllowsosmosisofH2O intovasa recta

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    TROUBLES WITH ADH?

    Diabetes insipidus

    Central

    Nephrogenic

    Nocturnal enuresis

    ADHdeficiency:

    ADHExcess:

    AKA Inappropriate ADHsecretion

    XSH2O retention

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    In presence of ADH: Insertionof H2O pores into tubularluminal CM

    At maximal H2O permeability:Net H2O movement stopsat equilibrium

    Maximum osmolarity of urineup to 1200 mOsm

    No ADH:

    DCT & CD

    impermeable to H2O

    Osmolarity can plunge

    to ~ 50 mOsm

    CONCENTRATED VS. DILUTE

    URINE

    Review:

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    LOH:COUNTERCURRENT

    MULTIPLIER

    leads to

    Hyperosmotic IF inmedulla

    Hyposmotic fluid

    leaving LOH

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    REGULATION OF BP:

    NA+ BALANCE AND ECF VOLUME

    [Na+] affects plasma & ECF osmolarity

    (Normal [Na+]ECF ~ 140 Mosm)

    [Na+] affects blood pressure & ECF volume

    [] Gradients

    Aldosterone stimulatesNa+ reabsorption and K+ excretion in last 1/3 of DCTand CD

    Type of hormone? Where produced? Type of mechanism?

    o Aldosterone secretiono Na+ absorption from DCT

    Secretion of aldosterone by two mechanisms o K+ in ECF

    BP

    The signal to release aldosterone is via angiotensin II

    Opposite ofAldosterone? ANP (from the atria) causes loss ofNa+

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    ALDOSTERONE MECHANISMALDOSTERONE MECHANISM

    Na+/K+ATPase activityo

    K+ secretion o

    Fig 20-13

    Here (unlike normally) H2O does

    not necessarilyfollowNa+

    absorption. Thisonly happens in

    presence of. . .

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    REGULATION OF BP:

    RAAS PATHWAYS

    RAAS = renin-angiotensin-aldosterone system

    JG cells release renin in responseto BP

    Renin converts Angiotensinogen toAngiotensin I

    ANG I converted to ANG II by ACE

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    RAAS PATHWAYS, CONTD

    ANG II causes BP via ADH Secretion

    Thirst

    VasoconstrictionSympathetic stimulation of heart

    HR and CO

    ACE inhibitors will BP

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    KEY PROCESSES

    Countercurrent Multiplication: Segments of Loop of Henle

    Countercurrent multiplication: Urea recycling

    Countercurrent Exchange: Vasa recta

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    ADH

    Produce by hypothalamus

    Stored in posterior pituitary gland

    Blood osmolarity

    Release ofADH intodistal convoluted tubule

    & collecting duct

    Act on aquaporin

    Aquaporin move tosurface

    Allow water to movefrom tubule to interstitial

    and then into capillary

    Act on medullary

    collecting duct

    Permeability

    to urea

    osmolarity

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    ALDOSTERONE

    Mineralocorticoid

    Produced in adrenal gland in kidney

    BP

    Low Na inMedulla densa

    RAAS

    Aldosterone

    sodiumreabsorption

    H20reabsorption

    Angiotensinogen

    Angiotensin I II

    vasoconstriction

    Blood volume BP