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