DEFINE & DIFFERENTIATE BETWEEN

OSMOLARITY, ECF/ICF, TONICITY,

PHYSIOLOGY OF FLUID & ELECTROLYTE
BALANCE

RUI
 DAILY INTAKE OF WATER
2 major sources:

 2100ml/day

 200ml/day

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

 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/day2L/hour
Water loss in faeces 100ml/day
Water loss by the kidneys  0.5L – 20L/day
 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

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
 OSMOLARITY

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

• Osmolality- osmoles per kg
• Total osmolarity of 3 compartments = 300mOsm/L
ISOSMOTIC, HYPEROSMOTIC, HYPO-OSMOTIC

• Isosmotic – solutions with the same Osm

• Hyperosmotic- solution with higher Osm than
another
• Hypo-osmotic- solution with lower Osm than the
another
↑Osm  ↓ [water]
↓Osm  ↑ [water]
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
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
TONICITY
Isotonic
 Water concentration in the ICF & ECF is equal
 Neither shrinks nor swells
 0.9% solution of NaCl (9g/L)
 5% solution of glucose (50g/L)
Hypotonic:
 Water concentration in the ECF is higher than ICF
 Water diffuse into cells diluting ICF
 Cells swell
Hypertonic:
 Water concentration in the ICF is higher than ECF
 Water diffuse out of the cells concentrating ICF
 Cells shrink
PHYSIOLOGY
 ↓ Extracellular fluid
volume

↓ Cardiac output

↓ Effective arterial blood

volume

Arterial underfilling

Unloading of high-pressure
volume receptors

Stimulation of sympathetic
nervous system

Nonosmotic ADH release Activation of RAAS

↑ peripheral and renal arterial vascular resistance and Na + & H2O retention
 65% of
5% of the
filtered load
Everything filtered
of H20, Na
- protein NaCl
& > Cl
Principle &
intercalated
cells

25% of
the >10%
20% of the filtered water filtered of
loads filtered
of Na, water
Cl & K & Na
 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 of mitochondria 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
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
LOOP OF HENLE: THIN ASCENDING SEGMENT
no brush borders, few mitochondria, minimal levels of metabolic activity

 Impermeable to water
 Lower reabsorptive capacity
LOOP OF HENLE: THICK ASCENDING SEGMENT
 Thick epithelial cells with high metabolic activity and are capable of active reabsorption of
sodium, chloride, and potassium
 Almost 25% of the filtered loads of sodium, chloride and potassium are reabsorbed here
 Sodium-potassium pump in the basolateral membraneimportant 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
DISTAL TUBULE
1st portion forms the macula densa, a group of closely packed
epithelial cells that is part of the 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 cell
 sodium-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
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 membrane
Permeability is controlled by the concentration of ADH
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 and
relatively few mitochondria
Permeability is controlled by the concentration of ADH
High level of ADH, water is avidly reabsorb into the medullary
interstitium, thereby reducing the urine volume and concentrating most
of the solutes in the urine
Medullary collecting duct is permeable to urea and there are special
urea transporters that facilitate urea diffusion across the luminal
and basolateral membranes.
Some urea is reabsorbed into the medullary interstitium, helping to raise
the osmolarity
Medullary collecting duct is capable of secreting hydrogen ions
against a large concentration gradient, as also occur in cortical
collecting tubule. Thus regulating the acid-base balance
 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
REGULATION OF PERITUBULAR CAPILLARY PHYSICAL
FORCES
2 determinants of peritubular capillary reabsorption that are directly influenced by
renal hemodynamic changes are the hydrostatic and colloid osmotic pressures of
the peritubular capillaries.
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
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.
Changes in peritubular capillary physical forces influence tubular reabsorption by changing
the physical forces in the renal interstitium surrounding the tubules.
URINE CONCENTRATION

Established by LOH, CD and

vasa recta  reabsorption
of varying amounts of H2O
and Na+
Key player: ADH (= Vasopressin)
 URINE CONCENTRATION, CONT’D

Often expressed in osmolarity

mM/L or osmolality mM/kg
 Blood: 300 mOsm
 Filtrate in Bowman’s 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
 EFFECT OF ADH

Controls Urine concentration via

regulation of water
reabsorption from the filtrate Hi [ADH] Lo [ADH]
in the collecting duct
Osmoreceptors in hypothalamus
↑ ADH caused by:
 ↑ Na+ and/or osmolality in the ECF
 H2O deprivation
 ↓ renal blood flow

Fig 20-5
 EFFECT OF ADH, CONT’D

•ADH Receptors in CD cells

•Luminal CM is generally
impermeable to H2O
•Aquaporins (remember Ch. 5)
on cell membranes of CD are
variably active, dependent on
ADH
• “Membrane Recycling”
via exocytosis of AQP2
• Allows osmosis of H2O
into vasa recta
TROUBLES WITH ADH?

ADH deficiency:
•Diabetes insipidus
• Central
• Nephrogenic
•Nocturnal enuresis

ADH Excess:
•AKA Inappropriate ADH secretion
•XS H2O retention
Review:
CONCENTRATED VS. DILUTE
URINE
In presence of ADH: No ADH:
Insertion of H2O pores DCT & CD
into tubular luminal CM
impermeable to
At maximal H2O H2 O
permeability: Net H2O
movement stops at Osmolarity can plunge
equilibrium to ~ 50 mOsm
Maximum osmolarity of
urine up to 1200 mOsm
 LOH:
COUNTERCURRENT MULTIPLIER

leads to
Hyperosmotic IF in
medulla
Hyposmotic fluid
leaving LOH
 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 stimulates Na+ reabsorption and K+ excretion in last 1/3 of DCT

and CD
 Type of hormone? Where produced? Type of mechanism?
  Aldosterone secretion   Na+ absorption from DCT
 Secretion of aldosterone by two mechanisms
  K+ in ECF
 ↓ BP
 The signal to release aldosterone is via angiotensin II
Opposite of Aldosterone?
 ANP (from the atria) causes loss of Na+
 REGULATION OF BP:
RAAS PATHWAYS

RAAS = renin-angiotensin-
aldosterone system
JG cells release renin in response
to ↓ BP
 Renin converts Angiotensinogen to
Angiotensin I

 ANG I converted to ANG II by ACE

RAAS PATHWAYS, CONT’D

ANG II causes ↑ BP via

↑ ADH Secretion
Thirst
Vasoconstriction
Sympathetic stimulation of heart  ↑
HR and CO
ACE inhibitors will ↓ BP
 KEY PROCESSES

Countercurrent Multiplication: Segments of Loop of Henle

Countercurrent multiplication: Urea recycling
Countercurrent Exchange: Vasa recta
ADH
Produce by hypothalamus
Stored in posterior pituitary gland

Blood osmolarity ↑

Release of ADH into

distal convoluted tubule
& collecting duct

Act on medullary
Act on aquaporin
collecting duct

Aquaporin move to
surface
↑ Permeability
to urea
Allow water to move
from tubule to interstitial
and then into capillary
↓osmolarity
 ALDOSTERONE
Mineralocorticoid
Produced in adrenal gland in kidney
↓BP

Low Na in
Medulla densa

RAAS

↑Aldosterone Angiotensinogen

↑ sodium
reabsorption Angiotensin I  II

↑ H20
reabsorption
vasoconstriction

↑Blood volume ↑BP