1
Disorders of
Sodium and Water
Metabolism
Homeostasis
 The maintenance of normal volume and normal
composition of the extracellular fluid.
 Homeostasis: the various physiologic arrangements,
which serve to restore the normal state, once it has
been disturbed
 Fluid balance
 Electrolyte balance
 Osmotic balance
 Acid-base balance
General principles
 Diffusion: movement of the particles in a
solution from the area of high concentration to
the area of lower concentration
 Electrolyte: inorganic substance that dissociates
into ions
 Osmosis: diffusion of solvent molecules (water)
into region in which there is a higher
concentration of a solute (electrolyte) to which
the membrane is impermeable
 Osmotic pressure: the pressure necessary to
prevent solvent migration
Osmol: concentration of osmotic active
General principles
 Osmolarity : number of osmoles per liter of solution
 Osmolality: number of osmoles per kilogram of solvent
 Measurement: depression of freezing point
 Calculation (plasma): 2x(Na+K)+glucose+BUN (mmol/l)
 Osmolality is the same in the ICF and the ECF.
 Tonicity: effective osmolality of a solution relative to plasma
 tonicity is only influenced by solutes that cannot cross this
semipermeable membrane, because these are the only
solutes influencing the osmotic pressure gradient.
Iso-osmolar solutions and isotonic?
Dextrose penetrates the cells so easily - it cannot contribute to
tonicity. Thus, the infused dextrose is iso-osmolar but hypotonic.
General principles
 Colloids: high molecular weight particles (> 20000 D)
 Oncotic pressure (colloid osmotic pressure): the
pressure necessery to prevent diffusion of solvent
molecules (water) into region in which there is a higher
concentration of a colloid to which the membrane is
impermeable
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Compartments of body fluids
 Total body water averages about 60% of body weight
 Aproximate volume of body fluids compartments:
 60% intracellular water
 40% extracellular water
 31%interstitial fluid
 7% plasma
 2% transcellular fluids (saliva, bile, etc.)
Intracellular spaceExtracellular space
Interstitial spaceIntravasal
space
Capillary wall
Oncotic pressure
Colloids
Electrolytes
Water
Cell membrane
Osmotic pressure
Compartements of body fluids
1
ExtraCellularSpace 1/3
ISS
3/4
IntraCellularSpace 2/3
epitheliumTRANSCELLULAR SPACE
endothelium
IVS
1/4
plasma
lymph
water
Na+
Osmosis
Decrease of osmolality Increase of osm.
Change of the cell volume in response to change
in extracellular osmolality
285280
280280
285
290
290
290
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
Blood plasma
 Osmolality 280-290 mosm/kg
 Osmotic pressure 745 kPa
 Onkotic pressure 3,3 kPa
 Na 135-145 mmol/l
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Note: Normal plasma Na concentrations 
roughly normal plasma osmolality 
normal osmolality of the cells. The
electrolyte content in the cells is roughly
fixed  normal volume of liquid in the cells
(IC space)
A large quantity of water is exchanged
between an organisms and the environment
via kidneys and a gut  a small percentual
derangement has large consequences for
the whole-body water and electrolyte
balance
Fluid compartment volume and
osmolar changes
Normal regulation of sodium
balance
 Extracellular fluid volume is controlled by the
amount of sodium in the body
 The kidneys regulate the sodium excretion or
retention
 The changes in osmolality are detected by
hypothalamus → changes in ADH secretion →
water secretion or reabsorption
Normal regulation of sodium
balance
Normal regulation of water
balance
 Extracellular fluid osmolality is controlled by the
amount of water in the body
 The kidneys regulate the water excretion
Water intake
 Food
 Metabolic water
 Drinking is the most important way of water
intake regulated by the thirst
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Water excretion
 Skin (perspiratio insensibilis, sweat)
 Respiratory system (perspiratio insensibilis)
 Stool
 Urine excretion is the most important way
of water loss regulation - ADH
Daily Water Balance (liters)
 FLUID INTAKE 1.5
 IN FOOD 0,8
 METABOLIC 0.3
 Total 2.6
 INSENSIBLE 0.8
 SWEAT 0.1
 FECES 0.2
 URINE 1.5
 Total 2.6
INPUT OUTPUT
Volume and tonicity regulation
 Tonicity is ultimately regulated by
water, the circulating volume by
sodium
 Tonicity – hypothalamic osmoreceptors →
neurohypophysis, thirst and ADH → renal water
reabsorption
 Volume – baroreceptors, more sluggish feedback than
osmoreceptors, under extreme conditions:
Volume overrides tonicity
Water Deficit
 INCREASED OSMOLARITY
SENSED BY HYPOTHALAMIC
RECEPTORS
 FALL IN ECF VOLUME
 FALL IN ARTERIAL BLOOD
PRESSURE
STIMULATION
OF HYPOTHALAMIC
NEURONS
INCREASED THIRST
INCREASED WATER INTAKE
DECREASED PLASMA OSMOLARITY
INCREASED VASOPRESSIN
OPEN PORES
IN COLLECTING
DUCT
MORE WATER REABSORBED
FALL IN URINE OUTPUT
ARTERIOLAR
VASOCONSTRICTION
DECREASED PLASMA OSMOLARITY
RELIEVES
RELIEVES
Blood pressure and renal
handling of sodium
FALL IN SODIUM LOAD
FALL IN ARTERIAL PRESSURE
FALL IN GFR
FALL IN FILTERED
SODIUM
INCREASE IN
ALDOSTERONE
SECRETION
INCREASE IN
SODIUM
ABSORPTION
FALL IN EXCRETION OF
SODIUM, CHLORIDE, AND
FLUID
INCREASED CONSERVATION
OF SODIUM AND FLUID
RELIEVES
3
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Regarding adiuretine and thirst regulation:
osmoreception (feedback No. 3) is functioning
more sensitively, volumoreception (feedback
No. 1) more sluggish, later more forcefully,
however  “volume overrides tonicity” when
the large deviations of volume and tonicity from
a norm take place. It is a consequence of the
type of dependency of the ADH production on
both these factors. A circulatory failure is
apparently evaluated to be more dangerous
acutely than the CNS disturbances.
Disturbances of fluid
homeostasis
 Disturbance of fluid balance (intake≠output)
 Dehydraton, Overhydration (hyperhydration)
 Disturbance of osmolarity (electrolyte
intake≠water intake)
 Isonatremic (isotonic)
 Hyponatremic (hypotonic)
 Hypernatremic (hypertonic)
Dehydration
 Signs: increased thirst (except: advanced age, hypotonic
dehydration), weakness, decreased skin turgor, dry
mucous membranes, empty neck veins, decreased urine
output, elevated Htk, fever, tachycardia, hypotension,
decreased CVP,lethargy, stupor, coma
 Mild (loss: 4% of body weight): decresed skin turgor, sunken
eyes, dry mucous membranes
 Moderate (loss: 5-8 % of body weight): + oliguria, orthostatic
hypotension, tachycardia
 Severe (loss: 8-10 % of body weight): + hypotension,
decreased level of consciusness, stupor
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Tonicity disorders  disorders of
water: states 1, 4, 6, 9
Volume disorders  sodium
disorders: states 2, 3, 8, 7
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9
Explanatory notes
a – overshooting compensation of hyperosmolality (state 9) by water
b – a trade off by means of ADH: hypervolemia does not rise so much
with a considerable NaEC enhancement that isoosmolality could
be maintained
c – loss of effective blood volume
d – three factors of Na retention (GFR, aldosterone, 3rd factor)
e – by means of ADH
f – nonsteroid antiphlogistics (acetylosalicylic acid, sodium salicylate,
phenacetin, paracetamol) depress the protective prostaglandins in
the kidney  decline of GFR
g – SIADH is euvolemic clinically, hypervolemic subclinically
h – by means of thirst and ADH, some loss of salt is presupposed,
however
i – although body dehydration may be considerable with the loss
of hypotonic fluids, loss of circulating volume used to be
negligible in this condition (loss of water is compensated in
90% from stores outside the circulating volume)
j – if the water loss is much higher than loss of salt, NaEC lowering
may be attended by PNa rise
k – an organismus has lost salt and water massively, it tries,
however, to maintain predominantly the volume by the quick
feedback by means of thirst and ADH in this extreme situation
(salt losses are compensated only by drinking); it succeeds only
partially, however, and it is paid by hypotonicity (a trade-off
again);
l – Na in urine < 10mmol/L
m – Na in urine > 20 mmol/L – the urine itself is effective in
the Na loss
n – with a small urine volume Na in urine > 600 mmol/L
The body receives (retains) Na mainly hyperosmolal
hyperhydratation
RdS: massive Na intake (per os, sea water)
RgS: primary surplus of mineralokorticoids
RgO: acute glomerular diseases
billateral parenchymatous
renal diseases with chronic
renal failure (GFR < 10mL/min)
CONDITION 3 Na
10
Fig. 10 – hyperosmolal hyperhydration (state 3)
Renal failure with the GFR value higher than 10
mL/min is not connected with a deranged G-T
balance  under the lowered GFR,
reabsorption is lowered, too. G-T balance is
disturbed in acure nephritic syndrome, however
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Body receives (retains) isoosmolal fluid mainly isoosmolal
hyperhydratation
RdS: i.v. infusion of isoosmolal fluids
nephrotic syndrome
cirrhosis
RgS: cardiac failure
RgO: non-steroid antiphlogistics
failing kidney ( GFR!)
acute & chronic, esp. when
isoosmotic solutions are administered
CONDITION 2 Na
11
Fig. 11 – isoosmolal hyperhydration (state 2)
Heart failure: a decline of effective blood volume
is signalized, RAS and SAS are activated
(Fig. 11), GFR, “3rd factor”
12
9
The body receives (retains) H2O mainly hypoosmolal
hyperhydratation
RD: infusion of glucose solutions, nephrotic syndrome
cirrhosis
RS: psychogenic polydipsia
renal oligo/anuria when tubular H2O reabsorption
with SIADH, chlorpropamid
cardiac failure
RO: renal oligo/anuria
 GFR
esp. in combination with H2O or glucose
solution administration
CONDITION 1 Na
13
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9
Consequences of hypervolemia:
Hypervolemia  enhanced left ventricle preload 
enhanced cardiac output
cardiac output * unchanged peripheral resistance
= arterial pressure
arterial pressure  hydrostatic capillary pressure
 filtration into the IC space 
edema
The body does not receive (loses) H2O mainly hyperosmolal
dehydratation
RdS: vomiting
diarrhoe
sweating
insesible losses
hyperventilation, fever, hot environment
hyperglycemia in diabetes mellitus
mannitol
CONDITION 9 Na
14
RgS:  thirst
unconsciousness
newborns
diabetes insipidus (central)
RgO: osmotic diuresis in diabetes mellitus
diabetes insipidus (nephrogenic)
polyuria in acute renal failure
14
If the water supply is not disturbed and Na is normal,
state 9 cannot last long
9
Body loses isoosmolal fluid isoosmolal
dehydratation
RD: loss of blood or plasma
burns, ascites draining
diarrhoe, gall drains, fistulas
escape into interstitium or 3rd space
crushing of tissues, intestinal obstruction,
pancreatitis
hemorrhage into body cavities
RO: abusus of saluretics
and many other renal loss types
CONDITION 8 Na
15
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9
Body does not receive (loses) Na mainly hypoosmolal
dehydratation
RD: alimentary lack of salt in combination with loses
RS: primary lack of mineralocorticoids
RO: renal salt losses:
polyuria in acute renal failure
loss of hypotonic fluids  trade off
preferring volume
pressure diuresis in extemely enhanced
blood pressure
BARTTER syndrome
abusus of diuretics
CONDITION 7 Na
16
9 17
Na AND H2O EXCRETION IN VARIOUS
PATHOLOGIC RENAL CONDITIONS
CONDITION Na H2O
ACUTE GLOMERULAR DISEASES RETENTION RETENTION
STENOSIS OF ART. RENALIS RETENTION RETENTION
CONSIDERABLY ENHANCED BP EXCRETION EXCRETION
PRESSURE DIURESIS
PRERENALAZOTEMIA RETENTION RETENTION
AIMED AT CORRECTING
BP OR VOLUME
A survey of the influence of renal pathology on volume and osmolality
Fig. 17
CONDITIOON Na H2O
ACUTE RENAL FAILURE RETENTION RETENTION
INITIAL PHASE (ANURIA,
OLIGURIA)
PREREN. AZOTEMIA MOST OFTEN
RESTITUTION PHASE (POLYURIC) EXCRETION EXCRETION
- SALT WASTING KIDNEY
CHRONIC RENAL FAILURE WITHOUT WITHOUT
(TO THE ADVANCED PHASE) DISTURBAN- DISTURBANCES
CES
GFR < 10 - 20 mL/min RETENTION RETENTION
TUBULOINTERSTITIAL DISEASES, EXCRETION EXCRETION
ADRENAL INSUFICIENCY, DIURETICS,
„WASTING SALT“ NEPHROPATHY
(i.g. CHRF) 17
Control of Interstitial Fluid
 Hydrostatic pressure
 Oncotic pressure
 Endothelial integrity
 Lymphatic system
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2.2 Edematous conditions
* with the exception of primary renal retention
Movement Of Fluid Across
Capillaries
 Capillary (hydrostatic) pressure
 Interstitial fluid (hydrostatic) pressure
 Plasma oncotic pressure
 Interstitial fluid oncotic pressure
Capillary Pressure
 Forces fluid from capillary to interstitium
 Arterial end higher than venous end
 Arterial approx. 30 mmHg
 Venous approx. 10 mm Hg
Interstitial Fluid Pressure
 Maybe positive or negative
 Negative - forces fluid into interstitium
 Positive - forces fluid into capillary
 Approx. minus 3 mm Hg in loose connective
tissue
 Higher in denser connective tissue
Plasma Oncotic Pressure
 Proteins are the only solutes which do not pass freely
between plasma and interstitium
 Thus it is only proteins which exert a significant
osmotic effect across capillary walls
 Albumin is the most abundant plasma protein
 Approx 28 mm Hg (Albumin = 21.8)
Interstitial Oncotic Pressure
 A small amount of protein is present in the
interstitium
 Tends to force fluid out of capillary
 Concentration is approx 40 % of that in plasma
 Approx 8 mm Hg
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Lymphatic System
 The lymphatic system provides a route for the
transport of fluids and protein away from the
interstitium
 System of fine lymphatic channels throughout
the body passing via lymph nodes to thoracic
duct
 Valves ensure one-way flow
Oedema
 Hydrostatic pressure
 Oncotic pressure
 Endothelial integrity
 Lymphatic integrity
Oedema
 Definition
An increased volume of interstitial fluid in a
tissue or organ
May be localised or generalised (systemic)
Causes of Oedema
 Raised capillary pressure
 Reduced oncotic pressure
 Endothelial damage (inflammation)
 Impaired lymphatic drainage
Raised Capillary Pressure
 Cardiac failure
 right ventricular failure - systemic oedema
 left ventricular failure - pulmonary oedema
 congestive cardiac failure - both
 Local venous obstruction
 deep vein thrombosis
 external compression
 SVC obstruction
Reduced Oncotic Pressure
 Renal disease
 loss of albumin across glomerulus
 Hepatic disease
 inadequate albumin synthesis
 Malnutrition
 inadequate albumin synthesis
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Lymphatic Obstruction
 Tumours
 Fibrosis
 Inflammation
 Surgery
 Congenital abnormality
Generalised Oedema
 Congestive cardiac failure
 Right ventricular failure
 Renal disease
 Liver disease
With the exception of the “primary”
hypervolemia conditioned by primary renal Na
retention, RAS is activated secondarily
(possibly secondary hyperaldosteronismus may
be elicited)  Na retention  edema
Not in Fig. : Cardiac failure  distortion of
baroreception  RAS, SAS, 3rd factor
activation, GFR