Review: Plasma Membrane

Phospholipid bilayer Freely permeable to non-polar molecules (CO2, O2, steroids)

Impermeable to large polar and charged molecules (ions, proteins, glucose)

Generally permeable to water (though some cells require aquaporins)

Age group Premature infant Newborn infant 12-24 months Adult

Approx water content in body 90% 70-80% 64% 60%

45% solids

40% solids

Some fluid is lost from blood in the interstitial tissues, and returned by the lymphatic system
2/3 Intracellular fluid (ICF)

55% fluids

60% fluids

(also lymph and other miscellaneous fluids)

female

male

1/3 (ECF)

80%
20%

Interstitial fluid

Plasma

Total Body Mass

2/3

(65%) of TBW is intracellular (ICF) 1/3 extracellular water

25 % interstitial fluid (ISF) 5- 8 % in plasma (IVF intravascular fluid) 1- 2 % in transcellular fluids CSF, intraocular

fluids, serous membranes, and in GI, respiratory and urinary tracts (third space)
5

Function of ICF & ECF: ICF: is vital to normal cell function, its contain solutes such as oxygen, electrolytes and glucose. It provides a medium to metabolic process.
ECF:

it is the transport system that carries nutrients and waste product from the cell.

 The

proportion of water decreases with aging because fat, age and sex effect of total body water. Infants have a greater proportion of extracellular fluid than older children and adults. Because extracellular fluid is more easily lost from the body than intracellular fluid, infants are more at risk of developing dehydration than older children and adults (infants also have a larger surface area to body mass ratio).

K+ Mg2+ PO43Na+ ClHCO3- - - + + + +

 Electrolytes

charged particles

Cations positively charged ions

Na+, K+ , Ca++, H+ Anions negatively charged ions Cl-, HCO - , PO 33 4

Non-electrolytes

- Uncharged
9

Proteins, urea, glucose, O2, CO2

ICF (mEq/L) Sodium 20 Potassium 150 Chloride --Bicarbonate 10 Phosphate 110-115 Protein 75

ECF (mEq/L) 135-145 3-5 98-110 20-25 5 10

o Osmolarity = solute/(solute+solvent)

o Osmolality = solute/solvent (275-295 mOsm/L) o Tonicity = effective osmolality o Plasma osmolility = 2 x (Na) + (Glucose/18) +
(Urea/2.8)

o Plasma tonicity = 2 x (Na) + (Glucose/18)

MW (Molecular Weight) = sum of the weights of atoms in a molecule mEq (milliequivalents) = MW (in mg)/ valence mOsm (milliosmoles) = number of particles in a solution

Tonicity Isotonic Hypertonic Hypotonic

13

14

Cell in a hypotonic solution

15

Cell in a hypertonic solution

16

MOVEMENT OF BODY FLUIDS

Diffusion Osmosis Filtration Active

transport

1. Osmosis: Is the movement of water across cell membranes, from the less concentrated solution to more concentrated solution. In other word water move toward higher concentration.

 Solutes are substance dissolved in liquid. Crystalloid: salts that dissolved readily in to true solution. Colloids: substance such as large protein molecules that

do not dissolved in true solution.

Sodium

is the major determinant of serum osmolality.

2. Diffusion:

Is the continual intermingling of molecules in liquid, gases by random movement of the molecules. Is the process where by fluid and solutes moved together across a membrane from one compartment to another.

3. Filtration:

4. Active transport: substance can move across cell membranes

from a less concentrated solution to amore concentrated one by active transport.

Sodium and potassium concentrations in extra- and intracellular fluids are nearly opposite This reflects the activity of ATP-dependent sodiumpotassium pumps (Na+-K+ ATPase)

Fluid Movement Among Compartments

Continuous

exchange and mixing of fluid among compartments - regulated by osmotic and hydrostatic pressures

Net leakage of fluid from the blood is picked up by lymphatic vessels and returned to the bloodstream Exchanges between interstitial and intracellular fluids are more complex due to the selective permeability of the cell membranes

ICF is determined by the ECF solute concentration

An

increase in ECF solute concentration [NaCl] would cause osmotic and volume changes in the ICF. Which way would water move, into or out of cells?
Hypertonic Solution or Hypotonic Solution?
solute H 2O H 2O H 2O H 2O solute H 2O H 2O H 2O H 2O H 2O solute H 2O H 2O H 2O H 2O H 2O H 2O H 2O solute solute solute solute H 2O solute solute H 2O solute

H 2O solute solute H 2O

solute

Less Soluteway = More Water Solute = Less Water Which will Water More move?

If the oncotic pressure in the interstitium increased, would this promote or inhibit the re-entry of fluid in a capillary bed?

solute

solute solute solute H 2O solute solute H 2O

H 2O solute

H 2O solute H 2O solute H 2O

solute

 Daily water intake must equal water output Water Intake

Stimulated by thirst center of hypothalamus

Water Output
Sensible loss: urine, feces, noticible sweat

Osmoreceptors detect an increase in fluid osmolarity Thirst center inhibited by distension of stomach wall

Insensible loss: respiration and nonnoticible sweat

Urine output is the primary regulator of water out (ADH from posterior pituitary gland)

To remain properly hydrated, water intake must equal water output

Water

intake:

Ingested fluid (60%) and solid food (30%) Metabolic water or water of oxidation (10%)
Water output: Urine (60%) and feces (4%) Lost via lungs and skin (28%), sweat (8%)

Fluid Gain and Loss

Why are you told to drink plenty of fluids when you have a fever? A fever increases water loss (maybe both insensible and sensible)

The

hypothalamic thirst center is stimulated by: A decline in plasma volume of 10%15% Increases in plasma osmolality of 12% Baroreceptor input, angiotensin II, etc.

Feedback signals that inhibit the thirst centers include: Moistening of the mucosa of the mouth and throat Activation of stomach and intestinal stretch receptors

Hormonal regulation

Regulation of ECF

 Body

fluids are: Electrically neutral Osmotically maintained Specific number of particles per

volume of fluid

 Ion

transport Water movement Kidney function

 Water

loss (output) exceeds water intake and the body is in negative fluid balance A common sequala to hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, and diuretic abuse Signs and symptoms: dry mouth, thirst, dry flushed skin, and oliguria Prolonged dehydration may lead to weight loss, fever, and mental confusion Other consequences include hypovolemic shock and loss of electrolytes

Accumulation

of fluid in the interstitial space, leading to tissue swelling, caused by anything that increases fluid flow out of the bloodstream or hinders its return

Factors that accelerate fluid loss include: Hypertension, increased capillary permeability, incompetent venous valves, localized blood vessel blockage, congestive heart failure

Edema
Decreased

fluid return usually reflects an imbalance in colloid osmotic pressures across capillary membranes

Hypoproteinemia low levels of plasma proteins, may result from protein malnutrition, liver disease, or glomerulonephritis Fluids are forced out of capillary beds at the arterial ends by blood pressure, but fail to return at the venous ends and interstitium becomes congested with fluid

Edema - lymphedema
Blocked

(or surgically removed) lymph vessels may result in the accumulation of plasma proteins in interstitial fluid

Interstitial colloid osmotic pressure increases, fluid leaves blood and moves into tissue Interstitial fluid accumulation could result in a decrease in blood volume, blood pressure, and impaired circulation

Protein Deficiencies

Kwashiorkor - a form of malnutrition caused by inadequate protein intake and consequent reduced albumin in the blood
hypoalbuminemia and reduced plasma oncotic pressure promote the extravasation of fluid from the plasma into the peritoneal cavity

:Signs of Hypervolemia
Hypertension Polyuria Peripheral edema Especially when hypoalbuminemia Wet lung Jugular vein engorgement

:Signs of Hypovolemia

Diminished skin turgor Dry oral mucus membrane Oliguria - <500ml/day - normal: 0.5~1ml/kg/h Tachycardia Hypotension Hypoperfusioncyanosis Altered mental status

:Clinical Diagnosis of Hypovolemia

Thorough history taking: poor intake, GI bleedingetc BUN : Creatinine > 20 : 1 - BUN: hyperalimentation, glucocorticoid therapy, UGI bleeding Increased specific gravity Increased hematocrit Electrolytes imbalance Acid-base disorder

Clinical parameters for evaluation of water balance

CVP Pulse Peripheral Weight Thirst Intake Skin Edema Lab

Veins

and Output

Values

Reasons for fluid therapy

Preserve oxygen delivery to tissues Correct hypovolaemia Maintain cardiac output Optimise gas exchange Replace electrolytes & water Maintain urine output
Identify what is the goal Choose fluid which best achieves the goal Crystalloids Colloids + RBCs

Methods of Estimating Maintenance Fluids

Methods

of estimating basal or maintenance fluid requirements

Basal Surface Area Need to know height and weight, requires table, does not allow for deviations from normal activity Basal or Calorie Expenditure Method Requires a table, involves calculations, permits correction for changes in activity or injury, drier Holliday-Segar System Easy to remember, does not require table or difficult calculations, does not allow for deviations from normal activity

:Crystalloids
Isotonic crystalloids - Lactated Ringers, 0.9% NaCl - only 25% remain intravascularly Hypertonic saline solutions - 3% NaCl Hypotonic solutions - D5W, 0.45% NaCl - less than 10% remain intravascularly, inadequate for fluid resuscitation

:Colloid Solutions

Contain high molecular weight substancesdo not readily migrate across capillary walls Preparations - Albumin: 5%, 25% - Dextran - Gelifundol - Haes-steril 10%

Common parenteral fluid therapy

Solutions ECF Lactated Ringers NaCl 0.9% NaCl 0.45% D5W D5/0.45% NaCl NaCl 3% 6% Hetastarch Albumin 5% 25% Albumin 500 250,500 20,50,100 77 513 154 130160 130160 2.5< 2.5< 77 513 154 130160 130160 50 406 1026 310 330 330 Volumes
+

Na

Ca+2 5 3

Mg+2

Cl

HCO3 27 28

Dextrose

mOsm/L 280-310 273 308 154

142 130 154 77

4 4

103 109 154 77

ISOTONIC SOLUTIONS
0.9% D5W D51/4NS D51/3NS LR

Normal Saline 5 % Dextrose* 5% Dextrose 0.2% NS 5% Dextrose 0.3% NS Lactated Ringers Solution

or RL

HYPERTONIC SOLUTIONS

3% N S 5%NS D 10 W D 20 W D5 NS D5NS D5LR

3% Normal saline 5% Normal Saline Dextrose 10% in water Dextrose 20% in Water 5%Dextrose,with 0.45% Normal Saline 5% Dextrose with 0.9% Normal Saline 5% Dextrose with Lactated Ringers

HYPOTONIC SOLUTIONS
1/3 1/2 D

NS NS

0.33% Normal Saline 0.45% Normal Saline Dextrose 2.5% in water

2.5 W

 Neonates

need relatively more fluid intake than older infants and children. kidneys in neonates have small immature glomeruli and for this reason the glomerular filtration rate is reduced (about 30ml/min/1.73m2 at birth to 100ml/min/1.73m2 at nine months). loops of Henle are short and the distal convoluted tubules are relatively resistant to aldosterone, leading to a limited concentrating ability

The

The

 For

oral feeding with standard formula milk, preterm babies may need 200ml/kg per day initially. babies need approximately 150ml/kg per day until fully weaned. and adolescents may drink up to 2-3 litres of fluid per day.

Term

Children

 Hourly

maintenance fluid requirements can be calculated using the following guide:

4ml/kg/hr or 100ml/kg/day for first 10kg body Weight 2ml/kg/hr or 50ml/kg/day for second 10kg body Weight 1ml/kg/hr or 20ml/kg/day for each additional kg body weight
The

recommended volume of oral feeds is greater than that calculated using this guide so that adequate calorie and protein intake can be achieved.

ElECTROLYTE REQUIREMENTS Na+ 3 mEq/100ml Cl- 4 mEq/100ml K+ 2 mEq/100ml

Deficit: Fluid
Definition:

Amount of fluid lost before treatment is begun One-time estimate; additional losses after therapy is begun are considered on-going losses Methods:
Preillness and current weight change

Fluid deficit (L) = Preillness weight (kg) current weight (kg) % Dehydration = (Fluid deficit (L)/Preillness weight (kg))x100

Clinical estimates of weight loss

Deficit: Electrolytes
Sodium:

usually in pediatrics, losses are gastrointestinal or due to a relatively short period of decreased oral intake
approximated by 0.45 NS

Potassium:

deficit replacement is based on rate of safe replacement and not amount since danger of hyperkalemia is greater than hypokalemia
Add 20 mEq potassium/L after UOP is established Potassium infusion rate should not exceed 1 mEq/kg/hour unless

in monitored setting

Ongoing losses: Fluid and Electrolytes

Fluid:

abnormal losses that occur after the one-time determination of a deficit

Diarrhea, vomiting, NG aspirates, polyuria Measured and replaced cc for cc

Electrolytes:
Consult tables for electrolyte composition of on-going

losses

GI losses = 0.45 NS Transudates = 0.9 NS Radiant losses = sodium free

Monitoring Effectiveness of Parenteral Therapy

Maintenance fluid requirements must be modified according to the childs clinical condition. All types of fluid intake and output must be measured . If the child is dehydrated or has excessive fluid losses, fluid intake must be increased. For zero fluid balance, fluid losses = fluid intake. Insensible fluid loss is fluid lost from the body in perspiration and breathing, and is proportional to body surface area (BSA). It is approximately 300ml/m2/day ,slightly higher in infants and young children, warm temperature, pyrexia, tachypnoea, etc.

Using indirect calorimetric measurements, energy expenditure in critically ill children may be as low as 50-60 kcal/kg/day. Mechanical ventilation decreases the work of breathing as well as evaporative water loss through the respiratory tract and the energy expenditure for thermal regulation. Warmed humidification of respiratory gases through the ventilator circuit can reduce insensible water losses by as much as one third. Hence, traditional estimates for maintenance fluid volumes particularly in critically ill children cannot be quantified from these general guidelines.

The most potent stimuli for ADH secretion are an increase In serum osmolality, hypovolemia and hypotension. However, multiple nonosmotic stimuli such as pain, drugs and anesthetic agents, stress, and even nausea and vomiting may also result in increased ADH activity. There will be very little if any excretion of EFW, as ADH limits renal water excretion in this setting, even in the presence of a low plasma osmolality. As a result, hyponatremia occurs due to a positive balance of EFW in association with an impaired ability to excrete hypotonic urine. Any exogenous sources of free water, such as the administration of hypotonic IV maintenance fluids, will therefore further exacerbate the fall in plasma sodium (PNa).

Recently conducted systematic review of maintenance fluids for hospitalized children revealed that the use of hypotonic fluids remarkably increased the odds of developing hyponatremia by 17 times when compared to isotonic fluids.

Fluid Compartments
Cells 28 Litres

Interstitial fluid 10.5 Litres

Blood volume 3.5 litres

Fluid shifts in haemorrhage

Fluid shifts in haemorrhage

Vasoconstriction & redistribution

Fluid shifts in haemorrhage

Interstitial fluid mobilisation

Fluid shifts in haemorrhage

Reduced interstitial fluid

Fluid shifts in haemorrhage

Intracellular fluid mobilisation

Fluid shifts in haemorrhage

Reduced intracellular fluid

What are we trying to achieve by giving intravenous fluid ? Scenario: Acute blood loss Replacement of RBCs, water and electrolytes haemostasis

Fluid shifts in trauma, infection, ischaemia-reperfusion injury

Inflammation

Fluid shifts in inflammation

Fluid shifts in blunt trauma

Inflammatory cytokines

Neutrophils

Fluid shifts in blunt trauma

Systemic capillary leak

Leak of Water, Na+ ClAlbumin to Interstitium Vasodilatation loss of SVR

Interstitial oedema Hypovolaemia

Na+ Clwater

Interstitial oedema

Na+ Clwater

injur y

Infla med mmatory iator relea se

Na+ and Cl- Loading Fluid retention Severe interstitial oedema Organ dysfunction

What are we trying to achieve by giving intravenous fluid ? Scenario: Acute inflammation Blood volume expansion, in the context of vascular dysfunction and leaky capillaries

Things to Remember
It is very easy to give salt & water to critically ill patients, and very difficult to remove Urine electrolyte measurement is essential for fluid management in the critically ill

Electrolyte Balance
Electrolytes

are salts, acids, and bases, but electrolyte balance usually refers only to salt balance Salts are important for:
Neuromuscular excitability Secretory activity Membrane permeability Controlling fluid movements

Salts

enter the body by ingestion and are lost via perspiration, feces, and urine

Electrolyte Concentration
Expressed

in milliequivalents per liter (mEq/L) - a measure of the number of electrical charges in one liter of solution
X

mEq/L = (concentration of ion in [mg/L] the atomic weight of ion

For

no. of electrica charges on one ion

monovalent ions, 1 mEq = 1 mOsm For bivalent ions, 1 mEq = 1/2 mOsm

The equivalent weight of a substance is equal to the amount in moles divided by the valence.
The equivalent (Eq or eq) is a measurement unit used in chemistry and the biological sciences - a measure of a substance's ability to combine with other substances - frequently used in the context of normality (GEW/liters of solution) The equivalent is defined as the mass (g) in grams of a substance which will react with 6.022 x 1023 electrons.
For

monovalent ions, 1 Eq = 1 mole For divalent ions, 1 Eq = 0.5 mol For trivalent ions, 1 Eq = 0.333 mol

ELECTROLYTE BALANCE
The

exchange of interstitial and intracellular fluid is controlled mainly by the presence of the electrolytes sodium and potassium

Na+ K+ K
+

K+ Na+ Na+

Na+

K+

ELECTROLYTE BALANCE
Potassium

is the chief intracellular cation and sodium the chief extracellular cation Because the osmotic pressure of the interstitial space and the ICF are generally equal, water typically does not enter or leave the cell

Na+

K+

ELECTROLYTE BALANCE
A

change in the concentration of either electrolyte will cause water to move into or out of the cell via osmosis A drop in potassium will cause fluid to leave the cell whilst a drop in sodium will cause fluid to enter the cell
H2O

Na

H2O

Na+ Na
+

K+
H2O H2O

K+ K
+

H2O

Na+
H2O

K+
H2O

H2O

ELECTROLYTE BALANCE
Aldosterone,

ANP and ADH regulate sodium levels within the body, whilst aldosterone can be said to regulate potassium
ADH

Na+

ANP

aldosterone

K+

ELECTROLYTE BALANCE
Sodium

(Na+) ions are the important cations in extracellular fluid

Na+

Anions

which accompany sodium are chloride (Cl-) and bicarbonate (HCO3-)

Cl Considered

HCO3-

an indicator of total solute concentration of plasma osmolality

 Sodium ions

are osmotically important in determining water movements

ELECTROLYTE BALANCE

discussion of sodium must also include Chlorine H2O Bicarbonate H2O H2O H2O H2O H2O H2O Hydrogen ions H2O H O H2O 2 H2O
H2O H2O H2O H2O

Potassium and

calcium serum concentrations are also important electrolytes in the living system

ELECTROLYTE BALANCES
Hypernatremia - elevated sodium levels Hyponatremia -- lowered sodium levels Hyperkalemia -- elevated potassium levels Hypokalemia ---- lowered potassium levels Hypercalcemia - elevated calcium levels Hypokalcemia -- lowered calcium levels

Click Click

SODIUM: Functions
Participates

in the Na-K pump Assists in maintaining blood volume Assists in nerve transmission & muscle contraction Primary determinant of ECF concentration Controls water distribution throughout the body Primary regulator of ECF volume Regulations: skin, GIT,Aldosterone increases Na retention in the kidney

HYPERNATREMIA
Normal

range for blood levels of sodium is app. 137 143 meq/liter to an elevated serum sodium level

Hypernatremia refers

(145 -150 mEq/liter)

Increased

levels of sodium ions are the result of diffusion and osmosis

Na+

SODIUM PRINCIPLES
1) Sodium ions do not cross cell membranes as quickly as water does
H2O H2O H2O Na+ Na+ H2O H2O

SODIUM PRINCIPLES
2) Cells pump sodium ions out of the cell by using sodium-potassium pumps

Na+ Na+ Na+ Na+

SODIUM PRINCIPLES
3) Increases in extracellular sodium ion levels do not
change intracellular sodium ion concentration Na+ Na
+

Na+
+

Na+ Na+ Na+

Na+ Na+ Na+

Na Na+ Na+
+

Na+ Na+ Na+ Na+

Na+

Na+ Na+

Na

RESULTS OF HYPERNATREMIA
1) Water is osmotically drawn out of the cells
Resulting in dehydration

Intracellular fluid volume

2) Increase in extracellular fluid volume Extracellular fluid volume

 In

the CNS tight junctions exist between endothelial cells of the capillary walls junctions restrict diffusion from capillaries to the interstitium of the brain
blood-brain barrier

CNS REACTION TO HYPERNATREMIA

These

Increased

levels of sodium ions in the blood does not result in increased sodium ions in brain interstitial fluid

CNS REACTION TO HYPERNATREMIA

the result of an osmotic gradient, water shifts from the interstitium and cells of the brain and enters the capillaries The brain tends to shrink and the capillaries dilate and possibly rupture Result is cerebral hemorrhage, blood clots, and neurological dysfunction
As

H2O

CNS PROTECTIVE MECHANISM

There

is an unknown mechanism that protects the brain from shrinkage about 1 day

Within

Intracellular osmolality of brain cells increases in

response to extracellular hyperosmolality

CNS PROTECTIVE MECHANISM

Idiogenic osmoles accumulate inside brain cells K+, Mg+ from cellular binding sites and amino acids from protein catabolism These idiogenic osmoles create an osmotic force that

H2O

draws water back into the brain and protects cells from dehydration

CAUSES OF HYPERNATREMIA
1) Water loss
2) Sodium ion overload Most cases are due to water deficit due to loss or inadequate intake Infants without access to water or increased insensible water loss can be very susceptible to hypernatremia

WATER LOSS
Diabetes

insipidus caused by inadequate ADH or renal insensitivity to ADH results in large urinary fluid loss Increased fluid loss also occurs as the result of osmotic diuresis (high solute loads are delivered to the kidney for elimination)

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney

Glucose

H2O H2O Glucose H2O H2O

Glucose Glucose Glucose 2 Glucose

H2O

H O

H2O

Glucose

H2O H2O

2 Glucose

H O

H 2O Glucose H2O

Glucose

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney
H2O H2O Glucose H2O H2O H2O

Glucose Glucose Glucose 2 Glucose

H O

Glucose

H2O

Glucose

H2O H2O

2 Glucose

H O

H 2O Glucose H2O

Glucose

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney
H2O H2O Glucose H2O H2O H2O

Glucose Glucose Glucose 2 Glucose

H O

Glucose

H2O

Glucose

H2O H2O

2 Glucose

H O

H 2O Glucose H2O

Glucose

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney
H O H2O H2O
2 Glucose

H2O

Glucose Glucose Glucose 2 Glucose

2 Glucose

H2O

H O

Glucose

H2O

Glucose

H2O H2O

H O

H 2O Glucose H2O

Glucose

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney
H O H2O H2O
2 Glucose

H2O H2O
Glucose 2 Glucose

Glucose Glucose

H O

Glucose

H2O H2O
Glucose

2 Glucose

H O

H2O H2O Glucose H2O

Glucose

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney
H2O H2O Glucose

H O Glucose H2O H2O Glucose H2O Glucose Glucose H2O H2O Glucose H2O Glucose H 2O Glucose Glucose H2O H2O
2 Glucose

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney
H O H2O
2 Glucose

H2O Glucose H2O

Glucose

Glucose

H2O H2O
Glucose

H2O Glucose H 2O Glucose H2O

H O H2O Glucose

Glucose 2 2 Glucose

H O

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney

H2O H2O Glucose H Glucose 2O Glucose H2O H2O Glucose HGlucose 2O Glucose H2O H2O Glucose HGlucose 2O H 2O Glucose Glucose H2O H2O

WATER LOSS
diabetes

mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney

H2O H2O Glucose H Glucose 2O Glucose H2O H2O Glucose HGlucose 2O Glucose H2O H2O Glucose HGlucose 2O H 2O Glucose Glucose H2O H2O

Re-animate

WATER LOSS
High

protein feedings by a stomach tube create high levels of urea in the glomerular filtrate producing an osmotic gradient the same as glucose does and increased urinary output results

SODIUM EXCESS
Occurs

less frequently than water loss or intake of excess sodium

Retention

ex: IV infusion of hypertonic sodium ion solutions

Aldosterone

promotes sodium and water retention by the kidney

High levels of aldosterone may result in mild

hypernatremia

CAUSES OF HYPERNATREMIA
CAUSE essential hypernatremia fever coma hot environment, or strenuous exercise vomiting diarrhea pituitary diabetes insipidus COMMENTS disorder in which thirst is impaired increased insensible fluid loss inadequate fluid intake sweat, hypotonic fluid loss often a hypotonic fluid loss often a hypotonic fluid loss deficiency of ADH; excessive fluid loss renal tubules insensitive to ADH; excessive urinary loss glucose in glomerular filtrate; osmotic diuresis urea is a product of protein metabolism; urea causes osmotic diuresis administration of excessive sodium ions mannitol in glomerular filtrate; osmotic diuresis

nephrogenic diabetes mellitus uncontrolled diabetes mellitus large amounts of protein and amino acids given by nasogastric tube excessive intravenous infusion of hypertonic sodium salt solutions mannitol used as diuretic

TREATMENT OF HYPERNATREMIA
Re-hydration

is the primary objective in most cases

Decreases sodium concentrations

point of concern is when and how rapid the re-hydration occurs

TREATMENT OF HYPERNATREMIA
After

24 hours the brain has responded by producing idiogenic osmoles to re-hydrate brain cells this adaptation has occurred and treatment involves a rapid infusion of dextrose for example:
There is danger of cerebral

If

edema with fluid being drawn into brain tissues

TREATMENT OF HYPERNATREMIA
Treatment

is best handled by giving slow infusions of glucose solutions

This dilutes high plasma

sodium ion concentrations

TREATMENT OF HYPERNATREMIA
Ideally

the goal is to avoid overloading with fluid and to remove excess sodium Diuretics can be used to induce sodium and water diuresis
However if kidney function is not normal peritoneal dialysis

may be required

Management
Two pronged approach: 1. Identify and treat the underlying cause. 2. Correct osmolar imbalance by replacing what was lost (water, hypotonic fluids +/electrolytes) or ridding the body of excess sodium

:Use the volume status to guide you

Hypovolemic:

Low total body Na, orthostasis: restore hemodynamics with NS, then change to D5W or NS Hypervolemic: Excess total body Na. Give loop diuretics to increase Na excretion and then replace D5W to correct hypertonicity. Dialyze if kidneys are not working. Euvolemic: Normal total body Na. Give D5W.

?How quickly can I decrease the serum Na

If

the Na has risen over a matter of <12 hours, it can be correctly quickly without consequence. If elevated for longer than 12 hours or if the onset is unclear, decrease Na by no more than 10 mmol/L/day or 0.5 mmol/L/hr. Goal is 145.

How do I decide how much fluid ?is necessary

One approach: 1. Calculate the total body water (TBW): 0.6 x (wt in kg) 2. Select your fluid and identify the amount of Na in mmol/L D5W 0 NS 34 NS 77 LR 130 NS 154

Calculate the effect of 1 L of your selected--3 :fluid on serum Na according to this formula Change in serum Na for 1L of fluid of choice =[IVF Na - serum Na] divided by [[TBW + 1 If you are also giving K in your IVF, modify the :formula as follows Change in serum Na for 1L of fluid of choice =[(IVF Na + IVF K) - serum Na] divided by [TBW + 1]

4-Decide how quickly you want to correct. In cases of prolonged hypernatremia, divide 10 (the desired drop) by the number obtained above to calculate the amount of IVF required over the next 24 hours to decrease the serum Na appropriately. When hypernatremia has been shorter-lived, divide the number necessary to reach 145 by the number of hours over which you want to correct. 5-Account for average obligatory 24 hour water losses (1.5L or so) 6-Convert to mL and divide by 24 to obtain mL/hour

HYPONATREMIA
Defined

as a serum sodium ion level that is lower than normal an increased ratio of water to sodium in extracellular fluid
Extracellular fluid is more dilute than

Implies

intracellular fluid

Results in a shift of water into cells

CNS RESPONSE TO HYPONATREMIA

Brain

cells lose osmoles creating a higher extracellular solute concentration Effect is to protect against cerebral edema by drawing water out of the brain tissue

GENERAL RESPONSE TO HYPONATREMIA

Suppression Suppression

of thirst of ADH secretion

Both favor decreasing water

ingestion and increasing urinary output

SYMPTOMS OF HYPONATREMIA
Primarily

brain) Sodium ion levels of 125 meq / liter are enough to begin the onset of symptoms Sodium ion levels of less than 110 meq / liter bring on seizures and coma

neurological (net flux of water into the

HYPONATREMIA
Produced by:
1) A loss of sodium ions 2) Water excess

Water excess can be due to:

Ingestion Renal retention

DILUTIONAL EFFECT
1) Isotonic fluid loss 2) Antidiuretic hormone secretion 3) Acute or chronic renal failure 4) Potassium ion loss 5) Diuretic therapy
H2 O H2 O Na+ H2 O Na+ H2 O Na+ H2 O H O H2 O Na+ 2 Na+ H2O H O H2 O H2 O 2 H2 O H2 O Na+ + Na H2 O H2 O H2 O H O Na+ 2

H2 O

H2 O

DILUTIONAL EFFECT
1) Isotonic fluid loss
Burns, fever, hemorrhage Indirect cause of hyponatremia Any volume loss stimulates thirst and leads to

increased water ingestion

Thus isotonic fluid loss can cause hyponatremia not because of sodium loss but because of increased water intake

DILUTIONAL EFFECT
2) Antidiuretic hormone secretion
Enhances water retention

3) Acute or chronic renal failure

The kidney fails to excrete water Can lead to hyponatremia

DILUTIONAL EFFECT
4) Potassium ion loss
Potassium ions are the predominant intracellular

cations When they are lost they are replaced by diffusion of intracellular potassium into extracellular fluid Electrical balance is maintained by the diffusion of sodium ions into the cells in exchange for potassium ions Thus a loss of extracellular sodium is realized and hyponatremia may ensue

POTASSIUM ION LOSS

3) intracellular electrical balance is maintained by diffusion of sodium ions into cells 1) extracellular potassium loss

K+

Na+

cell
K+

Na+

2) diffusion of potassium ions into extracellular compartments

K+ K+ interstitial fluid plasma

POTASSIUM ION LOSS

Na+ K+ K+ K+
Click to see animation

Na+

Cell

Na+

K+

K+ K+ Plasma

Interstitial fluid

5) Diuretic therapy

DILUTIONAL EFFECT

Common cause of hyponatremia Loss of sodium and potassium often occurs in addition

to fluid loss

CAUSES OF HYPONATREMIA
CAUSE psychogenic polydipsia syndrome of inappropriate secretion of ADH Addisons disease COMMENTS excessive ingestion of water ADH causes renal water retention aldosterone deficiency

K+ losses from extracellular K+ move out of cells to replace fluid losses; Na+ move into cells to maintain electrical neutrality

REACTIONS TO HYPONATREMIA
Osmoreceptors stimulated Increased ADH release Increased Thirst Decreased urinary H2O loss Increased H2O gain Additional H2O dilutes Na+ H2O loss concentrates Na+

Increased Na+

Homeostasis Normal Na+

Decreased Na+ Decreased ADH release Decreased Thirst

Osmoreceptors inhibited

Increased urinary H2O loss Decreased H2O gain

Good Formulas to Remember

Fo r TheHype rnatre m ic Patie nt: STOP THE ONGOING LOSS! To Calculate Water Deficit: Estim ate TBW: 50-60% body weight (KG) depending on body com position (W vs M) Calculate Free-Water deficit: [(Na+ - 140)/140] x TBW Adm inister deficit over 48-72 hrs Ongoing Water Losses: Calculate Free-Water clearance from urinary flow rate (V) and urine (U) Na+ & K + concentrations V V x (UNa + UK)/140 Insensible Losses: Approxim ately 10m L/kg per day: less if ventilated, m ore if febrile. Total: Add above com ponents to determ ine fluid adm inistration rate (typically approxim ately 50-250 m L/h)

More Pearls!

Co rre cting theHypo natre m ic Patie nt Y ou want to raise plasm a sodium by restricting water intake & prom oting water loss And to correct the underlying disorder! Rate of Correction: Rate should be slow (approxim ately 0.5 m m ol/L per hour of Na+ ) Rule of Thum b: lim it change in m m ol/L of Na+ to the total difference within the first 24 hours. More rapid correction is associated with central pontine m yelinolysis! Reserve hypertonic solutions for patients with SEVERE hyponatrem ia and ongoing neurologic com prom ise (ie: patients with Na+ < 105 m m ol/L in status epilepticus) Then you can raise it at a rate of 1-2 m m ol/L pre hour for the first 34 hours or until the seizures stop but really no m ore than 12 m m ol/L for the first 24 hours.

Hyponatremia Pearls Continued

Norm al TBW is 50-60% So for a 70kg m ale, if we wanted to raise the Na+ 10 concentration from 105 to 115 m m ol/L: [(115 105) x 70 10 X 0.6] which m eans we require 420 m ol for this patient 60 m

Calculating Drip Rate

In the age of m achines, we bare ly have to do this anym ore but if you ever need to go old skool, here is how to calculate the drip rate (drops/m inute):
gtt = Volum e to be infused (m L) x (gtt/m L) m in Tim e (m inutes) Drip Factor =(gtt/m L) Of the TUBING which is found on the m anufacturers pacakging Exam ple: Volum e =4000 m l Tim e =24 hours Drip factor of tubing =15 gtt/m l. So. [4000m L/(24h x 60m in/h)] X 15gtt/m l =approx 42 drops/m in

K+

HYPERKALEMIA
Normal

serum potassium level (3-5 meq / liter) of potassium (140-150 meq /

As compared to Na+ (142 meq / liter)

Intracellular levels

liter)
This high intracellular level is maintained by active

transport by the sodium-potassium pump

K+

Na+ / K+ Pump
Cells

pump K+ ions in and Na+ ions out of the cell by using sodium-potassium pumps
K+ K+ Na+ Na+ Na+ Na+ K+ K+

HYPERKALEMIA
Hyperkalemia is

an elevated serum potassium (K+)

ion level A consequence of hyperkalemia is acidosis

an increase in H+ ions in body fluids

Changes

in either K+ or H+ ion levels causes a compartmental shift of the other

K+

HYPERKALEMIA
When

hyperkalemia develops potassium ions diffuse into the cell

This causes a movement of H+ ions out of the cell to

maintain a neutral electrical balance

As

a result the physiological response to hyperkalemia causes acidosis

+

H+ H + H H+ H+ H+

H+

H+ K+ K+ K+ K+ K+ + H+ K

HYPERKALEMIA

HYPERKALEMIA
The

reverse occurs as well The body is protected from harmful effects of an increase in extracellular H+ ions (acidosis)
H+ ions inside the cells are tied up by proteins

(Pr -)
This

causes a shift of potassium ions out of the

cells

HYPERKALEMIA
The

reverse occurs as well The body is protected from harmful effects of an increase in extracellular H+ ions (acidosis)
H+ ions inside the cells are tied up by proteins (Pr -)

This

causes a shift of potassium ions out of the

cells
H+ H+ H+ H+ H+ H+ + H+ H ACIDOSIS

K+ K + K K+ K+ K+
+

H+

HYPERKALEMIA
Summarized: Hyperkalemia causes acidosis Acidosis causes hyperkalemia
HYPERKALEMIA H+ K
+

H+ H
+

H+

H+ H+ H+

K+ K
+

K+

K+ ACIDOSIS

K+ K+ K+

HYPERKALEMIA
Summarized: Hyperkalemia causes acidosis Acidosis causes hyperkalemia
H+ H
+

HYPERKALEMIA H+ K
+

H+

H+ H+ H+

K+ K
+

K+

K+ ACIDOSIS

K+ K+ K+

SYMPTOMS OF HYPERKALEMIA
Muscle

contraction is affected by changes in potassium levels blocks the transmission of nerve impulses along muscle fibers
Causes muscle weakness and paralysis

Hyperkalemia

Can

cause arrhythmia's and heart conduction disturbances

CAUSES FOR HYPERKALEMIA

1) Increased input of potassium

2) Impaired excretion of potassium 3) Impaired uptake of potassium by cells

INCREASED INPUT
A) Intravenous KCl infusion B) Use of K+ containing salt substitutes C) Hemolysis of RBC during blood transfusions with release of K+ D) Damaged and dying cells release K+
Burns, crush injuries, ischemia

E) Increased fragility of RBC

CELLULAR-EXTRACELLULAR SHIFTS
Insulin

deficiency predisposes an individual to hyperkalemia Cellular uptake of K+ ions is enhanced by insulin, aldosterone and epinephrine
Provides protection from extracellular K+
Insulin

overload
K K+
+

K+ K+ K+

Click to view animation

K+

CELLULAR-EXTRACELLULAR SHIFTS
Insulin

deficiency represents decreased protection if the body is challenged by an excess of K+ ions In the absence of aldosterone there is loss of Na+ in the urine and renal retention of K+

Inherited

disorder in which serum K+ level rise periodically

Caused by a shift of K+ from muscle to blood in

HYPERKALEMIC PERIODIC PARALYSIS

response to ingestion of potassium or exercise Reasons for the shift are not clear
Attacks

are characterized by muscle weakness

RENAL INSUFFICIENCY
Aldosterone

has a primary role in promoting:

Conservation of Na+ Secretion of K+ by the nephrons of the kidney

Addisons

disease is characterized by aldosterone deficiency

Thus the kidney is unable

to secrete potassium at a normal rate

OLIGURIC RENAL FAILURE

Kidney

loses the ability to secrete K+

SPINOLACTONE
Diuretic

that is antagonistic to the effects of aldosterone

Causes some rise in serum K+ levels by interfering

with K+ secretion in the kidneys

Increases

may not be significant

But individuals taking the

diuretic are at risk if potassium is administered

TREATMENT
1)

Counteract effects of K+ ions at the level of the cell membrane 2) Promotion of K+ ion movements into cells 3) Removal of K+ ions from the body

SALT INFUSIONS
Infusion

of calcium gluconate or NaCl

solutions
Immediately counteract the effects of K+ ions

on the heart Effective for only 1-2 hours

SODIUM BICARBONATE
NaHCO3 also

reverses hyperkalemic effects

on the heart If acidosis is a factor also raises the pH of body fluids

INSULIN-GLUCOSE INFUSION
Insulin

given with glucose

Effective in about 30 minutes Has a duration of action of up to 6

hours
Insulin

promotes the shift of K+ ions into cells Glucose prevents insulin-induced hypoglycemia

KAYEXALATE
Kayexalate

(cation exchange resin)

Removes K+ ions from the body by exchanging K+

for Na+
Exchange time is about 45 minutes Effective for up to 6 hours

DIALYSIS
Peritoneal

dialysis or hemodialysis Effectively clears the blood of high K+ levels as well

CAUSES OF HYPERKALEMIA
CAUSE hyperkalemic periodic paralysis COMMENTS inherited disorder in which there are sudden shifts of cellular K+ to extracellular compartments compensatory shift of H+ into cells in exchange for movement of K+ to extracellular compartments cell destruction with release of K+ release of K+ from hemolyzed red blood cells diuretic that is an aldosterone antagonist; interferes with reabsorption of Na+ and secretion of K+ special risk of hyperkalemia if their is impaired renal secretion of K+ excessive ingestion additional source of K+ impaired secretion of K+

acidosis

burns transfusion of blood that has been stored spironolactone

too rapid intravenous infusion of KCl use of K+ containing salt substitutes potassium salts of antibiotics acute oliguric renal failure

HYPOKALEMIA
Defined

as a serum K+ level that is below normal (< 3 meq / liter) Serum concentrations will decrease if:
There is an intracellular flux of K+ K+ ions are lost from the gastrointestinal or

urinary tract

K+

ALKALOSIS
Alkalosis causes

and is caused by

hypokalemia Alkalosis is defined as a decrease of hydrogen ions or an increase of bicarbonate in extracellular fluids Opposite of acidosis +

K+

HCO

ALKALOSIS
Alkalosis

elicits a compensatory response causing H+ ions to shift from cells to extracellular fluids
This corrects the acid-base

HCO3-

imbalance
H H
+ +

HCO3H+ H+ H+ HCO3HCO3HCO3-

HCO3-

H+ H+ H+

ALKALOSIS
H+

ions are exchanged for K+ (potassium moves into cells)

Thus serum concentrations of K+ are decreased And alkalosis causes hypokalemia
K H+ H H H+
+ + +

HCO3HCO3-

K+ K
+

K+ K
+

HCO3HCO3HCO3-

H+

H+ H+ H+

K+ HCO3-

K+ K+

ALKALOSIS
Conversely

when K+ ions are lost from the cellular and extracellular compartments
Sodium and hydrogen ions enter cells

in a ratio of 2:1 as replacement

This

loss of extracellular H+ causes alkalosis

Na+ Na Na+ Na+ K+ Na+ + Na Na+
+

HCO3H+ HCO3HCO3H+ H+ HCO

HCO3HCO3- H+ + H H+HCO 3 H+
3

K+ K+

K+ + K + + K K

KIDNEY FUNCTION
Kidney

function is altered by hypokalemia

Na+ ions are reabsorbed into the blood when K+ ions

are secreted into the urine by kidney tubules

Peritubular fluid

NORMAL
Na+ Na+ Na
+

K+ K+ K+ K+

Tubular lumen

K+ K
+

Na+ Na+

Na+

Na+

KIDNEY FUNCTION
Kidney

function is altered by hypokalemia

If adequate numbers of K+ are not available for this

exchange

H+ ions are secreted instead

Peritubular fluid

HYPOKALEMIA
Na+ Na+ Na
+

H+ K+ H+ H+

Tubular lumen

H+ K
+

Na+ Na+

Na+

Na+

KIDNEY FUNCTION
Hypokalemia

promotes renal loss of H+ ions and thus results in alkalosis

ormal nephron function s to secrete H+ and K+ in xchange for Na+

NORMAL NEPHRON
H+ K+

Na+ distal tubule

capillary

Blood Urine

NEPHRON ACTION IN HYPOKELEMIA

In Hypokalemia the kidney selectively secretes H+ ions in preference to K+ ions The loss of H+ ions may lead to alkalosis
H+ K+

Na+ distal tubule

capillary

Blood Urine

ALKALOSIS

) in alkalosis there is a ecrease in extracellular uid H+

3) the kidney then eliminates K+ ions which can lead to H+ Hypokalemia retained
K+

Na

excreted

K+

distal tubule

capillary

) the kidney retains ydrogen ions to orrect the alkalosis

Blood Urine

CAUSES OF HYPOKALEMIA
CAUSE
aldosterone excess diarrhea diuretics distal renal tubular acidosis hypokalemic periodic paralysis Bartters syndrome

COMMENTS
favors renal Na+reabsorption and K secretion + diarrheal fluid contains high amounts of K in general causes K+ loss kidney tubule defect in which K+ are secreted, and H+ are retained by the body cause unknown; periodic influx of K+ into cells syndrome in which aldosterone is sometimes elevated; + probably a renal tubular defect so that K are lost
+

TREATMENT OF HYPOKALEMIA
Replacement Diet Intravenous administration of K+ salt

of K+ either by:

Oral K+ salt supplements

solution Diuretic (spinolactone) if renal loss is at work

Hypokalemia Management
Maximum IV infusion rate: 1 mEq/kg/hr Marked hypokalemia: Monitor serum K closely 0.5-1 mEq/kg/dose given as an infusion of 0.5 mEq/kg/hr for 1-2 hour