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

Approx water content in body 90%

70-80%

24-12 months
Adult

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)

1/3 (ECF)

80%
20%

Interstitial fluid

female

male

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-, HCO3- , PO43-

Non-electrolytes - Uncharged
Proteins, urea, glucose, O2, CO2
9

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 sodium-potassium 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 H2O H2O H2O solute H2O H2O H2O H2O H2O H2O H2O solute H2O H2O H2O H2O H2O solute H2O solute H2O solute solute H2O solute solute solute solute H2O solute

H2O

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 H2O solute H2O solute H2O solute H2O

solute solute solute H2O solute H2O

solute

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 Veins Weight Thirst Intake and Output Skin Edema Lab Values

Reasons for fluid therapy

Preserve oxygen delivery to tissues

Correct hypovolaemia
Maintain cardiac output
Colloids + RBCs

Optimise gas exchange

Replace electrolytes & water Maintain urine output
Identify what is the goal Choose fluid which best achieves the goal Crystalloids

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 0.9% NaCl 0.45% NaCl D5W D5/0.45% NaCl 3% NaCl 77 513 500 250,500 20,50,100 154 130160 130160 <2.5 <2.5 77 513 154 130160 130160 50 406 1026 310 330 330 Volumes Na+ 142 130 154 77 K+ 4 4 Ca2+ 5 3 Mg2+ Cl103 109 154 77 HCO327 28 Dextrose mOsm/L 280-310 273 308 154

6% Hetastarch
5% Albumin 25% Albumin

ISOTONIC SOLUTIONS

0.9%
D5W D51/4NS

Normal Saline
5 % Dextrose* 5% Dextrose 0.2% NS

D51/3NS 5% Dextrose 0.3% NS LR or RL Lactated Ringers Solution

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 N S
1/2 N S D 2.5 W

0.33% Normal Saline

0.45% Normal Saline Dextrose 2.5% in water

Neonates need relatively more fluid intake than older infants and children. The 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). The loops of Henle are short and the distal convoluted tubules are relatively resistant to aldosterone, leading to a limited concentrating ability

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

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

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

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

no. of electrica charges on one X ion

For 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 + Na + Na

K+

Na+
K+

+ 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

H2O

Na+
H2O

K+

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

HCO3

Considered an indicator of total solute concentration of plasma osmolality

ELECTROLYTE BALANCE
Sodium ions are osmotically important in determining water movements A discussion of sodium must also include Chlorine Bicarbonate H2O H2O Hydrogen ions H2O H2O
H2O H2O

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

2

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

Click

Hypercalcemia - elevated calcium levels

Hypokalcemia -- lowered calcium levels

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 Hypernatremia refers to an elevated serum sodium level (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

CNS REACTION TO HYPERNATREMIA

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

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

CNS REACTION TO HYPERNATREMIA

As 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

H 2O

CNS PROTECTIVE MECHANISM

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

H 2O

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

H2O H2O Glucose H2O H2O

Glucose

H2O
Glucose Glucose Glucose 2 Glucose

HO

H2O H2O
Glucose

2 Glucose
Glucose

HO

H 2O 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 H2O H2O
Glucose

H2O
Glucose Glucose Glucose 2 Glucose

HO

H2O H2O
Glucose

2 Glucose
Glucose

HO

H 2O 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 H2O H2O
Glucose Glucose

H2O
Glucose Glucose Glucose 2 Glucose

HO

H2O H2O
Glucose

2 Glucose
Glucose

HO

H 2O 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 H2O H2O
Glucose Glucose

H2O
Glucose Glucose

Glucose 2 Glucose

HO

H2O H2O
Glucose

2 Glucose
Glucose

HO

H 2O 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 H2O
Glucose Glucose

H2O H2O
Glucose Glucose Glucose 2 Glucose

HO

Glucose

H2O
Glucose

2 Glucose

HO

H2O

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

Glucose

H2O H2O H2O

Glucose

HO

H2O H2O
Glucose

2 Glucose
Glucose

HO

H 2O 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 Glucose

H2O Glucose H2O

Glucose

H2O
Glucose

H2O H2O Glucose

Glucose 2 Glucose

HO

H2O

H2O Glucose H 2O Glucose 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 HGlucose Glucose 2O H2O H2O Glucose H2Glucose O Glucose H2O H2O Glucose H2Glucose O 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 HGlucose Glucose 2O H2O H2O Glucose H2Glucose O Glucose H2O H2O Glucose H2Glucose O 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 Retention or intake of excess sodium
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 essent i al hyp er nat r emi a f ever c oma hot envi r onment , or st r enuous exer c i se vomi t i ng d i ar r hea p i t ui t ar y d i ab et es i nsi p i d us COMMENTS d i sor d er i n w hi c h t hi r st i s i mp ai r ed i nc r eased i nsensi b l e f l ui d l oss i nad eq uat e f l ui d i nt ak e sw eat , hyp ot oni c f l ui d l oss of t en a hyp ot oni c f l ui d l oss of t en a hyp ot oni c f l ui d l oss d ef i c i enc y of ADH; exc essi ve f l ui d l oss r enal t ub ul es i nsensi t i ve t o ADH; exc essi ve ur i nar y l oss g l uc ose i n g l omer ul ar f i l t r at e; osmot i c d i ur esi s ur ea i s a p r od uc t of p r ot ei n met ab ol i sm; ur ea c auses osmot i c d i ur esi s ad mi ni st r at i on of exc essi ve sod i um i ons manni t ol i n g l omer ul ar f i l t r at e; osmot i c d i ur esi s

nep hr og eni c d i ab et es mel l i t us unc ont r ol l ed d i ab et es mel l i t us l ar g e amount s of p r ot ei n and ami no ac i d s g i ven b y nasog ast r i c t ub e exc essi ve i nt r avenous i nf usi on of hyp er t oni c sod i um sal t sol ut i ons manni t ol used as d i ur et i c

TREATMENT OF HYPERNATREMIA
Re-hydration is the primary objective in most cases
Decreases sodium concentrations

A 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

If this adaptation has occurred and treatment involves a rapid infusion of dextrose for example:
There is danger of cerebral 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

3--Calculate the effect of 1 L of your selected 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 Implies an increased ratio of water to sodium in extracellular fluid
Extracellular fluid is more dilute than 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 of thirst
Suppression of ADH secretion
Both favor decreasing water ingestion and increasing urinary output

SYMPTOMS OF HYPONATREMIA

Primarily neurological (net flux of water into the 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

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
H2O H2O Na+ H2O Na+ H2O H2O Na+ H2O Na+ H2O Na+ H2O H2O Na+ H2O Na+ H2O H2O H2O H2O

H2O
H2O H2O Na+

H2O

H2O

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

K+
1) extracellular potassium loss

Na+

cell
K+

Na+

2) diffusion of potassium ions into extracellular compartments

K+ K+ interstitial fluid plasma

POTASSIUM ION LOSS

Na+ Na+

Cell

K+ K+ K+ Na+

Click to see animation

K+ K+ K+ Plasma

Interstitial fluid

DILUTIONAL EFFECT
5) Diuretic therapy
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

Increased Na+

Homeostasis Normal Na+

Decreased Na+

Additional H2O dilutes Na+ H2O loss concentrates Na+

Osmoreceptors inhibited

Decreased ADH release Decreased Thirst

Increased urinary H2O loss Decreased H2O gain

10 10 60

+ K

HYPERKALEMIA
Normal serum potassium level (3-5 meq / liter)
As compared to Na+ (142 meq / liter)

Intracellular levels of potassium (140-150 meq / 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+ H+ K+

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

H+

H+ H+

K+ K+ K+

HYPERKALEMIA
Summarized:

Hyperkalemia causes acidosis

Acidosis causes hyperkalemia
HYPERKALEMIA H+ H+ H+ H+ H+ K+ K+ ACIDOSIS K+ K+ K+

H+

H+ H+

K+ K+ K+

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

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
Insulin

Provides protection from extracellular K+ overload +

K+ K
K+ K+ K+ K+

Click to view animation

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

HYPERKALEMIC PERIODIC PARALYSIS

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
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
1)

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 hyper k alemic per iodic par alysis COMMENTS inher it ed disor der in w hic h t her e ar e sudden shift s of c ellular K + t o ext r ac ellular c ompar t ment s c ompensat or y shift of H+ int o c ells in exc hange for movement of K + t o ext r ac ellular c ompar t ment s c ell dest r uc t ion w it h r elease of K + r elease of K + fr om hemolyzed r ed blood c ells diur et ic t hat is an aldost er one ant agonist ; int er fer es w it h r eabsor pt ion of Na+ and sec r et ion of K + spec ial r isk of hyper k alemia if t heir is impair ed r enal sec r et ion of K + exc essive ingest ion addit ional sour c e of K + impair ed sec r et ion of K +

ac idosis

bur ns t r ansfusion of blood t hat has been st or ed spir onolac t one

t oo r apid int r avenous infusion of K Cl use of K + c ont aining salt subst it ut es pot assium salt s of ant ibiot ic s ac ut e oligur ic r enal failur e

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

+ H HCO3

K+

ALKALOSIS
Alkalosis elicits a compensatory response causing H+ ions to shift from cells to extracellular fluids
This corrects the acid-base imbalance
HCO3H+ H+ H+ H+ HCO3HCO3-

HCO3-

HCO3-

H+

H+
H+ H+

HCO3-

ALKALOSIS
H+ ions are exchanged for K+ (potassium moves into cells)
Thus serum concentrations of K+ are decreased
And alkalosis causes hypokalemia K+ K+ H+ H+ H+ H+ K+ K+ K+ HCO3HCO3-

HCO3HCO3HCO3-

H+

H+
H+ H+ K+ K+

K+

HCO3-

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+ K+ K+ Na+ Na+ K+ K+ Na+ Na+ Na+ H+ HCO3H+ Na+ H+ HCO

HCO3HCO3- H+ + H H+HCO 3
HCO33 -

H+

K+
K+ K+ K+

HCO3-

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+

Tubular lumen

K+

K+ K+ K+

Na+

K+ K+
K+

Na+
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+

Tubular lumen

H+

K+ H+ K+

Na+

K+ H+
H+

Na+
Na+ Na+

Na+
Na+

KIDNEY FUNCTION
Hypokalemia

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

NORMAL NEPHRON
Normal nephron function is to secrete H+ and K+ in exchange for Na+
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
1) in alkalosis there is a decrease in extracellular fluid H+
H+
retained

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

K+

Na+

K+

excreted

distal tubule

capillary

2) the kidney retains hydrogen ions to correct 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 of K+ either by:
Oral K+ salt supplements Diet Intravenous administration of K+ salt 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