Which is more susceptible to dehydration - extracellular and intracellular fluid?

Which is more susceptible to dehydration - extracellular and intracellular fluid?

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I want to ask in human body, there is intracellular and extracellular fluid that makes up the total body water of our body, which is drained first when we do activities? extra or intra? if I want to do a bioimpedance measurement, does measuring only the extracellular fluid good? Thankyou

You should understand that the body is an open system which is held at a steady state. Water can diffuse in and out of the cell such that the osmolarity is balanced on both sides of the membranes. If the water potential changes in either of these compartments (intra- and extra- cellular) because of addition or removal of water molecules, both the compartments would be affected such that finally the osmolarity is same in both the compartments. It may, however, take some time to achieve the steady state.

If you refer to sweating when you say "activity" then you should note that it is a complex process with extensive neurological control. The water that is secreted by the eccrine sweat gland primarily comes from the blood. However, profuse sweating will lead to water loss from both the intra- and extra- cellular compartments.

Prolonged exposure to hyperthermic conditions and/or prolonged exercise in the heat can induce water deficits due to profuse sweating, resulting in hypohydration. This water deficit lowers both intracellular and extracellular volumes and results in plasma hyperosmolality and hypovolemia; both of which impair sweating.

Shibasaki, Manabu, and Craig G. Crandall. "Mechanisms and controllers of eccrine sweating in humans." Frontiers in bioscience (Scholar edition) 2 (2010): 685-696.

So, for your experiment it is better to measure the osmolarity of the extracellular fluid or the blood plasma because:

  • It is easier to measure
  • It would not be sensitive to local and temporary effects

Children require greater volumes of water than adults to maintain fluid equilibrium: Dr. Neelam Mohan

In an exclusive interaction Dr Neelam Mohan, Director Department of Pediatric Gastroenterology, Hepatology & Liver Transplantation Medanta – The Medicity Hospital discusses how hydration plays a crucial role in the recovery of pediatric patients.

What makes infants and young children particularly susceptible to fluids and electrolyte imbalance?

Infants and children have a higher proportion of water in terms of percentage of body weight with respect to adults. Also, we need to remember that they are not able to express their thirst, the way we adults can do. The diversity of the pediatric population results in a corresponding variability in fluid requirements. As the patient ages, the percentage of total body water (TBW) decreases from 85% in the preterm neonate, 70% in infants to 60% in older children, adolescents and adults.

Infants' and children’s higher body water content, along with their higher metabolic rates and increased body surface area to mass index, contribute to their higher turnover of fluids and solute. Therefore, infants and children require proportionally greater volumes of water than adults to maintain their fluid equilibrium and are more susceptible to volume depletion.

How does Fluid and Electrolyte Imbalance impact the body’s functioning?

Fluid and Electrolytes are central to the regular functioning of the body. They regulate nerve and muscle function, hydrate the body, balance blood acidity and pressure, and help rebuild damaged tissue. The first objective which is accomplished when a patient is admitted is to hydrate the patient to have satisfactory urine output and to take care of the electrolyte imbalances if any as well as to take care of the acid–base imbalance.

Sodium is the most abundant extracellular cation in the body. It has two primary functions, maintaining fluid balance and maintaining membrane potential. Potassium is primarily an intracellular fluid cation, essential for cell metabolism and maintenance of resting membrane potential. Magnesium is an essential cofactor in more than 300 enzymatic reactions, including those involved in glucose metabolism, fatty acid synthesis and breakdown, and DNA and protein metabolism. It plays a critical role in the functioning of the Na+-K+-ATPase pump, thus affecting neuromuscular transmission, cardiovascular excitability, vasomotor tone, and muscle contraction.

What are the risk factors of dehydration in children other than diarrhoea?

Dehydration is a common complication of illness observed in pediatric patients. Early recognition and early intervention are important to reduce the risk of progression to hypovolemic shock and end-organ failure.

The mechanisms of dehydration may be broadly divided into 3 categories: (1) decreased intake, e.g., due to diseases such as stomatitis, (2) increased fluid output, e.g., from diarrhea or increased urine output such as from uncontrolled diabetes mellitus, and (3) increased insensible losses, e.g., such as with fever, sweating or burns.

The commonest cause of dehydration in children is diarrhoea. The other causes common in pediatric patients include fever, malaria, hand-foot-mouth disease, typhoid, chickenpox, varicella, UTI, bronchiolitis, dengue, motion sickness, heat-related dehydration can vary from mild to severe, similar dehydration can occur due to burns and diabetes, chikungunya, acute pancreatitis and hepatitis A. Any condition that leads to decreased intake (Anorexia, Altered mental status, Cleft lip/ palate, Pharyngitis, Stomatitis, Respiratory distress and Child abuse) or increased output (Vomiting, Diarrhea, Fever, Sweating, Hyperventilation) and Congenital adrenal hyperplasia or when there is a movement of Fluids: Burns, Ascites, Paralytic ileus, Peritonitis, Sepsis, Renal failure and Heart failure.

Challenges for the clinician:

• Recognition of intravascular volume deficit and dehydration

• Prescription of an appropriate fluid in appropriate volumes

• Administration via the most suitable method

Mild or moderate volume depletion should be treated with oral rehydration when possible. Intravenous fluid therapy is necessary when oral therapy fails or volume depletion is severe.

How crucial is the need for rehydration during fever and how does it impact recovery?

It is extremely crucial to correct any dehydration present with appropriate measures either orally which are preferred or by intravenous fluids if it is not feasible to give orally. Dehydration can happen due to any reason mentioned above, but if it is not corrected, it can give rise to potential complications including lack of proper immune function and delay in recovery. It is advised to increase daily maintenance fluids by 12% for every degree body temperature above 37.5° C (rectal). It is important to remember that dehydration at the vascular level or at the cellular level would disrupt the normal metabolic functions and hamper the process of recovery. Guidelines recommend regular fluid intake in children with fever to prevent dehydration

What are the early signs if hospitalized children are undergoing fluid and electrolyte imbalance?

It varies on whether the patient is admitted in NICU or is in the wards. In NICU, the children are on strict monitoring and proper intake and out is maintained along with the calculation of deficit fluid to take care of the losses. But in children admitted in the wards, a strict vigil needs to be maintained on the signs and symptoms of dehydration.

Earliest signs are

· Passes less urine than normal, no urine for eight to 12 hours, or dark-coloured urine.

· Dry, cracked lips and a dry mouth

· Drowsiness or irritability.

· Low energy levels, seeming very weak.

Why is it crucial to emphasize on hydration in children?

In large cross-sectional surveys involving 6,469 children (4-17 years) from 13 countries, 60% of children did not meet the European food safety authority adequate intake for water from fluids. In these surveys, the contribution of sugar-sweetened beverages and fruit juices to total fluid intake in children exceeded that of water in 6 out of 13 countries. It is pertinent to better understand the barriers to drinking water at school and encourage the promotion of water intake through multicomponent interventions that combine educational, environmental, and behavioural aspects to support adequate hydration as well as optimal cognition in children.

What is the importance of nutrition and calories in the process of recovery?

Nutrition includes providing with adequate calories along with adequate intake of vitamin, proteins and minerals. Weight loss during illnesses indicates there is loss of lean body mass, fat mass and water from the body. If there is a weight loss happening during the active phase of the disease, it needs to be taken care of during the treatment and also after discharge. If the child continues the lose weight, then it hampers the immune system and also the entire recovery process increasing the costs of treatment and also increasing the chances of complications. Both nutrition and hydration are central to recovery for acute and chronic illnesses. Children should be encouraged to eat and drink at regular intervals even if they are not hungry or thirsty to take care of the increased caloric needs. Always keep in mind that children while suffering have got reduced appetite than normal due to medications and the disease process and so the calorie deficit is very common in these circumstances.


Fluid moves throughout cellular environments in the body by passively crossing semipermeable membranes. Osmolarity is defined as the number of particles per liter of fluid. Physiologic blood plasma osmolarity is approximately 286 mOsmoles/L. Less than this is hypoosmotic, and greater is hyperosmotic. Cellular osmotic concentration gradients are maintained largely through the active pumping of transmembrane ionic transport proteins. However, rapid changes in fluid volume without changes in ionic components cause dilation or concentration of those components. Blood plasma osmotic gradients are maintained through the absorption of solutes from the gastrointestinal tract or secretion into the gastrointestinal tract or urine. In addition to ionic components, osmolarity is partially composed of proteins such as albumin in the serum. Another important osmotically active component to consider is glucose. Fluid will move towards hyperosmotic compartments and away from hypoosmotic compartments. All body fluids should have an ionic net electrical charge close to zero, indicating a balance of cations and anions. Ionic components will diffuse through fluids selectively depending on the presence of permeable membranes. If a membrane is non-permeable to an ion, this creates a gradient of relatively higher concentration osmolarity. Solute gradients can be physiologically created by membrane pumping proteins, which expend energy in the form of ATP to move components from areas of low concentration into higher concentrations against their diffusion gradient. These processes create a cellular environment to osmotically “pull” water into fluid compartments. In addition to the osmotic pull of fluids, fluid movement within the body relies on created and maintained hydrostatic pressures. This is best utilized in the movement of fluid from plasma in the extracellular blood space into the interstitial spaces of tissue across the capillary membrane. Hydrostatic pressure is the “push” factor on fluid movement where increased pressures force fluid out of a space.  The combined “push” of hydrostatic forces and the “pull” of osmotic forces create a net movement of fluid. This is mathematically explained using the Starling equation:

Where Jv is the net rate of capillary fluid movement, Kfc is a capillary filtration fluid coefficient, Pc isꃊpillary hydrostatic pressure, Pi is interstitial hydrostatic pressure, n is the osmotic reflection coefficient, Op is plasma oncotic pressure, and Oi is interstitial oncotic pressure.[4]

Isotonic (Isonatremic) Dehydration

Isotonic (isonatremic, iso-osmolar) dehydration occurs when proportionally the same amount of water and sodium is lost from the body, so the sodium concentration of the extracellular fluid and hence its tonicity do not change. Isotonic dehydration is the most common type of dehydration 20 .

Lab test values in isotonic dehydration:

Blood tests:

  • Osmolality: 285-295 mOsm/kg (normal range)
  • Sodium: 130-150 mmol/liter (a slightly wider than normal range, which is 135-145 mmol/L)

Urine tests:

Possible causes of isotonic dehydration:

The Child with a Fluid and Electrolyte Alteration

Characteristics unique to children affect their fluid and electrolyte balance. Infants and young children are more vulnerable than adults to changes in fluid and electrolyte balance. Under normal conditions, the amount of fluid ingested during a day should equal the amount of fluid lost through sensible water loss (e.g., urine output) and insensible water loss (through the respiratory tract and skin). Insensible water loss per unit of body weight is significantly higher in infants and children. The faster respiratory rates of infants and young children also result in higher evaporative water losses. Any condition that prevents normal oral fluid intake (e.g., vomiting) or results in fluid losses (e.g., diarrhea, hyperventilation, burns, hemorrhage) is especially significant because it depletes the body’s store of water and electrolytes much more rapidly in infants and young children than in adults.

Body water is located in two major compartments: within the cell, in the intracellular compartment and outside the cell, in the extracellular compartment. These two compartments are separated by the cell membrane, across which body fluid is continually exchanged. Extracellular fluid (ECF) is located in several places: in interstitial spaces (surrounding the cells [e.g., lymph fluid]), intravascularly (within the blood vessels or plasma), and transcellularly (e.g., cerebrospinal fluid, pericardial fluid, pleural fluid, synovial fluid, sweat, digestive secretions). A child is more likely to lose ECF than intracellular fluid (ICF). ECF is lost first when fluid loss occurs (e.g., through illness, trauma, fever). The intracellular compartment is more difficult to dehydrate.

In the neonate, approximately 40% of body water is located in the extracellular compartment compared with 20% in the adolescent and adult. In the infant, half of the ECF may be exchanged compared with an adult exchange of one sixth of the ECF in a similar time. Because approximately 50% of this ECF is exchanged daily in an infant, dehydration can occur very suddenly and rapidly if fluid intake is inadequate or fluid losses are excessive. Because of the infant’s higher metabolic rate, the rate of water turnover is rapid. Depletion of ECF, often caused by gastroenteritis, is one of the most common problems among infants and young children. In adults and older children, because a greater proportion of fluid is located in the intracellular compartment, severe fluid depletion does not occur as


Infants and Young Children

rapidly. Maturity in body space distribution is usually reached around age 3 years.

Body fluids are basically composed of two elements, water and solutes. Water is the primary constituent, with the infant’s weight being approximately 75% water to the adult’s 55% to 60%. In general, the volume of total body water to total body weight decreases with increasing age. An inverse relationship exists between total body water and total body fat. Compared with adults, neonates, particularly premature infants, have a lower proportion of fat.

Solutes are composed of both electrolytes and nonelectrolytes. Most of the body’s solutes are electrolytes, primarily sodium (Na + ), potassium (K + ), chloride (Cl − ), calcium (Ca 2+ ), and magnesium (Mg 2+ ). The primary electrolyte of the ECF is sodium potassium and magnesium are the primary electrolytes in the ICF. The extracellular compartment contains more sodium and chloride during infancy, which increases the vulnerability of infants to electrolyte imbalances. Changes in the concentration of these electrolytes may result in cellular dysfunction and illness. Problems of fluid and electrolyte balance involve both water and electrolytes thus treatment includes replacement of both, calculated according to serum electrolyte laboratory values.

Alterations in Acid-Base Balance in Children

Alterations in acid-base balance can affect cellular metabolism and enzymatic processes. The body’s ability to regulate this status is crucial. Children can have acid-base imbalance as a result of many pathologic conditions. The pH, or measure of acidity or alkalinity of body fluids, is regulated within a narrow range (normal blood pH is 7.35 to 7.45). Maintenance of serum pH within normal limits is crucial to maintaining cellular function, enzyme activity, and neuromuscular membrane potentials. Chemical buffers, the respiratory system, and the kidneys work together to keep the blood pH within normal range. Acid is constantly produced as a byproduct of metabolism. The body attempts to maintain blood pH within normal limits by reducing the buildup of acid. Chemical and cellular buffer systems minimize the effect of alterations in blood pH by neutralizing excess acids and bases that accumulate in body fluids. Two of the most significant buffers are bicarbonate and proteins. Bicarbonate, the most important buffer for plasma and interstitial fluids, is responsible for most ECF buffering and can exert its effects relatively quickly (within minutes).

When alterations in pH become too much for the buffer systems to handle, compensatory mechanisms in the respiratory and renal systems are activated. The respiratory system works rapidly to compensate for acid-base disturbances. If the blood pH drops below normal (causing acidosis ), the respiratory rate and depth will increase, removing carbon dioxide and raising blood pH. Conversely, in the presence of alkalosis, the respiratory rate and depth decrease, thus lowering blood pH.

Kidneys regulate bicarbonate and remove hydrogen ions from the blood. If the blood is too alkaline, the kidneys conserve hydrogen ions, thus lowering blood pH. In the presence of acidosis, the kidneys excrete hydrogen ions and conserve bicarbonate, raising blood pH. Renal compensatory processes work more slowly than respiratory mechanisms—usually within 1 to 2 days. If compensatory mechanisms are ineffective, acid-base imbalances occur. When a dysfunction results in decreased hydrogen ion concentration in the blood, the arterial pH increases (causing alkalosis). When a dysfunction results in an increase in hydrogen ions, the arterial pH decreases (causing acidosis).


Treatment Goals in Acid-Base Imbalance

The treatment of metabolic acid-base disturbance is oriented toward correcting the underlying problem. The treatment of respiratory imbalance is directed toward reestablishing alveolar ventilation.

Sickle cell dehydration: Pathophysiology and therapeutic applications

Cell dehydration is a distinguishing characteristic of sickle cell disease and an important contributor to disease pathophysiology. Due to the unique dependence of Hb S polymerization on cellular Hb S concentration, cell dehydration promotes polymerization and sickling. In double heterozygosis for Hb S and C (SC disease) dehydration is the determining factor in disease pathophysiology. Three major ion transport pathways are involved in sickle cell dehydration: the K-Cl cotransport (KCC), the Gardos channel (KCNN4) and Psickle, the polymerization induced membrane permeability, most likely mediated by the mechano-sensitive ion channel PIEZO1. Each of these pathways exhibit unique characteristics in regulation by oxygen tension, intracellular and extracellular environment, and functional expression in reticulocytes and mature red cells. The unique dependence of K-Cl cotransport on intracellular Mg and the abnormal reduction of erythrocyte Mg content in SS and SC cells had led to clinical studies assessing the effect of oral Mg supplementation. Inhibition of Gardos channel by clotrimazole and senicapoc has led to Phase 1,2,3 trials in patients with sickle cell disease. While none of these studies has resulted in the approval of a novel therapy for SS disease, they have highlighted the key role played by these pathways in disease pathophysiology.

Keywords: Gardos channel K-Cl cotransport KCC KCNN4 Membrane transport Piezo-1 deoxygenation sickling.

Intracellular Bacteria

  • Those that can be cultured in microbiologic media in the laboratory (facultative) or
  • Those that required living cells/animals (obligate).

Facultative Intracellular Bacteria

  • Legionella pneumophila: It prefers the intracellular environment of macrophages for growth. Legionella induces its own uptake and blocks lysosomal fusion by an undefined mechanism.destroys the phagosomal membrane with which the lysosomes fuse.
  • Mycobacterium tuberculosis: M.tuberculosissurvives intracellularly by inhibiting phagosome-lysosome fusion.
  • Listeria monocyotogenes: Listeria quickly escapes the phagosome into the cytoplasm before phagosome-lysosome fusion.: Very resistant to intracellular killing by phagocytic cells.

Obligate intracellular bacteria

This group of bacteria can’t live outside the host cells. For e.g. Chlamydial cells are unable to carry out energy metabolism and lack many biosynthetic pathways, therefore they are entirely dependent on the host cell to supply them with ATP and other intermediates. Because of this dependency Chlamydiae were earlier thought to be a virus.

All viruses are obligate intracellular parasites.

Obligate intracellular bacteria cannot be grown in artificial media (agar plates/broths) in laboratories but requires viable eukaryotic host cells (eg. cell culture, embryonated eggs, susceptible animals).

    cannot be cultured in vitro it is an obligate intracellular parasite.
  1. Coxiella burnetti: The metabolic activity of Coxiella burnettiiis greatly increased in the acidic environment of the phagolysosome.
  2. Ricekettsia spp

Toxoplasma, Cryptosporidium, Plasmodium, Leishmania, Babesia, and Trypanosoma are obligate intracellular parasites.

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I have been working on a bacteria and I found it to be intracellular . TEM micrographs suggests that these bacteria forms vacuoles and tend to multiply within the vacuolated cups when infected with RAW macrophages cells.

My query: Can anyone suggest a paper wher they prove a particular bacteria to be intracellular. want a ref paper.TQ

Why the immune response to intracellular pathogens is different from extracellular pathogens?

Dear Manish
Thank you for your query. Did you studied Immunology? Your question requires understanding of various immunological concepts. If you have please look the chapters of Antigen processing and presentation. You will get answer there.

Tankeshwar Acharya, thank you for your blog explaining intracellular and extracellular bacteria. I am doing some desktop research on chronic urinary tract infections and found your description helpful. Did you know there are recent findings that incriminate intracellular bacteria and/or biofilm bacterial infections in chronic lower urinary tract symptoms (LUTS). Scientists in the US (Wolfe, A & Braubaker, L) and UK (Malone-Lee, J & Rohn, J) have recently discovered through the use of molecular technology, that urine in not at all sterile and up to 450 different bacterial species are found living in the bladder of healthy people. They believe these bacterial communities could be working in the same way that gut bacteria do by protecting the bladder from invading pathogenic bacteria. But in some people, this protective mechanism stops working for some reason, and a pathogenic bacteria takes over and invades cells or forms biofilm on the surface of cells (Hultgren, S). Being a microbiologist, I thought you’d be interested in this topic.

Dear Friend thank you so much for your comment and this useful information, I will go through this article. Generally we regard Blood, Urine and other body fluids are sterile after availability of molecular techniques and newer diagnostics, scientist/researcher are claiming that Blood is not sterile either. For routine diagnostics so far we believe and practice that these specimen are sterile or organisms if present in these specimen do not grow on our routine culture media. I am hopeful that with the use of novel diagnostic techniques, researcher/scientist will discover and validate new facts/findings.

The above link was about intracellular bacterial communities, which I shared because someone above asked for a paper that had evidence of bacteria being intracellular.

In relation to my comments above about urine not being sterile, you might be interested in reading the Wolfe & Baubaker paper. It’s hot science. I agree, I hope new technology and techniques provide medical solutions to a lot of unanswered questions. I hope you find it interesting.

Mr Acharya
I am biomedical science student
how does immune system switch between cell mediated and humeral in relation to intra or extra cellular bacteria..or both work along

Thank you prof for you great explanitation, but I have a query, does treponema as a jenus considered one of the obligate intracellular bacteria? I really need your help

Please what are the factors responsible for the predilection of intra-cellular bacteria? Thank you

Do you have any queries? Please leave me in the comments section below. I will be happy to read your comments and reply. Cancel reply

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Hydration Marker Diagnostic Accuracy to Identify Mild Intracellular and Extracellular Dehydration

Identifying mild dehydration (≤2% of body mass) is important to prevent the negative effects of more severe dehydration on human health and performance. It is unknown whether a single hydration marker can identify both mild intracellular dehydration (ID) and extracellular dehydration (ED) with adequate diagnostic accuracy (≥0.7 receiver-operating characteristic–area under the curve [ROC-AUC]). Thus, in 15 young healthy men, the authors determined the diagnostic accuracy of 15 hydration markers after three randomized 48-hr trials euhydration (water 36 ml·kg −1 ·day −1 ), ID caused by exercise and 48 hr of fluid restriction (water 2 ml·kg −1 ·day −1 ), and ED caused by a 4-hr diuretic-induced diuresis begun at 44 hr (Furosemide 0.65 mg/kg). Body mass was maintained on euhydration, and dehydration was mild on ID and ED (1.9% [0.5%] and 2.0% [0.3%] of body mass, respectively). Urine color, urine specific gravity, plasma osmolality, saliva flow rate, saliva osmolality, heart rate variability, and dry mouth identified ID (ROC-AUC range 0.70–0.99), and postural heart rate change identified ED (ROC-AUC 0.82). Thirst 0–9 scale (ROC-AUC 0.97 and 0.78 for ID and ED) and urine osmolality (ROC-AUC 0.99 and 0.81 for ID and ED) identified both dehydration types. However, only the thirst 0–9 scale had a common dehydration threshold (≥4 sensitivity and specificity of 100% 87% and 71%, 87% for ID and ED). In conclusion, using a common dehydration threshold ≥4, the thirst 0–9 scale identified mild intracellular and ED with adequate diagnostic accuracy. In young healthy adults’, thirst 0–9 scale is a valid and practical dehydration screening tool.

* Owen, Fortes, Walsh, and Oliver are with the College of Human Sciences, Bangor University, Bangor, United Kingdom. Ur Rahman and Jibani are with Gwynedd Hospital, Betsi Cadwaladr University Health Board, Bangor, United Kingdom.

Water Compartments

Water accounts for approximately 50% of body weight in females, and approximately 60% in males. Water is divided between two locations: intracellular (inside the cells) and extracellular (outside the cells). The extracellular compartments contain the water in the blood as well as the water located between the cells in the tissues. For the average person, about two thirds of the body's water is intracellular. Water can be exchanged between intracellular areas and extracellular components when necessary.

Educational Objectives

By the end of this session learners will be able to:

Distinguish between osmolarity and tonicity.

Use extracellular fluid (ECF) and intracellular fluid box diagrams to explain the effects of a solution on the body's osmolarity and compartment volumes.

Use body compartment box diagrams to calculate solute amount, compartment volume, and osmolarity of a person, and explain how those parameters change with fluid/solute gain or loss.

Utilize the principle of mass balance to predict how administering an IV solution would change the ECF concentration of a specific ion, such as potassium.

Explain how the volume of a cell would change over time when the cell is exposed to solutions of varying osmolarities and tonicity.