Introduction
The plasma osmolality and oncotic pressures in an organism can determine the direction of fluid movement within the system and, therefore, the relative concentration of ions and protein in the solvent. As a result, we can observe the fluid movement results, typically manifest as edema, dehydration, changes in blood pressure, seizures, and intracranial pressure. Furthermore, osmolality disturbances can be used as an indication for intravenous fluids, which can quickly alter the plasma osmolality and oncotic pressures in the vascular system.[1]
Osmolarity is the number of milliosmoles of solute per liter solution. This differs from osmolality (osm), which is the milliosmoles of solute per kilogram of solution.[2] Water flows from a low osmolality compartment to a high osmolality compartment. This can only occur if the membrane between the 2 compartments is permeable to water. An example of this is when comparing plasma osm and interstitial fluid osm. We can compare the intracellular osm to the extracellular matrix at the cellular level. In this system, the phospholipid bilayer is the semipermeable membrane through which water can flow.
Issues of Concern
Osmolarity is the number of osmoles of solute per liter solution, which is different from osmolality, which is the osmoles per kilogram of solution. Osmoles are different from moles in that they consider the dissociation of cations and anions in water.
For example:
If 1 kg of water gets added to 1 mole of NaCl salt, then we observe the salt separate into its ions. As a result, there is 1 mol of Na and 1 mol of Cl. Restated, this means there are 2 osmoles of ions in 1 kg of water, which results in a solution with an osmolality of 2osm/1kg.
Components that contribute to plasma osmolality:
- Any solute in the plasma contributes to the osmolality. Examples include proteins, ions, urea, and sugars. The relative osmoles of each are summed to give the total osmolality per 1 kg of plasma.
- How to calculate plasma osmolality?
- The Dorwart and Chalmers formula is widely used to estimate plasma osmolality. It utilizes the basic metabolic panel (BMP) to measure sodium, glucose, and blood urea nitrogen.
- Serum Osmolality=1.86 (Na)+(Glucose)/18 +(BUN)/2.8+9
- Normal serum osmolality ranges from 275 to 295 mmol/kg.[3][4]
Cellular Level
Water flows from a compartment of low osmolality to a compartment with high osmolality; this can only occur if the membrane between the 2 compartments is permeable to water. Comparing plasma osmolality and intracellular fluid osmolality is an example of this. For example, if a cell is in a relatively hyperosmolar solution, fluid diffuses from the cell towards the highly concentrated environment to reach homeostasis. As a result, the cell shrivels.
Organ Systems Involved
Posterior Pituitary/Renal Systems
- The posterior pituitary and renal organ systems are crucial to maintaining appropriate plasma osmolality. Although albumin contributes to oncotic pressure, it only makes up 5% of the plasma, which means it has a lesser effect. Albumin is formed in the liver and, in pathologic processes, can be underproduced or lost in the extracellular matrix and urine. See the Mechanism section below for details.
Renin Angiotensin Aldosterone System (RAAS)
The RAAS system is crucial because it maintains extracellular volume, sodium concentration, and blood pressure. The kidneys secrete a hormone called renin, which circulates to the adrenal glands, causing downstream effects. See the Mechanism section below for details.
Function
The function of albumin in the serum is multifaceted. Albumin is a protein that can carry lipid-soluble substances such as thyroid hormones, sex hormones, and triglycerides. It also plays a major role in contributing to plasma oncotic pressure, as it can comprise up to 50% of all circulating serum proteins.[5] It has been used as an agent to expand intravascular volume and control both intracranial and intraocular pressure.
Ions and glucose contribute to 95% of the osmotic pressure as they are the most abundant in the serum. Osmolality and, subsequently, osmotic pressure are not affected by the size or charge of the solutes but only by the number of solutes.
The function of osmolality and oncotic pressure is to keep the ions suspended in solution at optimal concentrations, which are set by the cells in the body. This helps create ion gradients, leading to action potential generation, muscle contractions, and adequate glucose supply in the serum.
Mechanism
Posterior Pituitary/Renal Systems
- The dehydrated state is an example of hyperosmolar plasma: When the body is dehydrated, there is less fluid in the plasma, making the plasma more concentrated. As a result of increased plasma osmolality, cells begin to have water flow out, and cells shrivel because they are now hypoosmolar compared to the surroundings. Neurons in the organum vasculosum terminalis and supraoptic and paraventricular nuclei of the thalamus act as osmoreceptors. When these neurons experience the stretch and negative pressure suction, which manifests as they shrink, they depolarize via transient receptor potential vanilloid (TRVP) cation channels. These channels increase the charge inside the cells and cause depolarization, signaling the posterior pituitary to release antidiuretic hormone (ADH). ADH works at the renal collecting ducts and principal cells via the V2 receptors, which increase the intracellular cAMP. The increase in cAMP induces aquaporin 2-channel insertion in the apical side of the plasma membrane. This creates a channel where water can be reabsorbed from the filtrate, reducing plasma osmolality and thus achieving homeostasis.[5]
- The Hypo-Osmolar state: In this state, no stretch or negative pressure suction is created in the cells responsible for osmoregulation. This state results in hyperpolarization of the cell. It decreases ADH release from the posterior pituitary, allowing the kidneys to excrete more urine and increase the plasma osmolality back to the physiologic set point.
Renin Angiotensin Aldosterone System (RAAS)
Macula densa cells are present in the wall of the distal convoluted tubule of the kidney; their primary function is to sense the concentration of sodium chloride in the filtrate. Only 2 physiologic scenarios exist:
- The filtrate has a decreased NaCl concentration: The macula densa senses this, and it signals for the dilation of the afferent renal arterioles, increasing the hydrostatic pressure and NaCl concentration. The macula densa also secretes prostaglandins, which signal the juxtaglomerular cells to release renin. Renin converts angiotensinogen, made in the liver, to angiotensin 1 in the vasculature. Angiotensin 1 is inactive and is converted to angiotensin 2 in the lungs by the angiotensin-converting enzyme (ACE).
- Effects of angiotensin 2
- Signals the Posterior Pituitary to release ADH. See the mechanism above.
- Contraction of vascular myocytes results in increased blood pressure, which in turn results in higher hydrostatic pressure, which in turn increases filtrate production and filtrate NaCl concentration.
- Angiotensin 2 increases sympathetic activity.
- Angiotensin 2 increases tubular NaCl reabsorption and Potassium and water excretion - the net result is an increased plasma NaCl concentration, which increases plasma osmolality.
- The filtrate has an increased NaCl concentration: In this scenario, the macula densa cells decrease their secretion of prostaglandins, inhibiting the RAAS pathway.[6]
Pathophysiology
Hypoosmolar plasma: The pathologies decrease the osmolality of plasma
Psychogenic polydipsia: This is a psychiatric condition characterized by self-induced water intoxication. There are 3 phases to the disease process. First, there is a polyuria and polydipsia phase in which the patient is thirsty and has excessive urine output. The second phase appears hyponatremia in the blood as the kidney cannot excrete all the water, resulting in hypo-osmolar plasma. The final phase consists of the sequelae from water intoxication and hyponatremia, including delirium, ataxia, seizures, nausea, and vomiting. Death may result if the electrolyte abnormalities are not corrected promptly. One must be aware that central pontine myelinolysis is a deadly sequelae of quick sodium correction.[9]
Syndrome of inappropriate ADH (SIADH): This condition occurs when the human body produces and secretes an excessive amount of ADH via CNS tumors, lung cancers, and medications, resulting in the kidneys reabsorbing too much water and manifests as a dilutional hypoosmolar plasma and hypertension. Treatment can involve vasopressin receptor blockers such as tolvaptan, removing cancer, creating the ADH, removing the medications inducing SIADH, and therapy with hypertonic saline.[10]
Nephrotic syndrome: This general term describes disease processes that result in proteinuria (over 3 g/d), accompanied by hypoalbuminemia, hypertriglyceridemia, and a hypercoagulable state. The characteristic proteinuria occurs when there is damage to the glomerular basement membrane or podocyte foot processes, which results in decreased plasma osmolality and oncotic pressure. Edema is frequently a presenting sign because there is insufficient oncotic pressure to draw water into the vasculature from the extracellular matrix.[11]
Liver cirrhosis: Albumin production occurs in the liver and is then secreted out of the hepatocytes and into the extravascular space and then returned to the blood via lymphatic drainage and directly released into a blood vessel, the space of Disse. When the liver incurs damage, it cannot produce albumin, resulting in a hypoosmolar plasma.[12]
Diabetes Insipidous (DI): This disease demonstrates excretion of a large volume of urine, which results in concentrated, hyperosmolar plasma (greater than 300 mOsm/liter) and dilute, hypoosmolar urine (less than 300mOsm/liter). It can result from central damage to the neurons, which are responsible for the creation of ADH. Examples of sources of damage include infarcts, germinomas, Langerhans histiocytosis, and sarcoidosis. Another cause for DI is end-organ resistance. Although ADH is present, the patient has a genetic mutation in the vasopressin receptors, which renders the hormone ineffective.[13]
Dehydration: see above.
Clinical Significance
There are many clinical implications of alterations to the plasma osmolar state and the oncotic pressure. Clinicians can monitor the following:
- Change in intracranial pressure
- Look for edema
- Seizures
Pathologies include (but are not limited to):
- Diabetes insipidus: A disease characterized by excretion of a large urine volume, resulting in concentrated, hyperosmolar plasma (over 300 mOsm/liter) and dilute, hypoosmolar urine (less than 300mOsm/liter).
- Liver cirrhosis: This is the final result of various hepatic insults which render the liver damaged, fibrosed, and ineffective at completing its functions. A few of its functions include synthesizing proteins, clearing bilirubin, and metabolizing drugs for excretion.[14]
- Congestive heart failure: This is a pathology characterized by the dilatation and hypertrophy of the left ventricle of the heart, which prevents forward blood flow, which results in decreased end-organ perfusion and increases hydrostatic oncotic pressure, which leads to hepatic congestion and pulmonary edema. Decreased renal perfusion activates the RAAS system (see above) and alters the composition of solutes in the blood and urine.[15]
- Dehydration: Acutely, this causes a hypertonic state, as discussed in the "Mechanism" section.
- Kwashiorkor: This disease presents with a lack of amino acids in an individual's diet due to severe malnutrition. The liver is unable to synthesize proteins because of the lack of amino acids, which results in decreased plasma oncotic pressure.
- Nephrotic syndrome: An insult to the renal system results in the spilling of proteins into the urine, resulting in hypo-osmolar blood plasma.
- Psychogenic polydipsia: See above in the "Pathophysiology" section.
It is essential to consider all differential diagnoses; ultimately, further lab testing is necessary to reach a diagnosis.
Physiology, Plasma Osmolality and Oncotic Pressure