Regulation of intravascular and extravascular volume and osmolarity - pathophysiological aspects

This article doesn't meet WikiLectures quality standards.

This article seems to not fulfill most of the items on our Editorial Process checklist. As such, it's going to be deleted soon. To the author of this article: if you still work on this article, make sure to replace this template with the Under construction template. However, be aware that if you don't make any changes to the article after that soon enough, the article will still be deleted. To find out what you need to do to improve this article, read Help:Editorial process. Feel free to ask for help on Forum:Support. To see how articles on WikiLectures should look like, check out articles in Category:Finished articles. For more information, contact the user who inserted this template, you can find them in the Page History (under the "Actions" button). Last user who modified this page: ShadyMedic

Introduction

The regulation of body fluid volume and osmolarity is essential for maintaining homeostasis. Body fluids are distributed between the intravascular (plasma) and extravascular (interstitial + intracellular) compartments. Their balance depends on coordinated actions of the kidneys, hormones, vascular forces, and the nervous system. Disturbances in this regulation can lead to serious pathophysiological conditions such as edema, dehydration, and shock.

Definition of Volume and Osmolarity Regulation

Volume regulation refers to maintaining adequate circulating blood volume to ensure tissue perfusion.

Osmolarity regulation ensures stable concentration of solutes, especially sodium, to prevent excessive shifts of water between compartments.

Both systems interact, but each has its own primary sensors and effectors.

---

Key Mechanisms

1. Regulation of Osmolarity

Osmolarity is mainly controlled by water balance and ADH (antidiuretic hormone).

Main components

• Osmoreceptors in the hypothalamus
• ADH release from the posterior pituitary
• Thirst mechanism
• Kidney collecting ducts (AQP2 channels)

When osmolarity increases (hyperosmolarity):

• ADH secretion ↑
• Water reabsorption in kidneys ↑
• Thirst ↑
• Plasma osmolarity returns toward normal

When osmolarity decreases (hypoosmolarity):

• ADH secretion ↓
• Dilute urine is excreted
• Osmolarity rises back to normal

Purpose

Prevent excessive water movement into or out of cells, protecting the brain from swelling or shrinkage.

---

2. Regulation of Intravascular Volume (Effective Circulating Volume)

Volume regulation is tightly connected to sodium balance, because sodium is the main extracellular cation.

Main sensors

• Baroreceptors (aortic arch, carotid sinus)
• Juxtaglomerular apparatus (renin release)
• Atrial stretch receptors
• Hepatic blood flow sensors

Main effectors

• RAAS system (Renin–Angiotensin–Aldosterone System)
• Sympathetic nervous system
• Natriuretic peptides (ANP, BNP)
• Kidneys (GFR and sodium reabsorption)

Volume depletion → compensatory response

• Renin ↑ → Angiotensin II ↑ → Aldosterone ↑
• Sodium + water retention ↑
• Vasoconstriction ↑
• ADH ↑ (secondary effect)
• Cardiac output and blood pressure stabilized

Volume expansion → compensatory response

• Natriuretic peptides ↑
• Sodium excretion ↑
• Vasodilation
• RAAS and sympathetic activity ↓

---

Pathophysiological Aspects

1. Edema Formation

Edema results from an imbalance between intravascular and extravascular forces.

Main mechanisms

• Increased hydrostatic pressure (e.g., heart failure → venous congestion)
• Decreased oncotic pressure (e.g., hypoalbuminemia in liver disease or nephrotic syndrome)
• Increased capillary permeability (e.g., inflammation)
• Lymphatic obstruction (e.g., malignancy, infection)

Result

Water shifts from intravascular to extravascular space → visible swelling.

---

2. Dehydration and Hyperosmolar States

Occurs with loss of water or inadequate intake.

Causes

• Vomiting, diarrhea
• Diabetes insipidus (ADH deficiency or resistance)
• Excessive sweating

Consequences

• Hypernatremia
• Cell shrinkage (especially neuronal cells)
• Confusion, irritability, seizures in severe cases

---

3. Hyponatremia (Low Na+, Low Osmolarity)

Usually due to excess water retention relative to sodium.

Mechanisms

• Inappropriate ADH secretion (SIADH)
• Heart failure
• Kidney failure
• Excessive water intake

Consequences

• Brain swelling → headache, nausea
• In severe cases, risk of neurological symptoms

---

4. Disorders of Effective Circulating Volume

Even when total body water is high, effective arterial volume may be low.

Examples

• Heart failure
• Liver cirrhosis
• Nephrotic syndrome

Why it happens

• Reduced perfusion sensed as “low volume” → RAAS and ADH activation → Retention of sodium and water → Worsening edema and volume overload

---

5. Shock States

Severe failure of intravascular volume to maintain tissue perfusion.

Types

• Hypovolemic (hemorrhage, dehydration)
• Cardiogenic (pump failure)
• Distributive (sepsis, anaphylaxis)

Physiological effects

• Severe hypotension
• Reduced oxygen delivery
• Organ dysfunction

---

Summary of Key Hormonal Systems

Hormone	Trigger	Effect
ADH	↑ Osmolarity or ↓ Volume	Water reabsorption ↑
Aldosterone	RAAS activation	Na+ retention ↑
Angiotensin II	Renin release	Vasoconstriction, aldosterone ↑
ANP/BNP	Atrial stretch	Natriuresis, vasodilation
Sympathetic NS	Low pressure/volume	Vasoconstriction, Na+ retention

---

Conclusion

The body maintains stable intravascular and extravascular fluid balance through tightly controlled mechanisms involving osmolarity regulation, sodium handling, and hormonal responses. Disruption of these systems can lead to clinically important conditions such as edema, dehydration, hyponatremia, and shock. Understanding these mechanisms is essential for recognizing how fluid imbalances develop and how they affect the body.

---

References

• Guyton & Hall. Textbook of Medical Physiology.
• Boron & Boulpaep. Medical Physiology.
• Hall JE. Control of extracellular fluid volume and osmolarity.
• Clinical methods in fluid balance and electrolyte disorders.