ECF, ICF Osmotic Equilibrium & Renal Blood Supply

Osmotic Equilibrium Between Extracellular Fluid (ECF) and Intracellular Fluid (ICF)

• Tonicity of a solution depends on the concentration of solutes
• Solutions with the same osmolarity as the cell, regardless of permeability, are isotonic and therefore iso-osmotic
• Solutions that have an osmolarity equal to that of the cell (independent of permeability) = isotonic and THUS iso-osmotic
• Factors that can cause volume shifts include water intake, dehydration, intravenous infusion, loss of fluid from the gastrointestinal tract (GIT), and loss of fluid through sweat or urine

Renal Blood Supply

• The kidneys have two capillary beds: glomerular capillaries and peritubular capillaries
• Afferent arterioles deliver blood to the glomerulus, while efferent arterioles carry blood away
• Glomerular capillaries are associated with high hydrostatic pressure (about ±60mmHg), leading to increased fluid filtration
• Peritubular capillaries have low hydrostatic pressure (about ±13mmHg), resulting in decreased fluid filtration

Glomerular Filtration

• Approximately 20% of the plasma flowing through the glomerulus is filtered through the glomerular filtration membrane
• The glomerular filtration membrane has three layers, in comparison to the two layers found in normal capillaries
• High filtration rate and prevention of plasma protein filtration is due to split pores between podocytes (negative charge), large pores between collagen and proteoglycan fibrillae (negative charge), and perforated (fenestrae) endothelium, negatively charged

Renal Blood Flow and Glomerular Filtration Rate (GFR)

• Macula densa feedback mechanism regulates glomerular hydrostatic pressure and GFR when renal arterial pressure decreases

Antidiuretic Hormone (ADH)

• ADH, also known as vasopressin, is synthesized and stored in supra-optic and paraventricular nuclei in the hypothalamus
• It is then transported to the posterior pituitary gland via neurohypophysial capillaries, synthesis is completed in the posterior pituitary gland and stored until released into circulation
• Release of ADH is controlled by various factors, with the two most important being changes in osmotic pressure and volume, other factors include exercise, angiotensin II, and even pain
• ADH release is inhibited by atrial natriuretic peptide (ANP), alcohol, and certain medications
• ADH works on the distal convoluted tubule and collecting ducts to increase water reabsorption
• Increased osmolarity leads to increased ADH secretion
• ADH increases transcription and insertion of Aquaporin-2 channels on the apical membrane of the distal convoluted tubule and collecting duct cells
• This increases the permeability of the distal convoluted tubule and collecting ducts to water
• Water moves down its concentration gradient out of the nephron and back into the bloodstream normalizing plasma osmolarity and increasing blood volume
• At high concentrations, ADH acts directly on blood vessels to increase peripheral vascular resistance (important mechanism in hypovolemic shock, increases blood pressure)

Clinical Application

• Decreased arterial pressure and/or blood volume will result in ADH being released
• Increased osmolarity can also trigger ADH release
• ADH is more sensitive to small changes in osmolarity than similar changes in blood volume, blood loss of 10% or more will rapidly increase ADH levels
• Cardiovascular reflexes play an important role in ADH release during significant blood loss

Regulation of ADH Release

• Increased ADH is associated with increased plasma osmolarity, decreased blood volume, decreased blood pressure, nausea, hypoxia, and certain drugs (morphine, nicotine, cyclophosphamide)
• Decreased ADH is associated with decreased plasma osmolarity, increased blood volume, increased blood pressure, alcohol, clonidine, and haloperidol

Thirst Mechanism

• Thirst is the conscious desire for water
• The central nervous system centers for thirst are located in the anteroventral wall of the 3rd ventricle , in the anterolateral in preoptic nucleus, when stimulated electrically, causes immediate drinking
• All of thiese areas together are known as Thirst centre
• These cells function as osmoreceptors to activate the thirst mechanism

Stimuli for Thirst

• Increased extracellular fluid (ESF) osmolarity leads to intracellular dehydration of thirst centers.
• Decreased ESV and arterial pressure, like with severe blood loss, provides neural input from cardiopulmonary and systemic baroreceptors.
• Angiotensin II acts directly on thirst centers outside the blood-brain barrier and its release is stimulated by hypovolemia and low blood pressure.
• Dry mouth and mucus membranes lead to sensation of thirst
• Upper gastrointestinal tract (GIT) and pharyngeal stimuli.

Formation of Dilute Urine

• With excessive water in the body, the kidneys can excrete nearly 20L/day of dilute urine
• Urine volume can increase by about six-fold within 45 minutes after water consumption
• Even after excessive water consumption, the kidneys rid the body of excess water, but not excrete excess amounts of solute

Summary For Formation of Dilute Urine

• Low ADH Levels
• Fluid flows through the proximal tubule water and solutes are reabsorbed
• Occurs with minimal change (iso-osmotic)

More detail on formation of Dilute Urine

• The tubular fluid becomes more dilute in the ascending limb of the loop of Henle
• Sodium (Na), potassium (K), and chloride (Cl) are reabsorbed
• This part of the tubular segment is impermeable to water

More detail

• Fluid in the distal and collecting tubules is further diluted in the absence of ADH
• This tubular segment remains impermeable to water

Formation of Concentrated Urine

• Kidneys can form concentrated urine to allow for survival in extreme conditions
• The three requirements for excreting concentrated urine are high ADH and a hyperosmotic renal medulla, and a counter-current mechanism

Three Clinical Factors that Hinder Kidney Ability

• Inappropriate secretion of ADH whether it is too little or too much
• Interference to with counter current exchange limiting degree of osmolarity
• Inability to respond to ADH in distal tubule

Central/Cranial Diabetes Insipidus

• Lack of ADH secretion
• Treated with ADH analogues

Nephrogenic Diabetes Insipidus

• Kidney is unable to respond to ADH
• Managed with medication like high-dose analogue and thiazide diuretics