Body Fluid Compartments & Balance

Body Fluid Compartments

• Total body water volume equals 40L, making up 60% of body weight
• Extracellular fluid volume totals 15L, which is 20% of body weight.
• Intracellular fluid volume is 25L, 40% of body weight.
• Interstitial fluid volume equals 12L, 80% of ECF.
• Plasma volume is 3L, 20% of ECF.

Water and Osmolality Balance

• Homeostasis shifts and pathology results if the balance between water input and output gets disrupted.
• Average water input per day includes 250ml from metabolism, 750ml from foods, and 1500ml from beverages, totaling 2500ml.
• Average water output per day includes 100ml in feces, 200ml in sweat, 700ml in insensible losses, and 1500ml in urine, totaling 2500ml.

Electrolytes and Non electrolytes

• Electrolytes dissociate into ions in water.
  • This includes Na+, Cl-, Ca2+, Mg2+, K+.
  • NaCl yields 2 particles, while MgCl2 yields 3 particles.
• Nonelectrolytes do not dissociate.
  • Included are glucose, proteins, and urea.
  • Glucose is 1 particle.
• For nonelectrolytes and electrolytes with a single charge, molar concentration equals osmolar concentration.
• mEq/L measures the quantity of charges in solution.
  • (ion concentration (mg/L) x # of electrical charges)/atomic weight
  • or defined as mmole/L x # of electrical charge.
  • Na+ measures 3.3g/L and 23g/mole.
  • Ca2+ measures 100mg/L and 40g/mole.

Thirst Mechanisms

• Thirst is triggered by plasma osmolality and plasma volume.
• The drinking reflex is mediated by the hypothalamus.
  • A decline in plasma volume of 10-15% can trigger the drinking reflex
  • Increases in plasma osmolality of 1-2% can trigger the drinking reflex.
  • Baroreceptor input, angiotensin II, and other stimuli can also trigger the drinking reflex.

Control of Water Reabsor

• The antidiuretic hormone (ADH), also called vasopressin, is a peptide hormone.
• It's secreted by the posterior pituitary
• ADH's target cells are those of the collecting duct, allowing the collecting duct epithelium to become permeable to water.
• Water moves out of the tubule because [Solutes]interstitium > [Solutes]tubule
• ADH's effects are graded
  • More ADH released results in better water permeability.
• ADH action involves the insertion of aquaporins on the apical (tubule) surface of collecting duct cells.
• Aquaporin refers to a membrane channel protein for water.

Control of ADH Release

• Osmoreceptors are the most potent stimulus for ADH release
• They are present in the hypothalamus
• They are activated at a plasma osmolarity of >280 mOsM
• Blood volume is a less potent stimulus for ADH release.
• It is sensed by atrial stretch receptors
• Decreased stretch activates ADH release to conserve water
• Blood pressure is a less potent stimulus for ADH release.
  • It's sensed by aortic and carotid baroreceptors
  • Decreased pressure activates ADH release to conserve water.
• Adult ADH release follows a circadian rhythm.
  • As a result, more ADH is released at night, and less urine is produced.
  • Less ADH is released during the day.
• Bedwetting in children, also known as nocturnal enuresis, could mean a delay in the circadian control of ADH release
  • Many children are successfully treated with a drug that acts like ADH

Homeostatic Response

• Renal absorption of Na+ is regulated.
• Stimuli that set Na+ balance in the body are intertwined with blood pressure and blood volume.
• Following salt ingestion: increased thirst/water intake + increased renal water reabsorption
• Increased ECF volume (slow response) and blood pressure (rapid response) follows.
• Osmolarity + volume/blood pressure can return to normal as a result.
• ADH and vasopressin are the identical molecule.

Aldosterone

• Aldosterone controls Na+ balance, and it's a mineralocorticoid secreted by the adrenal cortex.
• Aldosterone helps reabsorption of Na+ in distal tubules/collecting ducts.
  • It acts on the principal cells (P-cells) of the distal nephron.
• The target of aldosterone is water reabsorption, which also leads to potassium secretion.
• Aldosterone helps up-regulate proteins that help with sodium reabsorption.
• Na+ and H₂O reabsorption in the distal nephron are separately regulated.
• Water doesn't necessarily follow sodium.
• ADH has to be released.
• Aldosterone release is activated by increased extracellular [K+] (hyperkalemia), and also decreased blood pressure/blood volume/ decreased extracellular [NA+] (RAS Pathway).
• Aldosterone is inhibited by increase of ECF osmolarity if very high.

High [K+] and the Heart

• Normal ECG occurs when potassium levels are normal (3.5-5.5 mEq/L).
• Mild (5.5-6.5 mEq/L), Moderate (6.5-8.0 mEq/L) and Severe (>8.0 mEq/L) levels of potassium present an abnormal ECG.
• This is because of hyperkalemia (Increased extracellular[K+])

RAS system

• Renin Angiotensin Aldosterone System (RAS) begins with a decrease in GFR, which causes a decrease in blood pressure.
• A decrease in blood pressure also causes the increase in NaCL transport across the macula densa of the distal tubule, as wall as granular cell to produce renin.
• Liver constantly produces angiotensinogen in the plasma
• Renin converts angiotensinogen in the plasma to ANG I
• Blood vessel in endothelium contains ACE (enzyme) which converts ANG I in plasma to ANG II in plasma.

Angiotensin II

• Angiotensin II is a potent vasoconstrictor
• Effects include vasoconstriction of the arterioles, and cardiovascular response by the medulla oblongata.
• This leads to an increase of blood pressure.
• Vasopressin is involved in the hypothalamus and promotes thirst.
• This then increases volume and maintains osmolarity
• Aldosterone is involved from the Adrenal Cortext and promotes Na+ reabsorption,

High Blood Pressure Meds

• Physiology of the RAS/aldosterone system for drugs target various locations of the RAS pathway.
• These include, Angiotensinogen, Renin Inhibitor (Rasilez) converts to Renin, Angiotensiin I converts to ACE (_pril), Angiotensiin II, AT₁ Receptor Blocker (_sartan) from Angiotensin II Type 1 Receptor, and Aldosterone Receptor Blocker (sprionolactone) from Aldosterone.

Acid Production in the Body

• Most hydrogen ions come from cellular metabolism.
• Breakdown of phosphorus-containing proteins releases phosphoric acid into the ECF.
• Anaerobic respiration of glucose produces lactic acid.
• Fat metabolism yields organic acids and ketone bodies.
• Transporting carbon dioxide as bicarbonate releases hydrogen ions.

Hydrogen Ion Regulation

• Concentration of hydrogen ions is regulated sequentially
  • Chemical buffer systems act within seconds.
  • The respiratory center in the brain stem functions within 1-3 minutes.

Acid Buffering Systems

• The three major chemical buffer systems include the bicarbonate buffer system, the phosphate buffer system, and the protein buffer system.
• HPO₄²⁻ + H⁺-> H₂P0₄⁻
• H₂P0₄⁻ + OH⁻-> HPO₄²⁻ + H₂O

Physiological Buffer Systems

• Acid-base balance is regulated by Respiratory system via a physiological buffering system. There is an equilibrium between dissolved carbon dioxide and water and carbonic acid and the hydrogen and bicarbonate ions.
• CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻

Respiratory Acidosis and Alkalosis

• Normal PC02 levels fluctuate between 35 and 45 mm Hg.
• Values above 45 mm Hg indicates respiratory acidosis.
• Values below 35 mm Hg indicates respiratory alkalosis.

Metabolic Acidosis and Alkalosis

• Typical causes of acidosis are ingestion of too much alcohol and excessive loss of bicarbonate ions.
• Other causes include accumulation of lactic acid; shock; ketosis in diabetic crisis; starvation; and kidney failure.
• In alkalosis, the main cause is vomiting of the acid contents of the stomach, intake of excess base (e.g., from antacids), and constipation, where excessive bicarbonate is reabsorbed.

Reabsorption of Bicarbonate in the Kidney

• Bicarbonate is formed in filtrate dissociates, to release carbon dioxide and water
• The Carbon dioxide then diffuses into tubule cells, which acts to trigger further hydrogen ion secretion

Reabsorption of Bicarbonate

• Carbon dioxide combines with water in tubule cells, forming carbonic acid.
• Carbonic acid splits into hydrogen ions and bicarbonate ions.
• For each hydrogen ion secreted, a sodium ion and a bicarbonate ion are reabsorbed by the PCT cells.
• Secreted hydrogen ions form carbonic acid; thus, bicarbonate disappears from filtrate at the same rate that it enters the peritubular capillary blood.

Hydrogen Ion Excretion

• In response to acidosis, kidneys generate bicarbonate ions and add them to the blood
• Then equal amount of hydrogen ions are added to the urine.

Ammonium Ion Excretion

• This method uses ammonium ions produced by the metabolism of glutamine in PCT cells.
• Each glutamine metabolized produces creates two ammonium ions and two bicarbonate ions
• Bicarbonate moves to the blood and ammonium ions are excreted in urine