L6 Renal Regulation and Fluid Balance

Water

• Properties

  • Superb solvent: Crucial for transporting nutrients and waste.

  • High heat capacity: Stabilizes body temperature.

  • High latent heat: Aids cooling through sweat evaporation.

• Distribution

  • Intracellular fluid (ICF): Most fluid is within cells (2/3 of total body water).

  • Extracellular fluid (ECF): Includes interstitial fluid and plasma (1/3 of total body water).

  • Interstitial fluid (IF): Most extracellular fluid; surrounds cells outside blood vessels.

• Composition

  • Intracellular fluid (ICF): Fluid inside cells.

  • Interstitial fluid (IF): Fluid surrounding cells outside blood vessels.

  • Plasma: Fluid component of blood.

Maintaining Composition

• Key Components

  • Extracellular fluid: Sodium ($Na^+$).

  • Plasma.

  • Cytoplasm.

  • ATP.

  • Phosphate.

  • ADP.

  • Potassium ($K^+$).

  • Concentration: Proper ion concentrations are vital for cellular function.

Capillary Fluid Exchange

• Arterial End

  • Net filtration pressure = +10 mm Hg

  • Fluid exits capillary because capillary hydrostatic pressure (35 mm Hg) > blood colloidal osmotic pressure (25 mm Hg).

• Mid-Capillary

  • Net filtration pressure = 0 mm Hg

  • No net movement of fluid; capillary hydrostatic pressure (25 mm Hg) = blood colloidal osmotic pressure (25 mm Hg).

• Venous End

  • Net filtration pressure = -7 mm Hg

  • Fluid re-enters capillary because capillary hydrostatic pressure (18 mm Hg) < blood colloidal osmotic pressure (25 mm Hg).

How Much Fluid?

• Total Body Weight

  • Water (50-70%): Varies with age, sex, and hydration level.

  • Solids

• Distribution

  • 2/3 Intracellular fluid (ICF): Most of the body's water.

  • 1/3 Extracellular fluid (ECF): Remaining water outside cells.

• ECF Composition

  • 75% Interstitial fluid

  • 20% Plasma

• Example Calculation (70 kg Body Mass)

  • Total Body Water (TBW): 60% of body mass = 42 kg = 42 L

  • Non-Water Mass (NWM): 40% of body mass = 28 kg

  • Interstitial Fluid: 75% ECF = 10.5 L = 10.5 kg

  • Plasma: 25% ECF = 3.5 L = 3.5 kg

  • RBC volume: 2.8L

  • Blood volume: 6L

  • Normal HCT: 45%

Regulating Water

• Dehydration

  • Extracellular osmolarity increases.

  • Osmoreceptors detect this change.

  • ADH secretion increases.

  • Distal tubules & collecting ducts permeability increases.

  • Water reabsorption increases.

  • Water excreted decreases.

Nerves Involved with Regulating Water

• Increase in Extracellular Fluid Osmolarity.

• Osmoreceptor cells (anterior hypothalamus) shrink.

• Shrinkage causes firing.

• Nerve signals to supraoptic nuclei.

• Action potentials to posterior pituitary.

• Stimulate ADH release.

• Reabsorption of water.

• Excrete concentrated urine.

Antidiuretic Hormone (ADH)

• Factors Influencing Release

  • Osmolality.

  • Haemodynamic factors.

  • Nausea: Stimulates.

  • Atrial natriuretic peptide (ANP): Inhibits.

  • Angiotensin II: Stimulates.

• Main Physiological Factors

  • Main Site for ADH Synthesis:

    • Pituitary

    • Supraoptic neuron

    • Paraventricular neuron

    • Osmoreceptors

    • Baroreceptors

    • Cardiopulmonary receptors

  • ADH Storage: Posterior pituitary

  • Osmolality:

    • Osmoreceptors in the hypothalamus (outside the blood-brain barrier).

    • $↑$ osmolality = $↑$ ADH release

    • "Set point" 280-285 mOsm/kg H2O

  • Blood Volume:

    • $↓$ blood volume = $↑$ ADH release

    • Less sensitive than osmolality; needs 5-10% blood volume change.

    • Changes in blood volume affect osmolality.

    • Volume/BP set point

  • ADH

  • Urine: Decreased flow and concentrated

Three Stimulants for Thirst

• Insufficient $H_2O$ in the body.

  • Decreases blood volume.

  • Increases blood osmolality.

  • Increases angiotensin II.

  • Dry mouth.

  • Osmoreceptors in the hypothalamus.

  • Stimulates thirst center in the hypothalamus.

Thirst Regulation

• Produced by hypothalamus.

• Released by posterior pituitary.

• Increases thirst.

• $H_2O$ taken in.

• Decreases blood osmolality.

• Affects some social behaviors in mammals.

Water Balance

• Decreased volume of extracellular fluid = Stimulation of osmoreceptors in the hypothalamic thirst center.

• Increased osmolality of extracellular fluid = Stimulation of osmoreceptors in the hypothalamic thirst center.

• Decreased saliva secretion = Dry mouth.

• Sensation of thirst; a person seeks a drink.

• Water absorbed from the gastrointestinal tract.

• Increased volume of extracellular fluid = Decreased osmolality of extracellular fluid.

• Key: Stimulation = Inhibition

• To stay in balance: water intake = water loss.

• Fluid intake is regulated by the thirst mechanism.

• The desire for thirst is completely satisfied when: Plasma osmolarity, blood volume, or both return to normal.

Regulating Water (Excess)

• Dealing with being overfilled (excess water)

  • Extracellular osmolarity decreases.

  • Osmoreceptors detect this change.

  • ADH secretion decreases.

  • Distal tubules & collecting ducts permeability decreases.

  • Water reabsorption decreases.

  • Water excreted increases.

Balancing Fluid

Role of Lungs, Angiotensin II & Aldosterone

• They do not normally play a major role in controlling ECF osmolarity and $Na^+$ concentration.

• Their major role is to absorb sodium through distal convoluted tubules, leading to greater extracellular fluid volume and sodium quantity.

• Kidney releases renin into the blood.

• Liver releases angiotensinogen into the blood.

• Renin converts angiotensinogen to angiotensin I.

• Angiotensin-converting enzyme (ACE) in pulmonary blood converts angiotensin I to angiotensin II.

• Angiotensin II stimulates aldosterone secretion by the adrenal cortex.

• Aldosterone stimulates $Na^+$ and $H_2O$ reabsorption in the nephrons.

Renin

• Triggers for Increased Release

  • Hyponatraemia

  • Sympathetic nervous system stimulation

  • Reduced blood pressure

• Renin converts angiotensinogen to angiotensin I.

ACE

• Angiotensin-converting enzyme acts in the blood capillaries of the lungs.

• Angiotensin-converting enzyme is called ACE, and any chemical that reduces its action is called an ACE inhibitor (ACEi).

• Their names usually end with "pril," e.g., Ramipril.

• ACE converts angiotensin I to angiotensin II.

pH Control

Importance of pH

• Enzymes need a narrow range of pH to act effectively.

• Proteins are denatured.

• Death

What is pH?

• Acid: A substance that can donate an $H^+$ or dissociate an $H^+$.

• Base: A substance that can accept an $H^+$.

• Acid/Base Pair

  • $HA ⇌ A^- + H^+$

  • $B + H^+ ⇌ HB$

  • $HCl / Cl^−$

  • $NH4^+ / NH3$

  • $H_2O / OH^−$

  • $H3O^+ / H2O$

• Water ($H_2O$) can be an acid or a base.

  • $2 H2O ⇌ H3O^+ + OH^−$

  • $H−Cl + H2O → Cl^− + H3O^+$

  • (acid) (base) (base) (acid)

  • $NH3 + H2O ⇌ NH_4^+ + OH^−$

  • (base) (acid) (acid) (base)

• The term pH refers to the concentration of hydrogen ions ($H^+$.

  • $pH = −log[H_3O^+]$

  • $pH ↓, [H_3O^+]↑$

  • $pH ↑, [H_3O^+]↓$

pH in Blood

• The term pH refers to the concentration of hydrogen ions ($H^+$.

  • $pH = −log[H_3O^+]$

  • $pH ↓, [H_3O^+]↑$

  • $pH ↑, [H_3O^+]↓$

• Normal pH range: 7.35 - 7.45

• Survival range: 6.8 - 7.8

• Acidosis: < 7.35

• Alkalosis: > 7.45

pH in the Blood: Acidosis vs. Alkalosis

• Acidosis (Acidaemia)

  • Accumulation of acid

  • $H^+$ addition

  • Depletion of alkali

• Alkalosis (Alkalaemia)

  • Accumulation of base

  • Loss of $H^+$

  • Increase in base

Causes of Acidaemia

• Metabolic Causes

  • Production of ketones (diabetes or fasting)

  • Production of fatty acids (proteins in diet)

  • Breakdown of body proteins

  • Alcohol excess

  • Drug overdoses

  • Severe kidney disease

  • Poisons (ethylene glycol or methanol)

• Respiratory Causes

  • Lactic acid production (anaerobic respiration, shock)

  • Asthma, pneumonia, pulmonary oedema

  • Breath holding, airway blockage

  • Carbon dioxide retention

Causes of Alkalaemia

• Metabolic Causes

  • Drug overdoses

  • Fever or infection

  • Vomiting or drainage of stomach fluid

  • Overactive adrenal gland (or tumor)

  • Use of diuretics

• Respiratory Causes

  • Anxiety or panic attack

  • Low level of oxygen

  • Aspirin overdose causes an initial respiratory alkalosis followed by a metabolic acidosis.

Control of pH

• Quick-Acting

  • Buffering

  • Respiratory response

• Slow-Acting

  • Renal response

  • Vomit

Control of pH: Buffering

• $CO2 + H20 ⇌ H2CO3 ⇌ HCO_3^− + H^+$ (catalyzed by carbonic anhydrase)

Control of pH: Buffering (Body Fluids)

• $H2CO3$ (Carbonic acid): An acid, acts as a proton donor (source of $H^+$ ions).

• $HCO_3^−$ (Bicarbonate ion): A base, acts as a proton acceptor; alkaline reserve in the blood.

• $CO2 + H20 ⇌ H2CO3 ⇌ HCO_3^− + H^+$ (catalyzed by carbonic anhydrase)

Control of pH: Breathing Rate and Style

• Hyperventilation

  • Increases oxygen (no impact on pH)

  • Decreases carbon dioxide

  • Decreases acid

Control of pH: Renal Response

• Slow effect – days and weeks

• Greater effect on pH than any other method

• Apart from carbonic acid, all acids are eliminated by the kidneys

• 90% $HCO_3^−$ reabsorbed by PCT, 10% by DCT

• Whole nephron secretes excess $H^+$ into the lumen

• Reabsorption and regeneration of $HCO_3^−$

Acid Secretion in PCT

• $CO2$ combines with water within the tubule cell, forming $H2CO_3$.

• $H*2CO3$ is quickly split, forming $H^+$ and bicarbonate ion ($HCO3^−$).

  • a. $H^+$ is secreted into the filtrate.

  • b. For each $H^+$ secreted, an $HCO_3^−$ enters the peritubular capillary blood either via symport with $Na^+$ or via antiport with $Cl^−$.

• Secreted $H^+$ combines with $HCO3^−$ in the filtrate, forming carbonic acid ($H2CO3$). $HCO*3^−$ disappears from the filtrate at the same rate that $HCO3^−$ (formed within the tubule cell) enters the peritubular capillary blood.

• The $H2CO_3$ formed in the filtrate dissociates to release $CO2$ and $H*2O$.

• $CO_2$ diffuses into the tubule cell, where it triggers further $H^+$ secretion.

Control of pH: Renal Response (cont.)

• Slow effect – days and weeks

• Greater effect on pH than any other method

• Apart from carbonic acid, all acids are eliminated by the kidneys

• 90% $HCO_3^−$ reabsorbed by PCT, 10% by DCT

• Whole nephron secretes excess $H^+$ into the lumen

• Reabsorption and regeneration of $HCO_3^−$