Salt Balance Disorders

Lecture #2

How does osmolality function?

moves from area of low to high concentration until equal concentration

Tonicity?

-the state of osmotic pressure of a solution

-does this solution cause the cell to swell or shrink?

Hypotonic Solution (Alteration)

-low osmotic pressure

-causes the cell to swell or burst

-ECF Osmolality < ICF osmolality

Isotonic Solution (Alteration)

-Cell maintains shape/size

-ECF VOLUME change

-same osmotic pressure 

Hypertonic Solution (Alteration)

-cell shrinks

-higher osmotic pressure

-ECF Osmolality > ICF Osmolality

Hypertonic Volume Contraction

-dehydration due to water deficit (e.g. Sweating)

Loss of water from ECF → decreased ECF volume → increased ECF osmolarity → decrease ICF volume (osmotic gradient draws water from ICF) → increasing ICF osmolarity

-ECF + ICF Volume decreases while osmolality increases

Isosmotic Volume Contraction

-Dehydration due to volume deficit (e.g. blood loss, diarrhea)

-loss of salt and water from ECF → decreased ECF volume

-ICF volume and osmolality unchanged

Hypotonic Volume Expansion

-overhydration due to water excess (e.g. compulsive water excess

-gain of water in ECF → increases ECF volume → decrease ECF osmolarity → osmotic gradient causes ICF to draw water from ECF → decreasing ICF osmolarity

Isotonic Volume Expansion

-overhydration due to volume excess (e.g. infusion of isotonic saline)

gain of salt and h2o in ECF → increased ECF volume

-no change in ECF osmolarity or ICF volume and osmolarity

Why does Na+ have a greater influence on fluid balance than any other ion?

Sodium (Na⁺) has the greatest influence on fluid balance because it is the most abundant extracellular ion and it determines the osmotic gradients that control water movement throughout the body.

Describe Na+ reabsorption in the nephron?

• >90% of filtered Na+ (and water) absorbed at PT

• Collecting Duct reabsorbs variable amounts depending on body’s needs

What Hormones control Na+ uptake in kidneys?

-Aldosterone (RAAS System)

RAAS Purpose

-To raise blood pressure and increase salt uptake

What detects Na+ concentration?

Baroreceptors detect blood pressure which is determined by the concentration of sodium in the body

How do Baroreceptors work?

-located throughout circulatory system

-detect changes in blood pressure (controlled by [Na+])

-a drop in blood pressure sends neural signals to juxtaglomerular cells near the afferent arteriole to release renin

Explain RAAS

• a drop in blood pressure causes juxtaglomerular cells to release renin

• renin → angiotensin →angiotensin converting enzyme→ angiotensin II

• Angiotensin II causes vasoconstriction and aldosterone release

• Aldosterone enhances renal sodium retention (which raises blood pressure)

Describe the Collecting Duct and Blood Supply with no Aldosterone

-high blood pressure (because aldosterone is stimulated by low bp)

-the kidney is excreting Na+ into urine

Describe the Collecting Duct and Blood Supply w/Aldosterone

-Low bp causes Aldosterone release

-aldosterone binds MR (mineralocorticoid receptors)

-MR agonism (binding) causes the expression of sodium permeable channels (ENaC) in collecting duct cells

-MR agonism stimulates Na+/K+ ATpase pump to push Na+ into circulation and K+ into cells

Aldosterone and ADH Interplay”

Low BP → stimulates Aldosterone → increase Na+ uptake → raises plasma osmolality → stimulates ADH → increasing H2O uptake → bp and plasma osmolality normalized

What are diuretics?

-blockers of renal Na+ absorption

—if you can’t absorb Na+ then water can’t follow

-can lower blood pressure

-can treat edema

-increases urine output of Na+ and H2O

Hypertonic Volume Expansion?

Hypernatremia due to salt excess (e.g. too much salt in the diet)

-gain of salt in ECF → increased ECF osmolality → ECF draws water from ICF → increase ECF volume → increase ICF osmolarity

-increase BP

-ECF osmolarity and volume increase

-ICF osmolarity and volume increase

Hypotonic Volume Contraction

-hyponatremia due to salt deficit (e.g. low Na+ diet, adrenal insufficiency: low ALDO)

-loss of salt from ECF → decreased ECF osmolarity → water from ECF to ICF → increase in ICF volume → lowers ICF osmolarity

-ECF Volume and osmolarity decrease

-ICF volume and osmolarity decrease

What is potassium important for?

-regulation of cell volume

-DNA and Protein synthesis

-Resting membrane potential

-neuromuscular excitability

Intracellular vs Extracellular K+

150 mM vs 3.6-5.1 mM

Describe Potassium distribution (Na/K ATPase Pump)

-Na+/K+ ATPase pump loads cells with K+ (3 Na+ out, 2 K+ in)

-converts relatively large % changes in extracellular [K+] to relatively small changes in intracellular [K+]

Potassium and Membrane Potential?

-sincenmost cells are extremely permeable to K+

-the membrane potential of the cell is close to equilibrium potential for K+

-Nernst Equation calculates membrane potential

Electrical consequence of K+ disturbance?

Small changes in K⁺ levels can have dramatic effects on the heart and nervous system (excitable cells)

-Hyperkalemia → initially makes cells too excitable, later causes inactivation of Na+ channels, making cell less excitable

-Hypokalemia → makes cells less excitable

K+ deviating outside of its normal (ECF) range can cause life threatening cardiac arrhythmias and paralysis

Hyperkalemia?

-cell too excitable, then Na+ channels inactivate making cell less excitable

• >5.5mM K+ in ECF

Hypokalemia?

-makes cell not excitable enough

• <3.5mM K+ in ECF

Causes of Hyperkalemia?

• Excessive K+ intake

• Ineffective K+ secretion (kidney disease)

• Cell Damage (lysed cells release intracellular K+; lysed = cell membrane broken and cell contents leak into environment)

• Cell Shrinkage (increases intracellular K+, driving K+ into ECF)

• Any inhibition of Na/K ATPase pump (digitalis, hypoxia, acidosis)

Regulation of K+?

-High K+ stimulates aldosterone 

-Aldosterone promotes K+ sequestration (trapping or storing away K+ from bloodstream; short term response)

-Aldosterone promotes K+ secretion in urine and sweat (long term response)

How is excess K+ sequestered?

tissue uptake of K+ is enhanced by aldosterone, epinephrine, insulin

-Na+/K+ ATPase pump sequesters K+ (3 Na+ out, 2 K+ in)

Aldosterone Effect on K+ and Na+?

-Aldosterone MR Agonism expresses ENaC channels allowing sodium into collecting duct cell

-ATPase Pump switches Na+ and K+ in the bloodstream

-ALDO expresses ROMK (renal outer medullary K+ channel) which pushes K+ into urine from collecting duct cell

Hyperkalemia Treatment?

-stimulate K+ storage using insulin (stimulates Na+/K+ ATPase pump)

-Stimulate K+ secretion using aldosterone

Causes of Hypokalemia?

-anything that elevates K+ secretion (e.g. hyperaldosteronism caused adrenal tumor

-anything that causes ECF depletion (diarrhea, vomitting: elevates aldosterone)

Treatment of Hypokalemia?

-ECF Volume repletion (avocado, sweet potato, acorn squash, spinach, dried apricot, coconut water, kefir/yogurt, white beans, mushrooms, bananas)