Endocrinology

Question 1

Salt and Water Regulation

Answer 1

1. Na+ regulation is a/w water homeostasis yet it is regulated by independent mechanisms.
2. Changes in Na+ concentration are a reflection of water homeostasis, whereas changes in Na+ content (and subsequently, fluid volume) are a reflection of Na+ homeostasis.
3. Disturbance of Na+ balance > hypovolemia or hypervolemia; disturbance of water balance > hyponatremia or hypernatremia.

Question 2

Sodium Homeostasis

Answer 2

1. Sodium is actively pumped out of cells > restricted to the extracellular space. It is the main osmotically active cation of the ECF
2. An increase in sodium intake results in an increase in ECF volume > increase in GFR + sodium excretion. This occurs partially through release of ANP/BNP by the heart and decrease of renal renin release, which together
   promote natriuresis and inhibit norepinephrine, epinephrine, aldosterone, and ADH release.
3. A decline in the extracellular circulating volume > decreased GFR + less sodium excretion. This is a response to the sympathetic nervous system
   increasing cardiac output + decrease in renal perfusion pressure > activation of the renin-angiotensin-aldosterone system. Aldosterone increases sodium
   reabsorption + potassium secretion from the late distal tubules.
4. Diuretics inhibit Na+ reabsorption through various mechanisms in the renal tubular system. Furosemide and other loop diuretics inhibit the Na-K-CI transporter in the
   thick ascending limb of the loop of Henle, whereas thiazide diuretics inhibit the Na-CI cotransporter at the early distal tubule. However, the majority of Na+ reabsorption
   occurs in the proximal tubule.

Question 3

Water Homeostasis

Answer 3

1. Osmoreceptors in the hypothalamus are stimulated by plasma hypertonicity (usually >295 mOm/kg); activation of these stimulators produces thirst.
2. Hypertonic plasma also stimulates the secretion of antidiuretic hormone (ADH) from the posterior pituitary gland. When ADH binds to V2 receptors in the renal collecting
   ducts, water channels are synthesized and more water is reabsorbed.
3. ADH is suppressed as plasma tonicity decreases.
4. Ultimately, the amount of water intake/output (including renal, Gl, insensible losses from the skin/respiratory tract) must be equivalent over time to preserve a steady state.
5. When a steady state is not achieved, hyponatremia or hypernatremia usually occurs.

Question 4

Hyponatremia gen info

Answer 4

1. Too much water in relation to sodium in serum.
2. Defined: plasma Na+ <135 mmol/L
3. Symptoms usually begin when Na+ level falls to <120 mE/L. An important exception is increased intracranial pressure (ICP) (e.g., after head injury). As ECF osmolality decreases, water shifts into brain cells, further increasing ICP. (It’s critical to keep serum sodium normal or slightly high in such patients.)

Question 5

Hyponatremia causes/classification

Answer 5

1. Hypotonic hyponatremia- “true hyponatremia”: serum osmolality <280 mOsm/kg (can be measured or calculated using sodium, BUN, and glucose)
   a. Hypovolemic
   • Low urine sodium (<10 mEq/L)- implies increased sodium retention by the kidneys to compensate for extra-renal losses of sodium-containing fluid (e.g., diarrhea, vomiting, nasogastric suction, diaphoresis, third-spacing, burns, pancreatitis)
   • High urine sodium (>20 mEq/L)- renal salt loss is likely due to tubular dysfunction– for example, diuretic excess, ATN, decreased aldosterone (i.e., RTA type IV, causes include ACE/ARBs)
   b. Euvolemic– no evidence of ECF expansion or contraction on clinical grounds
   • SIADH: Causes are numerous and include CNS pathologies, malignancy (mc small cell lung cancer), surgery (postop hyponatremia), drugs (e.g., SSRIs, oxytocin, carbamazepine, haloperidol, cyclophosphamide, certain anti-neoplastic agents), infections (HIV, pulmonary infections), and more
   • Hypothyroidism: mechanism not fully understood
   • Adrenal insufficiency: cause is multifactorial
   • Psychogenic polydipsia
   • Administration/intake of a relative excess of free water– given D5W (or other hypotonic soln) to replace fluids, or if water alone is consumed after intensive exertion (with profuse sweating)
   • Low dietary solute intake: kidneys
   The relative
   bidess of water in relation to sodium results in hyponatremia)
   • CHF
   • Nephrotic syndrome (renal failure)
   • Liver disease
   2, Isotonic ay ponatteria (pseudohyponatremia)
   1’ ‘Ain nerease in plasma sal dye Sa proteins or lipids) artificialy lowers the plasma
   Sodium concentration measurement via laboratory artifact, but the amount ol
   sodium in plasma is normal (hence, pseudohyponatremia).
   - This can be caused by any condition that leads to elevated protein or lipid
   levels.
2. Hypertonic hyponatremia
   a” Caused by the presence of osmotic substances that cause an osmotic shift of
   water out of cells. These substances cannot cross the cell membrane and therefore
   create osmotic gradients
   b. These substances include:
   • Glucose–Hyperglycemia increases osmotic pressure, and water shifts from
   cells into ECF leading to a dilutional hyponatremia. For every 100 mg/dL
   increase in blood glucose level above normal, the serum sodium level
   decreases about 3 mEq/L. Note that the actual sodium content in the ECF
   is unchanged.
   • Mannitol, sorbitol, glycerol, maltose
   • Radiocontrast agents