2 clinical correlations Flashcards
Describe the normal water balance
- normal intake 1-1.5 L/day
- equilibration between extra and intracellular compartments
- total body water ~60% of body weight
- fixed water excretion/insensible losses ~0.5 L/day
- stool, sweat, lungs
- variable water excretion
- total urine output ~1-1.5 L/day
Define the osmolarity of the ECF
OsM= Total solute/ECF volume
What are the results of hypertonicity?
- stimulate hypothalamic receptors
- increase thirst/water intake
- increase ADH release/renal water retention
- opposite response to hypotonicity
What are the 2 main stimuli for ADH release?
- Osmoreceptor control: plasma osmolarity
- ADH is approximately constant over normal osmolarity changes (270-290)
- Baroreceptor control: blood volume depletion
- hypovolemia stimulates much more ADH release (than hypotonicity)
What are some clinical signs of hyponatremia?
- N/V
- weakness/lethargy
- headache
- seizures
- respiratory depression
- death
What are the 3 main factors that alter water balance?
- appropriate ADH elevation (during volume depletion)
- excessive water/hypotonic fluid intake
- renal water handling (altered in chronic kidney disease)
What can cause inappropriate ADH secretion?
- cancer (e.g. small cell lung)
- CNS disease
- pulmonary disease
- drugs (e.g. narcotics, SSRIs, etc)
- HIV
What is the primary determinant of ECF osmolarity? How is it regulated?
Serum sodium
**ECF OsM is tightly regulated by changes in thirst and ADH secretion
What is the problem with using creatinine to estimate GFR? What substance is better?
Creatinine is secreted in the nephron and its clearance therefore overestimates GFR… inulin is freely filtered and not secreted
What are 3 direct tubular effects that stimulate Na reabsorption?
- renal sympathetic nerves
- angiotensin II
- binds AT1 receptor and increases activity of proximal tubule Na/H counter-transporter
- stimulates aldosterone secretion
- aldosterone
- stimulates Na reabsorption in cortical collecting duct principle cells (increases number of luminal ENaCs and basolateral Na/K ATPases)
What’s the major control of water reabsorption?
ADH release due to baroreceptor activation
Describe the MOA of ADH on late distal tubules/collecting ducts
- ADH binds V2 receptor
- stimulates Gs/adenylyl cyclase
- increases cAMP production
- cAMP stimulates protein kinases
- protein phosphorylation inserts premade aquaporin-2 molecules into the tubular membrane
- water reabsorption increases
How is enhanced renal tubular Na/water reabsorption reflected in clinical tests?
- low urine Na
- low FENa
- elevated urine osmolarity
How is serum Ca regulated?
- PTH leads to increase Ca resorption from bone
-
1,25 OH Vit D increases intestinal Ca absorption
- 25-OH Vit D to 1,25 OH Vit D (active) conversion primarily takes place in the kidney
- low 1,25 OH Vit D leads to low serum Ca
How is the kidney involved in phosphate excretion?
High serum phosphate levels increase PTH secretion which leads to less phosphate reabsorption in the renal tubule
