5 - Clinical Correlations of Renal Physiology and Disease Flashcards
Describe normal water homeostasis in a cell? How would you calculate osmolarity?
Osmolarity = total solute / ECF volume
Biggest components of serum osmolarity is the sodium, and to regulate this we change our total body water.
How does our body respond to a hypertonic solution in order to maintain isotonicity?
Hypertonicity stimulates hypothalamic receptors to increase thirst to increase water intake. It also increases ADH release to increase renal water retention.
How does our body respond to a hypotonic solution in order to maintain isotonicity?
A hypotonic solution causes inhibition of hypothalamic receptors which causes a decrease in ADH release and increase in renal water excretion. It also causes a decrease in thirst to decrease water intake.
What are the two stimuli for ADH release? Which has more of an impact?
Plasma osmolarity and % blood volume depletion.
When plasma osmolarity increases, so does plasma ADH.
When the % of blood volume depletion increases (more blood volume loss), plasma ADH increases. This is due to baroreceptor control and has more of an impact on plasma ADH than osmoreceptor control.
How is water balance, and therefore serum sodium, maintained in the setting of increased water intake?
Excretion of a dilute urine.
What happens with a gain of water (ie from someone who drank a LOT of water)?
Some goes in the cell and some goes in the ECF and dilutes the sodium causing low serum sodium.
How did the man who ran a marathon right after drinking a gallon of water have osmotic failure?
He was hypotnoic which should have inhibited hypothalamic receptors to decrease ADH release and decrease thirst.
Instead, he overroad his lack of thirst and continued to drink water anyway becasue he was afraid of getting dehydrated.
He did not get an decrease in ADH because he has hypovolemic due to the sodium lost in his sweat (hypovolemia refers to the total sodium concentration)
What are clinical manifestations of hyponatremia? When does this occur?
Prominent when change in Na occurs rapidly
Signs and symptoms: nausea, vomiting, weakness, headache, lethargy, seizures, respiratory depression, and death.
What are some factors that alter water balance?
- Appropriately eleevated ADH from volume deppletion
- Excessive water intake - hypotonic fluids
- Altered renal water handling - chronic kidney disease
- Inappropriate secretion of ADH
What can cause inappropriate secretion of ADH?
- Cancer (small cell lung)
- CNS disease
- Pulmonary disease
- Drugs
- Narcotics
- Antiemetics
- SSRIs
- Antipsychotics
- Antiseizures
- HIV
What is the primary determinant of ECH osmolarity?
Serum Na
ECF osmolarity is tightly regulated by changes in what?
Thirst and ADH secretion
___________ is required to prevent hypoosmolarity due to increased water intake.
Excretion of a dilute urine (osm <100 mOsm/kg).
_______ can precipitate hyponatremia and hypoosmolarity since urinary dilution is impaired (osm >300 mOsm/kg).
Inappropriately elevated ADH
What is a normal GFR value? How is it usually estimated?
Amont of plasma filtered through the glomeruli per unit time; usually 90-125 ml/min
Usually estimated based on serum creatinine.
What is serum creatinine and what is a limitation of using it to estimate GFR?
- Breakdown product of skeletal muscle; production remains constant over time.
- Filtered at the glomerulus (like inulin) and creatinine clearance can be used to estimate GFR.
- The fold increase in serum cr estimates the fold decrease in GFR.
Limitations: unlike inulin, creatinine is also secreted in the nephron and creatinine overestimates GFR.
What is the equation that can be used to calculate renal clearance of creatinine?
Creatinine clearance = Urinary concentration of creatinine x urinary volume of creatinine per day / plasma concentration of creatinine x 1440 min (# min in a day)
creatinine clearance = U x V / P
What effect does AngII have on proximal tubular Na reabsorption?
It increases the Na/H transporter to increase Na reabsorption. This brings in more sodium into the cell so it can be brought into the renal interstitial fluid via the Na/K exchanger and the Na/HCO3 symporter.
What effect does aldosterone have on control of tubular Na reabsorption?
Stimulates Na reabsorption in cortical collecting duct principal cells and K+ secretion.
- ~2% of filtered load of Na has its excretion depdendent on aldosterone action.
- Increases number of luminal Na channels and basolateral Na/K ATPases.
What is the mechanism of action of ADH (AVP) on late distal tubules, collecting tubules, and collecting ducts?
ADH binds to the receptors which have a GPCR that causes cAMP to be made causing cascade.
Aquaporin channels are then inserted into the tubular side and allows water to come into the cell down its concentration gradient to absorb more water.
How does kidney disease impact Ca and phospohrous regulation?
Decrease in active Vitamin D (1,25 OH vitamin D) leading to decreased calcium absorption (low serum Ca), hypocalcemia, and secondary hyperparathyroidism (increased PTH in response to low calcium causing phosphorous retention).
High PTH leads to calcium resorption from bone to increase serum calcium. It also causes an increase in phosphorous that your damaged kidneys cannot get rid of.
