Clinical Correlations of Renal Physiology and Disease Flashcards
Exaplain the relationship between normal water input and output
input it 1-1.5 L
output is 1-1.5 in urine and 0.5 in insensible loss like stool, sweat, and pulmonary
WHat is osmolarity? What is the bigegst component?
Osmolarity is total solute/ECF volume
biggest component is Na (140mEq/L and is regulated by amount of ECW)
how does the body respond to hypertonicity?
It wants to get back to isotonicity!
- stimulate hypothalamic receptors
- increase thirst which increases water intake
- also increase ADH release which causes renal water retention
How does the body respond to hypotonicity?
it wants to get back to isotonicity!
- inhibit hypothalamic receptors
- decrease ADH release which leads to renal water excretion
- also decrease thirst which leads to decreased water intake
What 2 things stimulate ADH release?
- osmoreceptor control
- baroreceptor control
- hypovolemia (low Na) is the main driver
How does osolarity chaneg throughout the tubular fluid?
- iso-osmotic in the proximal tubule
- in the descednign loop of henle is increases in osmolarity
- in the ascending loop of henle is decreases in osmolarity
- it slowly increases throughout the distal tubule and collecting tubule and duct
- drastically increases in the medullary collecting duct until it is a concentrated urine! ADH is responsible for the big incerase in osmolarity!
A man drinks a gallon of wate then runs, he is hypovolemic. what lead him to osmotic failure?
He had hypovvolemia due to sweating and losing Na. so he did like decrease ADH leading to renal water excretion like he should have!
He also ignore his decreased thirst and drank water anyway!
What are the clinical manifestations of hyponatremia?
prominent when change in Na occurs rapidly
signs and symptoms:
- nausea
- vomiting
- weakness
- headache
- lethargy
- seizures
- respiratory depression
- death
What factors alter water balance?
- appropritely elevated ADH
- volume depletion
- excessive water intake
- hypotonic fluids
- altered renal water handling
- chronic kidney disease
- inappropriate secretion of ADH
- Cancer (eg small cell lung)
- CNS disease
- pulmonary disease
- drugs
- narcotic
- antiemetics
- SSRIs
- antipsychotics
- antiseizure
- HIV
what is the primary determinant of ECF osmolarity? ECF osmolarity is tightly regulated by what?
primary determinant of ECF osmolarity is Serum Na
ECH osmolarity is tightly regulated by changes in thirst and ADH secretion
What is required to prevent hypoosmolarity due to increased water intake?
__________can precipitate hyponatremia and hypoosmolarity since urinary dilution is impaired (osm>300mOsm/kg0
excretion of dilute urine (osm<100mOsm/kg) is required to prevent hypoosmolarity due to increased water intake
inappropriately elevated ADH can precipitate hyponatremia and hypoosmolarity since urinary dilution is impaired (osm>300mOsm/kg)
(what happen to the hyovolemic man)
What is glomerular filtration rate? what is it usually estimated on?
GFR: amount of plasma filtered through glomeruli per unit time
usually estimated based on serum creatine
what is serum creatine? what is it used for? what are its limitations?
- breakdown product of skeletal muscle
- production remains constant over time
- filtered at the glomerulus (like inulin) and creatine clearance can be used to estimate GFR
- the fold increase in serum Cr estimates the fold decrease in GFR (ie if Cr double GFR 1/2s)
- limitations: ulike inulin, creatine is also secreted in the nephron and creatine clearance overestimates GFR
What is the equation for Creatine Clearance?
What is the Cockcroft-Gault equation? and what do you multilpy by if female?
If female multiply by 0.85
GFR under what value is often underestimated with the MDRD equation, so labs using MDRD should only report those as ______`
other than MDRD what other equation is often used to represent GFR?
GFR>60 often underestimated with MDRD, so labs using MDRD should onyl report those as >60
CKD-EPI also used
Serum creatine can be used to estimate GFR is what 3 things are true? When are creatine based measures of GFR inaccurate?
- CrCl can be calculated by U*V/P
- GFR can be estimated by Cockcroft-Gault
- the fold change in serum Cr can estimate the fold chaneg in GFR
serum creatine based GFR estmates can be inaccurate due to extremes of age, obesity or muscle mass
what 3 inputs influence control of tubular Na reabsorption?
renal sympathetic tone
hormonal
blood pressure
these inputs ultimately effect tubular Na channels and transporters
What 2 things directly effect the tubule? and what is their effect?
- renal sympathetic nerves:
- multiple tubular receptrs stimulate Na reabsorption
- Angiotensin II
- tubular receptors
- increases activity of proximal tubule Na/H counter transporter
- aldosterone excretion
How does aldosterone influence tubular Na reabsorption?
- stimulates Na reabsorption in cortical collecting duct principal cells
- about 2% of filtered load of Na has its excretion dependent on aldosterone action
- increases number of luminal Na channels and basolateral Na/K/ATPases
_____ activation leads to ADh release
baroreceptor activation leads to ADH release to control water reabsorption
mechanistically how does ADH stimulate increased water reabsorption on the late distal tubules, colecting tubules and colelctingducts?
ADh binds to the receptor which is a Gs (GPCR) which activates AC which increases concentration of cAMP which activates PKA whic leads to placement of aquaporin channels to increase water reabsoprtion
what is the osmolarity of urine?
1200
the systemic respone to decreased ECF volume involves what 3 things? What do these factors lead to? How is this clinically reflected?
- baroreceptor and sympathetic nerve activation
- activation of renin-angII-aldo system
- increased ADH
these 3 factors (inresponse to decreased ECF volume) lead to enhanced renal tubular Na and water reabsorption
this is clinically reflected by low urine Na, low FENa, and elevated urine osmolarity
