Week 10 Flashcards
how does adding excess water to the body affect osmolality?
body osmolality decreases
what does hypernatremia mean?
too little water in the body relative to sodium
what does hyponatremia mean?
too much water in the body relative to sodium
what is ADH?
anti-diuretic hormone increase water reabsorbtion in the collection duct of the nephron
where does ADH work?
collecting duct of nephron
where is ADH secreted from?
posterior pituitary gland in the brain; supraoptic nucleus and paraventricular nucleus responsible for secreting ADH
how does ADH work?
inserts aquaporins into the collecting duct to allow movement of water from the urine back into the body
how does urine osmolality reflect ADH levels?
low urine osmolality indicates low ADH
triggers for ADH release
- increase in serum osmolality
- decrease in volume status
how does our body directly sense increase osmolality?
osmoreceptors in the brain detect serum osmolality
how does our body detect decreased volume status?
decreased firing of arterial baroreceptors and cardiopulmonary baroreceptors
Is ADH level more significantly influenced by osmolality or by fluid volume?
volume is prioritized over osmolality in release of ADH
ADH of a patient that is hypovolemic
will be high regardless of osmolality status
non-physiologic stimuli for ADH
- tumor, infection of brain or lungs
- feeling nauseous or having pain
where are the thirst centers located?
hypothalamus
triggers of the thirst centers
- decreased plasma volume (detected by baroreceptors)
- increased plasma osmolality
- angiotension II
- dry mouth
equation for urine osmolality
solute load / water
equation for water excretion
solute load / urine osmolality
normal serum [Na+]
135-145 meq/L
serum sodium level in cerebral edema
low serum sodium
cerebral dehydration serum sodium level
high serum sodium
when assessing TBW what should also be assessed?
Total Body Sodium
clinical presentation of patient with hypernatremia/hyponatremia
confusion, seizure, coma, death
laboratory tests to see if patient has hypernatremia/hyponatremia
Serum and Urine Osmolality
Serum Na+
lab tests to evaluate patients ECF
Hemoconcentration
Urine Na and Cl
clinical presentation of patient with ECF problem
Orthostatic
Hypotension
Tachycardia
Low BP
Dry Mucous membranes
Weight Loss
hyperosmolar hyponatremia
not true hyponatremia; appears like hyponatremia from perspective of looking at just sodium, but there is another substance that is pulling water into compartment (example = glucose)
how do you treat hyperosmolar hyponatremia?
figure out what the solute that is pulling water is and have it metabolized (often glucose)
what is isosmolar hyponatremia?
pseudohyponatremia due to lab error – ICF and osmolality are normal but patient has high lipid and cholesterol levels; the sodium is beaing measured against the volume that includes not only water but fats as well; concentration appears lower than it actually is
What does it mean a patient is hyponatremic with normal ECF and the urine osmolality is low
patient has healthy kidney and is drinking too much water
what does it mean if a patient is hyponatremic, has normal ECF, and the urine osmolality is higher than expected
increased ADH
“true” hyponatremia
low sodium and low serum osmolality
differential diagnosis: low sodium with high osmolality
hyperglycemia
mannitol infusion
differential diagnosis: low sodium and normal osmolality
patient has high lipids and/or high proteins
differential diagnosis: low sodium, low osmolality, low ECF (loss of some water and lots of sodium) – hypovolemia
Renal
- Diuretics
- Osmotic diuresis
Extra-Renal
- Vomitting
- Diarrhea
differential diagnosis: low Na, low osmolality, normal ECF, net water gain and no salt gain
- consuming too much water
- SIADH (syndrome of inappropriate ADH secretion)
- hypothyroidism
- primary polydipsia
- adrenal insufficiency
differential diagnosis: low Na, low osmolality, high ECF (gained water and salt) – more gain of water than salt
- renal failure
- heart failure
- liver failure
- nephrotic syndrome
Causes of SIADH (syndrome of inappropriate ADH secretion)
meningitis
encephalitis
seizures
lung cancer
antipsychotic medications
treatment of hyponatremia
osmolality of a patient that is hypernatremic
if a patient has hypernatremia their osmolality has to be high; can’t be hypernatremic without a high osmolality
differential diagnosis: hypernatremia with low ECF (+++ water loss, + sodium loss)
GI (diarrhea)
Skin (burns, sweat)
Renal (diuretics)
differential diagnosis: hypernatremia with normal ECF, pure water loss
diabetes insipidus
hypernatremia with high ECF (excess of salt, gained some water)
Hypertonic fluid administration
Mineralocorticoid excess
what is an example of when hypertonic fluids are given?
used when there is brain swelling (such as due to trauma); help decrease ICF volume to reduces the swelling
In diabetes insipidus there is a lack of ___
ADH
what is central diabetes insipidus and its causes?
no ADH is being produced
causes: neurosurgery, trauma to head
what is nephrogenic diabetes inspidius and what are its causes?
blocks ADH action at the level of the kidney; lithium, hypokalemia, hypercalcemia
what test do you conduct if a patient urinating excessively?
water deprivation test
what does it mean if a patient is urinating excessively and then urine osmolality increases as a result of a water deprivation test?
psychogenic polydipsia (excess drinking)
kidney function is healthy and patient is drinking excessive amounts of fluid
differential diagnosis: if patient undergoes water deprivation test and urine osmolality does not increase
either central DI or nephrogenic DI
differential between central DI vs. nephrogenic DI when urine osmolality is unchanged after a water deprivation test
patient given exogenous DDAVP (synthetic analog of ADH) and response is monitored
response = Central DI (not producing ADH)
no response = nephrogenic DI (ADH not able to act at level of kidney)
treatment of hypernatremia
how much potassium in each body compartment of the body and why?
98% in intracellular space; 2% extracellular – due to sodium-potassium pump
significance of K+ in the ECF
role in the excitability of nerve/muscle tissue (especially heart)
changes in extracellular concentration significantly affect resting potential of cell membrane; changes can lead to muscle and cardiac disturbances
how does a significant rise in extracellular potassium affect resting membrane potential?
leads to sustained depolarization
osmotic influence of potassium in body
makes up major osmotic component of ICF
effects of changes in intracellular potassum concentration
minimal effect due to the large amount of intracellular potassium compared to extracellular
extracellular concentration of potassium depends on:
- Total amount of potassium in the body
- Distribution of potassium between extracellular and intracellular spaces
how it the ingestion of potassium handled?
potassium short term in extracellular space and shuttled into skeletal muscle where concentration of potassium is not significantly changed
hormones that drive potassium into cells (ECF to ICF)
- Insulin
- Epinephrine
how does insulin drive potassium into into cells and why is this helpful?
- Increases activity of Na/K pump
- Insulin increases after meals, helps drive potassium intracellularly – helpful because we increase potassium intake in meals and insulin helps us absorb this
- Elevated serum [K+] stimulates insulin secretion
how does epinephrine drive potassium from ECF to ICF and in what cases is this important?
- Increases activity of Na/K pump
- Important in cases of:
- Exercise: K+ moves out of cells with rapidly firing action potentials
- Tissue trauma: Damaged cells release potassium
how does Acidemia affect ICF/ECF concentrations/movement of potassium?
an increase in H+ in the vasculature leads to increase H+ in cells
ICF gets too positive
Na+/K+ pump gets inhibited
K+ concentration in ICF decreases; increase in ECF
net movement of K+ to ECF neutralizes pH in vascular system
modes of excretion for potassium?
urine, sweat, GI tract (vomiting, diarrhea)
excretion in GI is in pathological states and can lose large amounts
how does the filtered load of potassium differ from sodium
Filtered load of sodium is 30-40X that of potassium
neccessity of reabsorbtion difference between potassium and sodium
Tubules have to reabsorb almost all filtered sodium; not true for potassium
can sodium and potassium be reaborbed and secreted?
Sodium is only reabsorbed; potassium is both reabsorbed and secreted – regulation is based on secretion
where in the nephron is K+ reabsorbed?
Almost all of filtered K+ is reabsorbed in the proximal tubule and loop of Henle
where in the nephron does K+ regulation occur?
Regulation is distal to LOH
kidney capacity for secretion of potassium
If the body needs to get rid of potassium it has secrete a large capacity of potassium such that it can even exceed a fractional excretion of over 100%
how to calculate total filtered load of potassium?
concentration of extracellular potassium x GFR
[K+]e x GFR
reabsorbtion vs. secretion along the nephron
proximal tubule
thick ascending limb
DCT cells, principal cells, connecting tubule, cortical collecting duct
proximal tubule: 65% reabsorbtion at any potassium level
thick ascending limb: 25% reabsorbtion at any potassium level
DCT cells, principal cells, connecting tubule, cortical collecting duct: little secretion in low potassium; 20-150% secretion in high potassium
what percentage of potassium ends up in urine?
20-150% in normal to high potassium levels
as low as 2% in low potassium levels
reabsorbtion mechamism of potassium in proximal tubule
high concentration of potassium in proximal tubule allows K+ to move down conc gradient via interstitial space
how is potassium reaborbed in the loop of henle?
Na/K/2Cl transporter on apical membrane
K+/Cl- transporter on basolateral membrane
the two main potassium channels in the principal cells and when they are activated
ROMK channels (renal outer medulla K+)
- Sequestered in intracellular vesicles until activated by increased concentration of potassium
- First channel to start secreting potassium
- Limited capacity – can get saturated at increasing potassium levels
BK channels
- Closed until activated
- Second channel to secrete potassium when ROMK channel is maximally secreting potassium
- Large capacity
how does sodium reabsorption from the lumen to the principal cells affect potassium?
Increase Na+ in the distal tubule increases secretion of K+
Na+ entry from the lumen depolarizes apical membrane creating a negative charge
K+ moves down both its concentration and electrical gradient from the principal cells to the lumen
factors that up-regulated and down-regulate potassium secretions
Up-regulate
- high potassium diet
- high Na delivery to principal cells
- aldosterone
- high plasma potassium
Down-Regulate
- angiotensin II
- low potassium diet
mechanism of Aldosterone effect on potassium in kidney
increases activity of sodium-potassium pump; K+ moves from interstitium to principal cells
triggers nucleus to make ENAC channels to go to apical membrane; allows Na+ to flow from lumen to principal cells
release of ROMK channels that go to apical membrane; K+ flows from principal cells to lumen
Angiotension II effect and mechanism in kidney potassium
Angiotensin II binds to basolateral membrane receptors; leads to cell signaling cascade that brings ROMK channels back into principal cells
term for low plasma potassium concentration
hypokalemia
term for elevated plasma potassium concentration
hyperkalemia
measuring potassium levels in ICF vs. ECF
- cannot measure intracellular potassium levels (ICF), but also not really clinically relevant
- plasma levels can be measured but does not reflect total body potassium
causes of hypokalemia
- Decreased intake (rare)
- Increased movement into cells
- Increased epinephrine, increased insulin, alkalemia
- Increased GI loses
- Increased urinary loses
- increased sodium in distal tubule
- increased mineralocorticoid activity
factors that can increase sodium delivery to distal tubules that increase risk of hypokalemia
diuretics
salt wasting nephropathies
factors that can increase mineralocorticoid activity
too much aldosterone from adrenal adenoma
licorice intoxication decreasing the capacity of kidney to decrease cortisol affect on the mineralocorticoid receptor (normally would be broken down and not affecting receptor)
level of serum potassium considered hypokalemic
less than 2.5-3.0
symptoms of hypokalemia
- Muscle cramps/weakness including GI and respiratory muscles
- Cardiac arrhythmias/ECG changes
cardiac affects of hypokalemia
PAC, PVC, sinus bradycardia, AV block, Vtach, Vfib
ECG affects of hypokalemia
- ST depression
- decrease T wave
- prominence of U wave
treatment of hypokalemia
- mainstay is K+ replacement (oral or IV)
- can often identify the cause of hypokalemia and then address the cause
- remove diuretic if diuretic; beta blocker if increased adrenergic activity
what is the limit of how much sodium a patient should eat in a day?
less than 2 grams (2,000 mg)
how does high bp in renal arteries lead to increased sodium excretion?
Higher pressure in the medulla = Higher interstitial pressure
leads to changes in proximal tubule – decreased Na+-H+ transporter
more sodium stays in urine; gets excreted
kindey response in exercise (high blood pressure, low sodium and water)
sodium and water are conserved despite high blood pressure
low volume detected
priority is to keep volume up instead of decrease the blood pressure
how does blood pressure change from head to feet?
blood pressure is highest by our feet and lowest at our head; this is due to gravity
what happens to blood pressure in patient that has been on long-term bed rest?
Shift of blood from lower legs to central areas with distention of head and neck veins
Central pooling increases renal system to increase fluid loss – Cardiopulmonary mechanoreceptors decrease sympathetic drive
ECF volume depletes over few days; BP okay when supine but problematic when patient tries to stand
reversal can take days to weeks
giving label to blood pressure value in a patient
BP change if patient’s back in unsupported
higher diastolic pressure
BP change in patient that is supine
higher systolic pressure
