How much of TBW is ICF? ECF? What are the main electrolytes in each?
2/3 1/3 ECF - Na ICF - K
Measure of a solute concentration per unit volume of a solvent that takes into account all solute concentrations.
Measure of solute concentration per unit mass of solvent that is preferred unit of measurement bc it stays constant.
Measure of osmotic pressure gradient bw 2 solns. What is it influenced by?
Tonicity Solutes that can cross the semipermeable membrane
What is plasma osmolality? What is normal pOsm?
ratio of plasma solutes and water 275-295
How do you measure osmolar gap? What should normal gap be?
Measured pOsm - expected pOsm 5-10 mOsm
What are some substances or situations that can cause an elevated osmolar gap?
Ethylene glycol, methanol, isopropyl etoh, ethanol severe hyperlipidemia and severe elevations in free serum light chains aka myeloma
Plasma Osmolality ECF Osmolality and ICF Osmolality are the -- since cell membranes are freely permeable to --.
How do you calculate plasma tonicity? Does urea contribute to it?
2 x Na + glc/18 No bc it freely crosses the membrane
What is acute hyponatremia?
Drop in plasma tonicity due to ICF resulting in water movement into cells
What is acute hypernatremia?
Increase in plasma tonicity compared to ICF resulting in movement OUT of cells (dehydration)
What do we call the ability of plasma solutes to generate an osmotic force)?
How does our body respond to increase in osmolality aka Na or glc?
Osmoreceptors in HT release aDH
When is ADH release suppressed?
Euvolemia pt resulting in water excretion and max dilute urine water
What are some ways our body regulates ECF volume esp in the setting of a low ECF? High ECF?
ADH is non-osmotically released in massive amounts when BP lowers renal hypoperfusion of JGA leads to activation of RAAS carotid sinus stim and increased SNS lead to retention of Na drop in ANP High ECF - decrease in RAAS and increase in ANP to retain water and Na
What are normal Na levels? Normal serum osmolality? What is hyponatremia? hyper-?
135-145 275-295 Hypo <135 Hyper >145
What are the 2 things ADH is released in response to?
Increase osmolality via osmoreceptor and decreased volume aka baroreceptor
Name the ADH targets.
V1a, V1b, V2 receptors
What is the principal receptor located in the CD principal cells in hyponatremia?
V2 ADH stim V2 that leads to increased cAMP and expression of AQP2 receptor
JVP, skin turgor over forehead or sternum, edema, crackles and a hx of fluid loss and sx of vol overload would hint at what dx?
Can serum osmolality be high in hyponatremia? Low?
Both - high is hyponatremia with hypertonicity and low is hypotonicity Hypertonicity aka glc, mannitol, etc
What are some causes of SIADH?
CNS disorders or pulm tumors infxns/inflammatory disorders
What are some meds that cause SIADH?
SSRIs, antipsychotics, COX-2 inhibitors, opiates, and TCAs
What are some infections that can cause SIADH?
HIV and Rocky Mt SF
Nursing home pts with dementia, intubated pts, neglected infant, or pts with a lack of access to water would be like to present with which Na disorder?
A solute diuresis of greater than 1000 would suggest what Na disorder?
Thirst, anorexia, ataxia, confusion, hyperreflexia, coma and rupture or bridging veins and intracranial hemorrhage would be indicative of what?
Polyuria with dilute urine is a hallmark sign of --. But to make sure you need to exclude this dx of a sub acute --.
DI psychogenic polydipsia
-- insipidus is due to the insufficient release of ADH; it is usually caused by CNS tumors. -- is due to a normal ADH release but an impaired renal response; it is usually caused by lithium use or congenital.
What is the confirmatory test for DI? What do you do if positive?
Water deprivation test - pt admissted and water deprived and urine volume and osmolality measured hourly. Confirmatory for hypernatremia if urine osmolality is stable for 3 consecutive hrs despite rising plasma osmolality. Cofirm. Then give desmopressin and urine osmolality measured every 30 min. If it rises, central DI. If minimal change then nephrogenic
When do we use free water deficit?
How much water to replace clinically in hypernatremia
What does rapid correction of hyponatremia result in? hyper-?
osmotic demyelination syndrome aka locked in syndrome cerebral edema
Why does water move into the brain with osmotic demyelination syndrome aka central pontine myelinosis?
Fall in serum tonicity causes water movement into brain
When do symptoms of CPM occur?
demyelination sx occur 2-6 days after rapid correction that exceeds >15 meq/L/day
What are the 3 ways in which we control the IC K: EC K ratio?
Na K ATPase, Na K 2Cl cotransporter, and K channels, colonic ability to absorb and secrete K, and kidney handling of K
Where is 90% of filtered K reabsorbed?
PT and LOH
Where does most K secretion occur?
principal cells and CD
How do the ENaC channels establish the gradient that promotes K secretion?
Na enters via ENac to generate a negative lumen that drives passive K exit thru apical K channels. Renal K excretion is enhanced by increased tubular fluid Na.
In principal cells, the -- channel moves K into and Na out of cells to generate a Na gradient for ENac.
Na K ATPase
How is K mainly secreted?
apical "small conductance K" SK channels (that are ROMK channel subtype aka renal outer medullary K channels)
Which type of K channels are activated by Ca and also aid in K secretion?
apical BK (big potassium) channels
Hyperkalemia induces -- release by the adrenal glands.
Aldosterone increases expression of the -- in the CD.
Regardless of aldosterone, a high K diet will induce expression of the -- channel.
pRBC and rhabdomyolosis are 2 ways to produce --.
What are 2 types of metabolic shifts that can induce hyperkalemia?
Acidosis and insulin deficiency
Forearm contraction during blood draw, fist clenching, tourniquet use, thrombocytosis, leukocytosis, acute anxiety, and cooling of blood are all examples of things that can induce --.
Why is hyperkalemia a medical emergency?
Bc of its effect on cardiac tissue- it depolarizes cardiac myocytes and increases cardiac excitability. Ascending paralysis and decreased ability to acidify urine
How do you tx hyperkalemia?
IV calcium for CV effects, sinulin and glc to shift K to SKM/hepatocytes, B agonist to activate Na K ATPase to shift it into the cell, Na HCO3-, and to remove the K use diuretics, mineralocorticoids, cation-exchange resins, and dialysis
Severe mm weakness, rhabdomyolosis, ECG changes, renal abnormalities, and glc intolerance are all signs of --.
What 2 diseases arise from ENac mutations?
Liddle syndrome and Pseudohypoaldosteronism type 1
Which pathologic state arises from a GOF mutation with Enac that increases Na reabsorption with susbequent K secretion and presents with HT and hypokalemia?
Which disease presents as the opposite of Liddle syndrome aka Enac function decreased? How is it similar to Liddle syndrome?
Pseudohypoaldosteronism type 1 In both types pts have hypotension and hyper K but in pseudo they have high aldo as well
-- syndrome is an AR disease stemming from a defect in the -- in the distal tubule presenting with hypokalemia, -magesemia, and -CALCEMIA + metabolic alkalosis. Usually dx later in adolescence.
What channel does the AR disease Bartter syndrome have a defect in?
Na2KCl, ROMK or basolateral Cl channel in TALOH resulting in loss of NaCl uptake and hypokalemia, metabolic alkalosis, polyuria with possible increase in Ca excretion or decreased Mg
Hyperkalemic periodic paralysis is a familial disorder where pts develop hyperkalemia and present with -- in response to --.
Flaccid paralysis cold weather, exercise, or fasting
Hypokalemic periodic paralysis is a rare syndrome that is strongly associated with hypokalemia and strongly associated with -- with a strong predisposition for (M/F) and (ethnic group).
hyperthyroidism, M and Asian
Elevated PTH activates -- to the active form of vitamin D ultiamtely leading to decreased -- loss and increased -- loss.
1 alpha hydroxylase Ca, phosphate
-- syndrome is hypercalcemia with metabolic alkalosis and renal insufficiency from excessive intake of calcium carbonate antacids.
What granulomatous diseases cause hypercalcemia?
Sarcoidosis, TB, granulomatosis with polyangitis
What types of hyper vitaminoses cause hypercalcemia?
A and D
What should hypercalcemia workup begin with?
measurement of PTH
What is the range for normal serum calcium levels?
What 2 (physical) tests can you do to test for hypocalcemia?
Trousseau sign and Chvostek's sign
What is Trousseau's sign?
Sphyngomanometer inflated causing tetany of forearm mm
What is Chovstek's sign?
Tapping over facial nerve to produce facial mm twitching
Bisphophanates, calcitonin, cincalcet, citrate, foscarnet, phenytoin, and fluoride posioning are all drugs that can potentially cause --.
When does hypophosphatemia occurr?
phos <3.0 m/dl most commonly seen in chronic Etoh use, malnutrition, critical illness. Gets severe if less than 1.0 and sx are weakness, myalgia, HF, rhabdo, resp failure, seizures, and hemolysis
What diuretics cause hyophosphatemia?
Acetazolomide and metolazone
Hyperphosphatemia is classified as what? How do pts present?
>4.5 mg/dl and asx
What hormone regulates calcium and phosphorous? How is homeostasis achieved?
PTH via kidney, bone, and gut
What is primary HT?
Pts who develop HT wo any risk factors like age obesity diet smoking sex DM fam hx and stress
If you are tx a pt with resistant HTN, what MUST be included in a regimen with 3+ drugs?
If a pt has spontaneous hypokalemia or marked hypokalemia after initiation of a diuretic, they should be screened for --.
-- results from aldosterone secretion WITHOUT response to FB loop mechanism. What causes this?
Primary hyperaldosteronism - FB response arising from high BP/baroreceptor response doesn't work bc of continuous aldosterone production without need for renin pathway tumor producing aldosterone or adrenal hyperplasia
Why do you get hypokalemia in primary hyperaldosteronism?
Continued secretion of aldos - ongoing reabsorption of Na via Enac and ongoing secretion of K via ROMK --> hypokalemia
What are the 2 main clinical presentations of primary hyperaldosteronism?
hypokalemia and metabolic alkalosis
Why do you get metabolic alkalosis in primary hyperaldosteronism?
Hypokalemia results in K being pumped from inside cell to outside cell and in exchange Na and H are pumped into the cell. This stim H K ATPase to reabsorb K and in turn secrete H_ into the urine.
In primary hyperaldosteronism, Na reabsorption leads to hypernatremia and --, K secretion leads to hypokalemia, and secretion of -- in exchange of -- leads to metabolic alkalosis.
HT H, K, metabolic acidosis
What does the serum aldosterone/renin ratio have to be greater than to suggest hyperaldosteronism?
If the aldo/renin ratio is elevated, then perform a -- for confirmation.
In a normal pt, Na loading should -- aldosterone production. In a pt with PH, aldosterone does not suppress and 24 hr urine will have elevated -- level despite the Na load.
How do you treat PH?
Adrenalectomy or pharm blocking of aldosterone action like spironolactone/epelerenone
What is the triad of Liddle Syndrome
HT, hypokalemia, and metabolic alkalosis
Do pts with Liddle syndrome have an elevated aldo/renin ratio?
How do you tx Liddle syndrome?
Inhibit ENac via amiloride or triamterene - no high aldo levels so no use in using spironolactone
-- is a genetic disorder that has a simiala presentation as PH.
Apparent Mineralocorticoid Excess
What other scenario leads to similar presentation as AME?
Chronic licorice ingestion
How does AME present?
hypercalciuria, nephrocalcinosis, and renal failure
What do you find in the lab results of pts with AME?
low serum renin and low serum aldo
What is the basis of the genetic mutation in AME?
def in 11 beta OH steroid dehydrogenase impairs cortisol to cortisone conversion. elevated cortisol leads to cortisol binding to mineralocorticoid receptor --> clinically presents as PH
What other syndrome presents similarly to AME?
-- is a catecholamine secreting tumor that arises from chromaffin cells of the adrenal medulla.
What gene is associated with pheochromocytomas?
What is the (rather uncommon) classic triad of pheochromocytomas?
episodic headache, sweating, tachy
What are the 3 hormones that are overproduced in pheos?
epi, norepi, and dopa
What lab measurements would you expect in a pheochromocytoma?
Plasma-fractionated metanephrines and urinary 24 h metanephrine and catecholamines
How do you tx a pheochromo?
Resect the tumor, combined alpha and beta adrenergic bockade COMBO (never beta alone) - phenoxybenzamine
In what subset of pts is renovascular HT increased?
pts w acute increase in BP, severe, or refractory HT
Due to the -- produced by the stenosis of the renal vasculature, -- production is increased and this activates the RAAS pathway leading to --.
iscemia, renin, HT
What cholesterol problem is related to renovascular HT?
What disease (and subset of pts) should be on your diff dx list for renovascular HT?
Fibromuscular dysplasia in young female
What is the major complication gestational HT can lead to?
GO OVER SLIDE 20
What meds must you avoid in pregnant women to prevent fetal defects? What do you rx instead?
Avoid ACE-I/ARB methyldopa
Name some meds that cause HT.
OCPs, etoh, caffeine, NSAIDs
What is the endocrine function of the kidneys?
synthesis of EPO, renin, PGs, and 1-25 di OH vit D
What is the hallmark sign of kidney pathology?
Urine specific gravity, urine osmolality, urine sodium and fractional excretion of filtered Na are renal function tests that assess what?
In chronic renal failure, how do you assess GFR?
creatinine clearance and GFR
A symptom complex resulting from acute or chronic renal failure. Multi-system symptoms - acidosis, nausea, anemia, water & electrolyte imbalance, neuropsychological disorders
"Nitrogen in the blood" Refers to an increase in the non-protein nitrogen compounds (BUN, Creatinine, Uric acid).
Are increased serum BUN and creatinine helpful?
No bc they lack sensitivity and specificity - aren't significantly increased until there is a significant reduction in renal function.
For oliguria/anuria/renal parenchymal pathology, which indicator do you use?
How is urea metabolized in the kidneys and what is the reference range?
Filtered in the kidneys and partially reabsorbed in the PT. 7-22 mg/dl
How does GFR vary with BUN level?
Decreased GFR correlates to a higher serum BUN and an increased GFR correlates to a lower serum BUN
How does GFR vary with dietary protein?
Hi protein diet correlates to a higher serum BUN and a lower protein diet correlates to a lower serum BUN
What happens to BUN levels in the setting of increased aa degradation?
higher serum BUN
What happens to BUN levels in the setting of liver damage/dysfunctional urea cycle?
lower serum bun
Prerenal hypoperfusion (CH, shock, bleeding) lead to a -- GFR with -- proximal reabsorption of urea lead to an increased serum BUN
Acute tubular necrosis leads to a -- GFR without -- PT reabsorption of urea leads to an increased serum BUN.
Postrenal obstruction leads to a decreased GFR with back diffusion of urea with -- PT reabsorption of urea that leads to an increased serum BUN.
Chronic renal failure leads to a -- GFR which leads to an increased --.
decreased serum BUN
How does increased tissue catabolism in 3rd degree burns or a postoperative state lead to an increased BUN?
increased aa degradation
How does increased dietary protein lead to increased serum BUN?
increased aa degradation
How does dehydration without renal failure lead to an increased serum BUN?
decreased GFR with increased proximal reabsorption of urea
Increased plasma volume in the setting of SIADH or pregnancy leads to -- that results in a decreased serum BUN
How do hepatic alterations leads to a decreased serum BUN?