4. Essentials of Renal Physiology Pt. II Flashcards
1
Q
Amount of Filtered Na is Huge
• Kidney is filter and throws everything away an takes back what it needs ○ Throws out: 25,500 mmol of sodium ○ And vast majority reabsorbed ○ 200x what you're taking in in a normal diet ○ 10x amount what you have in ECF ○ Preserve this: excrete more or less the same amount you take in to keep your \_\_\_\_ controlled
A
ECF
2
Q
Reabsorption Very Tightly Regulated
* Reabsorption has to be very \_\_\_\_ regulated * \_\_\_\_% resorption
A
tightly
99.6
3
Q
What if Reabsorption Drops to 95%?
• Go to 24,225 mmol/day • Increase urine A loss 100 to 1200 ○ Half of total EC fluid volume in a day and die of \_\_\_\_ • Inconsistent of life • Cannot make the kidney do this
A
hypovolemia
4
Q
What if It Increases to 99.9%?
* Dropped urine excretion to 25 mmol/day and taking in the same amount * In course of a month > would double EC content of Na > \_\_\_\_ and \_\_\_\_ * Increased urine sodium reabsorption > also problems
A
hypertensive
edematous
5
Q
- One nephron
- Glomerulus with arteriole in > tuft of capillaries > out
- High enough pressure > squeezing fluid > captured by BC > proto-urine travels along long tube > vast majority of stuff that’s filtered gets resorbed, and poisons secreted > net result is excretion
- ____ is where majority of absorption occurs (65-70%)
- LH dives in the medulla of the kidney > ____% of absorption occurs here
- DCT resorbs another ____%
- Fine tuning > ____
- Diuretic class acts on each four segment separately
A
PCT
25
5-10
cortical collecting duct
6
Q
Proximal Tubule
• Source of energy for Na absorption > \_\_\_\_ ○ Ubiquitous ○ Major source of energy for maintain cell gradients in life ○ Only thing where you see \_\_\_\_ getting used throughout the whole process § Everything else are \_\_\_\_, but energy comes from this pump • Lumen is the urine side (apical side) • Interstitium is the blood side • Many transporters on the apical side ○ Co-transporters that take back stuff you need ○ Glucose gets into the urine, and needs to be taken back § If peeing out glucose > lots of calories lost § Major site where \_\_\_\_ is reclaimed • Major mechanism here is \_\_\_\_ absorption thorugh the Na-H+ exchanger ○ Na+ going in, and \_\_\_\_ going out § If all that happened is this > buildup an acidic pH > stop being able to have protons travel up cxn gradient > little \_\_\_\_ absorption ○ H+ combines with \_\_\_\_ in the urine > facilitated by CA > yields \_\_\_\_ > can percolate through cell membranes without facilitations with channels > split back into a H+ and \_\_\_\_ > H+ can be recycled into the urine, and bicarb can leave cell via \_\_\_\_ transporter § Two CA > lumenal one, and a cytosolic one
A
NaK ATPase ATP transporters glucose Na-bicarb H+ Na bicarb CO2 bicarb Na-bicarb
7
Q
Proximal Tubule
• Inhibited by \_\_\_\_ ○ Diuretic • So much Na absorption occurs here > but, not a powerful diuretic > impossible to completely \_\_\_\_ this process without killing these cells ○ Still lose some sodium § But not powerful: □ Don't completely inhibit it □ A lot of tubule left after this can \_\_\_\_ and catch up and reabsorb the sodium • Used rarely ○ Not that strong ○ Makes you lose a lot of bicarb § Clinical circumstances > do not want to do that • One diuretic taken by young healthy people > \_\_\_\_ ○ Purposely make bicarb low in high altitude
A
acetazolamide
inhibit
compensate
altitude sickness
8
Q
Thin Limbs of the Loop of Henle
- Thin descending limb has ____ NaCl permeability
- But high ____ permeability
- Medullary interstitium has high ____ concentration
- NaCl concentration in the lumen increases along its ____
- NaCl is ____ reabsorbed from the thin ascending limb due to its high concentration in the lumen
- This segment is water ____• Doesn’t take part in Na reabsorption
○ Low permeability
○ Permeable to water though
○ Pssive action
• Dives into hypertonic nephrone > bc of actions of thick ascending limb
○ Water gets sucked out of thin descending, but NaCl trapped into it
• Thin ascending limb
○ Small segemnt - permeable to Na
○ Little passive Na absorption bc of how conc the urine is
• Major action in thick ascending
A
low water NaCl length passively impermeable
9
Q
Thick Ascending Limb of the Loop of Henle
• Impermeable to \_\_\_\_, unlike thin descending • Reabsorbs \_\_\_\_ ○ Transporter that has Na, 2 Cl, and K that all have to go together § \_\_\_\_ transporter ○ In order to work, all the ions have to be in this proportion ○ Can resorb a lot of Na as long as Cl and K is present § A lot of Cl in urine at this point, but not a lot of K at this point; if tried to have this transporter work on its own > depelte K in urine; need to recycle K > second channel allows K to leak out □ \_\_\_\_ transporter □ \_\_\_\_ □ Creates a net \_\_\_\_ charge in urine here > allows for absorption of other things ® A lot of transporters that facilitate things being absorbed > live in cell-cell junctions; net positive charge by back leak of K, drives through cell positive ions (\_\_\_\_) > clinically important where if you inhibit K you waste more \_\_\_\_ in your urine!
A
water salt NKCC ROMK unidirectional positive Ca++ Ca++
10
Q
• NKCC2 inhibited by ____
○ Used a lot
○ Very potent
○ Severe heart failure > retain a lot of fluid in body
A
loop diuretics
11
Q
Distal Convoluted Tubule
• \_\_\_\_ cotransporter • \_\_\_\_r impermeable, but pumps Na out > further \_\_\_\_ the urine • Inhibited by \_\_\_\_ diuretics ○ Most frequently used in general; not just severely volume overloaded, but also an \_\_\_\_ ○ The \_\_\_\_ medicine you're put on should be this
A
NaCl water dilutes thiazide antihypertensive first
12
Q
Question:
• What if you wanted to reabsorb Na+, but the anion it was paired with was not reabsorbable?
• Needed to get Na back, want to be able to resorb if you need to ○ Causes a problem, if resorb the sodium > rapidly develop \_\_\_\_ charge that prvenets from resorbing \_\_\_\_ ions
A
negatieve
positive
13
Q
How to reabsorb Na without anion:
Cation Exchanger
• Build a \_\_\_\_ exchanger, trade it for another cation > \_\_\_\_ ○ Not a problem that the anion is not resorbable
A
cation
K+
14
Q
Cortical Collecting Duct: Principal Cells
• ENaC ○ Epithelial sodium channel ○ Allows Na to come in by \_\_\_\_> generates net \_\_\_\_ charge in urine; separate \_\_\_\_ channel that allows it to leak out ○ Actual energy comes from \_\_\_\_ on the basolateral side § Also the same for the prior 3 slides ○ Major method of Na reabsorption that occurs in the CCD • Inhibited by another class: \_\_\_\_ ○ \_\_\_\_-sparing diuretics • Water permeability varies with \_\_\_\_ (hormone)
A
itself negative K+ NaK ATPase amiloride K AVP
15
Q
Regulation of Renal Sodium Excretion
• Vary the input of Na in a subject, and measuring the output • Solid = represents how Na is taken in a day • Dotted = output of Na from the urine • Start with Na being low > and two lines are superimposed ○ Taking in little Na a day, and putting out a little a day • Put a ton of Na in the diet ○ 10 mequiv to 150 mequiv - ACUTELY ○ Transiently taking in more Na than peeing out § Retaining \_\_\_\_ § Weight \_\_\_\_ § Then subject detects > amount of Na in the urine goes up each day > until it reaches a point where amount of Na peed out is the same as the \_\_\_\_ taken in § Body does in \_\_\_\_ curve, not a stepwise way □ Measuring the sodium on a daily basis here, so looks like steps □ If every 5 mins > curve ○ Leave person at this Na intake > won't change > will pee out as much as take in § Difference: weight has \_\_\_\_; NOT THE SAME! • Acutely drop the amount of Na in the diet ○ 150 to 10 ○ Taking in less than peeing out ○ First day: pee out \_\_\_\_ than take in; weight \_\_\_\_ ○ Next day: continue to pee out more, but not as much; and weight doesn’t drop as much; until the amount you excrete \_\_\_\_ the amount you're taking in
A
fluid increases amount continuous increased more drops equals
16
Q
• Stretch sensors in multiple vascular structures:
○ Kidney
○ Small arterial heading in the glomerulus
○ Multiple vital organs on arterial side
○ Cardiac atria
• Send signals via multiple pathways
○ In kidney
§ Direct impact on ____ release and RAT
§ Tells it to hang onto ____+ (lose less)
○ In vascular
§ Feedback through ANS back to brain, integrated and sent out thorugh the symp NS and impacts ____ release (high symp tone); and vascular ton/stiffness
§ Tells it to hang onto ____ (lose less)
○ In cardiac atria
§ Release a signal that causes natriuesis > casues Na ____
§ Stretch these structures > ANP > inhibits ____ from the kidney
§ Decrease ____ > decreased ANP bc decrease stretch > removing a negative signal > causes increase absorption and decreased excretion of Na+
§ ANP
Normally tells to lose Na, but have less of it > so then resorb more ____
A
renin Na+ renin Na+ reabsorption Na absorption eff circulating volume Na
17
Q
• Stretch receptors
○ Body isn’t detecting fluid in the EC space > knows how stretched BV are > knows you have plenty of fluid and stretched > decreased ____ tone
If BV aren’t stretched and collapsed > not enough fluid in BV > upregulate ____ retention > increased sympathetic tone and twill lead to increased Na ____, and bc symp tone acts directly on kidney (hang onto salt), and innervating the JG apparatus tells it to synthesize ____
A
sympathetic
Na
absorption
renin
18
Q
- Inc Na intake > inc ____ > inc plasma volume > increase ____ > inc ANP > inc Na+ ____ > inc stretch of JG apparatus > inhibit ____ > inhibit reabsorpiton of ____ (lose more of it)
- All stretch receptors throughout the vascular > feedback to CNS > dec ____ > dec signaling for Na reabsorption > excrete more ____
A
ECF volume stretch receptors excretion RAT Na symp tone Na+
19
Q
Neurohormonal Regulation of Proximal Tubule Sodium Reabsorption • Antinatriuretic factors – \_\_\_\_ – \_\_\_\_ • Natriuretic factors – \_\_\_\_
* A lot of ANP > pee out more Na * If it drops > resorb more Na
A
angiotensin II
sympathetic nervous system
atrial natruretic peptide (ANP)
20
Q
Little Evidence of Neurohormonal Regulation in ____
Also Little Evidence of Neurohormonal Regulation in ____
A
loop of henle
distal convuluted tubule
21
Q
Also Little Evidence of Neurohormonal Regulation in Distal Convoluted Tubule
• Function of this segment does get ____ locally with high Na delivery
• That means that when patient is on a ____ (which blocks reabsorption proximal to this), the DCT’s function is ____
• Important clinically > block the LH (loop diuretics) > deliver a lot of Na+ to the DCT > amount fo Na+ reabsorption does \_\_\_\_ for it over time
A
up-regulated
loop diuretic
up-regulated
increase
22
Q
Cortical Collection Tubule VERY Tightly Regulated
• Cortical collecting duct
– ____
– Vasopressin and Angiotensin II stimulate ____ transport
– Prostaglandins reduce ____ activity and antagonize effects of ____
• Almost all the time you have to resorb 97% > important control is in last fine tuning • Major way: Na reabsorption regulated with aldosterone ○ Stimulated by AT II acting on the adrenal gland ○ And vasopressin can stimulate ○ Prostagladins > inhibited by \_\_\_\_ and NSAID § Reduce Na+ absorption at this site § NSAIDs if taken chronically > Na \_\_\_\_ ○ [???]
A
aldosterone epithelial sodium channel (ENaC) ENaC AVP aspirin retention
23
Q
Cellular Actions of Aldosterone
• Substance that is \_\_\_\_ ○ Only one today that is! • Aldo binds mineralocorticoid receptor is inside the cell > impacts \_\_\_\_ > increased ENAC channels \_\_\_\_ to apical membrane ○ Can block it! ○ Has an inhibitor > \_\_\_\_ § Commonly used § Helps out with disease states
A
cytosolic
transcription
delivered
spiranolactone
24
Q
Hypovolemia
• decreased TB Na+ and water with decreased ”effective” circulating blood volume
• Causes – Renal: > \_\_\_\_—by far the most common > Osmotic diuretic (hyperglycemia) > \_\_\_\_ – Extrarenal: > \_\_\_\_: Vomiting/GI losses, diarrhea > Skin > Lungs > “\_\_\_\_” accumulations: ascites, edema, pancreatitis
• Implies too low TB Na+ and decreased eff circulating BV • Decreased EC volume > too little \_\_\_\_ in the body > where did you lose it? ○ Pee hole § Common in diuretics □ Hospitalized § Somebody has high \_\_\_\_ > cannot resorb all of it > once so much is there, it traps water, Na and Cl in the urine > osmotic diuresys § Missing hormone that resorbs Na > high Na in the urine □ Most frequent: aldosterone ® \_\_\_\_ attack on adrenal gland ® Damage to kidney from diabetes > decreases \_\_\_\_ and ultimately adolsterone ○ Most common source of volume depletion is via GI § Diarrhea (GI) □ More frequent than hypovolemia due to losses from kidney § Skin barrier □ \_\_\_\_ victims lose a lot of salt and water through skin § Hard to lose fluid through your \_\_\_\_ § "Third-space" accumulations □ Space that's not usually there, but is filled with fluid ® Abdomen isn't usually filled, but ascites ◊ Liver disease ◊ Cancer that coated intestines can cause this ® Severe \_\_\_\_ ◊ Pancreas is so inlfamed it becomes a sponge full of fluid
A
diuretics hypoaldosteronism GI third-space Na sugar autoimmune RAT burn lungs pancreatitis
25
Hypovolemia
• Clinical findings:
– ____, hypotension
– decreased Tissue turgor
– Organ ____ and shock
• Treatment:
– ____ and volume
> Salt-rich foods and water
> IV ____l
> Blood replacement for substantial hemorrhage
– Address underlying ____
> Stop diuretics, treat hyperglycemia, etc
• ____ > frequent way to assess volume status
○ Change position from lying to standing
○ The act of standing creates huge changes for circulatory system > veins and heart are on same level as far as gravity; then part of body goes below heart
○ If hypovolemic, cannot handle this ____
§ Take vitals flat, and stand them up and look to see how they change
□ What happens to the HR and BP (HR up or BP down)
® Changes in ____ is more sensitive than BP, but we measure both
• Decreased skin turgor
○ Pince someone's forhead
○ Normal hydration > goes back to where it's before; but if dehydrated > stays ____
• Blood tests to injury to vital organs
○ Hyperperfused organs
• Changes in HR when standing are signs of hypovolemia
• Treatment
○ Na is the key to volume
○ Give NaCl with H2O; if resources limited > just give ____ rich foods and oral rehydration solutions
○ In hospital > IV > saline into the body
○ Hemorrhaging > you'll give them blood
```
orthostatic tachycardia
hypoperfusion
NaCl
NaCl
cause
vital signs
adjustment
HR
tented
salt
```
26
Hypervolemia
• increased TB Na+ and water
• May be increased or decreased “effective” circulating blood
volume
```
• Causes:
– Renal:
> ____ injury/chronic renal disease
> ____ syndrome decreased or increased
– Extrarenal:
> ____ decreased
> Hepatic cirrhosis with ascites decreased (probably)
```
• Too much fluid in the body
• Condition where TB ____ is increased, and amount of water in body is increased
• Eff circ. volume can be either up or down, but it's usually ____
○ If you have working kidneys > and retained 20 L of fluid > eff intravascular volume status > will be LOW
§ Kidneys can ____ out that fluid
§ Body thinks hypovolemic but wrong > heart failure
□ Not pumping normally > body thinks you got stabbed, and hangs onto Na and H2O in effort to correct this
□ Typically people who have working kidneys but have edema > decreased eff intravascular volume depletion
• Causes:
○ Kidneys that don't work (acute or chronic) > increase intravascular eff volume
○ Nephrotic syndrome
§ Losing ____ in urine > decreases ability to hang onto fluid in BV
○ Damage to other organ
§ Heart failure
§ Liver failure
□ Removes toxins from the blood
□ Impact BV; not removed toxins > they ____, and body feels like you don't have enough fluid
acute kidney
nephrotic
Na
down
pee
protein
dilate
27
Hypervolemia
```
• Clinical findings:
– ____
– Acscites
– ____
– Increased JVP
– ____
```
```
• Treatment depends on cause:
– Restrict ____ intake
– Diuretics
– ____
– Heart failure management; heart transplant
– ____ transplant
```
• Fluid buildup in abdomen > ascites
○ Classic in liver failure (scarred) > pressure builds up in the BV in digestive system > fluid oozes into peritoneum
• Most feared outcome > ____
○ Fluid in lungs
○ Heart is failing > retaining fluid > into lungs > cannot breathe well
• Jugular veins > increased and dilated
• ____ is not a great way to assess
○ As HF gets worse > the pump gets so bad > people have low BP
○ But not good by itself to assess ____ status
• Treatment:
○ Rid of excess fluid
§ ____
○ Kidneys aren't working:
§ ____
○ Replace the organ that's failing is ideal
peripheral edema
pulmonary edema
BP variable
NaCl
dialysis
liver
```
pulmonary edema
BP
volume
diuretics
dialysis
```
28
Summary of Renal Handling of Na:
Glomerulus: Na is freely filtered
– Daily Na filtered = GFR x Pna = 180L x 140 meq/L = 25,200meq
– Kidneys have an enormous capacity for Na excretion
Tubules: >____% of filtered Na is reabsorbed
– Daily Na intake ____ meq
– Changes in daily Na intake only require very ____ adjustments in the rate of Na reabsorption
– Increased renin/AngII/aldo activity leads to increased ____ reabsorption
• Renal handling
○ Filtration via glomerulus
§ GFR isn't the major thing that body regulates; what it regulates is ____ (in 4 segments)
□ Bottom table - everything we need to know
99
small
Na
reabsorption
29
Summary of Disorders of ECF Volume
• Hypovolemia reflect ____ depletion
– Treatment is directed at NaCl repletion
• Hypervolemia reflects ____ accumulation
– Treatment is directed at restricting NaCl
• In each case, the underlying ____ must also be addressed
• The concept of the effective circulating blood volume can be helpful in understanding the pathophysiology of generalized hypervolemia from extrarenal causes
NaCl
NaCl
cause
30
• Hypotonic - ____
○ Something should happen that increases ____ (arginine/vasopressin they're both interchangeable)
○ Thirst
§ Both impact water balance
hyperaquemic
| ADh
31
Regulation of Tonicity
```
• Plasma tonicity is detected by ____
○ In hypothalamus, that detects tonicicty, via ____ and swelling of certain cells
○ Two nuclei in hypo:
§ Control ADH
□ Impact kidney and water ____
§ Control thirst
□ Impact whether you drink ____
® Both things will impact plasma tonicity
```
osmostat
shrinkage
reabsorption
water
32
Typical Water Balance in a Sedentary Adult at Temperate Climate
• Water balance in an average day
• Water intake varies hugely based on ____
• Doesn't coincide with ____ intake
• Water drinking may impact migraine prevention
• Need ____cc of water a day in a temperate environment in order to keep up with losses
○ If you lose more water than normal, by no longer being in a temperate environment; losing a lot of water through skin/sweat/diarrhea, if develop fever water loss not through just sweat, but via the lungs
○ Air you exhale is different from the inhale; what you may not realize that it's diff in water content
§ Exhaled air: 100% humidity
§ Inhaled air: never does
§ Each breath you lose ____, if you have fever > you breathe ____
```
habit
calorie
400
water
faster
```
33
Mechanism of ADH Action:
* Major function of ADH: insert ____ into collecting duct luminal surface to increase water reabsorption
* Without ADH medullary collecting tubule lumen is water ____
* High ____ between the medullary lumen and interstitium is critical
* Water channels allows water to exit out the lumen down its ____ and be reabsorbed
* Membrane is normally water impermeable; but with water channels, now water can now go through
* LH makes concentrated area in kidney like a sponge > this tubule dives back through that > if you have a concentrated interstitial fluid on this side that could bea s ponge > no permeability; but combo of concentrated interstitium and the permeability > you'll resorb the water nad pull it back into your ____
```
water chennels
impermeable
osmotic gradient
cxn gradient
body
```
34
• Thick ascending loop
○ Pumping out a lot of ____
○ Complete sodium resopriton via the ____ and ____
• Medullary CT dives back through cxn interstitium
○ If ADH acting; suck water out of this ____ back into the interstitium
Na
DCT
CCT
tubule
35
* Not just NaCl in this medulla; including urea, but for our purposes we're focusing on the NaCl resorption
* Thick ascending > pumps salt > sponge for water
* Tube dives back through > ADH acting on it > allows water to pass through the tubule and get ____
reabsorbed
36
Role of ADH on Water Excretion:
• Difference bt ADH present and absent
• Absent:
○ Numbers are osmols of urine:
§ Starts at 285 (same as the osmolity of blood)
§ PCT > all resorption is ____ - osmolality doesn't change; everything resorbed is resorbed in proportion to water
§ TDL > Na cant leave but water can (solid is Na, white is water) > ____ urine > 1200 (maximum)
§ TAL > pumping ____out > emptying salt from the urine > creating a ____ medulla > ____ the urine bc the urine is having the salt removed
□ Continue to ____ the urine (pumping out the salt, and water cannot travel with it)
□ A LOT OF IT
□ 12L of urine a day
• Present:
○ Similar until the TAL
○ Resorb water in the CCT, pumping out salt, water is leaving with it; big change: water can leave in MCT > sponge built by AL of LH > allows water to be pulled out > ____ urine > same cxn as medulla > so much of water wouldve peed out has been pulled back > amount of urine made over day > drops to ____L (vs. 12L if it was present)
```
isoosmotic
dilute
NaCl
hypertonic
dilute
dilute
cxn
0.5
```
37
Regulation of tonicity:
• How to regulate tonicity
○ Serum osmol: 285
○ If it gets below this > ADH will drop to ____
○ If it gets above this range >
○ Within this range > fine regulation of urine osmolitity
§ ADH levels ____
§ Urine cxn rises until you get to the maximize
§ If make more hypoosmolar > ____ will continue to rise, but 1200 is the maximum
○ Thirst doesn't kick in until later > less sensitive; more hyperosmolar before you get thirsty
nothing
rise
ADH
38
Osmotic and Hemodynamic Control of ADH
* ADH is very sensitive to small changes in ____
* ____ is much more potent than Tonicity in stimulating ADH
• If ADH is regulated by osmolity, can also be regulated by severe intravascular volume depletion
• As plasma osmol rise > ADH goes up; but if blood volume drops > 10% BV depeltion > ____ goes up also; ADH will go up even if plasma osmol is low
○ Y axis of both: completely different
§ ADH is controlled within range; when run into trouble with volume depletion > ADH levels shoot up very ____
§ When crossover of ADH affeting BP; ADH high > affect the volume status stuff
§ Both graphs on different scales
tonicity
severe volume depletion
ADH
high
39
• If become desperate; volume depletion is sevre (>10%) > secrete ADH to defend ____ status
○ Retain water; not th egreatest, but better than nothing
intravascular volume
40
Osmole Intake and Urine Volume:
• Osmole intake of 600-1000 mosmoles per day
– Na+, K+ salts, and protein (converted to urea)
• Osmolar balance must be maintained
– Osm intake = Osm output
* If ADH level fixed, Osm intake will dictate ____
* If Uosm is fixed at 300 mosm/liter and Osm intake is 600 mosm, then Uvolume will be ____ (600/300)
• ADH and urine osmol fixed > impact based on osmoms you have to get rid of
• Balance maintained (pee out as much as you put in)
○ If ADH is fixed > osmolality is fixed > urine output will vary with osmolar intake
§ If urine osmom is fixed at 300mosm/liter and take in 600 mosm > make 2 L of urine
□ How much it'll take to get rid of the 600 mosm
□ Urine output impacted by osmosm you have to remove
urine volume
| 2 L
41
Urine Output as a Function of Osmole Load and Uosm
• Solute excretion impacts urine output
• Fixed at 300 > have 600 > excrete 2 L; 900 excrete 3L
• Bigger impact on volume: something changes urine cxn
○ Osoms is fixed, but change how much water is used to get rid of that
• 900 mosm > urine in max cxn > less than a ____
○ If turn off ADH > same amount of stuff in urine will be excreted in ____L
○ Certain amount you eat and get rid of the byproducts of eating that > chug a lot of water > you're going to excrete that in many L of water, if drink a little > excrete in small amount of water
L
| 12
42
```
Stimuli for Thirst:
• ____
• Habit
– For normal people, drinking “8 glasses of water daily” has no proven health benefit!!
• ____
• Social conventions
• ____
• Effective volume depletion
```
hypertonicity
dry mouth
true volume depletion
43
Disorders of Thirst:
• Psychogenic polydipsia or ____ water drinking
– Normal individuals can excrete 12-15 liters/day of free water
– ____ illness or drugs for its treatment can interfere with water excretion
• Decreased water intake
– ____ limiting access to fluids
– ____ from lesions of the thirst center
– ____ hypodipsia
• Older patients lose sense of thirst > dehydrated/hypertonic without realizing it
```
compulsive
psychiatric
physical disability
primary hypodipsia
geriatric
```
44
Polyuria:
• Arbitrarily defined as >____ liters of urine daily
– Do not confuse polyuria with urinary ____
• Water diuresis: inability to ____ urine
– Uosm____
• “Mixed” diuresis: – Uosm ____
• Polyuria > volume of urine; urinary frequency > going frequently but it may be ____ volumes everytime
```
3
frequency
concentrate
150
water
300
150-300
smaller
```
45
Water Balance: Summary
• Water balance is assessed by ____ (tonicity)
• Hyponatremia indicates hypotonicity (water excess) which will ____ ADH activity to enable renal excretion of excess water
• Hypernatremia indicates hypertonicity (water deficit) which will stimulate thirst to increase water intake and ____ ADH activity to help renal water conservation
• Volume depletion will stimulate ADH even in the presence of ____ (hypotonicity) as the body’s primary goal is to maintain ____
• If ADH is not osmotically regulated, then water balance is dictated by ____
```
plasma sodium concentration
suppress
increase
hyponatremia
adequate circulation (ECV)
osmolar balance
```
46
Water’s Effect On Extra-Cellular Volume Status
• Relatively ____ (2/3 goes into cells)
• Impossible to become volume overloaded with JUST ____ water:
– You would have severe reduction of sodium concentration first, which would cause lethal brain ____
• Similarly, it’s virtually impossible to become dangerously volume ____losing JUST losing water
• Will not edema if consuming a lot water > you will get brain swelling first and you'll die of that
○ IMPOSSIBLE
§ Not impossible but difficult for water loss/depletion
attenuated
adding
swelling
depleted
47
Hyponatremia Diagnostic Steps
* Hyponatremia usually means ____
* Confirm this > Check ____
```
• Hypotonicity
• Serum Osm
○ High
§ Caused by ____
□ A lot of sugar due to diabetes > traps water in ____ space > sucks water from inside of cells out > sodium ____ but total osmol is high
○ Normal
§ Can have ____
□ Certain proteins/lipids can mess up how the machine in the lab reads the sodium
® High levels of this
○ Low - everything else
```
hyposmolality
serum [Osm]
hyperglycemia
EC
low
pseudo-hyponatremia
48
Hypo-Osmolar Hyponatremia
• Two points:
A. To develop Hypoosmolar Hyponatremia patients must have
• ____ (IV or PO)
• [Osm] of Fluid ____ < [Osm] Fluid ____
B. Interpretation of Urine Labs
• No such thing as “____”
• Decide ____ of time what kidney should be doing, then look at ____
• Fluid intake
○ Body cannot make net water (some via the Krebs cycle)
○ Will lose from body no matter, if not keeping hydration
• Urine labs
○ No such thing as a normal urine Na, osmol, etc.
○ Possibilities in urine is so great > normal becomes meaningless
```
fluid intake
In
Out
normal
ahead
urine labs
```
49
Question 1: Is the Kidney Doing the Right Thing?
* If Serum Osm low > ____ should be absent
* “Test” for ADH: ____
* If ADH absent, then Urine [Osm] < ____ mM
• When tonicity too low
• ADH should be suppressed
• And dilute urine
• ADH assay > not ____ enough; level of ADH body responds to that's below the lower limits of the test
○ Do not used clinically
○ But there is a ____ test
§ Urine osmolality > look at the urine, and see if urine is maximumally ____ > can get down to 50 osms/L; but cutoff is <100 mmol (mOSM/L)
```
ADH
urine osmolality
100
sensitive
functional
dilute
```
50
____ of Hyponatremic Patients Have Urine[Osm] < 100
• DDx of Urine[Osm] < 100mM is short:
– Psychogenic ____
– Beer Potomania (aka Tea + Toast, aka Low Osmolar Load hyponatremia)
– Reset ____ (if pt’s serum Osm is below their set-point)
– “____” Hyponatremia
• Pt with prior UOsm > 100, but ____ went away
• PP
○ Drinking so much that you're peeing out a lot of dilute urine
• LOLH
○ # of L urine is determined by the osms you take in
○ Low omsolar diet > limited in making 3 L of urine per day; basically peeing out water; but if you drink 5L you will retain and become ____
• Reset osmostat
○ Normal is 140
○ Drink a lot of water 139 > inhibit ADH and pee out water, and increase for the other case
○ Reset > to be at 120, will do same thing around that level (120)
§ And making a dilute urine, but the moment I get higher > ____ the urine again
• You fixed it hyponatremia
○ ONLY PAY ATTENTION TO THIS
○ Patient that used to have cxn urine, but the cause was ____ by treatment
§ Important bc the patients that now pee out dilute urine > very rapidly changing serum Na and ____ and getting in trouble from that
```
minority
polydipsia
osmostat
you fixed it
cause
```
hyponatremic
cxn
removed
brain size
51
Most Patients Have UOsm > 100
• ADH ____
• Next Question: Why is ADH Present? – Two possibilities:
1) ____ Intra-Vascular Volume Depletion 2) ADH “____” Switched “on”
• Most patients with hyponatremia have a ____ urine > have to bc the kidney can excrete a lot of water, and if doing what it should be doing > shouldn’t have water excess
○ Two possibilityes
§ Arrow of eff IV depletion
§ Or ADH inappropiately switched on
present
effective
inappropriately
cxn
52
How to Determine Cause of ADH Secretion?
• Evaluate Volume Status
• Hyper have ____
• For both cases, the arrow is activated (eff vol depletion); body thinks its volume deplete > depserately hangs onto ____ to maintain volume status
• No evidence of abonrmal volume status > arrow isn't turned on, and soemthing turned on about ADH
○ Inappropirate ADH release
§ ____
eff vol depletion
water
SIADH
53
REVIEW
• Check serum Osm
○ Will normally get ____
○ Check for ADH by looking at ____
§ How you check if ADH is present or not is via urine osm
§ <100 - no ADH present
§ Most significant > you fixed it; ADH swithcing off bc you removed cause for ADH to be secreted
○ If ADH is present > look at ____ > hyper/hypo likely have eff IV volume depletion
§ Hypo > volume depleted, and hyponatremic > give normal ____ > restor euvolemia (switch off the eff vol depletion arrow) > will start peeing out a dilute urine
low
urine osmol
volume status
saline
54
• Causes of hypervolemic
○ ____
○ Cirrhosis
○ ____
§ Disease lose ____ in urine and can't hang onto fluid in your blood
§ Not ____ ; these patients hang onto salt first; once disease gets bad then they hang onto water, so usually this is not a ____ for these patients
```
CHF
nephrosis
protein
subtle
clinical dilhemma
```
55
Distinguishing bt hypovolemic and euvolemic is much more ____
difficult
56
- hypervolemic
- hypovolemic
- euvolemic
- ____ can be associated with any of these
renal failure
57
Hypervolemic
____ Cirrhosis ____
```
Hypovolemic
____
Sweating (Marathon)
____
Cerebral Na Wasting
____ Def.
```
```
Euvolemic
____
Glucocort. Def.
____ (Myxedema)
Rest osmostat
```
• Hypovolemic usually depends on which ____ did you lose the fluid from
• Euvolemic (hyponatremia) > caused by syndrome of SI ADH
○ ____ disorders that cause this that's not tech SIADH, though the physio is similar
○ Reset osmostate > can make either ____ or dilute urine depending on which side of osmostate you're on
§ It's not reset to a low number
§ It's siimlar to SIADH
□ RO person will turn off ____ if serum osm gets low enough, SIADH will ____ turn off their ADH
```
CHF
nephrosis
GI losses
thiazides
aldosterone
SIADH
hypothyroidism
```
```
hole
hormonal
conc
ADH
never
```
58
Major Causes of SIADH
```
• Meds
– ____
– Carbamazepine
– ____ (methamphetamine)
• CNS Disease (trauma, infection, tumors, hemorrhage) • Pulmonary Disease (esp. ____, Small Cell CA)
• Carcinomas
• ____
• Stress (post-op, pain, nausea, ____ exercise)
• Idiopathic
```
* Bottom line is that there are several meds that cause SIADH
* Classic is ____ (an
```
SSRI's
ecstasy
pneumonia
AIDS/HIV
intense
```
SSRI's
59
Treatment of Hyponatremia
• Raise tonicity, but not too ____
fast
60
Feared Consequence of Over- Correction: Osmotic ____
```
• Signs/Symptoms:
– ____/Dysphagia
– Weakness/paresis
– ____
– ____/confusion/obtundation, ____
– Often ____
• Occurs ____ days after over-correction
• Incidence: ____
– Probably not that frequent
```
* aka if you shrink too fast
* most people don't get it but if you do see it it's scary
```
dysarthria
seizures
lethargy
coma
irreversible
2-6
unknown
```
61
```
Osmotic Demyelination • Risk factors
– Over-correction
- >____ mEq [Na] over 24
• >____ mEq [Na] per hour
– Females who have not had ____
– Alcoholism
– ____
– Liver disease
– ____
```
• **unclear what happened with formatting but the red box
should be on "Females who have not had menopause"**
• and he said ^ is the risk factor we should focus on
```
8
0.5
menopause
malnutrition
hypokalemia
```
62
• Everybody gets hypernatremic if you don’t give them ____
• Almost all in-hospital hypernatremia caused by... (drumroll please)
– Pt not getting enough water
• Management plan:
– Give them some ____ (IV or PO)
– If they are volume depleted, give some ____
– In severe hypernatremia, do not correct more than ____mEq/day
• Even people with SIADH will get hypernatremic if you lock
them in a room w/o water
◦ this is b/c EVERYONE loses water!
• Management:
◦ giving water by IV: ____
◦ giving water PO: drinking ____
• When correcting: don't do too rapidly b/c brain is shrunk like raisin and don't want to expand it too quickly
water
water
water
12
D5W
water
63
Diabetes Insipidus Work Up: Is kidney doing the right thing?
• If serum tonicity high > ADH should be ____
• Urine Osmolality should be at ____
• Urine [Osm] < ____ mM suggests DI
– NB: kidney dz impairs ____ ability
• Is kidney part of problem or solution?
• If tonicity too high, ADH should be present
◦ test w/urine osmolality (max is 1200)
◦ ^ should be at least 600
◦ so if urine osm is < 600, this suggests impaired ____ ability (could be diabetes insipidus, DI)
present
maximum
600
concentrating
concentrating
64
Central vs. Nephrogenic
```
• Central: pt is missing ____
• Nephrogenic: pt doesn’t ____ to it
• Test by giving dDAVP:
– If Urine [Osm] increases to > 600 > ____ DI
– If not > ____ DI
• Chronic Treatment:
– Central:
• ____
– Nephrogenic:
• d/c ____ meds
• ____ diuretic
```
• dDAVP = artificial ADH = modified AVP
• ____ is harder to treat
◦ mechanism for treating w/thiazide diuretic isn't certain
```
ADH
respond
central
nephrogenic
dDAVP
offending
thiazide
```
nephrogenic
