Pathophysiology: Water Disorders

Front 1

Discuss osmoles:
What different kinds are there?
What are the main cations, anions, and neutral osmoles?

Back 1

*Particles suspended in liquid diluent:

*In body fluids they range from large MW (immunoglobulins) to low MW (H+, ions).

*They are cations (Na+, K+, Ca++), anions (Cl-, HCO3-, proteins) or neutral (BUN, glucose).

Front 2

What is osmolality?

How do we express it?

Back 2

*Osmolality: Sum of all particles per volume of fluid compartment: cations (Na+, K+, Ca++, etc.), anions (Cl-, HCO3-, proteins), and neutral substances (BUN, glucose).

*Expressed as mOsm/kg water. Or mOsm/L.

Front 3

What 2 substances normally have the same concentrations intracellularly and extracellularly?

Back 3

*Glucose
*BUN

*They maintain permeability, and the IC and EC concentrations remain equal unless something goes wrong (like DM).

Front 4

What are the leading intra- (2) and extracellular (3) cations and anions? What are their concentrations?

Back 4

Front 5

Despite the fact they their osmoles' identities are different, the osmolality of the IC and EC spaces is equal. There is one exception to this. What is it?

Back 5

*Renal medulla. Medullary interstitial concentration is hypertonic (1300 mOsm) and the capillaries are much lower in osmolality. This allows us to reabsorb water.

Front 6

Clinically, how do we calculate the intracellular and extracellular osmolality?

Back 6

In ECF and ICF:
*Osmolality = [cations] + [anions] + [neutral particles]

*But since [cations] = [anions]...
*Osmolality = 2 [cations] + [neutral particles]

*In ECF, by far the most prevalent cation is Na+, so

*ECF osmolality = 2 [Na+] + [glucose] + [BUN]

Front 7

What's the normal osmolality of the ECF?

What single factor has the biggest impact on osmolality? Why?

What are other words for hypoosmolality and hyperosmolality?

Back 7

*In ECF:
-Osm = 2 (Na+) + BUN + glucose
-Osm = 2 (140 mEq/L) + BUN/2.8 + glucose/18
-Osm = 285 mOsm/kg

*In the ECF, Na+ is overwhelmingly the primary contributor to osmolality, and hyponatremia (Na < 130 mEq/L) is generally synonomous with hypoosmolality.

*Hypernatremia (Na > 145 mEq/L) is generally synonymous with hyperosmolality, but elevations in BUN (renal failure) and glucose CAN CAUSE hyperosmolality.

Front 8

What exogenous substances can result in hyperosmolality? 2

Back 8

*Antifreeze.
*Etoh.

*These substances have a low molecular weight, which enables them to increase the osmolality in the ECF. Presents with confusion and a metabolic acidosis. Levels of Na, Glucose, etc. will remain NORMAL.

Front 9

How do changes in osmolality or [Na+] occur?

Back 9

*Osmolar changes occur with changes in body
water, NOT with changes in total body solute amount.

Front 10

If you eat a big old bag of Cheetos, what will happen to the [Na] in the ECF?

Back 10

*The extracellular space will become more hyperosmolar than the intracellular space, and water will shift into the extracellular space, increasing its size.

*Addition of sodium to the body expands the extracellular space; the [Na] does not change.

*Similarly, losing sodium from the body (as in vomiting) does not drop the Na+ level. Removal of sodium involves its removal from the extracellular space, causes extracellular hypoosmolality, and water shifts from the extracellular space, decreasing its size.

Front 11

What do increases and decreases in TBW do to osmolality and [Na] in the blood?

Back 11

*An increase in total body sodium will expand the extracellular fluid compartment and increase the extracellular volume.

*A decrease in total body sodium will decrease the extracellular volume.

*An increase in total body water will dilute all fluid compartments and decrease [osm] and [Na+].

*A decrease in total body water will increase [osm] and [Na+].

Front 12

What is the definition of hypoosmolality?

What is the primary problem here?

Back 12

[Osm] < 280 mOsm/kg water
[Na +] < 135 mEq/L

ALWAYS due to increased total body water (increased water ingestion OR decreased water excretion).

Front 13

What is the definition of hyperosmolality?

What is the primary problem here?

Back 13

[Osm] > 290 mOsm/kg water
[Na +] > 145 mEq/L

GENERALLY due to decreased body water, but can also be due to excess BUN, glucose or other osmoles (toxic substances, alcohol).

Front 14

What are the regulatory factors that usually keep osmolality tightly regulated?

What is a normal osmolality?

Back 14

*Osmolality is generally kept normal, between 280 and 290 mOsm/kg water, by two regulatory factors:

1) Thirst
2) ADH (antidiuretic hormone, vasopressin)

Front 15

What factors lead to increased water ingestion? 2

What factors lead to decreased water ingestion? 2

Back 15

Front 16

Discuss the role of ADH in regulating water excretion? How is ADH regulated?

What situations cause ADH to be released and suppressed?

Back 16

*ADH is the primary regulator of renal water excretion.

*When osmolal receptors in the hypothalamus sense hyperosmolality, ADH is released, stimulating adenylyl cyclase in the medullary collecting duct; aquaporins are inserted in the luminal membrane of the medullary collecting duct, allowing tubular reabsorption of water.

*When hypoosmolality is present, ADH release is suppressed.

*Baroreceptors in the hypothalamus contribute to ADH regulation as well. They can sense volume depletion and expansion.

Front 17

How sensitive is ADH regulation to changes in plasma osmolality?

Back 17

*Very. This is how our osmolality is so tightly regulated.

Front 18

What 4 avenues do we have to excrete water? How much do they excrete daily?

Back 18

*GI tract (only 100 ml water excreted/day).
*Respiratory tract and skin (700 ml water excreted). *Kidneys.

*The kidneys are typically the culprit in hyponatremia situations, though, based on the bulk of water they manage.

Front 19

What are the 2 causes of decreased water excretion from the kidneys?

Back 19

*Decreased filtration of water.
*Increased reabsorption of water (high ADH).

Front 20

What are the 4 main causes of hyponatremia?

Back 20

1) Massive ingestion of water.
2) Acute kidney injury (AKI) or chronic kidney disease (CKD).
3) Volume depletion or effective volume depletion (CHF, cirrhosis, nephrotic syndrome).
4) SIADH

Front 21

Why does massive H2O ingestion cause hyponatremia?

Back 21

*It overwhelms the ability of the kidney to dilute the urine.

*Increased water intake has two effects: decrease in osmolality and increase in total body volume. Both effects suppress ADH, and water reabsorption in the medullary collecting duct will decrease. Water excretion will increase, and the urine osmolality (concentration of osmolar particles in the urine) will decrease: the urine will become dilute.

*But there is a limit to the ability of the renal tubule to dilute the urine: all humans are obliged to excrete a solute load, usually about 600 mOsm/24 hours.

*When ADH is maximally suppressed, the urine osmolality can drop to about 50 mOsm/kg.

Front 22

How much water do you have to drink to give yourself hyponatremia?

Back 22

*You have to excrete 600mOsm/day in your urine.
*600 mOsm/day / 50 mOsm/L =12 liters per day!

*In order to overwhelm the kidney’s ability to dilute the urine, and produce hyponatremia, an adult would need to ingest more than 12 L of water/day.

*This is very difficult, because thirst drops off well before all this water ingestion, and it is usually associated with psychiatric diseases (psychogenic polydipsia).

*Could also be seen in people with low solute intake (people on tea/toast diet and beer drinking alcoholics).

Front 23

Why does AKI/CKD cause hyponatremia?

Back 23

*The kidney has decreased ability to filter water or hypotonic fluids.

Front 24

How does volume depletion/effective volume depletion cause hyponatremia?

Back 24

*Seen in CHF, cirrhosis, nephrotic syndrome.

*Increased thirst (leads to increased ingestion of water) and increased ADH (leads to renal water reabsorption).

Front 25

Describe marathoner's hyponatremia:

Back 25

*Increased sweating leads to water and sodium loss.

*When this loss is replaced by hypotonic fluids (water), hypoosmolality occurs.

*This is "effective volume depletion."

Front 26

Describe how SIADH causes hyponatremia:

What are some causes?

Back 26

*SIADH: ADH release unrelated to volume depletion or osmolar effects.

*Can be seen in pneumonia, lung tumors, meningitis, CNS bleeding, nausea, pain, anxiety, or sometimes post-surgically.

Front 27

There are many causes of hyponatremia. How can you tell what the cause is?

Back 27

1) BUN and creatinine levels; if high, this is consistent with kidney injury and decreased GFR, leading to decreased filtration of water.

2) Urine osmolality: if very low (< 100 mOsm/kg, or a urine specific gravity of < 1.003), this is consistent with suppression of ADH and psychogenic polydipsia.

3) If the urine osmolality and urine specific gravity is not low, that means that ADH is not suppressed. The ADH elevation can be due to “appropriate” release (real or effective volume depletion) or “inappropriate” release.

Front 28

In hypoosmolality in high ADH states, how can you distinguish between Volume Depletion and SIADH as the cause?

Back 28

*In real/effective volume depletion, there's increased serum BUN, uric acid, and Na reabsorption. Urine Na is low. This is "appropriate" ADH release.

*SIADH is the opposite.

Front 29

What's the ∆ b/t real and effective volume depletion?

Back 29

*Real: There's an actual total body Na deficit (GI loss or urinary loss.

*Effective: As in CHF. Too little perfusion to the kidneys--> body tries to hang onto Na, and therefore fluid--> edema.

Front 30

How is hyperosmolality defined?

What causes it?

Back 30

*[Osm] > 290 mOsm/kg water
*[Na +] > 145 mEq/L

*GENERALLY due to decreased body water, but can also be due to excess BUN, glucose or other LMW osmoles (toxic substances, alcohol).

Front 31

What are the causes of hypernatremia?

Back 31

*Decreased TBW, due to losses of water from skin, respiratory tract, GI tract, and kidneys. Water losses from the skin and GI tract are very common.

*Skin: up to 4–5 liters of water lost with exercise, perspiration, fever. Higher amounts lost with burns.

*GI tract: losses of water in vomiting and diarrhea.

Front 32

Discuss how common hypernatremia is:

Who gets hypernatremic?

Back 32

*Very uncommon, because hypernatremia and hyperosmolality are both potent stimuli for THIRST.

*Virtually everybody with hypernatremia will attempt to correct this with ingestion of hypotonic fluids.

*Therefore, individuals with hypernatremia, are by definition, unable to do this—impaired cognitive ability, physical inability to ingest water, torture victims, absence of water availability.

Front 33

Discuss massive Na ingestion as a cause of hypernatremia:

Back 33

*Has the potential to overwhelm the ability of ICF to dilute ECF osmolality. But you have to ALSO have an inability to ingest water.

*So, this occurs in debilitated, comatose, or helpless individuals, torture victims.

Front 34

Discuss extra-renal water losses as a cause of hypernatremia:

When would this occur?

Back 34

*Vomiting/diarrhea.
*Sweating/burns/losses of water from the skin and respiratory tract.

*Again, must ALSO have an inability to ingest water, like a vomiting person with dementia in a nursing home.

Front 35

Discuss renal water losses as a cause of hypernatremia:

When would this occur?

Back 35

1) Osmotic diuresis (hyperglycemia and glycosuria, alcohol ingestion).

2) Low ADH levels or inhibition of ADH effect (diabetes insipidus).

Front 36

Explain the 2 types of DI:

Back 36

1) Decreased production of ADH, due to CNS disease: trauma, brain surgery, hemorrhage affecting pituitary or hypothalamus: CENTRAL DI.

2) Decreased action of ADH on medullary collecting duct: effect of LITHIUM, demeclocycline, renal tubular-interstitial diseases, hereditary abnormalities (Hopewell descendants...FRENCH CANUCKS): NEPHROGENIC DI.

Front 37

Using lab values, how do you discern the cause of hypernatremia?

Back 37

*ADH is LOW in Central DI.
*Urine volume is LOW if water is being lost from the GI tract/skin.
*Urine osmolality is LOW in either kind of DI.
*Nephrogenic DI does NOT respond to ADH. This is the only way to distinguish b/t the two types of DI.

Front 38

A 73 year old man with history of congestive heart failure, admitted with dyspnea. On exam, BP is 180/80. He has JVD, rales, an S3 gallop, and ascites and 2+edema. BUN is 40 mg/dL, creatinine is 1.1 mg/dL, serum Na+ is 128 mEq/L, urine Na+ is 14 mEq/L, urine specific gravity is 1.029, urine osmolality 750 mOsm/L.

What is the total body sodium?
A. Increased
B. Decreased
C. Normal
D. It is impossible to determine, with the information that is given.

Back 38

A. Increased

*TOTAL BODY SODIUM IS DETERMINED BY THE HISTORY AND PHYSICAL EXAM*

Front 39

A 19 year old college student presents with nausea, vomiting, and feeling weak. On exam, BP 100/70 sitting, 70/50 standing, pulse 110 sitting, 140 standing, dry mucous membranes, clear lungs, no edema. Serum BUN 40 mg/dL, serum creatinine 1.1 mg/dL, Serum Na 128 mEq/L, Urine sodium 10 mEq/L, urine osmolality 680 mOsm/L, urine specific gravity 1.030.

What is the total body sodium?
-Increased
-Decreased
-Normal
-It is impossible to determine, with the information that is given.

Back 39

Decreased

*TOTAL BODY SODIUM IS DETERMINED BY THE HISTORY AND PHYSICAL EXAM*

Front 40

A 19 year old college student presents with nausea, vomiting, and feeling weak. On exam, BP 100/70 sitting, 70/50 standing, pulse 110 sitting, 140 standing, dry mucous membranes, clear lungs, no edema. Serum Na+ is 128 mEq/L. Serum BUN 40 mg/dL, serum creatinine 1.1 mg/dL, Urine sodium 10 mEq/L, urine osmolality 680 mOsm/L, urine specific gravity 1.030

What is the total body water, relative to the total body sodium?
Increased
Decreased
Normal
It is impossible to determine, with the information that is given.

Back 40

*Increased, because her serum is LOW. It's low because there is relatively more water!

*Key word here is RELATIVE. The serum Na is what you need to look at here.

Front 41

A 73 year old man with history of congestive heart failure, admitted with dyspnea. On exam, BP is 180/80. He has JVD, rales, an S3 gallop, and ascites and 2+ edema. Na+ is 128 mEq/L. BUN is 40 mg/dL, creatinine is 1.1 mg/dL, urine Na+ is 14 mEq/L, urine specific gravity is 1.029, urine osmolality 750 mOsm/L.

What is the total body water, relative to the total body sodium?
Increased
Decreased
Normal
It is impossible to determine, with the information that is given

Back 41

Increased. Because serum Na is low.

Front 42

18 year old man with cerebral palsy, lives in nursing home, admitted with fever and diarrhea. Has not been able to eat in 7 days. On exam, temp 104, BP 80/40 mmHg, heart rate 120/minute, dry mucous membranes, parched skin, tenting, lungs clear, no edema. Na+ 158 mEq/L, K+ 2.9 mEq/L, BUN 67 mg/dL, Cr 1.4 mg/dL, urine specific gravity 1.038, urine Na+ 10 mEq/L, urine osmolality 1100 mOsm/L.

What is his total body sodium?
Increased
Decreased
Normal
It is impossible to state, with the information given.

Back 42

Decreased

Front 43

18 year old man with cerebral palsy, lives in nursing home, admitted with fever and diarrhea. Has not been able to eat in 7 days. On exam, temp 104, BP 80/40 mmHg, heart rate 120/minute, dry mucous membranes, parched skin, tenting, lungs clear, no edema. Na+ 158 mEq/L, K+ 2.9 mEq/L, BUN 67 mg/dL, Cr 1.4 mg/dL, urine specific gravity 1.038, urine Na+ 10 mEq/L, urine osmolality 1100 mOsm/L.

What is his total body water, relative to total body sodium?
Increased
Decreased
Normal
It is impossible to state, with the information given.

Back 43

Decreased, because serum Na is high.

*These distinctions have clinical implications-- this dude needs water and, actually, Na! Because look at his total body Na. It's actually low!

Front 44

A 62 year old woman presents to her physician with generalized malaise, a cough, and a fever. Exam shows a BP of 132/84, HR 80/min, rales at both bases, no S3, and no edema. Labs show a Na+ of 129 mEq/L, Cl- 88 mEq/L, BUN 6 mg/dL, creatinine 0.5 mg/dL. Urine specific gravity is 1.020, urine osmolality is 779 mOsm/L, urine Na+ is 102 mEq/L.

Which of the following is likely to be true?

a) The total body sodium content is decreased
b) The ADH level must be increased
c) The patient must be taking in large quantities of water
d) Water reabsorption in the distal nephron must be decreased

Back 44

b) The ADH level must be increased.

*We know total body Na is high (or even normal).
*Large water intake is possible, but ADH would the be turned off and urine would be dilute.
*Urine osmolality is higher than serum osmolality, so you know ADH is present.