Symptom To Diagnosis - Hyponatremia/Hypernatremia Flashcards
1
Q
Hyponatremia is defined as serum sodium concentration
A
<130.
2
Q
1st step in evaluating the hyponatremic patient is to?
A
Review the history and evaluate the lab results for a few diagnostic fingerprints that may be present.
3
Q
Diagnostic fingerprints for hyponatremia:
A
- History of thiazides ingestion.
- Hyperkalemia –> primary adrenal insufficiency.
- Urine osmolarity = 100 –> Psychogenic polydipsia.
- Marked hyperglycemia –> Hyperglycemia-induced hyponatremia.
4
Q
For most patients the few diagnostic fingerprints will NOT be diagnostic. What is the key pivotal point in the DDX of hyponatremia?
A
To determine the patient’s volume status and identify who is clinically hypervolemic, euvolemic, hypovolemic.
5
Q
DDX of hyponatremia –> Hypervolemia:
A
- HF.
- Cirrhosis.
- Nephrotic syndrome.
- Renal failure (GFR<5).
6
Q
DDX of hyponatremia - Euvolemia:
A
- SIADH.
- Hypothyroidism.
- Psychogenic polydipsia.
- Secondary adrenal insufficiency.
- Exercise-associated hyponatremia.
7
Q
Etiology of SIADH:
A
- Cancers (lung, pancreas).
- CNS disease (cerebrovascular accident, trauma, infection, hemorrhage, mass).
- Pulmonary diseases (infections, respiratory failure).
- Drugs.
8
Q
Drugs that cause SIADH:
A
- Thiazides.
- ADH analogues.
- Chlorpropamide (6-7%).
- Carbamazepine.
- Antidepressants (TCAs, SSRIs,) + antipsychotics.
- NSAIDs.
- Ecstasy (MDMA).
- Others (cyclophosphamide, vincristine, nicotine, opioids, clofibrate).
9
Q
DDX of hyponatremia - Hypovolemia:
A
- Salt and water loss with free water replacement.
- Primary adrenal insufficiency.
- Renal disease.
10
Q
Conditions in which we have salt and water loss with free water replacement:
A
- Severe diarrhea with free water ingestion.
- Large burns with free water ingestion.
- 3rd-spacing with free water replacement.
11
Q
Hyponatremia develops when patients do not excrete their daily ingested excess (or free) water. Free water excretion requires 3 distinct mechanisms:
A
- Glomerular filtration.
- Separation of water from solute so that free water can be excreted.
- Excretion of free water –> Requires low or absent levels of ADH.
12
Q
Manifestations of hyponatremia depend on?
A
Its severity and rapidity of development.
13
Q
Patients with serum Na levels >130?
A
Asymptomatic.
14
Q
Patients with Na 125-130?
A
- Nausea/vomiting.
2. Abdominal symptoms.
15
Q
Patients with <125?
A
- Headache.
- Agitation.
- Confusion.
16
Q
Patients with <120?
A
Seizures and coma.
17
Q
Distinguishing euvolemic from hypovolemic patients is a bit difficult in the evaluation of hyponatremia. The 3 most accurate biochemic parameters are:
A
- Spot urine sodium.
- Fractional excretion of Na (FENa).
- Fractional excretion of urea (FEUrea)
18
Q
Spot urine sodium - Hypovolemic patients have increased or decreased urine Na concentration?
A
Decreased - They avidly reabsorb Na.
18.4mEq/L, compared with 72mEq/L in euvolemic patients.
19
Q
Spot urine sodium - False(-) results (elevated urine sodium in hypovolemic patients) may be seen in hypovolemia 2o to?
A
- Primary adrenal insufficiency in which the hypoaldosteronism directly leads to sodium wasting.
- Vomiting with accompanying metabolic alkalosis.
20
Q
Why vomiting causes urine Na excretion?
A
The metabolic alkalosis in vomiting causes an obligatory urinary HCO3 loss, which is accompanied by sodium.
Urine Cl may be low in such cases.
21
Q
Spot urine Na - False(+) results (low urine sodium in euvolemic patients) may be seen in certain euvolemic patients:
A
- Psychogenic polydipsia –> Euvolemic, but usually have low urine Na concentration due to dilution of the excreted sodium in vast quantities of water.
- Some patients with SIADH ingest little Na causing decreased urinary Na output.
22
Q
Is FENa sensitive for hypovolemia?
A
Exceptionally sensitive. (Sens 100%).
FENa>0.5% rules OUT hypovolemia except in patients taking diuretics.
23
Q
Is FENa specific for hypovolemia?
A
Spec is imperfect. Certain hypovolemic patients may have low FENa. (SIADH with low Na intake + Psychogenic polydipsia).
24
Q
Fractional excretion of urea - Is sensitive/specific for hypovolemia?
A
2 studies suggest a combination of both low FENa (<55%) was HIGHLY sensitive and specific for hypovolemia.
25
In what hypovolemic patients is FEurea usually low and may be more useful than FENa in such patients?
In patients taking diuretics.
26
Bottom line about FENa and FEurea?
A high FENa rules OUT hypovolemia (except patients taking diuretics) and a low FENa combined with a low FEurea rules in hypovolemia.
27
Hyponatremia in cirrhosis?
Hypervolemic hyponatremia.
3% --> Child-Pugh A.
16% --> Child-Pugh B.
31% --> Child-Pugh C.
28
Hyponatremia and adverse effects in cirrhosis?
Higher freqeuncies of:
1. Hepatorenal syndrome.
2. Hepatic encephalopathy.
3. SBP.
4. Death.
29
Is there a clear precipitant in hyponatremia of cirrhosis?
NO.
30
Among patients with cirrhosis and ascites, ...% have sodium <130mEq/L.
22%.
31
Pathogenesis of hyponatremia in cirrhosis:
1. Hypoalbuminemia + Splanchnic dilatation (possibly due to elevated NO) --> UP ADH + DOWN GFR + Increased proximal reabsorption of solute causing decr. solute delivery to loop of henle.
2. Renal arteriolar vasoconstriction --> DOWN GFR + UP Na reabsorption.
3. NSAIDs may worsen edema by reducing GFR and worsen hyponatremia. NSAIDs also lower PGE2, which normally antagonizes ADH.
32
Hyponatremia and hepatic encephalopathy?
Hyponatremia may worsen hepatic encephalopathy.
33
2 physical exam findings common in cirrhotic patients WITH hyponatremia?
1. Ascites present in 100%.
| 2. Peripheral edema seen in 59%.
34
Patient with HF and hyponatremia:
Has marked increases in total body sodium retention and content.
35
Mechanism of impaired free water clearance in patients with HF and hyponatremia?
1. Largely due to elevated ADH levels - The fall in CO triggers carotid baroreceptors --> UP ADH.
2. Decreased GFR due to renal hypoperfusion --> Increase in proximal Na reabsorption also impair free water excretion.
36
In which patients with HF is hyponatremia observed?
In patients with severe hyponatremia - Associated with an increased risk of death.
37
Which particular class of diuretics can worsen the hyponatremia?
Thiazides.
38
Nephrotic syndrome and hyponatremia:
Patients with nephrotic syndrome are total body sodium overloaded.
The effective intravascular volume may be decreased or increased.
39
Hyponatremia in nephrotic syndrome - Patients with hypoalbuminemia:
Decr. Oncotic pressure --> Both edema + ineffective circulating volume --> Elevated ADH --> Reduces free water clearance --> Hyponatremia.
40
Hyponatremia in nephrotic syndrome - Patients with renal insufficiency:
Impaired Na and free water clearance --> Hypervolemic hyponatremia.
41
Hyponatremia in nephrotic syndrome --> Pseudohyponatremia:
Pseudohyponatremia secondary to marked hypertriglyceridemia.
42
Complication in hyponatremia treatment - Central pontine myelinolysis:
1. Typically, chronic hyponatremia that is rapidly corrected --> 2-6 days later spastic Quadriparesis and pseudobulbar palsy. Death may occur.
2. Rapid hyponatremia correction means --> >12mEq/L/d or >0.5mEq/L/h.
3. Pons is most commonly affected but other areas of white matter may be affected.
4. Premenopausal women appear to be at substantially higher risk for this complication than men.
43
SIADH - Textbook presentation:
Patients are often (but not always) elderly, with a chief complaint of confusion or weakness.
Alternatively, mild hyponatremia may be discovered incidentally on serum chemistries.
44
MCC of hyponatremia:
SIADH
45
Cancer as a cause of SIADH:
15% of SIADH:
1. Small cell lung cancer MC.
2. Pancreas.
3. Lymphoma/leukemia.
4. Endometrial cancer.
5. Other.
46
Neurologic disease as a cause of SIADH:
1. Meningitis.
2. Tumors.
3. Trauma.
4. CVA.
47
Intrathoracic disease as a cause of SIADH:
1. Pneumonia.
2. TB.
3. HIV.
48
AIDS and hyponatremia:
1. SIADH may be secondary to PCP, CNS infections, or Cancer.
| 2. Hyponatremia may also be due to HIV-related adrenal insufficiency or diarrhea (with free water ingestion).
49
Hypothyroidism as a cause of hyponatremia:
1. 10% of patients - Rarely symptomatic.
2. In part secondary to ADH release.
3. Elevated ADH 2o to decr. Cardiac output.
50
Standard criteria of SIADH:
1. Effective plasma osmolarity 40mEq/L.
3. FENa is usually >1%.
4. Urine osmolality not maximally dilute due to active ADH (urine osmolality >100mOsm/L, usually >300mOsm/L).
5. Patients clinically euvolemic.
51
...-... of patients have low urine sodium and low FENa due to low sodium intake.
13-42%.
52
All patients with SIADH have:
Elevated FEurea >55%.
53
Diuretic-induced hyponatremia - Textbook presentation:
MC clinical situation is a small elderly woman taking a thiazide diuretic for HTN.
Patients may be asymptomatic or complain of weakness, lethargy or occasionally confusion due to hyponatremia.
54
Diuretic-induced hyponatremia is a common cause of hyponatremia?
One of the MCCs of hyponatremia.
55
Diuretic-induced hyponatremia - Clinical dehydration is evident in only ...% of patients.
24%.
56
Diuretic-induced hyponatremia - Symptoms:
```
49% --> Lethargy.
47% --> Dizziness.
35% --> Vomiting.
17% --> Confusion.
0.9% --> Seizures.
```
57
Diuretic-induced hyponatremia - FEurea:
Usually LOW due to true volume depletion.
58
Several features help distinguish thiazide-induced hypovolemia and hyponatremia from thiazide-induced SIADH:
Features that suggest a thiazide-induced SIADH:
1. Rapid development of hyponatremia.
2. Clinical Euvolemia.
3. High FENa + High FEurea.
4. Serum uric acid <4mg/dL.
59
Textbook presentation of adrenal insufficiency:
1. May have chronic symptoms of fatigue, weight loss, nausea/vomiting, orthostasis, abdominal pain.
2. May have acute symptoms, such as a clinical constellation that suggests septic shock (hypotension and fever).
3. Adrenal insufficiency may also cause hypoglycemia.
4. Both primary and secondary adrenal insufficiency may cause hyponatremia.
60
Cortisol and ADH?
Cortisol normally SUPPRESSES ADH release.
| Decr. cortisol causes increased ADH levels and hyponatremia.
61
Etiology of primary adrenal insufficiency:
1. Autoimmune adrenalitis (80-90%).
2. TB in developing nations.
3. HIV infection --> Up to 20% of patients with HIV have adrenal insufficiency.
62
Less common etiologies of primary adrenal insufficiency:
1. Fungal or CMV infections.
2. Bilateral adrenal hemorrhage (seen in septic shock, post op patients, in patients taking anticoagulants).
3. Infiltration (cancer).
4. Inherited disorders and certain drugs (ketoconazole, rifampin, phenytoin, and others).
63
Difference between primary and secondary adrenal insufficiency?
Secondary results in ISOLATED cortisol insufficiency --> Which in turn causes elevated ADH levels and hyponatremia.
64
Main etiology of secondary adrenal insufficiency:
1. Iatrogenic (steroids).
2. Sepsis.
3. Pituitary Tumors (30% of patients with a pituitary macroadenoma exhibit adrenal insufficiency).
65
Less common etiologies of secondary adrenal insufficiency:
1. Pituitary infarction.
2. Irradiation.
3. Autoimmune hypophysitis.
4. Traumatic brain injury.
5. HIV.
6. Sarco.
7. Hemorrhage.
8. Hemochromatosis.
9. Empty sella syndrome.
66
...% of patients with secondary adrenal insufficiency had superimposed infection when presenting with hyponatremia.
43%.
67
Adrenal crisis: ...% per year.
3%.
| Often secondary to insufficient increases in glucocorticoid during times of stress.
68
Acute adrenal insufficiency presents similarly to ...?
```
Septic shock:
1. Hypotension.
2. Abdominal pain.
3. Vomiting.
4. Fever.
Rare in secondary adrenal insufficiency.
```
69
What is important to keep in mind about the symptoms of chronic adrenal insufficiency?
The frequency of presenting symptoms may be overestimated in the literature dominated by the very old case series that discovered advanced disease.
70
Hypotension in chronic adrenal insufficiency:
90% - due to concomitant aldosterone deficiency.
71
...% of patients with chronic adrenal insufficiency develop hyperpigmentation:
18%.
72
Other findings in chronic adrenal insufficiency:
```
100% --> Weakness, tiredness, fatigue.
100% --> Weight loss, anorexia.
86% --> Nausea.
75% --> Vomiting.
16% --> Dizziness.
5-50% --> Psychiatric manifestations (memory impairment, delirium, depression, psychosis).
10-20% --> Vitiligo.
16% --> Salt craving.
```
73
When is it appropriate to do adrenal imaging with CT scanning in the evaluation of adrenal insufficiency?
In patients with an abnormal cosytropin stimulation test.
74
Antibodies against ... are accurate in the diagnosis of autoimmune adrenalitis.
21-hydroxylase.
75
When to do a pituitary MRI in the evaluation of adrenal insufficiency?
In SECONDARY adrenal insufficiency.
76
Serum electrolytes are abnormal in many but not all patients with adrenal insufficiency:
88% --> Hyponatremia.
| 18-64% --> Hyperkalemia.
77
Urine electrolytes in hyponatremic patients with adrenal insufficiency:
1. Decr. Cortisol causes lack of suppression of ADH --> Incr. ADH.
2. Lab values similar to ADH.
3. Average urinary sodium: 110mmol/L.
4. Average urine osmolarity: 399mmol/L.
78
Eosinophilia has been reported in ...% of patients.
17%.
79
What hypovolemia must occur in order for ADH release to be stimulated independent of serum osmolarity?
SIGNIFICANT hypovolemia.
80
Typical URINE findings in hypovolemic hyponatremic patients:
1. Decreased urine sodium concentration 450.
4. Prerenal Azotemia Bun/Cr>20.
5. Elevated uric acid.
81
Symptoms of exercised induced hyponatremia?
Usually present during or within hours of completing an endurance event (marathon).
Symptoms range from weakness, nausea, coma, seizures, death.
82
Hyponatremia developed in ...-...% of endurance athletes completing marathons or ironman competitions.
13-29%.
83
Evidence-based diagnosis of psychogenic polydipsia:
1. Water restriction test can prove the diagnosis by demonstrating rapid resolution of hyponatremia.
2. Mean urine sodium concentration is 18mEq/L.
3. FENa >0.5% in 66%.
4. FEurea >55% in 100%!
5. Mean urine osmolarity 144 +/- mOsm/L vs 500mOsm/L in SIADH and 539mOsm/L in hypovolemic patients.
84
Ecstasy intoxication - Textbook presentation:
Patients are typically college students, attending clubs (raves), who may have delirium, agitation, seizures.
85
Hyponatremia in ecstasy?
Due to ADH release and subsequent SIADH-like syndrome.
86
Evidence-based diagnosis of ecstasy:
1. MDMA is excreted in the urine and can be detected by specific tests.
2. Numerous congeners of MDMA exist.
3. Urine studies may not detect various congeners and the diagnosis is often made clinically.
87
DDX of hypernatremia - 3 general categories:
1. Impaired water intake: urine osmolarity >700mOsm/L.
2. Osmotic diuresis with impaired water intake.
3. Rare etiologies.
88
Etiology of impaired water intake:
1. Neurologic disease (dementia, delirium, coma, stroke).
| 2. Water unavailable (desert conditions).
89
Etiology of osmotic diuresis with impaired water intake:
1. Hyperosmolar hyperglycemia.
| 2. Post obstructive diuresis.
90
Rare etiologies of hypernatremia:
1. DI (if associated with Decr. Water intake).
2. Hypothalamic lesions that cause Decr. Thirst.
3. Increased salt intake - salt water ingestion, hypertonic saline.
91
MCC of hypernatremia:
Inadequate water intake.
92
Hyponatremia develops when?
The body is unable to excrete free water.
