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Questions and Answers
Which action does ADH have on the blood vessels?
Which action does ADH have on the blood vessels?
ADH facilitates glycogenolysis in the liver.
ADH facilitates glycogenolysis in the liver.
True
What is the primary function of the counter-current multiplier in the nephron?
What is the primary function of the counter-current multiplier in the nephron?
To concentrate urine by reabsorbing water and solutes.
The ______ loop of Henle is responsible for water reabsorption in the counter-current exchange mechanism.
The ______ loop of Henle is responsible for water reabsorption in the counter-current exchange mechanism.
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Match the actions of ADH with their corresponding receptors:
Match the actions of ADH with their corresponding receptors:
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What is the classification of hyponatremia with a sodium level of 125 mg/dL?
What is the classification of hyponatremia with a sodium level of 125 mg/dL?
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Hypovolemic hyponatremia can lead to increased urine output.
Hypovolemic hyponatremia can lead to increased urine output.
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What causes the urine sodium level to be greater than 20 mEq/L in renal hyponatremia?
What causes the urine sodium level to be greater than 20 mEq/L in renal hyponatremia?
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In hypovolemic hyponatremia, the findings include decreased IVC diameter and __________.
In hypovolemic hyponatremia, the findings include decreased IVC diameter and __________.
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Match the following urine sodium findings with their corresponding cause:
Match the following urine sodium findings with their corresponding cause:
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What triggers the translocation of aquaporin-2 (AQP2) to the luminal membrane?
What triggers the translocation of aquaporin-2 (AQP2) to the luminal membrane?
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Aquaporin-1 (AQP1) is dependent on the presence of Antidiuretic Hormone (ADH) for its function.
Aquaporin-1 (AQP1) is dependent on the presence of Antidiuretic Hormone (ADH) for its function.
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What is the primary function of Aquaporin-2 (AQP2) in the kidney?
What is the primary function of Aquaporin-2 (AQP2) in the kidney?
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In the absence of ADH, the body is able to maintain water balance during __________ state.
In the absence of ADH, the body is able to maintain water balance during __________ state.
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Which serum sodium value range indicates mild true hyponatremia?
Which serum sodium value range indicates mild true hyponatremia?
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Match the following aquaporins with their specific roles:
Match the following aquaporins with their specific roles:
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Hypernatremia is commonly observed under normal physiological conditions.
Hypernatremia is commonly observed under normal physiological conditions.
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What are the two main stimuli for the release of Antidiuretic Hormone (ADH)?
What are the two main stimuli for the release of Antidiuretic Hormone (ADH)?
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ADH is produced in the supra-optic and ________ nuclei of the hypothalamus.
ADH is produced in the supra-optic and ________ nuclei of the hypothalamus.
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Match the serum sodium values with their corresponding severity features:
Match the serum sodium values with their corresponding severity features:
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What is the primary treatment for acute symptomatic hyponatremia?
What is the primary treatment for acute symptomatic hyponatremia?
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Rapid correction of acute hyponatremia carries a higher risk of osmotic demyelination than herniation.
Rapid correction of acute hyponatremia carries a higher risk of osmotic demyelination than herniation.
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What medication class is recommended for euvolemic hyponatremia?
What medication class is recommended for euvolemic hyponatremia?
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In severe cases of hyponatremia, the recommended administration of 3% saline may include _____ bottles of 100 ml over 24 hours.
In severe cases of hyponatremia, the recommended administration of 3% saline may include _____ bottles of 100 ml over 24 hours.
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Match the management strategies with their appropriate hyponatremia types:
Match the management strategies with their appropriate hyponatremia types:
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What is the primary cause of Primary Empty Sella Syndrome?
What is the primary cause of Primary Empty Sella Syndrome?
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Secondary Empty Sella Syndrome can be characterized by the presence of hypopituitarism features.
Secondary Empty Sella Syndrome can be characterized by the presence of hypopituitarism features.
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What testing method is used to evaluate ACTH deficiency?
What testing method is used to evaluate ACTH deficiency?
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The mechanism of Primary Empty Sella Syndrome involves a tear in the ______ mater, allowing CSF to enter the pituitary region.
The mechanism of Primary Empty Sella Syndrome involves a tear in the ______ mater, allowing CSF to enter the pituitary region.
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Match the following measurement methods with the hormones they evaluate:
Match the following measurement methods with the hormones they evaluate:
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What is the primary route of administration for hydrocortisone in cases of vomiting or low blood pressure?
What is the primary route of administration for hydrocortisone in cases of vomiting or low blood pressure?
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L-thyroxine is typically administered in dosages ranging from 50 to 200 mg per day.
L-thyroxine is typically administered in dosages ranging from 50 to 200 mg per day.
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What hormone is used for fertility when desired?
What hormone is used for fertility when desired?
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In adults, the daily subcutaneous dosage of growth hormone (GH) is ______ mg.
In adults, the daily subcutaneous dosage of growth hormone (GH) is ______ mg.
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Match the steroid with its equivalent dose:
Match the steroid with its equivalent dose:
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What is a characteristic criterion for SIADH?
What is a characteristic criterion for SIADH?
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Trauma is a possible cause of euvolemic hyponatremia.
Trauma is a possible cause of euvolemic hyponatremia.
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What type of cancer is associated with paraneoplastic syndrome in euvolemic hyponatremia?
What type of cancer is associated with paraneoplastic syndrome in euvolemic hyponatremia?
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In euvolemic hyponatremia due to SIADH, the urine Na+ level is typically greater than _____ mEq/L.
In euvolemic hyponatremia due to SIADH, the urine Na+ level is typically greater than _____ mEq/L.
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Match the following causes of euvolemic hyponatremia with their categories:
Match the following causes of euvolemic hyponatremia with their categories:
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What is the formula for calculating serum osmolality?
What is the formula for calculating serum osmolality?
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Ineffective osmoles can cross the cell membrane without changing osmolality.
Ineffective osmoles can cross the cell membrane without changing osmolality.
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What is the normal range for serum osmolality?
What is the normal range for serum osmolality?
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Which feature is NOT commonly associated with hypogonadism in acquired hypopituitarism?
Which feature is NOT commonly associated with hypogonadism in acquired hypopituitarism?
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In pseudohyponatremia, for every 100 mg/dL increase in blood glucose, the serum sodium level falls by __________.
In pseudohyponatremia, for every 100 mg/dL increase in blood glucose, the serum sodium level falls by __________.
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Match the following conditions with their corresponding osmolality and sodium status:
Match the following conditions with their corresponding osmolality and sodium status:
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Lymphocytic hypophysitis can affect both males and females as well as children.
Lymphocytic hypophysitis can affect both males and females as well as children.
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What is the primary imaging finding associated with Sheehan's syndrome?
What is the primary imaging finding associated with Sheehan's syndrome?
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Acquired hypopituitarism can lead to signs such as fatigue, hypoglycemia, and __________.
Acquired hypopituitarism can lead to signs such as fatigue, hypoglycemia, and __________.
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Match the following conditions to their associated features:
Match the following conditions to their associated features:
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Study Notes
ADH Actions on Different Receptors
- V1 & V2 receptors are found on blood vessels, liver, heart, and platelets.
- V1 receptors cause vasoconstriction, V2 receptors promote glycogenolysis in the liver, V1 receptors induce hypertrophy in the heart, and V1 receptors trigger platelet aggregation.
- V3 receptors are located in the anterior pituitary and promote ACTH release.
- V8 receptors are involved in the release of von Willebrand factor (VWF).
Counter-current Exchange
- Counter-current multiplier: Descending loop of Henle plays a vital role.
- Counter-current exchange: Water reabsorption increases osmolality four times, supported by the medullary interstitium.
- Medullary interstitial osmolality is maintained by urea, which is regulated by the vasa recta.
- ADH acts when the interstitial osmolality is maintained.
Hyponatremia Classification
- Mild: 130-134 mg/dL
- Moderate: 120-129 mg/dL
- Severe: 100-119 mg/dL
- Very Severe: Less than 100 mg/dL
Types of Hyponatremia: Hypovolemic Hyponatremia
- Findings include decreased IVC diameter, tachycardia, postural hypotension, decreased urine output, and decreased skin turgor.
- Urine sodium > 20 mEq/L suggests renal causes.
- Urine sodium and potassium > 20 mEq/L suggests tubular injury.
- Urine sodium > 20 mEq/L and potassium < 10 suggests diuretic use or mineralocorticoid excess.
True Hyponatremia
- Mild: 130-135 meq/L, symptoms include gastrointestinal issues, mild headache, and lethargy.
- Moderate: 120-129 meq/L, symptoms include confusion, disorientation, and gait abnormalities.
- Severe: 100-119 meq/L, symptoms include hiccups.
- Very Severe: Less than 100 meq/L, symptoms are not specified.
Hypernatremia
- Very Rare:
- Osmolality > 280 mmol/kg: ADH is activated.
- Osmolality > 290 mmol/kg: Thirst mechanism is activated.
- Increased sodium is not always observed.
ADH Physiology
- ADH, also known as vasopressin, is formed in the hypothalamus, specifically the supra-optic and paraventricular nuclei.
- Magnocellular neurons produce pro-vasopressin, which is cleaved into ADH, neurophysin, and copeptin.
- ADH is stored in the posterior pituitary gland.
Stimuli for ADH Release
- Osmotic: Changes in serum osmolality (most important, around 280 mOsm/kg).
- Non-osmotic: Decreased blood volume.
ADH Action in the Kidney
- ADH acts on the V2 receptors in the basolateral membrane of the cortical collecting duct.
- This triggers a cAMP and PKA pathway, leading to the translocation of aquaporin-2 (AQP2) to the luminal membrane.
Types of Aquaporins
- AQP1: Present in the proximal convoluted tubule (PCT) for ADH-independent water reabsorption (obligatory).
- AQP2: Found on the luminal membrane of the collecting duct for ADH-dependent water reabsorption (facultative).
- AQP3/4: Located on the basolateral membrane of the collecting duct.
Water Reabsorption
- Free water is reabsorbed from the collecting duct.
- Urine osmolality increases to 800-900 mOsm/kg.
Normal ADH Function
- PCT reabsorption is isotonic (same osmotic pressure inside and outside the tubule).
- Only solute reabsorption occurs in the PCT, not water.
- In the resting state, ADH concentration is very low, allowing for water balance without ADH activation.
Euvolemic Hyponatremia
- Rule out: Cortisol/thyroid hormone insufficiency.
SIADH Criteria
- Decreased serum osmolality.
- Increased urine osmolality (higher than serum osmolality).
Euvolemic Hyponatremia Causes
- Trauma: Head injury.
- Paraneoplastic: Small cell carcinoma of the lung, pancreatic cancer, duodenal malignancy, lymphoma.
- Infections: Necrotizing pneumonia, meningoencephalitis.
- Drugs: Chlorpropamide, chlorpromazine, cyclophosphamide, carbamazepine, clofibrate, oxytocin, nicotine, NSAIDs, psychiatric drugs, vincristine.
- Acute intermittent porphyria.
CSW vs. SIADH Comparison
| Feature | CSW | SIADH |
|---|---|---|
| Loss of adrenergic tone → RAS | - | - |
| Hypovolemic | ↑ S.K+ | S.K+ normal |
| ↑↑ urine Na+ | ↑↑ urine Na+ | |
| ↓ s.uric acid level | ↓ S.uric acid level ( # Management of Hyponatremia |
- Less than 48 hours (Acute, symptomatic):
- Increased intracranial tension (ICT) poses a risk of herniation.
- Risk of herniation outweighs the risk of osmotic demyelination during rapid correction.
- Treatment: 3% saline (3 bottles of 100 ml) administered over 10 minutes each (total: 30 minutes). Repeat if necessary.
- 48 hours/Chronic onset (compensated):
- If severe, administer 3 bottles of 100 ml 3% saline every 6 hours (total: 6 bottles per 24 hours) or 25 ml/hr.
- Decreased IVC diameter suggests hypovolemia.
- Admit and start normal saline (NS).
Euvolemic Hyponatremia Management
- Check sodium level.
- If sodium level is 120:
- Fluid restriction.
- V2 antagonists (vaptans), such as tolvaptan.
- Check LFT before starting.
- Do not administer if dehydrated.
Empty Sella Syndrome
- Primary Empty Sella Syndrome (1°):
- Cause: Benign intracranial hypertension (BIH).
- Mechanism: Tear in the dura mater, allowing CSF to enter the pituitary, with the pituitary rim intact.
- Features: No features of hypopituitarism.
- Secondary Empty Sella Syndrome (2°):
- Cause: Tumor or necrosis.
- Features: Hypopituitarism features present.
Management of Hypopituitarism
-
Evaluation of Pituitary Insufficiency Testing:
Hormone Measurement Method PRL (Prolactin) Direct measurement FSH/LH Direct measurement TSH Direct measurement GH Direct measurement ACTH Insulin Tolerance test, Cosyntropin stimulation test, metyrapone test -
GH Provocation Tests: Insulin Tolerance Test, Glucagon Stimulation Test.
-
ACTH Deficiency Testing (using metyrapone test):
- Normal: No cortisol decrease in 11-deoxycortisol.
- Decreased ACTH: Decreased 11-deoxycortisol.
- Increased ACTH: Increased 11-deoxycortisol.
Hormone Replacement Therapy
- Steroids (most important):
- Hydrocortisone: 10-5-5 (10 mg morning, 5 mg afternoon, 5 mg evening).
- Infection: Double the dose, triple for very severe infections.
- Vomiting or low BP: IV hydrocortisone.
- Thyroid: L-thyroxine 50-200 µg/day.
- FSH/LH:
- Fertility not desired: Testosterone (depot, patch, gel), estrogen.
- Fertility desired: HCG, GnRH.
- ADH: Nasal Desmopressin 20 µg (or) 0.1-0.2 mg Desmopressin PO.
- GH:
- Adults: 0.3 mg/day s/c.
- Children: 0.18-0.35 mg/kg/week s/c (> 12 cm height increase/year).
- Side effects: Benign intracranial hypertension (BIH), hypertension, scoliosis.
Nelson's Syndrome
- Occurs after bilateral adrenalectomy.
- Loss of negative feedback from the adrenals leads to increased ACTH.
- Features: ACTH-secreting adenoma, hyperpigmentation.
Acquired Hyopituitarism
- Clinical Features:
- Immediately after delivery: Lactational failure.
- 3-4 months after delivery: Fatigue, anorexia, hypoglycemia, low blood pressure (BP), lactational failure, secondary amenorrhea, hypogonadism (excessive facial wrinkling, hair loss, hypopigmentation, breast atrophy), psychiatric disturbances, rarely ADH features.
- Investigation: Imaging (empty sella [2°]).
Sheehan's Syndrome with Empty Sella
- Pathology: Postpartum necrosis.
- Features: Hypopituitarism, decreased prolactin, ADH rarely affected, females predominantly affected.
- MRI findings: Empty sella.
- Epidemiology: Developing nations.
Lymphocytic Hypophysitis
- Pathology: Postpartum inflammatory IgG4 mass.
- Features: Hypopituitarism, decreased prolactin, ADH: Diabetes insipidus, affects males, females, and children, IgG4 related disease.
- MRI Findings: Pituitary mass.
- Epidemiology: Developed nations.
ANTIDIURETIC HORMONE
Osmolality
- Serum osmolality is calculated as 2 x serum sodium + blood glucose + BUN.
- Normal range: 285 ± 290 mosm/kg of H2O.
Effective Osmoles
- Solutes that stay in the blood without crossing the cell membrane.
- Examples: Sodium, potassium, chloride, bicarbonate, proteins, urea.
Ineffective Osmoles
- Solutes that cross the cell membrane without changing osmolality.
- Examples: Glucose, urea, small organic molecules.
Tonicity
- Effective osmolality (concentration of solutes that don't easily cross the cell membrane).
- Maintained primarily by sodium.
Sodium Homeostasis
- Serum osmolality depends on sodium.
- Low sodium with low osmolality: True hyponatremia.
- Low Sodium with normal or increased osmolality: Pseudohyponatremia.
Pseudohyponatremia
- Causes:
- Translocational (effective solutes):
- Glucose (For every 100mg/dL increase in blood glucose, serum sodium falls by 1.6 meq/L).
- Mannitol, glycine, maltose.
- Hyperlipidemia (serum sodium is falsely lowered)
- Hyperproteinemia (serum sodium is falsely lowered)
- Translocational (effective solutes):
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Test your knowledge on the actions of ADH on different receptors, the mechanisms of counter-current exchange, and classifications of hyponatremia. This quiz covers key physiological principles and their implications in clinical settings.
