1. Pitutary Disorders.PPT
- 1. Emergency Lecture Series Disorders of the Pituitary By Ame M. (BSc, MSc in EMCC)
- 2. Hypothalamus and Pituitary The hypothalamus-pituitary unit is the most dominant portion of the entire endocrine system. The output of the hypothalamus – pituitary unit: regulates the function of the thyroid, adrenal and reproductive glands controls somatic growth, lactation, milk secretion and water metabolism.
- 3. Hypothalamus and Pituitary….. Pituitary function depends on the hypothalamus The pituitary gland lies in a pocket of bone at the base of the brain, just below the hypothalamus to which it is connected by a stalk containing nerve fibers and blood vessels. lies at the base of the skull in the sellaturcica, within the sphenoid bone. weighs 500-900 mg composed of two lobes Anterior pituitary Posterior Pituitary Anatomically and functionally the two lobes are distinct structures.
- 4. Pituitary Development The pituitary originate from different source. The anterior pituitary from Rathke´s pouch (which is an embryonic invagination of the pharyngeal epithelium). The posterior pituitary from an outgrow of the hypothalamus.
- 5. Pituitary Gland 1. The anterior lobe consists 2/3 of the gland originate from Rathke´s pouch (which is an embryonic invagination of the pharyngeal epithelium). Secretes A) Adrenocortico Tropic Hormone (ACTH) B) Growth hormone (GH) C) Prolactin (Prl) D) Thyroid stimulating hormone (TSH) E) Follicle stimulating hormone (FSH) F) Luteinizing Hormone(LH)
- 6. Posterior Pituitary/Lobe 2.Posterior Pituitary/Lobe consists of neural tissue & is an extension of hypothalamus. originate from an outgrow of the hypothalamus is composed of nerve fibers that have their cell bodies in the supraoptic and paraventricular nuclei of the hypothalamus. The neurosecretory cells in these nuclei synthesize Oxytocin and Vasopressin which pass down the nerve fibers to be stored in and released from the posterior pituitary.
- 7. Posterior Pituitary/Lobe Secretes/Store and releases Antidiuretic hormone (ADH) also called arginine vasopressin (AVP) & regulates water metabolism Oxytocin controls lactation or milk ejection from breasts uterine contraction
- 8. Antidiuretic hormone (ADH) or Arginine Vasopressin (AVP) The supraoptic nucleus (SON) is responsible predominantly for the synthesis of vasopressin which is the ADH. ADH is an octapeptide like oxytocin. The close structural similarity of vasopressin and oxytocin explains the overlap of their biological actions. The Arginine Vasopressin (AVP) is ADH in man and other mammals apart from the pig and the hippopotamus where Lysine Vasopressin is the ADH.
- 9. FUNCTION/ACTION OF ADH/AVP Primary effect of ADH is on the cells of the distal tubules and collecting ducts of the kidney is promoting reabsorption of water. This action is mediated via V2-receptors and formation of a specific protein known as aquaporin. Beside water, AVP enhances reabsorption of urea increasing tonicity of the renal medulla allowing more water to be reabsorbed.
- 10. FUNCTION…… Acting on V1-receptors in peripheral vessels AVP causes vaso-constriction and increase in BP. Normally this is balanced by its inhibitory effect on sympathetic cardiac stimuli causing bradycardia. During hypovolemia high plasma levels of AVP help maintain tissue perfusion. A lesser 2ndry effect that is mediated via V2 non-renal receptors is: stimulation of synthesis and release of factor VIII & Von Willebrand Factor.
- 11. REGULATION OF ADH SECRETION ADH release is stimulated by: A plasma osmolality >280 mosm/L A fall in plasma volume Emotional factors & stress Sleep Other factors Other ADH Stimulants Cholinergic stimulation -adrenergic stimulation Angiotensin II Prostaglandin E Ether, Histamine Opiates, Nicotine Phenobarbitone
- 12. ADH SECRETION IS INHIBITED BY: Alcohol Oropharyngeal water reflex β-adrenergic stimulants Atrial natriuretic factor (ANF) Phenytoin
- 13. Disorders of the Posterior Pituitary
- 14. Outline Diabetes Insipidus Definitions Causes Types Ass’t and Dx Mgt SIADH Definitions Causes Dx Mgt
- 15. Diabetes Insipidus (DI) Definitions DI is a condition ch’rized by excessive thirst and excretion of large amounts of severely dilute urine, with reduction of fluid intake. DI is a disorder resulting from deficiency of ADH or its action ch’zed by; the passage of copious amounts of dilute urine It must be differentiated from other polyuric states Primary polydipsia and polydipsia – Excessive thirst (as in cases of diabetes or kidney dysfunction) Osmotic diuresis.
- 16. Diabetes Insipidus (DI) Diabetes insipidus (DI) results from a group of disorders in which absolute or relative deficiency of ADH or insensitivity to its effects on the renal tubules. may complicate the course of critically and acutely ill patients and can result in acute fluid & electrolyte disturbances.
- 17. DI … Classification Different types of DI, each with a different cause. Neurogenic/Central DI: most common Nephrogenic DI: second most common Dipsogenic DI Gestational DI
- 18. Neurogenic DI more commonly known as central DI, also called central or primary pituitary DI. caused by a deficiency of Arginine vasopressin(AVP) AVP also known as ADH. is ADH-deficient is due to a lack of vasopressin production in the brain or is due to failure of the pituitary gland to release adequate ADH. secondary to Panhypopituitarism is generally caused by destruction of the neurohypophysis, which can result from genetic defects, tumors, trauma, or infection. However, most cases of neurogenic DI are considered idiopathic. Because the neurohypophysis is responsible for storing vasopressin, destruction of this structure results in vasopressin deficiency.
- 19. Etiology of Central DI It occurs when any organic lesion of the hypothalamus, infundibular stem or posterior pituitary interferes with ADH synthesis, transport or release. Idiopathic (30% of cases) Suprasellar tumours (30% of cases) Hypothalamic or pituitary tumors — craniopharyngioma, germinoma, histiocytosis, glioma, lymphocytic hypophysitis. Autoimmune Associated with thyroiditis Antibodies target ADH-producing cells. Familial (hereditary): 2 types AD and X-linked inheritance Genetic (autosomal dominant inheritance) Genetic — mutations in vasopressin gene and WFS1 gene (Wolfram syndrome) Midline brain defects — septo-optic dysplasia, holoprosencephaly
- 20. Etiology of Central DI….. Neoplasms Infections Tuberculosis Cryptococcosis Syphilis CNS infections Granulomatous diseases Infectious Granulomatous Ds (e.g., sarcoidosis, TB) Non-infectious granuloma e.g. Sarcoid, hand-schuller Christian disease (histiocytosis) Langerhans cell histiocytosis – in which 25% of pts develop DI.
- 21. Etiology of Central DI…… Brain injury, infection, or surgical resection Infections (Encephalitis, meningitis, TB, etc) Trauma and hypoxic ischemic brain injury Trauma or skull surgery basilar skull fractures, neurosurgical complications Leukemia Vascular Ds (e.g., aneurysms, lesions) Cerebrovascular hemorrhage Aneurysm (circle of Willis) Cerebral thrombosis Wolfram syndrome (also known as DIDMOAD syndrome) ch’zed by DI, DM, Nerve Deafness and Optic Atrophy.
- 22. Nephrogenic DI is characterized by renal tubule insensitivity to ADH and develops because of structural or functional changes in the kidney. This results in impaired urine-concentrating ability & free water conservation. is less dramatic than neurogenic DI in its onset and appearance. ADH-resistance (kidney does not respond to ADH) is due to inability/insensitivity of the kidneys to respond normally to ADH is due to the renal tubules of the kidneys fail to respond to circulating ADH. can also an iatrogenic artifact of drug use The resulting renal concentration defect leads to the loss of large volumes of dilute urine. This causes cellular and extracellular DHN and hypernatremia.
- 23. Causes of Nephrogenic DI Primary Familial (hereditary): X-linked recessive that is severe in boys and mild in girls. Secondary to: Renal disease chronic pyelonephritis chronic renal failure, obstructive uropathy, polycystic disease Electrolyte disorders Hypokalemia Hypercalcemia Sickle cell disease Protein deprivation Amyloidosis Drugs: Lithium, Colchicine, Fluoride, Rifampin, Cidofovir, Demeclocycline Methoyflurane, Cisplatin, Methicillin Amphotericin B, Gentamicin, Furosemide
- 24. CAUSES OF NEPHROGENIC DI Nephrogenic DI is caused by a renal resistance to the effects of vasopressin. Inherited as an X-linked recessive disorder chronic renal disease with failure to concentrate urine. can result from a genetic condition, certain medications e.g. lithium and general anesthetics, methoxyflurane and demeclocycline or renal disease.
- 26. Dipsogenic DI results from an abnormality in or damage to the hypothalamus, which alters the thirst mechanism. is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in abnormal increase in thirst and fluid intake that suppresses ADH secretion & increases urine out put. The altered thirst mechanism drives the patient to drink large quantities of fluid. In addition, the production of vasopressin is suppressed, which results in increased urine output. Excessive Water Intake (Secondary DI) Excessive IV fluid administration Psychogenic polydipsia (lesion in thirst center) Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.
- 27. Gestational Diabetes Insipidus (GDI) is extremely rare, only occurs during pregnancy. usually occurs after the 5th month of pregnancy. usually resolves spontaneously after childbirth. During pregnancy, the placenta of affected patients produces an enzyme (vasopressinase ) that destroys vasopressin. The resulting deficiency of vasopressin causes the classic symptoms of DI.
- 28. Regardless of the etiology, in DI the ability of the body to increase ADH secretion or respond to ADH is impaired.
- 29. Clinical Presentation S/Sx of DHN are present in those patients in whom: the thirst mechanism has been impaired or there is inadequate fluid replacement. In addition, if a hyperosmolar state exists; intracellular brain volume depletion occurs as water moves from within the brain cells to the plasma.
- 30. Clinical Presentation….. Signs and Symptoms ADH Deficiency Polydipsia (if alert) Polyuria (5-20 L in 24 hours) Fluid Volume Deficit Orthostatic hypotension Weight loss Tachycardia Decreased CVP, PCWP Poor skin turgor Dry mucous membranes Intracellular Brain Volume Depletion Confusion Restlessness Lethargy Irritability Seizures Coma
- 31. Clinical Presentation……. Polydipsia, Polyuria (>2 L/m2/day) & thirst. Nocturia or nocturnal enuresis Hypernatremic DHN Anorexia, constipation and FTT Hyperthermia and lack of sweating Symptoms of underlying cause Abnormalities of the CNS such as: irritability, altered consciousness, increased muscle tone, convulsions, and secondary to hypernatremia. these findings correlate with the degree and rapidity of the rise in serum Na. Typically, symptoms manifest when serum sodium levels exceed 155 mEq/L.
- 32. COMPLICATIONS Untreated DI can produce: Hypernatremic DHN & its neurological sequelea Growth retardation hypovolemia, hyperosmolality, circulatory collapse, loss of consciousness, and central nervous system damage. These Cxs are most likely if the patient has an impaired or absent thirst mechanism. A prolonged increase in urinary flow (excessive urine output) may produce: chronic complications, such as bladder distention, enlarged caliceal, hydroureter, and hydronephrosis. Cxs may result from an underlying condition, such as a metastatic brain lesion, a head trauma, or an infection.
- 33. COMPLICATIONS decreased bone mineral density at the lumbar spine and femoral neck in patients with central DI even in those treated with desmopressin (dDAVP). Anterior pituitary hormone deficiency, with decreased release of growth hormone, thyroid stimulating hormone, and adrenocorticotropic hormone , also may be present or develop in patients with idiopathic CDI.
- 34. Differential Diagnosis Psychogenic polydipsia Osmotic diuresis Diabetes mellitus Beer potomania Hypertonic DHN secondary to diarrhea Exogenous salt administration
- 35. DIAGNOSTIC WORKUP Careful history and examination U/A and microscopy Plasma/serum electrolytes Water deprivation test (Dehydration test)
- 36. DIAGNOSTIC WORKUP Assessment findings The patient's history shows an abrupt onset of extreme polyuria (usually 4 to 16 L/day of dilute urine, but sometimes as much as 30 L/day), extreme thirst, and consumption of extraordinarily large volumes of fluid. The patient may report weight loss, dizziness, weakness, constipation, slight to moderate nocturia and, in severe cases, fatigue from inadequate rest caused by frequent voiding and excessive thirst. In children, reports of enuresis, sleep disturbances, irritability, anorexia, and decreased weight gain and linear growth are common.
- 37. Assessment findings…… On inspection, you may notice: signs of DHN, such as dry skin & mucous membranes, fever, and dyspnea. colorless and voluminous urine Palpation may reveal: poor skin turgor, tachycardia, and decreased muscle strength. Hypotension may be present on BP auscultation.
- 38. Diagnostic Tests…… Urinalysis Specific gravity, Osmolality, Glucose, Sodium. Serum glucose & electrolytes Serum Osmolality BUN and creatinine Water deprivation test (dehydration test) U/A and microscopy together with plasma electrolytes help exclude most of the causes of polyuria. Measuring glucose, sodium, and osmolality in urine and serum can quickly distinguish DM, hypertonic DHN, psychogenic polydipsia, and exogenous salt intake from DI.
- 39. Diagnostic Tests…… Water deprivation test (dehydration test) is a simple, reliable way to diagnose DI and differentiate vasopressin deficiency from other forms of polyuria. It compares urine osmolality after DHN with urine osmolality after vasopressin administration. Fluids are withheld long enough to result in stable hourly urine osmolality values (an hourly increase of 30 mOsm/kg of water for at least 3 successive hours). After the third hour, the patient is given 5 units of aqueous vasopressin. Plasma osmolality is determined immediately before vasopressin administration, and urine osmolality is measured 30 and 60 minutes later. In patients with DI, the increase in urine osmolality after vasopressin administration exceeds 9%. Patients with neurogenic DI respond to exogenous vasopressin with decreased urine output and increased sp.gr. Patients with nephrogenic DI show no response to vasopressin.
- 40. Diagnostic Tests…… In critically ill patient, the Dx: shouldn't be delayed for more time-consuming tests; may be based on the following laboratory values: Serum sodium > 155 mEq/L Serum osmolality > 300 mOsm/kg/L Urine osmolality <200 mosm/kg/L Urine sp.gr. <1.005. Increased BUN and creatinine (hemoconcentration)
- 41. Diagnostic…. In a normal well hydrated subject: plasma osmolality is 275 – 295mosm/L and urine osmolality is 300-450 mosm/L. In patients with DI and free excess to water: plasma osmolality is >300 mosm/L & urine osmolality is 50-200 mosm/L.
- 42. Nephrogenic DI Patients unable to produce concentrated urine during fluid restriction.
- 43. WATER DEPRIVATION TEST Water deprivation test is needed for patients with partial AVP deficiency and also to differentiate DI from primary polydipsia. Should be done in the morning under observation In normal subjects: plasma osmolality hardly rises (< 300) but the urine output is reduced and its osmolality rises (800 – 1200) Fluid deprivation test — withhold fluids for 8-12 hours. Weigh patient frequently. Inability to slow down the urinary output and fail to concentrate urine are diagnostic.
- 44. WATER DEPRIVATION TEST Stop test if patient is tachic or hypotensive Monitor serum and urine osmolality and ADH levels Patients with primary polydipsia start with low normal plasma osmolality (280) but urine/plasma osmolality ratio rises to >2 after DHN. In patients with DI the plasma but not the urine osmolality rises and Urine/Plasma osmolality ratio remains < 1.5. At the end of the test, ADH is given (20 mg DDAV intranasally or 2 mg I.M.) and fluid intake allowed. Concentration of the diluted urine confirms central DI and failure suggest nephrogenic causes.
- 45. Diagnosis A persistent output of dilute urine and increasing hemoconcentration is the hallmark of DI. The cardinal diagnostic features are: a high rate of dilute urine flow (urine output >4 mL/kg/hr) clinical signs of DHN (wt loss, hypotension) mild to marked degree of serum hypernatremia (>150 mEq/L) serum hyperosmolality (>300 mOsm/kg) low urine osmolality (<200 mOsm/kg) and low urine sp.gr. (<1.010) despite a normal or elevated serum osmolality
- 46. Management Identify treatable causes of DI The DOC for central DI is DDAVP Desmopressin acetate (DDAVP) is synthetic ADH is an ADH analogue, can be given intranasally, SQ, IV, IM or po to stimulate the kidneys to retain water and reverse the polyuria, polydipsia, and hypernatremia.
- 47. Management……. Desmopressin (DDAVP) a synthetic analog is superior to native AVP b/c: it has longer duration of action (8-10 hrs Vs 2-3 hrs), more potent its antidiuretic activity is 3000 times greater than its presser activity. If renal in origin thiazide diuretics, NSAIDs (prostaglandin inhibition) and salt depletion may help. Educate patient about actions of medications, how to administer meds, wear medical alert bracelet.
- 48. Principles of Management for DI DI mgt is directed at correcting the profound fluid volume deficit and electrolyte imbalances associated. If fluid losses are not replaced, hypovolemic shock can rapidly develop. In some cases of DI, vasopressin or agents that simulate ADH release and renal response to ADH are prescribed to treat the disorder. Dx & Tx of the causes are priorities.
- 49. Principles of Management for DI Fluid Volume Replacement If the patient is alert and the thirst mechanism is not impaired, allow the patient to drink water to maintain normal serum osmolality. In many critically ill patients, this is not possible. Administer hypotonic volume, such as dextrose 5% in water, quarter-strength or half- strength saline, IV as prescribed to restore the hypotonic fluid lost through osmotic diuresis. The administration of N/S to replace volume is usually contraindicated because it presents an added renal load, promoting osmotic diuresis and worsening dehydration. In severe DI, where large amounts of fluid replacement are required, the IV intake is usually titrated to urine output; for example, 400 mL of urine output for 1 hour is replaced with 400 mL IV fluid the next hour. Hypotonic saline solutions are preferred (quarter-strength or half-strength saline). A good rule of thumb is to reduce serum sodium by 0.5 mEq/L every hour but no more than 12 mEq/L per day.
- 50. Principles of Management for DI Monitor fluid status: Hourly urine outputs along with measurements of urine sp.gr. every 1-2 hrs should be done along with daily weight and strict intake and output. Monitor for signs of continuing fluid volume deficit. If the serum Na+ is > 155 mEq/L, rehydration should occur over 48 hrs. A serum Na+ > 170 necessitates ICU care. Monitor neurologic status continuously. An altered level of consciousness indicates intracellular DHN of the brain and hypovolemia. Frequent electrolyte monitoring is recommended during the initial phase of Tx.
- 51. ADH Administration or Enhancement A definitive Dx regarding the type of DI the patient has should be made before Tx; inappropriate Tx can exacerbate symptoms and cause water intoxication and, possibly, severe brain damage. Medications may include the following: Aqueous vasopressin is a replacement agent administered by SQ injection. Its duration of action ranges from 3 to 6 hrs. This drug is used in the initial mgt of DI after head trauma or a neurosurgical procedure. Desmopressin acetate, a synthetic vasopressin analogue, affects prolonged antidiuretic activity and has no pressor effects. It may be given orally, by nasal spray that's absorbed through mucous membranes, or by SQ or IV injection. The duration of action of desmopressin acetate is 8-20 hrs, depending on dosage. Chlorpropamide (Diabinese), a sulfonylurea used in patients with DM, is also sometimes used to stimulate endogenous release of ADH and is effective if some pituitary function is present. Nephrogenic DI is treated with a low-sodium, high-protein diet and a thiazide diuretic. The mild diuretic action reduces blood volume and enhances sodium and water reabsorption in the proximal tubule.
- 52. ADH Administration or Enhancement…. In central DI, Desmopressin (DDAVP), an ADH analogue, is the DOC and is available in subcutaneous, IV, intranasal, and oral preparations. acts on the distal tubules and collecting ducts of the kidney to increase water reabsorption and has very specific actions with little or no ADH-like activity elsewhere in the body, most notably vasopressor effects that are prominent in another vasopressin analogue, aqueous AVP. Vasopressin is only given IM or IV and is useful only for very short duration in unconscious patients in whom recovery of ADH secretion is expected. However, aqueous vasopressin is less specific than DDAVP and can cause profound vasoconstriction in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels—thus it is not preferred for DI therapy in critically and acutely ill patients unless DDAVP is ineffective.
- 53. ADH Administration or Enhancement….. Adjunctive therapy to enhance ADH release includes nonhormonal agents such as: chlorpropamide, carbamazepine, thiazides, and NSAIDs. If the patient is unconscious, injectable DDAVP is given IV or IM 1 to 4 μg every 12 hours until therapeutic goals are achieved, such as a urine output of 2-3 ml/kg/hour, urine sp.gr. 1.010- 1.020 and serum Na 140-145 mEq/l. In conscious patients, the nasal replacement route is given 10 to 20 μg by spray 2 to 3 times a day.
- 54. ADH Administration or Enhancement….. It is important that DDAVP or other ADH analogues not be administrated unless serum Na is at least above 145 mmol/L, as serious hyponatremia may result. Oral formulations of ADH have a slower onset and duration of action and are not useful in acute situations. Major side effects to watch for include: headache, abdominal cramps, or allergic reactions such as facial flushing. Monitor for overmedication, which may precipitate hypervolemia. S/Sx of fluid volume excess include: dyspnea, hypertension, weight gain, and angina. Hyponatremia is another serious consequence and if it develops rapidly can cause extreme cerebral edema and osmotic demyelination syndrome. Therefore, close monitoring of serum sodium is necessary.
- 55. ADH Administration or Enhancement….. For nephrogenic DI, DDAVP intranasal or oral agents may be adminstered or alternative drugs such as chlorpropamide or NSAIDs (such as indomethacin) may be given. Volume excess remains a risk from treatment. Chlorpropamide, an older antidiabetic agent, may also result in hypoglycemia. Provision of adequate fluids and calorie Low sodium diet Diuretics High dose of DDAVP Correction of underlying cause DRUGS: Indomethacin, Chlorpropamide, Clofibrate and Carbamazepine.
- 56. Nursing interventions keeping accurate records of the patient's hourly fluid intake and urine output, vital signs, and daily weight. Close monitoring of the urine sp.gr. Also monitor serum electrolyte and BUN levels. During dehydration testing, watch for signs of hypovolemic shock. Monitor BP, pulse rate, and body weight. Also watch for changes in mental or neurologic status. instituting safety precautions to help prevent injury, if the patient has complaints of dizziness or muscle weakness. Make sure that the patient has easy access to the bathroom or a bedpan.
- 57. Nursing interventions Provide meticulous skin and mouth care. Use a soft toothbrush and mild mouthwash to avoid trauma to the oral mucosa. If the patient has cracked or sore lips, apply petroleum jelly as needed. Use alcohol-free skin care products, and apply emollient lotion to the patient's skin after baths. Use caution when administering vasopressin to a patient with coronary artery disease because the drug can cause coronary artery constriction. Closely monitor the patient's ECG, looking for changes and exacerbation of angina. Urge the patient to verbalize feelings. Offer encouragement, and provide a realistic ass’t of the situation. Help the patient identify his strengths, and help him see how he can use these strengths to develop effective coping strategies. As necessary, refer the patient to a mental health professional for additional counseling. Advise the patient to wear a medical identification bracelet at all times. Tell him he should also always keep his medication with him.
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- 59. ADH exerts its primary effects in the distal collecting tubules of the kidneys where it decreases water excretion, conserving body water, thereby increasing urine concentration (osmolality) and hemodilution. Osmoreceptors in the hypothalamus monitor changes in blood osmolality. An increase of osmolality by 2% leads to ADH release by the posterior pituitary. In high conc., usually via exogenous administration, ADH has potent vasopressor effects along with pro-coagulant (platelet aggregation) properties. Syndrome of Inappropriate ADH Secretion
- 60. Etiology, Risk Factors, and Pathophysiology The SIADH and DI are the most common disorders associated with ADH secretion in the critically ill. The SIADH is char’zed by excessive release of ADH unrelated to the plasma osmolality, or the conc. of electrolytes and other osmotically active particles. Normal mechanisms that control ADH secretion fail, causing impaired water excretion and profound hyponatremia. SIADH is a syndrome of water intoxication.
- 61. Etiology, Risk Factors, and Pathophysiology Vasopressin can be produced by a variety of malignancies, most commonly oat cell carcinoma of the lung. Therefore, patients who develop “idiopathic” SIADH are screened for malignant tumors. SIADH is also commonly associated with: pulmonary conditions, metabolic and traumatic CNS disorders, and drugs, particularly chlorpropamide, thiazide diuretics, opiates, and barbiturates. Surgical patients are also at risk because of increased vasopressin secretion due to perioperative surgical stress and t he use of opiate analgesics such as morphine. Clinically, SIADH is distinguished by hyponatremia and water retention that progresses to water intoxication.
- 62. Etiology, Risk Factors, and Pathophysiology The seriousness of the patient’s S/Sx depends on how fast the serum sodium falls. As water intoxication progresses and the serum becomes more hypotonic, brain cells swell, causing neurologic impairment. Without Tx, irreversible brain damage and death can occur. Excessive ADH secretion Retain fluids and develop a dilutional hyponatremia known as syndrome of hyponatremia with inappropriate increased secretion of Vasopressin (SIADH) There are many causes of SIADH. can be identified in an individuals with encephalitis, brain tumors, head trauma, or psychiatric disease.
- 63. Etiology, Risk Factors, and Pathophysiology ETIOLOGY One of the following causes of persistent ADH release is likely to be present in patients who fulfill the clinical criteria for the SIADH: CNS disturbances Any CNS disorder, including stroke, hemorrhage, infection, trauma, and psychosis, can enhance ADH release. hyponatremia associated with intracranial bleeding, as well as ther severe neurologic events, is due to ADH-mediated water retention and urinary sodium losses.
- 64. Etiology, Risk Factors, and Pathophysiology Malignancies Ectopic production of ADH by a tumor is most often due to a small cell carcinoma of the lung and is rarely seen with other lung tumors. Less common causes of malignancy-associated SIADH include: head and neck cancer, olfactory neuroblastoma (esthesioneuroblastoma), and extrapulmonary small cell carcinomas.
- 65. Etiology, Risk Factors, and Pathophysiology Drugs Certain drugs can enhance ADH release or effect, including: chlorpropamide , carbamazepine , oxcarbazepine (a derivative of carbamazepine), high-dose IV cyclophosphamide , and selective serotonin reuptake inhibitors. (e.g., fluoxetine , sertraline ). Many other drugs have been associated with the SIADH. These include vincristine , vinblastine , vinorelbine , cisplatin , thiothixene , thioridazine , haloperidol , amitriptyline , monoamine oxidase inhibitors, melphalan , ifosfamide , methotrexate , opiates, nonsteroidal antiinflammatory agents, interferon-alpha, interferon-gamma, sodium valproate , bromocriptine , lorcainide, amiodarone , ciprofloxacin , high-dose imatinib , and "ecstasy" (methylenedioxymethamphetamine), a drug of abuse that may also be associated with excessive water intake.
- 66. Etiology, Risk Factors, and Pathophysiology Surgery Surgical procedures are often associated with hypersecretion of ADH, a response that is probably mediated by pain afferents. hyponatremia may develop after other types of interventional procedures, such as cardiac catheterization. Rarely, hyponatremia after pituitary surgery is due to cerebral salt wasting. Pulmonary disease particularly pneumonia (viral, bacterial, tuberculous), can lead to the SIADH, although the mechanism is not clear. infrequently seen with asthma, atelectasis, acute respiratory failure, and pneumothorax.
- 67. Etiology, Risk Factors, and Pathophysiology Hormone deficiency Both hypopituitarism and hypothyroidism may be associated with hyponatremia and an SIADH picture that can be corrected by hormone replacement. Hormone administration The SIADH can be induced by exogenous hormone administration, as with vasopressin (to control gastrointestinal bleeding), desmopressin (dDAVP, to treat Von Willebrand disease or hemophilia or platelet dysfunction), or oxytocin (to induce labor). As with vasopressin and desmopressin, oxytocin acts by increasing the activity of the V2 (antidiuretic) vasopressin receptor.
- 68. Etiology, Risk Factors, and Pathophysiology HIV infection A common cause of hyponatremia is symptomatic HIV infection, either AIDS or early symptomatic HIV infection. Although volume depletion (due, for example, to GIT losses) or adrenal insufficiency may be responsible, many patients have the SIADH. Pneumonia, due to Pneumocystis carinii or other organisms, CNS infections, and malignant disease, are most often responsible in this setting.
- 69. Etiology, Risk Factors, and Pathophysiology Hereditary SIADH genetic disorders that result in antidiuresis. two genetic abnormalities have been identified, one affecting the gene for the renal vasopressin-2 (V2) receptor, and one affecting osmolality sensing in the hypothalamus. Idiopathic Idiopathic SIADH has been described primarily in elderly patients. However, some cases of apparently idiopathic disease were later found to be caused by an occult tumor (most often small cell carcinoma or olfactory neuroblastoma) and, in older patients, giant cell (temporal) arteritis.
- 70. Etiology, Risk Factors, and Pathophysiology CEREBRAL SALT WASTING A rare syndrome has been described in patients with cerebral disease (particularly SAH) that mimics all of the findings in the SIADH except that salt wasting is thought to be the primary defect, with the ensuing volume depletion causing a secondary rise in ADH release.
- 71. Etiology, Risk Factors, and Pathophysiology Among patients with SIADH, the combination of water retention and secondary solute (Na+ plus K+) loss accounts for essentially all of the reduction in serum sodium. Hyponatremia is initially mediated by ADH-induced water retention. may also be associated with potassium loss. Since potassium is as osmotically active as sodium, the loss of potassium contributes to the reductions in plasma osmolality and sodium concentration.
- 72. ETIOLOGIES OF SIADH (PARTIAL LISTING) Malignancies Lung Lymphoma Gastrointestine Often non-endocrine in origin — such as bronchogenic carcinoma. Pulmonary Diseases/Conditions Positive pressure ventilation Asthma Pneumonia COPD Acute respiratory failure Tuberculosis CNS Disorders Head injury, Brain surgery, Infections (Meningitis, encephalitis) Cerebrovascular accidents Brain tumors Guillain-Barré syndrome Drugs Many drugs are capable of interfering with free water clearance can either affect the pituitary or increase sensitivity to renal tubules to ADH. Vasopressin, Desmopressin Phenothiazine's, Carbamazepine, Thiazide diuretics Narcotics, Nicotine, Barbiturates Antineoplastic drugs Tricyclic antidepressants Others AIDS Senile atrophy
- 73. Clinical Presentation Early Urine volume decreased and concentrated Nausea, Vomiting Headache Impaired taste Dulled sensorium Muscle weakness and cramps Anorexia Weight gain Crackles Dyspnea Increased CVP, PCWP Weakness/fatigue Late Confusion Hostility Aberrant respirations Hypothermia Coma Convulsions Signs and Symptoms
- 74. Clinical Presentation…… Patients with normovolemic hyponatremia present with, relatively concentrated urine, and normal renal, thyroid, and adrenal function. Symptoms are related to the degree of hyponatremia and how rapid the hyponatremia progressed. symptoms unlikely with a Na+ >125 mEq/L. Headache, nausea, lethargy, and other CNS findings may occur when sodium falls ≤125 mEq/L.
- 75. Clinical Presentation…… In acute hyponatremia; the severity of symptoms generally reflects the severity of cerebral overhydration, which is related to the degree of hyponatremia. The major clinical manifestations of acute hyponatremia include : Nausea and malaise, which are the earliest findings, may be seen when the serum Na+ conc. falls below 125 to 130 mEq/L if the serum sodium conc. falls below 115 to 120 mEq/L: Headache, lethargy, obtundation and eventually seizures, coma, and respiratory arrest can occur. Noncardiogenic pulmonary edema has also been described. Acute hyponatremic encephalopathy can occur Overly rapid correction also may be deleterious, particularly in patients with chronic hyponatremia.
- 76. Diagnostic Tests Blood chemistries U/A BUN and creatinine Serum Na+ < 135 mEq/L Serum osmolality < 275 mosm/kg Increased urine osmolality > 500 mosm/kg Urine Na+ > 20 mEq/L BUN and creatinine decreased (hemodilution) A serum osmolality <275 mosm/kg combined with urine osmolality >200 mosm and urine Na+ conc. >20mEq/L are consistent with SIADH.
- 77. Principles of Management for SIADH Principles of mgt depend on the severity & duration of the hyponatremia. Hyponatremia in the SIADH results from ADH-induced retention of ingested or infused water. Although water excretion is impaired, Na+ handling is intact, since there is no abnormality in volume-regulating mechanisms such as the renin-angiotensin-aldosterone system or atrial natriuretic peptide. early recognition is key to prevent life-threatening cxns. Continued ass’t of neuromuscular, cardiac, GI, and renal systems is important.
- 78. Principles of Management for SIADH The choice of therapy of SIADH is dependent upon a number of factors including: the degree of hyponatremia, the presence or absence of symptoms, and, the urine osmolality (to some degree) Generally, Tx focuses on: restricting fluids, replenishing sodium deficits, and inhibiting antidiuretic actions – in severe cases of hyponatremia,. Tx of the underlying disorder is also a priority.
- 79. THERAPIES TO RAISE THE SERUM SODIUM A number of modalities can be used to correct hyponatremia in the SIADH, most importants are: fluid restriction, salt administration, and vasopressin receptor antagonists. When treating such patients, attention must be paid to the rate of correction. There are three components to the Tx of hyponatremia in SIADH: Treatment of the underlying disease, if possible Initial therapy to raise the serum sodium Prolonged therapy in patients with persistent SIADH
- 80. Treat the underlying disease SIADH is a Dx of exclusion. Eliminate the cause. Other causes of hyponatremia must be ruled out hyperglycemia, increased serum lipids or protein. A variety of causes of SIADH can be effectively treated, leading to resolution of the hyponatremia. These include: Hormone replacement in adrenal insufficiency or hypothyroidism Treatment of infections such as meningitis, pneumonia, or tuberculosis Cessation of offending drugs, such as Selective serotonin reuptake inhibitors or Chlorpropamide
- 81. Fluid Restriction is the mainstay of Tx. is a standard component of therapy in SIADH, but may promote cerebral vasospasm in patients with SAH who are usually treated with volume expansion. Tx of mild hyponatremia (Na+ level 125 – 135 mEq/L) includes fluid restriction of 800 to 1000 mL/d. this allows Na+ level to correct over 3 to 10 days.
- 82. Intravenous saline Severe, symptomatic, or resistant hyponatremia in patients with SIADH often requires the administration of NaCl. isotonic saline has no role in symptomatic hyponatremia due to SIADH. If the serum Na+ conc. is to be elevated, the electrolyte conc. of the fluid given must exceed the electrolyte conc. of the urine, not simply that of the plasma.
- 83. Replenish Sodium Deficits 3% saline infusion over 2-3 hrs, if; severe symptomatic hyponatremia of SIADH severe neurologic symptoms of SIADH are present along with severe hyponatremia (< 125 mEq/L). hyponatremic patients present with SAH to preserve cerebral perfusion and to prevent cxns from hyponatremia-induced brain swelling. infuse 3% saline at a rate of 0.1 mL/kg/min for 2 hrs to raise plasma Na+. b/c this Tx causes a transient increase in the serum Na+: Monitor closely for signs of: hypernatremia, fluid overload, and heart failure.
- 84. Inhibit ADH Actions Drugs that interfere with the renal effect of ADH are used: If fluid restriction alone is not effective, or In cases where SIADH does not resolve within 1 to 2 weeks. e.g. demeclocycline can be administered. Demeclocycline and lithium act on the collecting cell of the renal tubules, to diminish its responsiveness to ADH, or inhibits the effect of ADH on the renal tubules, thereby increasing water excretion. these drugs are not suitable for acute mgt of the syndrome due to their full effects.
- 85. High solute intake a high salt and protein diet without a increase in water ingestion. is one way to increase water excretion in patient with SIADH. The increase in water excretion would then tend to raise the plasma Na+ conc. toward normal. high solute diet can be combined with a loop diuretic, which interferes with concentrating ability and lowers the urine osmolality. These includes: Oral salt tablets Salt plus a loop diuretic Urea
- 86. High solute intake Oral salt tablets sodium chloride in tablet form Some patients with chronic SIADH have a major underlying illness (such as small cell carcinoma) that may limit compliance with increased dietary salt intake. Salt plus a loop diuretic The effect of salt tablets can be enhanced if given with a drug that lowers the urine osmolality and increases water excretion. This can be achieved by impairing the renal responsiveness to ADH by the administration of a loop diuretic or a vasopressin receptor antagonist.
- 87. High solute intake Loop diuretics e.g., furosemide 20 mg orally twice a day directly interferes with the countercurrent concentrating mechanism by decreasing NaCl reabsorption in the medullary aspect of the loop of Henle. will be effective if the Uosm is more than twice the Posm, which typically means a Uosm above 500 mosm/kg. Monitoring of the serum K+ is important, particularly in the early stages of therapy. Some patients require KCL supplementation or use of a potassium-sparing diuretic, such as amiloride . Urea increase urinary solute excretion and enhance water excretion usual dose is 30 g/day.
- 88. Vasopressin receptor antagonists There are three receptors for vasopressin (ADH): the V2 receptors – primarily mediate the antidiuretic response, the V1a & V1b receptors – primarily cause vasoconstriction & ACTH release, respectively. The vasopressin receptor antagonists produce: a selective water diuresis (aquaresis) without affecting Na+ and K+ excretion. The ensuing loss of electrolyte-free water will tend to: raise the serum Na+ in patients with SIADH and Some oral formulations selective for the V2 receptor are: tolvaptan , mozavaptan, satavaptan, and lixivaptan, while an IV agent, conivaptan , blocks both the V2 and V1a receptors.
- 89. RATE OF CORRECTION the initial rate of correction is determined by: the severity of neurologic symptoms attributable to hyponatremia. in patients with severe symptoms (e.g., seizures). initial rate of correction of 4 to 6 mEq/L in the first 2 to 4 hrs may be beneficial this requires careful monitoring of the serum Na+ conc. initially every 2 to 3 hrs until the patient is stable. the maximum rate of correction of chronic hyponatremia should be <9 mEq/L in any 24-hr period.
- 90. CHOICE OF THERAPY Choice of therapy Varies: with the severity of hyponatremia and the presence or absence of symptoms. Symptomatic hyponatremia approach varies with the severity of the neurologic symptoms.
- 91. Severe symptoms of hyponatremia e.g., seizures, inability to communicate, and/or coma are most likely to occur when serum Na+ <120 mEq/L in <48 hrs, leading to potentially fatal cerebral edema. the administration of hypertonic saline (3 %) is the only rapid way to raise the serum Na+ and improve neurologic manifestations. The rise in serum Na+ will pull water out of the brain, decreasing the degree of cerebral edema. If neurologic symptoms persist or worsen, a 100 mL bolus of 3 % saline can be rptd one or two more times at 10 min intervals. Rationale for this approach is that, in patients with symptomatic hyponatremia, rapid increases in serum sodium of 4 to 6 mEq/L can reverse severe symptoms such as seizures.
- 92. Severe symptoms….. If the symptoms resolve, careful monitoring with measurement of the serum Na+ conc. every 2 to 3 hrs is required for two reasons: A potential cxns of hypertonic saline therapy is overly rapid correction of the hyponatremia, The usual goals are an elevation in serum Na+ of <10 meq/L in the first 24 hrs and <18 meq/L in the first 48 hrs. In patients with severe hyponatremia who are correcting too rapidly, prevention of further short-term elevation in the serum Na+ or even relowering of the serum Na+ may be warranted.
- 93. Mild to moderate symptoms of Hyponatremia Less severe neurologic symptoms (e.g., dizziness, gait disturbances, forgetfulness, confusion, and lethargy) can be seen: in patients with a serum Na+ conc. <120 mEq/L that develops over more than 48 hrs, in patients with a lesser degree of hyponatremia that develops over <48 hrs, and in patients with chronic moderate hyponatremia (serum Na+ 120 – 129 mEq/L). Some of these patients may benefit from hypertonic saline, but do not require the aggressive approach suggested for those with severe neurologic symptoms. Initial hypertonic saline therapy to raise the serum Na+ at rates up to 1 mEq/L per hr may be justified in the first 3 to 4 hrs in patients with distressing symptoms (e.g., confusion and lethargy). The total elevation in serum Na+ in the first 24 hrs should be <10 mEq/L. Patients with less severe symptoms can be treated with less aggressive therapy, such as fluid restriction and oral salt tablets.
- 94. Maintenance therapy Unless the SIADH is reversible (e.g., postoperative or due to a drug that can be discontinued), effective therapy of symptomatic hyponatremia must be followed by maintenance therapy to prevent a subsequent reduction in serum Na+ and possible symptom recurrence. One or more therapeutic modalities may be required. The usual sequence of maintenance therapy is as follows: Fluid restriction The suggested goal fluid intake in hyponatremic patients with SIADH is <800 mL/day. An important exception is patients with a recent SAH in whom fluid restriction can be deleterious. Oral salt – In patients with SIADH, administering oral salt will increase the urine output; the usual initial dose is 3 g or one-half teaspoon three times daily, resulting in a total dose of 9 g per day. Since sodium handling is normal and the urine osmolality is relatively fixed in SIADH, increasing oral salt intake will, in a dose-dependent fashion, increase the urine volume. Reduce the urine osmolality to increase urinary water excretion by impairing the mechanism of urinary concentration. can be achieved by loop diuretic therapy (e.g., furosemide 20 mg orally twice a day).
- 95. Goal of serum sodium 130 mEq/L or higher in patients with SIADH b/c of the possible presence of subtle neurologic manifestations and falls when the serum Na+ is b/n 120 and 129 mEq/L. serum Na+ of 130 mEq/L or higher can be attained in almost all patients with SIADH with: fluid restriction, oral salt tablets alone or a loop diuretic, and, Urea – If necessary and where available.
- 96. Nursing Intervention Monitoring neurologic status closely and protect the patient from harm. Institute seizure precautions as necessary. Monitoring respiratory status closely. Monitoring closely for signs of: hypernatremia, fluid overload, and heart failure. Assess cardiovascular and respiratory functions closely to evaluate the effects of the excess volume on these systems. Right and left ventricular volumes may increase, causing heart failure. Indicators of fluid overload and impending heart failure are: Tachypnea, reports of SOB, and fine crackles Provide for patient comfort with limited fluid intake. Provide for frequent mouth care. Explain why fluid is being restricted and allow the patient to develop the schedule for allotted fluid intake. If the patient complains of nausea, administer an antiemetic prior to meals.
- 97. Summary Choice of therapy Varies: with the severity of hyponatremia and the presence or absence of symptoms. Management of SIADH: eliminate cause, fluid restriction, give diuretics (Lasix), monitor in put and out put daily wt., Restoration of electrolytes must be gradual May use 3% NaCl in conjunction with Lasix
- 98. The END