POLYURIA, POLYDIPSIA, POLYPHAGIA- LECTURE 3 POLYURIA DEFINITION: Polyutia isa clinical condition characterized by a urine output that i ‘nappropriately high (more than 3 Lin 24 h) forthe patient's blood pressure ard plasma sodium levels, CLASSIFICATION From a pathophysiological point of view, itis classified into two types i; __ Polyuria due toa greater excretion of solutes (urine osmolality >300 mOsm/L) he toan inability to increase solute concentration (urine osmolality <150 mOsm/L), Sometimes both mechanisms ean coexist (urine osmolality 150-300 mOsm/L). Folyuria isa diagnostic challenge and its proper treatment requires an evaluation of the medical record, determination of urine osmolality, estimation of fe water de, ance, use of water deprivation tests in aqueous polyuria, and measurement of electrolytes in blood and urine in the ease of osmotic polyuria, Differen I Diagnosis of Potyuria ; it Secretion of ADH (Central Diabetes Insipidus (D1)) Central diabetes insipidus (DI) may be secondary to lesions of the hypothalamicrpituitary axis and includes the following: 7 [iopathic: often familial and the most common form, + Surgery or irradiation to the pituitary gland, + Trauma: especially head injury. {Malignancy (eg. eraniopharyngioma, pinéaloma, glioma, and secondary depesits). + Anorexia nervosa, + Ischemia, + _ Infections (c.g., meningitis and pneumonia) +, Infltrtions (e.g, sarcoid and histiocytosis X). 2. Inhibition of ADH release [his leads to increased thirst and thus polydipsia. Examples include sychogenic DI and lesions affecting the thirst center. 5, Inability of the kidney to respond to ADH (Nephrogenie Diabetes Insipidus (D1) This is nephrogenic DI and may be congenital or acquired, The familial form is due toa primary renal tubular defect, jie secondary defect may be due to an inability to maintain enal medullary hyperosmolality and includes: + clectrolyte imbalances such as hypercaloemia and hypokalemia, + lithium toxicity + longstanding pyelonephritis longstanding hypdronephrosis renal papillary necrosis (analgesic nephropathy)=o Classifation of Diabetes ispidus Cass Acquistion | Pathophysiology Central or Congenital | Structural malformations affecting the ‘neurogenic hypothalamus or pituitary diabetes ‘Autosomal dominant (or rarely recessive) mutations insipidus Inthe gene encoding AVP-NPI precursor protein Acquired Primary tumors (caniopharyngioa) or metastases Infection (eg, mening encephalitis) Histiocytoss and granulomatous eseases Trauma Surgery I Idiopathic Feeesenc | Congenital [Xk ncating mutans AVPRD gene dabetes Autosomal recessive of dominant mutations in insipidus 40P-2 gene ‘Acquired | Primary renal esease Obstructive uropathy Metabole causes, hypokaemia, hypercalcemia) Sic cel disease Drugs (e lthiun, demeloylne) Acquired | Pychogenic ness characterized by exesive sia or dipsagenic ‘lid intake. Treatments almed atthe pschiatie abetesinspits| | dea Source :Tintnalis Emergency Meticine A Comprehensie Study Gulde_&th Classification of Diabetes Insipidus 4. Chronic Renal Failure Chronic renal failure may occur as a result ofthe depressed ability of the kidneys to {Concentrate urine. The volume of urine may therefore increase to excrete the same osmrotic load. 5. Acute Renal Failure Polyuria occurs in the diuretic phase of acute renal failure an in postobstructive uropathy. Osmotie Diuresis Incomplete reabsorption in the tubules of substances in the glomerular filtrate leads to ‘osmotic diuresis, i., increased solute per nephron. This occurs with: + glucose in diabetes mellitus (DM) + hypercalcemia in chronic renal failure + intravenous infusion with hypertonic solutions (mannitol) 7. Other Causes + Drugs (e.g, lithium carbonate, diuretics, amphoterecin B) + Psychogenic polydipsia (e.g., schizophrenia) + Excessive hypertonic fluid intakeEVALUATION OF POLYURIA POLYURIA (>3 L/24 h) Urine osmolality > 300 mosmol, Solute diuresis Glucose, mannitol, radiocontrast, urea (from high protein ‘Water feeding), History, low deprivation Medullary cystic. ear teccion Meee diseases, resolving ATN, ‘ADH level or obstruction, diuretics Diabetes insipidus (D!) Central DI (vasopressin-sensitive) posthypophysectomy, trauma, Supra: or intrasellar tumor / cyst histiocystosis or granuloma, encroachment by aneurysm, Sheehan's syndrome, infection, Guillain-Barré, fat embolus, empty sella Primary polydipsia Psychogenic Hypothalamic disease Drugs (thioridazine, chlorpromazine, anticholinergic agents) Nephrogenic DI (vasopressin-insensitive) Acquired tubular diseases: pyelonephritis, analgesic nephropathy, multiple myeloma, amyloidosis, obstruction, sarcoidosis, hypercalcemia, hypokalemia, Sjégren’s syndrome, sickle cell anemia Drugs or toxins: lithium, demeclocycline, methoxyflurane, ethanol, diphenylhydantoin, propoxyphene, amphotericin Congenital: hereditary, polycystic or medullary cystic disease Approach to the patient with polyuria. ADH, antidi- uretic hormone; ATN, acute tubular necrosis. ‘Source = Harrison's Principles of Internal Medicine (19th Ed)History in a Patient with Polyuria or Polydipsia Afler asking general questions, focus on suspected causes. The following should be ascertained: * Differentiate between polyuria (an increase in urine production) and frequency (the frequent passage of small amounts of urine), * eight loss: think of diabetes; malignancies (especially ofthe brain-does the patient have headaches?); myeloma leading to renal failure; ectopic production. of adienocorticotrophic hormone (ACTH); and bony metastases. Look for signs of anorexia nervosa (<15% of ideal body weight). + General features of infection: a history of recurrent infection should suggest diabetes, * Psychiatric symptoms: especially if thirst appears to dominate the picture, patients may resent investigations, especially a water deprivation test, and may drink surreptitiously. ‘There may be an inconsistency or variation in the severity of the symptoms, and an absence of nocturnal symptoms, There may also be other neurotic symptoms, + Symptoms of renal failure: such as hematuria, nausea and vomiting; likely precipitating factors. + Ifrenal failure is suspected, consider associated systemic conditions, such as collagenoses (c.g,, systemic lupus erythematosus and polyarteritis nodosa), gout, subacute bacterial endocarditis, amyloid, Wegener's granulomatosis, and Goodpasture’s syndrome. + Hypercalcemia: produces symptoms of nausea, vomiting, constipation, abdominal pain, and, if severe, confusion and coma. + Hypokalemia: leads to muscle weakness and paralysis. + Drug history: analgesic abuse may cause renal papillary necrosis lithium may cause _ nephrogenic DI; vitamin D or milk-alkali syndrome may lead to hypercalcemia; steroids and nephrotoxic drugs. a + History of head injury or childhood meningitis? F + History of hypertension? If so, suspect hypertensive renal disease. + Family history (c.g, in DI, DM, and nephrogenic DI).POLYPHAGIA (HYPERPHAGIA) Polyphagia (hy of this feelin, some cases, \yperphagia) isa feeling of ext 1B May or may not lead to extreme, insatiable hun weight gain dependin; ssociated with unexplained weightloss =" UMdel¥ing cus. In ier. Excess eating as a result AETIOLOGY 1. Diabetes mellitus, P of Diabetes: Polyphagi assage of large v. “olyphagia is one of the main three of di i sia (extreme hunger), Polydipsia z eee oe (extreme thirst), Polyuria (fiequent 2. Hyperthyroidism 3. Depression. progesterone and decreased level of serotonin 6. Insulinoma: This is a rare tumor that forms in the endoctine cells inthe Pancreas. The {amor causes the pancreas to release excess insulin, which results in recurrent hyposlyeemia Polyphagia may also be a symptom of the following rare conditions: |. Prader-Willi syndrome (PWS): This is a rare genetic condition that affects a child's metabolism and causes changes in the child's appearance and behavior. At the age of 2 years, children with PWS develop polyphagia, resulting in weight gain 2. Kleine-Levin syndrome: This is an extremely rare condition that eauses intermittent episodes where you sleep for long periods of time. These episode: including polyphagia, ANHIDROSIS, HYPERHIDROSIS AND GUSTATORY SWEATING-Iecture 4 ANHIDROSIS Anhidrosisf defined asthe inability to sweat. titinaly important o EE ty it --threatening due to heat-related illne idrosis as it can be potentially life-threatening d ea neuroeccrine mediator thus, anhidrosis is one of the clinical hallmarks of acute anticholinergic toxicity.include: | Peripheral alterations in the ecorine gland itself 2. Idiopathic, 3. Central oF neuropathic disease Tests of centraVneuropathic anhidtosis ean occu isturbance can occur at the sweating center in brain, the descending neural tac, or the Sweat gland. A disruption will lead to an absenoe of ‘sweating. Disruption inthe neural input fumes pa ters or infarctions ofthe hypothalanies eee ‘medulla. Spinal cord ‘umors, injuries, or infarctions ean disrupt the neural tae Other etiologies such as degenerative syndromes (Shy-Drager syndrome), autoinmune drugs nes neuropathy, peripheral neuropathy (diabetes aechol es disorder, leprosy), and rugs have al been implicated in central/neuropathie anhidrosis, HISTORY in a patient with anhidrosis ‘A detailed history is important in establishing the diagnosis. Het i Growsiness, episodic inability to concentrate while in a hot oncionn with @ decrease in the patient's normal sweating, which are elues te he diagnosis of Such as injuries, growths or radiation, alcohol consumption, the presence of autoimmune disease or diabetes mellitus, and family history. Drug history Drugs that interfere with the ‘synaptic transmission in the autonomic ganglia will leed to anhidrosis. + Nicotinic acetylcholine feceptor antagonists such as hexamethonium and trimethaphan + Muscarinic acetylcholine receptor antagonists such as atropine or scopolamine * Calcium channel blockers + Alpha-adrenergie blockers such as phentolamine + Alpha2-adrenergic agonists such as clonidine + S-fluorouracil = TopiramateHypethtsis is sweating ine ‘ is sweating in exces ofthat eid for no hyperhidrosis is a dematologi and neursioge ese ofthe ra ns Hyperion cholinergic sudomotor nerves. : mal thermoregulation. Essential laracterized by excessive sweating sed activity of the sympathetic Patients note excessive sweatin attention, Palmoplantar hyperhidrosis (excessive Persons with chronic alcoholism, : Localized hyperhidrosis, unlike adolescence. 8 in affected areas, which ultimately prompts medical ‘Sweating of the palms and sole) is observedin Seneralized hyperhidrosis, usually begins in childhcod or Hyperhidrosis beginning later in life should prompt a search for secondary causes i-systemie diseases eg diabetes mellitus, hyperthyroidism, and hyperpituitarism, pheochromocytoma, peripheral nerve injury, Parkinson disease, reflex sympathetic dystrophy, spinal injury, and Amold-Chiati malformation ii, adverse effects of medication use such as: .Cholinesterase inhibitors eg donepezil, tarine,galantamine, agents causing ‘organophosphorus poisoning (insecticides) ete bSSRIs ; fluoxetine, paroxetine ete ©. Tricyclic antidepressants eg amitryptlline d. opiods ii, psychiatric disease : Harlequin syndrome is characterized by unilateral hyperhidrosis and flushing, predoninanty ' induced by heat or exercise. The sympathetic deficits are usually limited to the face DIAGNOSIS OF HYPERHIDROSIS. Diagnostic criteria required for primary hyperhidrosis include excessive sweating of 6 months or more in duration, with 4 or more of the following: i.primarty involving eccine- dense (axillae/palms/soles/craniofacial sites; i-bilateral and symmett iihabsent nocturnally; ivepisodes at least weekly; v.onset at age 25 years or younger; v.positive family history; vi. and impairment of daily activities. ComplicationsSevere cases of hyperhidr may adversely affect the patient's quality of ite by causing reat emotional distress, social embarrassment, and work-related disability (due vo balmoplantar hyperhidrosis). It may also be linked with depressive symptoms. Palmoplantar sweating may result in irritation of the affected ski, ultimately Teacing to chafing, Axillary hyperhidrosis may be malodorous, causing social embarrassment