प्राणापान व्यानोदान समाना भवत्यसौ प्राणः स्वयमेव वृत्ति भेदत् , त्तवकृत्तत भेदात् सुवणण सत्तिित्तमव

ప్రాణాాన వ్యా నోదాన సమానా భవత్ా సౌ ప్రాణః సవ యమేవ వృత్తి భేదాత్

,

వికృత్త భేదాత్ సువర్ ణ సలిలమివ

ப்ராணாபாந வ்யான ாதாந ஸமா ா பவத்யஸஸௌ ப்ராணஃ ஸ்வயனமவ வ்ட்ற்த்தி னபதாத் , விக்ட்ற்தி னபதாத் ஸுவர்ண ஸலிலமிவ

– Praana – Apana – Vyana – Udaana – Samaana Respiration Digestion and UT (excretory) Circulation (CVS) Nervous System (Motor, Sensory) Equilibrium (Metabolic) These five are the five different life functions in us.

They are so differentiated due to the structural (anatomical) and functional (physiological) differences. Together, they all constitute life, just as the gold is same, though different apparently, in various ornaments.

Prof. Dr. Peter AGRE Nobel Laureate Nobel Prize in Chemistry 2003

Body Water (35 L)

Extra Cellular (60%) Intracellular

Plasma (2.5 L) Interstitial Cytoplasm

Source

Approximate Input per day Water drunk as fluid Water content of food we eat Water from biological oxidation Approximate Output per day Urine Perspiration Loss in breath Fecal loss

Qty. in liters

2.4

1.5

0.5

0.4

2.4

1.5

0.4

0.4

0.1

1. Solute – substance dissolved: Nacl, Glucose 2. Solvent – Liquid in which dissolved - Water 3. Milli Osmoles/ Kilogram (mOsm/kg) of Solvent - referred to as Osmolality 4. Milli Osmoles/ liter (mOsm/L) of Solution referred to as Osmolarity

• Depends on the # of particles in solution • Maintained within very narrow ranges • Sodium is the principal determinant • 2(Na + K) + (Glucose /18) + (BUN /2.8) • 2(132 + 4) + (108/18) + (14/2.8) = • (2 x 136) + 6 + 5 = 272 + 11 = 283

• Anti Diuretic Hormone (ADH) / Vasopressin • AVP is Arginine Vasopressin – In pigs, it is lysine vasopressin • Synthesized & Secreted by the Neurohypophysis – Includes nuclei in the hypothalamus which terminate in the pituitary

Primary Urine • GFR of 120 ml/mt x 60 min x 24 hrs = 170 L Final Urine • Only 1.5 to 2.5 liters/day • 99% of the filtered water is reabsorbed • Only 1% is finally excreted • 70% H 2 0 is reabsorbed in PCT by AQP1 • Rest 29% by AQP 2, 3 and 4 • Reabsorption of H 2 0 in CT – ADH mediated

• •  Volume – Renin secretion  Angiotensin formation – Angiotensin II is a dipsinogen – Angiotensin promotes AVP release  Osmolality – AVP is released – AVP leads to less urine produced – Without AVP, we will have a water diuresis

Schrier, R. W. J Am Soc Nephrol 2006;17:1820-1832

 Complex interactions among       Plasma Osmolality Plasma Volume The Thirst Center The Kidney The Posterior Pituitary (Neurohypophysis) The Hypothalamus.  Dysfunction in any of these areas results in Polyuria (PU) and Polydipsia (PD)

• Cardiac Failure • Cirrhosis, Renal failure • Hyper and Hypothyroidism • Addison’s Disease • Central Diabetes Insipidus (CDI) • Nephrogenic Diabetes Insipidus (NDI) • Psychogenic Polydipsia (PPD or CWD) • Pregnancy

• PU – Passage of Excessive quantity of urine – PU implies water or solute diuresis – At least more than 2.5 to 3.0 L /day – Or Urine of > 40 ml/kg/day [stress, exercise, summer / Winter - < 3L] • Polyuria usually associated with Polydipsia • Polydipsia or PD – – Water intake of more than 100 ml/kg/d (6 L /d) • Frequency of urine – Frequent passage of small amounts of urine – Many causes – UTIs, BPH, UT Stones, Urinary Incontinence

Four mechanisms 1. Increased intake of fluids – Psychogenic, stress, anxiety 2. Increased Glomerular Filtration Rate – Hyperthyroidism, Fever, Hyper metabolism 3. Increased output of solutes – DM, Hyperthyroidism, Hyperparathyroidism – Diuretics – increase the solute at the DCT 4. Inability of the kidney to reabsorb water in DCT – CDI, NDI, Drugs, CRF

• Is it increased volume or frequency ?

• Is there associated Polydipsia ?

• Weight loss – DM, Underlying malignancy • Family history – DM, DI • Past history – Neurosurgery, Meningitis, Head injury, Psychiatric illness – CWD • Drugs – Diuretics, Lithium, Analgesic abuse, Vitamin D – hypercalcemia, Nephrotoxic drugs • Recurrent Infections - DM • H/o HT, CKD, Hypercalcemia, UTO, PKD

1. Endocrine – DM, CDI, Cushing's syndrome 2. Renal – CRF, Relief of UT obstruction, CPN, NDI, Fanconi 3. Iatrogenic – Diuretic therapy, Alcohol, Lithium, Tetracyclines 4. Metabolic – Hypercalcemia, Potassium depletion 5. Psychologica l – PPD or CWD 6. Other causes : Sickle-cell Anemia, PSVT

• Wasting / Cachexia – DM, DI, Malignancy • Skin manifestations – Ca, DM • Nails – Clubbing, CKD nails, Ca Bronchus • Anemia – CKD, Malignancy • Lymph adenopathy – Infiltrative, Malignancy • Fundus exam – DM, HT, Papilledema

• Diabetes Insipidus refers to an abnormal state of water and not osmotic diuresis • DI can be an early sign of serious underlying disease - a brain tumor.

• Abrupt onset of Polyuria and preference for extremely cold or iced water – suggests CDI • Dx of DI is missed - sometimes for years • DI has FOUR main types, namely – CDI, NDI, PDDI, GDI

1. Central DI (Neurogenic) –  of the ADH or AVP 2. Nephrogenic DI , Non response of kidneys to ADH 3. Primary Polydipsic DI - suppression of ADH by excessive fluid intake Dipsogenic , Psychogenic or Iatrogenic DI – excessive water drinking as Rx. 4. Gestagenic DI , during pregnancy due to ADH destruction by vasopressinase from placenta.

Neurogenic • Acquired - Brain tumors; Head trauma; Granulomatous diseases; Autoimmunity; • Inherited - Genetic Mutation of Vasopressin Gene - Autosomal Dominant or Recessive or X-linked Recessive • Idiopathic

• Lack of AVP production and or secretion • May be partial or complete • Usually the urine volume is very high > 8 -10 L • Polydipsia is usually a feature -very troublesome • Any disturbance or injury of the hypothalamus & or pituitary is a potential cause – Idiopathic, Trauma, Neoplasia, Cysts, Inflammation

Schrier, R. W. J Am Soc Nephrol 2006;17:1820-1832

• NDI – Congenital and Acquired • V 2 Vasopressin Receptor Mutations • 180+ Mutations are documented • In Chromosome region Xq28 • Protein misfolding – V 2 Receptor • Not Translocated BLM of CT • 90% of NDI is genetic • 10% Acquired – see next slide

• Hypokalemia and hypercalcemia • Bilateral urinary tract obstruction • Lithium therapy • Acute renal failure • Advanced chronic renal failure • The Polyuria of Acquired NDI is of a moderate degree (3 to 4 L / 24 h)

• Nephrogenic DI commonly occurs at birth • Urinary frequency, Nocturia, Enuresis, and frequent or constant thirst – suspect NDI.

• Thirst and Polyuria can not be verbalized • Inconsolable crying, unusually wet diapers, frequent need to nurse, dry skin with cool extremities, and failure to thrive.

Polydipsic • Acquired • Idiopathic (mostly) • Chronic meningitis; Granulomatous Diseases; Multiple Sclerosis or other diffuse pathology of the brain • Psychiatric illness (CWD or PPD) Gestagenic – Placental Vasopressinase

• Clean, 5 liter, plastic container with 10 ml of acetic acid during normal fluid & food intake • PU is > 40 ml/kg body weight per day • Urine Osmolality < 300 mOsm/kg of water • Urine Specific Gravity <1.010

• PD is water intake of > 100 ml/kg per day • Measure Plasma Sodium on that day

24 Hour Urine Volume (fluids ad libitum) Less than 3 L More than 3 L Measure Urine Osmolality if urine volume is > 3 L < 300 mOsm/Kg > 300 mOsm/Kg If Urine Osmolality is > 300 mOsm/Kg (Solute



) DM Evaluation CKD Evaluation

Urine Osmolality < 300 - Fluid Deprivation 12 hrs > 750 mOsm/Kg < 750 mOsm/Kg Osmolality



> 750 mOsm/Kg – Serum ADH, RF, Na



Na and ADH, RF - N CWD (PPD) Osmolality



> 750 mOsm/Kg – Serum ADH, RF, Na N - Na, ADH, RF - Abn CKD / Renal /



Cal

Osmolality



but < 750 mOsm/Kg – Formal WDT No Response Positive Response No Response to WDT Nephrogenic (NDI) Genetic / Acquired Positive Response to WDT Central (CDI) MRI, evaluate causes

• Indication – Evaluation of Diabetes Insipidus • Technique – Complete Fluid Deprivation or Inj. Hypertonic Nacl – Injection of DDAVP exogenously • Measure ADH to Serum Osmolality ratio – Interpretation of ADH to Serum Osmolality ratio – Decreased ratio in Central Diabetes Insipidus – Increased ratio in Nephrogenic Diabetes Insipidus

Desmopressin (1-desamino-8-D-Arginine Vasopressin)

• Several formulations are available • Intranasal solution - 100 mcg/ml • Intranasal spray (10 mcg/spray) • Parenteral (i.v or i.m) - 4 mcg/ml - used rarely • Oral - 200 mcg tablets (roughly 10 mcg intranasal = 200 mcg oral)

• Circadian Rhythm disorder of AVP • Increase in ANP and BNP • Measurement of plasma AVP and urinary AVP • Urine AVP / Urine Cr ratio is good lab test to pick up NP due to defective AVP

• AVP or ADH from neuro hypophysis • ADH action on CT and DCT – Water reabsorb.

• Renal handling of water – homeostasis - AQP • Polyuria – multiple diseases cause it – DI imp.

• CDI, NDI, PDI, GDI – Congenital, Acquired.

• Algorithmic approach - 24 hr U, U Osmolality, • 12 hr fluid restriction and full WDT – DD of DI • DDAVP replacement in CDI and NDI