प्रा�णा�पा�न व्या�न�दा�न समा�न� भवत्यस� प्रा�णा�

स्वयमा�व व�त्ति� भ�दात्�, विवकृ� वित् भ�दा�त्� स�वणा� सलि��मिमाव

ప్రా� ణాప్రాన వ్యా�నోదాన సమానా భవత్య�సౌ ప్రా� ణః�

స�యమేవ వ�త్తి� భేదాత్, వికృ�త్తి భేదాత్ స�వర్ణ సలిలమివப்ரா�ணா�பா�ந வ்யா�னோ��தா�ந ஸமா��� பாவத்யாஸௌஸ� ப்ரா�ணாஃ

ஸ்வயானோமாவ வ்ட்ற்த்தா� னோபாதா�த், வ�க்ட்ற்தா� னோபாதா�த் ஸ�வர்ணா ஸலிலமா�வ

– Praana Respiration– Apana Digestion and UT (excretory)– Vyana Circulation (CVS)– Udaana Nervous System (Motor,

Sensory)– Samaana 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 LaureateNobel Prize in

Chemistry 2003

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% H20 is reabsorbed in PCT by AQP1

• Rest 29% by AQP 2, 3 and 4

• Reabsorption of H20 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. Psychological– 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

• V2 Vasopressin Receptor Mutations

• 180+ Mutations are documented

• In Chromosome region Xq28

• Protein misfolding – V2 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

• 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