प्राणापान व्यानोदान समाना भवत्यसौ प्राणः
स्वयमेव वत्तृ ि भेदत,् त्तवकृत्तत भेदात् सवु णण सत्तिित्तमव
ప్ర
ా ణాప్రన వ్యానోదాన సమానా భవత్ాసౌ ప్ర
ా ణః
సవయమేవ వృత్తి భేదాత్, వికృత్త భేదాత్ సువర్ణ సలిలమివ
ப்ராணாபாந வ்யான ாதாந ஸமா ா பவத்யஸஸௌ ப்ராணஃ
ஸ்வயனமவ வ்ட்ற்த்தி னபதாத், விக்ட்ற்தி னபதாத் ஸுவர்ண ஸலிலமிவ
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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%)
Plasma (2.5 L)
Interstitial
Intracellular
Cytoplasm
Source
Qty. in liters
Approximate Input per day
2.4
Water drunk as fluid
1.5
Water content of food we eat
0.5
Water from biological oxidation
0.4
Approximate Output per day
2.4
Urine
1.5
Perspiration
0.4
Loss in breath
0.4
Fecal loss
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% 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)
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•
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•
•
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•
•
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
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