COMPOSITION OF BODY FLUID COMPARTMENTS COMPOSITION OF ECF AND ICF ECFICF Na14110 K Cl1133 HCO PHOSPHATE2.0140(ORGANIC)
TOTAL BODY WATER= 0.6 X TOTAL BODY WEIGHT (0.5 IN THE ELDERLY OR OBESE, 0.7 IN INFANTS AND VERY YOUNG CHILDREN) 2/3 ICF1/3 ECF ¼ IVV ¾ ISV
CLINICAL APPROACH TO HYPONATREMIA zIS HYPONATREMIA REALLY HYPOTONICITY? yTranslocational vs. isotonic zWHAT IS THE VOLUME STATUS? yWhat are the physiological signals to the kidney and the brain zWHAT IS THE URINE SODIUM AND OSMOLALITY? yIs ADH present and is it physiologically appropriate
CASE STUDY 1 CASE STUDY 1 A 30 year old woman is admitted for an increase in edema and worsening jaundice. She is a known alcoholic and has had several admissions for jaundice and ascites. She stopped taking her diuretic approximately 10 days ago. Physical examination: blood pressure 128/80, heart rate 76 supine. No orthostatic change in BP noted. She has icteric sclera, ascites, sacral and pedal edema. Her liver span is 10 cm. Labs: bilirubin= 12mg/dL 80albumin= 2.5 g/Dl U Na = 1mEq/L Uosm= 300mOsm/kg H 2 O What is her Posm? What is her cell size?
CASE STUDY 1 z What is her effective arterial volume? y mild volume depletion( 4%) x history x change in body weight x no orthostatic changes BP or pulse y moderate volume depletion( 5% to 10%) x HR 15/min on standing x systolic BP 15mm Hg on standing y severe volume depletion( 10%) x supine hypotension x supine tachycardia
CASE STUDY 1 z Is her total body water high, low or normal? z Is her total body sodium high, low or normal?
NOT! NOT! NOT! EDEMA=INCREASED TOTAL BODY SODIUM AND WATER BUT DOES NOT! NOT! NOT! TELL YOU THE PROPORTIONS (SODIUM CONCENTRATION) NOT! NOT! NOT! ORTHOSTATIC HYPOTENSION= DECREASED TOTAL BODY SODIUM AND WATER BUT DOES NOT! NOT! NOT! TELL YOU THE PROPORTIONS (SODIUM CONCENTRATION)
BODY COMPARTMENT VOLUMES z 70 kg person 0.6 =42 liters total body water z 25 liters intracellular (ICF)-3/5 TBW 28 liters intracellular (ICF)-2/3 TBW z 17 liters extracellular (ECF)-2/5 TBW 14 liters extracellular (ECF)-13 TBW z 3.5 liters intravascular (IVV)-1/5 ECF 3.5 liters intravascular (IVV)-1/4 ECF z 13.5 liters interstitial (ISV)-4/5 ECF 10.5 liters interstitial (ISV)-3/4 ECF
PRINCIPAL SENSORS IN VOLUME REGULATION EFFECTIVE CIRC VOL / VENOUS RETURN / / CARDIAC OUTPUT / BP BARORECEPTOR STIMULATION / / SYMPATHETIC TONE VENOUS CONSTRICTION/ RELAXATION / CARDIAC CONTRACTILITY ARTERIAL CONSTRICTION or RELAXATION / RENIN SECRETION / TUBULAR Na + REABSORPTION / A II / ALDO
CASE STUDY 1 z Can you tell if ADH is being secreted? How? z Why is her ADH status the way it is? y What turns ADH off? y What turns it on?
CONTROL OF ADH ALL NONE ADH P OSM U OSM
CASE STUDY 1 CASE STUDY 1 A 30 year old woman is admitted for an increase in edema and worsening jaundice. She is a known alcoholic and has had several admissions for jaundice and ascites. She stopped taking her diuretic approximately 10 days ago. Physical examination: blood pressure 128/80, heart rate 76 supine. No orthostatic change in BP noted. She has icteric sclera, ascites, sacral and pedal edema. Her liver span is 10 cm. Labs: bilirubin= 12mg/dL 80albumin= 2.5 g/dL U Na = 1mEq/L Uosm= 300mOsm/kg H 2 O
CASE STUDY 1 z Which IV fluids would you select?
CASE STUDY 1 z What diuretic(s) would you use? z What would be the most likely or severe complications using diuretics in her case?
CASE STUDY 1 CLARISSA’S TEAM HAVE BEEN WORKING ON HER FOR THE LAST WEEK. WITH ‘JUDICIOUS’ USE OF DIURETICS AND FLUID RESTRICTION, THEY HAVE DROPPED HER WEIGHT BY 12 LBS AND INCREASED HER SODIUM BY 5 MEQ/L. THE ON-CALL CHECK- OUT TO YOU IS “DON’T WORRY ABOUT HER.” AT 2 AM YOU ARE CALLED BY THE NURSE BECAUSE CLARISSA’S BP IS 80/60 AND HER HR IS 110/MIN. WHAT DO YOU DO?
CASE STUDY 1 1.DON’T WORRY ABOUT IT. 2.START AN IV OF NS AT 150CC/HR 3.BOLUS HER WITH NS IN 100CC INCREMENTS UNTIL HER BP INCREASES 4.GIVE 25 GRAMS OF ALBUMIN IVPB 5.START DOPAMINE
A patient with severe congestive heart failure and massive edema is admitted to the hospital complaining of progressive dyspnea. Laboratory values CASE STUDY 2 What is his Posm? What is his cell size?
1-Spironolactone is administered but no diuresis occurs despite 2 days of treatment. Why? 2-A thiazide diuretic is then added to spironolactone with equally discouraging results. Why? 3-What single diuretic might result in successful diuresis? Why? CASE STUDY 2
CASE STUDY 2 zA loop diuretic is given with better results but still not impressive diuresis zWhat diuretic might you add to the loop diuretic to increase the loop diuretic potency?
A 60 year old man was evaluated for persistent cough and a 25 pound weight loss over a 3 month period. He smoked a pack a day for 40 years. P.E.: BP sitting 110/70, no signs of dehydration and no evidence of edema. A pleural effusion is present on the right. PPD was positive. Weight 65 kg. CASE STUDY 3
CASE STUDY P osm 245 mOsm/kg H 2 O U osm 340 mOsm/kg H 2 O U Na 39 mEq/L
In order to get rid of a water load, one needs to produce very dilute urine. What are the requirements for such urinary dilution? 1)Extrarenal requirements adequate GFR adequate solute delivery 2)Intrarenal requirements intact vasa recta and loop function absence of ADH
CAUSES OF SIADH z Carcinomas (lung, pancreas, duodenum) z Pulmonary disease(pneumonia, Tb, abscess, etc.) zCNS disorders (meningitis, encephalitis, SDH, SAH, CVA, trauma, etc)
CASE STUDY 4 A 40 year old man is brought to the ER by EMS after a witnessed seizure. His family states that he has been complaining of a severe headache and has had progressive mental deterioration over the last week or 10 days. They say he takes no medications and has no significant medical history. Physical exam is completely negative except for meningeal signs. There is no focal neurological deficit, no papilledema. He weighs 60 kg. Labs:11080Uosm=275mOsm/kg U Na =50 mEq/L 3.522CSF: 100WBC: 75%mononuclear
CASE STUDY 5 z Is ADH present? (hint: look at U osm ) z Why is this man hyponatremic?
(present TBW) (present S Na ) =present TBS (normal TBW) (normal S Na ) =normal TBS (0.6)(60kg) x (110) = (???) x (140) (36L)(110)/(140) = (???) = 28L 8 liters excess water 36 – 28 = 8 liters excess water
SYMPTOMS OF HYPONATREMIA zMainly neurologic y Symptoms of cerebral edema x Nausea and malaise xfollowed by headache, lethargy, obtundation, seizures, coma and death z The rate at which the hyponatremia develops determines the degree and severity of the symptoms y Several protective responses which act to minimize cell swelling y Within four hours of hyponatremia developing the cells start to lose solutes & as intracellular solute amount decreases, water moves back out of the cells, returning the cell volumes toward normal
CASE STUDY 5 z How would you treat this man? y For rapid correction of symptomatic euvolemic hyponatremia, hypertonic (3%) saline is used y Hypertonic (3%) saline has about 0.5mEq/ml. ( 500mEq/L) z What are your goals and end points? y Goal for rapid/initial S Na is to increase S Na to mEq/L or until symptoms improve- whichever is lower y Overly rapid correction of hyponatremia can lead to an osmotic demylination state y Patients should have plasma serum sodium concentrations increased at less than 12 mEq/L/day (0.5mEq/L/hr)
The amount of sodium needed to raise the serum sodium can be estimated by the sodium deficit. Multiply the total body water (0.5xlean body weight in kg in women, 0.6x weight in men) by the plasma sodium deficit per liter. 540 mEq Na need 36L x 15 mEq/L = 540 mEq Na need At <0.5mEq/L/hour need to change over 30 hours 30 mL/hour 1000mL/30hours 30 mL/hour
CASE STUDY 6 A 30 year old man comes in complaining of polyuria and polydipsia for the previous two weeks. He has a history of sarcoidosis diagnosed 10 years ago for which he has been on Prednisone intermittently. Except for bilateral pulmonary crepitants and for uveitis, the physical exam is normal. Labs: U/A: neg glucose, acetone Uosm=75 mOsm/kg H 2 O
What are the causes of polyuria? 1.Diabetes mellitus 2.Diabetes insipidus 3.Hypokalemia 4.Hypercalcemia 5.Psychogenic water drinking
HYPERNATREMIA VOLUME CONTRACTED EUVOLEMIC VOLUME EXPANDED BY DEFINITION, HYPERNATREMIA IS A HYPERTONIC STATE. YOU STILL DON’T KNOW THE VOLUME STATUS WITHOUT EXAMINING THE PATIENT. IN A VOLUME CONTRACTED STATE, WATER AND SODIUM ARE LOST-JUST MORE WATER THAN SODIUM. IN AN APPARENTLY EUVOLEMIC PATIENT, PURE WATER IS LOST. THERE ARE FEW SIGNS OF VOLUME DEPLETION AS MOST OF THE WATER LOSS IS INTRACELLULAR. VOLUME EXPANDED STATES ARE THOSE IN WHICH HYPERTONIC VOLUME EXPANSION TAKES PLACE.
CENTRAL DIABETES INSIPIDUS: Idiopathic Trauma Hypoxic encephalopathy Posthypophysectomy Neoplastic1 :craniopharyngioma, pinealoma, cyst metastatic: breast, lung Misc: sarcoidosis, aneurysm, Histiocytosis X, encephalitis, meningitis NEPHROGENIC DIABETES INSIPIDUS: Hereditary: usually X-linked, very rare AR form Drugs:lithium, cidofovir, foscarnet Electrolyte disorders: hypokalemia, hypercalcemia Misc: sickle cell anemia or trait, renal amyloidosis, Sjögren’s syndrome, transient DI in pregnancy
DIABETES INSIPIDUS THERAPY z DDAVP y a 2 amino acid substitute of ADH with potent antidiuretic effect but little to no pressor effects z Mild volume depletion(1-2 kg), a low salt diet and a thiazide diuretic y increases proximal sodium and water resorption and decreases water delivery to the ADH sensitive collecting tubule z Don ’ t use loop diuretics y induce a relative resistance to ADH by decreasing the maximal interstitial concentration z NSAIDs y potentiate ADH and are additive to the thiazide effect(renal prostaglandins oppose ADH effects)
A 78 year old woman was admitted with right hemiparesis. She had a 9 year history of hypertension. PE: Her BP was 190/95 mm Hg. Pulse 80 beats per min. CASE STUDY 7
LABS: Hct 40%. Urine: SpGr 1.025, negative for protein and glucose. Sediment: Occasional WBC and RBC. BUN 17, Creat. 1.0 mg/dl. Glucose 140 mg/dL, Na 140 mEq/L, K 3.7 mEq/L, CO 2 24 mEq/L and Cl 103 mEq/L. After admission she was managed with tube feedings and eventually transferred to a nursing home.
Three weeks later she was readmitted because of vomiting and tachypnea. PE: Wt. 67 kg., BP 115/80. P=120, Temp. = F. She was unresponsive and had poor skin turgor. LABS Urine: SpGr 1.022, protein 1+, glucose neg. Sediment: Few hyaline casts. BUN 120 mg/dl, creatinine 3 mg/dl, glucose 150 mg/dL, Na 160 mEq/L, K 5.9 mEq/L, Cl 125 mEq/L, CO 2 18 mEq/L. Hct 48%.
Is total body sodium increased, normal or decreased? It total body water increased, normal or decreased? How did this occur? CASE STUDY 7
Is total body water increased, normal or decreased? poor skin turgor Water Sodium NormalOur patient Is total body sodium increased, normal or decreased? BP 115/80 P=120
How did this occur? Loss of sodium and water-more water than sodium Water losses: insensible (temp 101 F), urine ( conc.), GI Sodium losses: poor intake and vomiting
THE TRAGEDY OF THE VERY YOUNG & VERY OLD zMobile people lose salt and water (N/V) but as IVV , ADH and they become thirsty/seek out fluids. y fluid intake with ADH present can lead to hyponatremia zNon-mobile people (playpens, restraints, strokes) cannot respond to thirst yif they lose more water than sodium, they become hypernatremic
CASE STUDY 7 z What is the first priority in her therapy? y IVV resuscitation z What IV would you first order? y 0.9% NaCl z How much would you give? y Until she is better
CASE STUDY 7 z Once she has a stable blood pressure, her total body sodium (TBS) has been returned to normal z How much water would be needed to lower her serum sodium to 140 mEq/L?
PE: Wt. 67 kg. LABS: BUN 120 mg/dl, creatinine 3mg/dl, glucose 150 mg/dL, Na 160 mEq/L, K 5.9 mEq/L, Cl 125 mEq/L, CO 2 18 mEq/L. 67kg x.5=33.5L=TBW 160 x 33.5=140 x desired TBW desired TBW=38 liters She needs 4.5 liters of water to drop her serum Na to 140 mEq/L
Rates of correction should be carefully controlled as cerebral edema can occur with over-rapid corrections. Correcting at less than 0.5mEq/L/hr (12 mEq/day) is safe. TREATMENT OF HYPERNATREMIA Eg: 5 liters of water need to be given to replace the water deficit. Serum sodium 165 140mEq/L 25mEq/L This will take 50 hours to drop it less than or equal to 0.5 mEq/hour 5000mL/50hours = 100 mL/hour of D 5 W or 200 mL/hour of D 2 1/2NS