4. BODY FLUID COMPOSITION
• ECF- composition of plasma and interstitial
fluids differs only slightly
- principal cation- Na+
- principal anion- Cl-, HCO3
-
• ICF- principal cations- K+, Mg+2
- principal anions- organic phosphate esters
(ATP, creatinine phosphate, phospholipids) and
proteins
2/16/2023 4
6. Composition of GI Secretions
Type of
Secretion
Volume
(mL/24 h)
Na (mEq/L) K (mEq/L) Cl (mEq/L) HCO3
–
(mEq/L)
Stomach 1000–2000 60–90 10–30 100–130 0
Small
intestine
2000–3000 120–140 5–10 90–120 30–40
Colon — 60 30 40 0
Pancreas 600–800 135–145 5–10 70–90 95–115
Bile 300–800 135–145 5–10 90–110 30–40
2/16/2023 6
7. FLUID MOVEMENT
• Fluid movement between plasma and
interstitial space depends on Starling forces
(hydraulic and colloid osmotic or oncotic
pressure)
• Fluid movement between ECF and ICF
depends on osmolality. An isotonic change in
volume in either one of the compartments is
not accompanied by the net movement of
water
2/16/2023 7
8. FLUID MOVEMENT ctd
- Total osmolality= effective + ineffective osmolality
- Effective osmolality- determined by solutes
restricted to their compartment.
- is equivalent to tonicity
- ECF - Na+, glucose, mannitol, glycine
- ICF - K+, amino acids, organic acids
- Ineffective osmoles- move freely between
compartments and don’t affect the water shift
- urea, ethanol, and methanol
2/16/2023 8
10. CLASSIFICATION OF BODY FLUID CHANGES
• Volume
• Concentration
• Composition
2/16/2023 10
11. Sodium Balance
• Total body sodium ~ 5000 mmol, of which 44% is in
the extracellular fluid, 9% in the intracellular fluid
and the remaining 47% in bone
• Normal plasma level= 135-145 mEq/L
• Intake
- Average consumption/day= 3-5 g of NaCl (130
to 217 mmol Na+)/day
- Results in ECF expansion and renal excretion
• Excretion
- Renal tubule reabsorption is the major
regulatory mechanism (not GFR)
2/16/2023 11
12. Tubular reabsorption
- 2/3 in proximal
convoluted tubule
- 25-30% in thick
ascending limb of
loop of Henle
- 5% in distal
convoluted tubule
- The rest in cortical
and medullary
collecting ducts
2/16/2023 12
13. Sodium Balance CTD…
• The output of sodium via urine and sweat is under the
control of the adrenal corticoids, the most powerful
conservator of sodium being aldosterone.
The sodium excretion shut down of trauma
• Following trauma/surgery there is a variable period of
reduced excretion of sodium (up to 48 hrs) due to increased
adrenocortical activity.
2/16/2023 13
14. HYPONATREMIA
- The commonest electrolyte abnormality in hospitalized
patients (up to 20%)
- A plasma Na+ concentration less than 135 mmol/L
- Cause:
A) Inadequate intake- reduced dietary or IV
replacement
B) loss of fluid containing sodium – sweat, GIT
(vomiting, diarrhea, fistula, ileus, obstruction),
urine (diuretics, recovery from ARF, lack of
aldosterone)
2/16/2023 14
15. Symptoms and signs
Body System Hyponatremia
Central nervous system Headache, confusion, hyperactive or
hypoactive deep tendon reflexes, seizures,
coma, increased intracranial pressure
Musculoskeletal Weakness, fatigue, muscle cramps/twitching
GI Anorexia, nausea, vomiting, watery diarrhea
Cardiovascular Hypertension and bradycardia if significant
increases in intracranial pressure
Tissue Lacrimation, salivation
Renal Oliguria
2/16/2023 15
16. Management
- Ix : Plasma osmolality will decrease
: Urine osmolality <100mosm/kg and SG <1.003
: Urine Na+ concentration < 20 mmol/l (less)
- Rx: Mild– no Rx
: Moderate (symptomatic)- water restriction, restore
blood volume with isotonic saline.
: Severe (neurological manifestation) – treat with
hypertonic saline with an aim of
correcting 0.5-1mmol/l per hr and a
maximum of 10-12mmol/L/day.
2/16/2023 16
17. HYPERNATREMIA
- Plasma Na+ concentration greater than 145 mmol/L.
- Cause:
A) Loss of water – the physically handicapped,
patients with impaired mental status, in the postop
state, and in intubated patients in the ICU
- renal loss due to drug induced (diuretics),
osmotic diuresis (DM, mannitol, endogenous urea
from high protein diet etc)
B) Excessive gain – excessive N/S given during post op
time
2/16/2023 17
18. Signs and symptoms
Body System Hypernatremia
Central nervous system Restlessness, lethargy, ataxia,
irritability, tonic spasms, delirium,
seizures, coma
Musculoskeletal Weakness
Cardiovascular Tachycardia, hypotension, syncope
Tissue Dry sticky mucous membranes, red
swollen tongue, decreased saliva
and tears
Renal Oliguria
Metabolic Fever
2/16/2023 18
19. Treatment
• The aim is to replace the water deficit and treat
the underlying condition
• Water deficit can be calculated as:
Water deficit(L)= (serum Na-140 )X TBW
140
• Corrected slowly over 48-72 hrs
• Rate of correction- no more than 0.5mmol/L/hr or
12 mmol/L/24 hr
• Aim for a decrease in serum sodium of 1 mEq/L/h
(1 mmol/L/h)
• Safest route is po but if it is not possible 5%D/W
or 0.45%NaCl
2/16/2023 19
20. Potassium Balance
• Serum levels are 3.5-5.0 mEq/L
• More than 98% of the potassium is found in the ICF
• Intake- Daily intake ~ 50-100 mEq/day
• Loss- pushed into cells by insulin and
cathecholamines Na-K ATPase
- excreted in urine
- GI loss- 10% (can increase to 50-60%)
- also affected by serum pH
2/16/2023 20
21. Tubular reabsorption
- 90% in proximal
convoluted tubule and
thick ascending limb of
loop of Henle.
- The rest in distal
convoluted tubule and
cortical collecting duct
- Regulated by aldosterone,
hyperkalemia and urine
flow rate
2/16/2023 21
22. HYPOKALEMIA
- Plasma K+ concentration <3.5 mmol/L
Cause :
A) Inadequate nutritional intake/ inadequate potassium
replacement Rx
B) Increased loss – renal (diuretics, steroid,
hyperaldestorinism, ↓tubular K+ re-absorption), GIT
(intestinal ileus, vomiting, ileostomy, fistula,
diarrhea, villous adenoma of colon)
C) K+ shift from ECF to ICF – insulin, alkalosis
2/16/2023 22
23. Signs and symptoms
System Potassium
GI Ileus, constipation
Neuromuscular Decreased reflexes, fatigue,
weakness, paralysis
Cardiovascular Arrest
ECG- inverted T wave, depressed ST
segment, prolonged PR
2/16/2023 23
24. Treatment
• Correct the deficit and minimize ongoing loss
• Safer to correct it po
• Dextrose containing fluids worsen
hypokalemia.
• KCl- corrects both hypokalemia and alkalosis
• KHCO3 and citrate- in diarrhea or renal tubular
acidosis
• 600 mg KCl tablet = 8 mmol of K+
2/16/2023 24
25. Treatment CTD…
- Asymptomatic, tolerating enteral nutrition:
- KCl 40 mEq per enteral access x 1 dose
- Asymptomatic, not tolerating enteral nutrition:
- KCl 20 mEq IV q2h x 2 doses
- Symptomatic: KCl 20 mEq IV q1h x 4 doses
- Recheck potassium level 2 h after end of infusion
- The rate of administration should not exceed 20 mEq
/hour.
- Hypomagnesemia frequently accompanies
hypokalemia and generally must be corrected to
successfully replenish K+.
2/16/2023 25
26. HYPERKALEMIA
Plasma potassium conc.>5.0mmol/l
Cause:
A) Increase intake - oral, parenteral (massive blood
transfusion, Iv potassium)
B) Reduced excretion – Renal failure, acidosis, drugs
(potassium sparing diuretics, ACE-inhibitors,
NSAID, β-blockers)
C) Shift from ICF to ECF –insulin deficiency,
acidosis, tissue injury (burn, surgery, poly trauma),
haemolysis
2/16/2023 26
27. Signs and symptoms
System Potassium
GI Nausea/vomiting, colic, diarrhea
Neuromuscular Weakness, paralysis, respiratory
failure
Cardiovascular Arrhythmia, arrest
ECG- peaked T waves, prolonged
PR intervals
2/16/2023 27
28. Treatment
• Goals:
- To minimize membrane depolarization
- Shift K + into cells
- Promote K + loss
- Decrease exogenous intake and antikalliuretic
drugs
- Protect cells from effects of increased K +
2/16/2023 28
29. Treatment CTD…
1) Mild hyperkalemia (K+ = 5 to 6 mmol/L)
- Conservative treatment :
- reduction of daily K+ intake
- loop diuretic (e.g., furosemide)
- discontinue any medication that is capable of
impairing K+ homeostasis (e.g., β-adrenergic
antagonists, ACE inhibitors, K+-sparing
diuretics, NSAIDs)
2/16/2023 29
30. Treatment CTD…
2) Severe hyperkalemia (K+ >6.5 mmol/L)
• Temporizing measures
– 10% Calcium gluconate (5 to 10 mL intravenously over
2 minutes) to stabilize the myocardium.
– Dextrose (0.5 g/kg body weight) with insulin (0.3 unit of
regular insulin/g of dextrose). The usual dose is 25 g
dextrose + 6-10 units of regular insulin iv bolus
– NaHCO3 [1 mmol/kg or 1 to 2 ampoules (50 mL each) of
8.4% NaHCO3] can be infused iv over a 3- to 5-minute
period. This dose can be repeated after 10 to 15 minutes
if ECG abnormalities persist.
– Inhaled β-agonists- e.g., albuterol sulfate, 2 to 4 mL of
0.5% solution (10 to 20 mg) delivered via nebulizer
2/16/2023 30
31. Treatment CTD…
• Therapeutic measures
– Sodium polystyrene sulfonate (Kayexalate):
- 20 to 50 g in 100 to 200 mL of 20%
sorbitol po every 4 hours
- 50 g of the resin as a retention enema
in 50 mL of 70% sorbitol added to 100
to 200 mL of water every 1 to 2 hours,
followed by administration every 6 hrs
– Hydration with 0.9% NaCl + loop diuretic +
thiazide diuretic
– Dialysis
2/16/2023 31
32. Calcium Metabolism
• Total body calcium ~ 1-2 kg
• 99% is in the skeleton
• Serum Ca level- 8.5 to 10.5 mEq/L of which 50%
(4.2 to 4.8 mg/dL) is ionized, 40% is bound to
proteins and 10% is complexed to phosphate
and other anions
• Alterations in serum protein affects total blood Ca
while acidosis affects the ionized part
• Controlled by PTH and 1,25(OH)2 D
2/16/2023 32
33. Calcium Metabolism CTD…
• Intake
- 10-37 mmol (400-1500mg/d)
- intestinal absorption actively and passively controlled
by 1,25(OH)2D
- require gastric acid, blunted in pancreatic or biliary
insufficiency
• Loss
- 100-200mg/d through the intestine
- kidneys - regulated by ionized Ca+2
- reabsorption- 65% in PCT, 20% in
TALH, ~10% in DCT
- PTH stimulates absorption from intestine and kidney
• If homeostatic mechanism fails PTH and Vit D activate
osteoclastic bone resorption
2/16/2023 33
34. HYPOCALCEMIA
• serum calcium level <8.5 mEq/L or ionized
calcium level <4.2 mg/dL
• Cause: After thyroid/parathyroid surgery,
hypoproteinemia, acute pancreatitis, Vit-D
deficiency, magnesium deficiency, alkalosis
• The most common cause of low total serum
calcium is hypoalbuminemia
2/16/2023 34
36. Treatment
• Severe, Symptomatic Hypocalcemia
- 10% Ca gluconate (10–20 mL) iv over 10–15
minutes
- followed by 10-15 mg/kg of calcium (6-8 10-
mL vials of 10% calcium gluconate) added to 1
L of D5W and infused over 4–6 hours.
- monitor serum levels frequently
• Asymptomatic Hypocalcemia
- Ca supplements (1000-1500 mg/d elemental
Ca) in divided doses
- Vit D2 or D3 25,000-100,000 IU/day
- Calcitriol 0.25-2 μg/d
2/16/2023 36
37. Hypercalcemia
• Serum Ca + 2> 10.5 mEq/L
• Most common causes are primary
hyperparathyroidism and malignancy-associated
hypercalcemia.
• Hypercalciuria usually precedes hypercalcemia.
• Most often, asymptomatic, mild hypercalcemia (11
mg/dL) is due to primary hyperparathyroidism,
whereas the symptomatic, severe hypercalcemia (14
mg/dL) is due to hypercalcemia of malignancy
2/16/2023 37
38. Signs and symptoms
• Mild hypercalcemia (up to 11-11.5 mg/dl)
- asymptomatic
- vague neuropsychiatric symptoms
- PUD, nephrolithiasis
• More severe (>12-13 mg/dl)
- lethargy, stupor, coma
- nausea, anorexia, constipation, pancreatitis
- polyuria, polydipsia
- bone pain, pathologic fracture
2/16/2023 38
39. Treatment
• Mild, asymptomatic- no immediate therapy
• Symptomatic
- Volume expansion- 4-6 L of N/S iv over 24 hrs
followed by loop diuretics
- Bisphosphonates- in malignancy related
- Zoledronic acid 4 mg iv over 30 min
- Pamidronate 60-90 mg iv over 2-4 hrs
- Etidronate 7.5 mg/kg/day for 3-7 dys
- Glucocorticoids- for Vit D related
- Hydrocortisone 100-300 mg iv/day
- Prednisone 40-60 mg po/day for 3-7 dys
2/16/2023 39
40. ACID-BASE BALANCE
• The pH is maintained in a narrow range (7.35-
7.45)
• Acid-base homeostasis represents equilibrium
among concentration of H+, PCO2, and HCO3
-
• The endogenous acid load is efficiently neutralized
by buffer systems and ultimately excreted by lungs
and kidneys
• Important buffers:
- ICF- proteins and phosphates
- ECF- bicarbonate-carbonic acid system
• Compensations can be by respiratory or metabolic
mechanisms
2/16/2023 40
41. ACID-BASE imBALANCE
• Arterial blood pH normally 7.4
– Acidosis – pH below 7.35
– Alkalosis – pH above 7.45
• Respiratory acidosis and alkalosis
– Disorders resulting from changes in partial pressure of CO2
in arterial blood
• Metabolic acidosis and alkalosis
– Disorders resulting from changes in HCO3
- concentration in
arterial blood
2/16/2023 41
42. Functional anatomy and physiology
of acid–base homeostasis
• A variety of physiological mechanisms maintain the
pH of the ECF. The first is the action of blood and
tissue buffers, of which the most important involves
reaction of H+ ions with bicarbonate to form carbonic
acid, which, under the influence of the enzyme
carbonic anhydrase (c.a.), dissociates to form CO2
and water
2/16/2023 42
43. • Respiratory compensation for acid–base
disturbancescan occur quickly. In response to acid
accumulation, pH changes in the brain stem stimulate
ventilatory drive, serving to reduce the PCO2 and
hence drive up the pH .
• Conversely, systemic alkalosis leads to inhibition of
ventilation (although this is limited because hypoxia
provides an alternative stimulus to ventilation).
2/16/2023 43
44. • The kidney provides a third line of defence against
disturbances of arterial pH. When acid accumulates
due to chronic respiratory or metabolic (non-renal)
causes, the kidney has the long-term capacity to
enhance urinary excretion of acid, effectively
increasing the plasma bicarbonate.
2/16/2023 44
45. • Distal nephron segments have an important role in
determining net acid excretion by the kidney. In the
intercalated cells of the cortical collecting duct and
the outer medullary collecting duct cells, acid is
secreted into the lumen by an H+-ATPase.
• The secreted H+ ions contribute to the reabsorption of
any residual bicarbonate present in the luminal fluid,
but also contribute net acid for removal from the
body, bound to a variety of urinary buffers
2/16/2023 45
46. Metabolic acidosis
Aetiology and assessment
• Metabolic acidosis occurs when an acid other
than carbonic acid (due to CO2 retention)
accumulates in the body, resulting in a fall in
the plasma bicarbonate.
2/16/2023 46
47. • If the kidneys are intact (i.e. not the cause of
the initial disturbance), renal excretion of acid
can be gradually increased over days to weeks,
raising the plasma bicarbonate and hence the
pH towards normal in the new steady state.
2/16/2023 47
49. Metabolic alkalosis
Aetiology and clinical assessment
• Metabolic alkalosis is characterised by an increase in
the plasma bicarbonate concentration and the plasma
pH.
• There is a compensatory rise in PCO2 due to
hypoventilation, but this is limited by the need to
avoid hypoxia.
2/16/2023 49
50. • The causes are best classified by the
accompanying disturbance of ECF volume.
A. Hypovolaemic metabolic alkalosis
is the most common pattern, typified by
disorders such as sustained vomiting in which
acid-rich fluid is lost directly from the body.
2/16/2023 50
51. B. Normovolaemic (or hypervolaemic) metabolic
alkalosis
• occurs when both bicarbonate retention and
volume expansion occur simultaneously.
• Classical causes include corticosteroid excess
states such as primary
hyperaldosteronism,Cushing’s syndrome and
corticosteroid therapy.
• Occasionally, overuse of antacid salts for
treatment of dyspepsia produces a similar pattern.
2/16/2023 51
52. Respiratory acidosis
• Respiratory acidosis occurs when there is
accumulation of CO2 due to reduced effective
alveolar ventilation .
• This results in a rise in thePCO2, with a
compensatory increase in plasma bicarbonate
concentration
2/16/2023 52
53. Respiratory alkalosis
• Respiratory alkalosis develops when there is a period
of sustained hyperventilation resulting in a reduction
of PCO2 and increase in plasma pH.
• If the condition is sustained,renal compensation
occurs such that tubular acid secretion is reduced and
the plasma bicarbonate falls.
2/16/2023 53
54. Treatment
A) Acidosis
- Alkali …reserved for - severe acidemia
- Severe acidosis, pH <7.2
- Monitoring of electrolytes
- Goal of Rx: pH >7.35,Bicarbonate >10mEq/L
- Correction of underlying condition
B) Alkalosis
- Correct underlying stimulus for bicarbonate
generation
- Remove factors that sustain bicarbonate re-
absorption
- Acidification by oral NH4Cl
- Hemodialysis
2/16/2023 54
