The lecture by Dr. Norman Jonas covers the physiology and clinical management of water and electrolyte imbalances, primarily focusing on sodium and potassium disorders. It discusses the pathophysiology, diagnosis, and treatment of conditions such as hyponatremia and hyperkalemia, including the assessment of fluid status and lab tests. Management strategies are outlined based on the severity of symptoms and the patient's volume status.

1. Presenter : Dr Norman Jonas MD
LECTURE IN MEDICINE
WATER AND ELECTROLYTE IMBALANCE

2. OBJECTIVE OF THIS SESSION
At the end of this session; medical students will be able to:
1. Understand basic physiology of water, electrolyte.
2. Understand the pathophysiology, diagnosis, and treatment of water,
electrolyte disorders.

3. BODY WATER AND ELECTROLYTES
ECFV (1/3 TBW) ICFV (2/3 TBW)
Sodium 135-145 mEqlL
Potassium 3.5-5.0 mEqL
Chloride 95-105 mEq/L
Bicarbonate 22-26 mEq1L
Glucose 90-1 20 mg/dl
Calcium 8.5-10.0 mg/dl
Magnesium 1.4-2.1 mEqL
Urea nitrogen 10-20 mg/dl
Sodium 10-20 mEqL
Potassium 130-140 mEqlL
Magnesium 20-30 mEqL
Urea nitrogen 10-20 mgldl
Women: Total body water (TBW) = .5 X Body weight (kg)
Men: Total body water (TBW) = .6 X Body weight (kg)
Intracellular fluid volume = 2/3 TBW
Extracellular fluid volume = 1/3 TBW
Calculated osmolality = 2 X [sodium] + [glucose]ll8 + [Blood Urea Nitrogenll2.8
Osmolal gap = OSM(measured) - OSM(calculated)

4. BODY FLUID COMPARTMENTS
Summary of body fluid regulation, including
the major body fluid compartments and the
membranes that separate these
compartments.
The values shown are for an average 70-
kilogram adult man.
% of fluid distribution between compartment
depends on age, gender, and degree of obesity

5. ELECTROLYTES IN BODY COMPARTMENTS
Major cations and anions of the intracellular and
extracellular fluids. The concentrations of Ca++
and Mg++ represent the sum of these two ions.
The concentrations shown represent the total of
free ions and complexed ions.

6. Nonelectrolytes of the plasma
Osmolar Substances in Extracellular and
Intracellular Fluids

7. OSMOLARITY AND TONICITY
• Osmolality is determined by the total solute concentration in a fluid
compartment
• Tonicity refers to the ability of the combined effect of all of the solutes to
generate an osmotic driving force that causes water movement from one
compartment to another.
• To increase ECF tonicity, a solute must be confined to the extracellular fluid
compartment.
• “effective osmoles”  Solutes capable of causing such movement of water
eg: sodium, glucose, mannitol, and sorbitol.
• The extracellular sodium concentration is the main determinant of plasma
tonicity.

8. HYPONATREMIA
Pseudohyponatremia
• serum sodium concentration is found to be low but extracellular fluid osmolality and
tonicity are normal.
• The low sodium concentration is an artifact due to accumulation of other plasma
constituents (either triglycerides or protein) in plasma.
• Severe hypertriglyceridemia (triglyceride concentrations in the thousands of mgldl)
• Severe hyperproteinemia, as may occur in multiple myeloma (plasma protein concentration > 10 mgldl)
Hypertonic Hyponatremia
Caused by hyperglycemia: The sodium is low because of transcellular shifting of water,
but both tonicity and measured serum osmolality are very high.
• Because glucose is an effective osmole, the high glucose concentration causes water
movement from the intracellular compartment to the extracellular compartment, thereby
reducing the extracellular sodium concentration.
o The sodium concentration falls by approximately 1.6 mEq/L for every increase of 100 mg/dl in
glucose concentration above 100 mg/dl.

9. HYPONATREMIA
Hypotonic Hyponatremia
Hyponatrernia with hypotonicity requires two things:
1. Impaired renal water excretion
2. Continued water intake
The impaired renal water excretion may be due to:
• Impaired GFR (renal failure)
• ECFV depletion (often from vomiting with continued ingestion of water)
• Edematous states: congestive heart failure, cirrhosis, and nephrotic syndrome
• Thiazide diuretics
• Syndrome of inappropriate ADH (SIADH)
• One of two endocrine abnormalities: hypothyroidism or adrenal insufficiency
• Markedly decreased solute intake combined with high water intake ("tea and toast diet" and excessive beer
drinking)

10. HYPOVOLAEMIC Reduced skin
turgor, dry membranes, low BP
or postural hypotension
EUVOLAEMIC HYPERVOLEMIC
Urinary Na
>20mmol/L
Urinary Na
<20 mmol/l
Urinary Na
>20 mmol/l
Urinary Na
<20 mmol/l
Urinary Na
>20 mmol/l
Renal losses -
Osmotic diuresis
- Diuretic
therapy -
Addison’s
disease - Salt-
losing
nephropathy -
Cerebral salt
wasting
Extra-renal
losses -
Diarrhoea -
Vomiting -
Burns - Fistulae
- Pancreatitis
- SIADH -
Secondary
adrenal
insufficiency -
Addison’s
disease (with
secondary ADH
response) -
Hypothyroidism
- Diuretic
therapy - Drugs
- Acute or
chronic renal
failure - Diuretic
therapy for
heart failure
- Nephrotic
syndrome -
Cirrhosis -
Cardiac failure

12. HYPONATREMIA
• HYPONATRAEMIA: SODIUM < 130 MMOL/L SIGNIFICANT.
• Symptoms/signs usually only occur when sodium < 125
mmol/L.
• Acute hyponatraemia is less well tolerated.
• Aetiology is often multifactorial in medical patients.

13. HYPONATREMIA - ASSESMENT
HISTORY:
• Symptoms include nausea and vomiting, headache, muscle cramps, confusion, lethargy, reduced
GCS and seizures.
• Consider the context e.g. known cancer or polydipsia. o Include accurate drug history.
• Common precipitants: Diuretics (predominantly thiazides, less with loop diuretics).
Antidepressants, antipsychotics, antiepileptics. Smaller contribution from PPIs
EXAMINATION:
• An accurate assessment of fluid status is vital to determine diagnosis and guide treatment.
SCREENING BLOOD/URINE PANEL:
• U&Es, glucose, plasma osmolality, LFTs, TFTs, lipids, cortisol. o Urine osmolality and urine Na+ +
K+ .

14. HYPONATREMIA - MANAGEMENT
MANAGEMENT IS DETERMINED BY
1. Severity of symptoms.
2. Chronicity of the hyponatraemia: Acute < 24 hours, chronic > 48 hours. Treat as chronic if
unclear and no severe symptoms.
3. Patient’s volume status.
•
•IN ALL PATIENTS
1. Stop any offending medications.
2. Review any IV fluids.
3. Treat the underlying cause.
4. Transfer to a Level 2 or ICU bed if severe symptoms are present.
5. Limit rise in sodium in first 24 hours to ≤ 10 mmol/L and ≤ 8 mmol/L in each following 24
hours.

15. POTASSIUM
• K+ is the second most abundant cation in the body ( ~3.5mol).
• Dietary K + amounts to 80 – 150mmol/day.
o Once absorbed, K + is rapidly removed from ECF into the ICF: insulin and B -
adrenergic catecholamines stimulate membrane Na + /K+ -ATPase to pump K + into
cells (in a 3:2 ratio).
• Potassium is a primarily intracellular ion, with skeletal muscle alone
containing more than 75% of the body’s total load.
o Less than 2% of this load is found in the extracellular fluid.
• The normal plasma concentration is between 3.5 and 5.0 mmol/L.
• K+ secretion is stimulated by hyperkalemia and acidosis and reduced by
hypokalemia and alkalosis.

16. POTASSIUM RENAL HANDLING

18. CAUSES OF HYPERKALEMIA
Pseudohyperkalemia
• Hemolysis during blood drawing
• Excessive fist clenching with tourniquet
during blood drawing
• Platelets > 1,000,000
• WBC >200,000
Redistribution (Potassium shifts out of
cells)
• Acidosis (metabolic and respiratory)
• Massive digitalis overdose
• Autosomal-dominant hyperkalemic
periodic paralysis
Aldosterone deficiency
• Primary adrenal failure (autoimmune, TB,
hemorrhage, tumor infiltration)
• Syndrome of hyporeninemic
hypoaldosteronism (SHH)
• Tubular unresponsiveness to aldosterone
Renal failure
• Hyperkalemia may develop rapidly from
exogenous potassium in patients with
renalfailure.
Drugs

19. HYPERKALEMIA
ACIDOSIS
• Shift potassium out of cells in exchange for hydrogen ion.
o metabolic acidosis the potassium will increase by roughly 0.7 mEqL for every 0.1
decrease in pH.
o respiratory acidosis the potassium will increase by roughly 0.3 mEq/Lfor every 0.1
decrease in pH.
Beta-adrenergic blocking agents
• can lead to modest (0.1-0.2 mEq/L) increases in potassium concentration, secondary to
redistribution.
Overdose with digitalis
• Results in redistribution hyperkalemia secondary to inhibition of cell membrane sodium-
potassium ATPase.

20. HYPERKALEMIA
Familial hyperkalemic periodic paralysis
• is an uncommon cause of hyperkalemia.
• This autosomal dominant disorder is associated with recurrent episodes of flaccid
paralysis with hyperkalemia.
• Serum potassium is often in the range 6.0-8.0 mEq/L.
• The attacks may be precipitated by the intake of a high potassium diet or exposure to
cold, and may last from minutes to hours.
Discussion  How Renal Failure cause hyperkalemia

21. Adopted from GrepMed

22. MANAGEMENT OF HYPERKALEMIA
History and Physical examination
• Neuromuscular signs (weakness, ascending paralysis, and respiratory failure)
ECG Changes
• K = 5.5 to 6.5 mEq/L ECG will show tall, peaked t-waves
• K = 6.5 to 7.5 mEq/L ECG will show loss of p-waves
• K = 7 to 8 ECG mEq/L will show widening of the QRS complex
• K = 8 to 10 mEq/L will produce cardiac arrhythmias, sine wave pattern, and asystole
https://www.youtube.com/watch?v=PxoRJN3SVZQ

23. MANAGEMENT OF HYPERKALEMIA
Step 1: Stop all administration of potassium (oral, enteral or IV).
Step 2: Obtain a stat ECG.
Step 3: Quickly seek possible hidden sources of potassium. -->Renal failure, Potassium
penicillin, Salt substitutes (many contain KCI), Hemolysis, Gastrointestinal hemorrhage,
Rhabdomyolysis, Drugs that cause or aggravate hyperkalemia
Step 4: Send stat repeat potassium (drawn without tourniquet to reduce risk
of hemolysis).
Step 5: Find the underlying cause of hyperkalemia  Is pseudohyperkalemia present?
Thrombocytosis, Leukocytosis, Is the sample hemolyzed? Is redistribution hyperkalemia
present? Is there aldosterone deficiency/unesponsiveness?
Step 6: Treat Hyperkalemia as soon as possible

24. MANAGEMENT OF HYPERKALEMIA
THERAPY MECHANISM CAUTION
Calcium gluconate 10 ml of
10% solution (1 gram) IV
slowly over 5-10 minutes.
Temporarily (1 hour)
antagonizes cardiac effects
of hyperkalemia while more
definitive therapy is begun.
May induce digitalis
toxicity: give only with
great caution to patients
receiving digitalis. May
precipitate if given with
solutions containing
NaHC03.
Glucose 100 ml of 25%
solution (25 gm) with 10 U
regular insulin.
Temporarily translocates
potassium into cells. Effect
occurs within 30-60 minutes
and lasts about 1 hour.
May induce hyperglycemia.
If patient is already
hyperglycemic, glucose
infusion is not required
Beta 2 agonists Temporarily translocate
potassium into cells.
Potentially dangerous in the
setting of coronary artery
disease.
1 standard ampule NaHC03
(50 mEq) N over 5-10 mins in patient
who is acidemic.
May be indicated when acidosis
is present with hyperkalemia
May cause ECFV overload, alkalosis,
hypematremia. May produce
seizuresltetany if hypocalcemia is
present. Will precipitate with calcium
solutions.

25. MANAGEMENT OF HYPERKALEMIA
THERAPY MECHANISM CAUTION
Sodium polystyrene
sulfonate (Kayexalatea)
15-30 grams
orally.
Each gram may remove
about 1 mEq potassium
from the body in exchange
for 1-2 mEq of sodium.
ECFV overload. Intestinal
necrosis
Hemodialysis Removes potassium from
the body.
Should be used in patients
with renal failure when
more conservative
treatments have been tried
without success.
Lactulose Removes potassium from
the body
Diarrhea

26. HYPOKALEMIA
• K + of 3 – 3.5mmol/L is generally well tolerated, hypokalaemia of
<2.5mmol/L can be life-threatening
Clinical complications of hypokalemia
• Neuromuscular manifestations (weakness, fatigue, paralysis, respiratory
muscle dysfunction, rhabdomyolysis)
• Gastrointestinal manifestations (constipation, ileus)
• ECG changes (prominent U waves, T wave flattening, ST segment
changes)
• Cardiac arrhythmias (especially with concurrent digitalis)

27. Adopted from: https://blackbook.ucalgary.ca/schemes/renal/hypokalemia/

28. HYPOKALEMIA
Spurious Hypokalemia
• In spurious hypokalemia, the potassium
concentration is not really low.
• Marked leukocytosis (> 100,000) rarely
may produce spurious hypokalemia if the
blood tube is allowed to sit at room
temperature. White cells may simply take
up the potassium in the blood specimen.
• A dose of insulin right before blood
drawing could cause temporary
movement of potassium into cells in the
blood tube and falsely lower the serum
potassium. The magnitude of the fall in
potassium is generally small (around 0.3
mEq/L).
Redistribution (potassium shifts into
cells)
Insulin administration just prior to blood
drawing
Alkalemia
Beta adrenergic agents
Theophylline toxicity
Familial hypokalemic periodic paralysis
Hypokalemic periodic paralysis with
thyrotoxicosis

29. HYPOKALEMIA
Hypokalemia caused by extrarenal loss
(urine potassium <20 mEql24 hours)
Diarrhea
Laxative abuse
Villous adenoma of recto-sigmoid colon
Sweat losses
Fastinglinadequate intake
Hypokalemia caused by renal loss (urine
potassium >20 mEql24 hours)
With metabolic acidosis
- Diabetic ketoacidosis
Ureterosigmoidostomy
Recovery phase of acute renal failure
Post obstructive diuresis
Osmotic diuresis
Saline administration
Magnesium depletion

30. HYPOKALEMIA
Inadequate intake <25mmol/day (either
dietary or IV).
Increased gut losses:
• Vomiting or NG losses ( ^Na+ loss in
vomitus)
• Diarrhoea or laxative abuse.
• Ileostomy or enteric fi stula, colonic villous
adenoma
• hyperaldosteronism: adrenal adenoma
(Conn’s syndrome), bilateral
• adrenal hyperplasia — plasma
aldosterone:renin ratio.
• Renin-secreting tumours
• Cushing’s disease.
• Hypomagnesaemia.
• Familial hypokalaemic periodic paralysis.
• Thyrotoxic periodic paralysis.
• Correction of vitamin B12 defi ciency.

31. DIAGNOSIS OF HYPOKALEMIA
• Total body potassium depletion may result from either renal or extrarenal potassium loss.
• Useful test to distinguish between renal and extrarenal loss is the measurement of 24-
hour urinary potassium excretion.
o A 24-hour determination of >20 mEq124 hours in the presence of hypokalemia implies that
renal potassium loss is the cause of the hypokalemia.
o Spot urine potassium determinations are less useful because hypokalemia induces a water
diuresis in many patients; the excess water dilutes the specimen and misleadingly lowers the
urine potassium concentration.
• Alternatively, spot urine potassium/creatinine ratio for determination of renal versus
extrarenal source of hypokalemia.
o A value of >20 mEq1gram supports the diagnosis of renal loss of potassium.

33. CALCIUM
• 99% of total body Ca 2+ ( 7 1kg) is stored in bone. Extracellular Ca 2+ accounts for a
small fraction: of this; > 40% is bound to albumin, with 50% available as physiologically
active, free (or ionized) Ca 2+.
• Free intracellular Ca 2+ is found at 10 4 higher a concentration than in the extracellular
space, a gradient maintained by an energy-dependent membrane Ca 2+ ATPase.
• The serum normal range is 2.1 – 2.5mmol/L ( 7 1.2mmol/L ionized), with Ca 2+ available
from both the gut and bone stores
• The ionized fraction is freely fi ltered across the glomerulus and mainly reabsorbed in the
PCT and loop of Henle.

34. CALCIUM
• Falling Ca 2+ activates parathyroid calcium-sensing receptors (CaRs),
leading to parathyroid hormone (PTH) release.
• PTH increases renal tubular Ca 2+ reabsorption and hydroxylation of
vitamin D 3 to the active metabolite, increasing intestinal uptake.
• PTH also enhances bone osteoclastic activity.

35. HYPOCALCEMIA
• Corrected Ca 2+ = measured Ca 2+ + [40 – serum Alb] X 0.02
Causes of hypocalcemia
Vitamin D deficiency
• Malnutrition (osteomalacia).
• Malabsorption (gastrectomy, short bowel, coeliac disease, chronic pancreatitis).
• CKD (loss of 1 A -hydroxylase).
• Vitamin D-dependent rickets (anticonvulsants, nephrotic or Fanconi syndrome).
Hypoparathyroidism
• Post-parathyroidectomy — ’ hungry bone syndrome ’ (
• Inherited, pseudohypoparathyroidism.

36. HYPOCALCEMIA
Hyperphosphataemia ( > phosphate increases bone Ca 2+ deposition):
• Tumour lysis
• Rhabdomyolysis
• Hypomagnesemia
• Acute alkalosis (reduction in ionized calcium).

37. HYPOCALCEMIA - SYMPTOMS
Neuromuscular symptoms
• Numbness and tingling sensations in the
perioral area or in the fingers and toes
• Muscle cramps, particularly in the back and
lower extremities; may progress to carpopedal
spasm (ie, tetany)
• Wheezing; may develop from bronchospasm
• Dysphagia
• Voice changes (due to laryngospasm)
Neurologic symptoms
• Irritability, impaired intellectual capacity,
depression, and personality changes
• Fatigue
• Seizures (eg, grand mal, petit mal, focal)
• Other uncontrolled movements
Chronic hypocalcemia may produce the following
dermatologic manifestations:
• Coarse hair
• Brittle nails
• Psoriasis
• Dry skin
• Chronic pruritus
• Poor dentition
• Cataracts

38. Algorithm for requesting investigations to
elucidate the cause of hypocalcaemia

41. LONG TERM MANAGEMENT OF CHRONIC HYPOCALCERMIA
• Oral calcium and vitamin D and its metabolites are essential in management, in addition
to correction of hypomagnesemia.
• Calcium supplement dosages are 1 to 2 g of elemental calcium 3 times daily.
• Magnesium supplementation corrects hypomagnesemia-related hypocalcemia
• Cholecalciferol is more potent than ergocalciferol. Administrating 100 000 IU of vitamin
D3 once every 3 months is also effective in maintaining adequate 25(OH)D levels

42. HYPERCALCEMIA
• Primary hyperparathyroidism and malignancy are the two most common causes of
increased serum calcium levels.

43. CAUSES OF HYPERCALCEMIA
Parathyroid hormone mediated
• Sporadic (adenoma, hyperplasia, or carcinoma)
• Ectopic parathyroid hormone in malignancy (rare)
• “Tertiary” hyperparathyroidism
Malignancy
• Humoral hypercalcaemia of malignancy (parathyroid
hormone related protein)
• Local osteolysis (cytokines, chemokines, parathyroid
hormone related protein)
Vitamin D related
• Granulomatous disease (for example, sarcoidosis,
tuberculosis, berylliosis, coccidiodomycosis, histoplasmosis,
leprosy, inflammatory bowel disease, foreign body
granuloma)
• Vitamin D intoxication (vitamin D supplements, metabolites,
or analogues)
Endocrine disorders
• Thyrotoxicosis
• Adrenal insufficiency
• Pheochromocytoma
• VIPoma (Verner-Morrison) syndrome
Drugs
• Thiazide diuretics
• Lithium
Other
Immobilisation
Chronic renal failure treated with calcium and calcitriol
or vitamin D analogues

44. CLINICAL FEATURES OF HYPERCALCEMIA
• Polyuria and thirst
• Anorexia, nausea and constipation
• Mood disturbance, cognitive dysfunction, confusion and coma
• Renal impairment
• Shortened QT interval and dysrhythmias
• Nephrolithiasis, nephrocalcinosis
• Pancreatitis
• Peptic ulceration
• Hypertension, cardiomyopathy
• Muscle weakness
• Band keratopathy

45. HYPERCALCEMIA
• History
• Examination
• ECG
• Bloods
• High calcium and high PTH = primary or tertiary
hyperparathyroidism*
• High calcium and low PTH = malignancy or other less common
causes

47. HYPERCALCEMIA
Management
• Rehydration
• Intravenous 0.9% saline 4–6 L in 24 h
If further treatment required after intravenous saline, consider intravenous bisphosphonates
• Zoledronic acid 4 mg over 15 min
• OR Pamidronate 30–90 mg (depending on severity of hypercalcaemia) at 20 mg/h
• OR Ibandronic acid 2–4 mg
Second-line treatments
• Glucocorticoids (inhibit 1,25OHD production)
• Calcimimetics, denosumab, calcitonin
• Parathyroidectomy