Dr.

Iqra Rasool
Pgr1 hematology
 Potassium

 It is the major intracellular cation,essential for the

maintainance of acid-base balance, isotonicita
and electrodynamic cellular function.
 Essential for transmission of nerve
impulse,contraction of skeletal,cardiac and smooth
muscle cells, gastric secretion, renal function,
tissue synthesis and carbohydrate metabolism.
 Glucose-Insulin-Potassium/GIK therapy is benificial
on ischemic myocardium by decreasing circulating
FFAs and myocardial uptake of FFAs shown to be
toxic to ischaemic myocardium.
 Potassium excretion

 Potassium excretion is chiefly renal.

 20mEq of k is lost daily regardless of levels of dietary
intake.

 Potassium excretion is determined by regulated secretion

in the cortical collecting duct(CCD) and the connecting
segment(CNT) of the distal nephron by principal cells.

 Dietary restriction of sodium decreases K+ secretion and

is enhanced by excess intake.
 Potassium reabsorption

 The proximal tubule and loop of henle

mediate the bulk of potassium
reabsorption and a considerable fraction
is reabsorbed prior to entering the distal
tubules.
 In addition to secretion, distal nephron
can reabsorb K+ during dietary
restriction in the outer medullary
collecting ducts via the H+-K+ATPase
pumps
 Hyperkalemia = plasma K+ concentration >
5.1mmol/L

 Critical hyperkalemia = plama K+

concentration > 6.5 mmol/L
-The normal serum level of potassium is 3.5 to 5
mmol/L

-Daily Requirements 1- 1. 5 mm o l/ k g

-Dietary sources include dried fruits; legumes; meats;

poultry; fish; soy; bananas; citrus fruits; potatoes;
tomatoes; broccoli; mushrooms; dark, leafy green
vegetables
 Intracellular concentration about 150 mmol/L
 The passive outward diffusion of K + is the
most important factor that generates the
resting membrane potential.
 Maintenance of steady state requires K+
ingestion = K+ excretion
 Nearly all regulation of renal K+ excretion
and total body K+ balance occurs in the
distal nephron, via principal cells
 Potassium secretion regulated by aldosterone
and plasma K+ concentration
 Potassium homeostasis

-Gastrointestinal absorption is complete, resulting in daily excess

intake of about 1 mmol/kg/d

This excess is
(10%) excreted through the gut
(90%) excreted through the kidneys

- The most important site of regulation is the distal nephron,

including the distal convoluted tubule, the connecting tubule,
and the cortical collecting tubule
I. Potassium release from cells

II. Excessive Intake

III. Decreased renal loss

IV. Iatrogenic

(Consider pseudohyperkalemia)
 Intravascular hemolysis
 Tumor Lysis Syndrome
 Rhabdomyolysis
 Metabolic acidosis
 Hyperglycemia
 Severe Digitalis toxicity
 Beta-blockers
 Succinylcholine; especially in case massive
trauma, burns or neuromuscular disease
 Excessive intake
- Uncommon cause of hyperkalemia.

-The mechanisms for shifting potassium intracellularly and for

renal excretion allow a person with normal potassium homeostatic
mechanisms to ingest virtually unlimited quantities of potassium in
healthy individuals.

-Most often, it is caused in a patient with impaired

mechanisms for the intracellular shift of potassium or for renal
potassium excretion
 Decreased excretion

-Is the most common cause

--The causes of decreased renal potassium excretion include:

-renal failure

diabetes mellitus

sickle cell

disease

Medications
(eg, potassium-
sparing diuretics,
 Causes
Excessive intake Decreased renal excretion Shift from (ICF to
ECF)
Oral or IV Diabetes mellitus (esp diabetic Hyperosmolality
Potassium nephropathy
Supplementatio rhabdomyolysis
n Renal failure
tumor lysis
Congestive heart failure
Salt substitute Succinylcholin
SLE
insulin deficiency
Blood Sickle cell anemia
transfusion acute acidosis.
NSAID

ACE Inhibitor

Potassium sparing Diuretics

Multiple Myeloma

chronic partial urinary tract

 Pseudohyperkalemia

 - I t is the term applied to the clinical situation

in which in vitro lysis of cellular contents
leads to the measurement of a high serum
potassium level not reflective of the true in
vivo level.
-Condition occurs most commonly with
red cell hemolysis during the blood draw
(tourniquet too tight or the blood left sitting too
long),
 Symptoms

Weakness and fatigue(most common)

fFank muscle paralysis

Shortness of breath

Palpitations
 Physical

-Vital signs generally are normal

Except
bradycardia due to heart block

or tachypnea due to respiratory muscle

weakness.
 Lab

Assess renal function.

Check serum BUN and creatinine levels to

determine whether renal insufficiency is present

Check 24-hour urine for

creatinine clearance
Estimate the glomerular
filtration rate (GFR)
 ECG

Changes occur when Serum Potassium >6.0 mmol

/L
A-Initial
T Waves peaked or Tented

B-Next
ST depression
loss of P Wave
QRS widening

C-Final
Biphasic wave
(sine wave)
QRS and T
fusion
 Measure complete metabolic profile

-Low bicarbonate may suggest hyperkalemia due

to metabolic acidosis.

-Hyperglycemia suggests diabetes mellitus.

 Treatment
The first step

-determine life-threatening toxicity.

By Perform an ECG to look for cardiotoxicity.

- if present
Administer Iv Calcium Gluconateto ameliorate
cardiac toxicity.

-Initial dose: 10 ml over 2 - 5 minutes

Second dose after 5 minutes if no response

-Effect occurs in minutes and lasts for

3 0 - 6 0 minutes
Anticipate EKG improvement within 3
 The second step

-Is to identify and remove sources of potassium

intake

-Change the diet to a low-potassium diet.

 The third step
-Potassium shift from intravascular to
intracellular
-Glucose and Insulin Infusion
Insulin Regular 10 units IV
50 ml 50% of dextrose

-Measure glucose and potassium every 2

hours

-Correct metabolic acidosis with sodium

bicarbonate. 50ml I/V bolus

-Ventolin Nebulization
 The fourth step

-Is to increase potassium excretion from the body

- i n normal kidney function by the administration of

parenteral saline accompanied by a loop diuretic,
such as furosemide Dose: 2 0 - 4 0 mg IV.
 -Discontinue potassium-sparing diuretics,
angiotensin-converting enzyme inhibitors,
angiotensin receptor blockers, and other drugs that
inhibit renal potassium
excretion.

Monitor volume status and aim to maintain

euvolemia.

- I n patients with hyporeninemia or hypoaldosteronism

Renal excretion can be enhanced by administration of
an aldosterone analogue, such as 9-alpha
fluorohydrocortisone acetate (Florinef).
Is a final recourse for unresponsive
hyperkalemia with renal failure.
Emergency
dialysis
 A 52-year-old man with hypertension and diabetes complains of
weakness, nausea, and a general sense of illness, that has progressed
slowly over 3 days. His medications include a sulonylurea, a diuretic, and
an ACE inhibitor. On examination, he appears lethargic and ill. His BP is
154/105 mm Hg, HR 70bpm, temperature 98.6° F, and respiratory rate 22
breaths/min. The physical examination reveals moderate jugular venous
distension, some minor bibasilar rales, and lower extremity edema. He is
oriented to person and place but is able to give further history. The ECG
shows a wide complex rhythm.

 Laboratory studies performed are significant for potassium 7.8 mEq/L,

BUN is 114 mg/dL and creatinine is 10.5.
 Easily Distinguished ECG signs:
◦ peaked T wave.
◦ prolongation of the PR interval
◦ ST changes (which may mimic myocardial infarction)
◦ very wide QRS, which may progress to a sine wave pattern
and asystole.

 Patients may have severe hyperkalemia with minimal ECG

changes, and prominent ECG changes with mild hyperkalemia.
 Diagnosis: Hyperkalemia- Severe

◦ Classification of Hyperkalemia
 NORMAL: 3.5 to 5.0 mEq/L.
 MILD: 5.5 to 6.0 mEq/L
 SEVERE: Levels of 7.0 mEq/L or greater

 It is important to suspect this condition from the history and

ECG, because laboratory test results may be delayed and the
patient could die before those test results become available.
Symptoms of hyperkalemia are usually nonspecific, so risk
factors must be used to suspect the diagnosis

 ECG changes consistent with hyperkalemia should be treated

immediately as a life-threatening emergency. Do not await
laboratory confirmation.

 Intravenous calcium is the antidote of choice for life-

threatening arrhythmias related to hyperkalemia, but its effect
is brief and additional agents must be used
 Definition

 Hypokalemia is defined as a persistently low

levels of serum potassium lower than 3.6
mEq/L.
 Normal serum levels are 3.5-5mEq/L.
 98% of body potassium is intracellular
(150mEq/L) whereas only 2% of it is
intracellular (3.5-5mEq/L)
 Importance
 Occurs in 20% of hospitalised patients.
 10 fold increase in mortality rates by its
adverse effects on cardiac rhythm,BP,
Respiratory depression.
 Precipitates hepatic encephalopathy in patients
with liver disease.
 Worsens BP in HTN patients on treatment with
diuretics.
 Leads to AKI and ESRD in longstanding
hypokalemia.
 Hypokalemic myopathy leading to
rhabdomyolysis.
 Increased risk of arrythmias in patients
on digitalis
therapy.
 Causes
 Decreased intake
 Redistribution / intracellular shifts
 Non renal losses(urinary k <15mEq/L)
 Renal losses (urinary K >15mEq/L)
 Spurious hypokalemia: Delay in sample
analysis may cause hypokalemia due to time
dependent intracellular shift of k.
Rarely profound leukocytosis due to acute
leukemia may cause artefactual hypokalemia
without any clinical or ECG manifestations.
This can be avoided by analysing
sample immediately after venepunture.
 Decreased intake
 K+ deficit I.V fluids,TPN.
 Decreased dietary intake when on
diuretic therapy, anorexia nervosa,
hypo-caloric protein diets for
rapid weight loss.
Redistribution of potassium
 Due to intracellular shift of K.
 Exogenous Insulin glucose infusion
increases K+ entry into skeletal and
hepatic cells by promoting Na-K-ATPase
activity. This effect is more prominent when
administered in settings of DKA or
nonketotic hyperglycemia.
 Carbohydrate load in malnourished patient
leading to endogenous insulin release can
cause the same effects.
 Increased beta-adrenergic activity: Promote
Na-K-ATPase activity.
-Beta adrenergic agonists like salbutamol,
ritodrine.
-Caffeine and theophylline intoxication by
downstream activation of cAMP.
-Occult sources of sympathomimetics like cough
syrup and slimming agents contain
pseudoephedrine and ephedrine, which are
commonly overlooked.
-Stress induced release of epinephrine and
cortisol in Alcohol withdrawal, head injury,MI leads
to transient hypokalemia.
Redistribution of potassium
 Metabolic alkalosis: Extracellular K+
exchanged by intracellular H+ ions to
maintain pH. Administration of sodium
bicarbonate to treat metabolic acidosis can
cause this condition.
 Increased hematopoiesis: GM-CSF used to
treat neutropenia and B-12 and folic acid
to treat megaloblastic anemia may cause
sharp rise in cell production and increased
K+ entry into cell causes hypokalemia.
Thyrotoxic periodic
paralysis
 Excess thyroid hormone increases Na-K-
ATPase activity , increased B-adrenergic
response and predisposes to paralytic
attacks with profound hypokalemia, Sr.K+
ranging between 1.1-2.5 mEq/L.
Redistribution of potassium
 Barium toxicity: Barium is a potent inhibitor if
passive K+ efflux channels. It occurs in suicidal or
accidental ingestion of barium carbonate
(rodenticide),barium containing shaving cream and
hair remover. Treatment with K+ repletion serves
to both rising serum K+ and to displace barium
from efflux channels. Hemodialysis is also
effective.
 Chloroquine toxicity: Causes intracellular shift of
K+ by an unclear mechanism and this can be
exacerbated by use of epinephrine to treat
intoxication.
 Hypothermia: Results In a drive of K+ into cells
which is reversible on rewarming.
 Non-renal losses
 Urinary k<15mEq/L or TTKG <3
 Sweating in extremes of physical exertion.
 Gastric losses (vomiting, ryles aspiration)-
ensuing hypochloremic alkalosis results
in persistent kaluresis due to secondary
hyperaldosteronism and bicarbonaturea.
 Diarrhoea is a known cause of K+ loss
and may present with acute complications
like myopathy and flaccid paralysis.
 Non anion gap acidosis with negative
urinary anion gap suggests diarrhoea as a
cause.
 Non-renal losses
 Non-infectious processes like ileostomy
villous adenoma,laxative abuse celiac
disease can present with acute
hypokalemic syndromes or with chronic
complications like ESRD.
 Bowel cleansing agents like oral sodium
phosphate can cause GI losses of K+.
 Renal losses
 Diuretics:
 Diuretics are an important cause of
hypokalemia by increasing distal delivery
of Na and increasing distal flow.
 Thiazides cause more hypokalemia than
loop diuretics despite their lower natriuretic
effect due to their differential effect on
calcium excrtetion.
 Hypercalciurea caused by loop
diuretics increases luminal calcium
which inturn inhibitd ENaC in the
principal cells.
 Renal losses
 Non-reabsorbable anions: Non-
reabsorbable anions in the distal
nephron like penicillin, nafacillin,
dicloxacillin,ticarcillin,oxacillin,carbencilli
n and other anions like bicarbonate
increase obligatory K+ excretion and
thereby kaliuresis.
 K+ excretion Increases to balance
negative charge of these anions.
 Renal losses
 Tubular toxins: Several tuular toxins can
cause combined K+ and Magnesium
wasting that can masquerade as
Bartter’s syndrome.
 Eg:gentamycin,amphoterecin, foscarnet,
cisplatin, ifosfamide.
 Hpokalemia is refractory to K+ repletion
unless concomitant Mg supplementation
is given.
 Syndromes of apparent

minerakocorticoid
Loss of function mutation in the 11-BHSD-2 gene
excess(SAME)
cause defective peripheral conversion of cortisol
to inactive cortisone.
 Cortisol has similar effects on the
mineralocorticoid receptor as aldosterone.
 11-BHSD2 converts cortisol to cortisone and
prevents this illicit activation of MLR.
 Pharmacological inhibition of 11-BHSD2 is seen with
consumption of liquorice which contains
glycyrrhizinic acid and carbenoxolone.
 Rarely, gain of function mutations on the MLR can
cause SAME.
 Liddle syndrome
 Liddle syndrome
 Autosomal dominant gain in function
mutation of amiloride sensitive ENaC
leading to overactivity and
overexpression on the cell membrane.
 Presents with severe HTN, hypokalemia
unresponsive to spironolactone but
responsive to amiloride and triamterene.
 Blunted aldosterone response to ACTH
and decreased urinary aldosterone
excretion.
 Clinical features
 Non severe hypokalemia is usually asymptomatic.
 Common acute manifestations are muscle
weakness
and ECG changes.
 Prolonged and profound hypokalemia may cause
arrythmias, rhabdomyolysis, renal
abnormalitiess.
 History may reveal the cause like
exertion,vomiting,diarrhoea,drugs,B-12 therapy
etc.
 Asymptomatic or growth retardation should
prompt the suspicion of RTA.
 S/O volume depletion.
 Kussumal breathing may suggest metabolic
acidosis
with respiratory compensation.
 Clinical features
• Cardiac arrythmias like sinus bradycardia,
premature beats, ventricular fibrillation, AV blocks.
• Skeletal muscle weakness or paralysis usually do
not develop unless hypokalemia develops
slowlyand levels are <2.5mEq/L.
• Constipation and ileus due to smooth muscle
involvement.
• Nausea/vomiting, abdominal cramps.
• Polyuria, nocturia, or polydipsia
• Psychosis, delirium, or hallucinations
• Depression
 Investigations
 Sr.Electrolytes,BUN,creatnine.
 ECG
 Urine electrolytes to differentiate non-renal
from renal causes.
 Exclude associated electrolyte
abnormalities especially in alcoholism.
 ABG to detect acidosis or alkalosis when
cause is
not apparent.
 Urinalysis and urine pH if RTA is suspected.
 Urinary calcium to exclude Bartters
syndrome.
 Aldosterone supression test if aldosterone
producing
adenoma is suspected.
 CT abdomen to R/O other pathologies.
 ECG changes

 Flat “T” wave  PR prolongation

 Prominent “U” wave  Wide QRS
 ST depression  Ventricular arrythmias
 QT prolongation  Decreased voltage
 Diagnostic approach
 History(drugs,diet,diarrhoea/vomiting)
 Physical examination(BP,s/o
hyperthyroidsm,cushings)
 Lab tests(serum
electrolytes,BUN,Sr.creatnine,CBP,urinary pH)
 ECG
 Treatment goals
 Prevent hypokalemia
 Correct hypokalemia
 Prevent complications
 Minimize losses
 Correct underlying etiology
 Prevention
 Especially important in patients on
digitalis,hepatic failure,previous MI,DM.
 Normal daily intake of 60mEq/day
 Supplementation in patients on
digitalis,diuretics and long term
steroids,hepatic failure.
 When to treat?
 3.5-5mEq/L: No supplement needed
Potassium rich foods
Change diuretics
 3-3.5mEq/L: Treatment needed in high
risk patients(h/o MI,CHF)
 <3mEq/L: Needs definitive treatment.
Precautions
 Oliguria/anuria
 Patients on ACE inhibitots,k-sparing
diuretics,renal failure.
 Digitalis (slower infusions
<20mEq/hr)
 Continuous ECG monitoring if infusion
rates >20 mEq/hr.
 Deficit should be corrected slowly over
four days.
 Treatment
 I.V supplementation:IV replacement carries a
higher risk of hyperkalemia and is required if
patient is unable to tolerate oral
supplements or in the settings of DKA and
non-ketotic hyperglycemia.
 Maximum recommended rate is 10 – 20
mEq/hr with a daily maximum of 240mEq/day.
 Faster rates may be considered in presence
of ECG manifestations, muscle weakness or
paralysis.
 Solutions more than 60mEq/L are painful and
may cause phlebitis and larger veins
preferably femoral vein is used.
 Functions of Chloride
 Chloride is the major extracellular anion.
 Functions of Chloride :
1.maintenance osmotic pressure ,acid base balance and electrical
neutrality
2.formation of HCl (provides optimum pH for action of pepsin ,activation of
pepsinogen, kills bacteria )
3. Maintains Homeostasis of Na⁺ ,K ⁺, Cl⁻
4. Activation of Salivary Amylase by Chloride
5. CSF protein content low , high chloride content in CSF is to keep “ Donan
membrane equilibrium )
6. Involved in chloride shift
Functions of Chloride
Chloride Metabolism
Role of Chloride in gastric acid
Functions of Chloride as HCl
 Chloride shift in systemic capillaries
In systemic capillaries
• Carbon dioxide is generated by cellular metabolism.
• Carbon dioxide diffuses from tissue to plasma and RBC.
• In RBC ,water and Carbon dioxide combine to form carbonic acid.
• carbonic acid dissociates to give hydrogen (H+ and bicarbonate ions (HCO3-.
• reduced Hb buffers (H+ and (HCO3-.
• Concentration of (HCO3- builds inside RBC.
• (HCO3- diffuses from tissue into plasma and chloride shifts into RBC.
• In pulmonary capillaries the process is reversed.
• Maintenance of electric balance : phenomenon is called Chloride shift
 ( catalysis by carbonic anhydrase 
 Chloride shift in systemic capillaries
In systemic capillaries
Carbon dioxide is generated by cellular metabolism
Carbon dioxide diffuses from tissue to plasma and RBC

In RBC ,water and Carbon dioxide combine to form carbonic acid

Carbonic acid dissociates to give hydrogen (H+ and bicarbonate ions (HCO3-
Reduced Hb buffers (H+ and (HCO3-
Concentration of (HCO3- builds inside RBC
(HCO3- diffuses from tissue into plasma and chloride
shifts into RBC In pulmonary capillaries the process is reversed. *
Maintenance of electric balance : phenomenon is called Chloride
shift
 Absorption and excretion of
Chloride
• Dietary Chloride : absorbed completely by the intestinal
tract
• It is filtered out by glomerulus and passively absorbed in
conjunction with sodium by proximal tubules.
• Excess Chloride ions are excreted in urine and through
sweating .
• Excess sweating stimulates Aldosterone secretion ,which
acts on sweat glands to conserve sodium and Chloride
ions.
Absorption and excretion of Chloride
 Disorders of Chloride
Metabolism
1. Hyperchloremia and Hypochloremia((high and low serum Chloride
ions concentration respectively 
2. Cystic fibrosis
3. Achlorhydria
4. Hyperchlorhydria
5. Hypochlorhydria
6. Achylia Gastrica
Comparison of Hyperchloremia and Hypochloremia
Hyperchloremia
dehydration
Cushing syndrome  minerocorticoid
increased  reabsorption of Chloride at
renal tubule decreases
Severe diarrhea  loss of bicarbonate
compensatory retention of chloride
Respiratory acidosis  shallow breathing 
CO₂ conc increases  H₂CO₃ conc increases
 HCO₃⁻decreases  Cl⁻ conc increases
Renal tubular acidosis
Hypochloremia
Excessive vomiting HCl lost
increase plasma bicarbonate “
Hyperchloremia alkalosis ”
Addison’s disease (Aldosterone decreases
,renal reabsorption of chloride ion
decreases ,excretion of chloride ions
increases ) Chloride ion concentration
decreases
Respiratory alkalosis  Hyperventilation
 elimination of CO₂ increases 
increase in concentration of blood
bicarbonate  Chloride ion
concentration decreases
Disorders of Chloride Metabolism
 Cystic Fibrosis
 Cystic Fibrosis (CF is a multisystem disease that presents
• in neonates ,with failure to pass the first feces containing bile,
intestinal debris and mucus ( meconium ileus 
• in early childhood with respiratory infections
• in the adults
 Inheritance of Cystic Fibrosis (CF : autosomal recessive
disorder
 Pathogenesis of Cystic Fibrosis
Cystic Fibrosis arises due to mutations in gene located on
chromosome 7 encoding the Cystic Fibrosis transmembrane regulator
(CFTR  protein that regulates transmembrane chloride transport .
The most common mutation is F 508 mutation which refers to
deletion of three base pairs , resulting in the absence of Phenylalanine at
position 508 in amino acid sequence of CFTR .
 Clinical Consequences of Cystic Fibrosis
Absence of Cystic Fibrosis transmembrane regulator (CFTR  /chloride
channel leads to following Consequences :
• Exocrine pancreatic insufficiency with impaired secretion of sodium,
bicarbonates and water resulting in increased viscosity (mucoviscoidosis
,obstruction of pancreatic duct , pancreatic fibrosis and obstruction of
pancreatic tissue.
• Chronic airways infection that affects mucus secretion in the bronchi
with recurrent respiratory infections ,bronchiectasis and chronic lung
disease
• Malabsorption ,cirrhosis of liver and cholelithiasis due to defective
secretion of chloride and water
• abnormal sweat gland function due to excessive excretion of
sodium and
chloride in sweat
• Abnormal urogenital functions
Cystic Fibrosis
Disorders of Chloride Metabolism
 Diagnosis of Cystic Fibrosis
 Diagnosis of Cystic Fibrosis is based on
• Clinical symptoms
•Measurement of pilocarpine induced sweat electrolyte concentration:
Na ⁺ and Cl⁻ in sweat ( 70 mmols /L or mequ /L )
• Neonatal screening test : increased plasma immunoreactive trypsin
• prenatal screening test : for F 508 mutation
Diagnosis of Cystic Fibrosis
Sweat test for Diagnosis of Cystic
Fibrosis
Silver nitrate Test for qualitative
analysis of chloride ions
 Management of Cystic Fibrosis
 Management of Cystic Fibrosis involves
• Prevention of respiratory infection by antibiotics and physiotherapy
• Maintenance of proper nutrition and pancreatic enzymes in diet
 Achlorhy
dria
• Achlorhydria refers to absence of HCL in gastric secretion.
• Physiological Achlorhydria :Aging
• Pathological Achlorhydria
1. Tuberculosis
2. Gastritis
3. Gastric carcinoma
4. Terminal stages of malignancy
 Hyperchlorhydria

Hyperchlorhydria refers to increase in concentration free

acid . The combined acidity may be normal.
• Hyperchlorhydria is common in
a) Duodenal ulcers
b) Zollinger Ellison syndrome
 THANK YOU