Pathophysiology, diagnosis and clinical management Bammens Potassium.pdf · Pathophysiology,...

Pathophysiology, diagnosis and clinical management

Bert Bammens UZ Leuven KU Leuven

Electrolyte disturbances

1

HYPOKALEMIA and K+ DEPLETION HYPERKALEMIA

*reference values lab UZ Gasthuisberg 3-2011

Hypokalemia and K+ depletion

2

•  Definition hypokalemia: plasma [K+] < 3.5 mmol/L

(normal plasma [K+] 3.5-5.1 mmol/L*)

Hypokalemia and K+ depletion

3

•  Definition K+ depletion: negative (external) K+ balance

•  Relationship plasma [K+] and K+ balance not linear!

Hypokalemia: pathogenesis

4

LOW INTAKE

EXCESSIVE LOSSES

SHIFT TO INTRACELLULAR COMPARTMENT

K+ depletion

K+ depletion

not necessarily K+ depletion


5

LOW INTAKE

Causes RARE in case of normal oral intake, except when combined

with

Renal K+ excretion can be reduced to 5 à 25 mmol/day! Adaptation to low K+ diet takes ± 14 days.

EXCESSIVE LOSSES

Kalium: fysiologie

K+ transport in nefronBIJ LAGE K+ INTAKE

PT en Lis van Henlereabsorptie

DCT, CNT, ICT, CCTreabsorptie

MCDbeperkte reabsorptie

15


6

LOW INTAKE

Causes Parenteral feeding with insufficient amounts of K+

Geofagia: clay ingestion, clay binds K+ in gastrointestinal tract

cultural heritage vs. psychiatric eating disorder?


7

EXCESSIVE LOSSES

Causes GASTRO-INTESTINAL

LOW gastro-intestinal losses: 20-50 mmol/L K+.

bv. diarrhea, enema, laxatives, cation exchangers low gastro-intestinal fistulisation/stoma, ileus villous adenoma VIPoma (vasoactive intestinal peptide) Particularly when long-lasting!

Hypokalemia: pathogenesis EXCESSIVE LOSSES

Causes GASTRO-INTESTINAL

HIGH (gastric) losses: only 5-10 mmol/L K+.

Gastric losses metabolic alkalosis à renal K+ loss volume contraction à aldosterone à renal K+ loss

Zuur-base: pathogenese/oorzaken

48

Oorzaken GASTRO-INTESTINAALINITIEREND: verlies van H+

braken van maagvocht, afzuigen van maagvocht, maagfistels

metabole alkalose met ECV contractie

Kalium: fysiologie

• Alkalose (metabool of respiratoir) = hogere pHà hogere intracellulaire pH principal cellsà actievere Na+-K+-ATPase en apicale K+-kanalenà meer K+ secretie

• Alkalose (metabool of respiratoir)à hogere flow door meer HCO3

-

à meer K+ secretie

DUS: beide renale effecten van alkaloseversterken effect op interne balans

Externe K+ balans

30

Kalium: fysiologie

• Mineralocorticoiden: aldosterone, DOCA (synth.)

4 effecten-Stimulatie Na+-K+-ATPase-Toename aantal Na+-K+-ATPase-Stimulatie ENaC-Stimulatie K+-kanalen

K+-secreterend effect van aldosterone werkt voornamelijk bij groot distaal Na+ aanbod!

Externe K+ balans

25

8


Causes RENAL

= increased K+ secretion by “DISTAL K+ SECRETORY SYSTEM”

à in other words: high aldosterone and/or high flow / high Na+

Kalium: fysiologie

LUMINALE en PERITUBULAIRE invloeden op “DISTAL K+ SECRETORY SYSTEM”

Luminale factoren

Peritubulaire factoren

Na+ aanbod en flow thv “distal K+ secretory system”

aldosterone

zuur-base

nierfunctie

Samengevat, de belangrijkste factoren die de renale eliminatie van K+ beïnvloeden:

Externe K+ balans

329


Causes RENAL

DIURETICS

carbo-anhydrase inhibitors (acetazolamide)

loop diuretics (furosemide, bumetanide)

thiazide diuretics (hydrochloorthiazide, chloortalidon)

osmotic diuretics

MECHANISM -  Site of action = proximal à increased flow and Na+ delivery to

“DISTAL K+ SECRETORY SYSTEM” -  Decrease of ECF volume stimulates RAAS à high aldosterone

inhibitie Na+ reabsorptiedoor blokkade Na+ transportin specifieke nefronsegmenten

DIURETICA

30

10


Causes RENAL

non-resorbable anions in glomerular filtrate

more Na+ retained in lumen of PT increased Na+ delivery to distal tubule

bv. HCO3

- in case of high gastro-intestinal losses in proximal RTA (type 2)

β-hydroxybutiric acid in diabetic keto-acidosis

Hippuric acid (toluene derivative) in glue addicts

11


Causes RENAL

Mineralocortoicoid excess (for other reasons than dehydration)

primary (hyper)aldosteronism (Conn’s syndrome) Cushing syndrome (glucocorticoid excess) licorice (glycyrrhetinic acid) secondary to renovascular disease secondary to stress (bv. post-surgery)

Na+ balans: RAAS

65

12


Causes RENAL

RENAL TUBULAR DEFECTS

Bartter’s syndrome (defect NKCC2 à mimics loop diuretics) Gitelman’s syndrome (defect NCC à mimics thiazide diuretics) RTA (type 1 and 2) Liddle’s syndrome

Liddle’s syndrome (autosomal dominant) Overexpression of ENac in principal cells

Na+ retention K+ secretion

Mimics primary aldosteronism with hypertension, hypokalemia and alkalosis, but NO increased renine or aldosterone levels (pseudo-aldosteronism)

13


Causes SWEATING, BURN WOUNDS

VERY RARE cause of hypokalemia, except when excessive and combined with low intake or other causes of excessive losses.

14


Causes

ALKALOSIS


Kalium: fysiologie

Zuur-base afwijkingen beïnvloeden interne K+ balans.“VUISTREGEL”

K+ wisselt uit voor H+

ACIDOSE à hyperkalemieALKALOSE à hypokalemie

Interne K+ balans

12

15


Causes

GLUCOSE ± INSULIN


Kalium: fysiologie

Insuline, β-adrenerge agonisten (adrenaline), aldosteronestimuleren Na+-K+-ATPase à K+ naar intracellulair

Interne K+ balans

11

16


Causes

GLUCOSE + INSULIN = essential part of treatment of diabetic keto-acidosis



16

Oorzaken DIABETISCHE KETO-ACIDOSE K(ook hyperglycemie + osm.diurese)

tekort aan insuline therapie-stopintercurrerende ziekte die insuline-nood verhoogt

overmaat aan glucagon (door wegvallen inhibitie insuline)

hoger aanbod vrije vetzuren, aminozuren, glucoseaan lever vanuit vet- en spierweefsel

high anion gap METABOLE ACIDOSE

17

Hypokalemia: pathogenesis SHIFT TO INTRACELLULAR COMPARTMENT


16






Dehydratatie: pathogenese

Renale oorzaken

Osmotische diurese: rijk aan “deeltjes”

glomerulair gefilterde abnormale osmolen

exogeen: mannitol, sorbitol…endogeen: glucose (ongecontroleerde diabetes)

ureum (hoog eiwit dieet, CNI)calcium (hypercalcemie)

primair waterverlies = hyperosmolaire dehydratatie

47 18

Causes




16







Renale oorzaken

Osmotische diurese: rijk aan “deeltjes”

glomerulair gefilterde abnormale osmolen

exogeen: mannitol, sorbitol…endogeen: glucose (ongecontroleerde diabetes)

ureum (hoog eiwit dieet, CNI)calcium (hypercalcemie)

primair waterverlies = hyperosmolaire dehydratatie

47

Hypokalemie: pathogenese/oorzakenTE GROOT VERLIES

Oorzaken RENAALDIURETICA

koolzuuranhydrase inhibitoren (acetazolamide)

lisdiuretica (furosemide, ethacrynezuur)

thiazide diuretica (hydrochloorthiazide, chloortalidon)

osmotische diuretica

MECHANISME- Door proximaal te werken, verhogen ze flow en Na+ aanbod thv

“DISTAL K+ SECRETORY SYSTEM”

- Door daling ECF volume, stimuleren ze aldosterone vrijzetting.

inhibitie Na+ reabsorptiedoor blokkade Na+ transportin specifieke nefronsegmenten

DIURETICA

30

19

Causes



20

Causes


Risk of life threatening hypokalemia as a consequence of K+ shift to intracellular compartment in already K+ depleted patient (osmotic diuresis, non-resorbable anions).


Causes

β-ADRENERGIC AGONISTS e.g. - treatment of astma - treatment of preterm labor -  stress usually only problematic if combined with


Kalium: fysiologie


Interne K+ balans

11

EXCESSIVE LOSSES 21


Causes

FAMILIAL HYPOKALEMIC PERIODIC PARALYSIS

autosomal dominant defect of Ca2+ of Na+ channels in striated muscle cells (sometimes acquired form, e.g. associated with hyperthyroidism)

Attacks of painless muscle weakness, triggered by physical excercise, calory-rich meal (insuline+glucose)

Hypokalemia during attacks. Normal kalemia in-between attacks. (DD other forms of hypokalemic paralysis)

SHIFT TO INTRACELLULAR COMPARTMENT http://www.youtube.com/user/vlivings

22


Causes

ANABOLIC CONDITIONS with INCREASED CELL GROWTH

uptake of K+ by “new” cells hypokalemia

e.g. treatment of anemia with Vit B12 of folic acid treatment of neurtropenia with GM-CSF


23


Causes

HIGH VOLUME TRANSFUSION OF RBC

Mechanisms -  alkalosis due to preservative à hypokalemia -  cold storage: Na+ K+ ATPase inhibited;

reactivation by warming à hypokalemia


24

*reference values van lab UZ Gasthuisberg 3-2011

Hypokalemia: symptoms

25

•  Definition hypokalemia: plasma [K+] < 3.5 mmol/L

(normal plasma [Na+] 3.5-5.1 mmol/L*)

•  Symptoms usually only when [K+] < 3.0 mmol/L or in case of ACUTE onset.

Muscle weakness due to change of resting membrane potential (hyperpolarisation)

increased activation status of Na+ channels


26

Muscle weakness

Striated muscle

decreased tendon reflexes paralysis (from lower limbs, through trunk to upper limbs)

rhabdomyolysis Smooth muscle nausea, anorexia abdominal distension and paralytic ileus bladder paralyse


27

Muscle weakness Heart muscle

hyperpolarisation resting potential à increased excitability of normal pacemaker and ectopic ventricular pacemakers

prolonged action potential à  slow ventricular repolarisation à  prolonged relative refractory period

arrhythmias (ectopic pacemakers and reentry phenomena) VES, VFib…


28

Muscle weakness Heart muscle

typical ECG changes ST depression, inversion T, U wave


29

Glucose intolerance

Hypokalemia inhibits insulin secretion by pancreatic β-cells and increases peripheral insulin resistance.

Cause of diabetogenic effect of thiazide diuretics?

FBG = fasting blood glucose


30

Renal problems loss of urine concentrating abilities, ao by

lower aquaporin-2 expression inhibition NKCC2 in TAL decreased ADH effect nefrogenic diabetes insipidus


Oorzaken- Idiopathisch- Familiaal (genetisch)- Chronische hypoK+ of hyperCa- Medicatie: lithium, colchicine- Sommige nierziekten, bv. bij Sickle Cell Anemia

nefrogene diabetes insipidus

renaal:te weinig respons op ADH

Activiteit van ADH op principal cells van ICT tot IMCD

Water balans: NIEREN

55


31

Renal problems increased synthesis NH3, increased reabsorption HCO3

- alkalosis

Hypokalemia

• Door interne K+ balans: hypokaliemie à daling pHi

• à zelfde effect als bij chronische acidosevia (pHo en) pHi door stimulatie NHE3, electrogene H+

pomp, NBC, ammoniagene enzymes (glutaminase, PEPCK), Na/citraat cotransporterà niet-titreerbaar/titreerbaar zuur stijgt!

• K+ depletie stimuleert ook apicale K-H uitwisselaar in α-intercalated cells van ICT en CCT

(Omgekeerde effecten bij hyperkaliemie. Bovendien competitie K+ en NH4

+ voor Na/K/Cl cotransport in TAL à minder NH4+ accumulatie in

interstitium medulla)


32

Renal problems vacuolisation tubular epithelial cells, interstitial edema interstitial nephritis

(acute and) chronic renal insufficiency


33

Mental disturbances drowsiness, apathy, confusion, coma

Pathophysiology, diagnosis and clinical management

Bert Bammens UZ Leuven KU Leuven

Electrolyte disturbances

34

HYPOKALEMIA and K+ DEPLETION HYPERKALEMIA


Hyperkalemia

35

•  Definition hyperkalemia: plasma [K+] > 5.0 mmol/L

(normal plasma [K+] 3.5-5.1 mmol/L*)

HIGH INTAKE

INSUFFICIENT (RENAL) ELIMINATION

SHIFT TO EXTRACELLULAR COMPARTMENT

Hyperkalemia: pathogenesis

36

HIGH INTAKE

Causes RARE with normal oral intake, except if combined with

thanks to early intracellular buffering followed by renal elimination.

INSUFFICIENT RENAL ELIMINATION

Kalium: fysiologie

Om extracellulaire [K+] constant te houden, is “opvang” vandeze externe kaliumbelasting nodig.

interne K+ balans = shift van K+ van extra- naar intracellulairsnel (< 1uur), “eerste opvang” voor 4/5 van K+ belasting

externe K+ balans = eliminatie van K+ uit het lichaamtrager (uren)

90-95% renaal5-10% gastrointestinaal (+ zweet)

K+ intake kan aanzienlijk groter zijn dan hoeveelheid extracellulair K+.

10


37

HIGH INTAKE

Causes Parenteral: (too fast) infusion of K+ containing substances (= iatrogenic hyperkalemia, cave renal insufficiency)

bv. kalium penicilline glucion®


38


Causes

= insufficient K+ secretion by “DISTAL K+ SECRETORY SYSTEM”

In other words: renal insufficiency and/or low aldosterone and/or low flow / low Na+ delivery

Kalium: fysiologie

LUMINALE en PERITUBULAIRE invloeden op “DISTAL K+ SECRETORY SYSTEM”

Luminale factoren

Peritubulaire factoren

Na+ aanbod en flow thv “distal K+ secretory system”

aldosterone

zuur-base

nierfunctie

Samengevat, de belangrijkste factoren die de renale eliminatie van K+ beïnvloeden:

Externe K+ balans

32


39


Causes Acute (oliguric, anuric) kidney injury Late stages of chronic kidney disease

Hyperkalemic RTA

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Hyperkalemie

MAAR NIET ALTIJD!

METABOLE ACIDOSE


40


Causes Addison’s disease + all other conditions with low aldosterone Kalium: fysiologie

• Mineralocorticoiden: aldosterone, DOCA (synth.)

4 effecten-Stimulatie Na+-K+-ATPase-Toename aantal Na+-K+-ATPase-Stimulatie ENaC-Stimulatie K+-kanalen

K+-secreterend effect van aldosterone werkt voornamelijk bij groot distaal Na+ aanbod!

Externe K+ balans

25

41

Conditions of low aldosterone

Palmer BF N Engl J Med

351: 585-592, 2004


42


Causes Dehydration with low effective circulating volume

low flow and low Na+ delivery to “DISTAL K+ SECRETORY SYSTEM”

Kalium: fysiologie

• Hogere flow in lumen à K+ in lumen laag à gradientapicaal principal cells hoog à hogere K+ secretie

• Hogere flow in lumen à hoger Na+ aanbod distaalà stimulatie Na+-K+-ATPase à meer K+ secretie

Externe K+ balans

22

• Hoger Na+ in lumen à Na+ opname via ENaCà apicaal membraan depolariseert à electrische gradientstimuleert K+ secretie

• Laag Na+ in lumenà hyperpolarisatieà minder K+ secretie

• Idem bij blokkade ENaCdoor amiloride (diureticum)

Kalium: fysiologieExterne K+ balans

23


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Causes USUALLY MULTI-CAUSALITY!

e.g. heart failure patient with chronic use of ACE-inhibitor and spironolactone, getting dehydrated due to intercurrent illness.


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45



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Causes ACIDOSIS


Kalium: fysiologie

Zuur-base afwijkingen beïnvloeden interne K+ balans.“VUISTREGEL”

K+ wisselt uit voor H+

ACIDOSE à hyperkalemieALKALOSE à hypokalemie

Interne K+ balans

12


47

Causes INSULIN RESISTANCE or LACK of INSULIN


Kalium: fysiologie


Interne K+ balans

11


48

Causes INSULIN RESISTANCE = why patients with or diabetic keto-acidosis may present LACK of with hyperkalemia INSULIN (despite K+ depletion)


Hypokalemie: pathogenese/oorzaken

OorzakenGLUCOSE + INSULINE TOEDIENING= essentieel bij behandeling diabetische keto-acidose

DUS risico op levensbedreigende hypokalemiedoor shift van K+ naar intracellulair bij patiënten dievaak reeds een K+ depletie hebben ontwikkeld!

SHIFT NAAR INTRA-CELLULAIR


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Causes β-ADRENERGIC ANTAGONISTS e.g. - treatment heart failure - treatment tachy-arrythmias usually only problematic if combined with


Kalium: fysiologie


Interne K+ balans

11



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Causes CELL- or TISSUE INJURY

bv. intravascular hemolysis tumorlysis syndrome physical exercise crush syndrome



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Causes PSEUDOHYPERKALEMIA K+ leaves cells after blood sample has been taken

e.g. traumatic venipuncture long interval between sampling and analysis thrombocytosis or leucocytosis (release during clotting)

hereditary spherocytosis (temperature dependent K+ leakage)



Causes

FAMILIAL HYPERKALEMIC PERIODIC PARALYSIS

usually autosomal dominant defect of Na+ channels striated muscle cells

Attacks of painless paralysis, sometimes triggered by cold, recovery after physical excercise, fasting, ingestion of K+

Slight hyperkalemia during attacks (or normal [K+]) Normokalemia in-between attacks.


52


Hyperkalemia: symptoms

53

•  Definition hyperkalemia: plasma [K+] > 5.0 mmol/L

(normal plasma [Na+] 3.5-5.1 mmol/L*)

•  Symptoms usually only when [K+] > 6.0 mmol/L or in case of ACUTE onset.

Symptoms due to change of resting membrane potential (depolarisation)

slight depolarisation increases neuromuscular excitability more pronounced depolarisation inhibits excitability (refractory)


54

Muscle weakness

Striated muscle

muscle weakness paralysis (lower limbs, through trunk up to upper limbs)


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Heart muscle

depolarisation resting potential à  decreased excitability normal pacemaker more ectopic ventricular pacemakers

arrhytmias (ectopic pacemakers and reentry phenomena) VES, VFib…


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Heart muscle

typical ECG changes tented T-waves, prolonged PR-interval, loss of P-waves, broadened QRS-complex, bradycardia


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flattened P-waves

Heart muscle

typical ECG changes tented T-waves, prolonged PR-interval, loss of P-waves, broadened QRS-complex, bradycardia


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Heart muscle

typical ECG changes


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Renal problems decreased NH3 synthesis, decreased reabsorption HCO3

- acidosis

Hypokalemia








Hypokalemia









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Mental disturbances drowsiness, apathy, confusion, coma

Hyperkalemia: treatment

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Indication depends on severity of symptoms. But actively look for symptoms if >6 mmol/L. Ca2+ to “stabilize” the membrane of cardiac muscle cells Insulin + glucose Bicarbonate Beta-2-adrenergic agonists Diuretics (loop and thiazide) Rehydration Dialysis Resins (cation exchangers)

Pathophysiology, diagnosis and clinical management Bammens Potassium.pdf · Pathophysiology,...

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