3. K physiology
• Total body K stores are approximately 3000 meq
• K: primarily intracellular cation {98 % of body K}
• Ratio of the K concentrations in the cells and outside:
major determinant of the resting membrane potential
across the cell membrane
• Generation of the action potential: essential for
normal neural and muscle function
• K abnormalities: Muscle weakness and arrythmia
4. Regulation of urinary potassium excretion
Connecting segment & Cortical duct
Na comes here
Lumen
Negative
ROMK
Electrical gradient
For K secretion
Na-K ATPase
Electrical and
chemical gradient for
Na reasbsorption
5. Regulation of urinary potassium excretion
Stimulation of K secretion by principal cells
• An increase in plasma potassium
concentration and/or potassium intake
• An increase in aldosterone secretion
• Enhanced delivery of sodium and water to the
distal potassium secretory site
6. An increase in plasma potassium
concentration and/or potassium intake
7. An increase in aldosterone secretion
Hyperkalemia
Renin angiotensin
Aldosterone system
(RAAS)
Na channel
Aldosterone deficiency,
blockade
8. Enhanced delivery of sodium and water to
the distal potassium secretory site
We need Na and
Water here.
No distal Na (decresed GFR),
No K secretion
e.g Renal failure
Increased distal flow,
Increased Na delivary,
Increased K secretion
Eg diuretics
9. Distribution of potassium between the cells
and the extracellular fluid
98 % K intracellular
Maintained by this
pump
Pump block
eg digitalis toxicity
Beta blockers
Pump stimulation
Insulin, beta2 stimulation
12. Hyperkalemia
• Increased intake: K adaptation, rapid
• Shift: intracellular to extracellular, alone again not
enough to sustain hyper K.
• Decrease excretion: almost always present
– Aldosterone
– Decreased distal delivery of Na/ water
– Renal dysfunction
13. Case 1
• 52/ male, DM and HT- 15 yrs
• Uncontrolled HT, Edema 3+
• Recent change in medications
• Adm: rapid onset quadriparesis over last 24
hours
14. Case1: examination
• ECG: HR of 30, broad QRS, CHB like pattern
• Rest vitals stable
• Higher functions normal
• Quadriparesis (grade 2 power, absent reflexes)
15. Case 1: Labs
• Na 129
• K 8.7
• Cl 96
• HCO3 16
• AG 17
• Creat 4.4
• Glucose 600
• CBC leucocytosis
• Urine
• Sugar- 4+
• Ketones- nil
• Plenty pus cells
18. Case analysis
• Decreased renal excretion (almost always)
• Was started on ramipril (ACEI) for HT
– RAAS blockade (decreased aldosterone)
Decreased GFR
so decreased distal delivery of Na and water,
no Na reabsorption, no electronegative potential in lumen
No secretion of K
20. Case analysis
• The patient was also
started on
spironolactone which
blocked aldosterone
action
• NSAIDS for fever
– Deceased GFR
– Renal failure
21. More mechanisms
• K loading increases ROMK expression and insertion into
CCD luminal membrane
• ? May be gut signal to kidney to change ROMK
• Another K channel in CCD
– High capacity K channels (big K or Maxi K)
– Activated of high flow (water and Na delivery)
– Activated by K depletion
– Aldosterone independent action
22. Another K channel: intercalated cells
• H-K exchanger in IC cells
of CCD
• Activated in K depletion
• Absorbs K+ and
secretion of H+
23. Evaluation of hyperkalemia
• Exclude Pseudohyperkalemia
– potassium movement out of the cells during or
after the blood collection
– Torniquet
– Thrombocytosis, high WBC counts (leukemias)
24. Assessing K excretion
• Kidneys can vary K excretion from < 5 Meq/L to 400
Meq/L, with decreased or increased intake
• Urine K/ Creatinine ratio
– < 15 mmol/gm in K depletion
– >200 mmol/gm in hyperkalemia
–
25. Case 1
• Urine Na- 120 Meq/L
• Urine K- 15 Meq/L
• SO distal delivery of Na is adequate
• Severely impaired K excretion
• Aldosterone deficiency: hyporeninemic
hypoaldosteronism in DM
• Drugs blocking aldosterone production and action
• Decreased GFR
26. Case 1
• NSAIDS: worsening of RFT (GFR)
• PG synthesis inhibited
– PG inhibit renin –reduce aldosterone
• So in this patients, almost all things to
increase his K has been done
– ACEI, aldosterone blockade
– NSAIDS
27. Treatment of severe hyperkalemia
• Calcium: if hypocalcemia or ECG changes
• Shift inside the cells:
– Insulin alone (hyperglycemia) or with 25 %
Dextrose
– B2 agonist
– Bicarbonate if acidosis
28. Treatment
• Excretion
– Saline, especially if depleted
– Thiazide and loop diuretic
– K binding resins, small effect, increasing GI
excretion, given with lactulose
• Dialysis- the most rapid and effective means in
the presence of renal dysfuction and fluid
overload
29. Case 1
• We started the patient on dialysis, normal
sinus rhythem in 45 minutes
• Stopped implicated drugs, treated UTI
• Baseline creatinine of 2 mg % on follow up.
• K normal
An increase in plasma K stimulates aldosterone, which increases the activity of basolateral Na-K ATPase, thus creating a base of reabsorbtion of Na and then K secretion
So aldosterone excess will lead to hypokalemia and deficiency or blockade will lead to hyperkalemia
Now once we understand the physiology, it is very easy to evaluate a patient of hyperkalemia
So severe hyperglycemia, as occuring in DKA/ HONKS can cause shift of K out of cells and cause hyperkalemia, even though, there is deficiency of total body potassium. So when we correct these conditions with insulin, the K shifts back to cells and actually cause significant hypokalemia, and replacement is necessary
Vigorous exercise and rapid breakdown of cells (like rhabdomyolysis after crush injury, tumor lysis after chemotherapy for hematological malignancies etc) can cause transient hyperkalemia. This becomes clinically significant when its associated with renal dysfunction
Insulin stimulatess
Increased intake of K alone is not enough to cause hyperkalemia. Our kidneys can adapt to increased intake from 100 to as high as 400 Meq/day. Can occur independent of aldosterone- increased density of apical ROMK and basolateral Na-K ATPase
SHIFT alone is not sufficient to sustain hyperkalemia, as renal adaptation will excrete the excess extracellular K.
So decreased excretion is almost always necessary to cause and maintain significant hyperkalemia
It could be due to aldosterone deficiency- RAAS blockade (aldosterone inhibition) or receptor blockade (spironolactone and eplerenone)
So we have a patient, who has hyperkalemia, acidosis and renal failure
Intake is most likely reduced because of severe hyperglycemia, probably precipitated by urinary tract infection
Severe hyperglycemia causing shift of K along with water
Similarly, acidosis causing shifting out of K in exchange with H
ACEI inhibition can cause afferent vasodilatation and further decrease in GFR, especially in patient with reno-vascular disease (micro vascular or macro vascular) and advanced renal disease.
Prolonged application of torniquet, hemolysed sample can cause pseudohyperkalemia
Also in thrombocytosis (platlet counts>6 lakhs) and severe leucocytosis (as in leukemias) the K can shift out of the cells after the sample is drawn and kept at room sample. If this is suspected, immidiate centrifugation after sample is drawn or storing the blood sample at 4 degrees is necessary
Because of the process of intrarenal urea recycling, the concept of TTKG has been discarded now. Halperin, KS Kamel 2011
Calcium is primarily given to protect the heart in presence of ECG changes, it helps to protect the heart from arrythmias transiently till further measures are taken to decrease the serum K
Saline if given in volume depleted, will increase the distal delivery of Na and water and promote K secretion
The diuretics increase the K excretion by similar mechanism, increasing the distal delivery of Na and water
