1. This lecture was conducted during the Nephrology Unit Grand Ground by Registrar under Nephrology Division under the supervision and administration of Prof. Jamal Al Wakeel, Head of Nephrology Unit, Department of Medicine and Dr. Abdulkareem Al Suwaida, Chairman of Department of Medicine. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. HYPOKALEMIA ASSOCIATED WITH HYPERTENSION SALEEM S. SALEEM AL-ANAZI

3. POTASSIUM HOMEOSTASIS Approximately 98% of total body K+ stores are intracellular. Normal serum [ K+ ] ranges from 3.5 – 5.0 mmol / L. Insulin, aldosterone, catecholamine and acid-base status influence K+ movement in to the cells. Potassium excretion is regulated at the distal nephron. K+ excretion = ( urine flow rate ) x ( urine K+ concentration ).

4. Cont, Serum levels of K+ is regulated by :- 1- Uptake of K+ in to cells by altering activity of the NA – K – ATPase pump in the cell membrane. 2- Renal excretion – mainly controlled by aldosterone. 3- Extrarenal loss, e.g. gastrointestinal.

5. HYPOKALEMIA WITH HYPERTENSION Definition of hypokalemia :- This is a serum potassium concentration of < 3.5 mmol / L. Aetiology :- -Primary hyperaldosteronism ( conn`s syndrome ). -Secondary hyperaldosteronism ( renovascular disease, renin tumor ). -Non aldosterone minrealcorticoid ( cushing`s syndrome ).

6. Cont, We approach these patients by check there U K+ excretion and look for TTKG ( transtubular potassium gradient ). TTKG = ( U k / P k ) / ( U osm / P osm ). increased loss 24 h Uk, TTKG Uk > 30 mEq / day, TTKG > 7 Renal loss Check BP

7. Primary hyperaldosteronism Definition :- diastolic hypertension without edema, decrease renin and increased aldosterone secretion Aetiology :- 1- aldosterone – producing adrenal adenoma ( conn`s syndrome ) 2- adrenal hyperplasia ( 25 % ). Clinical features :- hypertension Polyuria – polydipsia – nocturia Fatigue – weakness – paresthesia Headache Sever case there is tetany – intermittent paralysis

8. Investigation :- - Urea end Electrolytes :- hypokalemia, mild hypernatermia, hypomagnesemia. - High 24 h urinary or plasma aldosterone + low random plasma renin. - CT or MRI ( for differentiate adenoma from hyperplasia ). Treatment :- Medical :- spironolactone ( aldosternoe antagonist ) or amiolride, ACE might to be added for better blood pressure control. surgical :- removal of adenoma.

9. Secondary hyperaldosteronism Definition :- increase in the aldosterone in response to activation renin-angiotensin system. Renovascular Hypertension :- This is HTN caused secondary to renovascular disease. Suspected if :- Negative family history of HTN. Spontaneous hypokalemia. Sudden onset or exacerbation of HTN. Difficult to control with antihypertensive therapy. There is decreased in renal perfusion of one or both kidneys leads to increased renin release and subsequent angiotensin ( AII ) production. 2 types :- 1- atherosclerotic plague : proximal 1/3 renal artery, usually male > 55 y. 2- fibromuscular hyperplasia :- distal 2/3 renal artery usually in young females.

10. Cont, Investigation :- -Renal U/S -Gold standard is renal angiography. -Treatment :- -BP lowering medication ( ACE inhibitors ). -Surgical, angioplasty.

11. Cushing`s syndrome Definition :- Clinical syndrome results from chronic glucocorticoid excess. Aetiology :- 1- ACTH – dependent ( 85% ) : -ACTH secreting pituitary adenoma ( cushing`s disease 80% ). -Ectopic ACTH secreting tumor ( SCLC ). -2- ACTH – independent :- -Long term use of exogenous glucocorticoid ( cushing`s syndrome ). -Primary adrenocortical tumor ( adenoma, carcinoma ) uncommon.

12. Cont, Symptoms :- -Weight gain ( central ). -Depression, psychosis, insomnia. -Amenorrhea, oligomenorrhoea. -Thin skin, easy bruising. -Acne. -Polyuria, polydipsia. -Signs :- -Moon face. -Proximal myopathy. -Purple stria. -Buffalo-hump. -Kyphosis.

13. Algorithm for diagnosis 24 h urinary free cortisol Normal 4x increase No cushing`s low dose DST diagnosis of syndrome to confirm the diagnosis cushing`s syndrome measure ACTH ACTH increased ACTH decreased MRI pituitary CT adrenal

14. Treatment Pituitary :- - transsphenoidal resection. -Irradiation only 50% effective. Adrenal :- -Adenoma :- unilateral adrenalectomy ( curative ). -Carcinoma :- palliative. Ectopic ACTH :- -Chemotherapy, radiation. -Ketoconazole, metyrapone ( block adrenal steroid synthesis ).