7. Measure plasma renin High (>100 mU/L) Low (<20 mU/L) www.freelivedoctor.com + + s + +
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15. Poiseuille’s Law and Hypertension BP = Peripheral Resistance x Cardiac Output www.freelivedoctor.com
16. Poiseuille’s Law and Hypertension BP Renin Angiotensin II (AII) Aldosterone N or A drenaline Na+ Vasoconstriction Volume + + + + + BP = Peripheral Resistance x Cardiac Output www.freelivedoctor.com
17. Two types of hypertension: type 1 (high-renin) Angiotensinogen AI AII Renin arteries kidneys adrenal glands Aldosterone www.freelivedoctor.com Na+ Na+
18. Two types of hypertension: type 2 (low-renin) Angiotensinogen AI AII Renin arteries kidneys adrenal glands Aldosterone Na+ Na+ www.freelivedoctor.com
19. Two types of drugs for hypertension: 1 Brown MJ. Matching the right drug to the right patient. Heart 2001 ;86 :113-120. Angiotensinogen AI AII Renin arteries kidneys adrenal glands Aldosterone www.freelivedoctor.com A CE Inhibitors B eta-blockers AIIRA
20. Two types of drugs for hypertension: 2 Brown MJ. Matching the right drug to the right patient. Heart 2001 ;86 :113-120. Angiotensinogen AI AII Renin arteries kidneys adrenal glands Aldosterone www.freelivedoctor.com A CE Inhibitors B eta-blockers AIIRA C alcium Blockers D iuretics
21. Two types of drugs for hypertension Brown MJ. Matching the right drug to the right patient. Heart 2001 ;86 :113-120. Angiotensinogen AI AII Renin arteries kidneys adrenal glands Aldosterone www.freelivedoctor.com A CE Inhibitors B eta-blockers AIIRA C alcium Blockers D iuretics Spironolactone (Eplerenone)
22. Principal pathways and disorders altering sodium reabsorption in the nephron Monogenic Syndromes of Hypertension are due to molecular variants of the Na+ channels inhibited by the diuretics www.freelivedoctor.com
23. Principal pathways and disorders altering sodium reabsorption in the nephron Monogenic Syndromes of Hypertension are due to molecular variants of the Na+ channels inhibited by the diuretics www.freelivedoctor.com Mineralocorticoid receptor Glucocorticoid Remediable Aldosteronism (GRA) Apparent Mineralocorticoid Excess (AME) Geller’s syndrome Spironolactone
24. Principal pathways and disorders altering sodium reabsorption in the nephron Monogenic Syndromes of Hypertension are due to molecular variants of the Na+ channels inhibited by the diuretics www.freelivedoctor.com WNK1 & WNK4 (‘With No Lysine’ Kinase) Gordon’s syndrome Thiazide
25. Monogenic and secondary syndromes of hypertension: individual response to treatment www.freelivedoctor.com
26. Monogenic and secondary syndromes of hypertension: individual response to treatment www.freelivedoctor.com
27. Monogenic and secondary syndromes of hypertension: individual response to treatment www.freelivedoctor.com
35. MR angiogram 22 year old man BP 160/120 mmHg on atenolol & lisinopril Creatinine 110 umol/L Renin 23mU/l (9-56) on Atenolol, 578mU/l on Candesartan www.freelivedoctor.com
36. MR angiogram, suprarenal aortic stenosis 182/57 37 year old woman BP 210/52 mm Hg on 5 drugs Diffuse bruit front & back Plasma renin = 257 mU/L (5 x ULN) - repeated off B = 4672 www.freelivedoctor.com 182/57 78/23
42. CT Scan of Conn’s Tumour www.freelivedoctor.com
43. Untreated Amlodipine Spironolactone Adrenalectomy Brown & Hopper. Calcium-channel blockade can mask the diagnosis of Conn's syndrome. Postgrad Med J 1999; 75: 235-6. CT Scan of Conn’s Tumour www.freelivedoctor.com
It is likely that patients with Conn’s tumour represent the tip of the iceberg of patients for whom excessive aldosterone secretion contributes to hypertension. The finding of somatic variants in genes which might control aldosterone would provide a clue to genes which may explain the inappropriate levels of aldosterone in patients with low renin hypertension.
It is likely that patients with Conn’s tumour represent the tip of the iceberg of patients for whom excessive aldosterone secretion contributes to hypertension. The finding of somatic variants in genes which might control aldosterone would provide a clue to genes which may explain the inappropriate levels of aldosterone in patients with low renin hypertension.
