Secondary hypertension

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  • 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.
  • Secondary hypertension

    1. 1. Diagnosis of Secondary Hypertension www.freelivedoctor.com
    2. 2. Apparent Prevalence of Secondary Hypertension www.freelivedoctor.com 2  All
    3. 3. Apparent Prevalence of Secondary Hypertension www.freelivedoctor.com
    4. 4. http://www.hyp.ac.uk/bhs/images/abcd_bhsis_version.jpg www.freelivedoctor.com Investigate for 2  causes Investigate for 2  causes
    5. 5. Measure plasma renin www.freelivedoctor.com
    6. 6. Measure plasma renin ? Renal Artery Stenosis ? Conn’s Syndrome High (>400 mU/L) Low (<10 mU/L) www.freelivedoctor.com
    7. 7. Measure plasma renin High (>100 mU/L) Low (<20 mU/L) www.freelivedoctor.com + + s + +
    8. 8. Causes of secondary hypertension <ul><li>Reversible </li></ul><ul><li>Irreversible </li></ul>www.freelivedoctor.com
    9. 9. Causes of secondary hypertension <ul><li>Reversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Endocrine </li></ul></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><li>Iatrogenic/toxic </li></ul></ul><ul><li>Irreversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Monogenic syndromes </li></ul></ul>www.freelivedoctor.com
    10. 10. Causes of secondary hypertension <ul><li>Reversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Endocrine </li></ul></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><li>Iatrogenic/toxic </li></ul></ul><ul><li>Irreversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Monogenic syndromes </li></ul></ul><ul><ul><li>Renal artery stenosis </li></ul></ul><ul><ul><li>Small pyelonephritic kidney </li></ul></ul><ul><ul><li>Large hydronephrotic kidney </li></ul></ul><ul><ul><li>Renin secreting tumor </li></ul></ul>www.freelivedoctor.com
    11. 11. Causes of secondary hypertension <ul><li>Reversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Endocrine </li></ul></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><li>Iatrogenic/toxic </li></ul></ul><ul><li>Irreversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Monogenic syndromes </li></ul></ul><ul><ul><li>Adrenal </li></ul></ul><ul><ul><ul><li>Conn’s </li></ul></ul></ul><ul><ul><ul><li>Phaeochromocytoma </li></ul></ul></ul>www.freelivedoctor.com
    12. 12. Causes of secondary hypertension <ul><li>Reversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Endocrine </li></ul></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><li>Iatrogenic/toxic </li></ul></ul><ul><li>Irreversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Monogenic syndromes </li></ul></ul><ul><ul><li>Co-arctation </li></ul></ul><ul><ul><li>Vasculitis </li></ul></ul><ul><ul><ul><li>Takayasu </li></ul></ul></ul><ul><ul><ul><li>Polyarteritis </li></ul></ul></ul><ul><ul><ul><li>Scleroderma </li></ul></ul></ul>www.freelivedoctor.com
    13. 13. Causes of secondary hypertension <ul><li>Reversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Endocrine </li></ul></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><li>Iatrogenic/toxic </li></ul></ul><ul><li>Irreversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Monogenic syndromes </li></ul></ul><ul><ul><li>Drugs </li></ul></ul><ul><ul><ul><li>Glucocorticoids </li></ul></ul></ul><ul><ul><ul><li>NSAIDs </li></ul></ul></ul><ul><ul><ul><li>Decongestants </li></ul></ul></ul><ul><ul><li>Liquorice </li></ul></ul><ul><ul><li>Alcohol </li></ul></ul>www.freelivedoctor.com
    14. 14. Causes of secondary hypertension <ul><li>Reversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Endocrine </li></ul></ul><ul><ul><li>Vascular </li></ul></ul><ul><ul><li>Iatrogenic/toxic </li></ul></ul><ul><li>Irreversible </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><li>Monogenic syndromes </li></ul></ul><ul><ul><li>Chronic Renal Failure </li></ul></ul><ul><ul><li>Polycystic kidneys </li></ul></ul>www.freelivedoctor.com
    15. 15. Poiseuille’s Law and Hypertension BP = Peripheral Resistance x Cardiac Output www.freelivedoctor.com
    16. 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. 17. Two types of hypertension: type 1 (high-renin) Angiotensinogen AI AII Renin arteries kidneys adrenal glands Aldosterone www.freelivedoctor.com Na+ Na+
    18. 18. Two types of hypertension: type 2 (low-renin) Angiotensinogen AI AII Renin arteries kidneys adrenal glands Aldosterone Na+ Na+ www.freelivedoctor.com
    19. 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. 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. 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. 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. 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. 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. 25. Monogenic and secondary syndromes of hypertension: individual response to treatment www.freelivedoctor.com
    26. 26. Monogenic and secondary syndromes of hypertension: individual response to treatment www.freelivedoctor.com
    27. 27. Monogenic and secondary syndromes of hypertension: individual response to treatment www.freelivedoctor.com
    28. 28. Investigations for secondary hypertension <ul><li>Screening (i.e. all patients) </li></ul><ul><ul><li>Plasma electrolytes </li></ul></ul><ul><ul><li>Plasma renin </li></ul></ul><ul><ul><li>24-h urine VMA (or other index of catecholamine secretion) </li></ul></ul>www.freelivedoctor.com
    29. 29. Investigations for secondary hypertension <ul><li>Screening (i.e. all patients) </li></ul><ul><ul><li>Plasma electrolytes </li></ul></ul><ul><ul><li>Plasma renin </li></ul></ul><ul><ul><li>24-h urine VMA (or other index of catecholamine secretion) </li></ul></ul><ul><li>Specialised </li></ul><ul><ul><li>Renal </li></ul></ul><ul><ul><ul><li>Vascular </li></ul></ul></ul><ul><ul><li>MAG3 Scan </li></ul></ul><ul><ul><li>Angiography (MR/CT) MRI/CT Scan </li></ul></ul><ul><ul><li>(Renal vein sampling) </li></ul></ul>www.freelivedoctor.com
    30. 30. MAG3 Renogram Pre-Captopril www.freelivedoctor.com
    31. 31. MAG3 Renogram Pre-Captopril www.freelivedoctor.com Post-Captopril
    32. 32. MAG3 Renogram www.freelivedoctor.com
    33. 33. 3-D CT- and conventional angiogram 23 year old accelerated hypertension www.freelivedoctor.com
    34. 34. Renal Vein Sampling for Renin Renin (Random) : 9-56 mU/L LRV 522 RRV 259 IVC Suprarenal 307 IVC Infrarenal 242 Aorta 287 www.freelivedoctor.com
    35. 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. 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
    37. 37. www.freelivedoctor.com
    38. 38. Renin-secreting tumour WATANABE et al. Juxtaglomerular cell tumor. International Journal of Urology   9  (12), 704-706 www.freelivedoctor.com
    39. 39. Polycystic kidneys Polycystic kidneys www.freelivedoctor.com
    40. 40. Investigations for secondary hypertension <ul><li>Screening (i.e. all patients) </li></ul><ul><ul><li>Plasma electrolytes </li></ul></ul><ul><ul><li>Plasma renin </li></ul></ul><ul><ul><li>24-h urine VMA (or other index of catecholamine secretion) </li></ul></ul><ul><li>Specialised </li></ul><ul><ul><li>Adrenal </li></ul></ul><ul><ul><ul><li>Conn’s tumour </li></ul></ul></ul><ul><ul><li>Plasma aldosterone </li></ul></ul><ul><ul><li>MRI/CT Scan </li></ul></ul><ul><ul><li>Adrenal vein sampling </li></ul></ul>www.freelivedoctor.com
    41. 41. Coronal MRI Scan of Conn’s Tumour www.freelivedoctor.com
    42. 42. CT Scan of Conn’s Tumour www.freelivedoctor.com
    43. 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
    44. 44. Selective adrenal vein sampling www.freelivedoctor.com
    45. 45. Selective adrenal vein sampling www.freelivedoctor.com 1766 / 885 3300 / 1480 Aldosterone/Cortisol
    46. 46. Influence of ‘AB’ drugs on plasma renin www.freelivedoctor.com
    47. 47. Influence of ‘AB’ drugs on plasma renin www.freelivedoctor.com
    48. 48. Investigations for secondary hypertension <ul><li>Screening (i.e. all patients) </li></ul><ul><ul><li>Plasma electrolytes </li></ul></ul><ul><ul><li>Plasma renin </li></ul></ul><ul><ul><li>24-h urine VMA (or other index of catecholamine secretion) </li></ul></ul><ul><li>Specialised </li></ul><ul><ul><li>Adrenal </li></ul></ul><ul><ul><ul><li>Phaeochromocytoma </li></ul></ul></ul><ul><ul><li>Plasma catecholamines </li></ul></ul><ul><ul><li>MRI/CT Scan </li></ul></ul><ul><ul><li>MIBG Scan </li></ul></ul><ul><ul><li>Selective venous sampling </li></ul></ul>www.freelivedoctor.com
    49. 49. www.freelivedoctor.com
    50. 50. Adrenal phaeochromocytoma: CT and 123I-mIBG scans www.freelivedoctor.com

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