1. Primary hyperaldosteronism - Conn's Syndrome
1.1. Excessive aldosterone secretion
1.1.1. --> Increased sodium retention --> suppressed renin
1.1.2. --> sodium retention -> increased total exchangeable sodium -> ANP -> inhibition of Na+/K+ ATPase -> sodium escape
1.1.2.1. increased stretch of the heart will increase ANP - it does this in the kidney by inhibiting Na+K+ pump
1.1.3. -> inhibition of Na+/K+ ATPase -> increased intracellular Na+, NXC reversal, increased Ca2+ -> increased vascular smooth muscle contraction -> vasoconstriction -> increased peripheral resistance -> hypertension
1.1.3.1. reversible sodium calcium exchanger - reversal leads to an accumulation od intracellular sodium and calcium --> increased smooth muscle contraction
1.1.4. --> positive inotropic effect -> increased cardiac output -> hypertension
1.1.5. --> potassium depletion -> hypokalaemia -> vasoconstriction -> hypertension
1.1.6. --> increased fluid retention -> ECFV expansion -> increased plasma volume
1.2. up to 2% of hypertensives
1.3. Causes
1.3.1. Glucocorticoid suppressible hyperaldosteronism
1.3.2. Mineralocorticoid secreting carcinoma
1.3.3. Aldosterone secreting adenoma
1.3.4. Benign adrenal hyperplasia
1.4. 70% unilateral adenoma, 30% bilateral hyperplasia
1.5. severe hypertension +hypokalaemia
2. Primary vs. Secondary
2.1. Primary (essential or idiopathic) - no obvious cause. Accounts for 90-95% of cases.
2.2. Secondary - arises through a specific identifiable cause.
3. Causes of secondary hypertension
3.1. acute stress
3.2. renal
3.3. endocrine
3.4. coarctation of the aorta
3.5. pregnancy
3.6. neurological disorders
3.7. alcohol and drug use
3.8. increased intravascular volume
3.9. acute stress
4. Features of secondary hypertension
4.1. onset before 20 years or after 50 years
4.1.1. secondary tend to be quite young
4.2. elevated pressure (e.g. >200/120mmHg)
4.3. Features indicative of secondary causes
4.3.1. unprovoked hypokalaemia
4.3.2. variable pressure
4.3.3. family history o renal or endocrine disease
4.4. poor response to usually effective therapy
5. Function of kidneys
5.1. control of EC fluid volume
5.2. blood pressure control
5.3. Achieved by ...
5.3.1. Glomerular filtration rate
5.3.2. reabsorption of Na+ and water
5.3.3. Renin-angiotensinogen-aldosterone system --> vasoconstriction
5.3.4. defects in inappropriate renin secretion / Na+ retention
6. Renin-angiotensin mediated hypertension
6.1. Renal artery stenosis - (most common)
6.2. renin-secreting tumours
6.3. Renal parenchymal disease (parenchymal - functional tissue of the organ)
6.4. Coarctation (narrowing) of the aorta (above pressure is high, below pressure is low)
6.5. Oestrogen induced hypertension
7. Renin artery stenosis
7.1. 50% of elderly have renal artery atheroma (>70 age)
7.2. 8-17% stenosis progress to occlusion (stenosis -narrowing, occlusion -blockage) in 3-4 years
7.3. 50% reduction in renal perfusion pressure stimulates renin release
7.4. other causes
7.4.1. Fibro-muscular dysplasia (enlargement)(young) - muscle becomes more fibrous
7.4.2. Takayasu's arteritis (Asian)
7.5. Obstruction can be seen in renogram
7.5.1. pinch point due to blockage
7.6. you can lose 50% of kidney function before it is noticeable
7.7. renin is the rate limiting step which initiates RAA system
8. Renal baroreflex control of GFR
8.1. Macula densa - closely packed of specialised cells, lining the wall of the cortical thick ascending limb of the loop of Henle at the transition to the distal convoluted tubule.
8.2. Plaque formation will impinge upon the vessel, pressure downstream is reduced as the vessel is the block
8.3. The pressure of the gomerula is reduced and the amount of filtered plasma is reduced
8.4. Angiotensinogen - acted on by renin (an enzyme)
8.5. Angiotensinogen II is biologically active
8.6. Constriction - effect of plaque will increase resistance to flow
8.7. It initiates RAA system to maintain GR
9. Unilateral stenosis vs Bilateral stenosis
9.1. Unilateral stenosis
9.1.1. Increased renin acts to maintain GFR
9.1.2. Hyperfiltration of contralateral kidney maintains renal function
9.1.3. salt + water balance is normal
9.1.4. AngII - increased proximal Na+ reabsorption on both sides
9.1.5. Aldosterone - increased distal Na+ reabsorption on both sides
9.1.6. Pressure natriuresis in contralateral kidney
9.2. Bilateral stenosis
9.2.1. Reduced renal plasma flow
9.2.2. Increased filtration fraction due to efferent arteriole constriction
9.2.3. Both renal arteries are blocked
9.2.4. Constriction of efferent arteriole, it compensated with blood becoming thicker, which could also increase pressure
9.2.5. Salt and water retention
9.2.6. Aldosterone increases distal Na+ reabsorption on both sides
9.2.7. No pressure natruiresis
9.2.8. Pulmonary oedema, ventricular failure, hypokalaemia
9.2.9. more serious condition than unilateral
9.3. Both
9.3.1. increased blood volume inhibits renin secretion
9.3.2. hypertension is maintained by SNS
9.4. Renin suppression
9.4.1. Suppression of renin depends if it is uni or bilateral
9.4.2. Natruiresis - the balance between NP and salt loss
10. Antihypertensives
10.1. beta andrenergic blockers
10.2. diuretics
10.3. Ca2+ channel blockers
10.4. alpha-adrenergic bockers
10.5. angioplasty or by-pass graft
11. Pressure Natruiresis
11.1. Increased excretion of sodium along with water when there is an increase in arterial pressure
12. Hypertension of adrenal origin
12.1. Adrenal cortex
12.1.1. Steroids
12.1.1.1. mineralocortcoids (aldosterone)
12.1.1.2. glucocorticoids (cortisol)
12.2. Adrenal medulla
12.2.1. Catecholamines
12.2.1.1. adrenaline
12.2.1.2. noradrenaline
13. Cushing's Syndrome
13.1. Harvey Cushing -first clinical description in 1932
13.2. Cause
13.2.1. Prolonged exposure to free circulating glucocorticoids
13.2.2. Therapeutic misuse of glucocorticoids or adrenocorticotrophin (ACTH)
13.2.3. ACTH-dependent (83%) or ACTH-independent (17%)
13.2.4. 'Diabetes of a bearded woman'
13.3. Typical features
13.3.1. Thinning of the skin
13.3.2. Weight gain
13.3.3. Central obesity
13.3.4. Moon face
13.3.5. Backache
13.3.6. Malaise
13.3.7. Depression / psychosis, euphoria
13.3.8. Hirsuitism
13.3.9. Striae - stretch marks
13.3.10. HYPERTENSION
13.3.11. Buffalo hump
13.3.12. Sexual dysfunction
13.4. Increased cortisol
13.4.1. --> decreased vasodilators (kinins/PGs) --> increased total peripheral resistance --> hypertension
13.4.2. --> decreased catecholamine metabolism --> vasoconstriction --> increased peripheral resistance --> hypertension
13.4.3. --> increased sensitivity to vasoconstrictors -> vasoconstriction -> increased total peripheral resistance -> hypertension
13.4.4. increased renin substrate -> increased plasma renin activity (PRA) --> increased Ang II --> vasoconstriction --> increased peripheral resistance --> hypertension
13.4.5. --> increased ICFV to ECFV shift -> ECFV expansion -> increased plasma vol. -> increased CO -> hypertension
13.4.5.1. cortisol will bind to the same receptor as aldosterone, promoting shift between IC and EC fluid
13.4.6. --> increased PNMT (converts noradrenaline to adrenaline) activity in adrenal medulla -> increased adrenaline -> increased CO -> increased hypertension
13.4.7. Mineralocorticoid receptor (MR) increased activity --> increased Na+/fluid retention --> plasma volume --> increased CO --> hypertension
13.4.8. cortisol activated methyl transferal
13.4.9. elevated phenylethanolamine N-methyl transferase activity seen in hypertension.
13.5. Treatment
13.5.1. life expectancy < 5 years if not treated
13.5.2. adrenal adenoma + ectopic tumours
13.5.2.1. surgery
13.5.3. Adrenal carcinoma
13.5.3.1. pharmaceutical (adrenolytic drugs)
13.5.4. pituitary tumour
13.5.4.1. transphenoidal surgery
13.5.5. adrenalectomy
13.5.5.1. requires lifelong steroid replacement therpay
14. Adrenal medulla - Pheochromocytoma
14.1. Medulla secretes catecholamines (Adr/NAdr)/ dopamine
14.2. Up to 4Kg 100g normal
14.3. Chromafin cell tumours
14.3.1. Pheochromocytoma
14.4. Treatment
14.4.1. alpha-adrenergic antagonist (e.g. phenoxybenzamine) prior to surgery
14.5. severe adrenaline and / or noradrenaline
14.6. severe hypertension
14.6.1. increased peripheral resistance
14.6.2. increased cardiac output
14.7. continuous or episodic
14.7.1. induced by compression of tumour
14.7.2. frequency - several times a week for 15 minutes
15. Summary
15.1. Secondary hypertension is rare but usually severe
15.2. Common causes
15.2.1. Kidney