1. Function of kidneys
1.1. control of EC fluid volume
1.2. blood pressure control
1.3. Achieved by ...
1.3.1. Glomerular filtration rate
1.3.2. reabsorption of Na+ and water
1.3.3. Renin-angiotensinogen-aldosterone system --> vasoconstriction
1.3.4. defects in inappropriate renin secretion / Na+ retention
2. Renin artery stenosis
2.1. 50% of elderly have renal artery atheroma (>70 age)
2.2. 8-17% stenosis progress to occlusion (stenosis -narrowing, occlusion -blockage) in 3-4 years
2.3. 50% reduction in renal perfusion pressure stimulates renin release
2.4. other causes
2.4.1. Fibro-muscular dysplasia (enlargement)(young) - muscle becomes more fibrous
2.4.2. Takayasu's arteritis (Asian)
2.5. Obstruction can be seen in renogram
2.5.1. pinch point due to blockage
2.6. you can lose 50% of kidney function before it is noticeable
2.7. renin is the rate limiting step which initiates RAA system
3. Unilateral stenosis vs Bilateral stenosis
3.1. Unilateral stenosis
3.1.1. Increased renin acts to maintain GFR
3.1.2. Hyperfiltration of contralateral kidney maintains renal function
3.1.3. salt + water balance is normal
3.1.4. AngII - increased proximal Na+ reabsorption on both sides
3.1.5. Aldosterone - increased distal Na+ reabsorption on both sides
3.1.6. Pressure natriuresis in contralateral kidney
3.2. Bilateral stenosis
3.2.1. Reduced renal plasma flow
3.2.2. Increased filtration fraction due to efferent arteriole constriction
3.2.3. Both renal arteries are blocked
3.2.4. Constriction of efferent arteriole, it compensated with blood becoming thicker, which could also increase pressure
3.2.5. Salt and water retention
3.2.6. Aldosterone increases distal Na+ reabsorption on both sides
3.2.7. No pressure natruiresis
3.2.8. Pulmonary oedema, ventricular failure, hypokalaemia
3.2.9. more serious condition than unilateral
3.3. Both
3.3.1. increased blood volume inhibits renin secretion
3.3.2. hypertension is maintained by SNS
3.4. Renin suppression
3.4.1. Suppression of renin depends if it is uni or bilateral
3.4.2. Natruiresis - the balance between NP and salt loss
4. Antihypertensives
4.1. beta andrenergic blockers
4.2. diuretics
4.3. Ca2+ channel blockers
4.4. alpha-adrenergic bockers
4.5. angioplasty or by-pass graft
5. Pressure Natruiresis
5.1. Increased excretion of sodium along with water when there is an increase in arterial pressure
6. Adrenal medulla - Pheochromocytoma
6.1. Medulla secretes catecholamines (Adr/NAdr)/ dopamine
6.2. Up to 4Kg 100g normal
6.3. Chromafin cell tumours
6.3.1. Pheochromocytoma
6.4. Treatment
6.4.1. alpha-adrenergic antagonist (e.g. phenoxybenzamine) prior to surgery
6.5. severe adrenaline and / or noradrenaline
6.6. severe hypertension
6.6.1. increased peripheral resistance
6.6.2. increased cardiac output
6.7. continuous or episodic
6.7.1. induced by compression of tumour
6.7.2. frequency - several times a week for 15 minutes
7. Summary
7.1. Secondary hypertension is rare but usually severe
7.2. Common causes
7.2.1. Kidney
8. Primary hyperaldosteronism - Conn's Syndrome
8.1. Excessive aldosterone secretion
8.1.1. --> Increased sodium retention --> suppressed renin
8.1.2. --> sodium retention -> increased total exchangeable sodium -> ANP -> inhibition of Na+/K+ ATPase -> sodium escape
8.1.2.1. increased stretch of the heart will increase ANP - it does this in the kidney by inhibiting Na+K+ pump
8.1.3. -> inhibition of Na+/K+ ATPase -> increased intracellular Na+, NXC reversal, increased Ca2+ -> increased vascular smooth muscle contraction -> vasoconstriction -> increased peripheral resistance -> hypertension
8.1.3.1. reversible sodium calcium exchanger - reversal leads to an accumulation od intracellular sodium and calcium --> increased smooth muscle contraction
8.1.4. --> positive inotropic effect -> increased cardiac output -> hypertension
8.1.5. --> potassium depletion -> hypokalaemia -> vasoconstriction -> hypertension
8.1.6. --> increased fluid retention -> ECFV expansion -> increased plasma volume
8.2. up to 2% of hypertensives
8.3. Causes
8.3.1. Glucocorticoid suppressible hyperaldosteronism
8.3.2. Mineralocorticoid secreting carcinoma
8.3.3. Aldosterone secreting adenoma
8.3.4. Benign adrenal hyperplasia
8.4. 70% unilateral adenoma, 30% bilateral hyperplasia
8.5. severe hypertension +hypokalaemia
9. Primary vs. Secondary
9.1. Primary (essential or idiopathic) - no obvious cause. Accounts for 90-95% of cases.
9.2. Secondary - arises through a specific identifiable cause.
10. Causes of secondary hypertension
10.1. acute stress
10.2. renal
10.3. endocrine
10.4. coarctation of the aorta
10.5. pregnancy
10.6. neurological disorders
10.7. alcohol and drug use
10.8. increased intravascular volume
10.9. acute stress
11. Features of secondary hypertension
11.1. onset before 20 years or after 50 years
11.1.1. secondary tend to be quite young
11.2. elevated pressure (e.g. >200/120mmHg)
11.3. Features indicative of secondary causes
11.3.1. unprovoked hypokalaemia
11.3.2. variable pressure
11.3.3. family history o renal or endocrine disease
11.4. poor response to usually effective therapy
12. Renin-angiotensin mediated hypertension
12.1. Renal artery stenosis - (most common)
12.2. renin-secreting tumours
12.3. Renal parenchymal disease (parenchymal - functional tissue of the organ)
12.4. Coarctation (narrowing) of the aorta (above pressure is high, below pressure is low)
12.5. Oestrogen induced hypertension
13. Renal baroreflex control of GFR
13.1. 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.
13.2. Plaque formation will impinge upon the vessel, pressure downstream is reduced as the vessel is the block
13.3. The pressure of the gomerula is reduced and the amount of filtered plasma is reduced
13.4. Angiotensinogen - acted on by renin (an enzyme)
13.5. Angiotensinogen II is biologically active
13.6. Constriction - effect of plaque will increase resistance to flow
13.7. It initiates RAA system to maintain GR
14. Hypertension of adrenal origin
14.1. Adrenal cortex
14.1.1. Steroids
14.1.1.1. mineralocortcoids (aldosterone)
14.1.1.2. glucocorticoids (cortisol)
14.2. Adrenal medulla
14.2.1. Catecholamines
14.2.1.1. adrenaline
14.2.1.2. noradrenaline
15. Cushing's Syndrome
15.1. Harvey Cushing -first clinical description in 1932
15.2. Cause
15.2.1. Prolonged exposure to free circulating glucocorticoids
15.2.2. Therapeutic misuse of glucocorticoids or adrenocorticotrophin (ACTH)
15.2.3. ACTH-dependent (83%) or ACTH-independent (17%)
15.2.4. 'Diabetes of a bearded woman'
15.3. Typical features
15.3.1. Thinning of the skin
15.3.2. Weight gain
15.3.3. Central obesity
15.3.4. Moon face
15.3.5. Backache
15.3.6. Malaise
15.3.7. Depression / psychosis, euphoria
15.3.8. Hirsuitism
15.3.9. Striae - stretch marks
15.3.10. HYPERTENSION
15.3.11. Buffalo hump
15.3.12. Sexual dysfunction
15.4. Increased cortisol
15.4.1. --> decreased vasodilators (kinins/PGs) --> increased total peripheral resistance --> hypertension
15.4.2. --> decreased catecholamine metabolism --> vasoconstriction --> increased peripheral resistance --> hypertension
15.4.3. --> increased sensitivity to vasoconstrictors -> vasoconstriction -> increased total peripheral resistance -> hypertension
15.4.4. increased renin substrate -> increased plasma renin activity (PRA) --> increased Ang II --> vasoconstriction --> increased peripheral resistance --> hypertension
15.4.5. --> increased ICFV to ECFV shift -> ECFV expansion -> increased plasma vol. -> increased CO -> hypertension
15.4.5.1. cortisol will bind to the same receptor as aldosterone, promoting shift between IC and EC fluid
15.4.6. --> increased PNMT (converts noradrenaline to adrenaline) activity in adrenal medulla -> increased adrenaline -> increased CO -> increased hypertension
15.4.7. Mineralocorticoid receptor (MR) increased activity --> increased Na+/fluid retention --> plasma volume --> increased CO --> hypertension
15.4.8. cortisol activated methyl transferal
15.4.9. elevated phenylethanolamine N-methyl transferase activity seen in hypertension.
15.5. Treatment
15.5.1. life expectancy < 5 years if not treated
15.5.2. adrenal adenoma + ectopic tumours
15.5.2.1. surgery
15.5.3. Adrenal carcinoma
15.5.3.1. pharmaceutical (adrenolytic drugs)
15.5.4. pituitary tumour
15.5.4.1. transphenoidal surgery
15.5.5. adrenalectomy
15.5.5.1. requires lifelong steroid replacement therpay