1/24 Secondary Hypertension - Ruddy Flashcards
factors involved in control of bp
major effectors of these factors
4 basic mechanisms of bp upregulation
BP = cardiac output x peripheral resistance
- renal sodium retention
- SNS
- renin angiotensin aldosterone system
basic mechanisms
- kidneys: blunted pressure-natriuresis → renal salt-volume retention
- activation of RAAS
-
neurosympathetic activity
- alpha1 receptors → vasoconstriction
- beta1 receptors → incr HR/contractility and incr renal renin secretion
- vascular wall remodeling: decline of capacitance and elasticity
RAAS pathway
how do we get AII
actions of AII
angiotensinogen → angiotensin I [renin]
A I → A II [ACE]
AII hits…
-
AT1 receptor
- vascular sm muscle → vasoconstriction
- adrenal gland → aldosterone secretion (and subsequent incr in Na reabs)
- proximal nephron → incr Na reabs
- JGA cells → inhibits renin release
- cardiac and vascular tissue → profibrotic/remodeling
- AT2 receptor
physiologic regulation of renin
renin synth and release by JGA cells is under feedback control
incr secretion
- decr renal perfusion pressure → incr renin secretion
- incr renals SNS action (beta1 receptors) → incr renin secretion
- decr distal tubular Na content → incr renin secretion
decr secretion
- angiotensin II negative feedback (JGA AT1 receptors) → decr renin release
secondary HTN
renal causes
1. renal disease (CKD) ~10%
- usually bilateral (diabetic nephropathy
- mech: Na/fluid retention, usually decr renin
- → CO and SV increase bc of the fluid expansion
2. renovascular ~2-3%
- microvascular: vasculitis, hypertensive nephrosclerosis
- renal artery stenosis
- causes: atherosclerosis, fibromuscular dysplasia, trauma, tumor compression
- unilateral (2K1C): renin dependent
- bilateral (1K1C): usually non renin dependent
experiment: artificial renal artery stenosis (unilateral)
- bp rose
- salt balance became negative
- renin secretion increased
overall: animals lost fluid/diuresed, salt balance became negative
reasoning:
- salt balance is also perfusion-dependent
- incr perfusion → suppresses retention
- decr perfusion → promotes retention
WHY?
pl renin levels went up
- makes sense: decr renal perfusion pressure → incr release
this increase in blood pressure leads to increase in renal perfusion for the UNSTENOSED kidney!!!
experiment: remove kidney and stenose the remaining renal artery
- bp rose
- sal balance became positive
- renin levels incr and then level at normal levels
how does renin level off again?
increase in blood volume (sodium retention) → incr bp throughout body → kidney perfusion begins to approach normal again → renin levels fall to normal
- kidney perfusion maintained at expense of HTN to rest of body
1K1C vs 2K1C animal models
difference in renin activity and blood volume attributable to the presence of a HEALTHY KIDNEY that’s being hyperperfused due to the renin-induced HTN from the stenotic kidney!
when pressure felt by a good kidney increases:
- renin suppressed
- renal sodium reabs suppressed → incr Na wasting and diuresis
(conversely, decr perfusion pressure → renin increases, sodium reabs increases)
secondary HTN
adrenal cortex causes
1. Cushings Syndrome/Disease - rare
- excess glucocorticoid levels activate mineralocorticoid receptors → incr Na retention
- result in multiple complications
- incr bp
- incr blood glucose
- obesity, classic body habitus
- abd stria
- depression
- osteopenia
- immune def
- dx: 24hr u-free cortisol, ACTH levels
- causes: pituitary adenoma, ectopic ACTH, adrenal hyperplasia/tumor
2. primary hyperaldosteronism ~2.5%
- aldosterone acts at nuclear receptors of distal renal tubular cells to incr Na reabs in exchange for K secretion
- Na retention → incr BP and v decr plasma renin
- incr in K excretion → low serum K → mild nephrogenic DI!! → slight increase in serum Na
- chronic low K inhibits effect of ADH on kidney → kidney is unable to concentrate urine
- put out dilute urine, with slightly elevated serum Na
- types:
- bilateral hyperplasia
- adenoma
- neoplasm
- familial
primary hyperaldosteronism
dx criteria
treatment options
if on chronic diuretic tx: Na levels tend to be on low side of normal (not necessarily hypokalemic)
if slightly low K but normal Na instead…maybe primary hyperaldosteronism
secondary HTN
adrenal medulla
pheochromocytoma <0.1%
neuroectodermal chromaffin cell tumor
- usually norepi secreting (but can be epi)
- sx
- paroxysmal incr in bp
- attributable to diffuse intermittent vasoconst due to pulses of norepi
- orthostatic hypotension
- NOT PHYSIOLOGIC
- INTERMITTENT HIGH BP → inhibition of Na reabs → pressure natriuresis → volume depletion
- pallor, sweating, headache
- paroxysmal incr in bp
- diff characteristics: adrenal 75-90, familial 10-25, bilateral 10, malignant 10
multiendocrine neoplasia II:
pheo, medullary thyroid, parathyroid cancer
- pheo biochemical dx: plasma metanephrines, 24hr urine catecholamine secretion
- pheo localization: CT, MRI, MIBG scan, venous sampling
secondary HTN
other causes
- drugs
- sympathomimetic agents
- steroids
- NSAIDs, epo, calcineurin inhibitors (cpA)
- heavy metal poisoning
- pregnancy assoc/pre-eclampsia
- 3rd trimester incr bp and proteinuria
- fetal growth retardation/injury/death and maternal injury/death (HELLP - htn, elefated lft, low platelet) → induce delivery asap
- thyroid: hyper and hypo
- hyperparathyroidism
- coartcation of aorta
- HTN appears childhood/adolescence
- systolic murmur on front and back
- check leg bp
clinical clues for secondary HTN
- new onset, young age (under 30)
- treatment resistant
- history of kidney disease, periph vasc disease, smoking
- drugs - rx, recreation, PED
physical exam
- Cushingoid habitus, tremor, thyromegaly
- PVD - abdominal/carotid bruits, poor periph pulses
- postural hypotension
routine lab studies
- serum creatinine
- electrolytes
- glucose
- calcium
- u/a
