CVS - Control of BP - Hypertension Flashcards
What two methods can you use to determine MABP?
1/3 pulse pressure + diastolic pressure
CO x TPR
How does the baroreceptor reflex alter CO and TPR?
CO - via sympathetic/parasympathetic
TPR - via sympathetic tone to vessels to alter resistance
What are the 4 neurohumoral pathways that control BP longterm? How do they do this?
Sympathetic NS
RAAS
ADH
ANP
By increasing circulating plasma volume
Where is renin released from? Which 3 factors stimulate it’s release?
Released from granular cells of juxtaglomerular apparatus
In response to:
1) Reduce perfusion pressure in kidney afferent arteriole
2) Reduced NaCl delivery to distal tubule
3) Sympathetic stimulation of JGA
How does angioteninogen get to angiotensin I and ang I to ang II?
Angioteninogen is cleaved to ang I by renin
Ang I converted to Ang II by ACE
Name 4 effects of Ang II to increase BP?
1) Sympathetic stimulation
2) Increases ADH release
3) Stimulates aldosterone from the adrenals (Na+ reabsorption)
4) Vasoconstriction
Which types of Ang II receptors are there? Which is the main one? What type of receptor are they? Where would you find Ang II receptors in the body (5)?
AT1 (main actions)
AT2
GPCR
Hypothalamus - ADH Kidney - increases Na+ reabsorption Sympa NS - NA release Adrenal cortex - Aldosterone release Arterioles - Vasoconstriction
What type of hormone is aldosterone? What is is made from?
Steroid hormone made from cholesterol
What stimulates the release of aldosterone and from where?
Plasma Ang II stimulates release of aldosterone from adrenal cortex - acts on Na+ reabsorption.
Increased plasma ACTH
Increased K+ also stimulates aldosterone
What are 4 roles of aldosterone? What cells and location do they act on?
Act on principal cells of distal convoluted tubule and collecting duct
- Upregulate NaKATPase activity in basolateral membrane (K+ out of blood
- Increase ENacs - therefore increase H20 reabsorption
- Acts on apical K+ channels - K+ extrusion into urine
Which 2 ways does ACE increase BP?
Converts Ang I to Ang II - vasoconstrictor
Also is a kininase that breaks down the vasodilator bradykinin
How do ACE inhibitors work? What is a side effect and why? Name one ACEi
Block conversion of Ang I to Ang II, and block breakdown of bradykinin - side effect dry cough due to increased bradykinin. Ramipril
How does the SNS control blood pressure via the kidneys (4)?
Vasoconstriction of afferent arterioles - reduced GFR so reduced Na excretion
Activates Na/H+ exchanger in apical membrane of proximal tubule and NaKATPase in basolateral - enhances Na+ reabsorption into blood
Less renal perfusion also leads directly to reduced Na+ and less urine
Stimulates renin release from JG cells - stimulates Ang II and stimulates aldosterone levels - increased Na+ reabsorption
State three functions of ADH on blood pressure control. What stimulates release of ADH?
Main role is to stimulate translocation of aquaporins in collecting duct and distal convoluted tubule (AQP2) to enhance water reabsorption
Also has a vasoconstriction role (other name vasopressin)
Also acts to increase Na+ reabsorption by stimulating apical NaKCl co-transporter on thick ascending limb
Reduces blood osmolarity is detected by osmoreceptors in the hypothalamus that stimulate release of ADH from post pituitary. Also severe hypovolaemia can stimulate/ Ang II
How does ANP control BP (2)? Where is it synthesised and released?
Has opposite effect to others - acts to decrease BP
If circulating vol is low - ANP inhibited - so acts to support BP in this way
Synthesised and stored in atrial myocytes and released in response to stretch receptors.
Causes vasodilation in afferent arteriole
Inhibits Na reabsorption along nephron
What two other substances in the body have an effect on BP? How?
Dopamine - Vasodilation and increases renal blood flow, reduces reabsorption of NaCl
Prostaglandins - Vasodilators - locally acting PG (mostly PGE2) enhance glomerular filtration and reduce Na+ reabsorption
When are prostaglandins important?
Protective function - act as a buffer against excessive vasoconstriction by SNS and RAAS - important when Ang II levels are high
What is hypertension?
Sustained increase in BP e.g. over 140/90
What is accelerated hypertension?
Hypertensive emergency - significant rise in BP over a small amount of time accelerates damage to blood vessels
What is primary vs secondary hypertension?
Primary - 95% unknown cause - or multifactorial (genetic, environment, potentially DA receptors)
Secondary - to disease e.g. renal artery stenosis, chronic renal disease, hyperaldosteronism, Cushings disease
How does renal artery stenosis lead to hypertension?
Reduced renal blood flow at that kidney stimulates renin release –> vasoconstriction and increased Na+ reabsorption at other kidney leads to increased BP
How does renal parenchymal disease lead to hypertension?
Early stage might be loss of vasodilator substances
Later stage Na+ retention due to inadequate GFR - vol dependent hypertension
What is conns syndrome?
Aldosterone secreting adenoma
Hypertension and Hypokalaemia (due to effects on increased K+ excretion by aldosterone)
What is Cushings syndrome?
Excess cortisol
At high concentrations it acts on aldosterone receptors so increases Na+ reabsorption and water retention
(aldosterone receptors are sensitive to aldosterone and cortisol but normally have a mechanism to prevent overstimulation by cortisol)
What is Pheochromocytoma?
A tumour of the adrenal medulla that secretes catecholamines - vasoconstriction - increased BP
Why is hypertension called the silent killer?
Because it has no symptoms
What secondary diseases are caused by hypertension?
Vasculature - e.g. stroke, MI, AAA, retinopathy
What effect does HTN have on after load? how does this affect the heart?
Increases afterload
Leads to LVH - Heart failure
What non-pharmacological ways could you treat hypertension?
Diet - reduced salt and alcohol
Lifestyle - exercise
Which 4 pharmacological ways can you treat hypertension?
ACEi
Ca2+ channel blockers - smooth muscle relaxation in vasculature
Diuretics - K+ sparing and non sparing
Beta-blockers - not used alone - reduce HR and contractility
How do thiazide diuretics work?
Block NaCl co transporter on apical membrane of cells in distal tubule - reduce Na+ reabsorption
How does Spironolactone work?
Aldosterone antagonist
