deck_1637351 Flashcards
Where does medium and long term control of blood pressure stem from?
• Neurohumoral responsesDirected at controlling sodium balance and thus extracellular fluid volume
How does modification of ECF modify BP?
• Blood plasma part of ECF • Modifying ECF volume modifies volume of blood
What are the four parallel pathways which control BP?
• Renin-angiotensin-aldosterone system • Sympathetic nervous system • Antidiuretic hormone (ADH) • Atrial natriuretic peptide (ANP)
Where is renin released form?
• Granular cells of juxtaglomerular apparatus
What three factors control renin release?
• Reduced NaCl delivery to distal tubule (reduced perfusion, low GFR) • Reduced perfusion pressure in the kidney causes the release of renin (baroceptors in afferent arteriole cause release from granluar cells of JGA) • Sympathetic stimulation to JGA increases release of renin
What does the sympathetic system stimulate to cause renin release?
• B adrenergic receptors of granular cells of JGA
How is renin released by JGA as a result of decreased GFR?
• Less NaCl detected by macula densa cells in JGA • Stimulates granular cells to release prostaglandin PGI2 • PGI2 acts on granular cells to cause renin release
How is renin released by granular cells as a result of reduced perfusion pressure ?
• Decreased pressure decreases wall tension at granular cells, which stimulates renin release
What does renin do?
• Enzyme released by juxtaglomerular granular cells • converts angiotensinogen to angiotensin 1 • ACE converts angiotensin 1 to angiptensin 2
Where is ACE found?
• On the endothelium of cells, especially in lung
How does angiotensin 2 cause increase in BP?
• Vasoconstriction - arterioles • Stimulates Na+ reabsorption - kidney • Sympathetic nervous system - Increased release of NA • Aldosterone release - adrenal cortex (revise effects) (Na+ reabsorption) • Releases ADH - Hypothalamus, stimulated by thirst receptors
What two receptors does Ang 2 act on?
• AT1 and AT2
What is the main receptor Ang 2 acts on?
• AT1
What type of receptors AT1 and AT2
• G protein couples
What five places does angiotensin effect?
• Arterioles • Kidney • Sympathetic NSAdrenal cortex • Hypothalamus
Outline what angiotensin 2 does to the following-Arterioles
• Vasoconstriction • Vasoconstricts afferent and efferent arterioles
Outline what angiotensin 2 does to the followingKidney
• Stimulates Na+ reabsorption at the kidney
What does angiotension 2 do to the hypothalamus?
• Stimulates ADH release
Outline what angiotensin 2 do in the nephron
• Vasoconstriction of afferent and efferent arterioles • Enhanced Na+ reabsorption at the PCT in apical membrane
What does aldosterone do?
• Stimulates Na+ and water reabsorption • Acts on principal cells of collecting duct • Activates/increases expression apical Na+ channel (ENaC) and apical K+ channel • Also increases basolateral Na+ extrusion via activation/increased expression Na/K/ATPase
What inhibits aldosterone?
• Spironolactone
What does ACE do other than its direct effects?
• Breaks down bradykinin -> Peptide fragments
Why do ACE inhibitors cause a cough?
• Reduce breakdown of bradykinin • More bradykinin, more vasodilation • Also causes cough in lungs
Give three ways sympathetic nervous system effects BP
• High levels of sympathetic innervation reduces renal blood flow (Decreased GFR/Decreased Na+ excretion) • Activates apical Na/H-exchanger and basolateral Na/K ATPase in PCT • Stimulates renin release from Jgcells ○ Leads to increased Ang 2 levelsIncreased aldosterone
How does sympathetic stimulation effect the nephron?
• Acts on arterioles to reduce renal blood flow • Stimulates granular cells of afferent arteriole to release renin • Stimulates Na+ reabsorption from PCT via renin-ang-aldosterone axis
What is the main role of ADH?
• Formation of concentrated urine by retaining water and controlling plasma osmolarity
What is ADH release triggered by?
• Stimulated by increases in plasma osmolarity or severe hypovolaemia
How does ADH generate concentrated urine?
• Addition of aquaporin to collecting duct • Stimulates apical Na/K/Cl co-transporters in thick ascending limb, increasing water reabsorption down conc gradient
How does addition of aquaporin by ADH to collecting duct effect blood volume?
• Re-absorption of water • Forms concentrated urine
How does stimulation of Na/K/Cl co-transporter in the thick ascending limb increase reabsorption of water?
• Less Na+ moves out into the medulla, reduced osmotic
What occurs after a 5-10% drop in blood pressure?
• Low pressure baroreceptors in the atria and pulmonary vasculature send signals to the brainstem via the vagus nerve • This activity modulates both sympathetic nerve outflow, secretion of ADH and a reduction in ANP release
What occurs after a 5-150% drop in blood pressure?
• High pressure baroceptors (carotid sinus/aortic arch) • Impulses sent via vagus and glossopharyngeal nerves • Increase sympathetic nerve activity and secretion of ADH
What is the role of atrial natriuretic peptide?
• Promotes Na+ excretion • Released from atrial cells in response to stretch (high BP)
How is release of ANP inhibited?
• Synthesised and stored in atrial myocytes • Low pressure sensors in atria can inhibit release if detect low pressure
What does ANP do?
• Vasodilation of afferent arteriole of kidney • Increased blood flow increase GFR • Inhibits Na+ reabsorption along the nephron • Acts in opposite direction to the other neurohumoral regulators
What is the main role of prostaglandins?
• Act as vasodilators • Locally acting prostaglandins enhance glomerular filtration and reduce Na+ reabsorption • Act as a buffer to excessive vasoconstriction produced by SNS and RAA system • Important when levels of Ang 2 are high
What is an NSAIDs?
• Non-steroidal anti-inflammatory drug
How do NSAIDs effect prostaglandins?
• Inhibit cyclo-oxygenase (COX-1) pathway involved in formation of prostaglandins
Why would it be a terrible idea to administer NSAIDs when patient’s renal perfusion compromised?
• Further decrease GFR -> acute renal failure
Why should NSAID’s not be given to heart failure or hypertensive patients
• Can exacerbate the condition by increasing NaCl and water retention
How do you calculate mean arterial BP?
• CO x TPR
How do you calculate CO?
• SVxHR
What is hypertension?
• Sustained increase in BP • Hypertension - 140/90 +
What is mild hypertension
• 140-159/90-99
What is moderate hypertension?
• 160-179/100-109
What is severe hypertension
• >180/>110
What is the most common type of high blood pressure?
Essential hypertension (cause unknown
What do you call hypertension where cause can be defined?
• Secondary hypertension
Give four possible causes of secondary hypertension
• renovascular disease • chronic renal disease • aldosteronism Cushing’s syndrome
Give two possible causes of essential hypertension
• Genetic • Environmental
What is renovascular disease and how does it cause secondary hypertension?
• Occlusion of the renal artery causes fall in perfusion pressure • Decreased perfusion pressure leads to increased renin production • Activation of RAAS • Vasoconstriction and Na+ retention at other kidney
What is renal parenchymal disease?
• Loss of vasodilator substances • Causes Na+ and water retention due to inadequate filtration
Give three adrenal causes of secondary hypertension
• Conn’s syndrome • Cushing’s syndrome • Tumour of the adrenal medulla
What is conn’s syndrome?
• Aldosterone secreting adenoma ○ Causes hypertension and hyperkalaemia
What is Cushing’s syndrome and how does it cause high BP (get this wrong and you’re a disgrace)
• Excess secretion of cortisol • At high conc acts on aldosterone
How can a phaeochromocytoma cause secondary hypertension?
• Secretes catacholamines which increase BP
Why is it important to treat hypertension?
• Damages heart and vasculature • Can lead to heart failure, Mi, stroke, renal failure and retinopathy
Give the two main effects of hypertension?
• Increased afterload • Increased arterial damage
What does increased afterload cause?
• Left ventricular hypertrophy -> Heart failure • Increased myocardial oxygen demand -> Myocardial ischaemia and MI
Give two forms of arterial damage
• AtherosclerosisWeakened vessel
What are the results of arterial damage?
• Myocardial ischaemia and MI • Cerbro-vascular disease and stroke • Aneurysm • Nephro-sclerosis and renal failure • Retinopathy
Give five ways of treating hypertension
• ABCDE • ACE-inhibitors • Beta blockers • Calcium ion channel blockers (vasodilators) • Diuretic (Thiazide and loop) • Exercise and other lifestyle factors
What do ace inhibitors do?
• Block production or action of Ang 2 • Vasodilation, reduced aldosterone
What do diuretics do?
Reduce circulating volume of fluid
Name a diuretic
• Thiazide diureticInhibits Na/Cl co-transporter on apical membrane of cells in distal tubule
Name an aldosterone inhibitor
Spironolactone
Name two types of vasodilators
• L-type Ca channel blockers ○ Reduces Ca2+ entry to vascular smooth muscle cells ○ Relaxation of vascular smooth muscle • A1 receptor blockersReduces sympathetic tone (relaxation of vascular smooth muscle
What do Beta Blockers do?
• Reduce heart rate and contractility • Not used in first line treatment
Give four non-pharmacological approaches to reducing BP
• Exercise • Diet • Reduced Na+ intake • Reduced alcohol intake
What is responsible for short term regulation of BP?
• Baroceptor reflex
Outline the baroceptor reflex
• High mean arterial pressure detected by Baroceptors • Afferent pathway to medulla • Medulla processes response • Efferent pathway to heart and blood vessels • Bradycardia and vasodilation modify BP
Why are the baroceptors not suited to longer term control?
• Baroceptors firing recents and adapts to blood pressure
