Flashcards in deck_1637351 Deck (72):
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?
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?
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?
What is hypertension?
• Sustained increase in BP • Hypertension - 140/90 +
What is mild hypertension
What is moderate hypertension?
What is severe hypertension
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
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