Flashcards in Session 4 - Changes in Plasma Volume (Hormonal control) Deck (72)
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1
Where does medium and long term control of blood pressure stem from?
• Neurohumoral responses
Directed at controlling sodium balance and thus extracellular fluid volume
2
How does modification of ECF modify BP?
• Blood plasma part of ECF
• Modifying ECF volume modifies volume of blood
3
What are the four parallel pathways which control BP?
• Renin-angiotensin-aldosterone system
• Sympathetic nervous system
• Antidiuretic hormone (ADH)
• Atrial natriuretic peptide (ANP)
4
Where is renin released form?
• Granular cells of juxtaglomerular apparatus
5
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
6
What does the sympathetic system stimulate to cause renin release?
• B adrenergic receptors of granular cells of JGA
7
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
8
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
9
What does renin do?
• Enzyme released by juxtaglomerular granular cells
• converts angiotensinogen to angiotensin 1
• ACE converts angiotensin 1 to angiptensin 2
10
Where is ACE found?
• On the endothelium of cells, especially in lung
11
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
12
What two receptors does Ang 2 act on?
• AT1 and AT2
13
What is the main receptor Ang 2 acts on?
• AT1
14
What type of receptors AT1 and AT2
• G protein couples
15
What five places does angiotensin effect?
• Arterioles
• Kidney
• Sympathetic NS Adrenal cortex
• Hypothalamus
16
Outline what angiotensin 2 does to the following-Arterioles
• Vasoconstriction
• Vasoconstricts afferent and efferent arterioles
17
Outline what angiotensin 2 does to the following
Kidney
• Stimulates Na+ reabsorption at the kidney
18
What does angiotension 2 do to the hypothalamus?
• Stimulates ADH release
19
Outline what angiotensin 2 do in the nephron
• Vasoconstriction of afferent and efferent arterioles
• Enhanced Na+ reabsorption at the PCT in apical membrane
20
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
21
What inhibits aldosterone?
• Spironolactone
22
What does ACE do other than its direct effects?
• Breaks down bradykinin -> Peptide fragments
23
Why do ACE inhibitors cause a cough?
• Reduce breakdown of bradykinin
• More bradykinin, more vasodilation
• Also causes cough in lungs
24
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 levels
Increased aldosterone
25
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
26
What is the main role of ADH?
• Formation of concentrated urine by retaining water and controlling plasma osmolarity
27
What is ADH release triggered by?
• Stimulated by increases in plasma osmolarity or severe hypovolaemia
28
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
29
How does addition of aquaporin by ADH to collecting duct effect blood volume?
• Re-absorption of water
• Forms concentrated urine
30
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
31
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
32
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
33
What is the role of atrial natriuretic peptide?
• Promotes Na+ excretion
• Released from atrial cells in response to stretch (high BP)
34
How is release of ANP inhibited?
• Synthesised and stored in atrial myocytes
• Low pressure sensors in atria can inhibit release if detect low pressure
35
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
36
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
37
What is an NSAIDs?
• Non-steroidal anti-inflammatory drug
38
How do NSAIDs effect prostaglandins?
• Inhibit cyclo-oxygenase (COX-1) pathway involved in formation of prostaglandins
39
Why would it be a terrible idea to administer NSAIDs when patient's renal perfusion compromised?
• Further decrease GFR -> acute renal failure
40
Why should NSAID's not be given to heart failure or hypertensive patients
• Can exacerbate the condition by increasing NaCl and water retention
41
How do you calculate mean arterial BP?
• CO x TPR
42
How do you calculate CO?
• SVxHR
43
What is hypertension?
• Sustained increase in BP
• Hypertension - 140/90 +
44
What is mild hypertension
• 140-159/90-99
45
What is moderate hypertension?
• 160-179/100-109
46
What is severe hypertension
• >180/>110
47
What is the most common type of high blood pressure?
Essential hypertension (cause unknown
48
What do you call hypertension where cause can be defined?
• Secondary hypertension
49
Give four possible causes of secondary hypertension
• renovascular disease
• chronic renal disease
• aldosteronism
Cushing’s syndrome
50
Give two possible causes of essential hypertension
• Genetic
• Environmental
51
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
52
What is renal parenchymal disease?
• Loss of vasodilator substances
• Causes Na+ and water retention due to inadequate filtration
53
Give three adrenal causes of secondary hypertension
• Conn's syndrome
• Cushing's syndrome
• Tumour of the adrenal medulla
54
What is conn's syndrome?
• Aldosterone secreting adenoma
○ Causes hypertension and hyperkalaemia
55
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
56
How can a phaeochromocytoma cause secondary hypertension?
• Secretes catacholamines which increase BP
57
Why is it important to treat hypertension?
• Damages heart and vasculature
• Can lead to heart failure, Mi, stroke, renal failure and retinopathy
58
Give the two main effects of hypertension?
• Increased afterload
• Increased arterial damage
59
What does increased afterload cause?
• Left ventricular hypertrophy -> Heart failure
• Increased myocardial oxygen demand -> Myocardial ischaemia and MI
60
Give two forms of arterial damage
• Atherosclerosis
Weakened vessel
61
What are the results of arterial damage?
• Myocardial ischaemia and MI
• Cerbro-vascular disease and stroke
• Aneurysm
• Nephro-sclerosis and renal failure
• Retinopathy
62
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
63
What do ace inhibitors do?
• Block production or action of Ang 2
• Vasodilation, reduced aldosterone
64
What do diuretics do?
Reduce circulating volume of fluid
65
Name a diuretic
• Thiazide diuretic
Inhibits Na/Cl co-transporter on apical membrane of cells in distal tubule
66
Name an aldosterone inhibitor
Spironolactone
67
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 blockers
Reduces sympathetic tone (relaxation of vascular smooth muscle
68
What do Beta Blockers do?
• Reduce heart rate and contractility
• Not used in first line treatment
69
Give four non-pharmacological approaches to reducing BP
• Exercise
• Diet
• Reduced Na+ intake
• Reduced alcohol intake
70
What is responsible for short term regulation of BP?
• Baroceptor reflex
71
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
72
