M103 T3 L10 Flashcards
Why isn’t bp mainly measured at the GP?
white coat syndrome
What are the two main methods for measuring bp over a 24 hour period?
ambulatory bp monitoring
home bp monitoring
What is the range for a high and a normal bp?
high: x > 150 / 95 mmHg over 24hrs
normal: 120 / 80 mmHg
What is the equation for bp?
bp = cardiac output x total peripheral resistance
What is the equation for cardiac output?
cardiac output = stroke volume x heart rate
What is the process by which the symp NS constricts arterioles to increase bp?
baroreceptors detect low cardiac output and low bp in the aorta
sends messages to medulla oblongata
symp NS activated
releases noradrenaline and adrenaline from adrenal glands
noradrenaline binds to alpha-1 receptors present on the smooth muscle of the arterial
causes constriction of the arterioles
increase in afterload
causes the left ventricle to have to contract with more force to pump blood into the systemic circulation
bp increases
Which receptors does noradrenaline bind to?
a & b-1 receptors
In what three ways can the symp NS increase bp?
constricting arterioles / venules
increasing peripheral resistance
increasing the frequency and force of contraction of the heart
What is the process by which the symp NS constricts venules to increase bp?
noradrenaline binds to a-1 receptors present on the smooth muscle of the venules
constricts the veins - blood is squeezed back up which helps it return to the heart, increases preload
as preload increases, the force of contraction of the heart will increase to get rid of the additional blood that is returning
so cardiac output will increase
What is the relationship between preload and the force of contraction?
the greater the preload, the more powerful the contraction is
What types of drugs are used to treat hypertension?
a-1 antagonist
b-1 antagonist / beta blockers
What three things do a-1 antagonists reduce?
arterial constriction
peripheral resistance
preload
What effect do b-1 antagonists have on hypertension?
reduce the ability of the symp NS to increase the frequency and or to increase the force of contractility in the heart
What effect does the symp NS have on the heart?
increases frequency of contraction
increases force of contraction
What effect does the parasymp NS have on the heart?
decreases frequency of contraction
decreases force of contraction
How does the symp NS increase force and rate of contraction?
(nor)adr < b1 receptors < cAMP < ca2+ < SA node cells
releases adr and noradr that act on β1 receptors
increases cAMP which increases intracellular calcium in the SA node cells (increases rate) and in the ventricular myocytes (increases force of contraction)
How does the symp NS decrease the rate of contraction?
releases NT ACh
binds to M2 receptor
this decreases cAMP
which decreases the frequency of heart contractions
What are the two types of receptors that respond to ACh?
muscarinic
nicotinic
How are IP3 levels increased?
noradrenalin acts on a-1 receptors
How does IP3 control calcium movement?
increases calcium influx into the muscle cell from the outside
drives the release of calcium from intracellular stores
What are the effects of the release of calcium from intracellular stores?
the muscle cells constrict
the blood vessels constrict
increase in the amount of blood returning to the heart
peripheral resistance increases
What system is activated when the bp is low?
the RAAS system
What does the RAAS do on activation?
causes a decrease in renal perfusion
signals cells in the juxtaglomerular apparatus
What is the function of renin?
to catalyse angiotensinogen into Ang I
What happens to Ang I?
circulates in the bloodstream
is converted into Ang II - its active form by ACE
Where does Ang I converted into II by ACE?
bc the lungs and kidneys have such a rich vascular supply, most of the conversion occurs here
Where is ACE found?
in endothelial cells lining the blood vessels all over the body
What receptor does Ang II bind to?
AT-1 receptor
What happens when Ang II binds to the AT-1 receptor?
stimulates the release of the steroid aldosterone from the adrenal cortex
facilitates the release of noradrenaline from symp terminals into blood vessels
arteriolar vasoconstriction
What are the effects of increased salt and water absorption?
blood volume, stroke volume and bp ics in a knock on effect
What is the effect of aldosterone release?
stimulates the kidney to preserve salt and water in the body
Where is ADH located?
made by the hypothalamus
stored in the posterior pituitary gland
What are the effects of ADH?
makes the tubules in the kidneys more permeable towards collecting water
increases blood volume
increases the amount of blood returning to the heart
increases stroke volume and bp
causes renal perfusion to increase
negative feedback system turns off the signal for ADH
What types of drugs reduce bp?
ACE inhibitors
AT1-receptor blockers
renin inhibitors
What are the effects of ACE inhibitors?
block the action of ACE
this reduces the amount of Ang II produced
reduce Ang II’s effects on all of these systems
will reduce bp
What is the mechanism by which Ang II is released?
dcs in cardiac output, bp and in renal blood flow dcs'd pressure in the glomerulus reduces filtration in the kidneys kidney function is impaired the kidneys activate the RAAS Ang II released
How does Ang II regulate peripheral resistance?
acts on AT-1 receptor to increase IP3 levels
increases intracellular calcium, arteriolar vasoconstriction
increases peripheral resistance, bp
How does blood travel through the nephron?
enters the glomerulus via the affterent arteriole
filtered out into Bowman’s capsule
the glomerular filtrate passes into the PCT
down through the LoH, into the DCT
into the collecting duct where it’ll drain into the ureta and the bladder
exits via the effterent arteriole
Where does salt and water reabsorption occur in a nephron?
PCT, DCT
loop of Henle
What is the mechanism for how aldosterone works?
aldosterone activates cytoplasmic receptors
bind to the nucleus
increases the expression of Na+ channels
increased Na+ and water retention
Where are aldosterone receptors located?
inside the cytoplasm
not on the outside of the cell membrane
How does aldosterone reach its receptor?
aldosterone is a steroid - very lipophilic
so can easily pass through the cell membrane
to get inside of the cytoplasm
What happens when aldosterone binds to its mineralocorticoid receptors?
causes the receptor and the ligand (aldosterone ) to translocate to the nucleus
there aldosterone binds to various response elements on DNA
drives the transcription and translation of two proteins
Where is ENaC located?
it sits in the membrane of the DCT cell that lines the lumen where urine is being formed
What cells make up the lining of the DCT?
simple cuboidal cells
How does ATPase transfer ions into and out of the cell?
pumps 3Na+ into the cell via the ENaC, 2K+ out of the cell
as the concentration of na rises inside the DCT, gets pumped out into the blood - reversed
What patient features will guide a decision on choosing which drug to treat high bp?
Age, Race
Co-existing diseases
What two drug options are under 55s likely to be prescribed as 1LT when treating hypertension?
ACE inhibitor
Ang receptor blockers
How does race influence what drug is most effective when treating high bp?
ACE inhibitors / beta blockers may be less efficacious in black people
even if under 55, treated with ca channel blocker
How do co-existing diseases influence what drug is most effective when treating high bp?
the side effects of drugs in the treatment might make existing coexisting conditions that the patient is suffering from, worse
What two drug options are over 55s likely to be prescribed as first line treatment when treating high bp?
ca2+ channel blockers
How do calcium channel blockers work in over 55s to treat high bp?
Ca’s important for vasoconstriction, so if Ca channel blockers are used, blood vessels relax
peripheral resistance and bp decreases
Why might using other drugs that aren’t calcium channel blockers for over 55s be dangerous?
some of these drugs can reduce the rate and the force of contraction of the heart
What is another term for adrenaline?
epinephrine
How is bp measured instead of at the GP?
it is mostly measured over a 24hr period bc of white coat syndrome
Why is it called the juxtaglomerular apparatus?
bc it is next to (juxta-) the glomerulus
What is the role of the juxtaglomerular apparatus?
Quality Control
to maintain bp and to act as a quality control mechanism to ensure proper GFR and efficient Na+ reabsorption
