cvs Flashcards
What is the impact of increased preload in the early stages of heart failure?
A) It increases the force of contraction
B) It has no effect on the force of contraction
C) It decreases the force of contraction
D) It causes immediate heart failure
A) It increases the force of contraction
Initially, increased preload can stimulate stronger heart contractions, but continued increase leads to overstretching and reduced contractility.
What effect do Loop Diuretics have on the luminal Na+/K+/2Cl- transporter in the thick ascending limb of Henle’s loop?
Choices
A) They have no effect on the transporter.
B) They increase the concentration of the transporter.
C) They inhibit the activity of the transporter.
D) They increase the activity of the transporter.
C) They inhibit the activity of the transporter.
Loop diuretics are specifically designed to inhibit the Na+/K+/2Cl- transporter, resulting in a decrease in sodium reabsorption and an increase in urine output.
What is the mechanism by which NSAIDs interfere with the actions of Loop Diuretics?
Choices
A) NSAIDS directly inhibit the Na+/K+/2Cl- transporter.
B) NSAIDS compete with Loop Diuretics for binding sites on the transporter.
C) NSAIDS decrease the production of prostaglandins, which are necessary for the action of Loop Diuretics.
D) NSAIDS increase the production of prostaglandins, which counteract the effects of Loop Diuretics.
C) NSAIDS decrease the production of prostaglandins, which are necessary for the action of Loop Diuretics.
Prostaglandins
1) vasodilate afferent arterioles (PGE2, PGI2)
-> improves GFR
=> enhances renal blood flow
2) inhibit sodium reabsorption in the kidney
NSAIDs reduce production of prostaglandins,
thus reducing renal blood flow and limiting the delivery of the loop diuretic to its site of action,
thus also increasing sodium reabsorption, counteracting the effects of loop diuretics.
What is the primary function of the collecting tubule?
A) Secretion of potassium and hydrogen ions.
B) Regulation of blood pressure and red blood cell production.
C) Reabsorption of water and sodium.
D) Filtration of blood and production of primary urine.
C) Reabsorption of water and sodium.
The collecting tubule is the final segment of the nephron responsible for fine-tuning the volume and composition of urine, primarily through the reabsorption of water and sodium.
What combination of medications does sacubitril-valsartan replace in chronic heart failure treatment?
A) Calcium channel blockers and ACE inhibitors
B) Diuretics and beta-blockers
C) ACE inhibitors or angiotensin receptor blockers
D) Natriuretic peptides and angiotensin II
C) ACE inhibitors or angiotensin receptor blockers
Both serve the same purpose of inhibiting the RAAS
Functions of the diff classes:
1. Calcium channel blockers: Hypertension and Angina, NOT heart failure
<- can affect contractability
2. Beta-blockers: Reduce sympathethic activation and cardiac workload
-> used to complement ACE inhibitors / Sacubitril-Valsartan
3. Diuretics: For symptom relief in Heart Failure
What is the primary function of the thick ascending limb of Loop of Henle
Sodium absorption
via Na⁺/K⁺/2Cl⁻ cotransporter
impermeable to water
results in medulla having high conc of salt
-> generation of medullary osmotic gradient
-> ADH released during dehydration
-> water moves out of collecting duct and into medulla due to osmosis
=> reabsorbed by body
not where majority of sodium reabsorption occurs
-> proximal tubule (65-70%)
What is the primary function of the thin descending limb of Loop of Henle
Reabsorb water
via aquaporin-1
highly permeable to water and impermeable to solutes
water moves out of limb and into medulla as there is high conc of salt in medulla
How does aldosterone affect potassium levels in the body?
A) It has no effect on potassium
B) It decreases potassium secretion
C) It increases potassium reabsorption
D) It increases potassium secretion
D) It increases potassium secretion
recall effects of aldosterone:
promotes sodium reabsorption into bloodstream
-> increased water retention
=> increased BP
at the same time, potassium is transported into tubular lumen
in order to maintain electrical neutrality
as sodium is transported out of tubular lumen (i.e. reabsorbed)
MOA of loop diuretics
inhibit Na⁺/K⁺/2Cl⁻ cotransporter
in thick ascending limb of Loop of Henle
-> less sodium reabsorption
=> more sodium (and thus water) loss
MOA of thiazide diuretics
inhibit Na+/Cl- symporter
in distal convoluted tubule
-> decreased sodium reabsorption
=> increased sodium (and water loss)
sodium loss is less severe than with loop diuretics
one sounds like it, one doesnt
examples of thiazide diuretics
- hydrochlorothiazide
- indapamide
effect of loop and thiazide diuretics on acid-base balance
decreased Na+ reabsorption in loop of Henle and DCT
-> increased delivery of Na+ to collecting duct
-> increase in aldosterone-mediated H+ excretion (and K+ excretion) in the intercalated cells of the collecting duct as compensatory mechanism
-> decreased [H+] in blood
=> metabolic alkalosis
adverse effects of thiazide diuretics
- hyperglycaemia
due to hypokalaemia
-> K+ channels open for a long time
-> hyperpolarisation of cell
-> reduces exocytosis of insulin granules activated by calcium influx - hyperuricaemia
due to thiazides directly increasing urate reabsorption in proximal tubule
effect of thiazide diuretics on potassium
decreased Na+ reabsorption in loop of Henle and DCT
-> increased delivery of Na+ to distal tubule and collecting duct
-> increased K+ secretion (and H+ secretion) in exchange for increased Na+ reabsorption
-> decreased [K+] in blood
=> hypokalemia
also seen in loop diuretics,
but its MOA alr inhibits K+ reabsorption
-> hypokalemia
1st line treatment for HTN
-
ACEi (“pril”)
and ARB (“sartan”) - Beta-blockers (“lol”)
- CCB (DHP) (“dipine”)
- Diuretics (thiazides) (“ide”)
“ABCD”
2nd line treatment for HTN
- Hydralazine
- Alpha-adrenergic antagonists (“azosin”)
- Mineralocorticoid receptor anatagonists
“HAM”
two types of potassium-sparing diuretics (and their examples)
aldosterone antagonist:
1. eplerenone
2. spironolactone
inhibit sodium channels:
1. amiloride
2. triamterene
effect of eplerenone and spironolactone on potassium
blocks the effects of aldosterone, which normally promotes sodium reabsorption and potassium excretion in collecting tubules
-> decreased potassium excretion
=> hyperkalemia
effect of eplerenone and spironolactone on acid-base balance
blocks the effects of aldosterone, which includes H+ secretion
-> reduced H+ secretion and increased H+ retention in blood
-> higher [H+] in blood
=> metabolic acidosis
Aldosterone increases Na⁺ reabsorption
-> creates negative charge in tubular lumen
-> drives H+ (and K+) secretion to balance the charge
effect of amiloride and triamterene on potassium
inhibit sodium channels
-> reduce sodium reabsorption
(-> reduce negative luminal charge created)
-> reduce secretion of potassium via other channels
-> increased [K+] in blood
=> hyperkalemia
loop and thiazide diuretics work on more proximal parts of nephron (loop of Henle and DCT respectively)
-> affect amt of Na+ reaching DCT and collecting ducts
=> can be regulated one last time at DCT and collecting ducts
In contrast, potassium-sparing diuretics work on collecting tubule itself
THUS 2 different effects
effect of amiloride and triamterene on acid-base balance
inhibit sodium channels
-> reduce sodium reabsorption
(-> reduce negative luminal charge created)
-> reduce secretion of H+ via other channels
-> greater [H+] in blood
=> metabolic acidosis
loop and thiazide diuretics work on more proximal parts of nephron (loop of Henle and DCT respectively)
-> affect amt of Na+ reaching DCT and collecting ducts
=> can be regulated one last time at DCT and collecting ducts
In contrast, potassium-sparing diuretics work on collecting tubule itself
THUS 2 different effects
What is the primary role of lipoprotein lipase in the exogenous pathway?
A) Hydrolyzing triglycerides in chylomicrons to release free fatty acids
B) Transporting cholesterol from the liver to the tissues
C) Synthesizing new triglycerides in the liver
D) Removing excess cholesterol from the body and transporting it to the liver
A) Hydrolyzing triglycerides in chylomicrons to release free fatty acids
-> releases free fatty acids,
which can then be taken up by muscle and adipose tissue for energy or storage
What is the primary role of HDL-cholesterol in preventing coronary artery disease?
A) It promotes the formation of fatty plaques in arteries.
B) It removes excess cholesterol from the body and transports it to the liver.
C) It transports triglycerides to the tissues.
D) It inhibits the production of cholesterol by the liver.
B) It removes excess cholesterol from the body and transports it to the liver.
HDL plays a key role in reverse cholesterol transport:
collects excess cholesterol from peripheral tissues and blood vessels
-> transports to liver
-> where they are converted into bile acids
=> prevent cholesterol buildup and reduce risk of CAD
Why is LDL-cholesterol often referred to as “bad” cholesterol?
A) It is transported to the tissues via chylomicrons.
B) It is primarily composed of triglycerides.
C) It is produced by the liver.
D) It can contribute to the formation of fatty plaques in arteries.
D) It can contribute to the formation of fatty plaques in arteries.
LDL carries cholesterol from the liver to the tissues and blood vessels
-> excess or oxidisation results in deposition of cholesterol in wall of arteries
=> formation of atherosclerotic plaques
Which of the following is a beta-blocker that is contraindicated in slow metabolizers with asthma?
Choices
A) Atenolol
B) Nebivolol
C) Propranolol
D) Metoprolol XL
C) Propranolol
Non-selective B blocker, while others are B1-selective
-> can induce bronchoconstriction
+ Propranolol metabolised by CYP2D6 enzyme
-> slow metabolisers of CYP2D6 experience higher drug levels
=> increased risk of adverse effects (e.g. bronchoconstriction)
smooth muscle relaxation pathway
NO activates Guanylyl Cyclase
-> converts GTP to cGMP
-> cGMP then activates myosin light-chain phosphatase (MLCP)
-> which dephosphorylates Myosin Light Chain (MLC)
=> relaxation of smooth muscle
MOA of nitrates
- main mechanism: REDUCE myocardial O2 demand via
1. dilation of SYSTEMIC veins (venodilation)
-> increase venous capacitance and reduce amt of blood returning to heart
=> reduce preload
2. dilation of SYSTEMIC arterioles (arteriolar dilation)
-> lower TPR
=> reduce afterload - side mechanism: IMPROVE O2 supply
via dilation of CORONARY arteries
recall and link to smooth muscle relaxation pathway!
nitrates release NO
-> which activates Guanylyl Cyclase
-> converts GTP to cGMP
-> cGMP then activates myosin light-chain phosphatase (MLCP)
-> which dephosphorylates Myosin Light Chain (MLC)
=> relaxation of smooth muscle
which of the following is not an effect of nitrates?
A) Headache
B) Bradycardia
C) Reflex tachycardia
D) Hypotension
B) Bradycardia
nitrates cause hypotension (D)
due to its dilation of systemic blood vessels
(venodilation and arteriolar dilation)
-> decreased preload and afterload
-> decreased SV (and thus CO) and decreased TPR
=> decreased BP
which then causes reflex tachycardia (C), not bradycardia
as the drop in BP
-> activation of baroreceptor reflex in carotid sinus and aortic arch
-> sympathetic system activated
-> increased HR to compensate for reduced CO
BP = CO (= SV x HR) x TPR
headache (A) is due to
dilation of cerebral blood vessels
-> increased intracranial blood volume and pressure
(increase pressure instead of decrease as intacranial space is fixed)
what does Myosin Light Chain Kinase (MLCK) do
active form
-> phosphorylates MLC
=> contraction of smooth muscle
MOA of beta-blockers
antagonise beta-1 adrenergic receptors
-> prevent activation of Gs protein
-> reduce activity of adenylyl cyclase
-> less conversion of ATP to cAMP
-> decreased activity of PKA
-> reduced phosphorylation of L-TYPE Ca2+ channels,
-> decreased calcium influx,
which limits CICR from sarcoplasmic reticulum
-> reduce formation of calcium-calmodulin complex
-> decreased activation of MLCK
-> reduced MLC phosphorylation
=> decreased contractility of cardiac myocytes
BP = CO (SV x cardiac contractility) x HR
one adverse effect of beta blockers
C) CNS effects
known as “Beta-Blocker Blues”,
commonly include vivid dreams and clinical depression
example of mixed (3rd gen) beta blocker
nebivolol
“newbie-volol”
* B1-selective in low dose
* Non-selective in high dose
why might beta blockers be contraindicated in asthma
antagonise beta-2 adrenergic receptors
-> prevent activation of Gs protein
-> reduce activity of adenylyl cyclase
-> less conversion of ATP to cAMP
-> decreased activity of PKA
-> reduced inactivation of MLCK via phosphorylation
-> increased MLC phosphorylation
-> smooth muscle contraction
=> bronchoconstriction
think abt the pathway of angiotensin
what is the difference in MOA
between angiotensin converting-enzyme inhibitor (ACEi) and AT1 receptor blockers (ARB)
pathway:
Ang I converted into Ang II by ACE
-> Ang II binds to AT1 receptors in vascular smooth muscles, causing vasoconstriction
AND Ang II binds to AT1 receptors and stimulate aldosterone secretion, causing sodium and water retention
- ACEi inhibits ACE
-> less conversion of Ang I to Ang II
-> lower levels of Ang II
-> less vasoconstriction
AND less aldosterone secretion -> less sodium and water secretion - ARB prevents binding of Ang II to AT1 receptors
-> less vasoconstriction
AND less aldosterone secretion -> less sodium and water secretion
What is the key adverse effect that differentiates ACEi and ARB?
- ACEi prevent inactivation of bradykinin
- accumulation of bradykinin
- (a) irritation of respiratory tract
=> dry cough
(b) increase NO and PG
-> inflammation-like responses (e.g. angioedema)
Why should we avoid prescribing ACE inhibitors in patients with renal stenosis?
Decreased conversion of Angiotensin I to Angiotensin II
-> Decreased aldosterone
-> Decreased Na+ and H2O retention
-> Decreased BP and bloodflow to kidneys
-> Decreased eGFR
=> ACUTE RENAL FAILURE
decreased Na+ and H20 retention
-> decreased blood vol
-> decreased preload
-> decreased SV and thus CO
recall! BP = CO (SV x contractility) x HR
MOA of PCSK9 inhibitors
inhibit PCSK9
-> prevent the internalisation and degradation of LDL receptors
-> more LDL receptors remaining on liver cells
-> increased clearance of LDL from bloodstream
=> lower LDL levels
i.e. what type of hypercholesterolemia
when is PCSK9 inhibitors usually used
patients with severe hypercholesterolemia
who do not respond well to statins
usually used when statins alone DO NOT sufficiently lower LDL levels
(greater LDL reduction when combined due to diff MOA)
i.e. what type of hypercholesterolemia
when is fibrates usually used
patients with hypertriglyceridemias
with VLDL elevation
MOA of statins
inhibit HMG-CoA reductase,
the rate-limiting enzyme in cholesterol synthesis
=> reduce cholesterol synthesis in liver
What are the primary adverse effects associated with statin therapy?
A) Increased risk of stroke and heart attack
B) Respiratory problems and increased risk of infection
C) Liver and muscle problems
D) Gastrointestinal upset and diarrhea
C) Liver and muscle problems
Adverse effects include
- myopathy (muscle pain) and rhabdomyolysis (severe muscle breakdown)
- elevated liver enzymes
MOA of omega-3-acid ethyl esters
directly inhibit synthesis of triglycerides in liver
=> reduce VLDL production
What is the primary clinical application of omega-3 acid ethyl esters in the treatment of lipid disorders?
A) Treatment of hyperchylomicronemia.
B) Treatment of familial hypercholesterolemia.
C) Treatment of hypercholesterolemia alone.
D) Treatment of hypertriglyceridemia
and of hyperlipidaemia (in combination with statins).
D) Treatment of hypertriglyceridemia (Type IV)
and of hyperlipidaemia (in combination with statins).
Used alongside statins in patients with Familial Combined Hyperlipidemia (Type IIb)
[high TG and high LDL]
when control of TG is insufficient
recall! omega-3 acid ethyl esters directly inhibit synthesis of triglycerides in liver
=> reduce VLDL production
treatment of
- hyperchylomicronemia: low-fat diets (recall chylomicrons is exogenous source of TG)
- familial hypercholesterolemia: statins, PCSK9 inhibitors
What is the primary clinical application of bile acid binding resins in the treatment of lipid disorders?
A) Treatment of hyperchylomicronemia.
B) Treatment of familial hypertriglyceridemia.
C) Treatment of hypercholesterolemia alone.
D) Treatment of hypercholesterolemia
and of hyperlipidaemia (in combination with niacin).
D) Treatment of hypercholesterolemia (Type IIa)
and of combined hyperlipidaemia (Type IIb) (in combination with niacin).
Used alongside niacin in patients with Familial Combined Hyperlipidemia (Type IIb)
[high TG and high LDL]
bcos bile acid binding resins lower LDL
while niacin lowers TG
niacin (= Vit B3) lower TG levels
by reducing release of fatty acids into bloodstreams,
which are used by liver to synthesis TG
=> reduce TG synthesis
Which of the following is a common gastrointestinal adverse effect associated with the use of omega-3 acid ethyl esters?
A) Nausea.
B) Myositis.
C) Constipation.
D) Gallstones.
Recall! MOA of omega-3 acid ethyl esters:
directly inhibit synthesis of triglycerides in liver
=> reduce VLDL production
C) Constipation.
alongside abdominal distension, diarrhoea and flatulence
Whether diarrhoea or constipation depends on individuals
- diarrhoea due to increased fat content which have a laxative effect
(e.g. due to fat drawing water into gut)
- constipation due to slowing of gastric emptying, leadin to delayed bowel movements
Contraindication for omega-3 acid ethyl esters
patients who are allergic to fish
as omega-3 acid ethyl esters are derived from fish oil
Example of omega-3 acid ethyl esters
omacor
What is a potential concern associated with the use of omega-3 acid ethyl esters in certain patients?
A) Reduced liver function.
B) Increased risk of bleeding.
C) Increased risk of gastrointestinal ulcers.
D) Increased risk of kidney stones.
B) Increased risk of bleeding.
as it reduces production of thromboaxane A2 (TXA2)
which is essential for platelet clotting
-> increased bleeding time
=> special care needed for patients on anticoagulants such as aspirin and warfarin
recall! NSAIDs are the ones associated with increased risk of gastrointestinal ulcers
Which of the following is a common adverse effect associated with PCSK9 inhibitors?
A) Increased risk of stroke and heart attack
B) Liver damage and dysfunction
C) Muscle pain and weakness
D) Injection site reactions, such as redness, swelling, or pain
D) Injection site reactions, such as redness, swelling, or pain
PCSK9 inhibitors are administered via subcutaneous injection and thus can cause injection-related adverse effects including above and hypersensitivity reactions
recall!
liver toxicity and muscle-related side effects both associated with statins
Why is HMG-CoA reductase most active in the evening?
A) The body only synthesizes sufficient cholesterol in the evening.
B) Cholesterol synthesis is primarily driven by the body’s own production in the evening.
C) Cholesterol synthesis is significantly reduced in the evening.
D) Cholesterol synthesis is entirely dependent on external sources in the evening.
B) Cholesterol synthesis is primarily driven by the body’s own production in the evening.
Less food consumption and thus dietary cholesterol in evening
-> body has to synthesis own cholesterol
HMG-CoA reductase is the rate-limiting enzyme in cholesterol synthesis
also means that statins (= HMG-CoA reductase inhibitor) will have greater effect
=> best taken in evening
MOA of fibrates
are the ligand and thus activates PPAR-a, a transcription factor, resulting in increased expression of genes involved in lipid breakdown
1) including LPL
→ increased hydrolysis of TG
⇒ decrease in plasma TG levels
2) enzymes involved in FA B-oxidation pathway (e.g. CPT1)
→ increased FA B-oxidation
→ decreased hepatic production of TG
→ liver produces and secretes less VLDL into blood
⇒ decrease in plasma TG levels
(since VLDL is TG-rich)
and decrease in blood LDL
(since LDL <- VLDL)
2) apolipoproteins of HDL
→ increased HDL synthesis
⇒ increase in plasma HDL
contraindication for HMG-CoA reductase inhibitors
pregnancy, children and teenagers
as it affects neurodevelopment of fetus and children
unique adverse effect of fibrates
gall-stones
think abt intracellular cholesterol and plasma LDL
MOA of bile acid binding resins
bind to negatively charged bile acids and bile salts in small intestine
-> dereased bile acid reabsorption and increased excretion
-> liver senses bile acid shortage
-> compensates by converting more cholesterol into bile acids
=> decrease in intracellular [cholesterol]
-> liver upregulates LDL receptors to pull more LDL from bloodstream
=> decrease in plasma LDL levels
example of bile acid binding resins
cholestyramine
think abt intracellular cholesterol and plasma LDL
MOA of bile acid binding resins
bind to negatively charged bile acids and bile salts in small intestine
-> dereased bile acid reabsorption and increased excretion
-> liver senses bile acid shortage
-> compensates by converting more cholesterol into bile acids
=> decrease in intracellular [cholesterol]
-> liver upregulates LDL receptors to pull more LDL from bloodstream
=> decrease in plasma LDL levels
Which of the following is/are adverse effect(s) associated with the use of bile acid binding resins?
A) Constipation.
B) Diarrhoea.
C) Flatulence.
D) Impaired absorption of Vitamins A, D, E and K.
E) All of the above.
E) All of the above.
Constipation due to resins binding to bile acids
-> form insoluble complex
-> reduce water content in stool
=> slow intestinal motility
Diarrhoea due to some bile acids left unbound by resins
-> undigested bile acids reach colon
=> draw water into intestines
Flatulence due to resins binding to bile acids
-> reduce fat digestion
->more undigested fat reaches colon
=> gut bacteria ferment it and produce gas
Impaired absorption due to resins binding to bile acids
-> reduce fat digestion (via emulsification, micelle formation and absorption)
=> reduce absorption of fat-soluble vitamins
MOA of Ezetimibe
inhibits NPC1L1 transporter
-> less cholesterol transported from gut into enterocytes (intestinal cells)
-> less cholesterol enters bloodstream
-> liver responds by increasing LDL receptor expression
=> lower levels of LDL
cholesterol from food and bile absorbed in small intestine
-> packaged into chylomictons
-> enters circulation
Why Is Ezetimibe Often Used with Statins?
Statins reduce cholesterol production in the liver
while Ezetimibe reduces cholesterol absorption in the gut.
Thus, combining both targets two sources of cholesterol, leading to a greater LDL reduction
ezetimibe + simvastatin = vytorin
What is the role of prostacyclin (PGI₂) in platelets?
A) Promotes platelet aggregation
B) Inhibits platelet activation by increasing cAMP
C) Activates thromboxane A₂ synthesis
D) Causes platelets to release granules
B) Inhibits platelet activation by increasing cAMP
healthy blood vessel
-> endothelial cells release PGI2
-> causing synthesis of cAMP via its binding to platelet membrane receptors
-> which inhibits release of granules containing aggregating agents
=> prevent platelet activation and aggregation
What is the function of thromboxane A₂ (TXA2) in platelet aggregation?
A) Inhibits platelet activation
B) Promotes release of ADP and serotonin
C) Increases cAMP levels
D) Prevents platelet adhesion
B) Promotes release of ADP and serotonin
blood vessel w/ damaged endothelium
-> exposed collagen fibers
-> thrombin, TXA2 and exposed collagen stimulate platelets to release arachidonic acid (AA) from their membranes
-> AA is converted into TXA2 (via pathway involving Prostaglandin H2)
-> TXA2 binds to specific receptors on other platelets
-> releasing aggregating agents like ADP, serotonin and TXA2 itself
=> platelet aggregation
MOA of aspirin
acetylates cyclooxygenase (COX)
=> irreversibly inhibits synthesis of TXA2
What is/are the adverse effects of aspirin?
A) Bleeding
B) Blood clots
C) Gastric upset and ulcers
D) Nausea
A) Bleeding and C) Gastric upset and ulcers
Reduced levels of PGI2
-> blood vessels do not dilate as effectively
=> less efficient blood flow to tissues and thus slower healing at injury sites
Reduced levels of PGE2
-> less secretion of mucus and bicarbonate
-> compromised protective barrier of stomach liming
=> irritation (gastric upset), mucosal damage and eventual ulcer formation
Recall: In the pathway of AA -> TXA2, PGH2 not only forms TXA2, but also PGI2 and PGE2
MOA of GPIIb/IIIa receptor blocker
prevent fibrinogen from binding to GPIIb/IIIa receptors
(exposed on platelet surface upon activation)
-> prevent formation of bridge bet platelts (cross-linking)
=> prevent platelet aggregation
fibrinogen -> GPIIb/IIIa receptor occurs during PRIMARY hemostas
MOA all slightly diff,
with A irreversibly binding receptor (irreversible inhibitor),
T reversibly binding to receptor (competitive inhibitor)
and E reversibly binding to receptor (competitive mimicker inhibitor)
Which of the following agents is NOT a GPIIB/IIIA receptor blocker?
A) Eptifibatide
B) Abciximab
C) Tirofiban
D) Dipyridamole
fibrinogen -> GPIIb/IIIa receptor occurs during PRIMARY hemostas
D) Dipyridamole
Dipyridamole inhibits phosphodiesterase (PDE) enzymes
-> inhibit conversion of cAMP into 5’ -AMP
-> increase in intracellular cAMP in platelets
-> greater inhibition of the release of granules containing aggregating agents
=> prevent platelet activation and aggregation
Which of the following is a small molecule inhibitor of the GPIIB/IIIA receptor?
A) Dipyridamole
B) Eptifibatide
C) Abciximab
D) Tirofiban
fibrinogen -> GPIIb/IIIa receptor occurs during PRIMARY hemostas
D) Tirofiban
small molecule,
non-peptide agent that
competes with fibrinogen
to reversibly bind to GPIIb/IIIa receptor
What is the mechanism of action of clopidogrel and ticlopidine?
A) Inhibition of platelet activation by PAF
B) Blockade of the ADP receptor
C) Inhibition of the GPIIB/IIIA receptor
D) Inhibition of thromboxane A2 synthesis
B) Blockade of the ADP receptor
inhibit ADP receptor on platelets
-> prevent ADP-mediated activation of GPIIb/IIIa receptor complex
-> fibrinogen cannot bind to receptor
=> inhibit platelet aggregation
fibrinogen -> GPIIb/IIIa receptor occurs during PRIMARY hemostas
How does low-molecular-weight heparin (LMWH) differ from unfractionated heparin in its mechanism of action?
A) LMWH directly inhibits thrombin, while unfractionated heparin enhances the activity of ATIII.
B) LMWH primarily targets factor Xa, while unfractionated heparin targets both factor Xa and thrombin.
C) LMWH has a shorter half-life than unfractionated heparin, leading to a more rapid onset of action.
D) LMWH binds to ATIII but not to factor Xa, while unfractionated heparin binds to both.
B) LMWH primarily targets factor Xa, while unfractionated heparin targets both factor Xa and thrombin.
LMWH has a shorter chain length
-> lack of binding site for other enzymes (e.g. thrombin (IIa))
What is the mechanism of action of heparin?
A) Direct inhibition of thrombin
B) Inhibition of vitamin K-dependent clotting factors
C) Activation of antithrombin III
D) Direct inhibition of factor Xa
C) Activation of antithrombin III
active heparin binds to ATIII
-> conformational change (exposed active site) which allows for more rapid interaction
for greater inhibition of thrombin,
heparin must bind to BOTH ATIII and thrombin
however, for greater inhibition of factor Xa,
heparin can just bind to ATIII
How does low-molecular-weight heparin (LMWH) differ from unfractionated heparin in its mechanism of action?
A) LMWH directly inhibits thrombin, while unfractionated heparin enhances the activity of ATIII.
B) LMWH primarily targets factor Xa, while unfractionated heparin targets both factor Xa and thrombin.
C) LMWH has a shorter half-life than unfractionated heparin, leading to a more rapid onset of action.
D) LMWH binds to ATIII but not to factor Xa, while unfractionated heparin binds to both.
B) LMWH primarily targets factor Xa, while unfractionated heparin targets both factor Xa and thrombin.
LMWH has a shorter chain length
-> lack of binding site for other enzymes (e.g. thrombin (IIa))
What is the primary mechanism by which beta-blockers decrease contractility in cardiac myocytes?
A) Reduction in cAMP levels through inhibition of adenylyl cyclase
B) Inhibition of calcium influx through L-type calcium channels
C) Direct inhibition of myosin light chain kinase (MLCK)
D) Activation of nitric oxide synthase, leading to increased cGMP production
A) Reduction in cAMP levels through inhibition of adenylyl cyclase
What is the primary function of renin in the angiotensin conversion process?
A) To convert Angiotensin I to Angiotensin II
B) To cleave angiotensinogen to form Angiotensin I
C) To degrade angiotensin II to Angiotensin III
D) To inhibit the action of bradykinin
B) To cleave angiotensinogen to form Angiotensin I
What is the key difference between unfractionated heparin and low-molecular-weight heparin (LMWH)?
A) LMWH is primarily used for the treatment of deep vein thrombosis, while unfractionated heparin is used for prophylaxis.
B) LMWH is more potent than unfractionated heparin.
C) LMWH has a shorter half-life than unfractionated heparin.
D) LMWH has better bioavailability and a longer half-life than unfractionated heparin.
D) LMWH has better bioavailability and a longer half-life than unfractionated heparin.
longer half-life allows LMWH to be used for long-term prevention and treatment of conditions like deep vein thrombosis (DVT) and pulmonary embolism,
as compared to unfractionated heparin which is typically used for acute settings and more intensive treatments, such as in the hospital or during surgeries.
sth that is very uninstinctive
what is one unique adverse effect of heparin
thrombosis and thrombocytopenia
immune-mediated disorder with formation of antibodies against heparin-platelet complex
-> activate platelets
=> abnormal blood clot formation
platelets consumed in blood clot formation
=> decrease in platelet count
What is the primary clinical use of protamine sulfate?
A) To reverse the anticoagulant effects of warfarin.
B) To treat vitamin K deficiency.
C) To prevent and treat haemorrhage associated with heparin therapy.
D) To enhance the anticoagulant effects of heparin.
C) To prevent and treat haemorrhage associated with heparin therapy.
Protamine sulfate binds to heparin and neutralises its anticoagulant effects
Which of the following statements accurately describes the role of vitamin K in coagulation?
A) Vitamin K is a cofactor in the carboxylation of glutamate residues in clotting factors.
B) Vitamin K directly activates clotting factors by binding to their active sites.
C) Vitamin K is a precursor to vitamin K epoxide, which is the active form involved in coagulation.
D) Vitamin K directly inhibits the synthesis of clotting factors.
A) Vitamin K is a cofactor in the carboxylation of glutamate residues in clotting factors.
=> activtion of clotting factors
(C) is incorrect as vitamin K epoxide is the precursor to vitamin K,
and active form of vitamin K is vitamin K hydroquinone
Which of the following anticoagulants is contraindicated in pregnancy?
A) Heparin
B) Warfarin
C) Fondaparinux
D) LMWH
B) Warfarin
crosses placenta readily and can cause a hemorrhagic disorder in fetus
drug-drug interactions of warfarin
metabolised by cytochrome P450
=> must take note of P450-inhibiting/inducing drugs administered with it
(e.g. if P450-inhibiting drug administered with it
-> less P450 to metabolise warfarin
=> overdose of warfarin)
MOA of thrombolytic agents
converts plasminogen to plasmin
=> breakdown of fibrin and fibrinogen itself
process, which part they work and how it relates to CVS
summary of anticlotting drugs
link to CVS:
atherosclerotic plaque grows and becomes unstable
-> outer layer rupture
-> inner contents (e.g. cholesterol, lipids and tissue debris) come into contact with blood stream
-> trigger blood clotting response
=> blood clot formed can obstruct blood flow
classes (general) of drugs used, how they achieve overall aim
summary of treatment for angina
angina occurs when there is a demand-supply mismatch
=> aim of treatment: reduce Dd and/or increase Ss
- vasodilators dilate blood vessels
-> increase blood flow to heart
=> improve Ss and lower Dd - cardiac depressants reduce HR and contractility
=> lower Dd - cardiac pacemaker retardants slows HR w/o affecting contractility
-> improve Ss
vasodilators lower Dd by
- decreasing preload via
venodilation
-> reduced venous returin
-> reduced ventricular filling
=> lower cardiac workload
- decreasing afterload via
arterial dilation
-> decrease resistance heart has to pump against
=> lower cardiac workload
cardiac pacemaker retardants improve Ss
via lowering HR
-> increase diastolic filling time
-> increased coronary perfusion
=> improved oxygen supply to heart
but doesn’t really lower Dd as main factor of Dd is contractility
example of ACEi
Lisinopril
common adverse effect of ACEi
need to elaborate on this card
dry cough
due to bradykinin accumulation
why is Brain Natriuretic Peptide (BNP) / Atrial Natriuretic Peptide (ANP) released in CHF
CHF progresses, fluid accumulates, causing ventricular and atrial stretch.
This stimulates the release of:
Atrial Natriuretic Peptide (ANP) from the atria
Brain Natriuretic Peptide (BNP) from the ventricles
how do BNP/ANP promote natriuresis (Na+ excretion) and diuresis (fluid loss)
by
* Dilating afferent arterioles → ↑ GFR
* Inhibiting renin, aldosterone, and ADH
* Increasing Na⁺ excretion in urine
does so to counteract fluid overload,
but it is usually insufficient in CHF because ADH, RAAS, and sympathetic activation are more dominant
this is bcos CHF patients have persistent low effective circulating volume,
so the body prioritizes water retention (via ADH) over natriuresis
=> fluid overload + hyponatremia
Which of the following heart valves is located between the right atrium and right ventricle?
A) Aortic valve
B) Mitral valve
C) Tricuspid valve
D) Pulmonary valve
C) Tricuspid valve
recall that the valves bet atria and ventricle are the ones w/ numbers
=> bicuspid (= mitral) and tricuspid
Which heart valve prevents backflow of blood into the left ventricle?
A) Aortic valve
B) Pulmonary valve
C) Mitral valve
D) Tricuspid valve
C) Aortic valve
- backflow of blood into LV
=> valve stops blood going
from LV to rest of body - to do so, blood has to flow through aorta
=> aortic valve
Where is sound of aortic valve best heard (during auscultation)?
NOT location of valve
- Right
- 2nd intercostal space
- parasternal
Where is sound of pulmonary valve best heard (during auscultation)?
NOT location of valve
- Left
- 2nd intercostal space
- parasternal
What is the primary function of the chordae tendineae?
A) Open the semilunar valves
B) Anchor the atrioventricular valves to the ventricular walls and prevent prolapse
C) Assist in conduction of electrical impulses
D) Close the atrioventricular valves during systole
B) Anchor the atrioventricular valves to the ventricular
-> prevent prolapse
=> prevent regurgitation
atrioventricular vales = bicuspid (= mitral) and tricuspid valve
papillary muscles attach chordae tendinae to ventricular walls
superficial parts
location of cardiac referred pain
- neck
- shoulder
- medial surface of left arm
what’s the stimulation? which part of spine?
mechanism of cardiac referred pain
- (…) (carrying visceral pain) from heart travel along sympathetic fibres and enter spinal cord segments (…)
- (…) (carrying somatic pain from (…) dermatomes) also enter spinal cord segments (…)
- both nerve fibres enter spinal cord at same level, converge on the same (…) and are carried up to brain in similar way via (…)
- thus, when (…)
or buildup of (…)
stimulate pain nerve endings in myocardium, - brain misattributes pain coming from visceral afferent fibres as coming from somatic sensory fibres instead
- thus, pain from the heart is in correctly perceived by brain as coming from (…) dermatomes
- visceral afferent fibres (carrying visceral pain) from heart travel along sympathetic fibres and enter spinal cord segments T1-T4
- somatic sensory fibres (carrying somatic pain from T1-T4/T5 dermatomes) also enter spinal cord segments T1-T4
- both nerve fibres enter spinal cord at same level, converge on the same 2nd order neurons and are carried up to brain in similar way via spinothalamic tract
- thus, when oxygen deficiency
or buildup of metabolic waste products
stimulate pain nerve endings in myocardium, - brain misattributes pain coming from visceral afferent fibres as coming from somatic sensory fibres instead
- thus, pain from the heart is in correctly perceived by brain as coming from T1-T4/T5 dermatomes
where is the blood coming from
how does coronary circulation arise
- LCA and RCA arise from
L and R aortic sinuses respectively - which are small dilations in aortic valve cusps
cusp = leaflet = flap of tissue which open and close in valves
diastole or systole
when are the coronary arteries filled
Only during diastole
* Systole
-> ventricular contraction
-> blood is flowing from LV to rest of body through aorta
-> aortic valve is open and blood rushes past coronary openings
* Diastole
-> ventricular relaxation
-> aortic valve closes
=> blood backflows into aortic sinuses
and thus into coronary arteries
Implication:
Tachycardia
-> less time for diastole
-> less time for blood to backflow into aortic sinuses and thus into coronary arteries (i.e. coronary filling)
-> reduced O2 supply to heart muscle
=> ischaemia
what does the circumflex artery supply
LA and LV
Circumflex arises from LCA
what supplies the SA and AV nodes
RCA itself
what does the LAD artery supply
- RV and LV
- 2/3 of IV septum
- AV bundle
branches of RCA
(and what they supply)
- marginary artery (AMA): RV
- PDA: 1/3 of IV septum
(and adjacent portions of ventricles)
what is the most commonly occluded coronary artery
LAD
what is coronary dominance determined by
- which artery gives rise to PDA
- usually is RCA
(85% of the time)
in coronary circulation
explain venous drainage
-
great cardiac vein (runs alongside LAD),
middle cardiac vein (runs alongside PDA) and
small cardiac vein (runs alongside AMA)
-> drain into coronary sinus
-> opens into RA
there are also anterior cardiac veins
which drain directly into RA
structures in superior mediastinum
plus their relative order
branchiocephalic vein,
trachea,
oesophagus, nerves (vagus, phrenic),
thoracic duct,
azygos vein
branchiocephalic vein @ most anterior
trachea posterior to oesophagus
vagus and phrenic nerves run alongside oesophagus
thoracic duct quite posterior as it is near vertebrae
azygos vein @ most posterior
separation bet superior and inferior mediastinum
structures at sternal angle
plus their relative order
arch of aorta, pulmonary trunk, ligamentum arteriosum,
tracheal bifurcation,
nerves (vagus and phrenic), thoracic duct,
azygos vein
arch of aorta @ most anterior
ligamentum arteriosum connects arch of aorta to pulmonary trunk
thoracic duct quite posterior as they are near vertebrae
azygos vein @ most posterior
structures in anterior mediastinum
part of inferior mediastinum
thymus
structures in middle mediastinum
part of inferior mediastinum
HEART,
great vessels
(SVC, Ascending aorta, Pulmonary trunk)
structures in posterior mediastinum
part of inferior mediastinum
oesophagus,
thoracic duct,
azygos vein,
descending aorta,
sphlanchic nerves, sympathetic chain
descending aorta is now the most posterior blood vessel,
sympathetic chain @ most posterior,
<- run alongside vertebrae
sphlanchic nerves just slightly anterior as they branch off sympathetic chain
branches
aorta flow
- ascending aorta → arch of Aorta → descending aorta
-
Branchiocephalic artery (R),
L Common carotid and L Subclavian arteries
branch off from arch of aorta - branchiocephalic artery (R) further branches into R Common carotid and R Subclavian arteries
“ABCs”
ligamentum arteriosum can cause what related injury in a car accident
deceleration injury
→ aorta will continue to move forward
→ but ligamentum arteriosum holds it in place
⇒ can cause aorta to tear
what the abnormality is, L to R or R to L shunt
explain ventricular septal defect (VSD)
abnormal opening in interventricular septum
→ blood flows from higher pressure LV to lower pressure RV
⇒ left-to-right shunt
what the abnormality is, L to R or R to L shunt
explain patent ductus arteriosus (PDA)
failure of ductus arteriosus to close after birth
→ blood flows from higher pressure aorta into lower pressure pulmonary artery
=> left-to-right shunt
in fetus,
ductus arteriosus acts as shunt
→ connects pulmonary artery to aorta
→ divert blood away from non-functional lungs and into systemic circulation
upon starting breathing after birth,
increased oxygen levels in blood triggers ductus arteriosus to constrict and close
=> becomes ligamentum arteriosum
what the abnormality is, L to R or R to L shunt
explain tetralogy of fallot (TOF)
- 4 abnormalities:
1. pulmonary stenosis
→ increase RV pressure
2. thus R ventricular hypertrophy
3. ventricular septal defect
→ allow mixing of oxygenated and deoxygenated blood
4. overriding aorta
(where aorta is displaced over VSD, i.e. more to the right)
→ allow the mixed blood to enter systemic circulation - since blood is forced from RV through VSD into aorta
⇒ right-to-left shunt
flow of signals in conducting system
SA node
→ AV node
→ bundle of His (AV bundle)
→ L and R bundle branches
→ purkinje fibres
how does AV nodal delay enable complete ventricular filling
ventricular filling occurs in 2 phases
* passive filling
where blood flows passively from atria into ventricles due to pressure gradient,
accounts for most of ventricular filling
delays electrical transmission, allowing time for
* atrial contraction
where AV node delays electrical transmission
-> ensures that atria contraction is completed before ventricles start contracting
=> tops off ventricles
how does heart prevent direct transmission of impulses from atria to ventricles
fibrous rings which surround AV valves separate atria and ventricles
-> ensure that electrical impulses must go through AV node
Ventricular depolarisation:
During Phase 0, upon reaching threshold membrane potential,
there is (…) through fast voltage-gated (…),
causing a (…)
During Phase 1, there is (…) through (…),
causing a (…)
During Phase 2, there is efflux of K+ through other K+ channels, but this is countered by the (…) via (…),
thus (…)
(almost like a “plateau”)
During Phase 3, there is (…) through other (…),
resulting in (…)
During Phase 4, (…) remain open,
keeping the cell at a stable resting membrane potential
During phase 0, upon reaching threshold membrane potential,
there is rapid INFLUX of Na+ through fast voltage-gated Na+ channels,
causing a sharp depolarisation
During phase 1, there is EFFLUX of some K+ through K+ channels,
causing a small early repolarisation
During phase 2, there is efflux of K+ through other K+ channels, but this is countered by the INFLUX of Ca2+ via Ca2+ channels,
thus sustaining depolarisation
(almost like a “plateau”)
During phase 3, there is EFFUX of K+ through other K+ channels,
resulting in repolarisation
During phase 4, K+ leak channels remain open,
keeping the cell at a stable resting membrane potential
does increased ventricular volume lead to increased stroke volume of increase contractility?
increased stroke volume,
at least until a limit is reached,
according to Starling’s law
strength of contractility is only affected and in fact regulated by sympathetic nervous system,
(via B1-adrenergic receptors which result in Ca2+ influx)
NOT by parasympathetic nervous system
(only receptors in heart is M2 muscarinic receptors on SA and AV nodes)
direct factors affecting HR and contractility
and how
by acting directly on SA node
* Catecholamines (i.e. epinephrine and norepinephrine)
-> activate B1-adrenoceptor receptor
* Thyroxine
-> enhances expression of B1-adrenoceptor receptor
* Temperature
-> higher temp results in faster SA node firing
indirect factors affecting HR and contractility
and how
information is sent to vasomotor centre (in medulla)
-> activates ANS
* e.g. pain
* e.g. PO2 and PCO2 detected by chemoreceptors
* e.g. BP detected by baroreceptors
what happens at each point in ECG
p wave, qrs complex, t wave
p wave: atrial depolarisation
qrs complex: ventricular depolarisation,
atrial repolarisation (masked)
t wave: ventricular repolarisation
q wave: Depolarisation of bundle of His
r wave: Depolarisation of right and left bundles
s wave: Depolarisation of Purkinje fibres and ventricles
Which ECG interval represents the time for one complete cardiac cycle?
A) PR interval
B) RR interval
C) QRS complex
D) QT interval
B) RR interval
What does the PR interval represent?
A) Time for atrial depolarization
B) Time for signal to travel from SA node to ventricles (AV nodal delay time)
C) Time for ventricular depolarization
D) Time for ventricular repolarization
B) Time for signal to travel from SA node to ventricles (AV nodal delay)
measured as BEGINNING of p wave to BEGINNING of qrs complex
> 0.2s is abnormal
and represents heart block
The QT interval represents which of the following?
A) Atrial depolarization and repolarization
B) Ventricular depolarization and repolarization
C) Ventricular depolarization only
D) Conduction delay at the AV node
B) Ventricular depolarization and repolarization
how to determine HR using ECG
300/number of large squares in 1 cardiac cycle
1 cardiac cycle = e.g. between 2 qrs complexes
what does tall QRS in ECG indicate
ventricular hypertrophy
- if seen in V1 and V2 (septal) => RVH
what does ST depression in ECG indicate
partial occlusion or reduction of blood flow in coronary artery
-> subendothelial infarct
-> where only inner layers of heart muscle is affected
=> myocardial ischaemia
esp if many leads involved
if localised to a few leads
-> can be a reciprocal change opp to ST elevation seen in MI
(just rmb as
I ↔ II and III
aVL ↔ aVF)
what does ST elevation in ECG indicate
complete occlusion of coronary artery
-> transmural infarct
-> where all layers of heart muscle is affected
=> myocardial infarction
imagine where all the leads are
avR = towards R arm
(i.e. current heading there is (+))
avL = towards L arm
(i.e. current heading there is (+))
avF = towards Foot
(i.e. current heading there is (+))
leads found in septal area of heart
V1, V2
these 2 are the most “middle” alr
leads found in anterior area of heart
V3, V4
leads found in posterior area of heart
none!
must look for reciprocal changes in leads V1-4
V3 and V4 correspond to anterior area of heart
leads found in lateral area of heart
I, aVL,
V5, V6
* aVL points towards L arm
* lead I also points towards L arm
* V5 and V6 are the most “Left” out of V leads
Lateral = Left side of heart
leads found in inferior area of heart
II, III, aVF,
* aVF points towards Feet
* lead II and III also points towards Feet
inFerior = towards Feet (i.e. lower body)
which areas of heart (and leads) are supplied by LAD
- septal (V1, V2)
recall that LAD supplies 2/3 of septum - anterior (V3, V4)
V3 and V4 covers area only slightly to left of septum
which areas of heart (and leads) are supplied by LCx
Lateral (I, aVL, V5, V6)
since leads are towards Left and are towards many different directions
which areas of heart (and leads) are supplied by RCA
inferior (II, III, aVF)
which valve? open or close?
what marks the start of ventricular diastole
ventricular diastole = isovolumetric relaxation + filling
closure of aortic valve
(due to ventricular pressure dropping below pressure in aorta)
-> triggers isovolumetric relaxation
-> where ventricles relax in a closed chamber
(i.e. both valves are closed)
-> resulting in pressure dropping rapidly
w/ no change in volume
what does opening of mitral valve mark
start of filling phase of diastole
happens when pressure in LV < LA
-> mitral valve opens
-> volume increases
w/ only slight increase in pressure
which valve? open or close?
what marks the start of ventricular systole
ventricular systole = isovolumetric contraction + ejection
closure of mitral valve
-> triggers isovolumetric contraction
-> where ventricles contract in a closed chamber
(i.e. both valves are closed)
-> resulting in pressure increasing rapidly
w/ no change in volume
what does the opening of aortic valve mark
start of ejection phase of systole
happens when pressure in LV > aorta
-> aortic valve opens
-> volume decreases
but pressure continues to increase initially, before gradually decreasing
at first, rapid ejection: ventricles contract forecefully -> eject large vol of blood into aorta
=> pressure still increasing
then, reduced ejection: venticle contraction weakens -> blood still pushed out due to mometum from high-speed blood flow
=> pressure plateaus and starts decreasing
name? relation to valve?
what are the normal heart sounds
- S1: closure of mitral valve
- S2: closure of aortic valve
since closure of mitral valve = start of ventricular systole
and closure of aortic valve = start of ventricular diastole
=> time from s1 to s2 = systole
and time from s2 to s1 = diastole
why does S3 occur
a.k.a. 3rd heart sound
due to rapid flow of blood from atria to ventricles
-> occurs during passive filling of ventricles
=> early diastole (soon after s2)
what causes s4
a.k.a. 4th heart sound
due to stiffening of ventricles
(e.g. from ventricular hypertrophy)
-> atria needs to contract harder to complete filling of ventricles
=> late diastole (before S1)
why does physiological splitting occur
- inspiration lowers intrathoracic pressure
(recall: diaphragm and chest muscles contract -> increase in intrathoracic volume
=> decrease in intrathoracic pressure)
-> larger pressure gradient bet systemic veins and RA
(since RA is inside thorax and systemic veins are not)
-> increase in venous return to RA
-> more blood enters RA and thus later RV
-> RV takes longer to eject blood
-> PULMONARY valve closes later than usual - expansion of lungs result in expansion of alveolar capillaries
-> blood pooling in pulmonary veins
-> less blood return to LA and thus fill LV
-> LV doesn’t need as much time to eject blood
=> AORTIC valve closes earlier than normal -
inspiration
-> difference in closure of pulmonary and aortic valves
=> split S2 (into A2 and P2)
in which groups of individuals are physiological splitting more likely to occur
- young people
- athletes
when does fixed splitting occurs
i.e. splitting heard during both inspiration and expiration
when there is a septal defect
(specifically atrial septal defect (ASD))
that results in L-to-R shunt
-> more blood in RA (and RV) and less in LA (and LV)
-> pulmonary valves closes later and aortic valve closes earlier
=> S2 split into A2 and P2
how to identify if heart sound heard is diastolic or systolic
time with carotid pulse
* Diastolic (S2): occurs after carotid pulse
* Systolic (S1): occurs coincident with carotid pulse
when is aortic and pulmonary stenosis heard
during diastole or systole
systole
* bcos that is when ventricles contract
-> blood moves from
RV to lungs through pulmonary artery
and LV to rest of body through aorta
-> and thus have to pass through
pulmonary valve
and aortic valve
* thus if valves are narrowed
-> blood has to forecfully pass through during systole
=> murmur
mid-systolic (crescendo-decrescendo)
when is aortic and pulmonary regurgitation/incompetence heard
during diastole or systole
diastole
* bcos that is when ventricles relax
and blood is already in aorta and pulmonary artery
* thus if valves are incompetent
-> blood leaks back from blood vessels into ventricles
=> murmur
early diastole
when is mitral stenosis heard
during diastole or systole
diastole
* bcos that is when ventricles relax
-> blood from atria fill ventricles
-> and thus blood have to pass through mitral valve
* thus if mitral valve is narrowed
-> blood has to forecfully pass through
(via atria contracting harder to force blood)
=> murmur
mid-to-late diastole
bcos murmur happens during atria contraction
diastole = passive filling (at start) + atria contraction (towards end)
when is mitral regurgitation/incompetence heard
during diastole or systole
systole
* bcos that is when ventricles contract
while atria relaxes
-> blood is already in ventricles
* thus if mitral valve is incompetent
-> blood is pushed back into LA instead of being ejected into aorta
=> murmur
pan-systolic
where does Jugular Venous Pressure (JVP) arise from
and what does it reflect
- arise from internal jugular vein
- reflect changes in RA pressure
internal and external jugular vein
-> subclavian vein
-> branchiocephalic vein
-> SVC
=> RA
What does the a wave in the JVP correspond to?
A) Atrial contraction
B) Tricuspid valve bulging into the right atrium
C) Atrial relaxation
D) Atrial filling from the vena cava
A) atrial contraction
recall that ventricular filling (during diastole)
= passive filling + atria contraction
=> thus a wave always after y descent
What does the x wave in the JVP represent?
A) Atrial filling from the vena cava
B) Atrial relaxation
C) Tricuspid valve bulging into the right atrium
D) Passive filling of the ventricles
B) Atrial relaxation
The v wave in the JVP reflects:
A) Atrial contraction
B) Atrial filling from the vena cava
C) Passive filling of the ventricles
D) Tricuspid valve bulging into the right atrium
B) Atrial filling from the vena cava
What does the y descent in the JVP correspond to?
A) Atrial contraction
B) Passive filling of the ventricles
C) Atrial relaxation
D) Atrial filling from the vena cava
B) Passive filling of the ventricles
recall that ventricular filling (during diastole)
= passive filling + atria contraction
=> thus y desent always before a wave
what can a prominent a wave be due to
RV hypertrophy or tricuspid stenosis
-> increase in pressure needed to fill RV
-> increase in strength of atria contraction and thus increase in pressure in RA
=> bigger a wave
what can a prominent v wave be due to
tricuspid regurgitation
* if coincident with ventricular contraction
cos that is when tricuspid valve closes to prevent backflow of blood
* thus if tricuspid valve is incompetent
-> blood flows back into RA instead of going into pulmonary artery during systole
-> more blood in RA
-> increase pressure in RA
=> bigger v wave
how is CO calculated and what factors affect it
CO = stroke volume x heart rate
* preload
= volume of blood in ventricles at end of diastole
thus more blood in ventricles
-> more blood to be pumped out
=> increase stroke volume
* afterload
= resistance heart must overcome to eject blood during systole
thus increased resistance
-> harder for ventricles to pump blood out
=> decrease stroke volume
* contractility
increased contractility
-> stronger, more forceful contractions
-> more blood can be pumped out
=> increase stroke volume
what factors affect BP
BP = CO (stroke volume x heart rate) X TPR
TPR = total peripheral resistance
definition of ejection fraction
stroke volume/end-diastolic volume
x 100%
stroke vol = end systolic vol - end diastolic vol
2 types of heart failure
- Heart Failure with Reduced Ejection Fraction (HFrEF):
EF < 40% - Heart Failure with Preserved Ejection Fraction (HRpEF):
EF > 50%
normal EF = 55-75%
cause of HFrEF
LV becomes weak or damaged
-> pump function is impaired
(i.e. much less blood is ejected with each heartbeat)
common causes include MI and HTN
cause of HFpEF
LV becomes stiff and thickened
-> does not relax and fill as well
-> less overall blood being pumped out
even though pumping function is normal
common cause: LVH
what is body’s first response in acute heart failure?
A) Increased BNP/ANP
B) RAAS activation
C) Sympathetic activation
D) Parasympathetic activation
heart damage (ischaemic injury)
-> decreased contractility
-> decrease in CO and SV
-> body responds by activating SNS (i.e. adrenergic stimulation) and inactivating PNS
=> increase HR and contractility which increases CO,
but also excessive sweating due to activation of sweat glands
how does it affect forward and/or backward flow of blood?
effects of LHF
- forward failure
due to reduced stroke volume
=> hypotension
=> decreased organ perfusion
also leads to activation of RAAS
-> increases Na+ and H2O retention
and thus further exacerbates pulmonary oedema - backpressure
due to blood backing up into LA and pulmonary circulation
-> PULMONARY venous hypertension
and PULMONARY oedema
=> breathlessness on exertion, orthopnoea, paroxysmal nocturnal dyspnoea
pathophysiology of pulmonary oedema
decrease in LV ejection fraction causes blood to pool in L side of heart
-> increase in pressures of LV and LA
-> increase in pulmonary venous pressure
-> increase capillary pressure,
which is the major Starling force favouring filtration of fluid into the pulmonary interstitium
-> when filtration of fluid exceeds the capacity of pulmonary lymphatics to remove the fluid
=> pulmonary oedema
must write that capillary pressure is the “major Starling force favouring filtration of fluid into the pulmonary interstitium” in exams
how does pulmonary oedema lead to breathlessness
fluid in lungs
-> hinders efficient exchange of O2 and CO2
-> V/Q mismatch where there is perfusion but poor ventilation
=> shunt
must write that capillary pressure is the “major Starling force favouring filtration of fluid into the pulmonary interstitium” in exams
pathophysiology of exertional dyspnoea
increased O2 consumption and CO2 production during exertion
-> increased ventilatory demand
-> inability of lung to respond to increased demand
due to reduction of gas exchange by pulmonary congestion
=> dyspnoea
1st to develop (early symptom)
pathophysiology of orthopnoea
orthopnoea = dyspnoea that worsens when lying flat
lying down position
-> gravity no longer helps pool blood in legs
-> increased venous return to heart from lower limbs
-> overload on LV (preload)
-> back pressure effect in lungs
-> pulmonary congestion
=> dyspnoea
Last to develop (SNS not working anymore)
when standing up
-> blood pools in legs again
-> load on heart is removed
-> back pressure effect on lungs is eased
-> pulmonary congestion relieved
=> dyspnoea improves
pathophysiology of paroxysmal nocturnal dyspnoea (PND)
patient lies down to sleep
-> pulmonary congestion
through same mechanism as orthopnoeasame as orthopnoea
-> but patient is still awake, so sympathetic activation is adequate to compensate
-> however, when patient goes to sleep, sympathetic activity is reduced
-> pulmonary congestion continues until breathing is compromised
-> patient wakes up breathless, and sits or stands up
-> results in activation of sympathetic system again
and blood pooling in legs
-> pulmonary congestion relieved
and patient feels better
2nd to develop (SNS still working to counter it)
Which of the following happens during RHF?
A) Hepatosplenomegaly
B) Ascites
C) Pedal oedema
D) All of the above
D) All of the above
- Hepatosplenomegaly (A) occurs as
RHF results in blood backing up into venous system (i.e. SVC and IVC and beyond)
-> increased venous pressure
=> hepatic congestion and splenic enlargement - Ascites and pedal oedema occur as
RHF reult in blood backing up into venous system (i.e. SVC and IVC and beyond)
-> increased venous pressure
-> increased hydrostatic pressure in systemic and abdomina capullaries
=> oedema
pathophysiology of lung crackles
LHF results in blood backing up into pulmonary circulation
-> increased pressure in pulmonary circulation
-> increased hydrostatic pressure in pulmonary capillaries
-> fluid forced out into alveoli
-> alveoli collapse
-> however during inspiration, air forces alveoli open
=> alveoli snapping open causes a crackling sound
why collapse?
recall! surfactant produced by type 2 pneumocytes
helps to dispel fluid molecules lining alveoli
-> lowers surface tension which would otherwise cause alveoli to collapse
are the impulses fired by baroreceptors (to regulate BP)
excitatory or inhibitory
inhibitory
when BP increases
-> baroreceptors are streched more
-> increased firing of INHIBITORY impulses
-> REDUCES sympathetic outflow
-> decrease in HR and cardiac contractility
(=> decrease in CO),
as well as results in vasodilation
(=> decrease in TPR)
=> thus decrease in BP
definition of shock
arterial pressure is insufficient to maintain perfusion
symptoms of shock
- related to activation of SNS:
sweating, skin being pale and cold to touch - renal-related (and secondary RAAS activation):
decreased urine output
skin being pale and cold to touch
is due to vasoconstriction
which helps to increase TPR
and thus increase BP
H…
C…
O…
D…
types of shock
- hypovolaemic shock
- cardiogenic shock
- obstructive shock
- distributive shock
(sepsis, anaphylaxis, neurogenic)
who is more likely to have postural hypotension
elderly
due to degeneration of baroreceptor reflexes
which of the following can cause HTN?
A) chronic kidney disease
B) aortic coarctation
C) renal artery stenosis
D) all of the above
D) all of the above
* CKD (A) results in decreased GFR
-> impaired filtration of sodium and water
=> sodium and water retention
-> lower sodium levels detected by MD
-> triggers JG cells to release renin
=> activation of RAAS
* aortic coarctation (B) is congenital narrowing of aorta
-> increased TPR
=> HTN
* renal artery stenosis (C) results in decreased blood flow to kidney
-> kidney misinterprets as low BP and compensations by trying to increase BP
through activation of RAAS
just need to know 1st step
pathogenesis of atherosclerosis
endothelial injury
caused by the 4 modifiable risk factors
* HTN
* dyslipidemia
* diabetes
* tobacco smoking
basically 3 gao + 1
3 non-modifiable risk factors:
* age
* sex
* genetics (ethnicity)
seen in atherosclerosis
describe a stable plaque histologically
soft yellow lipid core,
w/ thick white fibrous cap
in contrast, unstable plaque has
large lipid core w/ thin fibrous cap
other than hypertensive nephropathy, atherosclerosis, arteriolosclerosis
effects of HTN
- aneurysm and aortic dissection
due to high BP
-> increases force exerted on arterial walls
-> progressive damage which
weakens tunica media of aorta
=> dilation of vessel,
resulting in aneurysm
OR tunica intima tearing,
resulting in blood entering vessel wall layers
and thus splitting them apart,
resulting in dissection - heart-related
(e.g. (concentric) hypertrophy of LV, HF, IHD, etc)
i.e. mechanical stress weakening tunica media
covers ALL types of blood vessles
* aneurysm happens in biggest vessel = aorta
* atherosclerosis happens in large vessels incl coronary arteries
* arteriolosclerosis happens in small vessels
What is the most common risk factor for the development of an arterial aneurysm?
A) Atherosclerosis
B) Hypertension
C) Syphilis (3º)
D) Genetic syndromes (e.g. Marfans)
A) Atherosclerosis
due to plaque formation
-> loss of structural integrity of arterial wall
(degeneration of tunica media)
=> dilation of vessel
i.e. ischaemic damage to tunica media
different mechanism from HTN, only thing same is layer affected
what is one clinical presentation of aneurysm?
pulsatile abdominal mass
bcos most common site of aneurysm is abdominal aorta
what are 2 common clinical presentations of aortic dissection?
- sharp shooting pain between the scapulae
- sudden severe stomach pain
both are due to dissection in descending aorta
however, most common site of dissection is ASCENDING aorta
what condition can aortic dissection lead to
one complication of aortic dissection
cardiac tamponade (haemopericardium)
where a dissection in ascending aorta
where tear involves ALL layers of aorta
-> blood can now flow into pericardial space
-> accumulation of blood
-> increases pressure on heart
-> reduce heart’s ability to expand fully
-> reducing its SV and thus CO
(since CO = SV x contractility)
a triad
clinical presentation of cardiac tamponade
Beck triad
* hypotension
due to blood being unable to pump effectively
-> reduced SV and thus CO
(BP = CO x HR)
* distended neck veins
due to heart being unable to pump effectively
-> blood backs up into venous system
=> increased pressure in venous system
and thus increased JVP
* distant heart sounds
due to **accumulation of blood **in pericardium dampening heart sounds
AMI can be indicated by high levels of …
high troponin levels
as troponin is a protein found in heart muscle cells
-> released into bloodstream when heart muscle is damaged
either I or T
but usually T cos Troponin T = heart aTTack
troponin plays a critical role in muscle contraction
what is stable angina characterised by
- arises with exertion
- relieved by rest or nitroglycerin
pain is predictable (i.e. occurs with similar levels of exertion)
bcos chest pain only occus
when exertion increases myocardial O2 demand,
resulting in it exceeding supply
which has been reduced due to FIXED atherosclerotic narrowing of coronary arteries
what is unstable angina characterised by
- chest pain that occurs even at rest or with minimal exertion
OR increased severity, frequency or duration of chest pain - relieved only by nitroglycerin,
but not as effectively (as stable angina)
cause of stable angina
stable plaque, no rupture
recall! histological finding is soft yellow lipid core w/ thick white fibrous cap
cause of unstable angina
unstable plaque
-> rupture
-> formation of thrombus
which partially occludes coronary artery
recall! histological finding of unstable plaque is large lipid core w/ thin fibrous cap
65 year old male
LAST TIME: only has chest pain on maximal exertion.
BUT NOW: In the past 1 week, just walking a short distance gives him chest pain. GTN tablets takes more than 15 minutes for him to have some relief.
His ECG shows non-specific ST depression in leads V1-4.
Serial cardiac troponin T is not elevated.
What does he have?
A) Stable angina which has turned to a myocardial infarction
B) Stable angina which has turned into unstable angina
C) Unstable angina which is complicated by coronary spasm
D) Unstable angina which has turned to a myocardial infarction
E) Stable angina with gastroesophageal reflux caused by aspirin
B) Stable angina which has turned into unstable angina
bcos troponin levels not affected
=> unstable angina
how to describe chest pain in AMI
acute retrosternal chest pain
w/ radiation to left shoulder and arm
retrosternal = behind sternum
(relate to retroperitoneal kidneys)
A: 2
B: 3
C: 1
D: 2
findings on CXR for congestive heart failure
-
Alveolar oedema,
leading to Bilateral perihilar shadowing (Batwing opacities) - Kerley A & B lines (Interstitial oedema)
- Blunting of costophrenic angle (Pleural effusion)
- Cardiomegaly
-
Dilated pulmonary vessels
<- pulmonary venous congestion - Upper lobe Diversion
<- increased visibility of upper lobe veins
(which are usually smaller than lower lobe veins)
<- pulmonary venous pressure forcing blood upwards
type of necrosis expected in myocardium in AMI
coagulative necrosis
bcos of ischemia in organs
recap! histological/microscopic findings:
* ‘ghost cellular outlines’ (i.e. cell structures present without nucleus)
<- denaturation of structual proteins BEFORE enzymatic digestion
* eosinophilic and amorphous cytoplasm
<- denaturation of structural proteins
=> denatured proteins stain pink
=> result in lack of structure
* neutrophil invasion
<- to remove dead cells
0-12h, 12-24h, 24-72h, 3-10 days, 6-8 weeks
describe the gross changes of heart in AMI
- 0-12h: NOT VISIBLE
- 12-24h: mottling, botchy discolouration
- 24-72h: pale yellow
- 3-10 days: hyperemic border around pale yellow area
(reddish area due to reperfusion) - 6-8 WEEKS: fibrous SCAR
0-12h, 12-24h, 24-72h, 3-10 days, 6-8 weeks
describe the histological changes of heart in AMI
- 0-12h: NOT VISIBLE
- 12-24h: eosinophilic and loss of nuclei
(both due to coagulative necrosis),
interstitial oedema
(due to increased capillary permeability and increased plasma hydrostatic pressure) - 24-72h: NEUTROPHIL INFILTRATION
- 3-10 days: granulation tissue starts forming
- 6-8 weeks: fibrous SCAR
0-12h, 12-24h, 24-72h, 3-10 days, 6-8 weeks
describe the complications of AMI
- first 24 hrs: IMMEDIATE AFTERSHOCK
(castle trembles -> electrical failure)
ventricular fibrillation/tachycardia (“power system fails”)
-> sudden cardiac death - 1-3 days: BURNING RUINS
(smoke and fire around castle walls)
inflammation (involves neutrophil infiltration)
-> spread of inflammation from myocardium to pericardium
=> fibrinous pericarditis - 3-10 days: STRUCTURAL COLLAPSE
(weakest point)
ventricular wall rupture (“outer wall collapses”)
-> cardiac tamponade
intraventricular septum rupture (“inner wall collapses”)
-> shunt formation - weeks to months: RECONSTRUCTION
ventricular wall undergoes fibrosis
-> weakened
-> dilation/bulging of walls
=> ventricular aneurysm
(“rebuilt walls are not as strong and can’t take the stress”)
autoimmune pericarditis
=> Dressler syndrome
(“castle’s defenses turn against itself)
Left ventricular wall is MOST LIKELY to rupture after AMI after:
A) 2-3 minutes
B) 2-3 hours
C) 2-3 Days
D) 2-3 months
E) 2-3 years
C) 2-3 Days
formation of granulation tissue (3-10 days after onset)
-> NOT as organised
-> thus does NOT have same tensile strength as normal myocardium or collagen scar
and is at its weakest
=> highest risk of ventricular rupture
thus ventricular rupture is an early complication of AMI
RHD involves which organism
Strep pyogenes
pathophysio of RHD
happens 1-3 weeks AFTER strep infection
-> M protein of GAS resembles human cardiac Myosin (Molecular Mimicry),
resulting in antibodies cross-reacting w/ self-antigens,
-> causing damage to tissues,
in particular fibrosis of heart valves
-> predispose to infective endocarditis
what type of hypersensitivity reaction occurs in RHD
type 2 (i.e. type B)
bcos molecular mimicry
-> antiBodies targeting self-tissues
Which valve is most commonly affected in rheumatic heart disease?
A. Mitral valve
B. Aortic valve
C. Mixed mitral/aortic valves
D. Tricuspid valve
E. Pulmonary valve
A. Mitral valve
options are actually arranged
from most commonly to least commonly affected
both are CCBs
Difference in MOA bet DHP and non-DHP
- DHP: primarily act on vascular smooth muscle
-> mainly vasodilation - non-DHP: act on both vascular smooth muscle and cardiac conduction system
-> mainly reduced HR and contractility
examples of non-DHP CCBs
- verapamil
- diltiazem
“like you broke up the dipine in DHP CCBs”
verapamil > diltiazem
as cardiac depressant
“very-pamil bcos it is very strong”
examples of DHP CCBs
- amlodipine
- nifedipine
nifedipine > amlodipine
as anti-hypertensive
MOA of Class I antiarrhythmic drugs
block Na+ channel
-> slows phase 0 depolarisation
“salty CAB driver gets 0 dollars”
CAB bcos there is class 1C, 1A and 1B
more legit recall! phase 0 depolarisation is due to Na+ influx
as Na+ channels open
MOA of class II antiarrhythmic drugs
beta blockers
-> reduces phase 4 depolarisation
“beta has 4 letters”
MOA of class III antiarrhythmic drugs
block K+ channel
-> prolongs phase 3 repolarisation
e.g. amiodarone
recall! phase 3 repolarisation is due to K+ influx
as K+ channels open
MOA of class IV antiarrhythmic drugs
non-DHP CCB
-> prolong phase 4 depolarisation
what anti-arrhythmic drug is used as emergency treatment of supraventricular tachycardia
i.e. originate from atria, AV node or junction bet atria and ventricles
adenosine
How do beta blockers mask the symptoms of hypoglycemia?
A. By increasing insulin secretion
B. By blocking adrenaline’s effect on glucose metabolism
C. By preventing the release of glucagon
D. By inhibiting the effects of cortisol on glucose metabolism
E. By suppressing the sympathetic nervous system’s response to low blood sugar
E. By suppressing the sympathetic nervous system’s response to low blood sugar
Drop in blood glucose levels
-> activation of SNS
-> symptoms including tremors, sweating and palpitations
-> serve as warning signs
which anti-clotting drug is used for prophylactic treatment of ischaemia?
(e.g. transient cerebral ischaemia)
aspirin
as it prevents initial step of platelet aggregation
-> lowers risk of clot formation
by inhibiting COX-1,
which is responsible for producing TXA2,
potent promoter of platelet aggregation
which anti-clotting drug is used to prevent clotting which results in worsening ischaemic injury?
(e.g. restenosis after coronary angioplasty)
platelet GPIIb/IIIa receptor blockers
as it blocks final step in platelet aggregation
-> prevent clot formation
i.e. blood clot formed already
which drug is used in a thrombotic event?
(e.g. emergency treatment of coronary artery thrombosis)
thrombolytics
as it dissolves fibrin
(protein that holds clot together0
=> thus dissolves clot
MOA of ivabradine
inhibition of cardiac pacemaker I(f) current
(i.e. funny current)
-> reduction in cardiac workload
=> reduction in myocardial O2 demand
I(f) current in SA node
adverse effects of ivabradine
-
visual problems
(luminous phenomena) - bradycardia
(and associated symptoms)
treatment for HF
- Beta-blockers
- Cardiac glycosides
- Diuretics (loop and potassium-sparing)
- Nitrates
- Hydralazine
- Sacubitril-Valsartan
“BCD n Hs”
difference from treatment for HTN:
- ACEi and ARB not commonly used
(replaced by Sacubitril-Valsartan)
- C stands for Cardiac glycosides, not CCBs
- Nitrates, Hydralazine and Sacubitril-Valsartan used
which beta-blockers are approve for HF
- beta-1 selective:
bisoprolol,
metoprolol XL - non-selective:
carvedilol - mixed:
nebivolol
not approved are PAP:
Propranolol,
Atenolol,
Pindolol
MOA of sacubitril-valsartan
- sacubitril:
inhibits neprilysin
-> thus inhibits breakdown of ANP and BNP
=> prolongs BNP effects of vasodilation, natriuresis and diuresis - valsartan (AT1 blocker / ARB):
blocks Ang II action
=> reduce vasoconstriction and aldosterone secretion
valsartan is needed as neprilysin also breaks down Ang II
=> inhibition of Ang II results in less breakdown of Ang II and thus more Ang II
adverse effects of Sacubitril-Valsartan
- hyperkalaemia
- renal failure
what should loop diuretics not be administered with
-
aminoglycosides
<- both have adverse effect of ototoxicity - NSAIDs
- recall! amiNOglycosides has adverse effects of Nephrotoxicity and Ototoxicity
- recall! NSAIDs reduce prostaglandin synthesis
-> decrease in vasodilation of afferent arteriole
-> reduction in renal blood flow
what is a unique clinical use of potasisum-sparing diuretics
hyperaldosteronism
spironolactone: 1
triamtherene: 2
what are some unique adverse effects of potassium-sparing diuretics
- spironolactone: gynecomastia
- triamterene: kidney stones,
acute renal failure
MOA of hydralazine
selectively dilates arterioles
(arteriolar dilation)
-> decrease in systemic vascular resistance (SVR)
=> reduced afterload
adverse effects of hydralazine
- symptoms associated with baroflex associated sympathetic activation
(e.g. flushing, hypotension) - hydralazine-induced lupus syndrome (HILS)
MOA of digitalis
includes digoxin and digitoxin
inhibits Na+-K+ exchange
-> increases [Na+]
-> increased Na+ leads to less Ca2+ efflux
-> greater [Ca2+] results in increased cardiac contractility
-> increased CO
(since CO = SV x HR and contractility affects SV)
-> leads to 2 effects:
1. decrease in sympathetic tone
-> reduced vasoconstriction of systemic veins
(venoconstriction)
-> less blood returning to heart
=> reduced PRELOAD
2. increased renal blood flow
-> reduced renin release
-> reduced production of Ang II
-> less vasoconstriction of arterioles
(arteriolar constriction)
-> decrease in SVR
=> reduced AFTERLOAD
clinical indications of digitalis
(a.k.a. cardiac glycosdides)
includes digoxin and digitoxin
-
atrial fibrillation
due to digitalis reducing sympathetic tone
-> increase parasympathetic activity
=> slows AV conduction - systolic dysfunction
AF = rapid, irregular atrial impulses that bombard AV node
1 adverse effect of digitalis
high intracellular Ca2+
-> increased automaticity
=> progressively more severe dysrhythmia
(AV block, AF, VF)
overload of electrical impulses
-> overwhelm AV node
-> functional block
4 ways to treat digitalis toxicity
- discontinue cardiac glycoside therapy
- correction of K+ or Mg2+ deficiency
(as hypokalaemia and hypomagnesemia
-> increase binding of digitalis to Na+-K+ ATPase) -
anti-arrhythmic drugs,
particularly lidocaine (class Ib)
and propranolol (class 2) - digoxin antibody
(bind to plasma digoxin
-> form complexes that are excreted renally)
recall!
* class I, 3 subclasses, sodium channel blocker, phase 0 depolarisation
“CAB driver salty bcos he got 0 dollars”
* class 2, beta blockers, phase 4 depolarisation
“beta has 4 letters, thus phase 4 depolarsiation + used for AFib”
definition of coarctation of aorta
and defining characteristic
- congenital narrowing (stenosis) of aorta
- defining characteristic:
higher BP (hypertension) in upper body,
lower BP (hypotension) in lower body
=> radio-femoral delay
what microscopy finding will be seen in LHF
macrophages containing haemosiderin
as LHF
-> pulmonary congestion and microhemorrhages in alveoli
-> macrophages ingest RBCs and break them down
=> presence of haemosiderin
(product of Hb breakdown)
where to listen for tricuspid murmurs,
not location of tricuspid valve
where is tricuspid valve best heard during auscaltation
- left
- 5th intercostal space
- lower sternal border
it’s the odd one out
in comparison, mitral (bicuspid) valve is best heard
* left
* 5th intercostal space
* midclavicular line
