Cardio Renal L4

Question 1

Cardiac failure is ….

Answer 1

Cardiac failure is a result of the heart failing to maintain an adequate circulation for the needs of the body

Question 2

The healthy heart shows a considerable degree of adaptation, being able to pump between approximately …… to ….. litres per minute (with the ‘normal’ resting quantity being 5 litres per minute).

Answer 2

The healthy heart shows a considerable degree of adaptation, being able to pump between approximately 2 to 25 litres per minute (with the ‘normal’ resting quantity being 5 litres per minute).

Question 3

describe what is meant by venous congestion?

Answer 3

If the heart cannot operate properly, more blood returns to it than it can deal with and this causes an increase in filling pressure.

The (venous) circulation becomes congested. Being distensible, the veins are able to accommodate a fair excess of blood, but the increased venous pressure increases the hydrostatic pressure on the venous capillaries and tends to force fluid across the capillary endothelium into the interstitial space and result in oedema

Question 4

If the right side of the heart is failing, then the oedema will be manifested in …….

Answer 4

If the right side of the heart is failing, then the oedema will be manifested in peripheral tissues (ankles, fingers and so on) and the liver (where fluid can be forced out of the liver into the abdomen

Question 5

If the right side of the heart is failing, then the oedema will be manifested in peripheral tissues (ankles, fingers and so on) and the liver (where fluid can be forced out of the liver into the abdomen - the phenomenon known as_____

Answer 5

If the right side of the heart is failing, then the oedema will be manifested in peripheral tissues (ankles, fingers and so on) and the liver (where fluid can be forced out of the liver into the abdomen - the phenomenon known as ascites

Question 6

If the left side of the heart fails, then the oedema will occur …..

Answer 6

If the left side of the heart fails, then the oedema will occur in the pulmonary circulation, producing pulmonary oedema which compromises the ability of the lungs to oxygenate blood, thus potentially making the heart failure worse.

Question 7

describe cardiogenic shock

Answer 7

Cardiogenic shock is a life-threatening condition in which your heart suddenly can’t pump enough blood to meet your body’s needs. The condition is most often caused by a severe heart attack, but not everyone who has a heart attack has cardiogenic shock. Cardiogenic shock is rare

Question 8

why does pooor renal perfusion compound heart failure more?

Answer 8

In addition, if there is insufficient renal perfusion, the kidney takes this as a signal that blood pressure is too low and secretes renin (see below) which ultimately leads to further fluid retention, worsening the situation and causing filling pressure to rise even further

Question 9

In addition both right and left-sided cardiac failure tend to cause … (3)

Answer 9

In addition both right and left-sided cardiac failure tend to cause breathlessness and cyanosis and fatigue.

Question 10

Cardiac failure can be caused by various factors. It may occur rapidly as a result of myocardial infarction (described above). On the other hand, it can develop slowly as a result of chronic excessive functional demands being made on the heart, these may be as a result of (among other factors):

give some:

Answer 10

• Dysrhythmias (which inhibit normal cardiac function)
• Coronary artery disease
• Past myocardial infarction
• Hypertension
• Abnormal heart valves
• Heart muscle disease (e.g. dilated cardiomyopathy, hypertrophic cardiomyopathy) or
• inflammation (myocarditis)
• Congenital heart defects
• Severe lung disease
• Diabetes
• Hyperthyroidism

Question 11

The New York Heart Association has classified cardiac failure into four degrees of severity:

what are they

Answer 11

Question 12

what is meant by dyspnoea

Answer 12

shortness of breath

Question 13

some more different causes of heart failure

Answer 13

• ■ Myocardial infarction
• ■ ß-haemolytic streptococci (causing ‘rheumatic fever’)
• ■ Protozoal infections
• ■ Dysrhythmias
• ■ Systemic or pulmonary hypertension
• ■ Heart valve insufficiency
• ■ Diabetes mellitus
• ■ Anaemia
• ■ Vitamin B1 deficiency

Question 14

Drug treatment of heart failure is based on what?

Answer 14

increasing the contractile force of the heart (or more specifically the ventricles), producing a positive inotropic effect, and reducing the load put on the heart (by reducing the filling pressure).

Question 15

what class of drugs?

The ‘classical’ type of drug for treatment of congestive heart failure

Answer 15

Cardiac glycosides

Question 16

give 2 exmaples of cardiac glycosides?

Answer 16

digoxin

ouabain - not used clincially as too powerful

Question 17

whast the target for cardiac glycosides?

Answer 17

Na+-K+ ATPase

Reducing its activity leads to a rise in intracellular Ca2+.

Question 18

Useful cardiac glycosides, like digoxin, raise intracellular Na+ by around …

Answer 18

Useful cardiac glycosides, like digoxin, raise intracellular Na+ by around 1 - 1.5 mM

Question 19

can we use beta 1 agonists to treat chronic ehart failure?

Answer 19

cort of - big disadvantages though

Question 20

what are the disadvantages of using b1 agonists for chronic heart failure

Answer 20

1. The ß1 receptor-induced positive inotropic effect increases cardiac oxygen demand (in contrast to cardiac glycosides, which produce positive inotropic effect without an increased requirement for oxygen).
2. ß1 agonists increase heart rate, and may, as a result, precipitate or reveal dysrhythmias
3. ß1 stimulation may precipitate hypertension, or potentiate hypertension if it is already present

Question 21

what is and giev uses for dobutamine?

Answer 21

dobutamine, a ßl-selective analogue of dopamine can be used intravenously for rapid effect. Its positive inotropic effect is greater than its chronotropic effect. It may be used for shock, or to improve cardiac output after open heart surgery, or in heart failure in the absence of hypertension.

Question 22

why are beta blockers good for heart failure?

Answer 22

1. in heart failure adrenergic stimulation is big (noramlly its tiny)
2. chronic adrenergic stimulation = bad for the heart due to downregulation of beta 1 and upreg of alpha 1
3. chronic stimulartion of adrenoceptors can enhance apoptosis in cardiomyocytes
4. Bisoprolol and carvedilol are in use currently in the UK for stable heart failure. Because of the potential danger of over-inhibition, the drug doses have to be carefully titrated while cardiac function is monitored.

Question 23

describe the use of. Inodilators in chronic heart failure

Answer 23

• Inodilators (phosphodiesterase inhibitors)
• Phosphodiesterases (of which there are several types) catalyse the breakdown of cAMP (and/or cGMP) and its action is thus to slow the heart and reduce its strength of contraction
• Inhibition of phosphodiesterase mimics sympathetic stimulation

Question 24

Answer 24

Question 25

The Type III phosphodiesterase inhibitor _____ is the inodilator most often used in heart failure

Answer 25

The Type III phosphodiesterase inhibitor milrinone is the inodilator most often used in heart failure

Question 26

why does milrinone have limited use therapeutically?

Answer 26

The Type III phosphodiesterase inhibitor milrinone is the inodilator most often used in heart failure. However, it has limited use because of its effect of sometimes producing dysrhythmias. Its use is confined to short-term treatment of severe heart failure unresponsive to more conventional therapy.

Question 27

explain how inodilators dilate blood vessles and why this is beneficial in chronic heart failure

Answer 27

The above doesn’t explain the ‘dilator’ part of the ‘inodilator’ name. In smooth muscle cells the increased cAMP levels as a result of phosphodiesterase III inhibition leads to vasodilatation. This decreases the after-load on the heart and is thus therapeutically beneficial.

Question 28

give some exmaples of Methylxanthines.

are they used in chronic heart failure?

Answer 28

Methylxanthines, such as caffeine and theophylline are non-selective phosphodiesterase inhibitors but they are also adenosine A1 and A2 antagonists and (at high concentrations) cause release of Ca2+ from intracellular stores.

The combination of the first two of these effects may be the reason that methylxanthines produce positive inotropic and chronotropic effects, and an increased tendency to give rise to dysrhythmias. The effects of methylxanthines on the central nervous system effects probably result from antagonism of adenosine receptors.

Question 29

levosimendan? what does it do?

Answer 29

It is one of a class of drugs called ‘calcium sensitisers’. They sensitise and increase the cardiac Ca2+ binding efficiency (to troponin) without a requirement for more energy consumption. They also cause peripheral vasodilatation by inhibiting phosphodiesterase III. The only drug of this class that has so far had any impact on human clinical practice is levosimendan, which is used in hospitals (though not licensed in the UK) for heart failure.

Question 30

might SERCA2 be a possible target in the future?

Answer 30

yep

Question 31

fat

Answer 31

mamba