Pathophysiology CARDIO EXAM

Give the “equation” of cardiac output:

stroke volume x heart rate

What is the normal range of cardiac output in a healthy adult?

6-7L/min

What is a normal heart rate?

60-80 bpm

What is a normal stroke volume?

100ml

What does stroke volume mean?

Volume of blood ejected from the left ventricle during systole

What is ejection fraction?

The percentage of the blood in the ventricle ejected at each systole

What is a normal ejection fraction?

65%

What is preload?

The force which stretches the cardiac cavity

Fill in the gap: Stroke volume increases as ……. augments

Preload

What is Afterload?

The amount of resistance the heart must pump against when ejecting blood

Is contractility dependent or independent on preload and afterload?

Independent

What is contractility?

The ability of the heart to eject a stroke volume

list the 4 factors that affect cardiac output:

1\.Preload

2\.Afterload

3\.Intrinsic contractility

4\.Extrinisic regulation (e.g hormones)

List 3 non-invasive ways to assess the heart:

1\.ECG

2\.MRI

3\.Electrocardiograph

What is the Langerdoff technique?

Use of an animal heart in the lab to study the effect of various things on cardiac output.

We can also record intraventricular pressure

Give the 4 main causes of death in heart failure:

1\.Cardiac output decrease

2\.Pulmonary edema

3\.Ventricular fibrillation

4\.Myocardial rupture

What is an arrythmia?

Condition where the heart rate is abnormal. Too fast, too slow or irregular

Heart rate is too slow in….

Bradycardia

Heart rate is too fast in…

tachycardia

List the 4 types of arrythmias according to origin of the problem:

1\.Atrial arrythmia

2\.Junctional (nodal) arrythmia

3\.Heart blocks

4\.Ventricular arrythmias

Atrial extrasystoles and atrial fibrillation are which type of arrythmia?

Atrial Arrythmia

Heart blocks can be broken down into three types, which ones?

1\.first-degree atrioventricular block

2\.second-degree atrioventricular block

3\.third-degree atrioventricular block

How do we see a first-degree atrioventricular block from an ECG?

PR interval is longer than normal

How do we see a second-degree atrioventricular block from an ECG?

Constant PR interval with intermittently dropped QRS complexes.

How do we see a third-degree atrioventricular block from an ECG?

A complete loss of electrical communication between the atria and the ventricles (Super abnormal ECG)

List a few examples of ventricular arrythmias:

1\.Premature ventricular contractions (extrasystoles)

2\.Ventricular fibrillation \n

Arterial hypertension induces …….. ventricle hypertrophy

Left

What 4 pathophysiological changes observed in Arterial hypertension?

1\.Coronary blood flow changes

2\. Arrhythmogenic substrate

3\.Diastolic dysfunction

4\.Systolic dysfunction

What is pulmonary arterial hypertension characterized by?

A mean pulmonary arterial pressure greater than 25 mm Hg at rest

Describe athlerosclerosis:

progressive thickening and hardening of the walls of medium-sized and large arteries as a result of fat deposits.

What is a myocardial ischaemia?

When blood flow to the heart is decreaesed and oxygen supplies are low.

Describe the cellular disturbances produced by ischaemia:

1\.Inhibition of oxidative phosphorylation

2\.Acceleration of glycolysis and glycogenolysis \n 3.Hyperproduction of lactate and intracellular acidosis. \n 4.ADP breakdown

5\.Calcium overload (irreversible)

6\.Lesions of cell membrane (irreversible)

7\.Cell osmolarity (irreversible)

8\.Cell death (irreversible)

What are some drugs to give to someone under Acute myocardial infarction?

Analgesics (pain)

Anticoagulants

Thrombolytics

Vasodilators

Beta blockers (nervous system hyperactivation)

Sedatives (stress)

What are Cardiomyopathies?

Diseases of the myocardium associated with mechanical and/or electrical dysfunction

Give a definition for heart failure

syndrome when the heart is unable to pump sufficiently to maintain blood flow to meet the body's needs.

\
Heart failure is a clinical syndrome in which heart disease reduces cardiac output, increases venous pressure (hemodynamic abnormality), and is accompanied by molecular abnormalities that cause progressive deterioration of the failing heart and premature myocardial cell death

Give a few characteristics of systolic failure

\-ventricular dilatation

\-diminished ejection fraction

\-LV end-diastolic volume (or pressure) may increase as the stroke volume (or CO) decreases

Give a few characteristics of diastolic failure

\-ejection fraction is normal (>50%) or supranormal

\-end-diastolic ventricular pressure is increased

\-myocardial contractility is normal or hyperdynamic

what is myocardial remodelling characterized by?

hypertrophy and heart failure

What two factors can you target in high blood pressure?

1. Cardiac output (Qc)
2. Vascular resistance (PVR)

\

Which target should we act on to target Caridac output?

Beta-1 adrenergic receptor

Which target should we act on to target PVR?

alpha-1 adrenergic receptor

alpha-adrenergic receptors have higher affinity for which neurotransmitter?

Noradrenaline

Beta-adrenergic receptrors have higher affinity for which neurotransmitter?

It has an equal affinity for both noradrenlaine and adrelanine

To vasoconstrict, do we prescribe a alpha-adrenergic agonist or antagonist?

Agonist

To vasocontrict, do we prescribe a beta-adrenergic agonist or antagonist?

Antagonist

Why do we use Beta-1 antagonists and not beta-2 antagonist when a patient has high blood pressure?

Beta-2 antagonists are not specific on the heart, they will also target the blood vessels which can further constrict. Beta-1 antagonists only act on the heart and the liver so we do not get unwanted effects.

Name 4 targets of the RAAS system:

1. AT receptor


2. ACE


3. Renin


4. The mineralocorticoid receptor

What is the type of calcium channels in the heart called?

L-type channels

What is the effect of an inhibitor of Cav1.2?

Vasodilation, chronotropic, ionotropic

Complete the sentence: To target heart failure we can either decrease the ……… needs or increase the ……… supply

OXYGEN

How can we increase oxygen supply to the myocardium?

Decrease heart rate to increase coronary perfusion

How can we decrease oxygen needs of the myocardium?

1\.decrease heart rate

2\.decrease contractility

3\.decrease wall tension

Name a type of drug used to increase the oxygen supply:

beta-blockers

Name a type of drug that can be used to decrease the oxygen needs:

ACE inhibitors, MR antagonists

PVR= ?

What is the effect of an increased radius of the vessel?

vasodilation

Which actin-binding protein is missing in smooth muscle cells?

Troponin

Calcium binds to what?

Calmodulin

What happens when calcium binds to MLCK?

myosin phosphorylation →CONTRACTION

What binds to MLCP to cause vasodilation?

cGMP

Name a method used to study arterial tone ex vivo?

Myography

What can you study in myography?

Effect of vasoconstricting and vasodilating drugs by measuring the resistance of the

what does the myograph look like?

Like that.

What is the effect of PDE inhibitors on the smooth muscle cell? why?

Vasodilation because there is an accumulation of CAMP which inhibits MLCK.

Write the 3 cardinal features of endothelial quiescence

1\.anti-inflammatory

2\.anti-thrombotic

3\.semi-permeable

Write the 3 cardinal features of endothelial activation (abnormal state)

1\.Pro-inflammatory

2\.Pro-thrombotic

3\.Not semi-permeable

Name a molecule that is responsible for disruption of endothelial junctions in an activated state ofthe endothelium

histamine

What is expressed on the endothelial during activation?

P and E selectins

During rolling, what do the cells circulating bind to ?

P and E selectins

During firm-adhesion, what is expressed by the endothelial cells?

ICAM-1 and VCAM-1

What are the 3 main steps of leukocyte recruitment from the endothelium?

rolling→firm adhesion→diapedesis

Explain how endothelial activation can trigger platelet accumulation:

VWF→Tissue Factor→thrombin→fibrin

What molecules are released from the weibel palade bodies?

VWF, P-selectin,Ang-2,endothelin-1

What is the slow and fast step of endothelial activation?

Rapid=exocytosis of weibel-palade bodies

Fast=Gene expression of ICAM-1 and VCAM1

What receptor is involved in the maintenance of a quiescent endothelium?

TIE2 receptor

How does the TIE2 receptor contribute to maintening a quiescent endothelium?

Ang-1 binds to TIE2 in order to keep the endothelial in a quiet state

What happens if Ang-2 binds to TIE2?

It will activate the endothelium

What is KLF2?

A transcription factor

What class of drug targets KLF2?

Statins

In terms of channel activity, what happens at 0

Na+ influx for depolarization

In terms of channel activity, what happens at 1

L-type open for calcium slow influx

In terms of channel activity, what happens at 2

K+ opening and Na+ closing→early repolarization

In terms of channel activity, what happens at 3

L-type Ca2+ closes slowly and K+ remains open

In terms of channel activity, what happens at 4

Cell depolarizes Na+

What does the patch clamp allow us to do?

allows to electrically isolate a fragment of membrane or an entire cell in order to apply a current (current clamp) or a potential (voltage clamp) to it and record the response

What is the funny current?

Current from pacemaker cells from the SA node, it is spontaneous

Cell signalling can be divided in three different stages, list them:

Reception→Transduction→Response

What kind of receptions are there?

Mechanical forces and Ligands

Site two second-messengers of GPCRs

cAMP and cGMP

What happens when adenylate cyclase is activated?

ATP is converted to cAMP→increase in concentration of PKA→activation of EPAC

Name a modulator of cAMP?

PDE

What happens when guanylate cyclase is activated?

GTP is converted to cGMP

What are the 5 steps of ECC?

1\.Depolarization

2\.Ca2+ influx

3\.Calcium-induced calcium release

4\.Contraction

5\.Relaxation

In ECC, where are the L-type calcium channels found?

In the T-tubules

Explain depolarization in ECC

Action potential leads to depolarization though opening of the Na/K pumps

Explain how calcium first enters the cell

The depolarization will trigger opening of L-type calcium channels located on the T-tubules. Leading to calcium influx

What is calcium-induced calcium release?

When the calcium enters the cells, it will trigger the phosphorylation of RyR (ryanodine receptor), which is on the sarcoplasmic reticulum. Ryr will open to release even more calcium into the cytoplasm.

How does contraction happen once the calcium is in the cytoplasm?

The calcium will bind to calmodulin, which will bind to MLCK to trigger the phosphorylation of myosin filaments. Leading to contraction as it interacts with the actin filament during cross-bridge.

How does relaxation occur after contraction?

Relaxation occurs when Ca is removed from the cytosol either back across the cell via NCX or back into the SR via the SR Ca-pump (SERCA).

What does Ryr stand for?

Ryanodine receptor