Intro

Question 1

What heart related issues can occur?

Answer 1

Malformed

Block Blood supply

Rupture

Cardiac Failure

Rhythm disturbance leading to failed cardiac output

Question 2

Why is cardiac energy essential?

Answer 2

Heart beats 100,000/day

Pumps 10 metric tons of blood/day

Requires more energy than any other organ

Cycles through 16kg of ATP/day (20-30X its own weight)

Energy produced in mitochondria

Mitochondria are 30% of myocardial cell volume

Question 3

What impacts the effectiveness of cardiac energy?

Answer 3

Energy reserves can ensure only 20secs of normal activity

Energy produced by oxidative phosphorylation

At maximum exercise uses 90% of its capacity

Question 4

What are some heart diseases/disorders?

Answer 4

Ischaemic Heart Disease
Congenital Heart Disease
Disorders of Cardiac Muscle
Disorders of Cardiac Rhythm
Disorders of the Vascular System

Question 5

The heart mainly produces (energy) ATP through oxidative pathways.

What are these?

Answer 5

1. Glucose Oxidation:

• Provides 10 - 40% of energy
• More oxygen efficient
• ATP/02=3
• Glucose converted to pyruvate to acetyl coa and then energy (ATP)

Efficient use of oxygen however results in less storage therefore other pathways such as fatty acid are oxidation considered

2. Fatty Acid B-oxidation:
   Provides 60-90% of energy
   Requires more 02 than glucose
   ATP/02=2.6

Question 6

If a heart transplant is pursued, why are the nerves not needed to be tied?

Answer 6

Heart does not require innovation

Question 7

Cardiac muscle is similar to striated muscle except the intercalated discs that form cardiac muscle into a syncytium differs from parallel fibres seen in skeletal muscle.

True or false

Answer 7

True

Question 8

Cardiac muscle similar to skeletal muscle rather than smooth muscle, particularly in concern to genes, however diseases differ. Although there may be some overlap such as Duchenne muscular dystrophy whereby cardiac involvement may also occur and this suggests that for dystrophin there is not much difference between skeletal and cardiac muscle.

True or false

Answer 8

True

Question 9

The heart is composed of which 3 major types of cardiac muscle?

Answer 9

1. Atrial
2. Ventricular
3. Specialised excitatory and conductive muscle fibres

Question 10

Which forms of cardiac muscle contract in much the similar way as skeletal muscle except that the duration of contraction is much longer?

Answer 10

Atrial and ventricular types

Question 11

Which forms of cardiac muscle contract only feebly?

Answer 11

Excitatory and conductive fibres

Question 12

Cardiac muscle fibers are made up of what and are parallel to what?

Answer 12

individual cells connected in series and in parallel to one another

Question 13

How are cardiac muscle fibers arranged?

Answer 13

In a latticework, with the fibers dividing, recombining and then spreading again

Question 14

How is cardiac muscle similar to skeletal muscle

Answer 14

Cardiac muscle is started in the same manner as in skeletal muscle

Cardiac muscle have myofibrils that contain actin and myosin filaments almost identical to those found in skeletal muscle.

These filaments lie side by side and slide along one another during contraction in the same manner as occurs in skeletal muscle

Question 15

What is the main difference between cardiac muscle and skeletal muscle?

Answer 15

Cardiac muscle do not tire with contractions

Question 16

What is an example of a gene that is important in cardiomyopathies that begin with skeletal forms expressed, however later cardiac forms play a more important role?

Answer 16

Genes such as troponin

Question 17

What composes the intercalated disc and is also important for transmission of messages?

Answer 17

Desmosomes

Question 18

Transverse tubules and thin and thick filaments essential for coordination of contraction and adequate functioning of heart and are all controlled by what?

Answer 18

Set of genes

Question 19

What is released within T tubules and what does the excite?

Answer 19

Calcium. Excites further calcium to be released from sarcoplasmic reticulum to bring about contraction

Question 20

What genes play a role in arrhythmias?

Answer 20

Many calcium genes that play a role in arrhythmias such as CPVT which is due to mutations in RYR2 gene, this gene is important for transferring calcium back into sarcoplasmic reticulum

Also calmodulin genes play role -n heart arrhythmia when mutated

Question 21

Cardiac cells are so interconnected that..

Answer 21

when one of these cells becomes excited, the action potential spreads to all of them, from cell to cell throughout the latticework interconections

Question 22

1. Cardiac muscle is composed of how many syncytium and what do they constitute?
2. What does this allow for?

Answer 22

1. 2

The atrial syncytium: Constitutes the walls of two atria

The ventricular syncytium: Constitutes the walls of the two ventricles

2. The atria to contract a short time ahead of ventricular contraction

Question 23

Overlap of genes between heart conditions creates difficulty to..

For now focus in clinics is placed upon what?

What can be used in the future? What is the advantage of this? What is the disadvantage?

Answer 23

1. Know which genes should be tested
2. Panel testing for arrhythmias and cardiomyopathies
3. WES and WGS with advantage that all info is there thus ability to look back when you know more if you don’t find mutants in currently known genes. Disadvantage is might not enable good coverage of well known genes compared to panels

Question 24

How is circulation different for foetus?

Answer 24

Low oxygen tensions because fed through placenta which has lost half its oxygen to maternal circulation

Question 25

Describe fetal circulation

Answer 25

Two sets of arteries- umbilical and pulmometry Placenta accepts unoxygenated blood through from the foetus through blood vessels that leave the foetus through the umbilical cord. When blood enters placenta it is oxygenated. The oxygen rich blood then returns to the fetus via the third vessel in the umbilical cord (umbilical vein). The oxygen rich blood that enters the fetus passes through the fetal liver and enters the right atrium. Ductus venosus which plays important role to lower pressure as blood goes into right side of heart. The hole between the top two heart chambers (right and left atrium) is called a patent foramen ovale (PFO). This hole allows the oxygen rich blood to transfer from right atrium to left atrium and then to the left ventricle and out the aorta. As a result the blood with the most oxygen gets to the brain.

Question 26

How can babies survive with low intrauterine oxygen tension?

Answer 26

1. Adequate O2 tension - Different form of haemoglobin: Foetal haemoglobin - ↓ foetal O2 Consumption - 0 thermoregulation - Reduced physiological functions compared to adults e.g do not need to shiver or utilise muscles 2. Differential blood flow - Liver directly from Umbilical Vein - Brain & Heart - high degree of O2 saturation – differential velocities of incoming venous blood streams directing oxygenated blood through the foramen ovale - Low fetal O2 saturation maintains architecture of the fetal circulation by causing pulmonary vascular constriction

Question 27

Why is foetal circulation very important?

Answer 27

Many issues are initiated antenatally such as maternal diabetes is the most common cause of hypertrophic cardiomyopathy in the Newborn infant

Question 28

In cardiac conduction pathways what is the pacemaker?

Answer 28

Sinus atrial node

Question 29

Number of genes during development of early disorders are well understood True or false

Answer 29

False Non well understood

Question 30

In cardiac conduction pathways where does the signal travel through?

Answer 30

AV node and once there, there is delay before travels through into ventricle

Question 31

Describe cardiac conduction

Answer 31

An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node). The atria are then activated. The electrical stimulus travels down through the conduction pathways and causes the heart's ventricles to contract and pump out blood. The 2 upper chambers of the heart (atria) are stimulated first and contract for a short period of time before the 2 lower chambers of the heart (ventricles).  The electrical impulse travels from the sinus node to the atrioventricular node (also called AV node). There, impulses are slowed down for a very short period, then continue down the conduction pathway via the bundle of His into the ventricles. The bundle of His divides into right and left pathways, called bundle branches, to stimulate the right and left ventricles.

Question 32

What is the most common arrhythmia in adults and professional sports players have a much higher incidence of this later in life

Answer 32

Atrial fibrillation

Question 33

What are forms of Atrial Dysrhythmias?

Answer 33

Atrial Tachycardias- Supra-ventricular Tachycardia (SVT) Atrial Fibrillation

Question 34

Problems at atrioventricular mode can lead to what?

Answer 34

Heart block

Question 35

What is observed in atrioventricular node disease?

Answer 35

Problems at atrioventricular node can lead to heart block Can bypass the AV node through accessory pathways Proportion of Wolfe Parkinson white cases have genetic cause although most of time this isn’t problem

Question 36

Bundle branch blocks may occur but do not seem to be major problem and underlying causes are unknown True or false

Answer 36

True

Question 37

Describe mitochondrial genetics?

Answer 37

Mitochondria contain their own DNA Multiple mitochondria/cell Multiple copies of mitochondrial DNA/ mitochondria Maybe different mitochondrial DNA mutations in different mitochondria - Heteroplasmy/homoplasmy - Most proteins within the mitochondria coded for by nuclear genes

Question 38

Different proportions of abnormal mitochondria may exist and in some cases can have excess which will then drive individual over threshold for disease True or false

Answer 38

True

Question 39

Importantly the nuclear genome provides key genes or the genes for key components of mitochondria as well as the mitochondrial genome, thus coordination needed between both genomes True or false

Answer 39

True

Question 40

What sort of Genes can effect Cardiac Function?

Answer 40

1. Developmental Genes - tend to cause congenital heart disease 2. House keeping Genes 3. Structural Protein - cardiomyopathies 4. Ion channels- arrhythmias 5. Energy Production 6. Molecular Switches

Question 41

Why does 1 phenotype not equate to 1 genotype?

Answer 41

There are also environmental influences which can push patient over threshold for disease or protection