PSIO 303B exam review 3: How a heart cell fails
1) Cellular organization
Chemical cellular tissue organ system level organism level
Hormones/proteins cardiac cells cardiac tissue heart/veins/arteries/capillaries
cardiovascular system human
2) Cellular specialization
Development divergence (differentiation)
• Intrinsic regulation
• Extrinsic regulation (nerves, hormones, environment)
3) Cellular structure and Function
Generic cell cardiac cell
• Sarcoplasmic reticulum
These can all adapt to stimulus.
4) Cellular homeostasis Relative constancy of internal environment: these include the physical
and chemical parameters like pH, temp, concentrations, of important molecules which tend to
remain constant over time.
• Negative feedback vs. positive feedback
• Acute vs. Long term
• Physiological vs. Pathological
• Extrinsic vs. Intrinsic
• Nongenetic vs. genetic
• Homeostasis vs. Steady state After a couple of minutes of exercise we reach a
steady state in which heart rate and rate of oxygen consumption tent to remain
constant at a constant rate of work.
These can also adapt.
5) Cellular failure
Cell failure Whole heart failure Same as homeostasis however these develop due to maladaption instead of regular adaptation
that result in a good change.
Circulatory system is the first system to develop during embryogenesis.
Heart beats 3 billion times in a average person's life.
Heart pumps about 2,000 gallons of blood each day.
60,000 miles of blood vessels
Cells are 100 microns away from a blood vessel.
5) Cellular failure cardiac heart cell failure
Initial insult ex. valve defect, blockage of coronary artery
Cellular signaling response
Organ remodeling remodeling ultrastructure
These lead to mal adaption; these signals which initiate cellular remodeling lead to mal
1. Clinical definition heart failure is a syndrome. It is not a disease that can be
transferred from person to person.
2. Clinical symptoms
5. Prevention/risk factors
Cardiac heart failure: Statistics
5 million Americans with heart failure.
450,000 700,000 cases will be diagnosed this year.
$33 billion per year.
Risk 40 years male 11%/ female 15%.
Increases with risk factors.
Difference with male + female heart intrinsically.
Evaluation of patients:
Identify structural or functional abnormalities
Full history and physical exam
Noninvasive imaging/functional analysis invasive imaging/functional analysis
Risk Factors Cellular Pathophysiology Ventricular Remodeling Ventricular dysfunction
Dyslipidemia Infarction LVH Systole
Diabetes Accelerated Apoptosis Dilation Diastole
Obesity Fibrosis Both Both
Stage A Stage B Stages C and D
Basic heart anatomy: Blood flow
Inferior/Superior vena cava Right atrium Right Av valve (tricuspid) Right ventricle
Pulmonary valve Pulmonary trunk Pulmonary arteries Capillaries in Lungs Pulmonary
veins left atrium Left Av Valve (bicuspid) Left ventricle Aortic valve Aorta Arteries
Arterioles Capillaries Venuoles Veins Inferior/Superior Vena Cava Noninvasive imaging/function
MRI magnetic resonance imaging
In MRI and Echocardiography we can measure the fractional shortening and ejection fraction by
looking at a contraction/relaxation imaging of the heart. LVIDs show contraction/systole where
LVIDd shows relaxation/diastole. This is called functional measuring of the heart where we can
measure whether contraction is abnormal or normal, likewise for relaxation of the ventricles.
• Bad when below 2530%
• Normal 5060%
Invasive imaging/functional analysis: No established role
Transesophageal Echocardiography gives sharper crisper view into the heart.
Right heart catheterization used to measure pressure (filling pressure/preload), sample
[O2], and determine functional capabilities of the heart chambers.
Serum BNP associated with kidneys
These are all used to evaluate patients who enter the hospital showing signs and symptoms of
heart failure or are having a hard time. So what's next?
Pharmacological improve symptoms or survival
Classification of Symptoms of heart failure:
Class I Patients with cardiac disease, without limitations from exercise or physical
Class II Cardiac disease with little cardiac limitations to physical activity.
Class III cardiac disease with marked limitations to physical activity
Class IV Cardiac disease with the inability to carry on any physical activity without
discomfort. Why do patient’s hearts fail? Stages are very important to identify
• Hypertension makes heart work harder to pump blood out.
• MI/atherosclerosis Coronary vascular events thrombosis/ blockage of coronary arteries
• Diabetes/obesity produced from dyslipidemia, too much fat contributes to
• Viral Myocarditis infection of myocardium
• Genetic mutation Inherited young students in shape can die suddenly.
Familial hypertrophic cardiomypathy
Not every person develops disease if they have mutation
Mutation focus In myosin head at the actin binding site (arg403)
Women with Hypertrophic cardiomyopathy were underrepresented, older, and
more symptomatic then men with a higher risk of progression. Thus more rapid in
females that are older than men.
Chambers of Heart:
The right atrium (smallest)
The right ventricle (thin medium).
The left atrium (thick small).
The left ventricle (thickest largest) clockwise spiral fibers outer myocardium of
ventricle anticlockwise spiral fibers inner myocardium of ventricle
Layers of Heart Muscle: produces wringing like movement of heart
Flow of Blood through systemic circulation:
Aorta Systemic capillaries of head, neck and upper limbs aorta continues and
branches off to celiac trunk the celiac branches to the splenic artery, left gastric, and
common hepatic artery these go to capillaries of spleen, stomach, and liver the vein coming off from the capillaries on the stomach and spleen is the hepatic portal vein
which goes through the liver capillaries This blood leaves via the hepatic vein and goes
to the inferior vena cava the branch opposite the celiac leads to the superior mesenteric
artery then inferior mesenteric artery common Iliac internal Iliac external iliac
arterioles and lastly the systemic capillaries of the lower limbs each of these leads to
their vein which ultimately leads to the inferior vena cava then right atrium.
Components of Heart wall including pericardium:
Endocardium (inner most layer)
Myocardium ( middle muscle layer)
Epicardium ( outermost layer)
Pericardial cavity (in between visceral (inner) and parietal (outer) layer of pericardium)
Pericardium maintains pressure in heart
Three components of Ventricular Remodeling/Adaptation:
Extracellular matrix in the Heart: Characteristics in the Heart
Provides structural integrity
Maintains alignment of myofibrils
Reservoir for bioactive molecules/ signaling components
Maintain the structural interaction with vascular system
• 3040% myocytes
• majority fibroblasts produce ECM
• However myocytes are the bulk of the heart
• collagen most abundant protein in body
1. Critical in many functions
2. makes up large portion of ECM
3. Made up of three chains A,B,C
4. 5 different types of collagen only type I and III found in heart
• Procollagen: Nterminal removal
• Hydroxylation of proline and lysines (modified)
• Glycosylation of lysines (folding)
• Protein disulfide isomerase
• Triple helix formation – forms procollagen molecule • Moves to Golgi for secretion
• Proteolytic cleavage (outside cell)
• Covalent crosslinking – Lysyl Oxidase catalyzation
• 3D structure (super rigid) collagen in structural format
Key concept: Lysyl Oxidase catalyzes the formation of covalent bonds between the ends
of collagen molecules – this connects the individual collagen helixes to form a collagen
fibril. – Covalent cross linking.
Key concept: With Myocardial infarction (tissue death) the heart replaces this tissue with
collagen which forms a scar – Thus no contractile cells are there any more.
Key concept: Normal tissue in left ventricle is spongy with less collagen. Whereas in
Patients with diseases in the myocardium experience an increase in collagen resulting in
unorganized tissue placement. Ex. Myocarditis leads to increase in collagen.
Key concept: Cardiac fibroblast makes collagen, thus is we target the fibroblast we
increase collagen production from fibroblast.
Key Concept: Fribronectin binds to cell surface integrin’s on myocytes and then links to
fibrin, collagen and glycosaminoglycan’s (Extracellular matrix).
Key concept: LamininA acts like fibronectin in that it binds to the myocytes (cells) and
links them to the extracellular matrix.
Key concept: Trace blood through heart and body – Function of heart is a pressure pump
which moves blood through the pulmonary and systemic circulation by pressure = this is
accomplished through work of the heart during each Cardiac Cycle.
Key concept: Diastole – relaxation (passive filling can occur here); systole – contraction
(chamber ejecting blood, also can happen with no change in volume during isovolumic
contraction). A complete sequence of systole and diastole is called a cardiac cycle.
The Cardiac Cycle
1. Passive filling during ventricular and atrial diastole – atria and ventricle is being filled
2. Atrial contraction during atrial systole – (ventricular filling during ventricular diastole)
3. Isovolumic ventricular contraction – (no volume change in ventricles but huge pressure
build up). At this point atria are in diastole.
4. Ventricular ejection (contraction with volume change in ventricles) – atria are in diastole
still some passive filling might ensue in atria not ventricles.
5. Isovolumic ventricular relaxation – Ventricles and atria are in diastole with no change in
volume in the ventricles. Valves: Open and closing of valves is controlled by pressure in atria and ventricles
Tricuspid valve (right AV valve) – opens when pressure inside right atria exceeds the
pressure in right ventricle. This blood is only filling with passive activity. The valve
closes when the pressure build of in the ventricle exceeds the pressure in the right atria.
This occurs after the atrium has contracted to initiate the atrial kick.
Pulmonary valve (semilunar valves) – opens when pressure in right ventricle exceeds the
pressure in pulmonary trunk. Closes when pressure in pulmonary trunk exceeds the right
Bicuspid valve (left AV valve) – opens when the left atrial pressure exceeds the left
ventricular pressure. The valve closes when the left ventricular pressure exceeds the left
Aortic valve (semilunar valves) – Opens when the left ventricular pressure exceeds the
aortic pressure. This valve closes when the pressure in the aorta exceeds the pressure in
the left ventricle.
KEY CONCEPT: this ensures a unidirectional motion of the blood.
Wiggers Diagram: Key concept – Increase V = Increase P Key Concept: Duration of Systole is shorter than diastole. 2/3 diastole and 1/3
systole. Any disruption of these offsets the cardiac cycle and the filling that
Key Concept: End diastolic volume is the volume if blood after contraction of the
atria finished and the tricuspid closes. This is the maximum amount that the
ventricle will contain before the blood is ejected.
Key Concept: End systolic volume is the volume of blood after contraction of the
ventricles and the aortic valve/pulmonary valve is closed. This is the minimum
amount that the ventricle will contain.
Key Concept: Stoke Volume is the amount of blood that is pumped out of each
ventricle with each contraction. This is determined by the end diastolic and
systolic volumes. SV = EDV – ESV
Ejection fraction = SV/EDV = % = amount of blood that is ejected per beat.
Determinants of Cardiac output: CO = HR x SV = mL/ min
• Heart Rate (beats/min)
• Stroke Volume (mL/beat)
• Heart does everything it can to maintain cardiac output thus the heart is dynamic over
course of its life.
What is the relationship ventricular pressure and volume?
This relationship consists of a passive curve and active curve. The active curve is pressure
developed in a purely isovolumic contraction. The passive curve is pressure developed by filling
• Stroke volume can be read off the PV loop = EDV ESV
• 4 distinct phases:
1. Filling phase ( during passive filling of ventricles)
2. Isovolumic contraction ( no volume change in ventricles) Tension increases
3. Ejection (blood ejected when aortic valve is open)
4. Isovolumic relaxation ( no volume change in ventricles) Tension decreases
• The total area of the PV loop is equal to the stroke work done by the heart
• Useful clinical tools
Cardiac output = is the volume of blood pumped by each ventricle per minute.
• CO = SV x HR
• Cardiac output can be altered by changing either HR or SV
• Stroke volume can be altered by 3 different ways: 1. Contractility is the strength of contraction of the cardiac muscle at a given end
diastolic volume ( i.e a given amount of filling volume)
• for example if Contractility was increased, for a given end diastolic
volume then the ventricular pressure developed during isovolumic
contraction is greater.
2. Preload work load placed on heart before contraction determined from EDV
which determines how stretched out the cardiac muscle fibers are.
3. Afterload Work load placed on heart after contraction Afterload is related to
the arterial blood pressure because that is the pressure the heart must work
What is there Affect on the PV loop?
• If we increase preload we are increasing the work load on the heart thus
end diastolic volume is also increased. If work load and end diastolic
volume is increased then the stroke volume is increased.
• An increase in afterload will result in higher pressures in the aortic trunk.
Thus if there is a greater pressure to overcome then less blood will be
ejected from the heart. The end systolic volume will increase but the
stroke volume will decrease.
How Does this all relate to the heart?
• The dynamic properties of the whole heart are based on the fundamental dynamics of an
The Sarcomere components:
I band isotropic
A band Anisotropic
H zone Bright M line Middle
Gap junction: This junction connects the two cytoplasm's of adjacent cells that allows various
molecules and ions to pass freely between cell. This is very impo