1
Q
Why is potassium such an important electrolyte
A
potassium gradient is crucial for normal physiological function
2
Q
Normal plasma calcium level
A
3.5-5 mM
3
Q
Hyperkalemia causes
A
excessive intake, or decrease removal in kidneys (kidney failure/ACE inhibition) , tissue damage and release form stores
4
Q
hyperkalemia effects
A
Impairment of neuromuscular, gastrointestinal and cardiac systems. Can cause fatal cardiac arrhythmias ie ventricular fibrillation
5
Q
Ventricular fibrillation
A
Erratic ECG, quivering no
6
Q
Asystole
A
Flatline
7
Q
Hypokalemia causes
A
usually excessive loss of potassium in urine (diuretics, vomiting, diarrhea or kidney disease)
8
Q
How does K+ alter cellular excitability
A
it alters membrane potential, this is what determines cellular excitability
9
Q
Hypokalemia effects
A
cardiac issues (Arrhyrthmias) skeletal muscle dysfunction like, myalgia, cramps or respiratory depression
10
Q
Ion pumps definition
A
span the membrane, use energy from ATP to pump ions across the membrane. Set up ionic gradient
11
Q
Ion channels definition
A
also span the membrane, use gradients to transport ions.
12
Q
features of ion channels
A
Ion selectivity filter, Activation gate (m), inactivation (h) gate
13
Q
basic structure of Na+ Ca2+ and channels
A
4 domains formed by 6 covalently linked and by transmembrane regions, linked my intra and extracellular loops. pore forming loop = s5-s6
14
Q
How are Kv channels different
A
Kv channels are not covalently linked, means that multiple genes involved, more diversity
15
Q
Inward rectified K+ channels
A
set resting membrane potential (-)
16
Q
Five phases of cardiac action potential (ventricular)
A
0- Rapid depolarization
1- Early repolarization
2- plateau phase
3 - repolarization
4- resting membrane potential
17
Q
Explain what the equilibrium potential is
A
the amount of negative charge inside cell needed to balance the concentration gradient outside cell, this is what Nernst equation is
18
Q
Why is it significant that cell membrane are permeable to K+ and not large anions
A
K+ ions travel out of the cell (down its concentration gradient), creating a slightly negative gradient, once this becomes strong enough K+ ions travel back into the cell
19
Q
what does the Nernst equation predict for K+
A
An Em of -86mV
20
Q
why is there deviation from Nernst for K+ in real life
A
membrane is not just permeable for potassium, thee are other ions
21
Q
Most important ion channel involved in rapid depolarization
A
Rapid influx of Na+ ions which is short lived! (Na+ channel). Rate of sodium influx determines rate of depolarization
22
Q
What is the ion responsible for repolarization in phases 1 and 3
A
potassium
23
Q
Significance of It0 channel
A
responsible fro phase 1 repolarization, its distribution changes across the heart (endo vs epicardio)
24
Q
Phase 2 plateau allows
A
systolic ejection of blood and time for ventricles to refill with blood before onset of next contraction
25
Phase 2 is controlled by
L-type calcium channels,
26
Phase 3 is brought about by which channels
Delayed rectifier potassium channels. Ikr (rapid) and Iks (slow)
27
Difference between hyperkalemic action potential and normal
resting potential is more positive, rate of depolarization is a lot slower, phase 3 also faster
28
Valve Stenosis
Narrowing of the heart valves
29
Aortic Stenosis
valve becomes thickened and calcified, reduced opening
30
Murmurs
Any turbulence in blood
31
Symptoms of Aortic stenosis
Dyspnea caused by back pressure on LA and pulmonary veins. Angina, ventricle worthing very hard, becomes hypertrophied. Syncope/Pre-syncope from insufficient blood supply to brain. SAD
32
Why do you get aortic stenosis
Degenerative AV disease, bicuspid AV, rheumatic valve disease ( rare)
33
How is aortic stenosis treated
Surgical AV replacement or trans catheter AV replacement
34
Aortic Regurgitation
Blood regurgitating into LV cavity in diastole
35
Phases of cardiac cycle
Ventricular filling, isovolumetric contraction, ventricular ejection, isovolumetric relaxation
36
During which phase of the cardiac cycle does the mitral and tricuspid valves close
during isovolumetric contraction
37
dicrotic notch
a small, downward deflection on the descending limb of an arterial pressure waveform, marking the end of systole and the onset of diastole
38
Parts of of ventricular filling
Passive filling and atrial filling
39
In isovolumetric relaxation and ejection what happen to pressure
decreases or increase WITHOUT a change in volume of blood
40
Stroke volume
Volume of blood pumped by each ventricle during a single cardiac cycle
41
How is cardiac output calculated
Stroke volume X Heart rate
42
How is cardiac output increased
By increasing stroke volume or heart rate
43
What factors modulate stroke volume
preload, afterload, contractibility and adrenergic stimulation
44
Define Preload
Venous return or volume of blood that fills the ventricle during each diastole, modulates diastolic volume and pressure
45
How does adrenergic stimulation increase cardiac output
increases heart rate, increase contractility that increases stroke volume, also accelerates relaxation and conduction thought the AV node
46
Contractility definition
innate strength of the heart muscle (myocardium) to contract and eject blood, depends primarily on intracellular calcium ion concentration
47
clinically what is the metric for measurements of systolic function
Exaction fraction which is calculated by stroke volume/end diastolic volume
47
Afterload means
Factors that oppose opening of aortic and pulmonary valves and ventricular systolic pumping such as blood pressure or aortic stenosis hypertension.
48
What ejection fraction indicates systolic dysfunction
< 55%
49
Systolic vs diastolic meaning
Systolic pressure is the measure of pressure when blood is being pumped out of heart, diastolic is pressure at rest.
50
Heart failure definition
Clinical syndrome (collection of signs and symptoms) caused by functional and/or structural abnormality of the heart that cause either elevated intracardiac pressure or inadequate cardiac output.
51
Most common cause of heart failure
Coronary Artery Disease (CAD)
52
Most common signs/symptoms of left heart failure
Waking up breathless cannot lie flat to sleep, confusion, tachycardia, also cyanosis and pulmonary congestion
53
Most common signs/symptoms of right sided heart failure
Pitting edema, fatigue, Jugular vein distended
54
What is occurring during left sided heart failure
the left ventricle cannot effectively pump oxygen-rich blood to the body (too weak or too stiff), causing blood to back up into the lungs
55
What is occuring during right sided heart failure
hearts right ventricle is too weak to pump blood into lungs to get oxygenated, fluid gets backed up and leading into tissue of the body, shows as edema, distended jugular veins
56
Why does heart failure cause edema
The pressure backup from the dysfunction heart pumping causes the hydrostatic pressure (in blood vessel) to be greater then the oncotic pressure (in interstitial space) causing fluid to filter out into the tissue
57
HFrEF
Heart failure with reduced ejection fraction, we know more about this condition and ways to treat it
58
Define, mild, moderate, and extreme HFrEF
<35% extreme, 35%-45% mild, and 45%-55% moderate
59
HFpEF
Heart failure with preserved ejection fraction
60
Main method for diagnosing HFrEF
Echo, easily visualizing the reduction in contraction
61
Neurohormonal response in HFREF
Activation if sympathetic nervous system and release of adrenaline and noradrenaline. Activation of renin angiotensin system. Release of natriuretic peptides
62
Chronic B-adrenergic stimulation in heart failure
sustained sympathetic nervous system activation lead to this maladaptive activation, causes hypertrophy, apoptosis, calcium overload
63
Activation of renin angiotensin system in heart failure
Renin released from kindey, acts on angiotensin I eventually to turn it into angiotensin II. This promotes apoptosis, hypertrophy, fibrosis in heart, Also promotes aldosterone production
64
Main medications for HFREF
beta-blockers, angiotensin converting enzyme inhibitor, mineralocorticoid receptor antagonists, SGLT2 antagonists, loop dietetics
65
How are loop dietetics used to treat HFREF
Reduce sodium and eater reabsorption at the level of the loop of henle,
66
Implantable cardioverter defibrillator can be used when
with previous cardiac arrest (secondary prevention)
67
ACEi drug action
target the renin angiotensin system. ACEi blocks conversion of angiotensin-I to angiotensin-II
67
ARNI drug action
ARNI is combination of 2 drugs valsartan an angiotensin II agonist and sacubitril and inhibitor of neprilisyn DOWNSIDE = can cause hypertension
68
Aldosterone antagonist drugs
Eplerenone and spironolactone
69
Purpose of giving loop diuretic in heart failure
Reduces sodium and water reabsorption at the level of loop of henle, no evidence it actually reduces the heart failure
70
Most common loop diuretics for heart failure
Furosemide and Bumetanide
71
Cardiac resynchronization therapy (CRT)
In patients with left bundle branch blocks inter-ventricular septum and LV free walls don't contract synchronously, CRT fixes this
72
When is CRT used
when QRS duration >150 ms in patients with EF <35% and symptoms despite treatment
73
Factors that predispose to HFPEF
obesity, hypertension, diabetes, age, atrial fibrilation, chronic kidney disease
74
Cardiovascular Alterations detected in HFPEF
75
Treatment of HFPEF
treat comorbidities, loop dieretics for edema, only effective treatment is SGLT2 inhibitors
76
Semaglutide action
Mimics GLP-1 hormone, causes feeling of sensation and cause release of insulin after a mean. Shown in HFPEF patient to increase quality of life and causes sig weight loss
77
from which germ layer does the primordial heart derive
mesoderm
78
Heart development timeline
first organ to be developed fully, by around week 3/4 continues until 8 weeks can see defects
79
Notch cell signaling in heart development
80
First step in cardiac development
cardiac cell fate acquired, angiogenic cells are located to cariogenic plate which is involved in the formation of blood vessels.
81
Where does the cardiogenic plate sit
in a cranial and lateral position to the neural plate
82
the heart is derived from cells from which two areas
Primary heart field, and secondary heart field
83
when is the crescent shaped heart fields structure formed by
Day 15
84
primary heart fields (PHF)
made of prechordal splanchnic mesoderm, contains precursors of many cardiac lineages formed when mesodermal cells migrate to embryos cephalic pole
85
Secondary heart fields (SHF)
Cells migrate from primary heart field. Will expand into cardiac chambers
86
what does secondary heart field contribute to
The outflow tract, arterial pole and right ventricle cardiac structures. Also is adds cells to developing heart tube
87
describe cardiac crescent fusion (linear heart tube)
PHF migrates anteriorly, they meet along the ventral midline to form primitive heart tube (day 21)
87
Name the main regions in the linear heart tube
dorsal aorta, aortic sac, bulbus cordis, primitive ventricle, primitive atria, sinus venosus
88
When does cardiac looping occur
Days 23-24 post fertilization
89
describe what happens in heart looping
undergoes a rightward looping (!)
90
How is cardiac looping controlled
differential expression of 'lefty' proteins control the rightward looping of heart tube
91
what is the first event to establish symmetry in the embryo
cardiac looping
92
Heterotaxy syndromes
93
when is cardiac chamber formation
atria and ventricle move into position and acquire specific identity, septation occurs weeks 4-9.
94
Atrial septation timing
Occurs from end of 6th through 8th week post-fertilization
95
Atrial septal defects
most common CHD to present in adulthood, often asymptomatic
96
Patent foramen ovale
When foraman ovalis doesn't close common birth defect, 10-25% adults, often asymptomatic
97
what are cardiomyocytes
the contractile/working cells of the heart, contract in unison to proved effective pump action
98
Structure of the cardiomyocytes
make up bulk volume of heart, can be branched or not, and attach end to end via intercalated discs
99
What are intercalated discs in cardiac muscle
specialized junctional complexes that connect cardiac muscle cells (cardiomyocytes) enable synchronization
99
Gap junctions cardiac function
Made up six connexin sub-units which form a hollow tube known as the connexon. The tube spans the 2-4nm intercellular gap enabling the myocardium to act as an electrically continuous sheet and all myocytes to be activated simultaneously.
100
Desmosomes cardiac function
‘glue’ cells together. Glycoproteins called cadherins span the 25nm gap between the cell membranes and desmin forms the intermediate filaments
101
Sarcolemma
membrane surrounding cardiomyocyte
102
Why do cardiac myocytes contain mitochondria
provide ready supply of ATP to sustain contraction
103
What are the contractile proteins in the cardiac myocyte
actin and myosin
104
sarcomere
The essential contractile unit of a cardiomyocyte Z-lines are attached to the thin filaments (actin) which form a ‘sandwich’ with the myosin thick filaments. A band is generated by myosin filaments. I band is composed mainly of actin filaments
105
what are T-tubules
transverse tubules - invaginations of the cell membrane which run into the interior of the cell and transmit the electrical stimulation there, promote synchronous action even to the internal parts of the cell
106
Significance of high systolic Ca2+ levels
Systolic Ca2+ has to be high enough to activate the contractile machinery in order to pump blood from the heart
107
Significance of low diastolic Ca2+ levels
Low diastolic Ca2+ levels are essential for relaxation of the cardiac muscle
108
What triggers active cardiac contraction
A rise in intracellular (cytosolic) Ca2+ in the cardiomyocyte is the trigger that activates contraction
109
Excitation-contraction coupling
The Ca2+ dependent pathway via which electrical activation of the myocyte induces contraction
110
Cardiomyocyte action potential
An action potential is the transient depolarisation of a cell as a result of ion channel activity. Characteristic shape of a ventricular cardiomyocyte AP
111
Cardiac cycle
Is the sequence of mechanical events that occurs during a single heart beat. Each single cycle is divided into two phases – diastole and systole
112
Which phases of the cardiac cycle are diastole
Phases 1 and 5-7
113
Which phases of the cardiac cycle are systole
Phase 2 3 and 4
114
Describe Phase 1 in the cardiac cycle
Atrial depolarisation -> P wave
Both atria contract -> ventricles full (LVEDV = 120ml blood)
115
Describe phase 2 in the the cardiac cycle
AV valves close
Ventricles contract, pressure increases, volume unchanged = isovolumetric contraction
Ventricular depolarisation -> QRS complex
116
Describe phases 3-4 of the cardiac cycle
Outflow valves open
Blood ejected into aorta and pulmonary artery
Volume decreases -> LVESV (50ml)
117
Describe phases 5-7 of the cardiac cycle
Ventricles are relaxed
Mitral and tricuspid valves open
Blood flows passively from atria into ventricles
118
What is the mechanism of contraction of cardiomyocyte
When calcium binds to cTnC it induces a rearrangement in the troponin–tropomyosin complex. Movement of tropomyosin exposes a myosin-binding site on actin resulting in cross-bridge formation and shortening of the sarcomere
119
Which ion channel is responsible for the plateau phase of the ventricular action potential?
L-Type Ca2+ channels
120
cTnC
Cardiac troponin C
121
What are the thick and thin filaments composed of
thick (myosin) and thin (actin) filaments arranged in sarcomeres
122
Where are the L-type calcium channels found on heart
primarily located in the sarcolemma (plasma membrane) of cardiac myocytes
123
The sympathetic nervous system innervates all regions of the heart including the
sinoatrial node, AV node, atrial and ventricular muscles and purkinje fibers
124
Describe how sympathetic stimulation can act as a compensatory mechanism in heart failure
Reduced cardiac output triggers baroreceptor-mediated sympathetic activation within seconds to minutes, increasing heart rate contractility, but chronic overstimulation can lead to myocardal remodeling
125
What are natriuretic peptides
cardiac hormones released in response to increased myocardial wall stretch caused by volume expansion or pressure overload
126
Primary role of natriuretic peptides
To reduce circulating volume, decrease vascular resistance, and counteract the renin–angiotensin–aldosterone system (RAAS) and sympathetic activation.
127
End diastolic volume
volume of blood present in a ventricle at the end of diastole, just before contraction. It represents the maximum ventricular filling volume.
128
End Systolic volume
volume of blood remaining in the ventricle at the end of systole, after contraction has occurred.
129
Typical end diastolic and systolic volume in healthy adults
EDV usually 120 mL, ESV usually 50 mL
130
Corrigans sign
sign of aortic regurgitation often seen in the neck, which is when there are visible pulsations of the carotid arteries caused by this rapid change in pressure.
131
What kind of murmur do you hear with Aortic stenosis
An ejection systolic murmur is heard on auscultation, which is described as a crescendo-decrescendo murmur that starts after the first heart sound and ends before the second
132
What kind of murmur do you hear with aortic regurgitation
An early diastolic murmur is heard on auscultation as early diastole is when the pressure gradients are highest.
133
Why would a patient with atrial fibrillation be prescribed anticoagulants
Used for prevention of stroke which AF patient are at higher risk for, heart beats irregularly causing blood to pool and form clots
134
Extracellular fluid can be divided into two components
Plasma (25%) and interstitial fluid (75%)
135
What is interstitial fluid
the thin layer of watery liquid that surrounds, bathes, and protects the cells
136
Significance of the proteins contained by plasma
These proteins generate plasma colloid osmotic (oncotic) pressure. In contrast, interstitial fluid normally contains very little protein.
137
Composition of intracellular fluid
ICF is rich in potassium (K+), which is the principal intracellular cation. It also contains high concentrations of magnesium (Mg2+), phosphate ions (PO43−), and negatively charged proteins. In contrast to the ECF, intracellular sodium and chloride concentrations are low.
138
Describe how the sodium–potassium ATPase pump maintains resting membrane potential
uses ATP to move three sodium ions out of the cell and into the ECF and two potassium ions into the cell or into the ICF. Created small negative charge inside the cell
139
Fluid exchange between plasma and interstitial fluid occurs across ...
capillary walls
140
Capillary hydrostatic pressure
the pressue exerted by blood within capillaries, pushes fluid outward into the interstitial space
141
Why is Capillary hydrostatic pressure higher in arterial end
because it is closer to the heart's pumping action and subjected to higher initial pressure, which drives fluid filtration
141
Plasma colloid (oncotic) osmotic pressure is generated by
albumin and other plasma proteins. Because these proteins cannot easily cross the capillary membrane, they exert an osmotic pull that draws water into the capillaries
142
Fluid exchange across capillaries is regulated by the balance between
hydrostatic and oncotic pressures
143
Explain why pulmonary edema occur in left sided heart failure
the left ventricle fails to pump effectively, blood begins to accumulate eventually in the pulmonary veins, increasing pulmonary capillary hydrostatic pressure. fluid accumulates and when lymphatics can no longer compensate, fluid will accumate in alveoil
144
What oxygen level should be used in patient with heart failure
Patients who have no history of COPD or hypercapnic respiratory failure should have a target oxygen saturation of 94-98%, but in patients at high risk of hypercapnic (type II) respiratory failure, a target of 88-92% should be used.
145
glyceryl trinitrate (GTN) mechanism of action
146
Year 1
flashcards
Decks in class (28)
# Cards
-
Terms Relating to Position and Movement27
-
1A ILOS: Early Embryology167
-
1B ILOS: Pregnancy171
-
2 ILOS: Chromosomal Abnormalities162
-
3 ILOS: Innate Immune system and Medelian Genetics137
-
4 ILOS: Post Natal Growth and Puberty169
-
5 ILOS: Adaptive immune system and viruses202
-
6 ILOS: Cell cycle, cancer genetics and malignancy162
-
7 ILOS: Aging, Fragility, and Polypharmacy161
-
Introduction to Medicine 1 Anatomy45
-
Introduction to Medicine 2 Anatomy54
-
Anatomy 1: Female Reproductive System 188
-
Anatomy 2: Female reproductive System 281
-
Anatomy 3: Introduction to the GI and Respiratory systems84
-
Anatomy 4: Male rep. system and imaging of the upper limb76
-
Anatomy 5: Lymphatic System and Muscles of the Forearm & Hand118
-
Anatomy 6: Breast, Axilla, and Muscles of the Shoulder and Arm111
-
Anatomy 7: Neurovascular supply of upper limb + Vertebral column57
-
Evidence Based medicine39
-
ILO Theme 8: Phneumothroax199
-
ILO Theme 9: Asthma191
-
ILO Theme 10: COPD130
-
ILO Theme 11: Heart Valve Dysfunction151
-
ILO Theme 12: Ischemic heart disease133
-
ILO Theme 13: Hypertension74
-
ILO Theme 14: Anaemia101
-
ILO Theme 15: DVT and PE18
-
ILO Theme 16: Shock35
