Cardio Zusammenfassung 3j16i

Electric- cell

Channel structure

-

4 subunits

Each with 6 alpha helixes (D1-D6)

D1,D2,D3: membrane interaction

D4: voltage sensor

D5, D6: aqueous pore

Na and Ca: one single tetramers, connected by a single polypeptide chain

K: 4 independent subunits

-

INa

Rapid activation kinetics

Activated at -70 to -80 mV until 0 mV

Depolarization

Fast response fibers

Transient outward

-

Ito

Immediately after depolarization

Initial repolarization

Subepicardial myocardium

Delayed rectifying

-

IK

Very slow kinetics

Main current for repolarisation

Fast and slow response fibers

IKur: very early repolarisation, atrial myocytes

IKr: early repolarisation

IKs: late repolarisation

Sodium currents

Potassium currents

rectifier

-

Acetylcholine activated

IK1

Fast activation

Fast response fibers

Activates at -20 mV during repolarisation -> anomalous rectification during Platou phase -> prolonging platou phase

Maintaining resting potential

- IK-Ach

- Sinus node, atrioventricular node, atrial myocardial cells

- Muscarinic receptors

- Hyperpolarization -> flowering firing rate ATP sensitive

- IK-ATP

- Inhibited by ATP presence f

- Hyperpolarization

Calcium Channels L type

- activated at 20 to 0 mV

- Inactivated at 0 to -50 mV

- Closure is triggered at high intracellular Ca concentration

- Slow current

- Fast response fibers: platou phase

- Slow response fibers: depolarization T type

- activated at - 55 mV

- Inactivated at sufficient depolarization

Hyperpolarization activated inward

- If for funny

- Mainly Na

- Spontanous depolarization

Na/K ATPase

- alpha subunit: binding of 3 Na, 2K and ATP binding and hydrolysis

- Beta subunit -> regulatory Ca ATPase

- one binding site

- Less important than Na/Ca exchanger

- Sarcolemma, but also sarcoplasmic reticulum

Na/Ca exchanger

- expells one Ca for the entering of three Na

Na/H exchanger

- expells one H for one Na entering

- Activated by acidic intracellular space during myocardial ischemia

- Problem: inactivity of Na/K ATPase during ischemia, leading to Na overload

Action potentials Fast response

-

Slow response

- sinuatrial and antrioventricular node

atrial and ventricular myocardium

Mainly Na and K currents

IKur only in atrial myocytes

IK and L Type Ca current-> Platou phase cells

- Mainly funny and Ca currents

Lidocaine

Blocks INa -> suppressing arrhythmias

Beta blockers (metoprolol or bisprolol

- Blocks sympathetic nervous system -

Amiodarone and sotalol

adrenergic receptors-> inhibit If (also reduces cardiac contractility)

Ivabradine selectively blocks If

- prolonging action potentials by blocking IK

- Stopping arrhythmia without influencing conduction velocity Adonosine

- stimulating IK-Ach current

Ca channel blockers (verapamil an dilitiazem)

- decreased depolarization in pacemaker cells

- Negative inotropic effect on contractility

- Inhibts smooth muscle cells in arterial walls (nifedipine only acts on vessels -> increase in heart rate

Na/K ATPase blockers (digital glycoldes, like digoxin)

- inhibit Na/Ca exchanger

- Increased contractility -> positive inotropic

- Conduction delay in atrioventricular node

electric- heart

Excitability - bathmotropy phases Absolute refractory period

- no reaction on stumuli, regardless of the intensity

- Inactivity of Na channels in fast response fibers, reactivation at -40 to -65 mV Effective refractory period

- local excitability with high intensity electric stimuli

Relative refractory period

- action potential can only be elicited with an higher stimulus then normal

- Slower action potentials with small amplitude Supernormal period

- higher excitability

- No cardioversion

Duration

- voltage dependent in fast response -

-

-

-

fibers, because Platou phase allows Na channels to recover

Time dependent in slow response fibers, because without platou phase Ca channels need to recover, before new action potential can be elicited

Increased activation rates leading to Na accumulation inside the cell, which in turn leads to higher Na/K ATPase activity -> deficit of positive ions, accelerates repolarization

Slow kinetics of Ca channels doesn’t allow them to counterbalance K efflux (fast kinetics) -> accelerating repolarization

Class 3 antiarrythmic drugs like amiodarone block IK channels -> prolonging depolarization

Automaticity (chronotropy) Influenced

- decreased slope of depolarization

- Increased treshold of ICa-L

- Decreased maximum diastolic potential

Conductivity (dromotropy)

- gap junctions

- Ratio between longitudinal and lateral conduction velocities:

- 3:1 in the ventricles

- 10:1 in the atrias

Myocyte Myosin Types

- isoenzyme V1 - two alpha chains (high ATPase activity)

- Isoenzyme V2 - alpha and beta chain (lower ATPase activity)

- Isoenzyme V3

- Atria: isoenzyme V1

- Ventricles: all isoenzymes in humans, mainly V1 in small animals

Tropomyosin

- blocking interaction between actin and myosin

Troponin

- Troponin C -> binds Ca

- Troponin T -> binds troponin to tropomyosin

- Troponin I -> inhibits interaction between myosin and actin Titin

- anchores myosin to the Z line

Electro-mechanical coupling

- inflow of Ca through mainly L-type channels

- Calmodulin activates the CA dependent ATPase pump (this is most important for Ca transport into the sarcoplasmic reticulum)

Sounds

Volume pressure curve

S1

-

vibrations of ventricular wall

S1a: isovolumic contraction

S1b: rapid ejection

S1c: rapid to slow ejection

S2

-

closure of sigmoid valves

S2A: aortic

S2P: pulmonary

Longer during inspiration

S3

- rapid ventricular filling

S4

- atrial systole

Preload

End diastolic volume

Afterload

Aortic pressure, discountcted during diastole

Evaluation of the mechanics

Pre and after load

Determination of end diastolic and and systolic volume

Contractility

- Maximum velocity of intraventricular -

pressure rise ( independent from afterload)

Maximum instantanous velocity of intraventricular pressure rise just before aortic valve opening (>1200 mmHg/sec)

Ejection phase

Ejection fraction (55-75%)

Ventricular diastolic function

- isovolumic relaxation time

- Ventricular stiffness (dP/dV)

- Ventricular compliante (dV/dP)

Cardiac output

- Fick principle

- O2 uptake by the lungs in 1 min (VO2) /

- Arteriovenous O2 difference (ml/L) (Conc.O2PV-Conc.O2Pa)

Carotidogramm

- half rise time - contractility of left ventricle

- Pre ejection time (time of electromechanical systole, Q-S2 Ejection time, E point to dicrotic notch)

Cardiac regulation

Sympathetic

- B-adrenergic stimulation

- -> Gs protein -> Phosphorylation

- If, ICaL, INa -> increased HR, conductivity, inotropy

- Myosin, TnC -> increased inotropy

- Phopholamban -> increased lusitropy

- Enzymes -> increased metabolism -

a- adrenergic stimulation

-> Gq protein -> C phospholipase

IP3 -> increased inotropy

DAG -> cell proliferation

Parasympathetic

- decreased NA release

- Gi proteins -> decreased cAMP, IK-Ach

- cGMP -> decreased Ca

Catecholamines

- noradrenalin -> A adrenergic

- Adrenalin -> A and B adrenergic

- Dopamine -> A and B adrenergic, dopamine

Renin angiotensin

- angiotensin 2

- -> type 1 receptors: IP3 DAG

Nitric oxide

-

Adenosine

- vasodilation

Opiod

- increasing parasympathetic tone

positive inotropic

Positive lusitropic

Positive chronotropic for low NO

Negative chronotropic for high NO

Decrease of myocardial O2 consumption

Kidney

Macula densa

- high blood pressure leads to:

- High glomerular flow and glomerular capillary pressure leading to

- High GFR leading to

- Delivery of NaCL to macula densa

- Decreasing glomerular capillary pressure

- ATP secretion -> break down to Adenosine

- -> afferent vasoconstriction (unlike in other vessels) which reduces

- Glomerular blood flow

- low blood pressure

- Decrease in delivery of NaCL to macula densa

- Vasodilation in afferent arterioles

- -> increase in glomerular blood flow

- Renin release Innervation

-

Maintance of body homeostasis

- excretion of K, Na, Ca, Mg, phosphate,

sympathetic

Reducing renal blood flow

Na reabsorbtion

Increase in Renin release

Most of kidney function are regulated by hormones Cl

- Control of pH, by excretion of H and HCO3

- Controlling osmolality reabsorption of water

- Controlled by antidiuretic hormone from hypothalamus -> water reabsorption

- Also controlling blood pressure this way, in case of high BP or release of renin in case of low BP Hormone production

- Calcitrol (active vitamine D) -> raising -

-

Ca levels together with parathyroid hormone

Erythropoietin -> stimulates RBC production as reaction to hypoxia

Renin -> catalyzes angiotensinogen into angiotensin 1 -> catalyzed into angiotensin 2 -> Aldosteron production in adrenal cortex

-> increase of water and Na reabsorption

Glomerular ultrafiltration

-

Nephritic disease Nephrotic disease

GFR = Kf x UP

Kf -> glomerular ultrafiltration coefficient

UP -> ultrafiltration pressure

GFR = Kf x (Pgc - Pbs - COP)

Pgc -> glomerular capillary hydrostatic pressure (55 mmHg)

Pbs -> bowmans hydrostatic pressure (15 mmHg)

COP -> colloid osmotic pressure by plasma proteins in glomerular blood (30mmHg)

- RBC and red cell casts in urine

- Fall in GFR - proteinuria (3,5 g/d per 1,73 m2 body surface) hypoalbuminemia (3 g/dl), generalized edema

Glomerulonephritis

- proteinuria and or hematuria

- Progressive loss of functioning nephrons

Clearance

- Cx= (Ux x V)/Px

- Cx -> Clearance

- Ux -> urine concentration of this substance

- Px -> plasma concentration of -

substance

V -> urine flow rate (urine volume/time)

Substance usually inulin

Usually 110 +- 15 ml/min young women

125 +- 15 ml/min young men

Decrease after 45-50y til 30/40 % at 80y

Calculation

-

filtered inulin = Pin x GFR

Pin -> plasma concentration of inulin

Excreted inulin = Uin x V

Uin -> concentration of inulin in urine

V -> urinary flow rate

Filtered inulin = excreted inulin

Cin = GFR = UinV/Pin

Creatine

- inverse relationship

- A drop in GFR leads to a significant increase in plasma Creatine

Na reabsorbtion

- Proximal tubules

- reabsorbtion into epithelial cells because of there low Na concentration

- Na/K pump transports Na into blood

- K is not reabsorbed in proximal tubules, but diffuses back to blood

- N/H+ antiporter

Na contransport for

-

Other transporters - reabsorption

- water diffuses into epithelial cells by -

Proximal tubules

Glucose

Amino acids

Vitamins

Electrolytes

Diffusion into blood

HCO3 cotransport into blood osmotic pressure due to Na and accompanying solutes

Cl is antiporter due to a base antiporter

Other transporters - into blood

- Cl is cotransportet with K

Urea

- coabsorbed with water in proximal tubules

Loop of hence

Descending limb of Henle Ascending limb of Henle

- Secreted in thin ascending loop of henle - highly water permeable

- Impermeable for solutes - highly permeable for Na and Cl

- Moderately permeable to urea

- Almost completely impermeable for water

- Na-K2-Cl contrasporter (inhibited by loop diuretic drugs)

- Na, K, Ca, Mg, NH4 are driven out of the lime by potential difference between lumen and blood, reabsorbed between cells

Distal nephron

- reabsorption of 9 % of Na and 19 % of -

K secretion

water, compared to 70 % for both in Proximal convoluted tube

Steep gradient

Na-Cl contransport (inhibited by thiazide diuretics) -> Calcium sparing

Aldosterone increases Na reabsorption and K and H secretion arginine vasopressin increases water reabsorption

- Na/K ATPase

- Lumen negative trasepithlial potential

- Increased permeability of luminal cell membrane

- High flow rate ADH

- lead to water permeability in loop of Henle

- Deficiency leads to diabetes insidious Reninangiotensinaldosteronsystem

Renin

- release and activation of RAAS is triggered by

- Macula Densa: reduced Na and Cl concentration in distal tubules

- Low BP in afferent arterioles

- Neural mechanisms: sympathicus

Angiotensin 2

- reduced renal perfusion -> vasoconstriction of efferent arterioles

- Increases tubular Na reabsorption

- Reduces medullary blood flow -> Aldosteron

- kidneys: increases expression of Na/K -

Circulation

increases Na reabsorption and urine concentration

Vasoconstrictor

Aldosteron release

Stimulates blood pressure, increase in thirst and salt appetite pumps, Increases luminal permeability of Na

Sweat glands: stimulates Na and water reabsorption in exchange for K

GI tract: stimulates Na and water reabsorption in exchange for K

Velocity flow relationship

-

v = Q/A

v -> velocity of blood flow

Q -> circulatory flow

A -> vascular section area

Inverse relationship between velocity and cross sectional area on the system

Types of blood flow

-

turbulent: high velocity

Laminar: usual

Re= (v x p x r)/ n

Re -> Reynolds number

v -> velocity of blood flow

p -> vessel density

r -> vessel radius

n -> blood viscosity

Pressure- velocity relationship

- constant = ps + 1/2 pv^2

- ps -> static pressure

- 1/2 pv^2 -> kinetic energy

Pressure- flow relationship

- Q = pressure gradient / R

- Q -> circulatory flow

- R -> Resistance

Vascular resistance

-

R = 8/pi x (n x L)/r^4

R -> resistance

n -> blood viscosity

L -> vessel length

r -> radius

Equation of poiseulli

-

Q = pi/8 x (p gradient x r^4)/(n x L)

Q -> circulatory flow

r -> radius

n -> blood viscosity

L -> vessel length