(ie, Captopril)

Block AngII & Aldosterone → ↓BP

↑ plasma osmolarity and ↓BV

(detected by atria strecth receptors aka cardiopulm barorcptrs)

Low blood volume in the atria.

(detected in Cardiopulm barorecptrs)

(skeletal muscles, gut, skin)

BF ↑ when metabolism ↑

Two Theories:

1. Vasodilation Theory: BF ↑ due to buildup of waste.

2. 02 Demand Theory: BF ↑ due to low 02 (except in lungs)

Tension (arterial pressure) against which ventricle must contact.

if ↑AP, then afterload↑.

(Afterload for left v. is determined by aortic pressure,

for right v. by pulmonary artery pressure.)

The pressure that has to be overcome

to eject blood from ventricle.

(ie, diastolic pressure)

↑DP → ↑ESV → ↓SV

(ie, hypertension - ↑DP due to ↑TPR)

Stimulus: Renin

↓BP → ↑renin → ↑AngII

Effect:

↑AngII → ↑TPR → ↑BP (short-term)

↑AngII → ↑Aldosterone (long-term)

Increases aldosterone (from adrenal medulla).

Increases TPR.

Increases water reabsorption (kidney)

↑BV and ↑BP

A short-term reg (hormonal) of BP

Stimuli: ↓BV (atrial stretch receptors)

           ↑Plasma osmolarity (P_osm)

Event:  ↓BV → ↓VR → ↓atrial stretch recptrs* → ↑ADH

                               (*cardiopulm barorcptrs)

           ↑ADH → vasoconstriction (high levels)

Most impt mechanism providing short-term reg of BP.

Neural reflex - negative feedback

Pressure receptors - respond to stretch

Located in Aortic Arch, Carotid Sinus, et al.

↓PNS and ↑SNS

Effector Organs:

Heart: ↑HR and contractility

Blood Vessels: ↑TPR and VR

Hormones/enzymes: ↑Epi/NE (adrenal), ↑renin (kidney)

Heart: ↑HR, contractility, SV, CO.

Blood vessels: ↑ TPR, VR.

Kidneys: ↑renin, AngII, aldoserone, TPR.

Adrenals: ↑ epi & norepi.

STAND→ blood pools in legs → VR↓ BP↓

Barorecptrs detect BP↓

↑SNS →  ↑HR, Contractility, TPR, VR, etc.

↑Epi/NE (adrenal), ↑renin (kidney)

Orthostatic Hypotension (elderly) - carotid arteries, less elasticity.

↑SNS → SA node → Epi/NE → everything SNS does will ↑

↑SNS → kidney →renin →AngII →aldosterone

alter ANS → ↑SNS → ↓PNS

Fibers going to effectors,

effector organs (↑HR, ↑contractility, ↑SV, ↑CO)

ABR ↓impulses if ↓BP.

If nerve endings on blood vessel stretch, then ↑impulses.

If not stretched, ↓impulses.

↑impulses when BP↑

Set point like a thermostat.

A short-term reg (hormonal) of BP

Protein released when atrial is stretched

Stim: ↑BP(BV) → ↑ANF

Effect: ↑ excretion of Na+

↑ excretion of H20

↓BV → ↓BP

Self regulation (may involve chemical signal)

Ex. Brain, kidney

Ability of tissue to change resistance to maintain steady flow.

↑BF → ↑resistance (vasoconstrict) → ↓BF

↓BF → ↓resistance (vasodilate) → ↑BF

1. Adaptation - most lose their capability after a few hours/days.

2. Cannot restore BP totally back to normal due to higher set point.

(in arterial barorecptrs)

Pressure diuresis (lose H20)

Pressure natriuresis (lose sodium)

Includes filtration/reabsorption

↑BP → ↑H20+Na⁺excretion → ↓BV → ↓CO → ↓BP

↑BP: Epi/norepi, AngII, ADH, Endothelin

↓BP: ANF, NO, Bradykinin & Histamine

1. Arterial Barorecptrs (Aorta) Most Impt.

- HR, contractlty, TPR, renin, epi/norepi, VR.

2. Cardiopulmonary Recptrs (atria)- ADH, stretch (volume)

3. Chemoreceptors - TPR

Nitric oxide (NO) and

ANF (atrial naturetic factor)

Major regulator of Na+ reabsorptn (and H20)

Stimulus:

↓BP → renin secretn → AngII → vasoconstriction

→ ↑TPR → ↑BP → ↑Aldosterone

Effect: ↑Aldosterone → ↑Na+(H20) reabsorptn → ↑BV+BP

Use sphygmomanometer and stethoscope.

Start w/ high pressure (no sound)

First sound heard (Korotkoff's) is systolic pressure.

Last sound heard is diastolic pressure.

Then sound disappears.

1. Flow (CO, volume forced into arteries)

2. Resistance (TPR, how much elastic arteries can be stretched)

BP = CO x TPR

TPR = BP/CO

BP = CO x TPR

BP: 120/70 mmHg

CO: 5.25 L/min

TPR: 17 mmHg/L/min

The greatest pressure is in the Aorta,

followed next by Arteries,

Arterioles,

Capillaries,

Venules,

Veins,

and the least pressure is in the Venae Cavae.

Volume of blood flowing through a vessel

in a given period of time.

ml/min or L/min

Ex. Cardiac Ouput = 5.25 L/min

Larger Arterioles: Maj. site of constiction

regulate BP

controlled by extrinsic factors (SNS, hormones)

Precapillary Arterioles:

regulate BF within tissues

controlled by intrinsic factors (nitric oxide, PGs)

Acute local control mechanisms:

1. Active Hyperemia

2. Flow Autoregulation

Force/unit area exerted on blood vessel wall.

(Pumping action of heart generates blood flow.)

Pressure results when flow of blood is opposed by resistance.

Pressure: hydrostatic pressure (water hose)

Normal BP: 120/80 mmHg

One of the short-term regs (hormonal) of BP

Effects: ↓TPR (vasodilation)

↑ capillary permeability

Diffusion (hi to lo concentration)

Filtration/Reabsorption (Bulk Flow) (Pressure differences)

Starling's Hypothesis of Capillary Ultrafiltration

Capillary Exchg: 

  Capillary Exchg:          arterial end                       venous end

                                      P_c        ∏_c                                   P_c    ∏_c

                                    35      19                          14    24    

                                              ↓        ↑                            ↓       ↑  

                                              ↑        ↓                            ↑       ↓ 

                                              P_i        ∏_i                                   P_i     ∏_i

                                              2       2                           2      2   

     Which factors favor filtration at arterial end? P_c  ∏_i

     Which favor reabsorption at venous end?     P_i ∏_c      

     Arterial: mmHg favoring filtration?  35+2 = 37 mmHg

                 mmHg favoring reabsorp? 19+2 = 21 mmHg

                 Net Filtration Pressure =   37-21 = 16 mmHg

     Venous: mmHg favoring filtration? 14+2 =16 mmHg

                  mmHg favoring reabsorp? 2+24 = 26 mmHg

                 Net Reabsorption pressure = 16-26 = -10mmHg

Amount of blood pumped out by each ventricle in one minute.

CO = HR x SV

normal 70-75 b/min

Congenital heart failure - pumping efficiency of heart ↓

Blood circ. inadequate to meet tissue needs.

Left side failure results in pulmonary congestion.

Right side failure results in peripheral edema.

Digitalis - ↓HR and ↑contractility (↑Ca++)

Other drugs: diuretics ↓blood volume

BP meds: vasodilators ↓BP

Effect on cardiac ctr and vasomotor ctr similar to arterial barorecptrs.

Event: Sudden ↓BV (hemorrhage)

Response: ↓atrial stretch → ↑ADH → H20 retention (kidney) → ↑BP

Decreased volume increases ADH which then restores volume.

Atrial stretch receptors (in atria)

Low pressure receptors.

Stretch when atria fill with increased venous return.

Impt in renal volume. Volume receptors, not pressure.

Control/modulate arterial baroreceptors.

Inhibitory to ADH (use it to ↑BV)

Cerebral Circulation (Regional Blood Flow)

Constant, good autoregulation.

Local control mechanisms.

Most Impt Factor: pH (H+)

Hydrogen ion tightly regulated.

Respiratory - control rate and depth of breathing.

Also control TPR (vasoconstriction).

Nerve endings sensitive to changes in O2↓, CO2↑, and pH↓

Event: Hemorrhage

↓BP → ↓O2 → ↑CO2 → ↑pH → stimulation of chemoreceptors

→ ↑vasomotor ctr → ↑TPR → ↑BP

Circulatory Shock - blood vessels inadequately filled, cannot circulate normally, inadequate CO.

1. Hypovolemic Shock (ie, hemorrhage)

2. Vascular Shock (ie, extreme vasodilation) -

septicemia, anaphylactic, neurogenic.

3. Cardiogenic Shock - insufficient pumping of heart

(ie, CHF)

4. Obstructive Shock

(ie, pulmonary embolism)

Sucks H20 back into vessel.

Oncotic prssure

Exerted by large molecules (ie, plasma proteins)

↑Force of Contraction w/o changing fiber length.

Different from Preload because

there is no change in fiber length or EDV.

More efficient ejection of blood.

↑SNS → ↑Contractility → ↓ESV → ↑SV

Intrinsic abilty of cardiac muscle

to develop force for a given muscle length.

Calcium

Inotropic Agents -- alter contractility (alter calcium)

Chronotropic Agents -- alter HR

↑preload → ↑EDV → ↑SV

↑contractlty → ↓ESV, ↑SV

↑afterload → ↑ESV → ↓SV

Heart unique;

extracts more 02 from blood than other organs.

Most Impt Factors: 02 levels & adenosine

Passive flow thru atria & OPEN AV valves,

atria contract, propel blood into v's,

v's fill to max (EDV), atria relax.

Normal DP (aorta) 80 mmHg.

Lowest pressure reached during ventricular relaxation.

normal value: 70-80 mmHg

Hi to Lo Concentration

1. Lipid soluble molecules diffuse thru lipid membrane (ie, 02, C02)

2. Small lipid-insoluble mols diffuse thru pores/clefts (ie, Na, H20)

3. Large lipid-insol mols diffuse slowly (transport) (ie, albumin)

Therefore there is little protein in IF.

They stay in vessel, draw water in via osmosis.

↓HR → ↑VR (due to more filling time)

↑EDV → ↑Force of Contraction (Frank-Starling Mechanism) → ↑SV

EDV is highest at the end of ventricular filling.

The amount that's ejected from the whole lot.  What percentage it is.

EF = SV/EDV x 100

One of the short-term (hormonal) regulators of BP

Stimulus: ↑SNS

Effect: ↑TPR, ↑VR

          ↑HR + Contractility

          ↑renin release by kidney

Percentage of blood in ventricle that is pumped out with each beat.

EF = SV/EDV x 100

normal: 60-67%

One of the short-term (hormonal) regs of BP

Potent vasoconstrictor

Comes from endothelium of blood vesels

Mechanism: ↑Ca++ into vascular smooth muscle

↓BF → ↑endothelin → ↑TPR

                   (MAP) BP    =           CO         x      TPR

                                                 ↑                   ↑

                             (Cardiac Ctrs) HR x SV        (Vasomotor Ctrs)       

                                                    ↑

                                               EDV-ESV

                                                 ↑       ↑  

                                               VR     Contractility

                                                 ↑       ↑

                                               BV     Cardiac Ctrs

Change in any variable will alter BP.

MAP = DP + 1/3 PP

(PP = SP - DP)

MAP = CO x TPR

CO = HR x SV

SV = EDV - ESV

EF = SV/EDV x 100 (for percentage)

Arterial end                                           Venous end

________________________________________________

Major Force P_c ↓     ∏_c                                  

_{_________________________}↓_{_____________________________________}

                            P_if      ∏_if ↑

Fluid forced thru membrane due to prssure diff.

(Note: Not for exchg of nutrients/gasses,

but is distribution of extracellular fluid.)

1. Hydrostatic Pressure (P) - blood prssure

2. Colloid Osmotic pressure (∏) - oncotic pressure

1. Autoregulation (chemical signal)

2. Myogenic Theory (rubberband theory)

Ventricle contracts more forcefully when it's more full.

(aka Frank-Starling Mechanism)

↑EDV = ↑FoC

↑FoC = ↑SV

Ventricle contracts more forcefully when it's more full.

(aka Force of Contraction)

↑EDV = ↑FoC

↑FoC = ↑SV

MAP = DP + 1/3 PP

(PP = SP - DP = 120-90 = 30)

MAP = 90 + 1/3(30) = 90 + 30/3 = 90 + 10 = 100 mmHg

EF = SV/EDV x 100 (percentage)

EF = 70/120 x 100 = .5833 x 100= 58%

80 beats/min x 75 ml/beat = 6,000 ml/min = 6L,

so answer is 3 two-liter soda bottles equal the volume produced.

Since the avg normal heart rate is 75,

a HR > 100 would be "tachycardia",

< 50 would be "bradycardia".

Positive Chronotropic (time) Agents ↑HR:

Autonomic Nervous System (ANS): ↑SNS

Temperature: ↑heat

Hormones: ↑Epi/Ne, ↑thyroid hormones

Ions: ↑Ca++ (↑HR and ↑contractility)

Negative Chronotropic (time) Agents ↓HR:

Autonomic Nervous System (ANS): ↑PNS*

Temperature: ↑cold

Hormones: ↑Epi/Ne, ↑thyroid hormones

Ions: ↑K+

*Resting = PNS dominates (vagal tone)

Closing of heart valves.

1 - Lub - AV valves closing (begin systole)

2 - dup - SL valves closing (begin diastole)

PUSHES out of vessel.

Pressure produced when blood pumped by heart

encounters resistance in the vessels.

↑ at arterial end than venous end.

Hydrostatic pressure favors filtration, colloid osmotic favors reabsorption.

Positive Inotropic Agents ↑contractility:

↑SNS: Fibers to v., norepi is neurotransmitter

Hormones: Epi/NE (↑Ca++), thyroid horms (metabolism), glucagon

Drug: digitalis (congestive heart failure)

Negative Inotropic Agents ↓contractility:

↓SNS (Note: PNS does not alter contractility)

Drug: verapamil (Ca++ channel blocker)

Acidosis or hyperkalemia (↑H+ or ↑K+)

Split second when V's are completely closed,

just after atria relax and AV VALVES have CLOSED,

and just before v's contract.

Early diastole - blood in aorta & pulm trunk flows back

CLOSING SL valves.

V's relaxed, completely closed,

pressure low in V's.

When V pressure less than atria, AV valves open,

V's begin to refill.

MAP converts pulsatile pressure (PP)

into a continuous pressure

that determines the avg rate of flow

from beginning to end of circuit.

MAP = DP + 1/3 PP

(PP = SP - DP)

MAP = DP + 1/3 PP

also

MAP (BP) = CO x TPR

Mechanical properties of cardiac mucle.

Cardiac muscle is not at optimal length for cross bridge formation.

(Length/tension relationship:

Skeletal muscle, unlike cardiac, is at optimal length.)

One of 2 mechanisms involved in Flow Autoregulation

(tissues with constant flow rates)

Theory: A built-in property of smooth muscles in vessels

allows them to keep flow thru a tissue constant.

Ex: If stretched: ↑BF → vasoconstrict reflex → ↓BF

If not stretched: ↓BF → vasodilate reflex → ↑BF

One of the short-term (hormonal) regs of BP

From the endothelium of blood vessels

(also released by noncholinergic, nonadrenergic neurons)

Stim: ↑BF (↑BP)

Effect: vasodilation → ↓TPR → ↓BP

(*nitroglycerine & sodium nitroprusside work by vasodilation via NO)

BP = 120/80 mmHg

CO = 5-6 L/min

HR = 70-75 b/min

SV = 70 ml/beat

TPR = 17 mmHg/L/min

SP = 110-120 mmHg, DP = 70-80 mmHg

EDV = 120-135 ml/beat, ESV = 50-60 ml/beat

VP = 2-15 mmHg

Pulm Artery pressure = 24/8 mmHg

One of 2 theories of Active Hyperemia.

BF ↑ due to low O2 (except lungs)

Ex: ↓O2 → ↑BF (vasodilation) → ↑O2 (delivered to tissues)

Vagal tone.

Resting conditions.

Normal value: 75 bpm

(SA node, via SNS, generates 90-100 bpm)

Preload is the muscle length

prior to contractility.

It is dependent on ventricular filling (EDV).

The most impt determinant for preload is Venous Return (VR).

Opposite of peripheral circulation because

low O2 → vasoconstricts (instead of dilates)

(blood will be kept out of poorly ventilated alveoli)

pressure ↓ → capillary pressure ↓ → favors reabsorption

Difference between systolic and diastolic pressures.

PP = SP - DP

normal values: PP = 50 mmHg

(SP 120 mmHg, DP 70 mmHg)

1. Pulmonary Circulation

2. Cerebral Circulation

3. Coronary Blood Flow

4. Skin

Liver secretes angiotensinogen,

kidneys secrete renin,

make Angiotensin I

Angiotensin-converting enzyme (ACE*) makes Angiotensin II

adrenal cortex secretes Aldosterone

(*ACE inhibitors (captopril) block  AngII & Aldosterine to ↓BP)

↑SNS →  ↑HR, SV, CO

also

Heart: ↑HR and contractility

Blood Vessels: ↑TPR and VR

Hormones/enzymes: ↑Epi/NE (adrenal), ↑renin (kidney)

SNS nerves go to the heart (SA node, AV node, ventricular muscle)

→ release Epi/NE → release Ca++ (more available for contractions).

SNS nerves also go to blood vessels, kidney, adrenal medulla.

↑SNS stimulation ↑contractility.

↑intracellular calcium stimulates contractions.

Excess renin

arteriosclerosis,

endocrine disorders such as hyperthyroidism and Cushing's

Highly vascular, vessels innervated

mainly to control body heat

Most Impt Factor: Nerves

Starling Factors:

P_c + ∏_i PUSH out - favor filtration

P_i + ∏_c SUCK in - favor reabsorption

Filtration:

P_c = Hydrostatic pressure in capillary

∏_i = Colloid osmotic pressure in IF

Reabsorption:

P_i = Hydrostatic pressure in IF

∏_c = Colloid osmotic pressure in capillary

Amount of blood pumped by each ventricle with every heartbeat.

SV = EDV - ESV

normal 70 ml/beat

PRELOAD - V. starts out with EDV

CONTRACTILITY - ejects the blood

AFTERLOAD - what's left is the ESV

SV = EDV - ESV

or

EDV - SV = ESV

Preload (volume the v. has available to pump,

as well as end diastolic length of the muscle)

Afterload (arterial pressure against which muscle will contract)

Contractility (force the muscle can create at the given length)

1. Preload (EDV)

2. Contractility (ESV)

3. Afterload (ESV)

SV = EDV - ESV

Normal arterial pressure: 120/80 mmHg (pulsatile)

Normal venous pressure: 2-15 mmHg (nonpulsatile)

Peak pressure when blood is ejected from heart.

Normal value: 110-120 mmHg

TPR cannot be measured directly,

but it can be calculated:

BP = CO x TPR

or

TPR = BP/CO

1. Radius (diameter/2) of vessel (Most impt factor!)

2. Viscosity.* (Hct)

3. Vessel length.*(obesity)

(* Usually remain constant.)

Tachycardia is ↑HR of >100 bpm, resting

Bradycardia is ↓HR of < 60 bpm, resting

Total resistance to flow throughout the system.

TPR = BP/CO

BP = CO x TPR

normal: 17 mmHg/L/min

Major site of resistance: vasoconstriction in small arteries & arterioles.

PNS fibers in vagus nerve.

Slow SA node (SNS) pacing from 90-100

to 70-75 (vagal tone).

One of 2 theories of Active Hyperemia.

Theory: BF↑ due to buildup of endogenous vasodilators.

Ex: ↑CO2 → ↑BF (vasodilation) → ↓CO2 levels

(waste products: CO2, lactic acid, H+)

Vasoconstriction = BP ↑ before blockage, ↓ BP after.

More reabsorption, less filtration.

Vasodilation = more filtration, less reabsorption. Draw PICTURE!

VR is the flow of blood back to the heart. Normally, VR must equal CO as cardiovascular system is a closed loop.

The amount of blood ejected by each ventricle

during one minute.

CO = HR x SV

Normal CO in resting adult = 5-6 L/min

Filering more = lose more in the urine.

↑pressure cause diuresis (lose water) and naturesis (lose sodium)

The amount of blood ejected from each ventricle

with each heartbeat.