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IBS II Final Winter 2005

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What are the general functions of the cardiovascular system?
-Transport
--brings nutrients to cells
--removes wastes from cells
--distributes heat
-Communication
--transports hormones
--transports paracrine secretions
-Fluid balance
--Plasma proteins
--Renal perfusion pressure
What are the functional divisions of blood vessels?
o Arteries: rapid transport of blood under high pressure.
o Arterioles: controls flow of blood through specific tissue beds.
o Capillaries: exchange segments.
o Venules: collects blood, coalesces to veins
o Veins: low pressure conduits, blood reservoir
What are the distributions of blood present in the different types of blood vessels?
o Veins, venules, venous sinuses: 64%
o Arteries: 13%
o Pulmonary circulation: 9%
o Heart: 7%
o Arterioles and capillaries: 7%
What are the basic functions of blood?
o Transportation
- Gases
- Nutrients
- Food products
- Processed molecules (liver)
- Waste products
- Regulatory molecules: cytokines and hormones
o Thermal balance
o Regulation of pH
- Plasma proteins (NH3, NH4+)
- Carbonic anhydrase equation: CO2 + H2O ↔ H2CO ↔ HCO3- + H+
o Ion homeostasis (osmoreceptors, thirst)
o Fluid balance
o Immune Response
o Clot formation
What is the transportation of different gasses in the body during times of rest and exercise?
o At rest:
- arterial: 21% O2, 0.3% CO2
- venous: 19% O2, 2% CO2
o During physical stress:
- arterial: 21% O2, 0.3% CO2
- venous: 17% O2, 5% CO2
What percentage of body weight does blood take up?
8%
What percentage by volume, is plasma and formed elements in the blood?
55% plasma, 45% formed elements
What is plasma made up of?
91% water
7% proteins
2% other solutes
What are the formed elements in blood?
250-400 thousand platelets
5-9 thousand WBCs
4.2-6.2 million RBCs
(per cubic mm)
What are the proteins present in plasma?
Albumins 58%
Globulins 38%
Fibrinogen 4%
What are the other solutes present in plasma?
-ions
-nutrients
-waste products
-gasses
-regulatory substances
What is the normal pH of the blood?
7.35-7.45, maintained by buffers
What do albumins do?
-Albumin is in the plasma
-Partly responsible for blood viscosity and osmotic pressure; acts as a buffer; transports fatty acids, free bilirubin, and thyroid hormones
-Important in regulation of water movement between tissues and blood.
What do globulins do?
- Present in blood plasma
- Transports lipids, carbohydrates, hormones and ions like iron and copper; antibodies and complement are involved in immunity.
What does fibrinogen do?
- Present in blood plasma
- Functions in blood clotting
What are the characteristics of RBCs (Erythrocytes)?
- Biconcave disk; no nubleus; contains hemoglobin, lipids, ATP, carbonic anhydrase
- Function: transports oxygen and CO2 between tissues and lungs
What are the formed elements in the blood?
- RBCs
- Granulocytes:
-- Neutrophils
-- Basophils
-- Eosinophils
- Agranulocytes:
-- Lymphocytes
-- Monocytes
- Platelets (thrombocytes)
What are the general characteristics of Leukocytes?
- Protect body against microorganisms and remove dead cells and debris
- Movements:
--Ameboid
--Diapedesis
--Chemotaxis
What are the types of Leukocytes?
-Neutrophils: Small phagocytic cells
-Eosinophils: releases chemicals that reduce inflammation
-Basophils: Release histamine and increase inflammatory response
-Lymphocytes: Immunity; produces antibodies and other chemicals for killing microorganisms; contributes to allergic rxns; regulates immune system
-Monocytes: phagocytic cell in the blood, become macrophages
What are the characteristics of thrombocytes (platelets)?
- Cell fragments pinched off from megakaryocytes in red bone marrow
- Important in preventing blood loss
-- Platelet plugs
-- Initiate formation and contraction of clots
What is hematopoesis regulated by?
- RBC: erythropoeitin
- WBC’s
-- colony stimulating factors (CSFs)
-- interleukins (IL).
What are the types of daughter stem cells that blood cells develop from?
Proerythroblasts: Develop into red blood cells
Myeloblasts: Develop into basophils, neutrophils, eosinophils
Lymphoblasts: Develop into lymphocytes
Monoblasts: Develop into monocytes
Megakaryoblasts: Develop into platelets
What is erythropoetin?
- 85% from kidney, 15% from liver
- release
-- most important stimuli: hypoxia or low hematocrit
-- stimulated by adenosine (inhibited by theophylline)
-- facilitated by alkalosis (hyperventilation) and SNS stimulation (catecholamines –b adrenergic system)
- actions
-- ↑ RBC precursors from committed stem cells
-- w/o erythropoietin, stem cells undergo apoptosis.
What are the steps in erythropoeisis?
- This is the production of RBCs
- stem cells → proerythroblasts → early erythroblast → intermediate erythroblast → late erythroblast → reticulocyte (nucleus removed) → RBC
What is involved in RBC recycling?
- 90% of RBC are recycled by liver, 10% hemolyzed.
-- Fe++ recycled (transferrin)
-- AA make new protein
-- heme broken down: biliverdin makes bilirubin (bile)
- 120 day life span
--Shorter during hemolysis
-- Accelerated loss in bleeding conditions
What does hemoglobin consist of?
- 4 globin molecules: Transport carbon dioxide (carbonic anhydrase involved), nitric oxide
- 4 heme molecules: Transport oxygen
-- Iron is required for oxygen transport
What are the steps of hemoglobin breakdown?
1. The globin chains of hemoglobin are broken down to individual AAs and are metabolized or used to make new proteins.
2. Iron is released from the heme. The heme is converted to biliverdin which converts to bilirubin.
3. Fe is transported in combination w/ transferrin in the blood to various tissues for storage or transported to the red bone marrow and used in prod. of new hemoglobin
4. Free bilirubin is transported in the blood to the liver
5. Conjugated bilirubin is excreted as part of the bile into the sm. intestine.
6. Bilirubin derivatives contribute to the color of feces or are reabsorbed from the intestine into the blood and excreted from the kideys in the urine.
What are the factors related to hemoglobin rxns?
- Hb + O2 gives oxyhemoglobin
- ability to bind = affinity
-binding affected by:
-- temperature (higher temp = lower affinity)
-- pH (lower pH = lower affinity)
-- 2,3 diphosphoglycerate, DPG (higher DPG = lower affinity) (increase in glycolysis leads to formation of DPG)
What are colony stimulating factors and interleukins?
- cause proliferation of stem cells
- colony stimulating factors (CSFs)
-- granulocyte-macrophage CSF (GM-CSF)
-- granulocyte CSF (G-CSF)
-- macrophage CSF (M-CSF)
-- multiple CSF (Multi-CSF)
-interleukins
-- IL-1, IL-3, and IL-6 most important for overall WBC stimulation
-- IL-4 and IL-5 more narrow in effect.
What are the characteristics of G-CSFs?
Source: monocytes, fibroblasts, endothelium

Increases: neutrophils
What are the characteristics of M-CSFs?
Source: monocytes, fibroblasts, endothelium

Increases: monocytes
What are the characteristics of GM-CSFs?
Source: T-cells, monocytes, endothelium, fibroblasts

Increases: neutrophils, monocytes, eosinophils, megakaryotes, RBCs
What are the characteristics of IL-1?
Source: macrophages, endothelium, fibroblasts

Increases: neutrophils, monocytes, megakaryotes, eosinophils, RBCs, basophils
What are the characteristics of IL-3?
Source: T-cells

Increases: neutrophils, monocytes, megakaryotes, eosinophils, RBCs, basophils
What are the characteristics of IL-4?
Source: T-cells

Increases: basophils
What are the characteristics of IL-5?
Source: T-cells

Increases: eosinophils
What are the characteristics of IL-6?
Source: macrophages, endothelium, fibroblasts

Increases: neutrophils, monocytes, megakaryotes, eosinophils, RBCs, basophils
What are the percentages of ABO blood types?
O (47%), A (41%), B (9%), AB (7%)
What is the Rhesus factor?
- First studied in rhesus monkeys
- Types:
-- Rh positive: Have these antigens present on surface of RBCs
-- Rh negative: Do not have these antigens present
- Hemolytic disease of the newborn (HDN)
--Mother produces anti-Rh antibodies that cross placenta and cause agglutination and hemolysis of fetal RBCs
What are the 3 steps of clotting?
1. Vascular spasm: Vasoconstriction of damaged blood vessels (endothelin)
2. Platelet plug formation (vonWillibrand factor)
3. Coagulation or clotting (13 clotting factors)
What happens during the vascular phase of clotting?
- local vasoconstriction from
-- tissue-derived factors (ADP, prostacyclins, endothelins)
-- platelet-derived factors (seratonin)
- lasts around 30 minutes
- can completely stop blood flow
What happens during the platelet phase of clotting?
- platelet attachment to damaged vessel walls and each other
- platelets are activated at site, release hemostatic factors
-- ADP: platelet aggregation
-- seratonin & thromboxane A2: vasospasms
-- clotting factors: extrinsic clotting system
-- Ca++
What happens during the coagulation phase of clotting?
- cascade of enzyme activations that lead to formation of an insoluble fibrin plug
- 3 pathways to fibrin formation:
1. extrinsic pathway: initiated by release of tissue thromboplastin
2. intrinsic pathway: initiated by exposure of plasma to collagen
3. common pathway: final 3 steps
What are the steps of coagulation?
- Stages
-- Activation of prothrombinase
-- Conversion of prothrombin to thrombin
-- Conversion of fibrinogen to fibrin
- Pathways
-- Extrinsic
-- Intrinsic
What is involved in fibrinolysis?
-Plasminogen is converted by thrombin, factor XII, tissue plasminogen activator (t-PA), urokinase, or lysosomal enzymes to the active enzyme plasmin.
-Plasmin breaks the fibrin molecules and therefore the clot into smaller pieces, which are washed away in the blood or are phagocytized.
What are the different clotting factors?
- 12 factors for intrinsic, extrinsic, and common paths, numbered I to XIII (factor VI is extinct)
- all but 3 are synthesized in the liver
- II, VII, IX, X require vitamin K
What is involved in anticlotting?
- thromboxane A2 (platelet aggregation) balanced with prostacyclin
-- therefore, clots form at injury, but lumen tends to stay patent
- antithrombin III (protease), inhibits clotting factors IX, X, XI, XII. Binding is facilitated by heparin.
What are some anticoagulants?
- Ca++ chelators
- heparin
-- facilitates antithrombin III
-- cofactor in lipoprotein lipase
- vitamin K inhibitors (dicumarol, warfarin)
-- vit. K dependent: factors II (prothrombin), VII, IX, X and protein C
What are some of the different diagnostic blood tests?
- Type and crossmatch
- Complete blood count
-- Red blood count
-- Hemoglobin measurement
-- Hematocrit measurement
- White blood count
- Differential white blood count
- Clotting
What are the general functions of the heart?
- Generating blood pressure
- Routing blood
-- Heart separates pulmonary and systemic circulations
- Ensuring one-way blood flow
-- Heart valves ensure one-way flow
- Regulating blood supply
-- Changes in contraction rate and force match blood delivery to changing metabolic needs
What are the functions of the pericardium?
Traps metabolites
Prevents distension/dilation
Reduces friction
What are the different heart valves?
- Atrioventricular
-- Tricuspid
-- Bicuspid or mitral
- Semilunar
-- Aortic
-- Pulmonary
- Prevent blood from flowing back
What are the characteristics of the "heart skeleton"?
- Consists of plate of fibrous connective tissue between atria and ventricles
- Fibrous rings around valves to support
- Serves as electrical insulation between atria and ventricles
- Provides site for muscle attachment
What are the functions of the left and right sides of the heart?
Right heart: venous return, blood to the lungs

Left heart: pumps blood to entire body – systemic circulation
What is the path of blood flow from the body tissues to the lungs?
- body tissues
- superior and inferior vena cava
- right atrium
- tricuspid valve
- right ventricle
- pulmonary semilunar valves
- pulmonary trunk
- pulmonary arteries
- lung tissue
What is the path of blood flow from the lungs to the body tissues?
- lung tissue
- pulmonary veins
- left atrium
- bicuspid valve
- left ventricle
- aortic semilunar valves
- aorta
- body tissues
What are the characteristics of cardiac muscle?
- Elongated, branching cells containing 1-2 centrally located nuclei
- Contains actin and myosin myofilaments
- Intercalated disks: Specialized cell-cell contacts
- Electrically, cardiac muscle behaves as single unit (syncytium)
What are the steps of cardiac contraction?
- Action potential
-- opening of fast sodium channels
- Long action potential and plateau
-- Slow calcium channels
-- Also called Ca2+/Na+ channels
- Low K+ permeability retards repolarization
What are the changes in systole/diastole with HR?
- with 75 bpm:
-- total cycle: around 800 msec
-- systole: 250 to 300 msec
-- diastole: 500 to 550 msec (~63% of total)
- with 180 bpm:
-- total cycle: around 350 msec
-- systole: 180-190 msec
diastole: 160-170 msec (~47% of total)
- Increased HR “costs” diastole more than systole.
What is inotropy?
- contractile state at given length
- (+) ionotropy = increased contraction
What is chronotropy?
- heart rate
- (+) chronotropy = increased rate
What is lusitropy?
- relaxation
- (+) lusitropy = relax faster or more easily
What is dromotropy?
- conduction
- (+) dromotropy = faster conduction
What are intrinsic and extrinsic regulators of HR?
- intrinsic
-- basic contractile properties inherent in myocardium itself
- extrinsic
-- myocardial response to influences from the outside (e.g, neural, hormones, drugs, disease)
What are the 4 factors that affect cardiac output?
myocardial contractility
preload
afterload
heart rate
How does myocardial contractility affect cardiac output?
- basic ability of myocardium to generate power
- affected by 3 general factors:
-- neurohumoral effects (SNS, PNS - vagus, circulating catecholamines)
-- chemical/pharmacologic effects (K+, Ca++, pH, digitalis, SNS blockers, etc.)
-- pathological effects (ischemia, septicemia, etc.)
How does preload affect cardiac output?
- wall tension at end of diastole (venous return)(stretch on myocardium when contraction begins)
- preload - stroke volume
- clinical measurement: EDV or EDP
-- right preload: “central venous pressure” in vena cava.
-- left preload: “pulmonary capillary wedge pressure.”
How does afterload affect cardiac output?
- load that must be overcome to eject blood
- includes:
-- aortic pressure
-- peripheral resistance
-- resistance to blood flow (viscosity)
-- ventricular wall stress
- best clinical measure: artery pressure
-- right side: mean pulmonary artery pressure
-- left side: SBP/DBP.
What is involved in self-excitation of the sa node?
- Resting potential is only about –55mV
- Sodium “leak” channels slowly depolarize
- Threshold is only about –40 mV
How does the AV node contract?
- A-V node delays the electrical signal
Allow time for ventricles to fill
Bundle of His (A-V bundle) conducts impulse to ventricles
Left and Right bundle branches provide rapid transmission to ventricles
What is the pattern of an electrocardiogram?
- P wave
-- Atria depolarization
- QRS complex
-- Ventricle depolarization
-- Atria repolarization
- T wave:
-- Ventricle repolarization
What are the depolarization and repolarization waves?
Single cardiac muscle fiber
A. Depolarization wave
B. Depolarization wave completed
C. Repolarization wave
D. Repolarization completed
What are some cardiac arrhythmias?
- Tachycardia: Heart rate in excess of 100bpm
- Bradycardia: Heart rate less than 60 bpm
- Sinus arrhythmia: Heart rate varies 5% during respiratory cycle and up to 30% during deep respiration
- Premature atrial contractions: Occasional shortened intervals between one contraction and succeeding, frequently occurs in healthy people
What are the extrinsic controls on the heart?
- Extrinsic regulation:
-- Involves neural and hormonal control
- Parasympathetic stimulation
-- Supplied by vagus nerve, decreases heart rate, acetylcholine secreted
- Sympathetic stimulation
-- Supplied by cardiac nerves, increases heart rate and force of contraction, epinephrine and norepinephrine released
What are the affects of acetylcholine on the heart?
1. activates K+ conductance
-- hyperpolarization
-- Prolongs diastole
2. decreases Ca++ current
-- decreased contraction strength
What are the effects of NorEpi or Epi on the heart?
- activates b1 receptors (primarily Epi)
-- ↑ HR (from steeper phase 4 slope in )
-- ↑ contraction force (from more Ca++ entry)
-- ↑ conduction rate through AV, atria, ventricles
-- ↑ tendency for Purkinje to act as pacemakers
--- Proarrhythmic
- sympathetic effect (primarily NorEpi)
1. increased # of open Ca++ channels (lowers excitability threshold, speeds node conduction)
2. alters threshold of pacemaker currents, ↑ rate
What are the effects of core temperature on heart rate?
- ↑ temperature = ↑ HR
-- ↑ spontaneous SA node activity
-- ↑ slope of repolarization
- 10 bpm increase per 1oC elevation
- cooling has opposite effects
What are the effects of altered K+ levels on the heart?
- hypokalemia: hyperpolarizes RMP
-- decreases rate & amplitude of rapid depolarization in nodal cells
-- slows conduction velocity
on ECG:
--- reduces P amplitude, widens P-R & QRS
--- accelerates repolarization, shortens AP plateau & QT interval—creates tall, peaked T waves
- hyperkalemia: hypopolarizes RMP
-- slows repolarization
-- on ECG: flattens T waves, prolongs P-R and QT
How does a K+ imbalance slow HR?
- hyperkalemia (hypopolarized RMP):
-- mechanism of slowing is from hypopolarized RMP affect on muscle cells:
---affects fast Na channels muscle type cells
--- reduces amplitude and slope of Phase 0 in muscle-type AP
- hypokalemia (hyperpolarized RMP):
-- mechanism of slowing is from hyperpolarized RMP affect on nodal cells:
--- depolarization from If and ICa,T in phase 4 takes longer to reach threshold levels.
What are the effects of altered Ca2+ on the heart?
- hypercalcemia
-- shortens AP, increases Ca++ entry, accelerates repolarization
-- on ECG: shortened QT, abnormal ST & T waves
-- increased contraction force
- hypocalcemia
-- prolongs AP, reduced AP amplitude
-- on ECG: longer QT, and ST segments
-- if extreme: asystole
What are the different heart sounds?
- First heart sound or “lubb”
-- Atrioventricular valves and surrounding fluid vibrations as valves close at beginning of ventricular systole
- Second heart sound or “dupp”
-- Results from closure of aortic and pulmonary semilunar valves at beginning of ventricular diastole, lasts longer
- Third heart sound (occasional)
-- Caused by turbulent blood flow into ventricles and detected near end of first one-third of diastole
What are the parasympathetic controls on HR?
1. Vagus (CN X)
- Slow heart rate
- Reduce contractility
- Neurotransmitter
- Acetylcholine
2. Acetylcholine:
- activates K+ conductance
-- hyperpolarization
-- Prolongs diastole
- decreases Ca++ current
-- decreased contraction strength
What are the sympathetic controls of HR?
1. Neural (sympathetic nerves)
- Increase heart rate
- Increase contractility
- Neurotransmitter Norepinephrine (alpha-1 receptors)
2. Hormonal (adrenal gland)
- Increase heart rate
- Increase conctactility
- Hormone: Epinephrine (beta-1 receptors)
What does the baroreceptor reflex involve?
- Sensory Input: Nerve endings located in walls of carotid arteries, juxtaglomerular tissue and aortic arch sense stretch and rate of change of stretch
- ↑ BP stretches BR and sends signal to brain to:
-- ↓HR *reflex bradycardia
-- ↓force of contraction
-- Vasodilate peripheral vessels to ↓ resistance
-- leads to ↓BP
- ↓ BP activates SNS to release epinephrine and norepinephrine to:
-- ↑HR *reflex tachycardia
-- ↑force of contraction
-- Vasoconstrict peripheral vessels to ↑ resistance
-- leads to ↑BP
What are the steps of the baroreceptor and chemoreceptor reflexes?
1. Sensory neurons carry action potentials from baroreceptors to the cardioregulatory center. Chemoreceptors in the medulla oblongata influence the cardioregulatory center.
2. The cardioregulatory center contols the frequency of action potentials in the parasym. neuons extending to the heart. The parasym. neurons ↓ HR.
3. The cardioregulatory center controls the frequency of action potential in the sympathetic neurons extending to the heart. Symp. neurons ↑ HR and stroke vol.
4. The cardioregulatory center influences the frequency of action potentials in the symp. neurons extending to the adrenal medulla. The symp. neurons ↑ the secretion of Epi and some NorEpi into the general circulation. These ↑ the HR and stroke vol.
What is the involvement of the chemoreflex on the control of HR?
- Metabolites produced by metabolically active tissue influence blood flow (Q)
-- pH and CO2
-- Potassium ions
-- Lactate
-- Inorganic phosphate
- Activate sensory afferents
-- Aortic arch and carotid sinus
-- Within tissues
How does the chemoreflex work in response to pH?
1. ↑ in blood pH, often caused by ↓ in blood CO2, causes parasympathetic stimulation of heart and a ↓ in sympathetic stimulation of heart and adrenal medulla (↓ Epi and NorEpi), leading to ↓ HR and stroke volume.
2. A ↓ in blood pH, caused by ↑ blood CO2, ↓ parasympathetic stimulation of the heart and ↑ sympathetic stimulation of heart and adrenal medulla, leading to release of Epi and NorEpi and ↑ of HR and stroke vol.
What are the HR and SV responses to exercise?
1. Heart rate
-Resting Values: cardiac autonomic balance
-Anticipatiory rise in HR: withdrawal of vagal suppression of HR
-Linear increase in HR with workload: increased cardiac sympathetic activity
-Plateau of HR near maximal workoad:increased rate results in decrease in SV (inadequate filling time)
2. Stroke volume
- Resting Values:
-No anticipatory rise in SV
-Increased preload and decreased afterload at onset of exercise increase SV quickly
What is the redistribution of Q (cardiac output) during exercise?
- vasodilation to active muscles (“the sleeping giant”) has the potential to outstrip the pumping capacity of the heart– the heart cannot provide enough Q to perfuse active musculature, dilate cutaneous circulation, and splanchnic & renal circulations.
-the solution is to redirect Q away from splanchnic and renal circulation
-some tonic vasoconstrition even in active skeletal muscle
What is cardiac drift?
- Cardiac drift is the upward “drift” of heart rate during prolonged steady-state exercise. Especially pronounced in hot/humid environments
- pressure diuresis during exercise
- extra fluid loss from perspiration and ventilation
*Increase in HR compensates for fall in SV to maintain Q
What are some general effects of aging on the heart?
- Gradual changes in heart function, minor under resting condition, more significant during exercise
- Hypertrophy of left ventricle
- Maximum heart rate decreases
- Increased tendency for valves to function abnormally and arrhythmias to occur
- Increased oxygen consumption required to pump same amount of blood
What are the layers of arteries and veins?
- 3 layers, except for venules and capillaries:
• Tunica intima
• Tunica media
– Vasoconstriction
– Vasodilation
• Tunica adventitia
– connective tissue
What are the properties of large elastic or conducting arteries?
– Largest diameters, pressure high and fluctuates.
– Greatest amount of elastic tissue and a smaller smooth
muscle.
– Tunica intima is pretty thick.
What are the properties of muscular or medium or distributing arteries
– Walls are thick, tunica media contains 25-40 layers of smooth muscles.
– Smooth muscle allows vessels to regulate blood
supply.
– Smallers range from 40-300 μm in diameter.
What are the properties of arterioles?
– Transport blood from small arteries to capillaries.
– Range from 9-40 μm in diameter.
– Tunica intima has no internal elastic membrane.
– Tunica media consists of 1-2 layers of circular smooth
muscle cells.
What are the properties of venules and small veins?
– Tubes of endothelium on the basement membrane.
– 40-50 μm in diameter, 0.2-0.3 mm in diameter in small
veins.
– Venules collect blood from capillaries and transport it
to small veins.
What are the properties of medium and large veins?
– Medium veins collect blood from small veins and deliver it to large veins.
– Large veins transport blood from medium veins to
the heart.
– Tunica intima and media is thin, tunica adventitia is
predominant.
What is the vasa vasorum?
In arteries and veins greater than 1 mm in diameter, nutrients are supplied by small blood vessels called “vasa vasorum”.
What are the different classifications of capillaries?
• Classified by diameter/
permeability.
• Continuous (7-9 μm)
– Do not have gaps (in muscle & nervous tissue).
• Fenestrated
– Have pores or fenestrae (70-100 μm), highly permeable
(intestinal villi, glomeruli of kidney).
• Sinusoidal
– Larger diameter with larger
fenestrae (endocrine glands).
– Sinusoids: large diameter
sinusoidal capillaries.
– Basement membrane is absent.
– In liver & bone marrow.
What are the characteristics of capillary networks?
Blood flows from arterioles
through metarterioles into
capillary network.
⬢ Smooth muscle in precapillary sphincters
regulates blood flow.
⬢ Capillary networks are
more extensive in highly
metabolic tissues.
⬢ Capillaries in skin function in thermo-regulation and heat loss. In muscle, nutrient and waste exchange.
What are arteriovenous anastomoses?
⬢ Allow blood to flow from arterioles to small veins
without passing through capillaries (the sole of foot, palm of hands, the nail beds).
⬢ Pathologic arteriovenous anastomoses
What is arteriosclerosis?
– General term for degeneration changes in arteries making them less elastic.
What is artherosclerosis?
– Deposition of fat like
materials/plaque on walls.
– Tunica intima becomes thicker.
– Tunica media becomes less
elastic.
– Risk factors: obesity, high
cholesterol, smoking, diabetes.
What are the different types of stroke?
– Thrombosis; the formation or presence of a blood clot within a blood vessel.
– Embolism; the sudden obstruction of a blood vessel
by an embolus.
– Hemorrhage; a large discharge of blood from the
blood vessels.
What are the major veins in the body?
– Coronary sinus (heart)
– Superior vena cava (head,
neck, thorax, upper limbs)
– Inferior vena cava
(abdomen, pelvis, lower limbs)
What is laminar flow?
– Fluid tends to flow in a streamlined fashion.
– The center layer moving
fastest and outermost layer moving slowest.
What is turbulent flow?
– Interrupted
– Rate of flow exceeds
critical velocity.
– Blood passes a constriction, sharp turn,
rough surface.
What is Poiseuille’s Law?
– Flow decreases when
resistance increases.
– Flow = π. (P1-P2). r4 / 8.v.l
• P = pressure
• r = blood vessel radius
(diameter)
• v = viscosity
• l = length of the vessel
• π / 8 = constant value
– Flow = Δ P . (1 / R)
– Flow = Δ P (π . r4 / 8.v.l)
– R = 8. v. l / π . r4
What are the characteristics of viscosity in blood?
- Viscosity of whole blood = 3.0 - 4.5
• Influenced largely by hematocrit.
– The ratio of the volume of packed red blood cells to
the volume of whole blood, or percentage of total blood volume composed of red blood cells.
• Flow = π (P1-P2) r4 / 8vl
What is the critical closing pressure?
– Pressure at which a blood vessel collapses and blood flow stops.
What is Laplace's Law?
– Force acting on blood vessel wall is proportional to diameter of the vessel times blood pressure.
– F = D x P
• F = force
• D = vessel diameter
• P = pressure
What is vascular compliance?
⬢ Tendency for blood vessel volume to increase as blood pressure increases.
⬢ More easily the vessel wall stretches, the greater
its compliance.
⬢ Compliances = increase in volume (ml) / increase in pressure (mmHg)
⬢ Venous system has a large compliance and acts as a blood reservoir
What are the different pressures within the CV system?
⬢ Aortic pressure fluctuate
(120 -80 mm Hg).
⬢ Blood pressure averages
100 mm Hg in aorta and drops to 0 mm Hg in the right atrium.
⬢ Greatest drop in pressure
occurs in arterioles which
regulate blood flow through tissues.
⬢ No large fluctuations in
capillaries and veins.
What is pulse pressure?
⬢ Difference between systolic
and diastolic pressures.
⬢ Increases when stroke volume increases or vascular
compliance decreases.
⬢ Pulse pressure can be used to determine heart rate and
rhythmicity.
⬢ Weak pulses indicate a
decrease stroke volume or
increased constriction of
arteries as a results of
sympathetic stimulation.
What are the major points at which the pulse can be taken?
- superficial temporal artery
- facial artery
- common carotid artery
- axillary artery
- brachial artery
- radial artery
- femoral artery
- popliteal artery
- dorsialis pedis artery
- posterior tibial artery
What is diffusion in capillary exchange?
– Distances involved are smaller.
– Concentration gradient is larger.
– Ions or molecules involved are smaller.
• Nutrients diffuse from capillaries to interstitial
fluids.
• Water soluble molecules (G, AA) diffuse through
the pores of endothelial cells (ECs).
• Ions (Na+, K+, Ca2+) diffuse by passing through
channels in cell membrane.
• Lipid soluble gases (O2, CO2) diffuse through plasma membrane of ECs.
• Large water soluble are unable to leave blood (except at kidney and intestine).
• Plasma proteins are unable to cross ECs.
What is filtration in capillary exchange?
⬢ Driving force for filtration is hydrostatic pressure.
⬢ Blood pressure in a capillary is the capillary
hydrostatic pressure (CHP).
⬢ BP grad. falls from 35 to 10 mm HG at the venous end of capillary.
⬢ Filtration occurs primarily at the arterial end of a capillary where CHP is highest.
What is reabsorbtion in capillary exchange?
⬢ Occurs as a result of Osmosis.
⬢ The greater the osmotic pressure of a fluid is, the greater is the tendency of water to move into that fluid.
⬢ Blood colloid osmotic pressure (BCOP)
What is Net Filtration Pressure?
Force responsible for moving fluid across capillary wall.
– NFP = Net hydrostatic pressure – Net osmotic pressure
– = 35 – 25 = 10 mmHg at arterial end, 18 - 25 = -7 mmHg at venous end
What is net hydrostatic pressure?
- Tends to push water and solutes out of capillaries and into interstitial fluids.
– = CHP – Interstitial fluid pressure (IFP)
– 35 – 0 = 35 mmHg (moves fluid out of the capillary at arterial end)
– 18 – 0 = 18 mmHg (moves fluid out of the capillary at venous end)
What is net osmotic pressure?
– = Blood colloid osmotic pressure (BCOP) - Interstitial colloid
osmotic pressure (ICOP)
– = 25 - 0 = 25 mmHg (moves fluid into the capillary)
What is the effect of gravity on blood pressure?
⬢ BP is almost 0 mm HG in the right atrium.
⬢ It averages about 100 mm HG in the aorta.
⬢ Pressure in vessels above and below the heart is affected by gravity.
⬢ In a standing position, hydrostatic pressure caused by gravity increases blood pressure below the heart and decreases pressure above the heart.
What is the local control of blood flow by tissues?
• Blood flow can increase 7-8 times as a result of vasodilation of precapillary sphincters in response to
increased rate of metabolism.
– Vasomotion is periodic contraction and relaxation of
precapillary sphincters.
- Vasodilator substances (CO2, lactic acid, adenosine,
AMP, ADP, endothelium derived relaxation factor
(EDRF; NO, PGI2, K+ & H+)
– Vasomotion: Metabolic by-products (e.g., CO2) can
cause precapillary sphincter to dilate.
– If auto-regulation is ineffective, neural mechanisms become activated.
What is the neuronal control of blood flow?
⬢ Nervous ctrl of arterial BP is important in min-to-min
regulation of local BF.
⬢ BP must be good enough to
cause BF in capillary at rest, exercise or shock.
⬢ By nervous regulation, blood can be shunted from one area to another.
⬢ e.g., in blood loss, BF to
visceral and skin is reduced,
to allow BF through the
capillaries of brain and
cardiac muscle.
⬢ Sympathetic vasoconstrictor
fibers less prominent in SKM,
cardiac muscle and the brain
and more in the kidney, gut,
spleen and skin.
What are some hormonal vasoconstrictors?
– Norepinephrine and epinephrine (α1 receptor)
– Angiotensin
– ADH (vasopressin)
What are some hormonal vasodilators?
– Acetylcholine (ACh)
– Bradykinin
– Serotonin
– Histamine
– Prostacyclin (PGI2)
What is mean arterial pressure?
• MAP = CO X PR
– CO = Cardiac output; the volume of blood pumped by heart each min.
– PR = Peripheral resistance; the resistance of blood flow in all the blood vessels.
• CO = HR X SV
– HR = Heart rate
– SV = Stroke volume
• MAP = HR X SV X PR
• MAP= diastolic pressure + (pulse pressure / 3)
– MAP = 90 + (120 - 90 / 3) = 90 + 10 = 100 mmHg
• at birth: 70, middle age: 100, older people: 110 to 130 mm Hg
What are pressoreceptors?
Pressoreceptors are sensory receptors scattered along the walls of large arteries (neck, thorax, carotid sinus and aortic arch).
When are chemoreceptors activated?
*Chemoreceptor act under emergency conditions and don’t regulate the CVS under resting condition.
1) Chemoreceptors in the carotid and aortic bodies monitor blood O2, CO2, and pH.
2) Chemoreceptors in the medulla oblongata monitor blood CO2 and pH.
What is the CNS ischemic response?
1. Lack of blood flow to medulla oblongata of brain
2. Reduced O2, increased CO2, and decreased pH
3. Stimulation of vasomotor center
4. Elevation of BP
What are the long-term regulations of blood pressure?
⬢ Renin-angiotensin-aldosterone mechanism
⬢ Vasopressin (ADH) mechanism
⬢ Atrial natriuretic mechanism
⬢ Fluid shift mechanism
⬢ Stress-relaxation response
What is the atrial natriuretic mechanism for controlling blood pressure?
1. There is an increase in venous return.
2. Atrial natriuretic hormone released from rt. atrium
3. In kidneys, increased sodium and water loss from urine, increased urine production, decreased blood volume.
4. Vasodilation, decreased peripheral resistance, decreased BP
What is the fluid shift mechanism?
⬢ Movement of fluid from interstitial spaces into
capillaries in response to decrease in blood pressure to maintain blood volume.
⬢ Important in dehydration/ or when a large volume of saline is administered.
What is the stress-relaxation response?
- Adjustment of smooth muscle of blood vessel walls to respond to change in blood volume.
- decrease in blood volume, decrease in blood pressure, decrease in force applied to VSMC, then SMCs contract and reducing the volume of blood vessels resists a further decline in BP.
What are the 3 stages of circulatory shock?
Three stages:
– Compensated: Blood pressure decreases only a
moderate amount and mechanisms able to reestablish normal blood pressure and flow.
– Progressive: Compensatory mechanisms insufficient
and positive feedback cycle develops; cycle proceeds to next stage or medical treatment reestablishes sufficient blood flow to tissues.
– Irreversible: Leads to death, regardless of medical
treatment.
What are some different kinds of shock?
⬢ Hemorrhagic shock
⬢ Plasma loss shock
⬢ Obstruction
⬢ Dehydration
⬢ Sever diarrhea or vomiting
⬢ Neurogenic shock
⬢ Anesthesia
⬢ Brain damage
⬢ Emotional shock
⬢ Anaphylactic shock
⬢ Septic or blood poisoning
⬢ Cardiogenic shock
What are the steps of platelet plug formation?
1. Platelet adhesion occurs when von Willebrand factor connnects collagen and platelets.
2. The platelet release reaction is the release of ADP, thromboxanes, and other chemicals that activate other platelets.
3. Platelet aggregation occurs when fibrinogen receptors on activated platelets bind to fibrinogen, connecting the platelets to one another. A platelet plug is formed by the accumulating mass of platelets.
What are the steps in the extrinsic clotting pathway?
1. Damaged tissue release tissue factor (TF)
2. In presence of Ca2+, TF forms a complex with factor VII, which activates factor X
3. On surface platelets, factor X, factor V, platelet phospholipids and Ca2+ complex to form prothrombinase
3. In stage 2, prothrombinase converts prothrombin to thrombin
4. In stage 3, thrombin converts fibrinogen into fibin
5. Fibrin forms the fibrous network of the clot and stimulates factor XIII activation, which stabilizes the clot.
What are the steps in the intrinsic clotting pathway?
1. In stage 1, damage to blood vessels exposes collagen in the CT. Plasma factor XII is activated in the presence of collagen.
2. Plasma factor XII stimulates factor XI, which in turn activates factor IX.
3. Factor IX, factor VII, platelet phospholipids, and Ca2+ activate factor X.
4. On the surface of platelets, factor X, factor V, platelet phospholipids, and Ca2+ complex to form prothrombinase.
5. Stages 2 and 3 are activated, and a clot forms.
How does the conducting system of the heart work?
1. Action potentials originate in the SA node and travel across the wall of the atrium from the SA node to the AV node.
2. Action potentials pass through the AV node and along the AV bundle, which extends from the AV node, through the fibrous skeleton, into the interventricular septum.
3. The AV bundle divides into right and left bundle branches and action potentials descend to the apex of each ventricle along the bundle branches.
4. Action potentials are carried by the Purkinje fibers from the bundle branches to the ventricular walls.
What are the permeability changes during an action potential in cardiac muscle?
1. Depolarization phase:
- Voltage-gated Na+ channels open
- Voltage-gated K+ channels close
- Voltage-gated Ca2+ channels begin to open
2. Early repolarization and plateau phases
- Voltage-gated Na+ channels close
- Some voltage-gated K+ channels open, causing early repolarization
- Voltage gated Ca2+ channels are open, producing the plateau by slowing further repolarization
3. Final repolarization phase
- Voltage-gated Ca2+ channels close
- Many voltage-gated K+ channels open
What are the permeability changes in the pacemaker cells?
1. Prepotential
- A small # of Na+ channels are open.
- Voltage-gated K+ channels that opened in the repolarization phase of t he previous action potential are closing.
- Voltage-gated Ca2+ channels begin to open.
2. Depolarization phase
- Voltage-gated Ca2+ channels are open.
- Voltage-gated K+ channels are closed.
3. Repolarization phase
- Voltage-gated Ca2+ channels close.
- Voltage-gated K+ channels open.
What are the steps in the cardiac cycle?
1. Systole: period of isovolumic contraction. Ventricular contraction causes AV valves to close, beginning of ventricular systole. Semilunar valves are closed.
2. Systole: period of ejection. Cont. ventricular contraction pushes blood out of the ventricles. Semilunar valves open.
3. Diastole: period of isovolumic relaxation. Blood flowing back toward the relaxed ventricles, semilunar valves close. Beginning of ventricular diastole. AV valves closed.
4. Diastole: passive ventricular filling. AV valves open and blood flows into relaxed ventricles.
5. Diastole: active ventricular filling. Atria contract and complete ventricular filling.
How does the cardiac cycle relate to the PQRST on the ECG?
1. Systole- period of isovolumic contraction:
- QRS complex completed, ventricles depolarized. Ventricles begin to contract.
- atrial repolarization masked by QRS complex. Atria are relaxed.
2. Systole- period of ejection:
- T wave results from ventricular repolarization.
3. Diastole- period of isolumic relaxation:
- T wave is completes and ventricles repolarized/relaxed.
4. Diastole- passive ventricular filling:
- P wave is produced when SA node generates action potentials and a wave of depolarization begins to propagate across the atria.
5. Diastole- active ventricular filling:
- P wave completed, atria stimulated to contract.
-QRS complex begins as action potentials are propagated from the AV node to ventricles.
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