CARDIOVASC

ULAR
SYSTEM
 HISTOLOGICAL FEATURES OF HEART & BLOOD VESSELS
PROPERTIE
DETAILS
S
HEART
1. Epicardium:
 Equal to tunica adventitia of blood vessels & also known as visceral pericardium.
 Located outer to it is pericardial cavity which is enclosed by fibrous sac of parietal pericardium.
 Divided into 2 layers:
a. Outermost layer (free surface):
 A single layer of flat epithelial cells (mesothelial layer).
 Secretes a small amount of serous fluid for lubrication.
b. Sub-epicardial layer:
 Thin layer of connective tissue (fibroelastic layer) with broad layer of adipose tissue.
 Contain blood vessels (coronary blood vessels) & autonomic nerves.
2. Myocardium:
 E shape: long & elongated.
 E nucleus: 1 0r 2 in no with centrally located & barrel in shape.
HEART  E muscle fibers branch & interdigitate, but each is a complete unit surrounded by a cell membrane.
WALL  Intercalated disks r present which provide a strong union b/w fibers, maintaining cell to cell cohesion to transmit
contraction.
 Present of sacromere & T tubules (diad formation).
 Power of regeneration is absent.
 E cardiac muscle is thick & compact in ventricles but loose in atria.
 Papillary muscles: extension of myocardium to stabilize e valves.
3. Endocardium:
 Near to e chamber of e heart.
 Lined by a single layer of flat endothelial cells.
 Acts as e heart supporting tissue (sub-endocardial layer): a delicate layer of collagenous tissue.
 Also acts as fibro-elastic layer: because of this layer, e endothelium cannot be damaged while myocardium in
contraction.
 May have a small amount of fat (may or may not).
 Leaflets of collagenous tissue which r covered by a thin layer of endothelial layer which is continuous with that of e
heart chambers & great vessels.
HEART  E collagenous tissue is tough central fibrous sheet called lamina fibrosa which represents a merging of e fibroelastic
VALVES supporting layers beneath e endothelium.
 At e attached margins of each valve, e lamina fibrosa becomes condensed to form fibrous ring (valve annulus)& e rings
of e 4 valves together to form a central cardiac skeleton.
1. AV & SA Nodes:
 Embedded in dense vascular connective tissue.
 Rich in ANS fibers.
 Small specialized myocardial fibers with electrochemical stimuli being transmitted via gap junction.
2. Purkinje fibers:
CONDUCTIN  Modified cardiac muscle.
G SYSTEM  Specialized conducting system for e contraction of e myocardium.
 Located subendocardially & r bundle in form.
 E cells r larger, sometimes binucleate, & have an extensive cytoplasm.
 No T tubules system seen with electron microscope.
 Have fewer myofibrils which r distributed peripherally, leaving a perinuclear zone of comparatively clear sarcoplasm.
1. Cardiac muscles:
a. Cardiac hypertrophy: no increase in myocardial fibers number but increase in size only.
CLINICAL b. Heart damage: no regeneration of cardiac muscle tissue if damaged. Dead muscle cells r replaced by fibrous connective
tissue.
CORRELATI c. Cardiac contraction: lack of calcium ions in e extracellular compartment leads to cessation of cardiac muscle
ON contraction within in one minute.
d. Energy: total anerobic condition cannot sustain ventricular contraction (only up to 12% during hypoxia).
2. Endothelial cells: abnormal endothelial functions can cause hemorrhage, thrombosis, & exudation.
GENERAL FEATURES OF ARTERIES & VEINS
 Basically, arteries & veins have 3 layers of vascular walls from e lumen to outward:
1. Tunica intima (consists of 3 layers):
a. E endothelium:
 Properties:
 Flat polygonal cells.
 Numerous pynocytic vesicles.
 Specialized membrane bound organelles called Weibel – Palade bodies which store von Willebrand factor (VIII) in coagulation
cascade.
 Functions:
 Acts as permeability barrier & basement membrane maintenance (collagen & proteoglycans).
 Promotes protective thrombus formation by secreting Willebrand factor (VIII).
 Produces vasoactive substances (for blood flow control such as protacyclin & N2O), growth factors for fibroblasts & platelets,
and stimulating factors for blood cells colony.
b. E basal lamina of e endothelial cells.
c. E subendothelial layer:
 Consists of loose connective tissues occasionally with smooth muscle.
  Contains a sheet-like layer or lamella of fenestrated elastic material called internal elastic lamina (IEL).
 Fenestrations enable substances to diffuse readily through e layer & reach cells deep within e wall of e vessel.
 Contains fibroblasts & myointimal cells which produce extra-cellular constituents. Lipid accumulation inside e myointimal cells
with increased age causes arthrosclerosis.
2. Tunica media:
 Consists of circumferentially arranged layers of smooth muscle cells which produce all of e extracellular components of e layer.
 Variable amounts of elastin, reticular fibers, & proteoglycan r interposed b/w e smooth muscle cells of tunica media.
 There is external elastic lamina consists of elastin which separates tunica media from tunica adventitia.
3. Tunica adventitia:
 Composed of longitudinally arranged colagenous tissue & a few elastic fibers.
 Contains vasa vasorum that supply blood to e vascular walls as well as autonomic nerves called nervi vascularis that control e
contraction of e smooth muscle of e vessels.
ARTERIES
PROPERTIE TUNICA TUNICA
TUNICA MEDIA EEL IEL EXAMPLES
S ADVENTITIA INTIMA

ELASTIC 1. Connective
tissue. Smooth muscle. √ √ Aorta & its major branches.
ARTERIES 2. Elastic fibers. 1.Endothelium.
3. Thinner than Smooth muscle (8
MUSCULAR 2.Connective Baranches of elastic arteries &
tunica media. – 10) & collagen √ but little. √
ARTERIES tissue. distributing arteries.
4. Vasa vasorum fibers.
3.Smooth muscle.
ARTERIOLE Thin & ill- Smooth muscle
X √ but thin. Terminal arteries.
S defined. (<6 layers)

VEINS
1. Tunica adventitia:
 Outstanding features: thick with longitudinally oriented smooth muscle.
 Vasa vasorum presents inside intervening connective tissue.
2. Tunica media:
 Thinner compared to tunica adventitia.
LARGE
 Circularly arranged smooth muscle with > loosely connective tissues in portal vein & compact connective tissue in
VEINS other veins.
3. Tunica intima:
 Endothelium with small amount of connective tissue.
 Internal elastic lamina present but not well developed like in artery.
4. Examples: IVC, SVC, pulmonary trunk, & vena cava.
PROPERTIE TUNICA
TUNICA MEDIA TUNICA INTIMA EXAMPLES
S ADVENTITIA
1. Smooth
1. Connective tissue. 1.Endothelium.
MEDIUM muscle (2 – 15
2. Some elastic 2.Connective tissue. Branches of large veins.
SIZED VEINS layers).
fibers. 3.Smooth muscle.
2. Collagen fibers.
3. Thicker than
tunica media. Smooth muscle (1 -2 1.Endothelium.
VENULES layers). 2.Pericytes.
Muscular & postcapillary veins.

CAPILLARIES
 E smallest blood vessel with average diameter of 8 µm (1/2 of e diameter of RBC).
 Range of size 3 – 4 µm to 30 – 40 µm.
 Types of capillaries:
1. Continuous capillaries:
 Found in muscles, lungs, & CNS.
 Numerous pinocytic vesicles underlie both e luminal & basal plasma membrane surfaces for e transportation of
materials b/w e lumen & e connective tissue.
 In some capillaries, pericytes (unspecialized cells) may be associated with e endothelium. It can give rise to
TYPES smooth muscle cells during vessel growth.
2. Fenestrated capillaries:
 Found in endocrine glands & sites of fluid & metabolite absorption such as gallbladder, kidney, & GIT.
 E fenestration provides channels across e capillary wall. It may have a thin, membranous diaphragm across its
opening with a central thickening.
3. Sinusoidal capillaries:
 Found in liver, spleen, & bone marrow.
 They r larger in diameter & > irregularly shaped than other capillaries.
 Eg: Kupffer cells & Ito cells in e liver occur in e association with e endothelial cells.
 Blood flow of microcirculation is d/t muscle contraction:
1. Arterioles.
MICRO- 2. Metarterioles: large diameter capillaries with discontinuous layer of smooth muscle cells.
CIRCULATI 3. Precapillary sphincter: a sphincter of smooth muscle which is located at their origin from either an arterioles or
ON metarterioles. It controls e amount of blood passing through e capillary bed.
4. AV shunts: allow blood to bypass capillaries by providing direct routes b/w arteries & veins. Commonly found in skin.
 Controlled by: ANS, circulating hormones (adrenaline), O2 concentration, & metabolites (lactic acids).
CLINICAL CORRELATION
1. Endothelial cells with Weibel – Palades bodies covered by glycoprotein:
  Contain von Willebrand factor which facilitates coagulation cascade.
 Manufactured by most of endothelial cells but it is stored only in arteries.
 Persons with von Willebrand disease (inherited disorder) have prolonged coagulation times & excessive bleeding at an injury site.
2. Weakened vessel wall d/t embryological disease or connective tissue disorders:
 Will cause balloon out at e affected site, forming an aneurysm.
 If ruptured can cause death.

THE GROSS ANATOMY OF THE HEART

POINTS EXPLANATION
1. Anterior (sternocostal) surface: mainly by Rt.
3. Lt. Pulmonary surface: mainly by Lt. ventricle (cardiac
ventricle.
SURFACES 2. Diaphragmatic (inf. surface): mainly by Lt.
impression of Lt. lung).
4. Rt. Pulmonary surface: mainly by Rt. atrium.
ventricle, & partly Rt. ventricle.
1. Rt. border (slightly convex): b/w Rt. atrium which 3. Lt. border (nearly vertical): mainly by Lt. ventricle n slightly
extends b/w SVC & IVC. by Lt. auricle.
BORDERS 2. Inf. border (oblique, nearly horizontal): mainly by 4. Sup. border: by Lt. n Rt. atria n auricle in ant. View & post. to
Rt. ventricle, n slightly by Lt. ventricle. aorta n pulmonary trunk n ant. to SVC, inf. to T. sinus.
- Formed by inferolateral part of Lt. ventricle. - Remain motionless throughout cardiac cycle.
APEX - Lies post. to e Lt. 5th interostal space n 9 cm from median pl. - Place where sound of mitral valve closure are maximal:
apex beat
 Heart’s post. aspect (opposite apex) which is formed mainly by Lt. atrium, lesser by Rt. atrium
 Faces post. towards e bodies of vertebrae T6-T9 & is separated from them by pericardium, oblique sinus, esophagus, &
aorta.
BASE  Extends sup. to e bifurcation of pulmonary trunk n inf. to coronary groove.
 Receives pulmonary veins on Rt. n Lt. side of Lt. atrial n sup. n inf. venae cavae at sup. n inf. ends of its Rt. atrial
position.
 Functions:
 Properties:
1. Keep e AV orifices & semilunar valves patent n prevent them
FIBROUS  Complex framework of dense collagen
from overly distended by ↑ blood volume.
forming 4 fibrous rings.
SKELETO  Surround e orifices of e valves, Rt. n
2. Provides attachment for leaflets & cups of valves as well as for
N myocardium.
Lt. trigone, membranous part of
3. Forms an electrical insulator by separating myenterically
interartrial & interventricular septa.
conducted impulses of atria & ventricles.
1. Endocardium: thin internal layer (endothelium n subendothelium) which is e lining membrane of e heart & its valves.
LAYERS
2. Myocardium: thick, helical middle layer which composed of cardiac muscle.
OF WALL 3. Epicardium: thin external layer (mesothelium) which is formed by visceral layer of serous pericardium.
 Part:
 Others:
 Receives venous blood from SVC, IVC, n coronary sinus.
1. Fossa ovalis: - Oval,
 Rt. auricle: conical muscular pouch that projects from this chamber:
thumbprint depression of IA
Increasing capacity of atrium as it overlaps e aorta.
septum.(Surrounding ridge:
 Has Rt. AV orifice where Rt. atrium discharges e blood to Rt. ventricle.
Limbus FO).
CHAMBER  Interior surface of Rt. atrium:
2. SA node: at sup. end of
S  Has smooth, thin walled, post, part (sinus venarum).
sulcus terminalis, near
 Has rough, muscular ant. wall of musculi pectinati.
RIGHT  Separated by ext: sallow vertical groove, sulcus terminalis, int: crista
junction with Rt. side of
ATRIUM SVC.
terminalis.
3. AV node: at IA septum,
 Openings: above attachment of septal
1. SVC: into sup. part at 3rd costal cartilage. cusp of 3cuspid valve n to e
2. IVC: into inf. part at 5th costal cartilage. Lt. of opening of coronary
3. Coronary sinus: b/w Rt. AV orifice n IVC orifice. sinus.
4. Tricuspid O., Ant. carciad vein, n Venae cordis minimae.
 Lt. auricle:
 Tubular, muscular, n its wall trabeculated with pectinate muscle (musculi pectinati).
 Form sup. part of heart, n overlaps root of pulmonary T.
 E remains of Lt. part of primodial atrium.
 Interior surface of Lt atrium:
LEFT  Larger, smooth-walled part: sinus venarum.
ATRIUM  Rough, muscular part: musculi pectinati ( ori. Auricular chamber of embryonic heart).
 Semilunar (oval thin) depression in IA setum: Fossa ovalis (surrounding ridge is valve of fossa ovalis).
 Others:
 A slightly thicker wall than that of e right atrium where e 4 pulmonary veins (2 sup. n 2 inf.) entering its smooth
post. wall.
 Has IA septum that slopes post. n to e right & e mitral V. replaces its ant. wall n leads to Lt. ventricle.
VENTRICL Papillary Muscle Moderator Band
Walls AV Valves Blood Pathway
ES (PM) (MB)

RIGHT 1. Sup. - Conus  Guards AV orifice, 1. Ant. PM: A curved muscular  U-shaped pathway.
arteriosus: an AVO(4th-5th ICS) largest n more bundle that traverses  Inflow of blood into
VENTRICL arterial cone which  Bases attached to prominent, Rt. ventricular Rt.
E leads to pulmonary fibrous ring which from ant. wall, chamber from inf. pt.  Ventricle enters
trunk keeps e caliber of CT attaches to of IVS to e base of post. through AVO.
(infundibulum). orifice constant. ant. n post. PM, carries pt of When ventricle
2. Int. - Trabeculae  Chordae tendineae cusps of Rt. branch of AV contracts, e outflow
 tricuspid valve.
2. Post. PM:
carnae: Irregular smaller,
(CT) attached to cups
muscular consists of
at free edges n
elevations, 3 pt. several pt.,
ventricular surfaces n
PM, CT, n MB. from inf. wall,
arises from e apices
3. Supraventicular CT attaches to of blood into
of PM.
crest: separates post. n septal bundle. pulmonary T.
 Attachment to 2 cups
inflow (rough) pt. cusps of leaves sup. n to e
prevents their
from outflow tricuspid valve. Lt.
separation n inversion
(smooth) pt. 3. Septal PM:
when tension is
4. Rt. ventricle less from IV
applied to chordae
thick n lower in septum, CT
tendinae.
pressure. attaches to ant.
n septal cusp of
tricuspid valve.
 2 to 3 times as  Double mitral valves,:
thick as of that Rt. post to sternum (4th
ventricle. costal cartilage), 2
 V-shaped pathway.
 Mostly covered cups: ant. & post.
Other - Aortic orifice:  As blood traverses
with trabeculae  3 PM n CT support
Lies in its Rt. Lt. ventricle, it
carnae: finer n > MV to resists e
LEFT Ant. & Post. PMs posterosuperior pt. n undergoes 2 Rt.
numerous than Rt. pressure during
are larger than Rt. surrounded by fibrous angle turns, which
VENTRICL ventricle. contraction of Lt. V.
ventricle. ring to which Rt., result in 180o
E  A conial cavity  CTs become taut post., n Lt. cusps of change in direction.
longer than Rt. before n during aortic valve r This reversal takes
ventricle. systole to prevent attached-aorta begins place around ant.
 Inflow (rough) pt. cusps into Lt. atrium.
cusp of MV.
from outflow  Ant. cup larger than
(smooth) pt. post. cusp: attached to
fibrous ring.
1. Semilunar valve:
a. Concave when viewed sup, n don’t have CT to support them.
b. Smaller in area than e cusps of AV valves.
c. Force exerted on them is less than half that exerted on AV valves.
d. E cusps project into artery but are pressed toward its wall.
e. E cups open up like pockets as they catch e reversed blood flow, coming together to completely close e orifice,
supporting each other n preventing any returning blood.
f. E edge of each cusp is thickened (contact region) forming lunule.
VALVES g. A sinus is a space at e origin of pulmonary T. n ascending aorta b/w dilated wall of vessel n each cusp of e semilunar
valves.
h. Rt. n Lt. aortic sinus: Rt. n Lt. coronary artery. No artery at pulmonary sinus.
2. Aortic valve:
 B/w Lt. ventricle n ascending aorta, post. to Lt. side of sternum at 3rd ICS.
 Obliquely placed & has post., Rt., n Lt. cups.
3. Pulmonary valve:
 At e apex of conus arteriosus at 3rd costal cartilage.
 Has Ant., Rt., n Lt. cups.
1. SA node (sinuatrial node) = Pace maker of the heart:
 Specialized type of cardiac muscle fibers. 5mm at its widest part.
 Develops from e wall of the sinus venosus of e developing heart.
 Supplied by both divisions of e ANS.
 Regulates the heart to beat at 70 beats/min. & lies in the Right atrium just below the S.V.C. near e top of crista
terminalis.
2. AV node(atrioventricular node): lies in e interatrial septum above and to e left of the opening of e coronary sinus.
CONDUCTI 3. AV Bundle = Atrio-ventricular bundle of (His) Purkinje bundle:
 Runs through the membranous part of e IVS which bridge between e atrial & e ventricular muscle tissue.
NG
 Divided into Rt. And Lt. limbs at the junction b/w e membranous and muscular part of IVS.
SYSTEM  Supply: anterior papillary muscle + ventricles walls.
4. E conducting pathway:
 Impulse from SA node → atria’s muscles (contract) → AV node→ Av bundle → fibrous skeleton → IV
(membranous) inf. border (lies inf. to septal cusp of 3cuspid valve → Junction of membranous n muscular:
a. →Rt. Branches → septomarginal band →ant. papillary muscle→ant. wall of ventricle→Purkinje fibre →
beneath endocardium → contraction of ventricular muscles.
b. →Lt. branches→ septal endocardium→ papillary muscle → chordae tendinae→ drawing AV valves together →
contraction of ventricular muscles.
CARDIAC  Pain originating at nociceptors at one site in e body (deep/visceral) is sensed as originating at another site (usually
REFFERED supercial).
 Referred to superficial regions sharing e same dorsal root as e deep/visceral site from which e pain actually originated.
PAIN  E pain of angina pectoris n myocardial infarction radiates from:
1. Substernal region.
2. Lt. pectoral region to Lt. shoulder.
3. Medial aspect of e Lt. arm.
 E heart is insentitive to touch, cold, cutting, & heat.
 Ischaemia n accumulations of metabolic products stimulate pain endings in myocardium.
 CRP: Lt. side of chest n medial aspect of Lt. arm. Commissural neurons may make synaptic contacts with e Rt. side of e
comparable area of e cord. This why CRP may be referred to Rt. or both sides.

Sympathetic Supply Cardiac Plexus Parasymphathetic Supply

NERVE SUPPLY OF THE HEART

Presynaptic fibers Superficial Deep Cardiac - From presynaptic fibers of
- Cell bodies in intermediolateral Cardiac Plexus Plexus Vagus nerves.
columns (IMLs) of sup. 5/6 - lies on aortic - lies to e Rt. of - Postsynaptic cell bodies in
segments of spinal cord. arch b/w phrenic ligamentum atrial wall n interatrial septum
Postsynaptic fibers n vagus nerves arteriosum, inf. n near SA n AV nodes n along
- Cell bodies in e cervical n sup. medial aortic coronary artery.
thoracic paravebtebral ganglia of arch.
sympathetic trunk.

Vagus cardiac - Decrease:

- Traverse branches: 1) Heart rate
Increase:
cardiopulmonary - Sup. n inf. from 2) Force of contraction
1) Rate of polarization of SA node.
splanchnic nerves n cervical region. - Constrict coronary artery:
2) Atrioventricular conduction.
cardiac plexus to end - Recurrent Saving energy b/w periods of
3) Atrial n ventricular contractility.
in SA n AV nodes. laryngeal nerve. increased demand.
4) Coronary artery dilatation.
 ARTERIAL SUPPLY OF THE HEART.
ARTERY ORIGIN COURSE DISTRIBUTION ANASTOMOSES
Rt. Coronary Follows coronary (AV) groove Rt. atrium, SA n AV Circumflex n ant. IV branches
Rt. aortic sinus
Artery(RCA) b/w atria n ventricle nodes, n post. part of IVS of Lt. coronary A.
RCA near its origin Pulmonary trunk n SA
SA Nodal (60%)
Ascends to SA node
node
Passes to inf. margin of heart n
Rt. Marginal RCA
apex
Rt. ventricle n apex IV branches

Rt. n Lt. ventricles n post. Ant. IV branch of Lt. coronary

Post. Interventricular RCA (67%) Runs post. IV groove to apex
third of IVS artery (at apex)
RCA near origin of
AV Nodal post. IV artery
Passes to AV node AV node

Most of Lt. atrium n

Lt. Coronary Runs in AV groove n gives off
Lt. aortic sinus ventricle, IVS, AV RCA
Artery(LCA) ant. IV n circumflex branches
bundles
Circumflex branch Ascends on post. surface of Lt.
SA Nodal (40%) atrium to SA node
Lt. atrium n SA node

Passes along ant. IV groove to Rt. n Lt. ventricles n ant. Post. IV branch of RCA (at
Ant. Interventricular LCA
apex 2 thirds of IVS apex)
Passes to Lt. in AV groove n
Circumflex LCA
runs to post. surface of heart
Lt. atrium n ventricle RCA

Lt. Marginal Circumflex branch Follows Lt. border of heart Lt. ventricle IV branches
Runs in post. IV groove to Rt. n Lt. ventricles n post.
Post. Interventricular LCA
apex third of IVS
Ant. IV branch of LCA (apex)

Posterior interventricular a.
Marginal a. Posterior sinus
Ascending aorta

Rt. Coronal a.
Rt. Coronal a. Circumflex a.

Anterior sinus

Lt. Coronal a.
Ascending aorta
Anterior sinus

Posterior sinus
Posterior interventricular a.

Lt. Coronal a.
Anterior interventricular a.

Marginal a.
Circumflex a. Anterior interventricular a.

THE VENOUS SUPPLY OF THE HEART

Great Cardiac Vein
- Begins near e apex n ascends with e
Oblique vein of Lt. atrium ant. IV branch of LCA.
Small, merges with great cardiac - Its 2nd part runs along Lt. side of heart
vein to form coronary sinus. with e circumflex of LCA to coronary
sinus.
- Drain most areas supplied by LCA

Coronary Sinus
Middle Cardiac Vein
- accompanies post. IV
artery branch
- Post. interventricular
Ant. Cardiac Vein
- drains ant. aspect of Post. Lt. ventricular vein
Rt. atrium n ventricle
before crossinf RCA
to enter Rt. atrium Small cardiac vein
- Open directly to chambers of heart(atria).
- Marginal branch of RCA
 THE PERICARDIUM
PROPERTIES EXPLANATION
 A fibro serous membrane that covers e heart at e beginning of its great vessels.
PERICARDIUM  A closed sac composed of 2 layers: ext. – fibrous, int. – serous.
 Influenced by e movement of e heart n great vessels, sternum, n diaphragm.
 Tough ext. layer.
 Continuous inf. with central tendon of diaphragm (pericardiophrenic ligament.
FIBROUS  Continuous sup. with e tunica adventitia of great vessels entering n leaving the heart n pretracheal layer of deep cervical fascia.
LAYER (FP)  Bound post. by loose connective tissue to structures in post. mediastinum.
 Attached ant. to e post. surface of sternum by sternopericardial ligament.
 Protects heart against sudden overfilling (it’s unyielding, closely related to great vessels).
1. Serous layer (general): A single layer of flattened mesothelium cells forming simple squamous ephitelium that lines both int. surface
of fibrous p. n ext. surf. of heart.
2. Parietal layer:
 Lines with e int. surface of fibrous pericardium.
 Reflected onto heart at great vessels: aorta, pulmonary trunk, IVC., n SVC.
3. Visceral layer:
SEROUS  Makes up e epicardium (outermost).
LAYER (SP)  Extend onto e beginning of great vessels.
 Tranverse pericardial sinus: lies b/w group of aorta n pulmonary trunk n group of SVC, IVC, n pulmonary veins n e reflection of
SP around them.
 Oblique pericardial sinus: Bounded laterally by pericardial reflection surrounding pulmonary vein n IVC n post. by pericardium
overlying e ant. aspect of esophagus. It’s a blind sac.
 It’s a wide pocket-like recess in pericardial cavity post. to e base of heart, formed by Lt. atrium.

PERICARDIAL  Is a potential space b/w parietal serous layer n visceral serous layer.
CAVITY (PC)  Contains a thin film of fluid that enables e heart to move n beat in a frictionless movement.

1. Branch of internal thoracic cavity: pericardiophrenic artery.

ARTERIAL 2. Bronchial, esophageal, n sup. phrenic artery of thoracic aorta.
SUPPLY 3. Musculophrenic artery: branch of internal thoracic artery.
4. Coronary arteries.

VENOUS 1. Pericardiophrenic veins: tributaries of barchiocephalic veins.

SUPPLY 2. Variable tributaries of e azygos venous system.

1. Phrenic nerves (C3-C5) (sensory fibres).

NERVE
2. Sympathetic trunks for vasomotor function.
SUPPLY 3. Vagus nerves.

Ant. View
Post. View

Right coronary a. Coronary

Sinus
Anterior interventricular a.

Great Cardiac Vein

Marginal a.

Ant. Border

Lt. Surface
Rt. Border
Lt atrium
Inf. View Lt. Border

Inf. Border
Borders of the Heart
 THE BODY FLUID
PROPERTIES EXPLANATION
 Definition: Body water n its dissolved substances. 60% of body weight is due to body fluid. In 70 kg man, 42 kg is due
to BF.
OVERVIEW  Calculation: Total BF = Plasma Volume x 100 > Plasma Volume = 3500 mL.
100 – haematocrit > Haematocrit = e % of blood cells volume.
1. Intracellular Fluid (ICF)
 Fluid inside e cells. 40% of body weight (25 L).
 Is measured using D2O, 3H20, n aminopyrine.
 Calculation: V= BF – ECF.
2. Extracellular Fluid (ECF)
 Fluid outside e cells. 20% of body weight (15 L).
COMPARTME  Is measured using insulin, mannitol, n sucrose (difficult to measure because e limits of thin space are ill-defined).
NTS  2 divisions:
a. Inside vascular system (25% of ECF n 3 L):
i. Plasma – measured using Evans Blue which bound to plasma proteins.
ii. Blood cells measured by using tagged blood cells.
b. Outside vascular system (75% of ECF n 12 L).
 Known as interstitial fluid.
 Found in synovial joints, bathing cells, as well as ant. & post. sites of cells.
1. Mainly water (excellent solvent). 2. Electrolytes (ions) n non-electrolytes (urea,
 Carries nutrients n waste products into n out of body glucose, etc).
COMPOSITION cells.  Control osmosis of water b/w compartments.
S  Participate in chemical digestion.  Maintain acid-base balance.
 Acts as lubricant such as mucus in respiratory tract.  Cellular excitability.
FACTORS 1. Weight of e body (2/3 is due to BF).
DETERMINE 2. Sex: for male n female of e same body weight, male has greater fluid volume than female (amount of water in adipose
AMOUNT OF tissue is low compared to muscle).
3. Age: infant is 75% is BF while adult is 60% is BF.
BF
1. Hydrostatic pressure: pressure exerted by water (blood pressure) <outward force>.
2. Oncotic pressure or colloid osmotic pressure: pressure exerted by plasma protein n colloids <inward force>.
PRESSURE 3. Osmotic pressure: pressure necessary to prevent solvent migration to e concentrated region <inward force>.
PROPERTIES 4. Osmoles: concentration of osmotically active particles.
5. Osmolarity: no. of osmoles per liter of solvent.
6. Osmolality: no. of osmoles per kg of solvent.
 Definition: Negative logarithm of proton (H+) <logarithm to e base of 10 of e reciprocal H+ concentration>.
 pH of pure water at 25oC, in which H+ n OH- present in equal no. is 7.
pH OF BF  For each pH unit less than 7, e H+ concentration is increased 10 folds, n for each pH unit above 7, it is decreased 10
folds.
 A buffer is a substance that has e ability to bind or release H+ in solution, thus keeping e pH of e solution relatively
BUFFER
constant despite e addition of considerable quantity of acid n base.
SYSTEM  Buffer system of BF: carbonic acid, H2CO3 n plasma protein.
CHEMICAL
CONSTITUENT  Electrolytes distribution in ECF n ICF is maintained by:
S& 1. Selectively permeable membrane (fully, semi, n impermeable).
2. Sodium-potassium pump – maintains sodium n potassium ions concentration in ECF n ICF.
ELECTROLYT  Factors affecting e passage of molecules across e membrane:
E 1. Molecular size (inversely proportionate).
DISTRIBUTIO 2. Solubility in lipids.
N
 Distribution of water inside n outside of cells is dependent on osmotic pressure. Normally, osmolarity inside n outside
e cells is equal: 290 – 300 mosm/L (ECF: 80% due to sodium n chloride ions, n ICF: > 50% due to potassium ions).
 Tonicity: term to describe e osmolarity of a solution relative to plasma.
TONICITY 1. Isotonitic: solution that has e same osmolarity with plasma.
2. Hypotonic: solution with lesser osmolarity than plasma.
3. Hypertonic: solution with greater osmolarity than plasma.
 Definition: E abnormal collection of fluid in e interstitial spaces.
 3 main causes:
APLLIED 1. Increased capillary hydrostatic pressure – due to obstruction of blood in venous system. Eg: failure of Rt.
PHYSIOLOGY ventricle.
OEDEMA 2. A decreased in e plasma colloid osmotic pressure. Eg: excessive loss of albumin in e urine (kidney disease).
3. Obstruction of lymph vessels – accumulation of albumin in interstitial space. As a result: significant rise in colloid
osmotic pressure of e interstitial fluid n eventually becomes oedema.
TISSUE FLUID EXCHANGE
Arteriole: 32 mm Venule: 10 mm 1) Hydrostatic pressure is higher in capillaries than in tissue space n tends to drive fluid out of
Hg capillaries by filtration (outward).
2) Colloid pressure is higher in blood plasma than in interstitial fluid because plasma proteins r
Capillary: 25 mm Hg retained inside it. This tends to draw water out of capillaries by osmosis (inward).
3) Colloid pressure is uniform throughout capillary length while hydrostatic pressure falls from
arteriolar to venular end.
4) Thus, at arteriolar end, water is mainly filtrated, while at venular end, water is reabsorbed
back. This is important to maintain blood volume.
5) In lungs, capillary hydrostatic pressure is lesser than colloid osmotic pressure, therefore
there is no filtration to keep e alveoli wet.
Filtration Absorption 6) In kidneys, hydrostatic pressure is higher than colloid osmotic pressure, therefore filtration
Interstitial Fluid
takes place w/o absorption.
MICROCIRCULATIO 7) About 90% of fluid filtrated into interstitial space is goes back to circulation n 10% is
 THE CARDIOVASCULAR PHYSIOLOGY
PORTIONS EXPLANATION
 Transportation of respiratory gases, nutrients, hormones, n enzymes to all cells of e body, as well as transportation of
waste materials from cells to e lungs n kidneys for elimination.
 Body temperature regulation:
FUNCTIONS 1. Blood vessels constrict to retain body heat.
2. Blood vessels dilate to dissipate heat at skin surface.
 Body protection: Protect through immune system, blood cells, n etc.
 Separated into 4 chambers by a single fibrous skeleton which comprises of 4 interconnected rings of dense connective
tissue.
 4 chambers: Rt. n Lt. atria n Rt. n Lt. ventricles.
HEART  4 valves:
1. Atrioventricular valves: Rt. – Tricuspid, Lt. – Mitral.
2. Semilunar valves: Rt. Pulmonary, Lt. – Aortic.
 3 types:
1. Atrial muscle.
2. Ventricular muscle.
3. Specialized conducting fibres.
 Microscopic appearance:
CARDIAC 1. Striated in appearance like skeletal muscle.
MUSCLE 2. Roughly quadrangular n usually have only a single centrally located nucleus.
3. Muscle fibers branch n connected to each other by intercalated disk (provide a strong union b/w fibers,
maintaining cell-to-cell cohesion, so that e pull of 1 contractile unit can be transmitted along its axis to e next)
which contain desmosomes n gap junction (provide low-resistance bridges for e spread of excitation from one
fiber to another).
4. Close contact with large no. of elongated mitochondria.
1. Autorhythmicity:
 E ability to generate electrical impulses spontaneously n rhythmically.
 Under normal resting condition, cardiac muscle can contract n relax continuously n rhythmically w/o stopping.
 It contracts w/o extrinsive nerve or hormonal stimulation, but these reactions can cause increased or decreased
discharge.
PROPERTIES 2. Conductivity:
OF CARDIAC  E ability of e heart muscle to conduct nerve impulses around its fibers.
MUSCLE  It is conducted by specialized conducting system.
3. Excitability:
 E ability of heart muscle to respond to a stimulus.
 Cardiac muscle has extra-long rsting potential.
4. Contractility: Cardiac muscle remains contracted (depolarized) longer than skeletal muscle due to prolonged
delivery of calcium ions from sarcoplasmic reticulum n ECF.
EFFECTS OF
 Decreased temperature of ECF: decreased cellular metabolism, lower heart rate, n strength of cardiac contraction.
ECF IN
 Variation in ECF electrolyte concentration has a direct effect on membrane potential of cardiac cells.
CARDIAC  Cardiac muscles are sensitive to ECF calcium concentration.
FUNCTION
1. Hypercalcaemia: cardiac muscles become extremely excitable. Its contraction ism powerful n prolonged (can be fatal,
ABNORMALITI stop in systole).
ES 2. Hypocalcaemia: less excitable→ weak contraction → weak heart beat.

ACTION POTENTIAL

Resting membrane potential = =90 mV

+ 40 ↓
Electrical activity of pacemaker: stimulus
+ 20 2 ↓
Membrane of a ventricular myocardial contractile is excited over -70 mV
3 (threshold potential) generates action potential.
0
↓
Explosive increase in membrane permeability to Na+ n a subsequent
Membrane Potential ( mv )

- 20
4 massive Na+ influx (opening of Na+ channels)
- 40 ↓
Rapid depolarization – 2 msec (overshoot)
- 60 1 ↓
- 70 5 Early rapid repolarization (closure of Na+ channels)
- 90 ↓
Subsequent prolonged plateau – 250 msec (Opening of Ca2+ - Na+ channels
– slow inward diffusion of Ca2+ n a marked decrease in K+ permeability).
↓
1= Depolarization (Na+ entry: Permeability to K+ ↓). Late rapid repolarization (inactivation of Ca2+ - Na+ channels – diminishes
2 = Early rapid repolarization. slow n inward movement of Ca2+ n activation of K+ channels – promotes
3 =Plateau phase (Ca2+ - Na+ open: Ca2+ influx). rapid outward movement of K+)
4= Repolarization (Ca2+ - Na+ close: Ca2+ influx, Permeability ↓
Inside of e cell: negative
to K+ ↑).
Outside of e cell: positive
5 = Base Line. - Result in resting membrane potential = -90 mV

CONTRACTILE RESPONSE - Significance of plateau phase: Cardiac muscle cannot be excited again
ACTION POTENTIAL during action potential. Thus, tetanus will not occur, which will ensure
safety supply of oxygen throughout e body.
 THE CARDIAC OUTPUT
PORTIONS EXPLANATION
 Definition: Amount of blood ejected from Lt. or Rt. ventricles into e aorta or pulmonary trunk per minute respectively (i.e.
amount of blood ejected by each ventricle, not e total amount pumped by both ventricles).
OVERVIEW  Means that volume of blood flowing through pulmonary circulation is equivalent to e blood flowing through e systemic one.
 Cardiac Output, CO = Stroke Volume, SV x Heart Rate, HR
 At rest, SV = 70 mL, HR= 75 beats/min, so, CO = 70 x 75 = 5.25 L/min.
EQUATION  During exercise, CO can be increased 4-5 folds.
 Cardiac reserve = (Maximum volume of blood e heart is capable to pump) – (CO at rest).
STROKE VOLUME
END DIASTOLIC VOLUME
 Frank-Starling Law of e heart: Energy of contraction is proportional to e initial length of e cardiac muscle fibers.
 E resting length of cardiac muscle < optimal length.
 Thus, in initial cardiac muscle length (stretch), ↑ e contractile tension of e heart following systole.
 Cardiac muscle length increases with increasing EDV.
 EDV ↑→ cardiac muscle length ↑ → Vigor (strength of cardiac muscle↑→ expulsion of greater blood volume into aorta ↑ →
stroke volume↑→ cardiac output↑.
 Factors affecting EDV:
1. Venous return (VR): ↑ VR, ↑ EDV.
 Sympathetic stimulation produces venous vasoconstriction →↑ venous pressure →↓ venous filling capacity → ↑ VR.
 Skeletal muscle pump: ↑ Muscular activities → ↓ venous filling capacity → ↑ venous pressure → ↑ VR.
 Respiratory pump: Pressure different (Lower pressure in chest wall, but higher in abdomen n limbs) → squeezes blood
from lower to chest veins → ↑ VR.
 During ventricular contraction, atrial cavities ↑ → ↓ atrial pressure → ↑ vein to atria pressure ratio → ↑ VR
 ↑ total circulating blood volume → ↑ VR.
2. Atrial contraction: e greater e atrial contraction, e greater will be e ventricular filling, e greater VR (but not that 70% of
ventricular occurs passively before atrial contraction).
3. Distensibility of ventricles: pericardial temponade, myocardial infarction, n myocardial infiltrative disease all decrease
ventricular distensibility, & reduce VR.
4. Duration of diastole: e longer e duration of diastole, e longer e blood filling into ventricles, e higher VR.
HEART CONTRACTION OR MYOCARDIAL ACTIVITY
Related to e extrinsic control by factors which are originating outside e heart, mainly e action of cardiac sympathetic nerve n
hormonal action.
SYMPATHETIC STIMULATION PARASYMPATHETIC STIMULATION
Sympathetic stimulation. Parasympathetic stimulation.
REGULATIO ↓ ↓
N Release of ephinephrine, norephinephrine, n dopamine. Release of acetylcholine.
↓ ↓
Increased Ca2+ influx into cytoplasm from sarcoplasmic reticulum n Decreased Ca2+ influx into cytoplasm.
ECF. ↓
↓ Reduced myocardial (atrial muscle) contraction.
Cardiac muscles generate > contraction force through greater cross- ↓
bridge cycling. Reduced stroke volume.
↓ ↓
> rapid n > forceful contraction of ventricles. Reduced cardiac output.
↓
Increased stroke volume (Inotropic Effect).
↓
Increased cardiac output.
HEART RATE
 Primarily determined by rate of spontaneous depolarization of SA node.
 Determinants:
1. ANS that innervate SA node. 3. Plasma electrolytes.
2. Hormone thyroxine. 4. Body temperature.
 Sympathetic Effect: Sympathetic stimulation → release of ephinephrine → increased Ca2+ influx into cytoplasm → increased
rate of spontaneous depolarization → shorthened e time required for SA node to reach threshold → SA node fires more
frequently → increase heart rate (Chromotropic Effect).
 Parasympathetic Effect: Parasympathetic stimulation → release of acetylcholine → increased membrane’s permeability
towards K+ → > K+ ions efflux → decreased rate of spontaneous depolarization → prolonged e time required for SA node to
reach threshold → SA node fires less frequently → decreased heart rate.
1. Hypertension.
 A condition due to e chronic elevated atrial blood pressure.
 Heart need to generate more pressure in order to eject a normal cardiac output.
CLINICAL  Heart may be able to compensate for a sustained increase in afterload by enlarging (hyperthrophy).
CORRELATI 2. Heart failure.
ON  Refers to e inability of e cardiac output to keep pace with body’s demand for supplies n removal of wastes.
 Either 1 or both ventricles may progressively weaken n fail.
 When a failing ventricle is unable to pump blood out, e veins behind it will be congested with blood.
 2 most common reasons of heart failure:
a. Damage to e heart muscle as a result of a heart attack or impaired circulation to e cardiac muscle.
 b. Prolonged pumping against a chronically increased afterload or sustained elevation in blood pressure.

THE CARDIAC CONDUCTING SYSTEM.

PORTIONS EXPLANATION
 Composed of modified cardiac muscle that is striated but has indistinct boundaries n fewer organelles n myofibrils.
OVERVIEW  It generates n distributes e electrical impulses that stimulate cardiac muscle fibers to contract.
1. Sinoatrial Node (SA Node):
 Located at e junction of e sup. vena cava n e Rt. atrium.
 Characteristics: Able to spontaneously n rhythmically generate action potential
 Explanation: Cell membrane of sinus fibers r periodically very permeable to Na+ ions even in 1 resting state. Thus,
Na+ entry causes depolarization n action potential. This leakiness to Na+ ions does not cause e sinus nodal fibers
to remain depolarized all e time because of e 2 events occur during e course of action potential, which r:
a. Inactivation of Ca2+ - Na+ channels after opening
b. Opening of K+ channel.
 Self-excitation, recovery from action potential, drift of e resting potential to firing level (this process continues
indefinitely throughout a person’s life).
 SA node’s action potential per minute = 70 – 80.
 >> Prepotential/pacemaker potential r normally prominent only in SA n AV nodes. Atrial n ventricular muscle
fibers do not have prepotential, they discharge spontaneously only when injured or abnormal>>
2. Internodal Tracts:
 3 bundles of atrial fibers which conduct impulses from SA node to AV node:
a.E ant. internodal tract of Bachman.
b. E middle internodal tract of Wenkebach.
c.E post. internodal tract of Thorel.
3. Atroventricular Node (AV Node).
COMPONENTS  Located in e Rt. post. portion of e interatrial septum near e mouth of e coronary sinus.
 E fibers of e internodal tracts converge n interdigitate with e fibers in e AV node.
 AV node slows down e speed of electrical transmission. This delay permits enough time for e contracting atria to
empty their contents into e ventricle before ventricular contraction is initiated.
 AV node has a one-way conduction from atrium to ventricle.
 AV node’s action potential per minute = 40 – 60.
 Causes of slow conduction through AV node:
a. Size of AV node muscle tissues r smaller than atrial muscle fibres.
b. Fewer gap junctions in AV node muscle results in greater resistance to conduction.
c. Resting membrane potential > negative than atrial muscle tissues.
4. AV Bundle / Bundle of His.
 Means a bundle of fibers from AV node running towards e interventricular septum.
 Gives off 2 branches at e top of e interventricular septum:
 Lt. bundle branch which divides into ant. n post. fascicles/branches, n continues along inner side of e Lt. ventricle n
gives rise to smaller Purkinje Fibers.
 A Rt. bundle branch which is e continuation of e bundle, continue along e inner side of e Rt. ventricle, n gives rise
to smaller Purkinje Fibers.
5. Purkinje System: e terminal ramifications of e conducting system which spreads to all parts of e ventricular
myocardium.
1. Abnormal heart rhythm (arrhythmias).
 May be caused by:
a.SA node irregularities.
b. AV node irregularities.
c.By disturbance of conduction system.
2. Heart block.
ABNORMALITI
 An interruption in conduction, i.e. some or all of e impulses fail to reach ventricles.
ES  2 types:
a.Incomplete heart block: Atria beat normally but conduction through AV node is slowed.
b. Complete heart block: Conduction from AV node is severely hampers atria beat normally, but ventricles beat
independently at 20 – 40/min.
3. Ectopic foci: in conduction defect, a site other than SA node may become excitable n initiate beat on its own but e
normal beat.

ELECTRICAL PATHWAY OF THE HEART.

Action potential originates in SA node n 1st spreads through out both atria, from cell to cell via gap junction.
Interatrial pathway: extends from SA node within Rt. atrium to Lt. atrium (A wave of excitation spreads across e gap junctions throughout e Lt. atrium
at e same time similar spread is being accomplished through out Rt. atrium.
Internodal pathway: extends from SA none to AV node. This pathway directs e spread of action potential originating at SA node to e AV node to
ensure sequential contraction of e ventricles following atrial contraction.
↓
A slow transmission of action potential from atria to ventricles through AV node. This delayed time (0.1 sec) enables atria to become completely
depolarized n to contract, emptying their contents into e ventricles, before ventricular depolarization n contraction occur.
↓
Depolarization of ventricular muscle starts at e septum of Lt. ventricle n then spreads to Rt. across e midportion of e septum.
↓
Spread down e septum to e apex of e heart via Rt. n Lt. bundle branches.
↓
Impulses enter Purkinje fibers n spread to entire endocardial surface of ventricular muscles.
↓
Spreads to epicardial surface of ventricle n e last parts to be polarized are posterobasal part of Lt. ventricle n Pulmonary conus.
 THE SYSTEMIC ATRIAL BLOOD PRESSURE
PORTIONS EXPLANATION
 Pressure: e force per unit area.
 Blood pressure (BP): e force exerted by e contained blood on a unit area of blood vessel wall, & e force is imported by e
contraction of e heart (expressed in terms of displacement in mm Hg).
 Systolic blood pressure (SBP): e peak pressure in e atrial system during systole.
 Diastolic blood pressure (DBP): e minimum pressure in e atrial system during diastole.
OVERVIEW  Pulse pressure, PP = Systolic BP, SBP – Diastolic BP, DBP.
 Mean atrial BP is e average pressure throughout e cardiac cycle (it is slightly less than e value halfway b/w SBP n DBP
because systolic is shorter than diastolic).
 Mean Pressure = DBP + 1/3(Pulse Pressure)
= DBP + 1/3(SBP – DBP)
 For resting young adult in e sitting n lying position, Branchial Atrial Blood Pressure:
NORMAL 1. SBP = 90 – 130 mm Hg
VALUE 2. DBP = 60 – 90 mm Hg
3. Pulse Pressure = 30 – 50 mm g
MEASUREMEN 1. Direct Measurement: cannula is inserted into an artery n connected to a mercury manometer or recording device.
T 2. Indirect Measurement or Clinically measured BP: e lateral or side-pressure exerted on e vessel wall by contained blood.

 E amount of blood entering e arterial system which is determined by cardiac output.

DETERMINANT  E amount of blood leaving arterial system through e arterioles which is determined by e resistance offered by e arterioles of
S various vascular beds – total peripheral resistance.
 Thus, Blood Pressure = Cardiac Output, CO x Total Peripheral Resistance, TPR.
1. Age: SBP n DBP gradually rise with age. 4. Physical Exertion: Particularly isometric exercise rose BP.
PHYSIOLOGICA
2. Circadian Rhythm: SBP of 5-10 mm Hg rise in afternoon. 5. Eating (after meal): SBP rise due to increase in CO.
L VARIATIONS 3. Emotional Excitement: Transient rise. 6. Gravity.
 Reasons of regulation:
1. It must be high enough to ensure sufficient driving pressure in order for e brain n other tissues to receive adequate flow,
REGULATIONS no matter what local adjustments are made in e resistance of e arterioles supplying them.
2. E pressure must not be so high that it creates extra work for e heart n increases e risk of vascular damage n possible
rupture of small blood vessels.
 Within seconds.
 Adjustment is accomplished by alterations in cardiac output n total peripheral resistance, mediated by means of ANS
influences on e heart, veins, & arterioles.
1. Neural: E cardiovascular Reflex.
a. Baroreceptor Reflex:
 Includes a receptor, an afferent pathway, an integrating centre, an efferent pathway, n effector organs.
 Low pressure baroreceptors: atrial baroreceptor (volireceptor) n in pulmonary circulation.
 High pressure baroreceptor: systemic arterial baroreceptor (carotid sinus baroreceptor n aortic arch baroreceptor)
n Lt. ventricular baroreceptor).
 E integrating centre: e cardiovascular control centre located in e medulla within e brain stem.
 When BP rises: High pressure baroreceptors increase e rate of firing in their respective afferent neurons, n as a
result, cardiovascular control centre increases parasympathetic activity n decreases sympathetic activity.
 When BP falls: Low pressure barorecetors increase e rate of firing in their respective afferent neurons, n as a
SHORT TERM result, cardiovascular centre increases sympathetic activity n decreases parasympathetic activity.
b. Chemoreceptor Feedback Control:
 Receptors located in e carotid n aortic arteries.
 Sensitive to low oxygen or high acid level in blood.
 Act by reflexly increasing BP by sending excitatory impulses to cardiovascular centre. Eg: Hypoxic,
hypercepnie, acidosis resultant from stagnation due to hypotension stimulates e receptors.
 Central Nervous System to Ischcaemic response.
 Compensating rise in e BP as a result of intense vasoconstriction.
 May be high enough to cause reflex bradycardia.
2. Hormonal Reflex.
 Noradrenaline: Adrenaline system – increases BP.
 Renin-angiotensin: Aldosterone system – increases BP.
 Antidiuretic hormones: Vasopressin system – increases BP.
 Minutes to days.
 Control involves adjusting total blood volume by restoring normal salt n water balance through mechanisms that regulate
LONG TERM urine output n thirst.
 Mediated by renal body fluid pressure control system.
 Lt. atrial volume receptors n hypothalamic osmoreceptors: important in water-salt n balance n affect BP by controlling plasma
v.
 Cardiovascular responses associated with certain behaviors n emotions n r mediated through e cerebral cortex-hypothalamic
OTHERS pathway. Responses include e widespread changes in cardiovascular activity accompanying fight-to-flight response n etc n
slightly increase BP.
 Hypothalamic control over cutaneous arterioles: results in cutaneous vasoconstriction which help maintain adequate TPR, n
increases BP.
 THE HEART SOUND
PORTIONS EXPLANATION
 Normal heart produces 2 heart sounds which can be heard with a stethoscope during cardiac cycle.
 E sounds are caused by vibrations set up within e walls of e ventricles n major arteries during valves closure, not by valves
OVERVIEW snapping shut.
 Opening of valves does not produce any sound.
 Normal sound: “lub-dup-lub-dup-lub-dup”.
 Low –pitched, soft, n relatively long.
 Often said to sound like “LUB”.
 Associated with e closure of AV valves (tricuspid n mitral valves).
1ST HEART
 Signals e onset of ventricular systole.
SOUND  Duration ~ 0.15 sec n frequency ~ 25 – 45 Hz.
 Softer when heart rate is low because e ventricles are well filled with blood n e leaflets of e AV valves float together before
systole.
 High-pitched, shorter n sharper.
 Often said to sound like “DUB”.
 Associated with e closure of semilunar valves (pulmonary n aortic valves).
2ND HEART  Signals e onset of ventricular diastole.
SOUND  Duration ~ 0.12 sec & frequencies ~ 50 Hz.
 May become split during inspiration (physiological splitting) which due to e delay in closure of pulmonary valve.
 Mechanism during inspiration: Intrathoracic pressure becomes > negative → ↑ venous return → ↑ stroke volume → ↑ muscular
contraction of e heart → ↑ ejection time (prolonged) → pulmonary valve closes later than usual.
 Soft n low-pitched.
3RD HEART  Heard about 1/3 of e way through diastole in many young normal adult.
SOUND  It coincides with e period of rapid ventricular filling n is probably due to vibration set up by e inrush of blood.
 Duration ~ 0.1 sec.
 Can sometimes be heard immediately before e 1st sound when atrial pressure is high or e ventricle is stiff in conditions such as
4TH HEART
ventricular hyperthrophy.
SOUND  Due to ventricular filling n rarely heard in normal adult.
 Refers to abnormal heart sound.
 2 types:
1. Pathologic: involving heart diseases.
2. Non-pathologic: called functional murmur - > common in young people.
 Caused by turbulent blood flow which creates vibrations in e surrounding structures.
 2 types:
1. Systolic murmur: A murmur occurring b/w 1st n 2nd heart sounds (lub-murmur-dup).
2. Diastolic murmur: A murmur occurring b/w 2nd n 1st heart sounds (lub-dup-murmur).
MURMUR  2 characteristics:
1. Stenotic: Whistling murmur.
2. Insufficient: Swishy murmur.
 2 common causes:
1. Stenotic valve: A stiff, narrowed valve that does not open completely. Blood must be forced through e constricted opening at
tremendous velocity, resulting in turbulence that produces an abnormal whistling sound.
2. Insufficient (leaky) valve: Valves which cannot close completely, usually because e valve edges are scarred n do not fit
together properly. Turbulence is produced when blood flows backward through e insufficient valve n collides with e blood
moving in e opposite direction, creating a swishing or gurgling murmur.
THRILLS  Vibration which can be felt by e hand.
BRUITS  Heard over higher vascular region.
 THE CARDIAC CYCLE
PORTIONS EXPLANATION
 Defined as e sequence of events associated with 1 heart beat.
 Consists of a systole n diastole of both atria n ventricles,
OVERVIEW  Systole: Contraction phase (Occurs as a result of e spread of excitation across e heart).
 Diastole: Relaxation phase (Follows e subsequent repolarization of e cardiac musculature).
1. Stroke Volume: E amount of blood pumped out / ejected by each ventricle with each contraction at rest. Normal value: 70
– 90 mL.
2. End-systolic Volume: E amount of blood remaining in e ventricle at e end of ventricular systole when ejection IS
complete. Normal volume: 50 mL.
3. End-diastolic volume: E volume of blood in e ventricle at e end of diastole. Normal value: 120 -1 30 mL.
PROPERTIES 4. Ejection fraction = Stroke Volume - Normal value: 60% (valuable index of cardiac function).
End-diastolic volume
OF CARDIAC  Although Rt. n Lt. sides of heart have different atrial n ventricular pressure, they contract n relax at e same time n eject an
CYCLE equal volume of blood simultaneously.
 During cardiac cycle, although events of e 2 sides of e heart are similar, they are somewhat asynchronous.
 E processes:
1. Rt. atrial systole proceeds Lt. atrial systole (SA node located on Rt. atrium).
2. Lt. ventricle systole proceeds Rt. ventricle systole (Depolarization starts on Lt. ventricle septum).
3. Rt. ventricle ejection before Lt. ventricle ejection (Resistance is low n pressure of pulmonary artery > aortic pressure).
VARIATION IN PORTIONS HEART RATE (75 beats/min) HEART RATE (200 beats/min)
E LENGTH OF Duration of cardiac cycle 0.80 0.30
SYSTOLE N Duration of systole 0.27 0.16
DIASTOLE Duration of diastole 0.53 0.14

NORMAL RANGE
 Normal cardiac cycle: 0.8 sec.  1 heart beat = 60 sec = 0.8 sec.
 Normal heart beat: 75 beat/min. 75 beats
DURATION OF SYSTOLE N DIASTOLE
 Duration of systole is much more fixed than diastole.
PHYSIOLOGICA  When heart rate increased, diastolic period is shorthened.
L N CLINICAL  During diastole:
IMPLICATIONS 1. Heart muscles rest.
2. Ventricular filling occurs.
3. Coronary blood flows to subendocardial portion of ventricles occurs.
 Heart rate → ↓ period of diastole → physiological needs of heart cannot be done adequately → heart failure (prolonged).
 Example:
1. Tachycardia >> High heart rate: > 100 beats/min.
2. Bradycardia >> Low heart rate: < 60 beats/min.

E
→ VENTRICLE FILLING).
2) ATRIAL SYSTOLE
elaxed.
When nSA
re of both ventricles is lower than that of aorta n pulmonary artery so that aortic node fires,
pulmonary atrialrcontraction
valves closed. occurs emptying 30% of remaining blood from atria to ventricles.
Volume
r than that in e great veins, so that blood flow into e atria n ventricles on each of bloodr in continuity
side (which ventricles at
as ee end of ventriclesvalves
atrioventricular at e end of diastole is 120 – 130 mL (End-Diastole Volume).
r open).
as e ventricle become distended (70% of blood flows passively from atria to ventricle).

OLE

e impulse passes through e AV node n specialized conduction system to excite e ventricle, n results in ventricles contraction.
ressure which causes AV valve to close (1st heart sound).
exceeds aortic n pulmonary pressure, aortic n pulmonary valves open.
ntricle to aorta n Rt. ventricle to pulmonary arteries (Ventricular ejection).
becomes lesser than aortic pressure, semilunar valves close (2nd heart sound) n ventricular filling occur again. (Dicrotic notch: Disturbance or notch produced on e aortic curve pressure du
 THE ELECTROCARDIOGRAM
PORTIONS EXPLANATION
 Fluctuations in potential that represent e algebraic sum of e action potentials of myocardial fibers can be recorded
extracellularly.
OVERVIEW  This is because, e body fluids are good conductors (e body is a volume conductor).
 ECG: E record of these potential fluctuations during cardiac cycle.
 Can be recorded by using an active or exploring electrode connected to an indifferent electrode at zero potential (unipolar
recording) or by using 2 active electrodes (bipolar recording).
 In a volume conductor, e sum of potentials at e points of an equilateral triangle with a current source in e centre is zero all e
MEASUREMEN time.
T  A triangle with e heart at e centre (Einthoven’s triangle) can be approximated by placing electrodes on both arms n e Lt. leg
called standard limb leads. If connected to a common terminal, an indifferent electrode that stays near zero potential is
obtained.
 Depolarization (positive) moves towards an active electrode n repolarization (negative) moves in opposite direction.
1. Bipolar leads: these record e potential difference b/w 2 active electrodes.

Standard Limb Leads:

Leads Positive Electrodes Negative Electrodes Results
I Lt. Arm (LA) Rt. Arm (RA) LA - RA
II Lt. Foot (LF) Rt. Arm (RA) LF - RA
III Lt. Foot (LF) Lt. Arm (LA) LF - LA

2. Unipolar leads: these have an active (exploring) electrode placed or a chosen site linked with an indifferent elsctrode. 1 being
zero, e potential difference b/w e 2 represents e actual local potential. They r called “V” leads because they record values
LEADS approaching meaningful voltages. Can also be placed at e tips of catheters n inserted into e esophagus or heart.
 Unipolar Limb Leads: aVR, aVL, as well as aVF for Rt. arm, Lt. arm, n Lt. foot respectively. (a = augmented, when e
amplitude of deflection increased (These r recording b/w one limb n another 2).
 Unipolar Chest Leads (Precordial Leads).
V1 4th ICS, Rt. sternal border.
V2 4th ICS, Lt. sternal border.
V3 Equidistance b/w V2 n V4. APEX
V4 5th ICS, midclavicular line. LEADS
V5 5th ICS, ant. axillary line.
V6 5th ICS, midaxillary line.
1. P Wave.
 Represents atrial depolarization.
 Begins as e impulse spread from SA node across e atria. E activity of SA node itself cannot be detected in ECG.
 Duration: 0.1 sec – indicates e time taken for e impulse to spread through atrial muscle.
 E magnitude of P wave is some guide to e function of atria.
 Because e impulse spread from Rt. to Lt. n downward, e P wave is:
 Upright in leads I, II, aVF.
 Inverted in leads aVR, III, aVL, n V1.

2. PR Interval.
 Measured from onset of P wave to e beginning of QRS complex.
 It measures e AV conduction time which includes atrial depolarization, AV nodal delay, n conduction down e bundle of
His to e ventricular myocardium.
 Duration: 0.12 to 0.20 sec (normal adult with normal heart).

3. QRS Complex.
SEGMENTS  Represents ventricular depolarization.
 Q wave is a downward deflection preceeding an R wave which is an upward deflection of QRS.
 S wave is a downward deflection following an R wave.
 In e routine 12 leads ECG, e manifestation of atrial repolarization is submerged in QRS complex.
 Duration: 0.10 sec (upper limit for normal person).

4. ST Segment n T Wave.
 Represents ventricular repolarization.
 ST segment is e part b/w e end of QRS complex n e beginning of T wave.
 T wave is normally in e same direction as e largest part of QRS complex since repolarization takes place in e reverse
direction from depolarization.
 Derivation from normal r commonly associated with myocardial ischaemic.
 E hall mark of myocardial ischaemial infarction is ST segement elevation in leads overlying e area of infarction, n ST
segment depression in leads on e opposite side of e heart. At a later stage, ST segment elevation less pronounced as T
wave inversion developed.

1. Detection of heart rate (both atrial n ventricular).

2. Rhythm (regular or irregular) for diagnosis of arrhytmias.
3. Conduction of cardiac impulse (delayed or block at e side of defect).
USES 4. Change in myocardial perfusion (ischaemic), structure (infarction n hyperthrophy), n function (ventricular fibrillation or
cardiac arrest).
5. Change in plasma electrolytes (potassium n calcium), eg: when blood potassium decreases, T wave decreases also.
6. To detect heart block, atrial extrosystoli, atrial tachycardiac, atrial flutation, atrial fibrillation, n myocardial infarct.
 aVR aVL

R V1
1.0 V2
V3
Isoelectric
line
0.5 V4 V5 V6

0 PR Segment ST Segment
T
P
U

-0.5
Q
PR interval
S
QRS duration
QT interval aVF

0 0.2 0.4 0.6

Unipolar electrocardiographic
TIME (s)
leads
Waves of the ECG

V1 V2
aVR aVL
V3 V4 V5 V6

V1 V2 V3 V4 V5 V6

III
II aVF
 THE CARDIOVASCULAR REFLEX
POINTS DETAILS
 Baroreceptors r stretch receptors in e wall of e heart & blood vessels.
 They r 2 types of baroreceptors:
1. Low pressure baroreceptors:
a. Baroreceptors in pulmonary circulation.
b. Atrial baroreceptors (volireceptor).
 In atrial–caval & atrio–pulmonary vein junction.
 2 types:
i. Type A receptors: discharge primarily during atrial systole.
ii. Type B receptors: discharge primarily during peak atrial filling.
2. High pressure baroreceptors:
BARORECEPT a. Systemic arterial baroreceptors:
 2 types of baroreceptors:
ORS i. Carotid sinus baroreceptors: a small dilation of e internal carotid artery just above e bifurcation of e
common carotid.
ii. Aortic arch baroreceptors: found in e adventitia of e wall of e aortic arch.
 These baroreceptors respond to changes in e wall stretch produced by:
i. Mean BP changes.
ii. Changes in pulse pressure.
iii. External pressure.
 Increased baroreceptor discharge inhibits e tonic discharge of e vasoconstrictor nerves & excites e vagal
innervations of e heart, producing vasodilation, venodilation, a drop in BP, bradycardia, & a decrease in
CO.
b. Left ventricular baroreceptors: maintenance of e vagal tone that keeps e heart rate low at rest.
BARORECEPTOR REFLEX
 There r 2 baroreceptor afferents:
1. Carotid sinus (from neck): Glossopharyngeal nerve (IX craninal nerve).
2. Aortic arch (from thorax): Vagus nerve (X cranial nerve).
 E above cranial nerves r called buffer nerves because their roles in e baroreceptor reflex:
BARORECEPTO 1. Buffer e changes in e arterial BP.
R AFFERENT 2. Maintain BP homeostaisis.
 Buffer nerves activities:
1. Secrete glutamate which stimulates GABA-secreting inhibitory neurons.
2. Discharge at a slow rate at normal BP.
3. E discharge increases when pressure in carotid sinus & aortic arch increase & vice versa.
1. Vasomotor centre in medulla (CMV): increased baroreceptor discharge inhibits neuron of VMC while decreased
discharge stimulates e neuron.
INTEGRATING
2. Vagal nuclei in e medulla: impulses in e baroreceptor afferent excite vagal nuclei.
CENTRE 3. Vasopressin stretching neuron in e hypothalamus: increased baroreceptor discharge inhibits vasopressin secretion &
decreased discharge stimulates hormone secretion.
1. Heart: adjustment in CO.
2. Arterioles: variation in total peripheral resistance.
EFFECTORS 3. Veins: alteration in amount of blood stored in capacitance vessels.
4. Capillaries: fluid shift 2o to BP changes.
1. Fall in BP → decreased baroreceptor discharge:
a. Stimulate VMC → sympathetic stimulation.
b. Less stimulation of vagal nuclei → decreased vagal tone.
MECHANISM OF c. Less inhibition of vasopressin secretion → secretion of vasopressin.
REFLEX 2. Rise in BP → increased baroreceptor discharge:
a. Inhibit VMC → decreased sympathetic stimulation.
b. More stimulation of vagal nuclei → increased vagal tone.
c. Inhibition of vasopressin secretion → decreased secretion of vasopressin.
CHEMORECEPTOR REFLEX
 E CVS response to chemoreceptor stimulation consists of peripheral vasoconstriction & bradycardia.
 Hypoxia produces hyperpnea & increased cathecolamine secretion from e adrenal medulla which lead to tachycardia & increased CO.
 A rise in arterial PCO2 stimulates e vasomotor area but e direct effect of hypercapnia is vasodilation.
 Exposure to high concentration of CO2 is associated with marked cutaneous & cerebral vasodilation but vasoconstriction occurs elsewhere &
usually there is a slow rise in BP.
HORMONAL MECHANISM
1. Adrenal medullary (naroadrenaline – adrenaline system): cathecolamines → vasoconstriction.
2. Renin – angiotensin – aldosteron system:
3. Vasopressin: causes generalized vasoconstriction (particularly splanchnic vasculature) & water retention (anti-diuretic act).
OTHER CVS REFLEX
1. Renal body fluid control system:
 Is a long term mechanism.
 Rise in arterial BP greatly increases e rate at which e kidney excrete water and salt (pressure diuresis & pressure natriuresis ) → loss of ECF
volume → lower BP.
2. Coronary chemoreflex (Bezold-Jarisch Reflex): injection of certain chemical (e.g. serotonin) into coronary artery supplying e left ventricle results
in hypotension, bradycardia & apnea followed by tachycardia.
3. Somato-sympathetic reflex: during muscular activity, proprioceptors & pain receptors r stimulated leading to increased sympathetic discharge
4. Emotional stress reflex: limbic cortex → VMS & vagal centre (anger excite . . .).
 5. Lung inflation reflex: lung inflation → vagal afferent → VMS inhibited → BP decreases.
6. Reflex from otherSummary ofregion:
pressure sensitive Baroreceptor Reflex
blow on abdomen Regulation
& pressure on e eyeball leadof
to arterial
bradycardia BP
& vasodilation.

Fall in blood vol. and / or pressure

Decreased discharge of baroreceptors

Increased activity Decrease Hypothala

of group of d Vagal mus
neurons in VMC Discharg
 Sympathetic e
discharge to : Increased
Vasopress
Arterio Veins Heart Adr. in
JGA
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Adrenalin
e RA.
  Venous system
tone  Increased
Arteriola Myocardial heart rate
r  Venous contractility  Water
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 End Sodium
diastolic reabsorpti
volume on in
 Stroke Increased kidney
 volume Cardiac
Adrenaline Output
Angiotensi  Total peripheral
n II resistance

Chemoreceptor Feedback
Fall in BP
Control of BP
Stagnan Chemoreceptor Impulses in
t s in Carotid IX, X cronial
[ up to 40- Hypoxia and Aortic nerves
80 mmHg ] bodies Excite neurons
in VMC
Hypoxia ( Due to
Hypotension )
Stimulat
ion of
Chemoreceptors Respiratory centre Adr. Medulla
Stimulat
VMCion of Hypercapnoea Increased
( secretion of
respiration) catecholamines
Tachycardia Tachycardia Tachycardia
(
heart rate )
 THE REGIONAL CIRCULATION
CIRCULATIO DETAILS
N
 At rest, e coronary blood flow is ~ 200 ml/min (4% of CO).
 Rt. & Lt. coronary arteries arise from e root of e aorta.
 Factor influencing coronary blood flow:
1. Haemodynamic determinants:
 Pressure gradient b/w e aorta & e Lt. ventricle determines coronary blood flow.
 During systole there is less blood flow in e subendocardial portion of e Lt. ventricle because e contracting
muscle compresses e blood vessels but this force is dissipated in e more superficial portion of e Lt. ventricle
musculature to permit some flow in this region.
2. Chemical control (autoregulation):
CORONARY  Metabolic theory of autoregulation: coronary blood flow is reduced → accumulation of vasodilator metabolites
→ dilation of e coronary blood vessels → restoration of e blood back to normal.
CIRCULATIO  Hypoxia increases coronary blood flow to 200 – 300%.
N 3. Neural regulation:
 E coronary arterioles contain both α & β-noradrenagic receptors mediating vasoconstriction & vasodilatation
respectively.
 α-receptors r more sensitive to noradrenaline, thus e direct effect of noradrenergic sympathetic stimulation is
vasoconstriction.
 Noradrenaline increases cardiac rate & contraction as well as e work of e heart which lead to accumulation of
VDM & dilation of e coronary vessels.
 This effect overrides e direct vasoconstriction effect via α-receptors so that e overall effect of sympathetic
noradrenergic activity is coronary vasodilatation.
 Increased vagal activity to e heart causes coronary vasodilatation & increased coronary flow.
SKELETAL 1. Sympathetic nerves stimulation: causes vasoconstriction which is mediated by α-adrenergic receptors in reflex response
to decreased arterial pressure.
MUSCLE
2. Epinephrine causes vasodilatation when present in low concentration & vasoconcentration (via α-adrenergic) when
CIRCULATIO present in high concentration.
N 3. Controlled by local metabolic factors during exercise.
 Involves GIT, spleen, pancreas, & liver which consists of 2 capillary beds which r in series with each other.
SPLANCHNI  Blood from e capillaries of GIT, spleen, & pancreas flow via portal vein to e liver which also receives a separate arterial
blood supply.
C
 Sympathetic nerves cause vasoconstriction (α-adrenergic) in reflex response to decreased arterial pressure & during
CIRCULATIO stress. Also, venous constriction causes displacement of a large volume of blood from e liver to e veins of e thorax.
N  Increased blood flow occurs following ingestion of meal & is mediated by local metabolic factors hormones secreted by
e GIT.
RENAL  Flow autoregulation is a major factor.
CIRCULATIO  Sympathetic nerve causes vasoconstriction via Angiotensin II which is e major contrictor.
N  This reflex conserves sodium & water.
 Controlled mainly by sympathetic nerves & mediated by α-adrenergic receptors.
CUTANEOUS  Reflex vasoconstriction occurs in response to decreased arterial pressure & cold.
CIRCULATIO  Reflex vasodilatation occurs in response to threat.
N  Substances released from e sweat glands & noradrenergic neurons also cause vasodilatation.
 Venous plexus contains large volumes of blood which contributes to skin.

PULMONAR  E circulation is in a very low resistance compared to systemic circulation.

 Controlled mainly by gravitational forces & passive physical forces within e lung.
Y  Constriction which is mediated by local factors occurs in low O2 concentration, just opposite to that occurs in e systemic
CICULATION circulation.
 E volume of blood & e extravascular fluid in e brain is relatively constant.
 Thus, changes in either of this fluid volume must be accompanied by a reciprocal change in other.
 In contrast to most other organs, e cerebral blood flow is held within a relatively narrow range which in human e average
is 55 mL/min/ 100 g of brain.
BRAIN  E brain is least tolerant organ to ischemia because if there is interruption of cerebral blood flow for as a little as 5
CIRCULATIO seconds, loss of consciousness occurs.
N  Ischemia lasts for just a few minutes (~ 5 mins) will result in irreversible tissue damage.
 E regulation of cerebral circulation is mainly under e direction e brain itself.
 Local regulatory mechanisms & reflexes that originate in e brain tend to maintain cerebral circulation relatively constant.
 This constancy prevails even in e preence of possible adverse extrinsic effects such as sympathetic vasomotor nerve
activity, circulating humoral vasoactive agents, & changes in arterial blood flow.
 E fetal circulation differs from that of an adult by:
FETAL 1. Low pulmonary blood flow.
CIRCULATIO 2. High placental blood flow.
N 3. Shunting of from Rt. atrium to e Lt. atrium through e foramen ovale & from e pulmonary artery to e aorta via e
ductus arteriosus. This shunts allow e blood to bypass e fetal lungs.
MICRO –  Definition: e flow of blood in e system of linear blood vessels (50 µm or less in diameter).
CIRCULATIO  It includes e capillary, precapillary arterioles, & postcapillary venules.
 Consists of 5% of e circulatory blood volume.
N  E functions:
1. Exchange of respiratory gases.
2. Exchange of nutrients & metabolic waste products.
3. Exchange of water (formation of interstitial fluid & its regulation).
 4. Exchange of other substance such as hormones.
5. Exchange of heat in thermoregulation.
 Causes of edema:
1. Increased filtration pressure: arteriolar dilatation & venular constriction.
2. Increased venous pressure d/t venous pressure & gravity.
3. Decreased oncotic pressure because of:
EDEMA a. Diet: starvation or poor protein intake.
b. Liver failure: failure to synthesis plasma protein as in cirrhosis.
c. Kidney disease: loss of protein.
4. Increased capillary permeability d/t histamine, substance P, or kinins.
5. Inadequate lymph flow d/t surgical removal of lymph nodes or obstruction of lymphatic vessels as in flariasis.

THE EFFECTS OF EXERCISE ON CVS

POINTS DETAILS
 Exercise is associated with very extensive alterations in e CVS.
 Mainly it is associated with increased oxygen consumption & e amount of O2 required depends on intensity of exercise.
OVERVIE  Muscles convert about 20% of e energy of ATP to external work, e remaining energy appearing as heat.
 Consumption of O2 by aerobic system takes time to develop & continues for some time after exercise stops.
W  There are two types of exercises:
1. Isotonic exercise (dynamic/rhythmic contraction).
2. Isometric exercise (static/sustained).
TYPES OF EXERCISE
1. Blood flow to muscle increases during isotonic exercise as a result of:
a. Vasodilatation in skeletal muscle blood vessels due to:
 Increased action of sympathetic cholinergic nerves to blood vessels in muscle.
 Catecholamine released from adrenal medulla (especially adrenaline acts on 2 receptors in blood vessels of skeletal
muscle causing vasodilatation).
 Local factors:
ISOTONIC  [↑PO2, ↑PCO2, ↓pH, ↑K+ → Vasodilatation]
EXERCISE  Increased in temperature also causes vasodilatation.
b. Shifting of blood from certain peripheral circulation (such as splanchnic & renal circulation) to exercising muscles as a
result of increased sympathetic stimulation causing vasoconstriction.
2. Increased CO: d/t increased heart rate & stroke volume.
3. Increased oxygen transfer or oxygen extraction d/t 2 things:
 Recruitment of previously closed capillaries.
 Increased in release of O2 from haemoglobin due to local factors (↑H+, ↑temperature, & etc).
 E sequence isometric exercise:
 Sustained contraction of muscles → Vasodilator metabolic accumulate in muscle → Stimulation o f sensory nerves →
Cardiovascular centre → Increased sympathetic activity.
ISOMETRI  E effects of isometric exercise:
1. Increased heart rate d/t:
C
a. Increased sympathetic discharge.
EXERCISE b. Decreased vagal discharge.
2. Increased DBP d/t increase in total peripheral resistance.
3. Increased SBP d/t increase in contractility of e heart.
4. Mean arterial BP increases.
COMPARISONS
ISOTONIC EXERCISE PROPERTIES ISOMETRIC EXERCISE
Heart rate increased d/t:
Increase in CO mainly d/t heart rate not d/t stroke
volume.
CO & HEART RATE 1. Increase in sympathetic discharge.
2. Decrease in vagal tone.
Net total peripheral resistance decreased/not Total peripheral resistance increased d/t increase in
changed.
Total Peripheral Resistance sympathetic discharge.
1. Systolic BP increase d/t contractility. 1. Systolic BP increases.
2. Diastolic BP decreases d/t decrease in net total 2. Diastolic BP decreases d/t increased total
peripheral resistance. BP peripheral resistance.
3. Mean BP slightly increases or stays e same. 3. Mean Arterial BP largely increases.
4. Pulse Pressure increases. 4. Pulse Pressure only has a little change.
O2  If exercise is started abruptly & a constant moderate work output is maintained, e O2 uptake takes several minutes to reach a
DEFICIT steady state.
 E oxygen deficit: e missing O2 that would have been consumed if e body’s response to e O2 demand of exercise was immediate.
& DEBT  For mild to moderate exercise e O2 deficit is accounted for by:
1. E lower content of ATP & creatinine phosphate in e active muscles.
2. E reduction in O2 content of myoglobin in e active muscle.
 E O2 debt or excess post-exercise O2 consumption represents repayment of e O2 deficit:
 When e exercise is vigorous or prolonged, e debt is considerably greater than e deficit.
 Following such exercise e ATP & cutreatinine phosphate stores & e O2 content of myoglobin & venous blood return to
normal within a min or two, but there is a residual elevated O2 consumption that can last for min to hours.
 This depends on e intensity & duration of the exercise where e extra O2 consumption is attributed to:
1. E energy needed to dissipate heat & restore intracellular electrolytes to normal concentrations
 2. E higher metabolic rate caused by e increase in body temperature & in e circulating levels of catecholamine &
thyroxine.
 Regeneration of intramuscular glycogen stores also produces a very small increase in O 2 consumption over a period of a day or
two following e exercise.
Exercise
Rest
Light Medium Heavy
Oxygen consumption (ml min ) -1 250 1500 2800 3500
Oxygen consumption of muscles (ml min-1) 50 1250 2200 3150

Cardiac output (L min-1) 5 13 16 21

100 127 130

Arterio venous oxygen difference (ml L-1)
50
PvO2 (mmHg) 40 26 23 20
72 144 160 190
Heart rate (beats min-1)
200 170 150
Diastolic filling time (ms) 500
70 90 100 110
Stroke volume (ml)
90 95 100
Mean blood pressure (mmHg)
85

Pulse pressure (mmHg) 40 60 90 120

Systolic / diastolic pressure (mmHg) 110/70 130/70 155/65 180/60

Cardiorespiratory variables and indices at rest and during exercise.

Stroke Volume Heart Rate

(mL) (Beats / min.)
Resting
 Non-athlete 75 75
 Marathoner 105 50

Maximum:
 Non-athlete 110 195
 marathoner 162 185

COMPARISON OF CARDIAC OUTPUT BETWEEN MARATHONER AND NON-

ATHLETE

1500

O2 deficit
VO2 (ml min-1)

1000
O2 debt

500
Work

0
2 4 6 8 10 12
Time (min.)

Time-course of O2 consumption (VO2) during moderate exercise, illustrating the O2 deficit and debt
 THE HYPERTENSION
POINTS DETAILS
 There r 2 types of hypertension:
1. Essential hypertension:
 Also known as primary hypertension.
OVERVIEW  I.e. e hypertension which is caused by multiple factors & in most instances, e causes remain unknown.
2. Secondary hypertension: hypertension in which e cause is known.
 Epidemiologic evidence point to genetic inheritance, psychological stress, & environmental & dietary factors which
perhaps may contribute to e pathogenesis of hypertension.
AETIOLOGY & PATHOGENESIS
 E neural components which r important in dealing with blood pressure:
1. Vasomotor center
2. Dorsal motor nuclei of e vagus nerves.
3. Nucleus tractus solitaries.
4. Hypothalamus.
5. Parts of cerebral cortex i.e. motor cortex.
6. Anterior temporal lobe.
7. Orbital areas of e frontal cortex.
8. Cingulate gyrus, amygdala, septum, & hippocampus.
 E normal physiological process:
1. E adrenergic junction:
 α-adrenergic stimulation within CNS decreases BP through an inhibitory effect on e vasomotor center.
ABNORMAL  Increased Angiotensin II increases sympathetic outflow from e vasomotor center, resulting in an increase in BP.
 Pre-synaptic receptors: stimulation of pre-synaptic α–receptors inhibits NE release while stimulation of pre-
NEURAL synaptic β-receptors increases NE release.
MECHANISM  Post-synaptic receptors: Stimulation of post-synaptic α-receptors on arterioles & venules causes
vasoconstriction.
 Stimulation of β1-receptors in e heart causes increase in HR & contractility.
 Stimulation of β2-receptors in arterioles & venules causes vasodilatation.
2. E baroreceptor reflex: they r responsible for rapid, moment-to-moment adjustments in BP, such as in change from
a reclining to an upright posture.
 E hypertension can be a result of any primary defect that can occur in any of these major components:
1. Central Nervous System.
2. Autonomous Nervous System.
3. Adrenergic receptors.
4. Baroreceptor-reflex.
 They r so physiologically interrelated because a defect in one component may disturb e normal function in another & e
combined abnormalities may then cause hypertension.
 The kidney is mainly responsible for long-term BP control by controlling blood volume.
 E reflex mechanisms of kidney in controlling BP:
1. Decrease in renal perfusion pressure → intrarenal redistribution of flow → increase water & salt reabsorption.
DEFECTS IN 2. Decrease in renal perfusion pressure → increase Renin → increase Angiotensin II → increase PVR & aldosterone
→ increase sodium reabsortion → increase blood volume → increase BP.
PERIPHERAL
 An initial defect in e renal adaptive mechanism could lead to plasma volume expansion & blood flow to peripheral
AUTOREGULATI tissue even when BP is normal.
ON  To offset this increased blood flow, local tissue autoregulatory processes would induce arteriole vasoconstriction
which can lead to increase peripheral vascular resistance, PVR. If this continues then in time a thickening of arteriolar
wall may occur resulting in a sustained increase in PVR.
 An increased PVR is a common underlying problem in patients with essential hypertension.
 Vascular endothelium plays an important role in regulating blood vessel tone.
 Endothelial cells synthesize following vasoactive substances:
DISTURBANCE 1. Prostacyclin.
2. Bradykinin.
IN VASCULAR
3. Endothelium-derived-relaxing factor (EDRF – NO).
ENDOTHELIAL 4. Angiotensin II.
MECHANISM 5. Endothelin I.
 Deficiency in the local synthesis of vasodilator substances such as i, ii, iii or increase in e production of
vasoconstricting substances such as Factor IV & V may contribute to the pathogenesis of hypertension.
 In general, population studies indicate that high salt intake is associated with a high prevalence of hypertension.
INFLUENCE OF
 Clinical studies have shown that restriction of salt intake in e diet lowers blood pressure in hypertensive
DIETARY SALT patients.
CLINICAL  E symptoms: headaches, fatigue, & dizziness.
PRESENTATIO  E complication: MI, CHF, thrombotic & hemorrhagic strokes, hypertensive encephalopathy, & renal failure.
N  Physical findings: hypertensive retinopathy, retinal hemorrhage & exudates, & Lt. ventricular hypertrophy.
ft
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COMPLICATION OF HYPERTENSION
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 ANTIHYPERTENSIVE DRUGS
DRUGS DETAILS
DIURETICS
 They r antihypertensive when used alone & when used with other anti-hypertensive agents, they increase those agents’ efficacy.
 Initially: decrease EFV (15%) & CO.
 Later on: EFV remains reduced (5%), CO returns to pretreatment value, & PVR decreased.
 E mechanisms for reduction of PVR by Diuretics:
1. Decrease in EFV.
2. Fall in smooth muscle Na+ concentration leading to reduced intracellular Ca 2+ concentration, resulting in cells more resistant to contractile
stimuli.
3. A change in affinity & response of cell surface receptors to vasoconstrictor hormones.
 3 types of Diuretics:
1. Thiazide & related agents:
 Among e drugs: hydrochlorothiazide & chlorthalidone.
 Mild antihypertensives & more effective in e elderly.
 E therapy:
a. Short-term therapy: used alone in low doses i.e. 12.5 mg to 25 mg/day & 50 mg daily dose if BP is not controlled by 3 or > drugs.
b. Long-term therapy: used in combination with K-sparing agent such as amiloride (1 mg) + hydrochlorothiazide (10 mg).
 Adverse effects of thiazides which mostly d/t fluid & electrolytes imbalance:
a. Extra-cellular vol. depletion. f. Hypomagnesemia.
b. Hypotension. g. Hypercalcemia.
c. Hypokalemia. h. Hyperuricemia.
d. Hyponatremia. i. Metabolic alkosis.
e. Hypochloremia
 Other adverse effects of thiazides:
a. Sexual impotence. e. Lipid profile: adverse effect.
b. Gout. f. Decrease Glucose tolerance.
c. Muscle cramps. g. Crosses Placenta.
d. Ventricular arrhythmias. h. Appear in breast milk.
2. Loop diuretics:
 Among e drugs: furosemide & erhacrynic acid.
 Strong diuretic but weaker antihypertensive than thiazides.
 Dose: 20 to 80 mg daily in chronic renal failure & coexisting refractory CHF patients.
 E thiazide-type diuretics r more effective anti-hypertensive agents than r e loop diuretics in patients with normal renal functions. This is
most likely related to e short duration of action of loop diuretics as single daily dose does not cause a significant net loss of Na + for an
entire 24 hours period.
3. Pot.-sparing diuretics: spironolactone, amiloride, & triamterene.
 Drugs interaction with diuretics:
1. NSAIDs decrease e effectiveness of thiazide diuretics.
2. Corticosteroids increase e risk of hypokalemia.
3. Diminish e effects of insulin, sulfonylureas, & anticoagulants.
4. Increase e effects of lithium, cardiac glycosides, & anaesthetics.
5. Contraindicated for who r hypersensitive to sulfonamides.
SYMPHATOLYTIC DRUGS
CENTRALLY 1. Clonidine:
ACTING AGENTS  α2- agonist which stimulates α2A subtype of α2- adrenergic receptors in e brainstem, resulting in a reduction in
sympathetic outflow from e CNS.
 Imidazoline – preferring binding sites in brain & peripheral tissues which may mediate hypotensive effect of
clonidine r specific to clonidine & other imidazolines but not to CAs.
 Pharmacological effects:
 At higher doses, it causes initial vasoconstriction d/t stimulation of α2B-receptors on vascular smooth muscle
cells.
 It also reduces PVR, CO & HR while maintains renal blood flow & GF rate.
 It has no effect on lipid profile but salt & water retention may occur.
 It reduces renin secretion.
 Adverse effects:
1. Sedation, nausea, & vomiting.
2. Xerostomia: dry nasal mucosa, dry eyes, parotid gland swelling, & pain.
3. Impotence.
4. Sleep disturbances, restlessness, & depression.
5. Withdrawal Syndrome.
 Drug interactions: tricyclic anti-depressants & chlorpromaxine may inhibit anti-hypertensive effect of clonidine by
blocking α-receptors.
 Dose: 0.05 – 0.1 mg thrice daily.
2. Methlydopa:
 Methyldopa → methlydopamine → methylnorephinephrine.
 Methylnorepinephrine acts as an α2- agonist in e brainstem to inhibit sympathetic output to e peripheral
sympathetic nervous system.
 Pharmacological effects:
 Reduces PVR without causing many changes in CO & HR.
 Renal blood flow & functions remain unchanged.
 Renin secretion is reduced.
 Lipid profile not disturbed
 Salt & water retention: pseudo-tolerance.
 Left ventricular hypertrophy can be reversed.
  Adverse reactions:
a. Sedation with decreased psychic energy.
b. Depression & reduction in libido.
c. Dryness of mouth.
d. Parkinsonian signs.
e. Hepatotoxicity & hemolytic anemia.
 Dose: 250 mg twice daily.
 Used mostly in mild to moderate cases of hypertension.
 Can be usefully combined with other drugs
 First choice for relatively young hypertensives & those with ischemic heart disease.
 E actions: decrease myocardial contractility, CO, renin (β1 effect), & angiotensin II formation.
 Pharmacological effects:
β-ADRENERGIC  All the β-blockers r equally effective as antihypertensive agents, regardless of their lipid solubility,
RECEPTOR cardioselectivity, partial agonist or ISA, & membrane stabilizing activity.
ANTAGONISTS  Renal blood flow & GFR reduced with an adverse effect on lipid profile.
 No salt & water retention.
 Adverse effects:
1. Withdrawal syndrome.
2. Cold extremities.
3. Avoided in patients with asthma, SA or AV nodal dysfunction, & insulin-dependent diabetic patients.
 Drugs interaction: NSAIDs can blunt e antihypertensive effect of β- blockers.
 Drugs acting according to e receptors:
1. α1= prazosin, terazosin, & doxazosin .
2. α2= yohimbine.
3. α1 α2= phentolamine.
 E actions:
 Blockade of α1-receptors inhibits vasoconstriction induced by endogenous CAs.
 Vasodilatation occurs in both arterioles & venules which lead to decrease in PVR & fall in BP.
 Fall in BP causes sympathetically mediated reflex increase in HR, CO, plasma renin activity & fluid retention.
 Reflex mediated changes exaggerate if α2-receptors r also blocked, leading to increased NE & increased
α-ADRENERGIC stimulation of post-synaptic β1-receptors in e heart & on juxtaglomerular cells.
RECEPTOR  During long term HR, CO & renin activity returns while vasodilation persists.
ANTAGONISTS  Pharmacological effects:
1. Renal blood flow unchanged.
2. Lipid profile is favorable.
3. Salt & water retention – add a diuretic.
4. Postural hypotension – depending on plasma volume.
 Adverse effects:
1. First-Dose phenomenon: orthostatic hypotension.
2. Risk for developing CHF during monotherapy.
3. Dizziness, palpitation, headache, lassitude, & etc.
 Dose: 1 mg thrice daily.
 Among e drug is labetalol:
 An α1-receptor blocker which is also a non-selective β-antagonist with partial agonist activity like pindolol.
MIXED  α1-receptor blockade & stimulation of β2-receptors cause decreased PVR resulting in fall in BP, while CO & HR r
ADRENERGIC not much altered.
ANTAGONISTS  Side effects: nasal stuffiness & epigastric pain.
 Not used in patients with bronchial asthma.
 Dose: Hypertensive emergency 20-80 mg as bolus by IV.
1. Guanethidine:
 Specifically inhibits e function of peripheral postganglionic adrenergic neurons by depleting e normal
neurotransmitter NE.
 Side effects: diarrhoea, nasal congestion, parotid pain, & postural hypotension.
 Dose: 10 – 50 mg once daily.
ADRENERGIC
2. Reserpine:
NEURON
 Binds tightly to storage vesicles in central & peripheral adrenergic neurons & these vesicles cannot synthesize &
BLOCKING
store NE.
AGENTS
 Already formed NE leaks from e vesicles into e cytoplasm where it is destroyed by intraneuronal MAO which
results in very little or no active transmitter is released from nerve endings when they r depolarized.
 Side effects: psychotic depression (can lead to suicide), sedation, inability to concentrate or perform complex
tasks, nasal stuffiness, & exacerbation of peptic ulcer.
 Dose: 0.25 – 0.5 mg daily.
VASODILATORS
ARTERIAL 1. Hydralazine:
 Direct relaxation of arteriolar smooth muscle which dilates arterioles but does not relax venous smooth muscle.
 Vasodilatation is associated with powerful stimulation of sympathetic nervous system, which results in increased
HR & contractility, increased plasma renin activity. & fluid retention.
 Combine with a sympatholytic agent & a diuretic drug.
 Side effects:
a. Headache, nausea, flushing, hypotension, palpitation, & dizziness.
b. Angina pectoris.
c. Salt retention with CHF.
d. Lupus-syndrome & hemolytic anemia.
 Dose:
 a. Oral: 25-100 mg twice daily.
b. IM: 20-40 mg urgent need to lower BP.
2. Minoxidil:
 A prodrug which is metabolized by hepatic sulfo-tranferase to active minoxidil N-O sulfate.
 Minoxidil sulfate opens K+ channels by activating ATP-modulated K+ channels in smooth muscles.
 Results in K+ efflux which leads to hyperpolarization & relaxation of smooth muscles.
 Side effects:
a. Angina & MI in patients of CAD.
b. Retention of salt & water.
c. Tachycardia, palpitation, headache, sweating, & hypertrichosis.
 Dose: Initial 1.25 mg, can be increased gradually to 40 mg in single or twice daily.
3. Diazozide:
 Non-diuretic thiazide which acts like minoxidil.
 Used for hypertensive emergency.
 Side effects:
a. Salt & water retention.
b. Hypotension.
c. Hyperglycemia & transient diabetes may occur.
 Dose: 300 mg IV rapidly over 30 seconds.
1. Sodium nitroprusside:
 Used for hypertensive emergencies, short term reduction of cardiac preload or afterload, & controlled hypotension.
 Its action:
 Dilates both arterioles & venules.
 Metabolized by smooth muscle cells to active metabolite nitric oxide (NO).
ARTERIAL &
 NO activates guanylate cyclase, leading to formation of cyclic GMP.
VENOUS
 Vasodilatation: unlike arterial vasodilators, it causes only modest increase in HR & overall reduction in
myocardial O2 demand while renal functions maintained.
 Side effects: hypotension & cyanide & thiocynate toxicity.
 Dose: Infusion rate within 5 µg/kg/min
 Onset of action within 30 sec, peak within 2 min, disappears within 3 minutes.
CALCIUM IONS CHANNEL BLOCKERS
 Among e drugs: nifedipine, verapamil, diltiazem, felodipine, & amlodipine.
 Contraction of vascular smooth muscle depends on free intracellular Ca2+ content.
 Inhibition of Ca2+ influx decreases intracellular Ca2+.
 All CCBs lower BP by relaxing arteriolar smooth muscle & decreasing PVR.
 All CCBs r equally effective when used alone for mild to moderate hypertension.
 Reduce left ventricular hypertrophy (less than ACE inhibitors & methyldopa).
 Efficacy increased when combined with ACE inhibitor, β-blockers, methyldopa or diuretics (data not consistent).
 Advantages:
1. Safe in hypertensive patients with asthma, hyperlipidemia, diabetes, & renal dysfunction.
2. Do not alter plasma concentration of lipids, uric acid, or electrolytes.
 Side effects:
1. Oedema, flushing, dizziness, gingival hyperplasia, nausea, & constipation.
2. Should be avoided in patients with SA or AV nodal dysfunction or CHF.
3. Verapamil or diltiazem with β-blockers can cause AV block, decrease ventricular function & heart failure.
ACE INHIBITORS
 Angiotensinogen Ang. I Ang. II
Renin ACE
 Among e drugs: captopril, enalapril, lisinopril, & ramipril.
 Modes of action:
 Lower BP by decreasing PVR.  Also inhibit bradykinin inactivation which leads to PG
 CO & HR not significantly changed. synthesis. PG is a potent vasodilator which reduces PVR & BP.
 Do not cause reflex sympathetic activation.
 Advantages:
1. Special advantage in e treatment of hypertensive patients with diabetes, by slowing e development of diabetic glomerulopathy.
2. Preferred as initial agent in e treatment of hypertensive patients with left ventricular hypertrophy.
3. Patients with hypertension & ischemic heart disease with abnormalities in left ventricular systolic function.
4. Hypertensive patients in immediate post-myocardial infarction period.
 Side effects:
 Hypotension  Skin rash, proteinuria, & angioneurotic edema (0.1-0.2%).
 Dry Cough (5-20%)  Dysgeusia (alteration or loss of taste, more with captopril).
 Hyperkalemia  Neutropenia & hepato toxicity (rare)
 Contraindicated in pregnancy.  Glycosuria (glucose in urine without hyperglycemia).
ANGIOTENSIN II RECEPTOR ANTAGONISTS
 E drug – Losartan:
 By preventing effects of Angiotensin II, these agents relax smooth muscle.
 Promote vasodilatation.
 Increase salt & water excretion, reduce plasma volume.
 Decrease cellular hypertrophy.
 Side effects: dry cough & angioedema not associated with ARBs.
 Dose: 25-100 mg/day.
 Full effect in 3-6 weeks. If BP not controlled add hydrochlorothiazide (12.5 mg) or some other diuretic.
 ATHEROSCLEROSIS
PORTIONS DETAILS
 Means hardening of e arteries.
 Characterized by:
1. Types:
a. Elastic arteries: aorta, carotid, & iliac arteries.
b. Large & medium sized muscular arteries: coronary & popliteal arteries.
c. Smaller vessels which r less than 2-3 mm in diameter: uncommon phenomena.
OVERVIEW
2. Sites:
a. Abdominal aorta: > involved than thoracic aorta.
b. Origins (ostia) of major branches such as e coronary arteries, e popliteal arteries, e internal carotid
arteries, & e vessels of e circle of Willis: lesions tend to be much more prominent.
 In descending order, e arteries affected r: Lower abdominal aorta → coronary arteries → popliteal arteries →
internal carotid arteries → vessels of e circle of Willis.
NON  Age: risk of complications (IHD) increases 5x between 40 and 60.
MODIFIABL  Sex: men at higher risk than women, risk becoming equalized in post menopausal women.
E  Family history and genetic predisposition: probably polygenic.
 Hyperlipidemia : usually refers to hypercholesterolemia, and increased LDL (HDL – good
cholesterol, raised by exercise and moderate ethanol consumption).
 Saturated fat, trans fat – increased plasma cholesterol.
MODIFIABL  Hypertension: both systolic and diastolic pressures are important for risk.
RISK FACTORS E  Smoking: cigarettes’ products r very radical & dangerous to human.
 Diabetes mellitus: induces hypercholesterolemia.
 Hyperhomocystinemia: strong relationship with coronary artery diease, peripheral vascular
disease, stroke, & venous thrombosis.
 Obesity.  High carbohydrate intake.
 Physical inactivity.  Lipoprotein A.
OTHERS
 Stress (type A personality).  Trans (unsaturated) fat intake.
 Postmenopausal estrogen deficiency.  Chlamydia pneumonia
 AHA plaque classification:
1. Type 1: Early – normal intima or minimal intimal thickening.
2. Type 2: Early – fatty streak: little intracellular lipid deposit of smooth muscle. Lesion initiation occurs when
endothelial cells, activated by risk factors such as hyperlipoproteinemia, express adhesion, and
chemoattractant molecules that recruit inflammatory leukocytes such as monocytes and T lymphocytes.
3. Type 3: Intermediate – preatheroma: increased extracellular lipid deposits. Evolution to fibro-fatty stage.
Monocytes recruited to the artery wall become macrophages and express scavenger receptors that bind
modified lipoproteins. Macrophages become lipid-laden foam cells by engulfing modified lipoproteins.
Leukocytes and resident vascular wall cells can secrete inflammatory cytokines and growth factors that
amplify leukocyte recruitment and cause smooth muscle cell migration and proliferation.
4. Type4: Advanced – massive confluence lipid deposits covered mainly by intima. As lesion progresses,
inflammatory mediators cause expression of tissue factor, a potent procoagulant, and matrix-degrading
proteinases that weaken the fibrous cap of the plaque.
5. Type 5: Advanced – fibroatheroma, calcific, or fibrotic type. If fibrous cap ruptures at point of weakening,
PATHOLOGY
coagulation factors in blood can gain access to thrombogenic, tissue factor-containing lipid core, causing
thrombosis on nonocclusive atherosclerotic plaque. If balance between prothrombotic and fibrinolytic
mechanisms prevailing at that particular region and at that particular time is unfavorable, occlusive thrombus
causing acute coronary syndromes may result.
6. Type 6: Complicated: disruption, hemorrhage, or thrombotic deposits. When thrombus resorbs, products
associated with thrombosis, such as thrombin and mediators released from degranulating platelets, including
platelet-derived growth factor and transforming growth factor-beta, can cause healing response, leading to
increased collagen accumulation and smooth muscle cell growth. In this manner, the fibro-fatty lesion can
evolve into advanced fibrous and often calcified plaque, one that may cause significant stenosis, and produce
symptoms of stable angina pectoris.
7. Type 7: In some cases, occlusive thrombi arise not from a fracture of the fibrous cap, but from superficial
erosion of the endothelial layer. Resulting mural thrombus, again dependent on local prothrombotic and
fibrinolytic balance, can cause AMI. Superficial erosions often complicate advanced and stenotic lesions, as
shown here. However, superficial erosions do not necessarily occur following a fibrous cap rupture.
MORPHOLOGY 1. Fatty streak:
 Composed of lipid-filled foam cells.
 R not significantly raised & thus causes no disturbance in blood flow.
 Begins as multiple minute yellow, flat spots that can coalesce into 1 cm/ > of elongated streaks.
 Can appear in e aorta of infants younger than 1 year & r present in virtually all children older than 10 years
old.
 Not all r destined to become advanced atherosclerotic plaque.
2. Atherosclerotic plaque or atheroma:
 Identified by intimal lesion called atheromas (atheromatous/ atherosclerotic plaque/ fibrofatty plaques) that
potrude into vascular lumina.
 Key process: intimal thickening & lipid accumulation.
 Appearance of e atheromas:
a. A raised focal lesion initiating within e intima.
b. A soft, yellow, grumous core of lipid: mainly cholesterols & cholesterol ester.
c. White to whitish yellow.
d. Patchy, eccentric, & involves only a portion of any given arterial wall only partial of its circumference.
e. Impinges on e lumen of e artery.
 f. Thrombosis superimposed over e surface of ulcerated plaque is red-brown in color.
g. Plaque varies from 0.3 cm to 1.5 cm in diameter but can coalesce to form larger masses.
h. E focality is almost certainly due to e vagaries of vascular hemodynamics.
i. Becomes > numerous & > diffuse by time.
 Principles of atherosclerotic plaque:
a. Cells, including SMCs, macrophages, & T cells.
b. ECM, including collagen, elastic fibers, & proteoglycans.
c. Intracellular & extracellular lipid.
 Fibrous cap:
a. A firm, white cap containing smooth muscle cells & dense collagen superficially.
b. Beneath & to e side of e cap: cellular area containing macrophage, lymphocytes, & SMCs.
c. Deep to e fibrous cap: necrotic area containing lipid, debris from dead cells, foam cells, fibrin,
organized thrombus, plasma protein & crystalline aggregates of cholesterols.
 Effects of e atheromas:
a. Obstructs blood flow.
b. Weakens e underlying media.
c. Can rupture & cause acute catastrophic vessel thrombosis.
 Clinical significance of atherosclerotic plaque:
1. Rupture, ulceration, or erosion of luminal surface of atherosclerotic plaque:
 Exposes e bloodstream to highly thrombogenic substances & induces thrombus formation.
 E thrombi can lead to occlusion & ischemia.
 If survival ensues, thrombi may become organized & incorporated into e growing plaque.
2. Hemorrhage into a plaque:
 Rupture of e fibrous cap or e thin-walled vessels in e area of neovascularization leads to intra-
plaque hemorrhage.
 A contained hematoma may expand e plaque or induce plaque rupture.
3. Atheroembolism:
 Plaque rupture can discharge debris into e bloodstream.
 Results in e production of microemboli composed of plaque contents.
4. Aneurysm formation: Atherosclerosis-induced pressure or ischemic atrophy of e underlying media
with loss of elastic tissue causes weakness of e vessel wall & development of aneurysm that may
rupture.
1. Focal rupture, ulceration or erosion:
 Exposure of highly thrombogenic substance that induces thrombi formation.
 Debris discharge into blood – microemboli.
2. Hemorrhage:
 Initiated by rupture of fibrous cap.
 Hematoma within plaque may cause lumen reduction or further plaque rupture.
COMPLICATIONS OF 3. Thrombosis:
PLAQUE  Worst complication, use superimposed on complicated plaques.
 May partially or completely occlude lumen.
 Thrombi may eventually be incorporated into plaque, making the plaque much larger.
4. Aneurysmal dilatation:
 Pressure induced atrophy of media and elastic tissue.
 Weakening of the wall with potential rupture.
5. Calcification: e plaque becomes calcified & hardened with calcium.
1. Myocardial Infarction.
2. Cerebral Infarction.
3. Peripheral vascular disease with gangrene of extremities.
4. Aneurysm:
 Localized abnormal permanent dilatation of an artery or vein.
 True versus False Aneurysms.
 Clinical features / complication:
a. Pulsatile mass
b. Rupture with catastrophic hemorrhage
c. Pressure effect on adjacent structures
COMPLICATIONS OF d. Vascular occlusion
ATHERO-SCLEROSIS e. Aortic root dilatation with aortic regurgitation
f. Thromboembolism
5. Aortic Dissection: The aorta is atherosclerotic and blood could dissected into e wall of aorta.
6. Ischemic Heart Disease (IHD):
 As a result of inadequate blood / oxygen supply.
 Majority of cases r due to coronary atherosclerosis.
 Clinical features:
a. Angina Pectoris (Stable or Unstable).
b. Myocardial Infarction.
c. Chronic Ischemic Heart Disease.
d. Sudden Cardiac Death.
GENERAL  Primary prevention:
TREATMENTS 1. Stop smoking.
2. Control of blood pressure.
3. Weight reduction.
4. Regular exercise.
5. Dietary modifications.
 Secondary To reduce cardiac prevention:
1. Treatment of events hypertension & hyperlipidaemia.
2. For diabetic patient, control of disease.
3. Localized arterial disease: angioplasty or by-pass operation.
 ews atherosclerosis as chronic inflammatory response of arterial wall towards endothelial injury.
Lesion progression occurs through interactions of modified LDL, macrophages, T cells
PATHOGENESIS OF
ATHEROSCLEROSIS

itive endothelial injury.

namic disturbance, hypercholesterolemia, toxins from cigarette smoke, homocysteine, or infectious agents >>> may cause e release of ROS that deactivate NO.
lial injury & dysfunction which lead to increased permeability, leukocyte adhesion (attracts macrophages & other inflammatory cells into e site of injury), & thrombot

(2) Insudation of lipoprotein into e vessel wall, mainly LDL with its high cholesterol content.
Lipoproteins accumulate within e intima at sites of increased endothelial permeability.

ages or endothelial cells in e arterial wall: LDL is oxidized into oxidized 0r modified LDL which:
ates e release of growth factors & cytokines. receptor distinct from e LDL receptor, thus
nduce endothelial cell dysfunction.

helial adhesion molecules induced on e surface of dysfunctional endothelial cells) followed by their migration into e intima & their transformation into macrophages &

(5) Adhesion of platelets.

media into e intima. Then, smooth muscle cells proliferate in e intima & extracellular matrix elobrates which lead to e accumulation of collagen & proteoglycans. This

(7) Enhanced accumulation of lipids both within cells (macrophages & smooth muscle cells) & extracellularly.
 ANGINA PECTORIS
POINTS DETAILS
 Definition: intermittent chest pain caused by transient, reversible myocardial ischemia.
OVERVIEW  It occurs when e demand for blood by e heart exceeds e supply of e coronary arteries.
 It can be associated to e dyspnea, diaphoresis, nausea, & vomiting.
1. Usual pain sites: 2. Less common pain sites:
a. Substernal region. a. Medial aspect of e Rt. arm.
DISTRIBUTION
b. Lt. pectoral region. b. Epigastric area.
OF PAIN c. Lt. shoulder. c. Lt. jaw.
d. Medial aspect of Lt. arm. d. E back.
1. Typical or stable angina:
 I.e. episodic chest pain associated with exertion or some other form of myocardial O2 demand.
 Pain is described as a crushing or squeezing substernal sensation.
 Referred pain: Lt. arm & Lt. jaw.
 Can be relieved by rest & nitroglycerins.
2. Prinzmetal or variant angina:
 I.e. an angina occurring at rest d/t coronary artery spasm.
TYPES
 Typically responds promptly to nitroglycerins.
3. Crescendo or unstable angina:
 Characterized by:
a. An increasing frequency of chest pain.
b. Precipitated by progressively less exertion.
c. Episodes tend to be > intense & longer lasting than stable angina.
 Sometimes is called pre-infarction angina d/t its seriousness & severity.
1. Atherosclerosis: obstruction of e large epicardial vessels (coronary artery).
2. Spasm: vasoconstriction mediated by histamines, serotonin, catecholamines, & endothelium derived factor.
ETIOLOGY 3. Emboli: can occur from vegetations in patients with endocarditis.
4. Congenital: a rare cause.
 Mostly r caused by inadequate coronary perfusion relative to myocardial demand:
1. Increase O2 demand: ↑ heart rate, ↑ myocardial tension, ↑ basal metabolism, ↑ contractility, hypertrophy, excessive
inotropic drive, & Lt. ventricle dilatation.
2. Reduced O2 supply: ↑ heart rate, ↓ aortic diastolic pressure, intramyocardial pressure (d/t hypertrophy & edema), ↓
arterial O2 content, & coronary artery disease (thrombosis & spasm).
 Atherosclerosis cause:
 3 most common vessels of coronary artery affected:
1. Lt. anterior descending (LAD).
2. Lt. circumflex (LCX).
3. Rt. coronary artery (RCA).
PATHOGENESI  E pathophysiology:
S 1. ↑ blood levels of LDL irritate or damage e inner layer of coronary vessels.
2. LDL enters e vessel after damaging e protective barrier, accumulates, & forms a fatty streak.
3. Smooth muscle cells move to e inner layer to engulf e fatty substance, produce fibrous tissue stimulate
calcium deposition.
4. This cycle continues resulting in transformation of e fatty streak into fibrous plaque & CAD lesions.
5. O2 deprivation forces e myocardium to shift from aerobic to anaerobic metabolism, leading to accumulation of
lactic acids & reduction in cellular pH.
6. A combination of hypoxia, reduced energy availability, & acidosis rapidly impair Lt. ventricular functions.
7. Strength of contraction reduced d/t shortened fibers which r in less force & velocity.
8. Wall motion is abnormal in ischemic area, resulting in less blood being ejected from e heart with each
contraction.
CLINICAL
FEATURES
INVESTIGATIO
NS
 THE BLOOD
POINTS DETAILS
 E commonest of blood cells: 5.0 to 5.5 x 108/ cu mm.
 Morphology:
 E shape is that of a biconcave disk with a diameter of 8 µm: e shape gives e best surface to volume ratio, but
may vary in pathological situation.
 RBCs r anucleate cells devoid of typical organelles but full of hemoglobin.
ERYTHROCYTES  E life span is 120 days & function only within e bloodstream.
 Metabolism of RBCs:
1. ~ 90% r phagocytosed by macrophages in e spleen, bone marrow, & liver.
2. ~ 10% break down intravascularly, releasing hemoglobin into e blood.
 Function: gaseous transport.
LEUKOCYTES
 E commonest granulocytes: 2500 to 7500/cu mm.
 Morphology:
 Short half life (6 - 8 hours), total pool exchanged 2x daily.
 Measure 10 – 12 µm in diameter & larger than erythrocytes.
 A polymorphonuclear cell due to its multilobed nucleus (3 -4 lobes).
 Have a fine cytoplasmic granules which r divided into 3 types:
1. Specific granules:
 E smallest granules which r twice as numerous as azurophilic granules.
 Contain various enzymes (type IV collagenase, phospholidase), compliment activators, & lysozymes.
2. Azurophilic granules (1o granules):
 Larger & less numerous than specific granules.
 They r lysosomes of e neutrophils & contain myeloperoxidase (bactericidal hypochlorite &
NEUTROPHILS chloramines).
3. Tertiary granules - consist of 2 types:
a. Phosphasome: contains phosphatase.
b. Other type contains metalloproteinases (gelatinases & collagenases) which r thought to facilitate e
migration of e neutrophil t/out e connective tissue.
 Functions:
1. 1st cells to arrive at site of infection.
2. Chemotaxis towards bacterial products, neutrophil products, & AgAb complexes.
3. Produce chemoattractants for other cells for building inflammatory response.
4. Receptors for bacterial CHO, IgG Fc, C3b.
5. Engulf bacteria in phagosome, fuses with granules, & oxidative burst.
6. Numbers in blood increase dramatically in bacterial infection.
7. Need for efficient & well regulated production.
 Count for 2% – 4% of leukocytes: 40 to 400/cu mm.
 They r 12 – 14 µm in diameter which r binucleated.
 Contains 2 types of large eosinophilic granules:
1. Specific granules – contents:
a. Crystalloid bodies which r responsible for e refractivity of e granules in e light microscope.
b. 4 major basic proteins that account for e intense acidophilia of e granules.
c. Histaminases, arysulfatase, collagenase, & cathepsins.
EOSINOPHILS
2. Azurophilic granules: lysosomes which contain lysosomal acid hydrolases for destruction of paracytes &
hydrolysis of AgAb complexes.
 Functions:
1. Weakly phagocytic.
2. Release granule contents.
3. Receptors for IgG & C3b, activated one have IgE receptors.
4. Numbers increase in parasitic infection & allergic conduction.
 Rarest of WBCs: 15 – 100/cu mm.
 They r 10 – 14 µm in diameter with lobed nucleus (obscured).
 Contain 2 types of granules:
1. Specific granules: contain heparin sulfate, histamine, & SRS-A.
2. Azurophilic granules: lysosomes of e basophils which contains lysosomal acid hydrolase.
BASOPHILS
 Functions:
1. Not phagocytic.
2. Degranulate on activation.
3. Receptors for IgE.
4. Similar to those of mas cells (important in allergic reaction).
 Account for 200 – 600/cu mm.
 They r 15 – 25 µm in diameter.
 Morphology:
1. An excentric indented nucleus.
2. Ruffled indistinct membranes.
MONOCYTES 3. Fine granules containing peroxidase & acid hydrolases.
4. Pinocytic vacuoles.
 Functions:
1. Highly motile & phagocytic.
2. Receptors for IgG & C3b.
3. Precursors of tissue macrophages (some dendritic cells).
LYMPHOCYTES  Account for 1500 – 3000/cu mm.
  They r small in size with 8 – 10 µm in diameter.
 Have a little cytoplasm but w/out granules.
 Divided into 2 types: T & B cells.
 Have a short half – life in blood, but sequester to lymph nodes, spleen, have life span of days to years.
 Functions:
1. Not phagocytic.
2. Proliferate & differentiate on activation.
3. Receptors for Ag.
 Account for 300,000/cu mm.
 E platelets arise from e cytoplasmic fragmentation of megakaryocytes in e bone marrow & circulate in blood as
disc-shaped anucleate particles.
 Morphology:
 Discoid in shape with 3 x 1 µm.
 They r anucleate.
PLATELETS  Have microtubules, organelles, glycoprotein coat, & granules which store fibrinogen & adrenalin.
 Circulate 8-10 days & then destroyed in the spleen or pulm vascular bed.
 Functions:
1. Important for blood clotting & fibrinolysis.
2. Adhere to damaged vessels & blood clots.
3. Required for normal haemostasis.
1. Water:
 90% of plasma weight.
 Serves as e solvent for a variety of solutes.
2. Proteins:
a. Albumin:
 Main protein constituent of plasma responsible for exerting e concentration gradient b/w blood & ECF.
 Serves as a carrier protein which binds & transports hormones, metabolites, & drugs.
PLASMA b. Globulin: include immunoglobulins (antibodies) & non-immunoglubulins (maintain e osmotic pressure within e
vascular system & act as carrier proteins).
c. Fibrinogen: e largest protein important in coagulation cascade.
3. Other solutes:
a. Nonprotein nitrogen substances: urea, uric acid, creatine. & creatinine.
b. Nutrients: glucose, lipids, & amino acids.
c. Blood gases: O2, CO2, & nitrogen.
d. Regulatory substances: hormones & enzymes.

HAEMOPOITIC CELL LINEAGE.

 THE HAEMOPOIESIS
POINTS DETAILS
 Prenatal period (fetus):
1. 0 – 2 months: yolk sac.
2. 2 – 7 months: liver & spleen.
Continue until about 2 weeks after birth.
SITES 3. 5 – 9 months: bone marrow.
 Postnatal period:
1. Infants: bone marrow (practically all bones).
2. Adults: vertebrae, ribs, sternum, skull sacrum, pelvis, & proximal ends of femur.
1. Haemopoietic stem cells:
 Also known as pluripotential stem cell which is rare: 1 in 20 million nucleated cells in bone marrow.
 Its phenotype most probably is CD34+ CD38-.
 Characteristics of stem cells:
a. Has e capability for self-renewal so that marrow cellularity remains constant in a normal healthy state.
b. It can give rise to e separate cell lineages.
c. 1 stem cell is capable of producing about 106 mature blood cells after 20 divisions.
d. Able to traffic around e body & r found in peripheral blood in low numbers.
 Bone marrow is e most suitable place for stem cell survival, growth, & development:
 Contents of bone marrow:
a. Stromal cells:
 E cells: adipocytes, fibroblasts, endothelial cells, & macrophages.
 Functions:
i. Secrete extracellular molecules such as collagens, glycoproteins (fibronectin &
thrombospondin), & glycosaminoglycans (hyaluronic acid & chondroitin derivatives) to form
HAEMOPOIETI extracellular matrix.
ii. Secrete several growth factors necessary for stem cell survival.
C CELLS  Mesenchymal stem cells r thought to be critical in stromal cell formation.
b. Microvascular network:
 E developing cells r situated outside e bone marrow sinuses.
 E mature cells r released into e sinus spaces, e marrow microcirculation, & e general circulation.
 E progression of bone marrow:
 Infancy: all e bone is haemopoietic.
 Childhood: there is progressive fatty replacement of marrow t/out e long bones.
 Adulthood: haemopoietic marrow is confined to e central skeleton & proximal ends of femur &
humerus.
 E remaining fatty marrow is capable of reversion to haemopoiesis.
2. Haemopoietic progenitor cells:
 Cell differentiation occurs from e stem cell via e committed haemopoietic progenitors which r restricted in
their developmental potential.
 2 types of progenitor cells:
a. Mixed myeloid progenitor cell.
b. Lymphoid stem cells.
REGULATION OF HAEMOPOIESIS
 Several transcription factors regulate differentiation along e major cell lineage.
TRANSCRPTION  Example:
FACTORS 1. PU.1 commits cells to e myeloid lineage.
2. GATA-1 has an essential role in erythropoietic & megakaryocytic differentiation.
 Characteristics of e growth factors:
1. Glycoprotein hormones that act at very low concentrations & hierarchically.
2. May act locally at e site of production or circulate in plasma.
3. Bind to extracellular matrix to form niches to which stem cell & progenitor cells adhere.
4. Usually produced by many cell types but mostly by stromal cells except erythropoietin.
5. Usually affect > than 1 cell lineage, but active on stem, progenitor, & functional end cells.
6. Usually show synergistic or additive interactions with other growth factors.
GROWTH
7. Often act on e neoplastic equivalent of a normal cell.
FACTORS 8. Multiple functions: proliferation, differentiation, maturation, functional activation, prevention of apoptosis of
progenitor cells.
 Actions of e growth factors:
1. Act on stromal cells: IL-1 & TNF.
2. Act on pluripotential stem cells: SCF & Flt-L.
3. Act on multipotential progenitor cells: IL-3, GM-CSF, IL-6, G-CSF, & thrombopoietin.
4. Act on committed progenitor cells: G-CSF, MCSF, IL-5, erythropoietin, & thrombopoietin.
 Other factor that regulates e haemopoiesis is e intimate contact with one or more types of bone marrow stromal cells
OTHERS & components of extracellular matrix.
 THE ERYTHROPOIESIS

Pluripotential stem cell → progenitor cells colony – forming unit granulocyte, erythroid, monocyte, &

megakaryocyte (CFUGEMM) → burst – forming unit erythroid (BFUE) → erythroid CFU (CFUE) → pronormoblast

→ normoblast → reticulocyte → mature erythrocyte.

1. Pronormoblast:
 Large cell with dark blue cytoplasm.
 A central nucleus with nucleoli & slightly dumped chromatin.
2. Normoblast:
 Contain > haemoglobin in e cytoplasm.
 E cytoplasm stains blue when it loses its RNA & protein synthetic apparatus & when nuclear chromatin becomes > condensed.
 Does not appear in normal human peripheral blood.
3. Reticulocytes:
 Results when nucleus of normoblast is extruded within e marrow.
 Slightly larger than mature RBC.
 Spends 1 – 2 days in marrow & circulates in e peripheral blood for 1 – 2 days before maturing mainly in spleen, when RNA is
completely lost.
4. Erythrocytes: non – nucleated biconcave disk shaped cell.

ERYTHROPOIETIN
 The regulator of erythropoiesis which is produced mostly by e kidney (90%).
 Its production is influenced by e O2 tension in e tissue of kidney.
 Its production is increased when:
1. Anemia occurs.
2. Hemoglobin is unable to give up O2 normally.
3. Atmospheric O2 is low.
4. Defective cardiac or pulmonary function.
5. Damage to e renal circulation affects O2 delivery to kidney.
 Erythropoietin stimulates erythropoiesis by:
1. Increasing e no. of progenitor cells committed to erythropoiesis.
2. Activating e transcription factors CATA-1 & FOG-1 which is important for enhancing expression of erythroid – specific genes.
3. Enhancing e expression of anti – apoptotic genes & of e transferring receptor (CD71).
4. Stimulate erythropoietin receptors on BFUE & CFUE to proliferate, differentiate, & produce haemoglobin.

RED CELL METABOLISM

 ANAEMIA
POINTS DETAILS
 Anaemia is defined in 3 ways:
1. A reduction in e haemoglobin concentration of e blood.
2. A fall in red cell count.
3. A decrease in packed cell volume (PCV).
 Typical values of anaemia according to groups:
1. Adult males: < 13.5 g/dL.
OVERVIEW 2. Adult female: < 11.5 g/dL.
3. Age of 2 years to puberty: < 11.0 g/dL.
4. Newborn infants: < 14.0 g/dL.
 Anaemia is considered to be present if e [Hb] or hematocrit is below e lower limit of 95% reference interval for e
individual’s age, sex, & geographic location.
 Anemia is not a disease but it is an important marker of an underlying disorder that may be basic or complex.
1. Classification based on e causes:
a. Excess loss of blood: acute or chronic.
b. Impaired production of RBCs (hypoproliferative):
i. Iron deficiency.
ii. Megaloblastic (nuclear-cytoplasmic dyssynchrony): vitamin B12 or folic acid.
iii. Anemia of chronic disease.
iv. Myelophthisic (infiltration).
v. Aplastic anaemia: congenital or acquired.
c. Increase destruction of RBCs (hemolysis):
 Extrinsic to RBCs:
CLASSIFICATI
i. Autoimmune or isoimmune.
ON ii. Infections.
iii. Physical or chemical agents.
 Intrinsic to RBCs:
i. Membrane defects.
ii. Enzyme deficiencies (metabolic).
iii. Hemoglobinopathies: chain synthesis defects & amino acid substitutions.
2. Classification based on e red cell indices (MCV & MCH):
a. Hypochromic microcytic (↓ MCH, ↓ MCV). This type suggests e underlying defect &
b. Normochromic normocytic (~ MCH, ~ MCV). excludes certain causes.
c. Macrocytic (↑ MCV).
 Clinical signs & symptoms result from diminished delivery of O2 to e tissues.
 E features can be influenced by 4 factors:
1. Speed of onset: acute onset causes more symptoms than e chronic one because there is less time for adaptation in e
CVS & e O2 dissociation curve of hemoglobin.
2. Severity: mild anaemia often has no symptoms or signs but these r usually present when Hb < 9 – 10 g/dL.
3. Age: e elderly tolerate anaemia less well because of e effect of lack of O 2 on organs when normal cardiovascular
compensation is impaired.
4. Hemoglobin O2 dissociation curve.
 Among e symptoms seen:
 Shortness of breath especially during exercise, weakness, lethargy, palpitation, & headaches.
CLINICAL  In older patients: symptoms of cardiac failure, angina, or intermittent claudication or confusion.
 In rapid onset & very severe anemia: visual disturbances d/t retinal hemorrhage.
FEATURES  Among e signs seen:
1. General signs:
a. Pallor of mucous membrane when Hb < 9 – 10 g/dL.
b. Presence of hyperdynamic circulation with tachycardia, a bounding pulse, cardiomegaly, & a systolic murmur
at e apex.
2. Specific signs:
a. Koilonychias (spoon nails) in iron deficient anaemia.
b. Jaundice in hemolytic or megaloblastic anaemia.
c. Leg ulcers in sickle cell or hemolytic anaemia.
d. Bone deformities in thalassaemia major.
e. Neutropenia or thrombocytopenia in anaemia associated with infections.
LAB 1. Red cell indices:
INVESTIGATI  Used to mathematically define e size & concentration of hemoglobin within RBC.
 They r:
ON a. Mean Corpuscular Volume (MCV):
 Expresses e average volume of an erythrocyte.
 MCV = Patient’s packed cell volume or hematocrit (L/L) = fL.
Erythrocyte count (x 1012 /L)
b. Mean Corpuscular Hemoglobin (MCH):
 Expresses e average weight of hemoglobin in an average erythrocyte.
 It is directly proportional to e amount of hemoglobin & e size of erythrocytes.
 MCH = Hemoglobin (x 10 gm/dL) = pg.
Erythrocyte count (x 1012 /L)
c. Mean Corpuscular Hemoglobin Concentration (MCHC):
 Expresses e average concentration of hemoglobin per unit volume of erythrocytes.
 Also means ratio of e weight of Hb to e volume of erythrocyte.
 MCHC = Hemoglobin (gm/dL) = gm/dL.
Packed cell volume or hematocrit (L/L)
 2. Reticulocyte count:
 In anemia, it should rise d/t erythropoietin increase.
 If it is not raised in an anaemic patient this suggests impaired marrow function or lack of erythropoietin stimulus
3. Blood film (smear): examination of a fixed smear stained with Wright’s or Giemsa stain allows identification of
various changes of blood cell morphology typical of certain diseases.
4. Bone examination:
a. Bone marrow aspirates:
 Provide films on which e cytological details of developing cells can be determined.
 E proportion of different cells r assessed.
 E appearances of e individual cells r examined.
 Search r made for e presence of foreign cells & iron stores assessed.
b. Bone marrow biopsy:
 Produce core of bones & marrow which r decalcified & processed for histological assessment.
 Examination of marrow architecture, assessment of cellularity, & detection of marrow infiltrates.

THE NORMAL VALUES.

LAB INVESTIGATIONS PORTIONS
1. Hemoglobin: Male: 13.5 – 17.5 g/dL.
Female: 11.5 – 15.5 g/dL.
2. Red cell count: Male: 4.5 – 6.5 x 1012 /L.
Female: 3.9 – 5.6 x 1012 /L.
3. Haematocrit: 40.0 – 52.0%
4. PCV: 36.0 – 48.0%
5. MCV: 80.0 – 95.0 fL.
6. MCH: 27 – 34 pg.
FULL BLOOD COUNT 7. MCHC: 30 – 35 g/dL.
8. Reticulocyte count: 0.5 – 2.0%
9. TWBC: 4.0 – 11.0 x 109 /L.
10. Neutropils: 2.5 – 7.5 x 109 /L (40.0 75.0%).
11. Lymphocytes: 1.5 – 4.5 x 109 /L (22.0 – 40.0%).
12. Monocytes: 0.2 – 0.8 x 109 /L (1.0 – 10.0%).
13. Eosinophils: 0.04 – 0.4 x 109 /L (1.0 – 7.0%).
14. Basophils: 0.01 – 0.1 x 109 /L (0 – 2.0%).
1. Child < 2 years: ~ 100%.
BM TREPHINE BIOPSY
2. Adults: 40.0 – 50.0% fat.
(Normal cellular marrow) 40.0 – 60.0% haemopoietic elements.
1. Myeloblast: 0.1 – 3.5%.
2. Promyelocytes: 0.5 – 5.0%.
3. Myelocytes:
a. Neutrophils: 5.0 – 20.0%
b. Eosinophils: 0.1 – 3.0%.
c. Basophils: 0 – 0.5%.
4. Metamyelocytes & band forms: 10.0 – 30.0%.
BM DIFFERENTIAL 5. Segmented forms:
COUNT a. Neutrophils: 7.0 – 25.0%
b. Eosinophils: 0.2 – 3.0%.
c. Basophils: 0 – 0.5%.
6. Erythroid precursors: 5.5 – 20.0%.
7. Megakaryocytes: 0.1 – 0.5%.
8. Lymphocytes: 5.0 – 20.0%.
9. Plasma cell: 0 – 3.5%.
10. Monocytes: 0 – 0.2%.

CLASSIFICATION OF ANAEMIA
NORMOCHROMIC
HYPOCHROMIC MICROCYTIC MACROCYTIC
NORMOCYTIC
MCV <80 fL. MCV 80 – 95 fL. MCV >95 fL.
MCH <27 pg. MCH >27 pg.
1. Many haemolytic anaemias.
1. Iron deficiency. 2. Anaemia of chronic disease (some cases). 1. Megaloblastic: vitamin B12 or folate
2. Thalassaemia. 3. After acute blood loss. deficiency.
3. Anaemia of chronic disease (some cases). 4. Renal disease. 2. Non-megaloblastic: alcohol, liver disease,
4. Lead poisoning. 5. Mixed deficiencies. myelodysplasia, aplastic anaemia, & etc.
5. Sideroblastic anaemia (some cases). 6. Bone marrow infiltration (e.g. post
chemotherapy, infiltration by carcinoma.)
The best and the most beautiful things in the
world cannot be seen or even touched, but
they must be felt with the heart…
 HYPOCHROMIC MICROCYTIC ANAEMIA
POINTS DETAILS
 In hypochromic microcytic anaemia, MCV & MCH r reduced & blood film shows small (microcytic) & pale
(hypochromic) red cells.
OVERVIEW  E most common cause is iron deficiency & e major differential diagnosis is thalaessaemia & anaemia of chronic
disease.
1. Iron deficiency.
2. Anemia of chronic disease: microcytosis occurs in about 20% of patients with anemia of chronic disease
(pathophysiology is impaired transfer of iron to the plasma from its site of storage in macrophages).
CAUSES 3. Thalassemias. May be due to impaired globin synthesis.
4. Abnormal hemoglobins (Hb C & Hb E).
5. Sideroblastic anemias: causes microcytosis include those resulting from lead poisoning & pyridoxine deficiency.
ANAEMIA OF IRON DEFICIENCY
1. Chronic blood loss:
a. In pre-menopausal women e source is usually menstruation.
b. In men & in postmenopausal women, e usual cause is gastrointestinal hemorrhage.
c. Less common sources include hemoptysis, epistaxis, hematuria, & intrapulmonary hemorrhage.
d. A rare cause is intravascular hemolysis with iron loss in e urine in the form of ferritin, hemosiderin, &
hemoglobin. (This process may occur in such disorders as paroxysmal nocturnal hemoglobinuria or red cell
fragmentation from a prosthetic cardiac valve).
2. Physiological demand:
a. Inadequate dietary intake:
 Most foods, including the majority of fruits and vegetables, provide little absorbable iron.
 Exceptions are meat, fish, poultry, beans, and peas.
b. Increased iron utilization:
CAUSES  In infants during growth.
 When there is concurrent blood loss, especially in menstruating women (menorrhagia).
c. Additional contributing factors in women:
 During pregnancy iron is diverted to e fetus for haematopoiesis & increased maternal red cell mass of 35%.
 After delivery iron is lost through lactation.
d. Since adult males have sparse iron losses, primarily a small amount in e stool, deficiency from an inadequate
intake is rare.
3. Malabsoprtion:
 Iron absorption can occur anywhere in e intestine, but it is most efficient in e duodenum.
 Occasionally, iron deficiency results from malabsorption due to disease of e small intestine or following gastric
resection (which may contribute to inadequate absorption by causing intestinal contents to travel more rapidly
through e duodenum or to bypass it by entering surgically created anastomoses).
 Mild iron deficiency anemia is commonly asymptomatic, but e clinical features of severe anemia may emerge as e
hematocrit decreases.
 2 unusual findings r:
1. Pica: e bizarre craving to ingest certain unusual substances, such as clay, ice, dirt, or cardboard.
2. Koilonychia: spooning of e nails.
 Patients often have no symptoms or signs attributable to anemia, especially when it is mild & gradual in onset.
CLINICAL  Other features:
1. When complaints occur, fatigue & lack of energy r common.
FEATURES 2. With severe anaemia, dyspnea may develop because of e decreased oxygen-carrying capacity of e blood.
3. Palpitations as a result of tachycardia & increased force of ventricular contraction.
4. Cardiac murmurs (characteristically systolic & most commonly in e pulmonic area) results from e combination of
greater flow rate, lowered blood viscosity, & increased turbulence.
5. Neurologic symptoms sometimes present in severe anemia: dizziness, faintness, headache, & decreased
concentration.
6. Pallor in e conjunctiva, face, or palms suggests anemia, especially when present in all three sites.
LABORATORY 1. Full blood count haemogram.
2. Red cell indices:
INVESTIGATI
 Anaemia : Hb is below e acceptable level for age & sex.
ON  RDW: N <15%.
 MCV = PCV / RBC (fL).
 MCH = Hb / RBC (pg).
 MCHC = Hb / PCV.
3. Reticulocyte count:
 Reticulocytes:
 R juvenile red cells.
 Number of reticulocytes in periperal blood is a fairly accurate reflection of erythropoietic activity.
 Range of reticulocyte count in health = 50 – 100 x 109/L (0.5 – 2.5%).
4. Serum iron & TIBC:
 Rmeasures of iron availability, hence affected by many factors besides iron stores.
 Marked diurnal & day to day variation, very low during acute phase response but raised in liver disease &
haemolysis.
5. Transferring saturation:
 Iron/Total Iron Binding Capacity.
 If TS < 16%, is consistent with iron deficiency.
6. Serum ferritin:
 E best single test to confirm iron deficiency.
 Only small fraction of total body ferritin circulates in serum but it is related to total iron stores.
  Differentiate iron deficiency & AOCD as well as assess iron overload in Thalassemia Major.
 In few situations may not true reflection of iron stores: acute & chronic leukaemia, some malignancies (e.g.
neuroblastoma), acute hepatic failure, & infection.
 Normal range of serum ferritin:
a. Ferritin:
 Male: 16 – 323 µg/L.
 Female: 7 – 282 µg/L.
 Normal values in child similar to adult female, but higher in infant 1-3 months i.e. up to 350 µg/L.
b. Iron:
 Male: 11 – 28 µg/L.
 Female: 7 – 26 µg/L.
7. Zinc protoporphyrin (ZnPP):
8. Bone marrow iron:
 BM examination is not essential to assess iron stores except in complicated cases.
 In IDA complete absence of iron from stores (macrophages) & from developing erythroblasts.
 E erythroblasts are small and have a ragged cytoplasm.
9. Hb analysis:
 TEST for haemoglobinopathy/thalassemia.
 Traditionally this consist of:
a. Screening for abnormal Hb.
b. Quantitation of A2 & F.
 In iron deficiency anemia, e serum iron level is decreased, e total iron binding capacity increased, & e percent
saturation diminished to less than 20%.
 E serum ferritin level is usually low (but since e presence of inflammation can elevate it, e concurrence of iron
deficiency anemia & an inflammatory process may result in a normal or nearly normal serum ferritin level.
 An examination of e blood smear & characteristic findings in e serum studies usually allow a confident diagnosis of
iron deficiency anemia to be made.
 But if these r confusing, a definitive diagnosis can be made on iron stains of a bone marrow aspirate or on e basis of a
haematology response to a therapeutic trial of iron replacement.
 When iron deficiency anemia is recent & mild, e smear & erythrocyte indices (MCV, MCH, & MCHC) may be
normal.
CLASSICAL
 An early change is anisocytosis, reflected by increased red cell distribution width (RDW) on automated counters.
LAB FINDINGS  With increased severity: hematocrits typically less than 36 in men, 30 in women (e MCV & MCHC diminish).
 Changes on e smear r:
1. Anisocytosis, microcytosis, hypochromia, & poikilocytosis, including hypochromic (increased central pallor),
elongated / elliptical erythrocytes (pencil & cigar cells).
2. Tiny microcytes & occasional target cells may be present.
3. Basophilic stippling is rarely found.
4. E red cells vary widely in shape & size.
5. Comparison with e lymphocyte reveals that e erythrocytes r microcytic.
 Occasionally, mild leukopenia is present.
 In many cases thrombocytosis occurs, especially with active bleeding.
DIFFERENTIAL DIAGNOSIS
 1 of e most common anaemia occurs in patients with a variety of chronic inflammatory & malignant diseases.
 E pathogenesis:
ANAEMIA OF 1. Decreased release of iron from macrophages to plasma: d/t hepcidin released by liver n response to inflammation.
CHONIC 2. Reduced red cell lifespan.
DISEASE 3. An inadequate erythropoietin response to anaemia caused by e effects of cytokines (IL-1 or TNF) on
erythropoiesis.
 This type of anaemia may be complicated by other causes such as iron or vitamin B 12 deficiency, renal failure, & etc.
 Defined by e presence of many pathological ring sideroblasts containing numerous iron granules arranged in a ring or
collar around e nucleus.
 I is diagnosed when 15% or > of marrow erythroblasts r ring siderolasts.
SIDEROBLAST  Classifications:
1. Hereditary: usually occurs in males but can be transmitted by females.
IC ANAEMIA 2. Acquired:
a. Primary: myelodysplasia.
b. Secondary: malignant diseases of e marrow, drug reactions, & other benign conditions such as haemolytic
anaemia, or rheumatoid arthritis.

LABORATORY DIAGNOSIS OF HYPOCHROMIC MICROCYTIC ANAEMIA

IRON DEFICIENCY AOCD LAB THALASSAEMIA SIDEROBLASTIC
INVESTIGATIONS
Reduced in relation to e Low in congenital type but
Normal or mild reduction MCV & MCH Reduced
severity of anaemia raised in acquired type
Reduced Reduced SERUM IRON Normal Raised
Raised Reduced TIBC Normal Normal
SERUM
Raised Normal or low TRANSFERRIN Variable Normal
RECEPTOR
Reduced Normal or raised SERUM FERRITIN Normal Raised
Absent Present BM IRON STORES Present Present
 ERYTHROBLAST
Absent Absent Present Ring form
IRON
HHAEMOGLOBIN
Normal Normal Hb A2 raised in β form Normal
ELECTROPHORESIS

MACROCYTIC ANAEMIA
POINTS