The Cardiovascular System: The Heart

Heart Anatomy

Approximately the size of your fist

Location
Superior surface of diaphragm
Left of the midline
Anterior to the vertebral column,
posterior to the sternum
Heart Covering

Pericardial physiology
Protects and anchors heart
Prevents overfilling
Heart Covering

Pericardial anatomy
Fibrous pericardium
Serous pericardium (separated by
pericardial cavity)
Epicardium (visceral layer)
Heart Wall

Epicardium visceral layer of the serous

pericardium

Myocardium cardiac muscle layer

forming the bulk of the heart

Fibrous skeleton of the heart

crisscrossing,
interlacing
layer
of
connective tissue

Endocardium endothelial layer of the

inner myocardial surface
External Heart: Major Vessels of the
Heart (Anterior View)

Returning blood to the heart

Superior and inferior venae cavae
Right and left pulmonary veins

Conveying blood away from the heart

Pulmonary trunk, which splits into
right and left pulmonary arteries
Ascending aorta (three branches)
brachiocephalic, left common carotid,
and subclavian arteries
External
Heart:
Vessels
that
Supply/Drain the Heart (Anterior View)

Arteries right and left coronary (in

atrioventricular
groove),
marginal,
circumflex, and anterior interventricular

Veins small cardiac vein, anterior

cardiac vein, and great cardiac vein
External Heart: Major Vessels of the
Heart (Posterior View)

Returning blood to the heart

Right and left pulmonary veins
Superior and inferior venae cavae

Conveying blood away from the heart

Aorta
Right and left pulmonary arteries

External
Heart:
Vessels
that
Supply/Drain the Heart (Posterior View)

Arteries right coronary artery (in

atrioventricular groove) and the posterior
interventricular artery (in interventricular
groove)

Veins great cardiac vein, posterior vein

to left ventricle, coronary sinus, and
middle cardiac vein
Gross Anatomy of Heart: Frontal Section

Frontal
section
showing
interior
chambers and valves

Major vessels leading to and from the

heart
Gross Anatomy of Heart: Frontal Section
Atria of the Heart

Atria are the receiving chambers of the

heart

Each atrium has a protruding auricle

Pectinate muscles mark atrial walls

Blood enters right atria from superior

and inferior venae cavae and coronary
sinus

Blood enters left atria from pulmonary

veins
Ventricles of the Heart

Ventricles are the discharging chambers

of the heart

Papillary
muscles
and
trabeculae
carneae muscles mark ventricular walls

Right ventricle pumps blood into the

pulmonary trunk

Left ventricle pumps blood into the

aorta
Pathway of Blood through the Heart and
Lungs

Right atrium tricuspid valve right

ventricle

Right ventricle pulmonary semilunar

valve pulmonary arteries lungs

Lungs pulmonary veins left atrium

Left
atrium bicuspid
valve left
ventricle

Left
ventricle aortic
semilunar
valve aorta

Aorta systemic circulation

Coronary Circulation

Coronary circulation is the functional

blood supply to the heart

Collateral routes insure blood delivery to

heart even if major vessels are occluded
Heart Valves

Heart valves insure unidirectional blood

flow through the heart

Atrioventricular (AV) valves lie between

the atria and the ventricles

AV valves prevent backflow into the

atria when ventricles contract

Chordae tendineae anchor AV valves to

papillary muscles

Aortic semilunar valve lies between the

left ventricle and the aorta

Pulmonary semilunar valve lies between

the right ventricle and pulmonary trunk

Semilunar valves prevent backflow of

blood into the ventricles
Microscopic Heart Muscle Anatomy

Cardiac muscle is striated, short, fat,

branched, and interconnected

Connective tissue endomysium acts as

both tendon and insertion

Intercalated discs anchor cardiac cells

together and allow free passage of ions

Heart muscle behaves as a functional

syncytium
Cardiac Muscle Contraction

Heart muscle:
Is stimulated by nerves and selfexcitable (automaticity)
Contracts as a unit
Has a long (250 ms) absolute
refractory period

Cardiac muscle contraction is similar to

skeletal muscle contraction
Heart Physiology: Intrinsic Conduction
System

Autorhythmic cells:
Initiate action potentials
Have unstable resting potentials
called pacemaker potentials
Use calcium influx (rather than
sodium) for rising phase of the action
potential
Heart Physiology: Intrinsic Conduction
System
Heart
Physiology:
Sequence
of
Excitation

Sinoatrial (SA) node generates impulses

about 75 times/minute

Atrioventricular (AV) node delays the

impulse approximately 0.1 second

Impulse passes from atria to ventricles

via the atrioventricular bundle (bundle of
His)
Heart
Physiology:
Sequence
of
Excitation

AV bundle splits into two pathways in

the
interventricular
septum
(bundle
branches)
Bundle branches carry the impulse
toward the apex of the heart

Purkinje fibers carry the impulse to

the heart apex and ventricular walls
Extrinsic Innervation of the Heart

Heart is stimulated by the sympathetic

cardioacceleratory center

Heart
is
inhibited
by
the
parasympathetic cardioinhibitory center
Electrocardiography

Electrical activity is recorded by

electrocardiogram (ECG)

P wave corresponds to depolarization of

SA node

QRS complex corresponds to ventricular

depolarization

T wave corresponds to ventricular

repolarization

Atrial repolarization record is masked by

the larger QRS complex
Electrocardiography
Cardiac Cycle

Cardiac cycle refers to all events

associated with blood flow through the
heart
Systole contraction of heart muscle
Diastole relaxation of heart muscle
Phases of the Cardiac Cycle

Ventricular filling mid-to-late diastole

Heart blood pressure is low as blood
enters atria and flows into ventricles
AV valves are open then atrial systole
occurs

Ventricular systole
Atria relax
Rising ventricular pressure results in
closing of AV valves
Isovolumetric contraction phase
Ventricular ejection phase opens
semilunar valves
Phases of the Cardiac Cycle

Isovolumetric relaxation early diastole

Ventricles relax
Backflow of blood in aorta and
pulmonary trunk closes semilunar
valves

Dicrotic notch brief rise in aortic

pressure caused by backflow of blood
rebounding off semilunar valves
Heart Sounds

Heart sounds (lub-dup) are associated

with closing of heart valves
Cardiac Output (CO) and Reserve

CO is the amount of blood pumped by

each ventricle in one minute

CO is the product of heart rate (HR) and

stroke volume (SV)

HR is the number of heart beats per

minute

SV is the amount of blood pumped out

by a ventricle with each beat

Cardiac reserve is the difference

between resting and maximal CO
Cardiac Output: Example

CO (ml/min) = HR (75 beats/min) x SV

(70 ml/beat)

CO = 5250 ml/min (5.25 L/min)

Regulation of Stroke Volume

SV = end diastolic volume (EDV) minus

end systolic volume (ESV)

EDV = amount of blood collected in a

ventricle during diastole

ESV = amount of blood remaining in a

ventricle after contraction
Factors Affecting Stroke Volume

Preload amount ventricles are

stretched by contained blood

Contractility cardiac cell contractile

force due to factors other than EDV

Afterload back pressure exerted by

blood in the large arteries leaving the
heart
Frank-Starling Law of the Heart

Preload, or degree of stretch, of cardiac

muscle cells before they contract is the
critical factor controlling stroke volume

Slow heartbeat and exercise increase

venous return to the heart, increasing SV

Blood
loss
and
extremely
rapid
heartbeat decrease SV
Preload and Afterload
Extrinsic Factors Influencing Stroke
Volume

Contractility
is
the
increase
in
contractile
strength,
independent
of
stretch and EDV

Increase in contractility comes from:

Increased sympathetic stimuli
Certain hormones
Ca2+ and some drugs

Agents/factors
that
decrease
contractility include:
Acidosis
Increased extracellular potassium
Calcium channel blockers
Contractility and Norepinephrine

Sympathetic
stimulation
releases
norepinephrine and initiates a cyclic AMP
second-messenger system
Regulation of Heart Rate: Autonomic
Nervous System

Sympathetic nervous system (SNS)

stimulation is activated by stress, anxiety,
excitement, or exercise

Parasympathetic nervous system (PNS)

stimulation is mediated by acetylcholine
and opposes the SNS

PNS
dominates
the
autonomic
stimulation, slowing heart rate and
causing vagal tone
Bainbridge Reflex

Bainbridge
(atrial)
reflex

a
sympathetic reflex initiated by increased
blood in the atria
Causes stimulation of the SA node
Stimulates baroreceptors in the atria,
causing increased SNS stimulation
Chemical Regulation of the Heart

The
hormones
epinephrine
and
thyroxine increase heart rate

Intraand
extracellular
ion
concentrations must be maintained for
normal heart function
Factors Involved in Regulation of
Cardiac Output
Homeostatic Imbalances

Hypocalcemia reduced ionic calcium

depresses the heart

Hypercalcemia dramatically increases

heart irritability and leads to spastic
contractions

Hypernatremia

blocks
heart
contraction by inhibiting ionic calcium
transport

Hyperkalemia leads to heart block and

cardiac arrest
Homeostatic Imbalances

Tachycardia heart rate over 100

beats/min

Bradycardia heart rate less than 60

beats/min
Congestive Heart Failure (CHF)

Congestive heart failure (CHF), caused

by:
Coronary atherosclerosis
Increased blood pressure in aorta
Successive myocardial infarcts
Dilated cardiomyopathy (DCM)
Developmental Aspects of the Heart

Embryonic heart chambers

Sinus venous
Atrium
Ventricle
Bulbus cordis
Developmental Aspects of the Heart

Fetal heart structures that bypass

pulmonary circulation

Foramen ovale connects the two atria

Ductus arteriosus connects pulmonary
trunk and the aorta
Age-Related Changes Affecting the
Heart

Sclerosis and thickening of valve flaps

Decline in cardiac reserve

Fibrosis of cardiac muscle

Atherosclerosis
Blood
Overview of Blood Circulation

Blood leaves the heart via arteries that

branch repeatedly until they become
capillaries

Oxygen (O2) and nutrients diffuse across

capillary walls and enter tissues

Carbon dioxide (CO2) and wastes move

from tissues into the blood

Oxygen-deficient blood leaves the

capillaries and flows in veins to the heart

This blood flows to the lungs where it

releases CO2 and picks up O2

The oxygen-rich blood returns to the

heart
Composition of Blood

Blood is the bodys only fluid tissue

It is composed of liquid plasma and

formed elements

Formed elements include:

Erythrocytes, or red blood cells (RBCs)
Leukocytes, or white blood cells
(WBCs)
Platelets

Hematocrit the percentage of RBCs

out of the total blood volume
Physical Characteristics and Volume

Blood is a sticky, opaque fluid with a

metallic taste

Color varies from scarlet (oxygen-rich)

to dark red (oxygen-poor)

The pH of blood is 7.357.45

Temperature is 38C, slightly higher

than normal body temperature

Blood accounts for approximately 8% of

body weight

Average volume of blood is 56 L for

males, and 45 L for females
Functions of Blood

Blood performs a number of functions

dealing with:
Substance distribution
Regulation of blood levels of particular
substances
Body protection
Distribution

Blood transports:
Oxygen from the lungs and nutrients
from the digestive tract
Metabolic wastes from cells to the
lungs and kidneys for elimination
Hormones from endocrine glands to
target organs
Regulation

Blood maintains:
Appropriate body temperature by
absorbing and distributing heat
Normal pH in body tissues using
buffer systems
Adequate
fluid
volume
in
the
circulatory system
Protection

Blood prevents blood loss by:

Activating
plasma
proteins
and
platelets
Initiating clot formation when a vessel
is broken

Blood prevents infection by:

Synthesizing and utilizing antibodies
Activating complement proteins
Activating WBCs to defend the body
against foreign invaders
Blood Plasma

Blood plasma contains over 100 solutes,

including:
Proteins albumin, globulins, clotting
proteins, and others
Nonprotein nitrogenous substances
lactic acid, urea, creatinine
Organic
nutrients

glucose,
carbohydrates, amino acids
Electrolytes sodium, potassium,
calcium, chloride, bicarbonate
Respiratory gases oxygen and
carbon dioxide
Formed Elements

Erythrocytes, leukocytes, and platelets

make up the formed elements
Only WBCs are complete cells
RBCs have no nuclei or organelles,
and platelets are just cell fragments

Most formed elements survive in the

bloodstream for only a few days

Most blood cells do not divide but are

renewed by cells in bone marrow
Erythrocytes (RBCs)

Biconcave discs, anucleate, essentially

no organelles

Filled with hemoglobin (Hb), a protein

that functions in gas transport

Contain
the
plasma
membrane
protein spectrin that:

Gives erythrocytes their flexibility

Allows them to change shape as
necessary

Erythrocytes are an example of the

complementarity of structure and function

Structural
characteristics
that
contribute to its gas transport function
are:
Biconcave shape that has a huge
surface area to volume ratio
Discounting
water
content,
erythrocytes are 97% hemoglobin
ATP is generated anaerobically, so the
erythrocytes do not consume the
oxygen they transport
Erythrocyte Function

Erythrocytes
are
dedicated
to
respiratory gas transport

Hemoglobin
reversibly
binds
with
oxygen and most oxygen in the blood is
bound to hemoglobin

Hemoglobin is composed of:

The protein globin, made up of two
alpha and two beta chains, each bound
to a heme group
Each heme group bears an atom of
iron,
which
can
bind
one
to
oxygen molecule

Each
hemoglobin
molecule
can
transport four molecules of oxygen
Hemoglobin (Hb)

Oxyhemoglobin hemoglobin bound to

oxygen
Oxygen loading takes place in the
lungs

Deoxyhemoglobin hemoglobin after

oxygen diffuses into tissues (reduced Hb)

Carbaminohemoglobin hemoglobin
bound to carbon dioxide
Carbon dioxide loading takes place in
the tissues
Production of Blood Cells

Hematopoiesis blood cell formation

Hemopoiesis occurs in the red bone

marrow of the:
Axial skeleton and girdles
Epiphyses of the humerus and femur

Hemocytoblasts give rise to all formed

elements
Production
of
Erythrocytes:
Erythropoiesis

A hemocytoblast is transformed into a

committed cell called the proerythroblast

Proerythroblasts develop into early

erythroblasts

The developmental pathway consists of

three phases
Phase 1 ribosome synthesis in early
erythroblasts
Phase 2 hemoglobin accumulation in
late erythroblasts and normoblasts
Phase 3 ejection of the nucleus from
normoblasts
and
formation
of
reticulocytes

Reticulocytes then become mature

erythrocytes

Circulating erythrocytes the number

remains constant and reflects a balance
between RBC production and destruction
Too few red blood cells leads to tissue
hypoxia
Too many red blood cells causes
undesirable blood viscosity

Erythropoiesis is hormonally controlled

and depends on adequate supplies of iron,
amino acids, and B vitamins
Hormonal Control of Erythropoiesis

Erythropoietin (EPO) release by the

kidneys is triggered by:
Hypoxia due to decreased RBCs
Decreased oxygen availability
Increased tissue demand for oxygen

Enhanced erythropoiesis increases the:

RBC count in circulating blood
Oxygen carrying ability of the blood
increases
Erythropoiesis: Nutrient Requirements

Erythropoiesis requires:
Proteins, lipids, and carbohydrates
Iron, vitamin B12, and folic acid

The body stores iron in Hb (65%), the

liver, spleen, and bone marrow

Intracellular iron is stored in protein-iron

complexes
such
as ferritin and hemosiderin

Circulating iron is loosely bound to the

transport protein transferrin
Fate and Destruction of Erythrocytes

The life span of an erythrocyte is 100

120 days

Old erythrocytes become rigid and

fragile, and their hemoglobin begins to
degenerate

Dying erythrocytes are engulfed by

macrophages

Heme and globin are separated and the

iron is salvaged for reuse
Fate of Hemoglobin

Heme is degraded to a yellow pigment

called bilirubin

The liver secretes bilirubin into the

intestines as bile

The intestines metabolize it into

urobilinogen

This degraded pigment leaves the body

in feces, in a pigment called stercobilin

Globin is metabolized into amino acids

and is released into the circulation
Life Cycle of Red Blood Cells
Erythrocyte Disorders

Anemia blood has abnormally low

oxygen-carrying capacity
It is a symptom rather than a disease
itself
Blood oxygen levels cannot support
normal metabolism
Signs/symptoms
include
fatigue,
paleness, shortness of breath, and chills
Anemia: Insufficient Erythrocytes

Hemorrhagic anemia result of acute or

chronic loss of blood

Hemolytic
anemia

prematurely
ruptured erythrocytes

Aplastic anemia destruction or

inhibition of red bone marrow
Anemia: Decreased Hemoglobin Content

Iron-deficiency anemia results from:

A secondary result of hemorrhagic
anemia
Inadequate intake of iron-containing
foods
Impaired iron absorption

Pernicious anemia results from:

Deficiency of vitamin B12
Often caused by lack of intrinsic factor

needed for absorption of B12

Anemia: Abnormal Hemoglobin

Thalassemias absent or faulty globin

chain in hemoglobin
Erythrocytes are thin, delicate, and
deficient in hemoglobin

Sickle-cell anemia results from a

defective gene coding for an abnormal
hemoglobin called hemoglobin S (HbS)
HbS has a single amino acid
substitution in the beta chain
This defect causes RBCs to become
sickle-shaped in low oxygen situations
Polycythemia

Polycythemia excess RBCs that

increase blood viscosity

Three main polycythemias are:

Polycythemia vera
Secondary polycythemia
Blood doping
Leukocytes (WBCs)

Leukocytes, the only blood components

that are complete cells:
Are less numerous than RBCs
Make up 1% of the total blood volume
Can leave capillaries via diapedesis
Move through tissue spaces

Leukocytosis WBC count over 11,000

per cubic millimeter
Normal response to bacterial or viral
invasion
Classification
of
Leukocytes:
Granulocytes

Granulocytes neutrophils, eosinophils,

and basophils
Contain cytoplasmic granules that
stain specifically (acidic, basic, or both)
with Wrights stain
Are larger and usually shorter-lived
than RBCs
Have lobed nuclei
Are all phagocytic cells
Neutrophils

Neutrophils have two types of granules

that:
Take up both acidic and basic dyes
Give the cytoplasm a lilac color
Contain
peroxidases,
hydrolytic
enzymes, and defensins (antibiotic-like
proteins)

Neutrophils are our bodys bacterial

slayers
Eosinophils

Eosinophils account for 14% of WBCs

Have red-staining, bi-lobed nuclei
connected via a broad band of nuclear
material
Have red to crimson (acidophilic)
large, coarse, lysosome-like granules
Lead the bodys counterattack against
parasitic worms
Lessen the severity of allergies by
phagocytizing immune complexes
Basophils

Account for 0.5% of WBCs and:

Have U- or S-shaped nuclei with two
or three conspicuous constrictions
Are functionally similar to mast cells
Have large, purplish-black (basophilic)
granules that contain histamine
Histamine inflammatory chemical
that acts as a vasodilator and
attracts other WBCs
Agranulocytes

Agranulocytes lymphocytes and

monocytes:

Lack visible cytoplasmic granules

Are similar structurally, but are
functionally distinct and unrelated cell
types
Have spherical (lymphocytes) or
kidney-shaped (monocytes) nuclei
Lymphocytes

Have large, dark-purple, circular nuclei

with a thin rim of blue cytoplasm

Found mostly enmeshed in lymphoid

tissue (some circulate in the blood)

There are two types of lymphocytes: T

cells and B cells
T cells function in the immune
response
B cells give rise to plasma cells, which
produce antibodies
Monocytes

Monocytes account for 48% of

leukocytes
They are the largest leukocytes
They
have
abundant
pale-blue
cytoplasms
They have purple staining, U- or
kidney-shaped nuclei
They leave the circulation, enter
tissue,
and
differentiate
into
macrophages

Macrophages:
Are highly mobile and actively
phagocytic
Activate lymphocytes to mount an
immune response
Production of Leukocytes

Leukopoiesis is hormonally stimulated

by two families of cytokines (hematopoetic
factors) interleukins and colonystimulating factors (CSFs)
Interleukins are numbered (e.g., IL-1,
IL-2), whereas CSFs are named for the
WBCs they stimulate (e.g., granulocyteCSF stimulates granulocytes)

Macrophages and T cells are the most

important sources of cytokines

Many hematopoietic hormones are used

clinically to stimulate bone marrow
Formation of Leukocytes

All
leukocytes
originate
from
hemocytoblasts

Hemocytoblasts
differentiate
into
myeloid stem cells and lymphoid stem
cells

Myeloid stem cells become myeloblasts

or monoblasts

Lymphoid
stem
cells
become
lymphoblasts

Myeloblasts develop into eosinophils,

neutrophils, and basophils

Monoblasts develop into monocytes

Lymphoblasts develop into lymphocytes

Leukocyte Disorders: Leukemias

Leukemia refer to cancerous conditions

involving white blood cells

Leukemias are named according to the

abnormal white blood cells involved
Myelocytic
leukemia

involves
myeloblasts
Lymphocytic leukemia involves
lymphocytes

Acute leukemia involves blast-type cells

and primarily affects children

Chronic leukemia is more prevalent in

older people
Leukemia

Immature white blood cells are found in

the bloodstream in all leukemias

Bone marrow becomes totally occupied

with cancerous leukocytes

The white blood cells produced, though

numerous, are not functional

Death is caused by internal hemorrhage

and overwhelming infections

Treatments
include
irradiation,
antileukemic drugs, and bone marrow
transplants
Platelets

Platelets
are
fragments
of
megakaryocytes with a blue-staining outer
region and a purple granular center

The granules contain serotonin, Ca2+,

enzymes,
ADP,
and
platelet-derived
growth factor (PDGF)

Platelets function in the clotting

mechanism by forming a temporary plug
that helps seal breaks in blood vessels
Genesis of Platelets

The stem cell for platelets is the

hemocytoblast

The sequential developmental pathway

is
hemocytoblast,
megakaryoblast,
promegakaryocyte, megakaryocyte, and
platelets
Hemostasis

A series of reactions designed for

stoppage of bleeding

During hemostasis, three phases occur

in rapid sequence
Vascular
spasms

immediate
vasoconstriction in response to injury
Platelet plug formation
Coagulation (blood clotting)
Platelet Plug Formation

Platelets do not stick to each other or to

the endothelial lining of blood vessels

Upon damage to a blood vessel,

platelets:
Are stimulated by thromboxane A2

Stick to exposed collagen fibers and

form a platelet plug
Release serotonin and ADP, which
attract still more platelets
The platelet plug is limited to the

immediate area of injury by PGI2

Coagulation

A set of reactions in which blood is

transformed from a liquid to a gel

Coagulation
follows
intrinsic
and
extrinsic pathways
Coagulation

The final thee steps of this series of

reactions are:
Prothrombin activator is formed
Prothrombin
is
converted
into
thrombin
Thrombin catalyzes the joining of
fibrinogen into a fibrin mesh
Detailed Reactions of Hemostasis
Coagulation Phase 1: Two Pathways to
Prothrombin Activator

May be initiated by either the intrinsic

or extrinsic pathway
Triggered by tissue-damaging events
Involves a series of procoagulants
Each pathway cascades toward factor
X

Once factor X has been activated, it

complexes with calcium ions, PF3, and
factor V to form prothrombin activator
Coagulation Phase 2: Pathway to
Thrombin

Prothrombin activator catalyzes the

transformation of prothrombin to the
active the enzyme thrombin
Coagulation
Phase
3:
Common
Pathways to the Fibrin Mesh

Thrombin catalyzes the polymerization

of fibrinogen into fibrin

Insoluble fibrin strands form the

structural basis of a clot

Fibrin causes plasma to become a gellike trap

Fibrin in the presence of calcium ions

activates factor XIII that:
Cross-links fibrin
Strengthens and stabilizes the clot
Clot Retraction and Repair

Clot retraction stabilization of the clot

by squeezing serum from the fibrin strands

Repair
Platelet-derived growth factor (PDGF)
stimulates rebuilding of blood vessel
wall
Fibroblasts form a connective tissue
patch
Endothelial cells multiply and restore
the endothelial lining
Factors
Limiting
Clot
Growth
or
Formation

Two homeostatic mechanisms prevent

clots from becoming large
Swift removal of clotting factors
Inhibition of activated clotting factors
Inhibition of Clotting Factors

Fibrin acts as an anticoagulant by

binding thrombin and preventing its:
Positive
feedback
effects
of
coagulation
Ability to speed up the production of
prothrombin activator via factor V
Acceleration of the intrinsic pathway
by activating platelets

Thrombin not absorbed to fibrin is

inactivated by antithrombin III

Heparin, another anticoagulant, also

inhibits thrombin activity
Factors Preventing Undesirable Clotting

Unnecessary clotting is prevented by

the
structural
and
molecular
characteristics of endothelial cells lining
the blood vessels

Platelet adhesion is prevented by:

The smooth endothelial lining of blood
vessels
Heparin
and
PGI2 secreted
by
endothelial cells
Vitamin
E
quinone,
a
potent
anticoagulant
Hemostasis
Disorders:
Thromboembolytic Disorders

Thrombus a clot that develops and

persist in an unbroken blood vessel
Thrombi
can
block
circulation,
resulting in tissue death
Coronary thrombosis thrombus in
blood vessel of the heart

Embolus a thrombus freely floating in

the blood stream
Pulmonary emboli can impair the
ability of the body to obtain oxygen
Cerebral emboli can cause strokes
Prevention of Undesirable Clots

Substances used to prevent undesirable

clots include:

Aspirin an antiprostaglandin that

inhibits thromboxane A2
Heparin an anticoagulant used
clinically for pre- and postoperative
cardiac care
Warfarinin used for those prone to
atrial fibrillation
Flavonoids substances found in tea,
red wine, and grape juice that have
natural anticoagulant activity
Hemostasis
Disorders:
Bleeding
Disorders

Thrombocytopenia condition where

the number of circulating platelets is
deficient
Patients show petechiae (small purple
blotches
on
the
skin)
due
to
spontaneous, widespread hemorrhage
Caused by suppression or destruction
of bone marrow (e.g., malignancy,
radiation)
Platelet
counts
less
than
50,000/mm3 is
diagnostic
for
this
condition
Treated with whole blood transfusions
Hemostasis
Disorders:
Bleeding
Disorders

Inability to synthesize procoagulants by

the liver results in severe bleeding
disorders

Causes can range from vitamin K

deficiency to hepatitis and cirrhosis

Inability to absorb fat can lead to

vitamin K deficiencies as it is a fat-soluble
substance and is absorbed along with fat

Liver disease can also prevent the liver

from producing bile, which is required for
fat and vitamin K absorption

Hemophilias hereditary bleeding

disorders caused by lack of clotting factors
Hemophilia A most common type
(83% of all cases) due to a deficiency of
factor VIII
Hemophilia B results from a
deficiency of factor IX
Hemophilia C mild type, caused by a
deficiency of factor XI

Symptoms include prolonged bleeding

and painful and disabled joints

Treatment is with blood transfusions

and the injection of missing factors
Blood Transfusions

Transfusions are necessary:

When substantial blood loss occurs
In certain hemostatis disorders

Whole blood transfusions are used:

When blood loss is substantial

In treating thrombocytopenia

Packed red cells (cells with plasma

removed) are used to treat anemia
Human Blood Groups

RBC membranes have glycoprotein

antigens on their external surfaces

These antigens are:

Unique to the individual
Recognized as foreign if transfused
into another individual
Promoters of agglutination and are
referred to as agglutinogens

Presence/absence of these antigens are

used to classify blood groups

Humans have 30 varieties of naturally

occurring RBC antigens

The antigens of the ABO and Rh blood

groups
cause
vigorous
transfusion
reactions when they are improperly
transfused

Other blood groups (M, N, Dufy, Kell,

and Lewis) are mainly used for legalities
ABO Blood Groups

The ABO blood groups consists of:

Two antigens (A and B) on the surface
of the RBCs
Two antibodies in the plasma (anti-A
and anti-B)

An individual with ABO blood may have

various
types
of
antigens
and
spontaneously preformed antibodies

Agglutinogens and their corresponding

antibodies cannot be mixed without
serious hemolytic reactions
Rh Blood Groups

There
are
eight
different
Rh
agglutinogens, three of which (C, D, and E)
are common

Presence of the Rh agglutinogens on

RBCs is indicated as Rh+

Anti-Rh
antibodies
are
not
spontaneously formed in Rh individuals

However, if an Rh individual receives

Rh+ blood, anti-Rh antibodies form

A second expose to Rh+ blood will result

in a typical transfusion reaction
Hemolytic Disease of the Newborn

Hemolytic disease of the newborn

Rh+ antibodies of a sensitized Rh mother
cross the placenta and attack and destroy
the RBCs of an Rh+ baby

Rh mother become sensitized when

Rh+ blood (from a previous pregnancy of
an Rh+ baby or a Rh+ transfusion) causes
her body to synthesis Rh+ antibodies

The drug RhoGAM can prevent the

Rh mother from becoming sensitized

Treatment of hemolytic disease of the

newborn involves pre-birth transfusions
and exchange transfusions after birth
Transfusion Reactions

Transfusion
reactions
occur
when
mismatched blood is infused

Donors cells are attacked by the

recipients plasma agglutinins causing:
Diminished oxygen-carrying capacity
Clumped cells that impede blood flow
Ruptured RBCs that release free
hemoglobin into the bloodstream

Circulating hemoglobin precipitates in

the kidneys and causes renal failure
Blood Typing

When serum containing anti-A or anti-B

agglutinins
is
added
to
blood,
agglutination will occur between the
agglutinin
and
the
corresponding
agglutinogens

Positive reactions indicate agglutination

Plasma Volume Expanders

When shock is imminent from low blood

volume, volume must be replaced

Plasma or plasma expanders can be

administered

Plasma expanders:
Have osmotic properties that directly
increase fluid volume
Are used when plasma is not available
Examples: purified human serum
albumin, plasminate and dextran

Isotonic saline can also be used to

replace lost blood volume
Diagnostic Blood Tests

Laboratory examination of blood can

assess an individuals state of health

Microscopic examination:
Variations in size and shape of RBCs
predictions of anemias
Type and number of WBCs
diagnostic of various diseases

Chemical analysis can provide a

comprehensive picture of ones general
health status in relation to normal values
Developmental Aspects

Before birth, blood cell formation takes

place in the fetal yolk sac, liver, and
spleen

By the 7th month, red bone marrow is

the primary hematopoietic area

Blood cells develop from mesenchymal

cells called blood islands

The fetus forms HbF, which has a higher

affinity for oxygen than adult hemoglobin
Developmental Aspects

Age-related blood problems result from

disorders of the heart, blood vessels, and
the immune system

Increased leukemias are thought to be

due to the waning deficiency of the
immune system

Abnormal
thrombus
and
embolus
formation
reflects
the
progress
of
atherosclerosis
The
Cardiovascular
Vessels

System:

Blood

Blood Vessels

Blood is carried in a closed system of

vessels that begins and ends at the heart

The three major types of vessels are

arteries, capillaries, and veins

Arteries carry blood away from the

heart, veins carry blood toward the heart

Capillaries contact tissue cells and

directly serve cellular needs
Continuous Capillary Structure
Fenestrated Capillary Structure
Discontinuous
Sinusoidal
Capillary
Structure
Generalized Structure of Blood Vessels

Arteries and veins are composed

of three tunics tunica interna, tunica
media, and tunica externa

Capillaries
are
composed
of
endothelium with sparse basal lamina

Lumen central blood-containing space

surrounded by tunics
Tunics

Tunica interna (tunica intima)

Endothelial layer that lines the lumen
of all vessels
In vessels larger than 1 mm, a
subendothelial
connective
tissue
basement membrane is present

Tunica media
Smooth muscle and elastic fiber layer,
regulated by sympathetic nervous
system
Controls vasoconstriction/vasodilation
of vessels

Tunica externa (tunica adventitia)

Collagen fibers that protect and
reinforce vessels
Larger vessels contain vasa vasorum
Elastic (Conducting) Arteries

Thick-walled arteries near the heart; the

aorta and its major branches
Large lumen allow low-resistance
conduction of blood
Contain elastin in all three tunics
Withstand and smooth out large blood
pressure fluctuations
Allow blood to flow fairly continuously
through the body
Muscular Arteries and Arterioles

Muscular arteries distal to elastic

arteries; deliver blood to body organs
Have thick tunica media with more
smooth muscle and less elastic tissue
Active in vasoconstriction

Arterioles smallest arteries; lead to

capillary beds
Control flow into capillary beds via
vasodilation and constriction
Capillaries

Capillaries are the smallest blood

vessels
Walls consisting of a thin tunica
interna, one cell thick
Allow only a single RBC to pass at a
time
Pericytes on the outer surface
stabilize their walls

There are three structural types of

capillaries: continuous, fenestrated, and
sinusoids
Continuous Capillaries

Continuous capillaries are abundant in

the skin and muscles, and have:
Endothelial cells that provide an
uninterrupted lining
Adjacent cells that are held together
with tight junctions
Intercellular
clefts
of
unjoined
membranes that allow the passage of
fluids

Continuous capillaries of the brain:

Have tight junctions completely
around the endothelium
Constitute the blood-brain barrier
Fenestrated Capillaries

Found
wherever
active
capillary
absorption or filtrate formation occurs
(e.g., small intestines, endocrine glands,
and kidneys)

Characterized by:
An endothelium riddled with pores
(fenestrations)
Greater permeability to solutes and
fluids than other capillaries
Sinusoids

Highly modified, leaky, fenestrated

capillaries with large lumens

Found in the liver, bone marrow,

lymphoid tissue, and in some endocrine
organs

Allow large molecules (proteins and

blood cells) to pass between the blood and
surrounding tissues

Blood flows sluggishly, allowing for

modification in various ways
Capillary Beds

A
microcirculation
of
interwoven
networks of capillaries, consisting of:
Vascular
shunts

metarteriole
thoroughfare channel connecting an
arteriole directly with a postcapillary
venule
True capillaries 10 to 100 per
capillary bed, capillaries branch off the
metarteriole
and
return
to
the
thoroughfare channel at the distal end
of the bed
The Respiratory System
Respiratory System

Consists of the respiratory and

conducting zones

Respiratory zone
Site of gas exchange
Consists of bronchioles, alveolar
ducts, and alveoli

Conducting zone
Provides rigid conduits for air to reach
the sites of gas exchange
Includes all other respiratory
structures (e.g., nose, nasal cavity,
pharynx, trachea)

Respiratory muscles diaphragm and

other muscles that promote ventilation
Major Functions of the Respiratory
System

To supply the body with oxygen and

dispose of carbon dioxide

Respiration four distinct processes

must happen
Pulmonary ventilation moving air
into and out of the lungs
External respiration gas exchange
between the lungs and the blood
Transport transport of oxygen and
carbon dioxide between the lungs and
tissues
Internal respiration gas exchange
between systemic blood vessels and
tissues
Function of the Nose

The only externally visible part of the

respiratory system that functions by:
Providing an airway for respiration
Moistening and warming the entering
air
Filtering inspired air and cleaning it of
foreign matter
Serving as a resonating chamber for
speech
Housing the olfactory receptors
Structure of the Nose

The nose is divided into two regions

The external nose, including the root,
bridge, dorsum nasi, and apex
The internal nasal cavity

Philtrum a shallow vertical groove

inferior to the apex

The external nares (nostrils) are

bounded laterally by the alae
Nasal Cavity

Lies in and posterior to the external

nose

Is divided by a midline nasal septum

Opens posteriorly into the nasal

pharynx via internal nares

The ethmoid and sphenoid bones form

the roof

The floor is formed by the hard and soft

palates

Vestibule nasal cavity superior to the

nares
Vibrissae hairs that filter coarse
particles from inspired air

Olfactory mucosa
Lines the superior nasal cavity
Contains smell receptors

Respiratory mucosa
Lines the balance of the nasal cavity
Glands secrete mucus containing
lysozyme and defensins to help destroy
bacteria

Inspired air is:

Humidified by the high water content
in the nasal cavity
Warmed by rich plexuses of capillaries

Ciliated mucosal cells remove

contaminated mucus

Superior, medial, and inferior conchae:

Protrude medially from the lateral
walls
Increase mucosal area
Enhance air turbulence and help filter
air

Sensitive mucosa triggers sneezing

when stimulated by irritating particles
Paranasal Sinuses

Sinuses in bones that surround the

nasal cavity

Sinuses lighten the skull and help to

warm and moisten the air
Pharynx

Funnel-shaped tube of skeletal muscle

that connects to the:
Nasal cavity and mouth superiorly
Larynx and esophagus inferiorly

Extends from the base of the skull to

the level of the sixth cervical vertebra

It is divided into three regions:

Nasopharynx
Oropharynx
Laryngopharynx
Nasopharynx

Lies posterior to the nasal cavity,

inferior to the sphenoid, and superior to
the level of the soft palate

Strictly an air passageway

Lined with pseudostratified columnar

epithelium

Closes during swallowing to prevent

food from entering the nasal cavity

The pharyngeal tonsil lies high on the

posterior wall

Pharyngotympanic (auditory) tubes

open into the lateral walls
Oropharynx

Extends inferiorly from the level of the

soft palate to the epiglottis

Opens to the oral cavity via an archway

called the fauces

Serves as a common passageway for

food and air

The epithelial lining is protective

stratified squamous epithelium

Palatine tonsils lie in the lateral walls of

the fauces

Lingual tonsil covers the base of the

tongue
Laryngopharynx

Serves as a common passageway for

food and air

Lies posterior to the upright epiglottis

Extends to the larynx, where the

respiratory and digestive pathways
diverge
Larynx (Voice Box)

Attaches to the hyoid bone and opens

into the laryngopharynx superiorly

Continuous with the trachea posteriorly

The three functions of the larynx are:

To provide a patent airway

To act as a switching mechanism to

route air and food into the proper
channels
To function in voice production
Framework of the Larynx

Cartilages (hyaline) of the larynx are:

Shield-shaped anterosuperior thyroid
cartilage with a midline laryngeal
prominence (Adams apple)
Signet ringshaped anteroinferior
cricoid cartilage
Three pairs of small arytenoid,
cuneiform, and corniculate cartilages

Epiglottis elastic cartilage that covers

the laryngeal inlet during swallowing
Vocal Ligaments

Attach the arytenoid cartilages to the

thyroid cartilage

Composed of elastic fibers that form

mucosal folds called true vocal cords
The medial opening between them is
the glottis
They vibrate to produce sound as air
rushes up from the lungs

False vocal cords

Mucosal folds superior to the true
vocal cords
Have no part in sound production
Vocal Production

Speech intermittent release of expired

air while opening and closing the glottis

Pitch determined by the length and

tension of the vocal cords

Loudness depends upon the force at

which the air rushes across the vocal cords

The pharynx resonates, amplifies, and

enhances sound quality

Sound is shaped into language by

action of the pharynx, tongue, soft palate,
and lips
Sphincter Functions of the Larynx

Both the epiglottis and the vocal cords

can close the larynx

The larynx is closed during coughing,

sneezing, and Valsalvas maneuver

Valsalvas maneuver
Air is temporarily held in the lower
respiratory tract by closing the glottis
Causes intra-abdominal pressure to
rise when abdominal muscles contract
Empties the bladder or rectum
Acts as a splint to stabilize the trunk
when lifting heavy loads
Trachea

Flexible and mobile tube extending from

the larynx into the mediastinum

Composed of three layers

Mucosa made up of goblet cells and
ciliated epithelium
Submucosa connective tissue deep
to the mucosa
Adventitia outermost layer made of
C-shaped rings of hyaline cartilage
Conducting Zone: Bronchi

The carina of the last tracheal cartilage

marks the end of the trachea and the
beginning of the right and left bronchi

Air reaching the bronchi is:

Warm and cleansed of impurities
Saturated with water vapor

Bronchi subdivide into secondary

bronchi, each supplying a lobe of the lungs

Air passages undergo 23 orders of

branching in the lungs
Conducting Zone: Bronchial Tree

Tissue walls of bronchi mimic that of the

trachea

As conducting tubes become smaller,

structural changes occur
Cartilage support structures change
Epithelium types change
Amount of smooth muscle increases

Bronchioles
Consist of cuboidal epithelium
Have a complete layer of circular
smooth muscle
Lack cartilage support and mucusproducing cells
Respiratory Zone

Defined by the presence of alveoli;

begins as terminal bronchioles feed into
respiratory bronchioles

Respiratory bronchioles lead to alveolar

ducts, then to terminal clusters of alveolar
sacs composed of alveoli

Approximately 300 million alveoli:

Account for most of the lungs
volume
Provide tremendous surface area for
gas exchange
Respiratory Membrane

This air-blood barrier is composed of:

Alveolar and capillary walls
Their fused basal laminas

Alveolar walls:
Are a single layer of type I epithelial
cells
Permit gas exchange by simple
diffusion
Secrete angiotensin converting
enzyme (ACE)

Type II cells secrete surfactant

Alveoli

Surrounded by fine elastic fibers

Contain open pores that:

Connect adjacent alveoli
Allow air pressure throughout the lung
to be equalized

House macrophages that keep alveolar

surfaces sterile
Gross Anatomy of the Lungs

Lungs occupy all of the thoracic cavity

except the mediastinum
Root site of vascular and bronchial
attachments
Costal surface anterior, lateral, and
posterior surfaces in contact with the
ribs
Apex narrow superior tip
Base inferior surface that rests on
the diaphragm
Hilus indentation that contains
pulmonary and systemic blood vessels
Lungs

Cardiac notch (impression) cavity that

accommodates the heart

Left lung separated into upper and

lower lobes by the oblique fissure

Right lung separated into three lobes

by the oblique and horizontal fissures

There are 10 bronchopulmonary

segments in each lung
Blood Supply to Lungs

Lungs are perfused by two circulations:

pulmonary and bronchial

Pulmonary arteries supply systemic

venous blood to be oxygenated
Branch profusely, along with bronchi
Ultimately feed into the pulmonary
capillary network surrounding the
alveoli

Pulmonary veins carry oxygenated

blood from respiratory zones to the heart
Blood Supply to Lungs

Bronchial arteries provide systemic

blood to the lung tissue
Arise from aorta and enter the lungs
at the hilus
Supply all lung tissue except the
alveoli

Bronchial veins anastomose with

pulmonary veins

Pulmonary veins carry most venous

blood back to the heart
Pleurae

Thin, double-layered serosa

Parietal pleura

Covers the thoracic wall and superior

face of the diaphragm
Continues around heart and between
lungs

Visceral, or pulmonary, pleura

Covers the external lung surface
Divides the thoracic cavity into three
chambers
The central mediastinum
Two lateral compartments, each
containing a lung
Breathing

Breathing, or pulmonary ventilation,

consists of two phases
Inspiration air flows into the lungs
Expiration gases exit the lungs
Pressure Relationships in the Thoracic
Cavity

Respiratory pressure is always

described relative to atmospheric pressure

Atmospheric pressure (Patm)

Pressure exerted by the air
surrounding the body
Negative respiratory pressure is less
than Patm
Positive respiratory pressure is
greater than Patm

Intrapulmonary pressure (Palv)

pressure within the alveoli

Intrapleural pressure (Pip) pressure

within the pleural cavity
Pressure Relationships

Intrapulmonary pressure and

intrapleural pressure fluctuate with the
phases of breathing

Intrapulmonary pressure always

eventually equalizes itself with
atmospheric pressure

Intrapleural pressure is always less than

intrapulmonary pressure and atmospheric
pressure

Two forces act to pull the lungs away

from the thoracic wall, promoting lung
collapse
Elasticity of lungs causes them to
assume smallest possible size
Surface tension of alveolar fluid draws
alveoli to their smallest possible size

Opposing force elasticity of the chest

wall pulls the thorax outward to enlarge
the lungs
Lung Collapse

Caused by equalization of the

intrapleural pressure with the
intrapulmonary pressure

Transpulmonary pressure keeps the

airways open
Transpulmonary pressure difference
between the intrapulmonary and
intrapleural pressures (Palv Pip)
Pulmonary Ventilation

A mechanical process that depends on

volume changes in the thoracic cavity

Volume changes lead to pressure

changes, which lead to the flow of gases
to equalize pressure
DV DP F (flow of gases)
Boyles Law

Boyles law the relationship between

the pressure and volume of gases
P1V1 = P2V2

P = pressure of a gas in mm Hg
V = volume in cubic millimeters
Subscripts 1 and 2 represent the
initial and resulting conditions,
respectively
Inspiration

The diaphragm and external intercostal

muscles (inspiratory muscles) contract and
the rib cage rises

The lungs are stretched and

intrapulmonary volume increases

Intrapulmonary pressure drops below

atmospheric pressure (-1 mm Hg)

Air flows into the lungs, down its

pressure gradient, until intrapleural
pressure = atmospheric pressure
Expiration

Inspiratory muscles relax and the rib

cage descends due to gravity

Thoracic cavity volume decreases

Elastic lungs recoil passively and

intrapulmonary volume decreases

Intrapulmonary pressure rises above

atmospheric pressure (+1 mm Hg)

Gases flow out of the lungs down the

pressure gradient until intrapulmonary
pressure is 0
Physical Factors Influencing Ventilation:
Airway Resistance

Friction is the major nonelastic source of

resistance to airflow

The relationship between flow (F),

pressure (P), and resistance (R) is:
F = DP
R
Physical Factors Influencing Ventilation:
Airway Resistance

The amount of gas flowing into and out

of the alveoli is directly proportional to DP,
the pressure gradient between the
atmosphere and the alveoli
DP = D (Patm Palv)

Gas flow is inversely proportional to

resistance with the greatest resistance
being in the medium-sized bronchi
Airway Resistance

As airway resistance rises, breathing

movements become more strenuous

Severely constricted or obstructed

bronchioles:
Can prevent life-sustaining ventilation
Can occur during acute asthma
attacks which stops ventilation

Epinephrine release via the sympathetic

nervous system dilates bronchioles and
reduces air resistance
Alveolar Surface Tension

Surface tension the attraction of liquid

molecules for one another at a liquid-gas
interface

The liquid coating the alveolar surface is

always acting to reduce the alveoli to the
smallest possible size

Surfactant, a detergent-like complex,

reduces surface tension and helps keep
the alveoli from collapsing
Lung Compliance

The ease with which lungs can be

expanded

Specifically, the measure of the change

in lung volume that occurs with a given
change in transpulmonary pressure

Determined by two main factors

Distensibility of the lung tissue and
surrounding thoracic cage
Surface tension of the alveoli
Factors That Diminish Lung Compliance

Scar tissue or fibrosis that reduces the

natural resilience of the lungs

Blockage of the smaller respiratory

passages with mucus or fluid

Reduced production of surfactant

Decreased flexibility of the thoracic

cage or its decreased ability to expand

Examples include:
Deformities of thorax
Ossification of the costal cartilage
Paralysis of intercostal muscles
Respiratory Volumes

Tidal volume (TV) air that moves into

and out of the lungs with each breath
(approximately 500 ml)

Inspiratory reserve volume (IRV) air

that can be inspired forcibly beyond the
tidal volume
(21003200 ml)

Expiratory reserve volume (ERV) air

that can be evacuated from the lungs after
a tidal expiration (10001200 ml)

Residual volume (RV) air left in the

lungs after strenuous expiration (1200 ml)
Respiratory Capacities

Inspiratory capacity (IC) total amount

of air that can be inspired after a tidal
expiration (IRV + TV)

Functional residual capacity (FRC)

amount of air remaining in the lungs after
a tidal expiration
(RV + ERV)

Vital capacity (VC) the total amount of

exchangeable air (TV + IRV + ERV)

Total lung capacity (TLC) sum of all

lung volumes (approximately 6000 ml in
males)
Dead Space

Anatomical dead space volume of the

conducting respiratory passages (150 ml)

Alveolar dead space alveoli that cease

to act in gas exchange due to collapse or
obstruction

Total dead space sum of alveolar and

anatomical dead spaces
Pulmonary Function Tests

Spirometer an instrument consisting

of a hollow bell inverted over water, used
to evaluate respiratory function

Spirometry can distinguish between:

Obstructive pulmonary disease
increased airway resistance
Restrictive disorders reduction in
total lung capacity from structural or
functional lung changes
Pulmonary Function Tests

Total ventilation total amount of gas

flow into or out of the respiratory tract in
one minute

Forced vital capacity (FVC) gas forcibly

expelled after taking a deep breath

Forced expiratory volume (FEV) the

amount of gas expelled during specific
time intervals of the FVC

Increases in TLC, FRC, and RV may

occur as a result of obstructive disease

Reduction in VC, TLC, FRC, and RV result

from restrictive disease

Alveolar Ventilation

Alveolar ventilation rate (AVR)

measures the flow of fresh gases into and
out of the alveoli during a particular time

Slow, deep breathing increases AVR and

rapid, shallow breathing decreases AVR
Nonrespiratory Air Movements

Most result from reflex action

Examples include: coughing, sneezing,

crying, laughing, hiccuping, and yawning
Basic Properties of Gases: Daltons Law
of Partial Pressures

Total pressure exerted by a mixture of

gases is the sum of the pressures exerted
independently by each gas in the mixture

The partial pressure of each gas is

directly proportional to its percentage in
the mixture
Basic Properties of Gases: Henrys Law

When a mixture of gases is in contact

with a liquid, each gas will dissolve in the
liquid in proportion to its partial pressure

The amount of gas that will dissolve in a

liquid also depends upon its solubility

Various gases in air have different

solubilities:
Carbon dioxide is the most soluble
Oxygen is 1/20th as soluble as carbon
dioxide
Nitrogen is practically insoluble in
plasma
Composition of Alveolar Gas

The atmosphere is mostly oxygen and

nitrogen, while alveoli contain more
carbon dioxide and water vapor

These difference result from:

Gas exchanges in the lungs oxygen
diffuses from the alveoli and carbon
dioxide diffuses into the alveoli
Air is humidified by the conducting
pathways
The mixing of alveolar gas occurs with
each breath
External Respiration: Pulmonary Gas
Exchange

Factors influencing the movement of

oxygen and carbon dioxide across the
respiratory membrane
Partial pressure gradients and gas
solubilities

Matching of alveolar ventilation and

pulmonary blood perfusion
Structural characteristics of the
respiratory membrane
Partial Pressure Gradients and Gas
Solubilities

The partial pressure oxygen (PO2) of

venous blood is 40 mm Hg; the partial
pressure in the alveoli is
104 mm Hg
This steep gradient allows oxygen
partial pressures to rapidly reach
equilibrium (in 0.25 seconds), and thus
blood can move three times as quickly
(0.75 seconds) through the pulmonary
capillary and still be adequately
oxygenated

Although carbon dioxide has a lower

partial pressure gradient:
It is 20 times more soluble in plasma
than oxygen
It diffuses in equal amounts with
oxygen
Ventilation-Perfusion Coupling

Ventilation the amount of gas reaching

the alveoli

Perfusion the blood flow reaching the

alveoli

Ventilation and perfusion must be

tightly regulated for efficient gas exchange

Changes in PCO2 in the alveoli cause

changes in the diameters of the
bronchioles
Passageways servicing areas where
alveolar carbon dioxide is high dilate
Those serving area where alveolar
carbon dioxide is low constrict
Surface Area and Thickness of the
Respiratory Membrane

Respiratory membranes:
Are only 0.5 to 1 mm thick, allowing
for efficient gas exchange
Have a total surface area (in males) of
5070 m2 (40 times that of ones skin)
Thicken if lungs become waterlogged
and edematous, whereby gas exchange
is inadequate and oxygen deprivation
results
Decrease in surface area with
emphysema, when walls of adjacent
alveoli break
Internal Respiration

The factors promoting gas exchange

between systemic capillaries and tissue
cells are the same as those acting in the
lungs

The partial pressures and diffusion

gradients are reversed
PO2 in tissue is always lower than in
systemic arterial blood
PO2 of venous blood draining tissues is
40 mm Hg and PCO2 is 45 mm Hg
Oxygen Transport

Molecular oxygen is carried in the blood

bound to hemoglobin (Hb) within RBCs and
dissolved in plasma
Each hemoglobin molecule binds 4
oxygen in a rapid and reversible
process
The hemoglobin-oxygen combination
is called oxyhemoglobin (HbO2)

Hemoglobin that has

released oxygen is
called reduced
hemoglobin (HHb)
Hemoglobin (Hb)

Saturated hemoglobin when all four

hemes of the molecule are bound to
oxygen

Partially saturated hemoglobin when

one to three hemes are bound to oxygen

The rate in which hemoglobin binds and

releases oxygen is regulated by:
PO2, temperature, blood pH, PCO2, and
the concentration of BPG (an organic
chemical)
These factors insure adequate
delivery of oxygen to tissue cells
Influence of PO2 on Hemoglobin
Saturation

Hemoglobin saturation plotted against

PO2 produces a oxygen-hemoglobin
dissociation curve

98% saturated arterial blood contains

20 ml oxygen per100 ml blood (20 vol %)

As arterial blood flows through

capillaries, 5 ml oxygen are released

The saturation of hemoglobin in arterial

blood explains why breathing deeply
increases the PO2 but has little effect on
oxygen saturation in hemoglobin
Hemoglobin Saturation Curve

Hemoglobin is almost completely

saturated at a PO2 of 70 mm Hg

Further increases in PO2 produce only

small increases in oxygen binding

Oxygen loading and delivery to tissue is

adequate when PO2 is below normal levels

Only 2025% of bound oxygen is

unloaded during one systemic circulation

If oxygen levels in tissues drop:

More oxygen dissociates from

hemoglobin and is used by cells
Respiratory rate or cardiac output
need not increase
Other Factors Influencing Hemoglobin
Saturation

Temperature, H+, PCO2, and BPG:

Modify the structure of hemoglobin
and alter its affinity for oxygen
Increases:
Decrease hemoglobins affinity for
oxygen
Enhance oxygen unloading from
the blood
Decreases act in the opposite manner

These parameters are all high in

systemic capillaries where oxygen
unloading is the goal
Factors That Increase Release of
Oxygen by Hemoglobin

As cells metabolize glucose, carbon

dioxide is released into the blood causing:
Increases in PCO2 and H+ concentration
in capillary blood
Declining pH (acidosis) weakens the
hemoglobin-oxygen bond (Bohr effect)

Metabolizing cells have heat as a

byproduct and the rise in temperature
increases BPG synthesis

All these factors insure oxygen

unloading in the vicinity of working tissue
cells
Hemoglobin-Nitric Oxide Partnership

Nitric oxide (NO) is a vasodilator that

plays a role in blood pressure regulation

Hemoglobin is a vasoconstrictor and a

nitric oxide scavenger (heme destroys NO)

However, as oxygen bind to

hemoglobin:
Nitric oxide binds to a cysteine amino
acid on hemoglobin
Bound nitric oxide is protected from
degradation by hemoglobins iron
Hemoglobin-Nitric Oxide Partnership

The hemoglobin is released as oxygen is

unloaded, causing vasodilation

As deoxygenated hemoglobin picks up

carbon dioxide, it also binds nitric oxide
and carries these gases to the lungs for
unloading
Carbon Dioxide Transport

Carbon dioxide is transported in the

blood in three forms:
Dissolved in plasma 7 to 10%

Chemically bound to hemoglobin

20% is carried in RBCs as
carbaminohemoglobin
Bicarbonate ion in plasma 70% is
transported as bicarbonate (HCO3)
Transport and Exchange of Carbon
Dioxide

Carbon dioxide diffuses into RBCs and

combines with water to form carbonic acid
(H2CO3), which quickly dissociates into
hydrogen ions and bicarbonate ions

In RBCs, carbonic anhydrase reversibly

catalyzes the conversion of carbon dioxide
and water to carbonic acid

At the tissues:
Bicarbonate quickly diffuses from
RBCs into the plasma
Chloride shift to counterbalance the
outrush of negative bicarbonate ions
from the RBCs, chloride ions (Cl) move
from the plasma into the erythrocytes

At the lungs, these processes are

reversed:
Bicarbonate ions move into the RBCs
and bind with hydrogen ions to form
carbonic acid
Carbonic acid is then split by carbonic
anhydrase to release carbon dioxide
and water
Carbon dioxide then diffuses from the
blood into the alveoli
Haldane Effect

The amount of carbon dioxide

transported is markedly affected by the P O2

Haldane effect the lower the PO2 and

hemoglobin saturation with oxygen, the
more carbon dioxide can be carried in the
blood

At the tissues, as more carbon dioxide

enters the blood:
More oxygen dissociates from
hemoglobin (Bohr effect)
More carbon dioxide combines with
hemoglobin, and more bicarbonate ions
are formed

This situation is reversed in pulmonary

circulation
Influence of Carbon Dioxide on Blood pH

The carbonic acidbicarbonate buffer

system resists blood pH changes

If hydrogen ion concentrations in blood

begin to rise, it is removed by combining
with HCO3
If hydrogen ion concentrations begin
to drop, carbonic acid dissociates,
releasing H+

Changes in respiratory rate can also:

Alter blood pH
Provide a fast-acting system to adjust
pH when it is disturbed by metabolic
factors
Control of Respiration: Medullary
Respiratory Centers

The dorsal respiratory group (DRG), or

inspiratory center:
Is located near the root of nerve IX
Appears to be the pacesetting
respiratory center
Excites the inspiratory muscles and
sets eupnea (12-15 breaths/minute)
Becomes dormant during expiration

The ventral respiratory group (VRG) is

involved in forced inspiration and
expiration
Control of Respiration: Pons Respiratory
Centers

Pons centers:
Influence and modify activity of the
medullary centers
Smooth out inspiration and expiration
transitions and vice versa

Pneumotaxic center continuously

inhibits the inspiration center

Apneustic center continuously

stimulates the medullary inspiration center
Respiratory Rhythm

A result of reciprocal inhibition of the

interconnected neuronal networks in the
medulla

Other theories include:

Inspiratory neurons are pacemakers
and have intrinsic automaticity
and rhythmicity
Stretch receptors in the lungs
establish respiratory rhythm
Depth and Rate of Breathing

Inspiratory depth is determined by how

actively the respiratory center stimulates
the respiratory muscles

Rate of respiration is determined by

how long the inspiratory center is active

Respiratory centers in the pons and

medulla are sensitive to both excitatory
and inhibitory stimuli
Depth and Rate of Breathing: Reflexes

Pulmonary irritant reflexes irritants

promote reflexive constriction of air
passages

Inflation reflex (Hering-Breuer) stretch

receptors in the lungs are stimulated by
lung inflation

Upon inflation, inhibitory signals are

sent to the medullary inspiration center to
end inhalation and allow expiration
Depth and Rate of Breathing: Higher
Brain Centers

Hypothalamic controls act through the

limbic system to modify rate and depth of
respiration
Examples: breath holding that occurs
in anger

A rise in body temperature acts to

increase respiratory rate

Cortical controls direct signals from

the cerebral motor cortex that bypass
medullary controls
Examples: voluntary breath holding,
taking a deep breath
Depth and Rate of Breathing: PCO2

Changing PCO2 levels are monitored by

chemoreceptors of the brain stem

Carbon dioxide in the blood diffuses into

the cerebrospinal fluid where it is hydrated

Resulting carbonic acid dissociates,

releasing hydrogen ions

PCO2 levels rise (hypercapnia) resulting

in increased depth and rate of breathing

Hyperventilation increased depth and

rate of breathing that:
Quickly flushes carbon dioxide from
the blood
Occurs in response to hypercapnia

Though a rise CO2 acts as the original

stimulus, control of breathing at rest is
regulated by the hydrogen ion
concentration in the brain

Hypoventilation slow and shallow

breathing due to abnormally low
PCO2 levels
Apnea (breathing cessation) may
occur until PCO2 levels rise

Arterial oxygen levels are monitored by

the aortic and carotid bodies

Substantial drops in arterial PO2 (to 60

mm Hg) are need before oxygen levels
become a major stimulus for increased
ventilation

If carbon dioxide is not removed (e.g.,

as in emphysema and chronic bronchitis),
chemoreceptors become unresponsive to
PCO2chemical stimuli

In such cases, PO2 levels become the

principle respiratory stimulus (hypoxic
drive)
Depth and Rate of Breathing: Arterial
pH

Changes in arterial pH can modify

respiratory rate even if carbon dioxide and
oxygen levels are normal

Increased ventilation in response to

falling pH is mediated by peripheral
chemoreceptors

Acidosis may reflect:

Carbon dioxide retention
Accumulation of lactic acid
Excess fatty acids in patients with
diabetes mellitus

Respiratory system controls will attempt

to raise the pH by increasing respiratory
rate and depth
Respiratory Adjustments: Exercise

Respiratory adjustments are geared to

both the intensity and duration of exercise

During vigorous exercise:

Ventilation can increase 20 fold
Breathing becomes deeper and more
vigorous, but respiratory rate may not
be significantly changed (hyperpnea)

Exercise-enhanced breathing is not

prompted by an increase in PCO2 nor a
decrease PO2 or pH
These levels remain surprisingly
constant during exercise

As exercise begins:
Ventilation increases abruptly, rises
slowly, and reaches a steady-state

When exercise stops:

Ventilation declines suddenly, then
gradually decreases to normal

Neural factors bring about the above

changes, including:
Psychic stimuli
Cortical motor activation
Excitatory impulses from
proprioceptors in muscles
Respiratory Adjustments: High Altitude

The body responds to quick movement

to high altitude (above 8000ft) with
symptoms of acute mountain sickness
headache, shortness of breath, nausea,
and dizziness

Acclimatization respiratory and

hematopoietic adjustments to altitude
include:
Increased ventilation 2-3 L/min
higher than at sea level
Chemoreceptors become more
responsive to PCO2
Substantial decline in PO2 stimulates
peripheral chemoreceptors
Chronic Obstructive Pulmonary Disease
(COPD)

Exemplified by chronic bronchitis and

obstructive emphysema

Patients have a history of:

Smoking
Dyspnea, where labored breathing
occurs and gets progressively worse
Coughing and frequent pulmonary
infections

COPD victims develop respiratory failure

accompanied by hypoxemia, carbon
dioxide retention, and respiratory acidosis
Asthma

Characterized by dyspnea, wheezing,

and chest tightness

Active inflammation of the airways

precedes bronchospasms

Airway inflammation is an immune

response caused by release of IL-4 and IL5, which stimulate IgE and recruit
inflammatory cells

Airways thickened with inflammatory

exudates magnify the effect of
bronchospasms
Tuberculosis

Infectious disease caused by the

bacterium Mycobacterium tuberculosis

Symptoms include fever, night sweats,

weight loss, a racking cough, and splitting
headache

Treatment entails a 12-month course of

antibiotics
Lung Cancer

Accounts for 1/3 of all cancer deaths in

the US

90% of all patients with lung cancer

were smokers

The three most common types are:

Squamous cell carcinoma (20-40% of
cases) arises in bronchial epithelium
Adenocarcinoma (25-35% of cases)
originates in peripheral lung area
Small cell carcinoma (20-25% of
cases) contains lymphocyte-like cells
that originate in the primary bronchi
and subsequently metastasize
Developmental Aspects

Olfactory placodes invaginates into

olfactory pits by the 4th week

Laryngotracheal buds are present by

the 5th week

Mucosae of the bronchi and lung alveoli

are present by the 8th week

By the 28th week, a baby born

prematurely can breathe on its own

During fetal life, the lungs are filled with

fluid and blood bypasses the lungs

Gas exchange takes place via the

placenta
Developmental Aspects

At birth, respiratory centers are

activated, alveoli inflate, and lungs begin
to function

Respiratory rate is highest in newborns

and slows until adulthood

Lungs continue to mature and more

alveoli are formed until young adulthood

Respiratory efficiency decreases in old

age
The Digestive System
Digestive System: Overview

The alimentary canal or gastrointestinal

(GI) tract digests and absorbs food

Alimentary canal mouth, pharynx,

esophagus, stomach, small intestine, and
large intestine

Accessory digestive organs teeth,

tongue, gallbladder, salivary glands, liver,
and pancreas
Digestive Process

The GI tract is a disassembly line

Nutrients become more available to
the body in each step

There are six essential activities:

ingestion, propulsion, and mechanical
digestion
chemical digestion, absorption, and
defecation
Essential Activities of Digestion

Ingestion taking food into the

digestive tract

Propulsion swallowing and peristalsis

Peristalsis waves of contraction and
relaxation of muscles in the organ walls

Mechanical digestion chewing, mixing,

and churning food

Chemical digestion catabolic

breakdown of food

Absorption movement of nutrients

from the GI tract to the blood or lymph

Defecation elimination of indigestible

solid wastes
GI Tract

External environment for the digestive

process

Regulation of digestion involves:

Mechanical and chemical stimuli
stretch receptors, osmolarity, and
presence of substrate in the lumen
Extrinsic control by CNS centers
Intrinsic control by local centers
Receptors of the GI Tract

Mechano- and chemoreceptors respond

to:
Stretch, osmolarity, and pH
Presence of substrate, and end
products of digestion

They initiate reflexes that:

Activate or inhibit digestive glands
Mix lumen contents and move them
along
Nervous Control of the GI Tract

Intrinsic controls
Nerve plexuses near the GI tract
initiate short reflexes
Short reflexes are mediated by local
enteric plexuses (gut brain)

Extrinsic controls
Long reflexes arising within or outside
the GI tract
Involve CNS centers and extrinsic
autonomic nerves
Digestive System Organs and
Peritoneum

Peritoneum serous membrane of the

abdominal cavity
Visceral covers external surface of
most digestive organs
Parietal lines the body wall

Peritoneal cavity
Lubricates digestive organs
Allows them to slide across one
another

Mesentery double layer of peritoneum

that provides:
Vascular and nerve supplies to the
viscera
A means to hold digestive organs in
place and store fat

Retroperitoneal organs organs outside

the peritoneum

Peritoneal organs (intraperitoneal)

organs surrounded by peritoneum
Homeostatic Imbalance

Peritonitis inflammation of the

peritoneum caused by a piercing wound,
perforating ulcer, or burst appendix

Often, infected membranes tend to stick

together localizing the infection

Generalized or widespread peritonitis is

dangerous and often lethal

Treatment includes removing infectious

debris and massive doses of antibiotics
Blood Supply: Splanchnic Circulation

Arteries and the organs they serve

include
The hepatic, splenic, and left gastric:
spleen, liver, and stomach

Inferior and superior mesenteric:

small and large intestines

Hepatic portal circulation:

Collects nutrient-rich venous blood
from the digestive viscera
Delivers it to the liver for metabolic
processing and storage
Histology of the Alimentary Canal

From esophagus to the anal canal the

walls of the GI tract have the same four
tunics
From the lumen outward they are the
mucosa, submucosa, muscularis
externa, and serosa

Each tunic has a predominant tissue

type and specific digestive function
Mucosa

Moist epithelial layer that lines the

lumen of the alimentary canal

Its three major functions are:

Secretion of mucus
Absorption of the end products of
digestion
Protection against infectious disease

Consists of three layers: a lining

epithelium, lamina propria, and muscularis
mucosae
Mucosa: Epithelial Lining

Consists of simple columnar epithelium

and mucus-secreting goblet cells

The mucus secretions:

Protect digestive organs from
digesting themselves
Ease food along the tract

Stomach and small intestine mucosa

contain:
Enzyme-secreting cells and
Hormone-secreting cells (making
them endocrine and digestive organs)
Mucosa: Lamina Propria and Muscularis
Mucosae

Lamina Propria
Loose areolar and reticular connective
tissue
Nourish the epithelium and absorb
nutrients
Contains lymph nodes (part of MALT)
important in defense against bacteria

Muscularis mucosae smooth muscle

cells that produce local movements of
mucosa
Mucosa: Other Sublayers

Submucosa dense connective tissue

containing elastic fibers, blood and
lymphatic vessels, lymph nodes, and
nerves

Muscularis externa responsible for

segmentation and peristalsis

Serosa the protective visceral

peritoneum
Replaced by the fibrous adventitia in
the esophagus
Retroperitoneal organs have both an
adventitia and serosa
Enteric Nervous System

Composed of two major intrinsic nerve

plexuses
Submucosal nerve plexus regulates
glands and smooth muscle in the
mucosa
Myenteric nerve plexus:
Major nerve supply that controls GI
tract mobility

Segmentation and peristalsis are largely

automatic involving local reflex arcs

Linked to the CNS via long autonomic

reflex arc
Mouth

Oral or buccal cavity:

Is bounded by lips, cheeks, palate,
and tongue
Has the oral orifice as its anterior
opening
Is continuous with the oropharynx
posteriorly

To withstand abrasions:
The mouth is lined with stratified
squamous epithelium
The gums, hard palate, and dorsum of
the tongue are slightly keratinized
Lips and Cheeks

Have a core of skeletal muscles

Lips: orbicularis oris
Cheeks: buccinators

Vestibule bounded by the lips and

cheeks externally and teeth and gums
internally

Oral cavity proper area that lies within

the teeth and gums

Labial frenulum median fold that joins

the internal aspect of each lip to the gum
Palate

Hard palate underlain by palatine

bones and palatine processes of the
maxillae
Assists the tongue in chewing
Slightly corrugated on either side of
the raphe (midline ridge)

Soft palate mobile fold formed mostly

of skeletal muscle

Closes off the nasopharynx during

swallowing
Uvula projects downward from its free
edge

Palatoglossal and palatopharyngeal

arches form the borders of the fauces
Tongue

Occupies the floor of the mouth and fills

the oral cavity when mouth is closed

Functions include:
Gripping and repositioning food
during chewing
Mixing food with saliva and forming
the bolus
Initiation of swallowing, and speech

Intrinsic muscles change the shape of

the tongue

Extrinsic muscles alter the tongues

position

Lingual frenulum secures the tongue to

the floor of the mouth
Homeostatic Imbalance

Ankyloglossia congenital situation

where the lingual frenulum is extremely
short

Commonly referred to as being tonguetied

Corrected surgically by cutting the

frenulum
Tongue

Superior surface bears three types of

papillae
Filiform give the tongue roughness
and provide friction
Fungiform scattered widely over the
tongue and give it a reddish hue
Circumvallate V-shaped row in back
of tongue

Sulcus terminalis groove that

separates the tongue into two areas:
Anterior 2/3 residing in the oral cavity
Posterior third residing in the
oropharynx
Salivary Glands

Produce and secrete saliva that:

Cleanses the mouth
Moistens and dissolves food
chemicals
Aids in bolus formation
Contains enzymes that breakdown
starch

Three pairs of extrinsic glands parotid,

submandibular, and sublingual

Intrinsic salivary glands (buccal glands)

scattered throughout the oral mucosa

Parotid lies anterior to the ear

between the masseter muscle and skin
Parotid duct opens into the vestibule
next to the second upper molar

Submandibular lies along the medial

aspect of the mandibular body
Its ducts open at the base of the
lingual frenulum

Sublingual lies anterior to the

submandibular gland under the tongue
It opens via 10-12 ducts into the floor
of the mouth
Homeostatic Imbalance

Mumps inflammation of the parotid

glands caused by myxovirus
Signs and symptoms moderate fever
and pain in swallowing acidic foods
In adult males, mumps carries 25%
risk that testes may become infected,
leading to sterility
Saliva: Source and Composition

Secreted from serous and mucous cells

of salivary glands

A 97-99.5% water, hypo-osmotic,

slightly acidic solution containing
Electrolytes Na+, K+, Cl, PO42, HCO3
Digestive enzyme salivary amylase
Proteins mucin, lysozyme, defensins,
and IgA
Metabolic wastes urea and uric acid
Control of Salivation

Intrinsic glands keep the mouth moist

Extrinsic salivary glands secrete serous,

enzyme-rich saliva in response to:
Ingested food which stimulates
chemoreceptors and pressoreceptors
The thought of food

Strong sympathetic stimulation inhibits

salivation and results in dry mouth
Teeth

Primary and permanent dentitions have

formed by age 21

Primary 20 deciduous teeth that erupt

at intervals between 6 and 24 months

Permanent enlarge and develop

causing the root of deciduous teeth to be
resorbed and fall out between the ages of
6 and 12 years
All but the third molars have erupted
by the end of adolescence
There are usually 32 permanent teeth
Classification of Teeth

Teeth are classified according to their

shape and function

Incisors chisel-shaped teeth adapted

for cutting or nipping
Canines conical or fanglike teeth
that tear or pierce
Premolars (bicuspids) and molars
have broad crowns with rounded tips
and are best suited for grinding or
crushing

During chewing, upper and lower

molars lock together generating crushing
force
Dental Formula

A shorthand way of indicating the

number and relative position of teeth
Written as ratio of upper to lower
teeth for the mouth
Primary: 2I (incisors), 1C (canine), 2M
(molars)
Permanent: 2I, 1C, 2PM (premolars),
3M
Tooth Structure

Two main regions crown and the root

Crown exposed part of the tooth

above the gingiva (gum)

Enamel acelluar, brittle material

composed of calcium salts and
hydroxyapatite crystals is the hardest
substance in the body
Encapsules the crown of the tooth

Root portion of the tooth embedded in

the jawbone

Neck constriction where the crown and

root come together

Cementum calcified connective tissue

Covers the root
Attaches it to the periodontal
ligament

Periodontal ligament
Anchors the tooth in the alveolus of
the jaw
Forms the fibrous joint called a
gomaphosis

Gingival sulcus depression where the

gingival borders the tooth

Dentin bonelike material deep to the

enamel cap that forms the bulk of the
tooth

Pulp cavity cavity surrounded by

dentin that contains pulp

Pulp connective tissue, blood vessels,

and nerves

Root canal portion of the pulp cavity

that extends into the root

Apical foramen proximal opening to

the root canal

Odontoblasts secrete and maintain

dentin throughout life
Homeostatic Imbalance

Root canal therapy blows to the teeth

can cause swelling and consequently
pinch off the blood supply to the tooth
The nerve dies and may become
infected with bacteria
Then the cavity is sterilized and filled
with an inert material
The tooth is then capped
Tooth and Gum Disease

Dental caries gradual demineralization

of enamel and dentin by bacterial action
Dental plaque, a film of sugar,
bacteria, and mouth debris, adheres to
teeth
Acid produced by the bacteria in the
plaque dissolves calcium salts
Without these salts, organic matter is
digested by proteolytic enzymes
Daily flossing and brushing help
prevent caries by removing forming
plaque
Tooth and Gum Disease: Periodontitis

Gingivitis as plaque accumulates, it

calcifies and forms calculus, or tartar

Accumulation of calculus:
Disrupts the seal between the
gingivae and the teeth
Puts the gums at risk for infection

Periodontitis serious gum disease

resulting from an immune response

Attack of the immune system against

intruders:
Also carves pockets around the teeth
and
Dissolves bone away
Pharynx

From the mouth, the oro- and

laryngopharynx allow passage of:
Food and fluids to the esophagus
Air to the trachea

Lined with stratified squamous

epithelium and mucus glands

Has two skeletal muscle layers

Inner longitudinal
Outer pharyngeal constrictors
Esophagus

Muscular tube going from the

laryngopharynx to the stomach

Travels through the mediastinum and

pierces the diaphragm

Joins the stomach at the cardiac orifice

Homeostatic Imbalance

Heartburn (gastroesophageal reflux

disease or GERD) burning, radiating
substernal pain caused by acidic gastric
juice regurgitated into the esophagus

Caused by excess eating or drinking,

and conditions that force abdominal
contents superiorly (e.g., extreme obesity,
pregnancy, and running)
Hiatus hernia structural abnormality
in which the superior part of the
stomach protrudes slightly above the
diaphragm

Prolonged episodes can lead to

esophagitis, ulcers, and cancer
Esophageal Characteristics

Esophageal mucosa nonkeratinized

stratified squamous epithelium

The empty esophagus is folded

longitudinally and flattens when food is
present

Glands secrete mucus as a bolus moves

through the esophagus

Muscularis changes from skeletal

(superiorly) to smooth muscle (inferiorly)
Digestive Processes in the Mouth

Food is ingested

Mechanical digestion begins (chewing)

Propulsion is initiated by swallowing

Salivary amylase begins chemical

breakdown of starch

The pharynx and esophagus serve as

conduits to pass food from the mouth to
the stomach
Deglutition (Swallowing)

Involves the coordinated activity of the

tongue, soft palate, pharynx, esophagus
and 22 separate muscle groups

Buccal phase bolus is forced into the

oropharynx

Pharyngeal-esophageal phase
controlled by the medulla and lower pons
All routes except into the digestive
tract are sealed off

Peristalsis moves food through the

pharynx to the esophagus
Stomach

Chemical breakdown of proteins begins

and food is converted to chyme

Cardiac region surrounds the cardiac

orifice

Fundus dome-shaped region beneath

the diaphragm

Body midportion of the stomach

Pyloric region made up of the antrum

and canal which terminates at the pylorus

The pylorus is continuous with the

duodenum through the pyloric sphincter

Greater curvature entire extent of the

convex lateral surface

Lesser curvature concave medial

surface

Lesser omentum runs from the liver to

the lesser curvature

Greater omentum drapes inferiorly

from the greater curvature to the small
intestine

Nerve supply sympathetic and

parasympathetic fibers of the autonomic
nervous system

Blood supply celiac trunk, and

corresponding veins (part of the hepatic
portal system)
Microscopic Anatomy of the Stomach

Muscularis has an additional oblique

layer that
Allows the stomach to churn, mix and
pummel food physically
Breaks down food into smaller
fragments

Epithelial lining is composed of:

Goblet cells that produce a coat of
alkaline mucus

Gastric pits containing gastric glands

that secrete:
Gastric juice
Mucus
Gastrin
Glands of the Stomach Fundus and Body

Gastric glands of the fundus and body

have a variety of secretory cells
Mucous neck cells secrete acid
mucus
Parietal (oxyntic) cells secrete HCl
and intrinsic factor
Chief (zymogenic) cells produce
pepsinogen
Pepsinogen is activated to pepsin
by:
HCl in the stomach
Pepsin itself by a positive
feedback mechanism
Enteroendocrine cells secrete
gastrin, histamine, endorphins,
serotonin, cholecystokinin (CCK), and
somatostatin into the lamina propria
Stomach Lining

The stomach is exposed to the harshest

conditions in the digestive tract

To keep from digesting itself, the

stomach has a mucosal barrier with:

A thick coat of bicarbonate-rich mucus

on the stomach wall
Epithelial cells that are joined by tight
junctions
Gastric glands that have cells
impermeable to HCl

Damaged epithelial cells are quickly

replaced
Digestion in the Stomach

The stomach:
Holds ingested food
Degrades it both physically and
chemically
Delivers chyme to the small intestine
Enzymatically digests proteins with
pepsin
Secretes intrinsic factor required for
absorption of vitamin B12
Regulation of Gastric Secretion

Neural and hormonal mechanisms

regulate the release of gastric juice

Stimulatory and inhibitory events occur

in three phases
Cephalic (reflex) phase: prior to food
entry
Gastric phase: once food enters the
stomach
Intestinal phase: as partially digested
food enters the duodenum
Cephalic Phase

Excitatory events include:

Sight or thought of food
Stimulation of taste or smell receptors

Inhibitory events include:

Loss of appetite or depression
Decrease in stimulation of the
parasympathetic division
Gastric Phase

Excitatory events include:

Stomach distension
Activation of stretch receptors (neural
activation)
Activation of chemoreceptors by
peptides, caffeine, and rising pH
Release of gastrin to the blood

Inhibitory events include:

A pH lower than 2
Emotional upset which overrides the
parasympathetic division
Intestinal Phase

Excitatory phase low pH and partially

digested food enters the duodenum

Inhibitory phase distension of

duodenum, presence of fatty, acidic, or
hypertonic chyme, and/or irritants in the
duodenum

Initiate inhibition of local reflexes and

vagal nuclei
Closes the pyloric sphincter
Releases enterogastrones that inhibit
gastric secretion
Regulation and Mechanism of HCl
Secretion

HCl secretion is stimulated by ACh,

histamine, and gastrin

All work through second messenger

systems

Release of hydrochloric acid:

Is low if only one ligand binds to
parietal cells
Is prolific if all three ligands bind to
parietal cells

Antihistamines and cimetidine block

H2 receptors and decrease HCl release
Response of the Stomach to Filling

Stomach pressure remains constant

until about 1L of food is ingested

Relative unchanging pressure results

from reflex-mediated relaxation and
plasticity

Reflex-mediated events include:

Receptive relaxation as food travels
in the esophagus, stomach muscles
relax
Adaptive relaxation the stomach
dilates in response to gastric filling

Plasticity intrinsic ability of smooth

muscle to exhibit the stress-relaxation
response
Gastric Contractile Activity

Peristaltic waves move toward the

pylorus at the rate of 3 per minute

This basic electrical rhythm (BER) is

initiated by pacemaker cells (cells of Cajal)

Most vigorous peristalsis and mixing

occurs near the pylorus

Chyme is either:
Delivered in small amounts to the
duodenum or
Forced backward into the stomach for
further mixing
Regulation of Gastric Emptying

Gastric emptying is regulated by:

The neural enterogastric reflex
Hormonal (enterogastrone)
mechanisms

These mechanisms inhibit gastric

secretion and duodenal filling

Carbohydrate-rich chyme moves

through the duodenum quickly

Fat-laden chyme is digested more

slowly causing food to remain in the
stomach longer
Homeostatic Imbalance

Vomiting (emesis) the stomach

empties via a different route (oral)
Causes include extreme stretching,
irritants such as bacterial toxins,
excessive alcohol, spicy foods, and
certain drugs

The emetic center of the medulla

initiates a number of motor responses
Diaphragm and abdominal wall
muscle contract
Cardiac sphincter relaxes and soft
palate closes off the nasal passages

Excessive vomiting can cause

dehydration and upset electrolyte and pH
balance
Small Intestine: Gross Anatomy

Runs from pyloric sphincter to the

ileocecal valve

Has three subdivisions: duodenum,

jejunum, and ileum

The bile duct and main pancreatic duct:

Join the duodenum at the
hepatopancreatic ampulla
Are controlled by the sphincter of
Oddi

The jejunum extends from the

duodenum to the ileum

The ileum joins the large intestine at the

ileocecal valve
Microscopic Anatomy of the Small
Intestine

Structural modifications of the small

intestine wall increase surface area
Plicae circulares: deep circular folds of
the mucosa and submucosa
Villi: fingerlike extensions of the
mucosa
Microvilli: tiny projections of
absorptive mucosal cells plasma
membranes
Small Intestine: Histology of the Wall

The epithelium of the mucosa is made

up of:
Absorptive cells and goblet cells
Interspersed T cells (intraepithelial
lymphocytes), and
Enteroendocrine cells

Intestinal crypts cells secrete intestinal

juice

Peyers patches are found in the

submucosa

Brunners glands in the duodenum

secrete alkaline mucus
Intestinal Juice

Secreted by intestine glands in

response to distension or irritation of the
mucosa

It is slightly alkaline and isotonic with

blood plasma

Is largely water, enzyme-poor, but

contains mucus
Liver

The largest gland in the body

Superficially has four lobes right, left,

caudate, and quadrate

The falciform ligament:

Separates the right and left lobes
anteriorly
Suspends the liver from the
diaphragm and anterior abdominal wall

The ligamentum teres:

Is a remnant of the fetal umbilical
vein
Runs along the free edge of the
falciform ligament
Liver: Associated Structures

The lesser omentum anchors the liver to

the stomach

The hepatic blood vessels enter the

liver at the porta hepatis

The gallbladder rests in a recess on the

inferior surface of the right lobe

Bile leaves the liver via

Bile ducts which fuse into the
common hepatic duct
The common hepatic duct fuses with
the cystic duct
These two ducts form the bile duct
Microscopic Anatomy of the Liver

Hexagonal-shaped liver lobules are the

structural and functional units of the liver
Composed of hepatocyte (liver cell)
plates radiating outward from a central
vein
Portal triads are found at each of the
six corners of each liver lobule

Portal triads consist of a bile duct and

Hepatic artery supplies oxygen-rich
blood to the liver
Hepatic portal vein carries venous
blood with nutrients from digestive
viscera

Liver sinusoids enlarged, leaky

capillaries located between hepatic plates

Kupffer cells hepatic macrophages

found in liver sinusoids

Hepatocytes functions include:

Production of bile
Processing bloodborne nutrients
Storage of fat-soluble vitamins
Detoxification

Secreted bile flows between

hepatocytes toward the bile ducts in the
portal triads
Homeostatic Imbalance

Hepatitis inflammation of the liver

often due to viral infection

Viruses causing hepatitis are catalogued

has HVA through HVF

HVA and HVE are transmitted enterically

and cause self-limiting infections

Hepatitis B is transmitted via blood

transfusions, contaminated needles, and
sexual contact, and increases the risk of
liver cancer

Hepatitis C produces chronic liver

infection

Nonviral hepatitis is caused by drug

toxicity and wild mushroom poisoning

Cirrhosis diffuse and progressive

chronic inflammation of the liver

Typically results from chronic alcoholism

or severe chronic hepatitis

The liver becomes fatty and fibrous and

its activity is depressed

Scar tissue obstructs blood flow in the

hepatic portal system causing portal
hypertension
Composition of Bile

A yellow-green, alkaline solution

containing bile salts, bile pigments,
cholesterol, neutral fats, phospholipids,
and electrolytes

Bile salts are cholesterol derivatives

that:
Emulsify fat
Facilitate fat and cholesterol
absorption
Help solubilize cholesterol

Enterohepatic circulation recycles bile

salts

The chief bile pigment is bilirubin, a

waste product of heme
The Gallbladder

Thin-walled, green muscular sac on the

ventral surface of the liver

Stores and concentrates bile by

absorbing its water and ions

Releases bile via the cystic duct which

flows into the bile duct
Regulation of Bile Release

Acidic, fatty chyme causes the

duodenum to release:

Cholecystokinin (CCK) and secretin

into the bloodstream

Bile salts and secretin transported in

blood stimulate the liver to produce bile

Vagal stimulation causes weak

contractions of the gallbladder

Cholecystokinin causes:
The gallbladder to contract
The hepatopancreatic sphincter to
relax

As a result, bile enters the duodenum

Homeostatic Imbalance

Gallstones crystallization of
cholesterol which can obstruct the flow of
bile

Current treatments include: dissolving

the crystals with drugs, pulverizing them
with ultrasound, vaporizing them with
lasers, and surgical removal of the
gallbladder

Obstructive jaundice yellowish skin

caused by bile pigments deposited in the
skin
Due to blocked bile ducts
Pancreas

Location
Lies deep to the greater curvature of
the stomach
The head is encircled by the
duodenum and the tail abuts the spleen

Exocrine function
Secretes pancreatic juice which
breaks down all categories of foodstuff
Acini (clusters of secretory cells)
contain zymogen granules with
digestive enzymes

The pancreas also has an endocrine

function release of insulin and glucagon
Composition and Function of Pancreatic
Juice

Water solution of enzymes and

electrolytes (primarily HCO3)
Neutralizes acid chyme
Provides optimal environment for
pancreatic enzymes

Enzymes are released in inactive form

and activated in the duodenum

Examples include
Trypsinogen is activated to trypsin
Procarboxypeptidase is activated to
carboxypeptidase

Active enzymes secreted

Amylase, lipases, and nucleases
These enzymes require ions or bile for
optimal activity
Regulation of Pancreatic Secretion

Secretin and CCK are released when

fatty or acidic chyme enters the
duodenum

CCK and secretin enter the bloodstream

Upon reaching the pancreas:

CCK induces the secretion of enzymerich pancreatic juice
Secretin causes secretion of
bicarbonate-rich pancreatic juice

Vagal stimulation also causes release of

pancreatic juice
Digestion in the Small Intestine

As chyme enters the duodenum

Carbohydrates and proteins are only
partially digested
No fat digestion has taken place

Digestion continues in the small

intestine
Chyme is released slowly into the
duodenum
Because it is hypertonic and has low
pH, mixing is required for proper
digestion
Required substances needed are
supplied by the liver
Virtually all nutrient absorption takes
place in the small intestine
Motility of the Small Intestine

The most common motion of the small

intestine is segmentation
It is initiated by intrinsic pacemaker
cells (Cajal cells)
Moves contents steadily toward the
ileocecal valve

After nutrients have been absorbed:

Peristalsis begins with each wave
starting distal to the previous
Meal remnants, bacteria, mucosal
cells, and debris are moved into the
large intestine
Control of Motility

Local enteric neurons of the GI tract

coordinate intestinal motility

Cholinergic neurons cause:

Contraction and shortening of the
circular muscle layer
Shortening of longitudinal muscle
Distension of the intestine

Other impulses relax the circular muscle

The gastroileal reflex and gastrin:

Relax the ileocecal sphincter
Allow chyme to pass into the large
intestine
Large Intestine

Has three unique features:

Teniae coli three bands of

longitudinal smooth muscle in its
muscularis
Haustra pocketlike sacs caused by
the tone of the teniae coli
Epiploic appendages fat-filled
pouches of visceral peritoneum

Is subdivided into the cecum, appendix,

colon, rectum, and anal canal

The saclike cecum:

Lies below the ileocecal valve in the
right iliac fossa
Contains a wormlike vermiform
appendix
Homeostatic Imbalance

Appendicitis inflammation of the

appendix resulting from blockage that
traps infectious bacteria in its lumen

If the appendix ruptures, feces

containing bacteria spray over the
abdominal contents causing peritonitis

Treatment is surgical removal of the

appendix
Colon

Has distinct regions: ascending colon,

hepatic flexure, transverse colon, splenic
flexure, descending colon, and sigmoid
colon

The transverse and sigmoid portions are

anchored via mesenteries called
mesocolons

The sigmoid colon joins the rectum

The anal canal, the last segment of the

large intestine, opens to the exterior at the
anus
Valves and Sphincters of the Rectum
and Anus

Three valves of the rectum stop feces

from being passed with gas

The anus has two sphincters:

Internal anal sphincter composed of
smooth muscle
External anal sphincter composed of
skeletal muscle

These sphincters are closed except

during defecation
Large Intestine: Microscopic Anatomy

Colon mucosa is simple columnar

epithelium except in the anal canal

Has numerous deep crypts lined with

goblet cells

Anal canal mucosa is stratified

squamous epithelium

Anal sinuses exude mucus and

compress feces

Superficial venous plexuses are

associated with the anal canal

Inflammation of these veins results in

itchy varicosities called hemorrhoids
Bacterial Flora

The bacterial flora of the large intestine

consist of:
Bacteria surviving the small intestine
that enter the cecum and
Those entering via the anus

These bacteria:
Colonize the colon
Ferment indigestible carbohydrates
Release irritating acids and gases
(flatus)
Synthesize B complex vitamins and
vitamin K
Functions of the Large Intestine

Other than digestion of enteric bacteria,

no further digestion takes place

Vitamins, water, and electrolytes are

reclaimed

Its major function is propulsion of fecal

material toward the anus

Though essential for comfort, the colon

is not essential for life
Motility of the Large Intestine

Haustral contractions
Slow segmenting movements that
move the contents of the colon
Haustra sequentially contract as they
are stimulated by distension

Presence of food in the stomach:

Activates the gastrocolic reflex
Initiates peristalsis that forces
contents toward the rectum
Homeostatic Imbalance

Diverticulosis small herniation

(diverticula) of the mucosa of the colon
walls caused by lack of bulk in the colon

Most common in the sigmoid colon in

people over 70

Diverticulitis inflamed diverticula that

can be life threatening if the diverticula
rupture
Defecation

Distension of rectal walls caused by

feces
Stimulates contraction of the rectal
walls
Relaxes the internal anal sphincter

Voluntary signals stimulate relaxation of

the external anal sphincter and defecation
occurs
Homeostatic Imbalance

Diarrhea watery stool resulting from

any condition that rushes food residue
through the large intestine too quickly
This causes insufficient time for water
absorption

Prolonged diarrhea may result in

dehydration and electrolyte imbalance

Constipation hard stool that is difficult

to pass resulting from residues staying in
the intestine too long
May result from lack of fiber in the
diet
Food Poisoning: Salmonella

Salmonella is spread by:

Contaminated eggs and egg products
Infected food handlers with fecescontaminated hands

Salmonella can cause:

Bacteremia 4 to 7 days after infection
Endocarditis, thrombi, bone infections,
arthritis, and meningitis

Diagnosis is by positive stool samples

Salmonellosis is treated
symptomatically
Chemical Digestion: Carbohydrates

Absorption: via cotransport with Na+,

and facilitated diffusion
Enter the capillary bed in the villi
Transported to the liver via the
hepatic portal vein

Enzymes used: salivary amylase,

pancreatic amylase, and brush border
enzymes
Chemical Digestion: Proteins

Absorption: similar to carbohydrates

Enzymes used: pepsin in the stomach

Enzymes acting in the small intestine

Pancreatic enzymes trypsin,
chymotrypsin, and carboxypeptidase
Brush border enzymes
aminopeptidases, carboxypeptidases,
and dipeptidases
Chemical Digestion: Fats

Absorption: Diffusion into intestinal cells

where they
Combine with proteins and extrude
chylomicrons
Enter lacteals and are transported to
systemic circulation via lymph
Glycerol and short chain fatty acids

 are absorbed into the capillary

blood in villi
transported via the hepatic portal
vein

Enzymes/chemicals used: bile salts and

pancreatic lipase
Fatty Acid Absorption

Fatty acids and monoglycerides enter

intestinal cells via diffusion

They are combined with proteins within

the cells

Resulting chylomicrons are extruded

They enter lacteals and are transported

to the circulation via lymph
Chemical Digestion: Nucleic Acids

Absorption: active transport via

membrane carriers

Absorbed in villi and transported to liver

via hepatic portal vein

Enzymes used: pancreatic

ribonucleases and deoxyribonuclease in
the small intestines
Electrolyte Absorption

Most ions are actively absorbed along

the length of small intestine
Na+ is coupled with absorption of
glucose and amino acids
Ionic iron is transported into mucosal
cells where it binds to ferritin

Anions passively follow the electrical

potential established by Na+

K+ diffuses across the intestinal mucosa

in response to osmotic gradients

Ca2+ absorption:
Is related to blood levels of ionic
calcium
Is regulated by Vitamin D and
parathyroid hormone (PTH)
Water Absorption

95% of water is absorbed in the small

intestines by osmosis

Water moves in both directions across

intestinal mucosa

Net osmosis occurs whenever a

concentration gradient is established by
active transport of solutes into the
mucosal cells

Water uptake is coupled with solute

uptake, and as water moves into mucosal
cells, substances follow along their
concentration gradients
Malabsorption of Nutrients

Results from anything that interferes

with delivery of bile or pancreatic juice

Factors that damage the intestinal

mucosa (e.g., bacterial infection)

Gluten enteropathy (adult celiac

disease) gluten damages the intestinal
villi and reduces the length of microvilli
Treated by eliminating gluten from the
diet (all grains but rice and corn)
Embryonic Development of the
Digestive System

3rd week endoderm has folded and

foregut and hindgut have formed

The midgut is open and continuous with

the yolk sac

Mouth and anal openings are nearly

formed

8th week accessory organs are

budding from endoderm
Homeostatic Imbalance

Cleft palate palatine bones, palatine

process of the maxillae (or both) fail to
fuse

Tracheoesophageal fistula opening

between the esophagus and trachea

Cystic fibrosis impairs pancreatic

activity
Developmental Aspects

During fetal life, nutrition is via the

placenta, but the GI tract is stimulated
toward maturity by amniotic fluid
swallowed in utero

At birth, feeding is an infants most

important function and is enhanced by
Rooting reflex (helps infant find the
nipple) and sucking reflex (aid in
swallowing)

Digestive system has few problems until

the onset of old age

During old age the GI tract activity

declines, absorption is less efficient, and
peristalsis is slowed
Cancer

Stomach and colon cancers rarely have

early signs or symptoms

Metastasized colon cancers frequently

cause secondary liver cancer

Prevention is by regular dental and

medical examinations

Colon cancer is the 2nd largest cause of

cancer deaths in males (lung cancer is 1 st)

Forms from benign mucosal tumors

called polyps whose formation increases
with age

Regular colon examination should be

done for all those over 50
The Urinary System

Urinary System Organs: Kidneys

Filter 200 liters of blood daily, allowing

toxins, metabolic wastes, and excess ions
to leave the body in urine

Regulate volume and chemical makeup

of the blood

Maintain the proper balance between

water and salts, and acids and bases

Produce renin to help regulate blood

pressure and erythropoietin to stimulate
red blood cell production

Activate vitamin D and produce glucose

during prolonged fasting
Other Urinary System Organs

Urinary bladder provides a temporary

storage reservoir for urine

Paired ureters transports urine from

the kidneys to the bladder

Urethra transports urine from the

bladder out of the body
Location and External Anatomy

The bean-shaped kidneys lie in a

retroperitoneal position in the superior
lumbar region and extend from the twelfth
thoracic to the third lumbar vertebrae

The right kidney is lower than the left

because it is crowded by the liver

The lateral surface is convex and the

medial surface is concave, with a vertical
cleft called the renal hilus leading to the
renal sinus

Ureters, renal blood vessels, lymphatics,

and nerves enter and exit at the hilus
Kidney: Associated Structures

The functionally unrelated adrenal gland

sits atop each kidney

Three supportive tissues surround the

kidney
Renal capsule adheres to the kidney
surface and prevents infections in
surrounding regions from spreading to
the kidneys
Adipose capsule cushions the kidney
and helps attach it to the body wall
Renal fascia dense fibrous
connective tissue that anchors the
kidney
Internal Anatomy

A frontal section shows three distinct

regions
Cortex the light colored, granular
superficial region
Medulla exhibits cone-shaped
medullary (renal) pyramids

Pyramids are made up of parallel

bundles of urine-collecting tubules
Renal columns are inward
extensions of cortical tissue that
separate the pyramids
The medullary pyramid and its
surrounding capsule constitutes a
lobe
Renal pelvis flat, funnel-shaped tube
lateral to the hilus within the renal sinus

Major calyces large branches of the

renal pelvis
Collect urine draining from papillae
Empty urine into the pelvis

Urine flows through the pelvis and

ureters to the bladder
Blood and Nerve Supply

Approximately one-fourth (1200 ml) of

systemic cardiac output flows through the
kidneys each minute

Arterial flow into and venous flow out of

the kidneys follow similar paths

The nerve supply is via the renal plexus

The Nephron

Nephrons are the blood-processing units

that form urine, consisting of:
Glomerulus a tuft of capillaries
associated with a renal tubule
Glomerular (Bowmans) capsule
blind, cup-shaped end of a renal tubule
that completely surrounds the
glomerulus
Renal corpuscle the glomerulus and
its Bowmans capsule
Glomerular endothelium fenestrated
epithelium that allows solute-rich,
virtually protein-free filtrate to pass
from the blood into the glomerular
capsule
Anatomy of the Glomerular Capsule

The external parietal layer is a

structural layer

The visceral layer consists of modified,

branching, epithelial podocytes

Extensions of the octopus-like

podocytes terminate in foot processes

Filtration slits openings between the

foot processes that allow filtrate to pass
into the capsular space
Renal tubule

Proximal convoluted tubule (PCT)

composed of cuboidal cells with numerous
microvilli and mitochondria
Resorbs water and solutes from
filtrate and secretes substances into it

Loop of Henle a hairpin-shaped loop of

the renal tubule
Proximal part is similar to the
proximal convoluted tubule
Proximal part is followed by the thin
segment (simple squamous cells) and
the thick segment (cuboidal to
columnar cells)

Distal convoluted tubule (DCT)

cuboidal cells without microvilli that
function more in secretion that
reabsorption
Connecting Tubules

The distal portion of the distal

convoluted tubule nearer to the collecting
ducts

Two important cell types are found here

Intercalated cells
Cuboidal cells with microvilli
Function in maintaining the acidbase balance of the body
Principal cells
Cuboidal cells without microvilli
Help maintain the bodys water
and salt balance
Nephrons

Cortical nephrons 85% of nephrons;

located in the cortex

Juxtamedullary nephrons:
Are located at the cortex-medulla
junction
Have loops of Henle that deeply
invade the medulla
Have extensive thin segments
Are involved in the production of
concentrated urine
Capillary Beds of the Nephron

Every nephron has two capillary beds

Glomerulus
Peritubular capillaries

Each glomerulus is:

Fed by an afferent arteriole
Drained by an efferent arteriole

Blood pressure in the glomerulus is high

because:
Arterioles are high-resistance vessels
Afferent arterioles have larger
diameters than efferent arterioles

Fluids and solutes are forced out of the

blood throughout the entire length of the
glomerulus
Capillary Beds

Peritubular beds are low-pressure,

porous capillaries adapted for absorption
that:

Arise from efferent arterioles

Cling to adjacent renal tubules
Empty into the renal venous system

Vasa recta long, straight efferent

arterioles of juxamedullary nephrons
Vascular Resistance in Microcirculation

Afferent and efferent arterioles offer

high resistance to blood flow

Blood pressure declines from 95mm Hg

in renal arteries to 8 mm Hg in renal veins

Resistance in afferent arterioles:

Protects glomeruli from fluctuations in
systemic blood pressure

Resistance in efferent arterioles:

Reinforces high glomerular pressure
Reduces hydrostatic pressure in
peritubular capillaries
Juxtablomerular Apparatus (JGA)

Where the distal tubule lies against the

afferent (sometimes efferent) arteriole

Arteriole walls have juxtaglomerular (JG)

cells
Enlarged, smooth muscle cells
Have secretory granules containing
renin
Act as mechanoreceptors

Macula densa
Tall, closely packed distal tubule cells
Lie adjacent to JG cells
Function as chemoreceptors or
osmoreceptors

Mesanglial cells appear to control the

glomerular filtration rate
Filtration Membrane

Filter that lies between the blood and

the interior of the glomerular capsule

It is composed of three layers

Fenestrated endothelium of the
glomerular capillaries
Visceral membrane of the glomerular
capsule (podocytes)
Basement membrane composed of
fused basal laminas of the other layers
Mechanism of Urine Formation

The kidneys filter the bodys entire

plasma volume 60 times each day

The filtrate:
Contains all plasma components
except protein
Loses water, nutrients, and essential
ions to become urine

The urine contains metabolic wastes

and unneeded substances

Urine formation and adjustment of

blood composition involves three major
processes

 Glomerular filtration
Tubular reabsorption
Secretion
Glomerular Filtration

Principles of fluid dynamics that account

for tissue fluid in all capillary beds apply to
the glomerulus as well

The glomerulus is more efficient than

other capillary beds because:
Its filtration membrane is significantly
more permeable
Glomerular blood pressure is higher
It has a higher net filtration pressure

Plasma proteins are not filtered and are

used to maintain oncotic pressure of the
blood
Net Filtration Pressure (NFP)

The pressure responsible for filtrate

formation

NFP equals the glomerular hydrostatic

pressure (HPg) minus the oncotic pressure
of glomerular blood (OPg) combined with
the capsular hydrostatic pressure (HPc)
NFP = HPg (OPg + HPc)
Glomerular Filtration Rate (GFR)

The total amount of filtrate formed per

minute by the kidneys

Factors governing filtration rate at the

capillary bed are:
Total surface area available for
filtration
Filtration membrane permeability
Net filtration pressure

GFR is directly proportional to the NFP

Changes in GFR normally result from

changes in glomerular blood pressure
Regulation of Glomerular Filtration

If the GFR is too high:

Needed substances cannot be
reabsorbed quickly enough and are lost
in the urine

If the GFR is too low:

Everything is reabsorbed, including
wastes that are normally disposed of

Three mechanisms control the GFR

Renal autoregulation (intrinsic
system)
Neural controls
The renin-angiotensin system
(hormonal mechanism)
Intrinsic Controls

Under normal conditions, renal

autoregulation maintains a nearly constant
glomerular filtration rate

Autoregulation entails two types of

control
Myogenic responds to changes in
pressure in the renal blood vessels
Tubuloglomerular feedback senses
changes in the juxtaglomerular
apparatus
Sympathetic Nervous System (SNS)
Controls

When the SNS is at rest:

Renal blood vessels are maximally
dilated
Autoregulation mechanisms prevail

Under stress:
Norepinephrine is released by the SNS
Epinephrine is released by the adrenal
medulla
Afferent arterioles constrict and
filtration is inhibited

The SNS also stimulates the reninangiotensin mechanism

Renin-Angiotensin Mechanism

Is triggered when the JG cells release

renin

Renin acts on angiotensinogen to

release angiotensin I

Angiotensin I is converted to
angiotensin II

Angiotensin II:
Causes mean arterial pressure to rise
Stimulates the adrenal cortex to
release aldosterone

As a result, both systemic and

glomerular hydrostatic pressure rise
Renin Release

Renin release is triggered by:

Reduced stretch of the granular JG
cells
Stimulation of the JG cells by
activated macula densa cells
Direct stimulation of the JG cells
via b1-adrenergic receptors by renal
nerves
Angiotensin II
Other Factors Affecting Glomerular
Filtration

Prostaglandins (PGE2 and PGI2)

Vasodilators produced in response to
sympathetic stimulation and
angiotensin II
Are thought to prevent renal damage
when peripheral resistance is increased

Nitric oxide vasodilator produced by

the vascular endothelium

Adenosine vasoconstrictor on renal

vasculature

Endothelin a powerful vasoconstrictor

secreted by tubule cells
Tubular Reabsorption

A transepithelial process whereby most

tubule contents are returned to the blood

Transported substances move through

three membranes
Luminal and basolateral membranes
of tubule cells
Endothelium of peritubular capillaries

Only Ca2+, Mg2+, K+, and some Na+ are

reabsorbed via paracellular pathways

All organic nutrients are reabsorbed

Water and ion reabsorption is

hormonally controlled

Reabsorption may be an active

(requires ATP) or passive process
Sodium Reabsorption: Primary Active
Transport

Sodium reabsorption is almost always

by active transport
Na+ enters the tubule cells at the
luminal membrane
Is actively transported out of the
tubules by a Na+-K+ ATPase pump

From there it moves to peritubular

capillaries due to:
Low hydrostatic pressure
High osmotic pressure of the blood

Na+ reabsorption provides the energy

and the means for reabsorbing most other
solutes
Reabsorption by PCT Cells

Active pumping of Na+ drives

reabsorption of:
Water by osmosis
Anions and fat-soluble substance by
diffusion
Organic nutrients and selected
cations by secondary active transport
Nonreabsorbed Substances

A transport maximum (Tm):

Reflects the number of carriers in the
renal tubules available
Exists for nearly every substance that
is actively reabsorbed

When the carriers are saturated, excess

of that substance is excreted

Substances are not reabsorbed if they:

Lack carriers
Are not lipid soluble
Are too large to pass through
membrane pores

Urea, creatinine, and uric acid are the

most important nonreabsorbed substances

Absorptive Capabilities of Renal Tubules

and Collecting Ducts

Substances reabsorbed in PCT include:

Sodium, all nutrients, cations, anions,
and water
Urea and lipid-soluble solutes
Small proteins

Loop of Henle
H2O, Na+, Cl-, K+ (descending)
Ca2+, Mg2+, and Na+ (ascending)

DCT
Ca2+, Na+, H+, K+, and water
HCO3- and Cl
Collecting duct
Water and urea
Na+ Entry into Tubule Cells

Passive entry: Na+-K+ ATPase pump

In the PCT: facilitated diffusion using

symport and antiport carriers

In the ascending loop of Henle:

facilitated diffusion via Na+-K+2Cl- symport system

In the DCT: Na+-Cl symporter

In collecting tubules: diffusion through

membrane pores
Tubular Secretion

Essentially reabsorption in reverse,

where substances move from peritubular
capillaries or tubule cells into filtrate

Tubular secretion is important for:

Disposing of substances not already in
the filtrate
Eliminating undesirable substances
such as urea and uric acid
Ridding the body of excess potassium
ions
Controlling blood pH
Regulation of Urine Concentration and
Volume

Osmolality
The number of solute particles
dissolved in 1L of water
Reflects the solutions ability to cause
osmosis

Body fluids are measured in milliosmols

(mOsm)

The kidneys keep the solute load of

body fluids constant at about 300 mOsm

This is accomplished by the

countercurrent mechanism
Countercurrent Mechanism

By the time the filtrate reaches the loop

of Henle, the amount and flow are reduced
by 65% but it is still isosmotic

The solute concentration in the loop of

Henle ranges from 300 mOsm to 1200
mOsm

The loop of Henle functions as a

countercurrent multiplier

Dissipation of the medullary osmotic

gradient is prevented because the blood in
the vasa recta equilibrates with the
interstitial fluid
Loop of Henle: Countercurrent
Multiplier

The descending loop of Henle:

Is relatively impermeable to solutes
Is permeable to water

The ascending loop of Henle:

Is impermeable to water
Actively transports sodium chloride
into the surrounding interstitial fluid

Collecting ducts in the deep medullary

regions are permeable to urea

The vasa recta is a countercurrent

exchanger that:
Maintains the osmotic gradient
Delivers nutrient blood supply to the
cells in the area
Formation of Dilute Urine

Filtrate is diluted in the ascending loop

of Henle

Dilute urine is created by allowing this

filtrate to continue into the renal pelvis

This will happen as long as antidiuretic

hormone (ADH) is not being secreted

Collecting ducts remain impermeable to

water; no further water reabsorption
occurs

Sodium and selected ions can be

removed by active and passive
mechanisms

Urine osmolality can be as low as 50

mOsm (one-sixth that of plasma)
Formation of Concentrated Urine

Antidiuretic hormone (ADH) inhibits

diuresis

This equalizes the osmolality of the

filtrate and the interstitial fluid

In the presence of ADH, 99% of the

water in filtrate is reabsorbed

ADH-dependent water reabsorption is

called facultative water reabsorption

ADH is the signal to produce

concentrated urine

The kidneys ability to respond depends

upon the high medullary osmotic gradient
Diuretics

Chemicals that enhance the urinary

output include:

Any substance not reabsorbed

Substances that exceed the ability of
the renal tubules to reabsorb it

Osmotic diuretics include:

High glucose levels carries water out
with the glucose
Alcohol inhibits the release of ADH
Caffeine and most diuretic drugs
inhibit sodium ion reabsorption
Lasix inhibits Na+-K+-2Cl- symporters
Renal Clearance

The volume of plasma that is cleared of

a particular substance in a given time

Renal clearance tests are used to:

Determine the GFR
Detect glomerular damage
Follow the progress of diagnosed renal
disease
RC = UV/P
RC = renal clearance rate
U = concentration (mg/ml) of the
substance in urine
V = flow rate of urine formation (ml/min)
P = concentration of the same substance
in plasma
Physical Characteristics of Urine

Color and transparency

Clear, pale to deep yellow (due to
urochrome)
Concentrated urine has a deeper
yellow color
Drugs, vitamin supplements, and diet
can change the color of urine
Cloudy urine may indicate infection of
the urinary tract

Odor
Fresh urine is slightly aromatic
Standing urine develops an ammonia
odor
Some drugs and vegetables
(asparagus) alter the usual odor

pH
Slightly acidic (pH 6) with a range of
4.5 to 8.0
Diet can alter pH

Specific gravity
Ranges from 1.001 to 1.035
Is dependent on solute concentration
Chemical Characteristics of Urine

Urine is 95% water and 5% solutes

Nitrogenous wastes include urea, uric

acid, and creatinine

Other normal solutes include:

Sodium, potassium, phosphate, and
sulfate ions

Calcium, magnesium, and bicarbonate

ions

Abnormally high concentrations of any

urinary constituents may indicate
pathology

Disease states alter urine composition

dramatically
Ureters

Slender tubes that convey urine from

the kidneys to the bladder

Ureters enter the base of the bladder

through the posterior wall
This closes their distal ends as
bladder pressure increases and
prevents backflow of urine into the
ureters

Ureters have a trilayered wall

Transitional epithelial mucosa
Smooth muscle mucosa
Fibrous connective tissue adventitia

Ureters actively propel urine to the

bladder via response to smooth muscle
stretch
Urinary Bladder

Smooth, collapsible, muscular sac that

temporarily stores urine

It lies retroperitoneally on the pelvic

floor posterior to the pubic symphysis
Males prostate gland surrounds the
neck inferiorly
Females anterior to the vagina and
uterus

Trigone triangular area outlined by the

openings for the ureters and the urethra
Clinically important because
infections tend to persist in this region

The bladder wall has three layers

Transitional epithelial mucosa
A thick muscular layer
A fibrous adventitia

The bladder is distensible and collapses

when empty

As urine accumulates, the bladder

expands without significant rise in internal
pressure
Urethra

Muscular tube that:

Drains urine from the bladder
Conveys it out of the body

Sphincters keep the urethra closed

when urine is not being passed
Internal urethral sphincter
involuntary sphincter at the bladderurethra junction
External urethral sphincter voluntary
sphincter surrounding the urethra as it

passes through the urogenital

diaphragm
Levator ani muscle voluntary
urethral sphincter

The female urethra is tightly bound to

the anterior vaginal wall

Its external opening lies anterior to the

vaginal opening and posterior to the
clitoris

The male urethra has three named

regions
Prostatic urethra runs within the
prostate gland
Membranous urethra runs through
the urogenital diaphragm
Spongy (penile) urethra passes
through the penis and opens via the
external urethral orifice
Micturition (Voiding or Urination)

The act of emptying the bladder

Distension of bladder walls initiates

spinal reflexes that:
Stimulate contraction of the external
urethral sphincter
Inhibit the detrusor muscle and
internal sphincter (temporarily)

Voiding reflexes:
Stimulate the detrusor muscle to
contract
Inhibit the internal and external
sphincters
Developmental Aspects

Three sets of embryonic kidneys

develop, with only the last set persisting

The pronephros never functions but its

pronephric duct persists and connects to
the cloaca

The mesonephros claims this duct and it

becomes the mesonephric duct

The final metanephros develop by the

fifth week and develop into adult kidneys
Developmental Aspects

Metanephros develop as ureteric buds

that incline mesoderm to form nephrons

Distal ends of ureteric tubes form the

renal pelves, calyces, and collecting ducts

Proximal ends called ureteric ducts

become the ureters

Metanephric kidneys are excreting urine

by the third month

The cloaca eventually develops into the

rectum and anal canal

Infants have small bladders and the

kidneys cannot concentrate urine,
resulting in frequent micturition

Control of the voluntary urethral

sphincter develops with the nervous
system

E. coli bacteria account for 80% of all

urinary tract infections

Sexually transmitted diseases can also

inflame the urinary tract

Kidney function declines with age, with

many elderly becoming incontinent