BIOL 215 LIBERTY UNIVERSITY Anatomy and Physiology II _NOTES_2024.pdf

Anatomy and Physiology II

Cardiovascular System

Blood

Transports nutrients, proteins, and hormones

Removes waste

It’s the first system to be developed in the womb at 16 days

Whole Blood

Fluid connective tissue

Transports gases, nutrients, hormones, metabolites, water and waste

Restricts fluid loss at injury sites

Defends the body from pathogens/toxins

Regulates body temperature

Properties of whole blood

Temperature- 38.0 * C

pH: 7.4

viscosity: 5x water

fluid component- blood plasma

cellular component- formed elements

Hematocrit or PCV

separating blood components measuring the percent formed

40-60% PCV

< 35% is considered anemic

Complete Blood Count (CBC)

Red Blood Count- number of RBC/microliter of blood

Hemoglobin measurement- grams of hemoglobin/100 mL

Male: 14-17g/100mL

Female: 12-15g/100mL

Hematocrit measurement- percent of blood that is RBC’s

WBC count- 4,500 – 11,000/ microliter of blood

Formed Elements

WBC=1

RBC= 600

Platelets= 40

Plasma

Water- 91%

Proteins- 7%

Small solutes- 2% (electrolytes, organic and inorganic components)

Accounts to 40-60% of blood volume

Higher concentration of dissolved oxygen and proteins than interstitial fluid

1. Albumins

a. 60% of plasma proteins

b. Responsible for viscosity and osmotic pressure of blood

c. Transports fatty acids and lipid soluble compounds

2. Globulins

a. 35% of plasma proteins

b. Include immunoglobulins (antibodies) which attack foreign proteins and

pathogens

c. Include transport globulins which bind ions, hormones and other compounds

d. Enzymes

3. Fibrinogen

a. 4% of plasma proteins

b. Converted to fibrin during blood clotting

c. Removal of fibrinogen from blood plasma leaves blood serum

Red Blood Cells- Erythrocytes

Hemopoiesis- process of blood cell formation

Hemocytoblasts- pluripotent stem cells that divide to form all types of blood cells

Lymphoid stem cells -> lymphocytes

Occurs in lymphoid tissues

Myeloid stem cells -> all other formed elements

Occurs in myeloid tissue (red bone marrow)

Erythropoiesis- process of erythrocyte formation

Stimulated directly by the kidney peptide hormone erythropoietin

Stimulated indirectly by growth hormone and androgens

RBC count is higher in men

Account for 98% of blood volume

25 trillion erythrocytes total

Biconcave disc- provides a large surface area-to-volume ratio

Shape allows RBC’s to stack, bend and twist

Lack organelles

Degenerate in about 120 days

Structure and abundance

Smallest cell in female body

Membrane skeleton

Maintains the shape of most cells

Hemoglobin

95% of RBC proteins

Made of two alpha chains and two beta chains

Contains a molecule of heme

Fe2+ atom in ring shaped carbon atom structure

Hemoglobin consists of 4 globin chains and 4 heme groups

Heme

Reversibly binds O2 (metabolic fuel)

Reversibly binds CO2 (metabolic waste)

Reversibly binds NO (a vasodilator)

Irreversibly binds CO (in car exhaust)

Sickle Cell Anemia

Caused by a mutation in the hemoglobin beta gene

Affects 1 in 50 black population

Distorts RBC into a sickle or crescent shape

Causes Hb to link into a long, curved chain

Carbonic Anhydrase

Converts CO2 to carbonic acid

CO2 + H20 -> H2CO3

Catalyzes reaction to 1 million fold

H2CO3 decomposes to bicarbonate in the plasma

Carbonic acid/bicarbonate buffering system keeps blood pH at 7.4

RBC lifespan

120 days

3 million new RBC’s enter blood per second

EPO can increase by 10 fold

Heme stripped of iron and converted to biliverdin then bilirubin (yellow color)

Blood Types

Determined by surface antigens

A, B, and Rh (D)

Antibodies will be deployed against other blood types if they enter your body

Cross reactions- when antigens meet corresponding antibodies, causing agglutination

Agglutinate- antibody induced clumping and lysing

Coagulate- blood clotting

Blood Typing

Blood sample- mixed with anti-a anti-b and anti-d antibodies

Pattern of agglutination- reveals blood type

Rh Factor and HDN

HDN= hemolytic disease of the newborn, where the mothers blood attacks the baby’s

blood

Only affects Rh+ babies with Rh- moms

Rh- mom with a Rh+ baby means the dad will be Rh+

White Blood Cells- Leukocytes

Main job= clean up and defense

Contain nuclei and organelles

Defend body against pathogens and toxins

Some are capable of phagocytosis

Granulocytes

a. Neutrophil

-Multilobed nucleus

-50-70% total WBC population

-Dense, dark segmented nucleus

-Lysosomal enzymes and bacteria compounds

-Release prostaglandins and leukotrienes (inflammation)

b. Eosinophil

-Bilobed nucleus, red cytoplasmic granules

-2-4% of total WBC population

-Deep red granules and bilobed nucleus

-Release toxic compounds onto large invading organisms with antibodies

- Inflammation reducing enzymes- mast cells and neutophils

c. Basophil

-Bilobed nucleus purple/black cytoplasmic granules

-<1% of WBC population

-Migrate to damaged tissue and release histamine and heparin

oHeparin- slows blood clotting

oHistamine- dilates blood vessels

Agranulocytes

d. Small lymphocytes

-Large spherical nucleus

-20-30% of WBC population

-Mostly found in lymph, not blood

- Includes t cells, b cells, and NK (natural killer) cells

oT cells- directly attack foreign cells

oB cells- humoral immunity, produce and release antibodies

oNK- immune surveillance, destroys abnormal human cells (cancer)

e. Monocyte

- Large Kidney shaped nucleus

-2-8% of WBC population

-migrate through tissues as macrophages

-release chemicals to attract other WBC and fibroblasts

- fibroblasts produce scar tissue to isolate injured site

Differential WBC Count

% of each of the 5 types of WBC

Platelet count: 150k to 400k/microliter; reduced= thrombocytopenia

Prothrombin time measurement: how long it takes for blood to start clotting 9-12 seconds

Thromboplastin is added to whole plasma

Blood chemistry: composition of materials dissolved or suspended in the plasma

Leukemia: inordinate number of leukocytes

Mononucleosis: elevated monocyte and lymphocyte

WBC Production

Stimulated by release of colony stimulating factors (CSF’s)

Platelets and Blood Clotting

Hemostasis

Flattened discs, very small, anucleate

Move around for 9-12 days before being removed by phagocytes

Transports clotting factors, forms clots in walls of broken blood vessels, active

contraction of clot

Prevents the loss of blood through vessel walls

Vascular phase

Caused by smooth muscle fiber constriction in vessel wall

Reduces blood loss

Endothelial cells release paracrine factors to stimulate vascular

spams and attract fibroblasts to site of injury

Become sticky

Lasts 30 mins after injury

Platelet phase

Platelets stick to endothelial cells (platelet adhesion)

Platelet plug begins in vessel- 15 sec after injury

ADP- stimulates platelet adhesion

Serotonin- stimulates vascular spasms and clotting factors

PDGF- platelet derived growth factor

Ca2+ ions

Coagulation phase

Fibrinogen is converted to large insoluble fibers (fibrin)

Thrombus- clot formed by platelets and endothelial cells

1. Intrinsic pathway

2. Extrinsic pathway

3. Common pathway

Clot Retraction

Final phase of healing

Plasmin- dissolves clot

Active form of plasminogen

Plasminogen circulates in plasma

Can be prevented with clot depressing drugs (anticoagulants)

tPA= tissue plasminogen activator

thrombomodulin- controls thrombin balance through endothelial vessel walls

keeps blood fluid in vessels, causes coagulation at injuries

The Heart

pulmonary circulation- RIGHT side of the heart pumps blood to the lungs

systemic circulation- LEFT side of the heard pumps blood to tissues of the body

generates pressure by heart contractions

ensures one way blood flow by using valves

Circuits

pulmonary circuit- brings deoxygenated blood to the lungs to pick up oxygen and

unload carbon dioxide

heart -> lungs -> heart

pulmonary arteries are blue, pulmonary veins are red

systemic circuit- brings oxygenated blood to all parts of the body to unload O2 and pick

up CO2

heart-> everywhere -> heart

systemic veins are blue, systemic arteries are red

both circuits:

arteries- (efferent) carry blood away from the heart

Veins- (afferent) carry blood toward the heart

Capillaries- connect arteries to veins

Heart Characteristics

Left ventricle is bigger than right ventricle

Apex- blunt rounded point of cone

Base- flat part of superior end of the heart

Mediastinum- central core of the thoracic cavity, everything except lungs

enclosed between the sternum, esophagus, lungs, and diaphragm

Pericardium

fibrous pericardium- tough fibrous outer layer, prevents overdistention, used as an

anchor

stabilizes heart valves

physically isolates atria from ventricles

electrically isolates atria from ventricles

serous pericardium- thin transparent inner layer, made of simple squamous epithelium

parietal pericardium- lines fibrous outer layer

visceral pericardium- covers the heart surface (epicardium)

have a pericardial cavity between them filled with pericardial fluid

Heart Wall

epicardium- visceral pericardium, serous membrane, smooth outer surface of the heart

myocardium- middle layer, made of cardiac muscle and causes contractions

endocardium- smooth inner surface of chambers of the heart

pectinate muscles- muscular ridges in auricles and right atrial wall

trabeculae carneae- muscular ridges and columns on inside of walls and ventricles

Surface Anatomy of the heart

2 atria and 2 ventricles

Auricles- extensions of atria

Blood enters the heart through:

Superior vena cava

Inferior vena cava

Pulmonary veins

Blood leaves the heart through

Pulmonary trunk

Aorta

Surface grooves

Coronary sulcus

Anterior/posterior interventricular sulci

(Coronary vessels are here)

Coronary Circuit

Arteries- right and left coronary arteries

Marginal arteries

Anterior and posterior interventricular arteries

Circumflex artery

Veins- great cardiac vein

Anterior and posterior cardiac veins

Middle cardiac vein

Small cardiac vein

Coronary veins empty into the right atrium via the coronary sinus

Internal anatomy of the heart

Atria

Right atrium- end of systemic circuit

Left atrium- end of pulmonary circuit

Thin walled chambers that get blood from the vena cava or pulmonary veins

Ventricles

Right ventricle- pump for pulmonary circuit

Left ventricle- pump for systemic circuit

thick walled chambers separated from atria by AV valves (atrioventricular)

Chordae Tendineae (heart strings)

Tendinous fibers attached to the AV valves

Papillary muscle and trabeculae carneae

Muscular projections on the inner wall of ventricles

Heart Valves

Atrioventricular valves (AV)

Leaf like cusps attached to papillary muscles via chordae tendineae

Tricuspid valve- three cusps on the right

Bicuspid valve (mitral)- two cusps on the left

Blood pushes valves open

Prevents backflow of blood from the ventricles to the atria

Semilunar valves

two cup shaped cusps that close when filled

blood pushed out of ventricles causes SL valves to open

right- pulmonary SL

left- atrial SL

prevents backflow of blood into the ventricles from the pulmonary trunk and aorta

Blood Flow Through the Heart

1. deoxygenated blood goes from the systemic circulation into the R atrium through the

vena cavae, and from the heart wall through coronary sinus

2. most of the blood goes into the R ventricle, causing the R atrium to contract and push the

rest of the blood into the R ventricle to fill it up

3. R ventricle contraction causes the tricuspid valve to close which prevents blood from

backflowing. Blood pushes into the pulmonary SL valve causing it to open and flow into

the pulmonary trunk

4. Pulmonary trunk forms the pulmonary arteries to bring blood to the lungs where CO2 and

O2 are exchanged

5. Blood comes back into the left atrium via the 4 pulmonary veins

6. Most of the blood goes from the left atrium ->bicuspid valve -> relaxed L ventricle. L

atrium contraction results in the L ventricle filling

7. L ventricle contraction pushes blood against the bicuspid valve which makes it close and

prevent blood from backflowing into the L atrium. The aortic SL valve opens and allows

blood to enter aorta when blood pushes on it.

Heartbeat

Two atria contract together first

Two ventricles contract together next

Sound generates from valves closing

AV= louder

SL= quieter

Cardiac Muscle

Striated- has sarcomeres

Involuntary- like smooth muscle

Intercalated discs- site where neighboring cells in cardiac muscle are connected together

Functional syncytium- many gap junctions ensure that cells are synchronized

Conducting System of the Heart

Brings action potentials through the heart

SA node: sinoatrial node

Pacemaker

Specialized cardiac muscle cells

Makes spontaneous action potentials

Action potentials pass to atrial muscle cells and AV node

Medial to opening of superior vena cava

AV node- atrioventricular node

Action potentials are slower than other parts of the system

Medial to right AV valve

Causes ventricles to receive signal to contract after atria

AV bundle- passes through hole in fibrous skeleton to reach interventricular septum

R and L bundle branches- extend beneath endocardium to apex of right and left

ventricles

Purkinje fibers- large diameter of cardiac muscle cells with few myofibrils

many gap junctions

conduct action potentials to ventricular muscle cells

1. heart is at rest and relaxed

2. action potentials are generated in SA node and go from SA node to cardiac cells in atrium

3. atrial wall muscle contracts in response to action potentials

4. AV node delays signal for 0.1 sec letting atria finish contraction into ventricles. Signal

proceeds into fibrous skeleton and interventricular septum for ventricle stimulation

5. Ventricular contraction starts at the apex and goes throughout the ventricles aiming at the

base of the heart. The spiral muscle structure causes a wringing movement. Heart

“scrunches” and blood is forced upward from the apex towards the great vessels.

Automaticity of the heart

Autorhythmic- stimulates itself to contract at regular intervals

Pacemaker potential- spontaneously develops local potential due to movement

of sodium potassium and calcium.

AP is generated once at threshold

SA= 90 bpm

AV= 50bpm, max 230

Hyperpolarize- the nodal cells slow the heart down

Depolarize- nodal cells speed heart up

Resting membrane potential (cardiac myocytes): -90mV

Threshold: -70mV

Steps: depolarization->plateau phase-> repolarization

1. Depolarization- achieved by influx of Na+ ions

2. Plateau phase- maintained by influx of Ca2+ ions, Ca2+ enters the cell membrane

3. Additional Ca2+ ions are released from reserves in SR

4. Repolarization- achieved in efflux of K+ ions

Electrocardiogram

P wave- depolarization of atril myocardium and signals onset of atrial contraction

QRS complex- ventricular depolarization and signals onset of ventricular contraction

Repolarization of atria simultaneously

T wave- repolarization of ventricles, precedes ventricular relaxation

PQ interval- 0.16 second, atria contract and begin to relax, ventricles begin to contract

QT interval- 0.36 second, ventricles contract and begin to relax

Used by cardiologist to diagnose heart conditions

The Cardiac Cycle

The period between the start of one heartbeat and the beginning of the next

Atrial systole- atria contract, rising atrial pressures push blood into ventricles to top off

the ventricles

EDV (end diastolic volume)- the volume of blood in the ventricles at the end of

ventricular diastole just before ventricular contraction

Ventricular systole- ventricles contract,

Isovolumetric contraction- ventricles contract, pressure rises and closes AV

valves, all valves closed with no blood flow

Ventricular ejection- ventricular pressure increases beyond arterial pressure of

SL valves, forcing blood through the valves into great arteries

ESV (end systolic volume)- 50mL

Ventricular diastole- ventricles relax

Early ventricular diastole- period of isovolumetric relaxation when SLV close

Late ventricular diastole- blood returns to the heart forcing AVV open, ventricles

fill passively

Heart Sounds

Auscultation- listening to body sounds with stethoscope

Heart sounds come from the valves closing

Loud closing of the AV valves- “lubb”

Softer closing of the SL valves- “dupp”

Murmurs

Incompetent valves- blood flows through backwards when valve is closed,

causes gurgling or swishing sound

Stenotic valve- abnormally narrow opening producing turbulent blood flow that

produces a rushing sound before the heart sounds

1. Bicuspid/apex area

2. Tricuspid area

3. Pulmonary area

4. Aortic area

Cardiodynamics

Stroke volume (SV):

SV=EDV - ESV

=150mL-50mL

=100mL

Cardiac Output (CO):

CO=HR x SV

CO=70bpm x 100mL/beat = 7000mL/min = 7L/min

Cardiac Reserve- the difference between resting and maximal cardiac output

Heavy exercises can increase output by 300-500%

Increases are limited by filling time at rates >180 bpm

Sympathetic stimulation INCREASES HR

Parasympathetic stimulation DECREASES HR

Circulating hormones (E, NE, T3) INCREASE HR

Increased venous return INCREASE HR

EDV is determined by fill time and rate of venous return

ESV is determines by preload, degree of contractility, and afterload

Vessels

Arteries- carry blood away from the heart

Veins- carry blood toward the heart

Capillaries- connect arteries to veins

RED BLOOD CELLS ARE 7.5 MICROMETERS

Tunics

Tunica intima/interna

Endothelium

Basement membrane

Lamina propria

Internal layer of elastic fibers

Tunica media

Smooth muscle layer

Vasoconstriction= smooth muscles contract, vessel narrows, blood flow reduced

Vasodilation= smooth muscle relaxes, vessel widens, blood flow increases

Tunica externa

 Connective tissue outer layer for structure and support

Types of arteries and veins

Elastic arteries- 1-2.5 cm diameter, conducting arteries

Muscular arteries- 1mm-1cm diameter

Arterioles- 30µm diameter, resistance vessels

Possess precapillary sphincter that control the flow of blood through capillaries

Vasomotion

Capillaries- 10µm diameter

Only one layer (tunica interna)

Continuous capillaries are most common because of their pores that allow for

things to pass through (water, sugar, urea, molecules)

Fenestrated capillaries allow larger molecules (proteins) to pass through, located

in liver and hormonal areas

Sinusoidal capillaries 10-40 µm in diameter and allow RBC’s to pass through the

blood stream, located in bone marrow, liver and spleen

Vasomotion- occurs in sphincters controlled by local pH

Venules- 30 µm diameter

Small/medium veins- 0.1mm-1cm diameter

Large veins- 1-3 cm diameter

Blood distribution

Veins are more distensible than arteries and can expand more for a rise in BP

Veins are capacitance vessels

Veins make it so that a large change in blood volume doesn’t effect arterial BP as much

During blood loss, vasoconstriction shunts blood from venous system to arteries and

capillaries

Special Circulation

Portal systems- hepatic portal, hypophyseal portal

Two capillary systems connected by a portal vein

Fetal circulation

Cardiovascular Physiology

Autoregulation- vasodilators speed up blood flow in response to

Decreased oxygen levels in tissues

Release of nitric oxide from vessel cells

Local inflammation

Heightened temperature

Vasomotion

Sharing of blood

Precapillary sphincters close off portions of the capillary bed, momentarily

depriving tissues of nutrients and O2

Collection of CO2 lowers pH in tissues without perfusion, the sphincters open at a

certain level while others close

Blood Pressure

Measured with a sphygmomanometer

Korotkoff sounds- vibrations from blood and tissues, that can be heard through the

stethoscope

Systolic pressure- the first sound heard in a heartbeat

Diastolic pressure- the second sound heard in a heartbeat

Blood viscosity

Viscosity- measure of resistance of liquid to flow

Resistance is directly proportional to flow

As viscosity increases, pressure increases

When hematocrit increases, viscosity increases

Dehydration and/or uncontrolled RBC production leads to increased viscosity and

higher workload on the heart

Blood flow

CSA = pi x r^2

Aorta- 3.14 x (1.25 cm)^2 x 1=5cm^2

(1.25 cm)^2 diameter of blood vessel

x1 number of blood vessels

5cm^2 total CSA

Arterioles- 3.15 x (0.0015 cm)^2 x billions =5000cm^2

(0.0015 cm)^2 diameter of blood vessel

x billions number of blood vessels

5000 cm^2 total CSA

Blood pressure- Systemic system

BP averages 100mm Hg in aorta

Drops to 0mm Hg by the time it reaches R atrium

Large pressure fluctuations in elastic and muscular arteries

No fluctuations in arterioles, capillaries, and veins

Pulse pressure- difference between systolic and diastolic pressures

Systemic arterial blood pressure= 120/80

Pulse pressure can be used to take a pulse to determine heart rate and rhythmicity

Frequent site used to measure pulse rate in the carpus w radial artery (radial pulse)

Baroreceptors- sensory receptors that monitor blood pressure

In the aortic arch and measure at the start of the systemic circuit

In the carotid sinuses monitor BP in the brain

Pulse Points

Can’t be found in veins or arteries smaller than elastic arteries

Most are too deep in the body to find a pulse

A pulse point is where an artery comes close enough to the skin to palpate

Temporal

Facial

Carotid

Apical

Brachial

Aortic

Femoral

Radial

Popliteal

Posterior tibial

Dorsalis

Vasodilation and Vasoconstriction

Vasodilation- increasing the diameter

Vasoconstriction- decreasing the diameter

Vasomotor tone- type of muscle tone, maintains slight, constant constriction of arterioles

Diameters vary from 0.5x-1.5x resting diameter

R= 1/r^4

Vasomotor center- in lower pons and upper medulla oblongata

Excitatory part is tonically active, causing vasomotor tone, norepinephrine

Inhibitory part uses vasodilation by decreasing sympathetic output

Endocrine control of blood perfusion

Adrenal gland

Active when stimuli result in a substantial increase in sympathetic stimulation of

heart and blood vessels

Adrenal medulla- releases epinephrine and norepinephrine

Hormones mimic sympathetic stimulation of heart and blood vessels

Antidiuretic Hormone

Triggered when BP is too low

Targets kidney to remove less water from blood when making urine

Targets blood vessels causing vasoconstriction, increases BP

Atrial Natriuretic Mechanism

ANH is released from cardiac muscle cells from the atria of the heart

Acts on the rate of urine production and Na+ loss

Dilates arteries and veins

Water loss causes decrease in blood volume

Regulation of BP

Baroreceptor reflexes- change peripheral resistance, HR, and SV in response to changes

in blood pressure

Adrenal medullary mechanism- activated by substantial increase in sympathetic

stimulation of the heart and vessels such as sudden large decrease in blood pressure,

increase in exercise or stressors

Chemoreceptors- sensory receptors sensitive or oxygen, CO2 and pH levels of blood

Central nervous system ischemic response- results from high carbon dioxide or low pH

levels in medulla and increases peripheral resistance

Properties of blood flow

Resistance = 8vL/3.14 r^4

Directly proportional to blood viscosity (^ viscosity, ^ resistance)

Directly proportional to vessel length (^ length, ^ resistance)

Inversely proportional to vessel diameter ( dec. diameter, inc. resistance)

Viscosity and length do not change in the body

Radius is used to regulate resistance

Small change radius = big change of resistance

Capillary Exchange

The flow of water and solutes between capillaries and interstitial fluid

Filtration

Separation of small and large components by size

Small molecules pass through capillary walls with water

Driven by capillary pressure

Reabsorption via osmosis

Movement of water and small molecules back into the capillaries

Driven by osmosis

Capillary exchange- produced by the heart

Blood colloid osmotic pressure- produced by the high conc. of protein in the blood

Opposing forces

Direction of filtration depends on the stronger force

Filtration pressure- CP- BCOP

may be positive or negative

arterial side

FP = CP – BCOP = 35 – 25 = 10mmHg

If FP is positive movement goes out of capillary

Venous side

FP = CP – BCOP =18 – 25 = -7mmHg

If FP is negative movement goes into capillary

Aging and arteries

Arteriosclerosis- degenerative changes in arteries making them less elastic

Atherosclerosis- deposition of plaque on walls, effects medium and larger arteries,

including coronary arteries

Endocrine System

Intercellular communication

Direct- chemical communication via gap junctions

Paracrine chemicals-

Cytokines released into ECF

Local cellular communications within a tissue

farts

Nervous system

Action potentials and synapses

Performs short term crisis management

Endocrine system

Chemicals released into bloodstream

Long distance communication with other tissues

Regulates overall metabolism and slow, cyclic needs

Hormones target specific cells

Endocrine system

Includes all glands and tissues that release a hormone

Some glands are pure organs

Some glands are mixed organs

Organs from other systems also produce hormones

Hormones

- Chemical messengers sent through the bloodstream

Amino acid

Derived from either tyrosine or tryptophan

Peptide (proteins)

Water soluble

Usually large

Most common

Shorter half-life

Lipid

Nonpolar

Steroid hormones, thyroid hormones

Travel with binding proteins

Longer half-life

Derived from cholesterol

Hormone circulation

Freely circulating in the bloodstream (hydrophilic)

Water soluble

Rapidly removed from bloodstream

2-60 mins

Bound to transport proteins (hydrophobic)

Low water solubility

<1% circulating freely

Several weeks supply in bloodstream

Mechanisms of hormone action

Hormones- chemical messengers meant to affect distant targets

Hormone receptors- only affects targets with matching receptors

Receptors are found in the cell membranes

- Action 1

oEicosanoids, catecholamines, and protein/peptide hormones bind to G protein

receptors

oG proteins use GTP instead of ATP

oCan alter amount of cAMP in cytoplasm

ocAMP is a secondary messenger

ocAMP alters metabolism via the protein kinase PKA

- Action 2

oG proteins alter the concentration of calcium ions in the cytoplasm

oCalcium alters metabolism via kinase PKC

oCa2+/Calmodulin = secondary messenger

- Action 3

oThyroid and steroid hormones cross the membrane and bind to receptors in the

cytoplasm or nucleus

Cytoplasmic and nuclear hormone receptors

Thyroid hormones and steroids bind to cytoplasmic and nuclear receptors

They are lipid soluble hormones that freely cross membranes

Hypothalamus and Pituitary Gland

Closely related physically and functionally

Pituitary is attached to hypothalamus via the infundibulum

Pituitary- near the middle of the skull, within the sphenoid bone

Releases 11 hormones: (peptide hormones)

Adrenocorticotropic hormone

Thyroid stimulating hormone

Growth hormone

Prolactin

Follicle stimulating hormone

Luteinizing hormone

Melanocyte stimulating hormone

Lipotropins

Oxytocin

Antidiuretic hormone

-They all bind to membrane receptors

-Use cAMP as a second messenger

Pituitary is divided into two lobes- anterior and posterior

Anterior- epithelial cells that manufacture and secrete hormones

Posterior- nervous tissue that releases hormones ADH and OT

Hypothalamus

Secretes regulatory hormones that control anterior pituitary

Secretes ADH and OT via the posterior pituitary

Exerts direct neural control over endocrine cells of adrenal medulla

Regulatory hormone action

Hypothalamus releases regulatory hormones to control pituitary

Regulatory hormones stimulate the pituitary and release releasing hormones (RH)

Regulatory hormones that inhibit the pituitary gland are inhibiting hormones

Hypophyseal portal system

Regulatory hormones enter primary capillary plexus in hypothalamus

Travel through portal vein

Exit via secondary capillary plexus into anterior pituitary

Pituitary hormones enter bloodstream via secondary capillary plexus

Hormones from the posterior lobe (made in the hypothalamus)

Antidiuretic hormone (ADH)

 Decreases the amount of water lost by the kidneys

Elevates BP

Oxytocin (OT) “sex hormone”

Stimulates contractile cells in mammary glands

Stimulates smooth muscle contraction in uterus

Produced by fetus to initiate labor contractions

Produced during sexual arousal in males and females

Hormones of the anterior pituitary

Thyroid stimulating hormone (TSH)

Triggers release of thyroid hormones

Thyrotropin releasing hormone (TRH) promotes release of TSH

Adrenocorticotropic hormone (ACTH)

Stimulates release of glucocorticoids by adrenal gland

Corticotrophin releasing hormone (CRH) from hypothalamus causes secretion

of ACTH

Follicle stimulating hormone (FSH)

Stimulates development of ovarian follicles and secretion of estrogen in females,

sperm in males

Luteinizing hormone (LH)

Causes ovulation and progesterone production in females, androgen in males

Prolactin (PRL)

Stimulates development of mammary glands and milk production

Growth Hormone (GH) or Somatotropin

Stimulates cell growth and replication through the release of somatomedins or

IGF

Growth hormone releasing hormone (GH-RH)

Growth hormone inhibiting hormone (GH-IH)

Beta-endorphins

Analgesia in response to stress and exercise

Lipotropins

Bind to adipocytes and cause lipolysis

Hormone of the Pars Intermedia

Melanocyte Stimulating Hormone (MSH)

Secreted by the pars intermedia

Secreted during fetal development

Stimulates melanocytes to produce melanin

Clinical trials of a synthetic MSH causes skin tanning

Pure endocrine glands

Adrenal glands

Paired glands on top of the kidneys

Closely affiliated with the diaphragm

Protected by ribs 11 and 12

Divided into superficial cortex and deep medulla

Adrenal cortex releases corticosteroids

Mineralocorticoids- mineral balance

Glucocorticoids- basal metabolism and glucose utilization

Androgens

Cortisol- released according to the circadian rhythm

Adrenal medulla releases adrenaline/epinephrine

Thyroid and Parathyroid Glands

Thyroid- located at the base of the neck @ jugular notch

Two lobes connected by an isthmus

Parathyroid- located on the posterior aspects of the thyroid lobes

Pair of nodules on each thyroid lobe

Histology of Thyroid and Parathyroid

Thyroid contains many, spherical follicles filled with a fluid

Wall of follicle composed of simple cuboidal epithelia

The colloid is extracellular

Interstitial cells are between follicles, called C cells

Parathyroid gland is non descript

T3 and T4- produced extracellularly because iodine is used at toxic levels

Ions are added to Thyroglobulin (TG) by the enzyme thyroid peroxidase (TPO)

The same enzyme moves 1 tyrosine onto the modified tyrosine

Modified TG returns to the cell, releasing T3/4 by lysosomes

T4 is the basic form of T3

Thyroid Gland Disorders

Hypothyroidism- inadequate production of thyroid

Reduced metabolic rate, lethargy

Caused by iodine insufficiency (goiter)

Controlled in the US by iodized salt

Cretinism (congenital) in infants- iodine deficiency

Hyperthyroidism- excessive thyroid hormones

Increased metabolic rate, irregular heart rate

Mood shifts, irritability

Thyroid hormone action

Thyroid hormones enter cell via transporter

Receptors are found in mitochondria and nucleus

Activate gene expression

C Cells and Calcitonin

T3/4 are produced by follicles in thyroid

Calcitonin produced by thyroid C cells found between follicles

Lowers calcium ion levels in the blood by having bone cells remove excess Ca2+

Parathyroid Glands

Two pairs of small glands in the posterior thyroid

Parathyroid hormone(PTH)

Produced in response to lower than normal calcium levels

PTH raises blood calcium levels

PTH and calcitriol are primary regulators of calcium in healthy adults

Calcium homeostasis

1. Calcium rises above set point

2. Thyroid releases calcitonin to “tone it down”

3. Blood calcium levels fall

1. Calcium falls below set point

2. Parathyroid releases PTH

3. Blood calcium levels rise

Pineal Gland

Within the cranial cavity

Produces melatonin

Higher in winter (seasonal affective disorder)

Pancreas

Mixed endocrine gland

Has both endocrine and exocrine functions

Endocrine- insulin/glucagon

Exocrine- digestive enzymes

Insulin- instructs somatic cells to remove glucose from the blood

Glucagon- instructs somatic cells to conserve glucose use, instructs liver to manufacture

glucose

Kidneys

Endocrine and urinary systems

Filters blood from metabolic waste, forms urine

Releases EPO, renin, and calcitriol

EPO- RBC production

Renin- functions in RAAS (renin-angiotensin-aldosterone system)

Calcitriol- absorption of CA2+

RAAS- The dehydration response

Blood volume decrease -> kidney releases renin

Renin converts angiotensinogen to angiotensin 1 in the blood

Angiotensin 1- converted to angiotensin 2 by ACE enzyme in the lungs

Angiotensin 2- powerful vasocontstrictor

Also stimulates aldosterone from adrenal gland

Aldosterone stimulates sodium retention by the kidneys, which draws water

from tissues into the blood (stimulates thirst)

RAAS stimulates release of ADH from pituitary, stimulating water retention by

kidneys

Thymus

Produces thymosin

Only affect thymus due to thymus-blood barrier

Thymosin’s function like organ-level paracrine factors

Thymosin’s cause maturation of T lymphocytes in the thymus

Heart

Natriuretic peptide production

ANP- atrial natriuretic peptide

BNP- brain natriuretic peptide

Released when ventricles are over-stretched, indicating that blood volume/pressure is too

high

ANP and BNP cause water removal by the kidneys (opposite of ADH)

Adipose Tissue

Releases leptin and resistin

Leptin- regulates body fat deposition

Involved in appetite

Resistin- insulin obedience , obesity, and inflammation

GI tract

18 hormones released from stomach and small intenstine

GIP- gastric inhibitory peptide

CCK- cholecystokinin

VIP- vasoactive intestinal peptide

Lymphatic System

Cleanup and defense

Refreshes interstitial fluids

Provide specific immunity

Fat absorption- from digestive tracts via lacteals

Lacteals- lymphatic capillaries in the small intestine that absorb dietary lipids and

participate in the gut immune response

Refresh Interstitial Fluids

Not circulatory

3.5L/day is taken up by lymphatic vessels

Lymph nodes cleanse lymph

Subclavian veins return clean lymph to the blood

Lymphatic drainage

Drainage is asymmetric

75% of the body is drained through L lymphatic duct (thoracic duct) into venous system

Movement through Lymphatic System

Lymphatic Capillaries

Join to form lymphatic vessels

Lymphatic vessels

Have valves to ensure one way flow

Lymph nodes

Distributed along lymphatics filter the lymph

Lymphatic trunks

Large lymphatic vessels that drain major regions of the body

Lymphatic ducts

Empty lymph into major veins (subclavian)

Female Breast Lymphatics

Highly developed

Mammary lymph node chain

Drain away from the nipple for protection of mother and baby

75% of lymph drains into axillary region

Provides a route for metastatic breast cancers

60% of breast cancer is found in the SLQ (superior lateral quadrant)

5% in the inferior medial quadrant (ILQ)

Lymphocytes and Immunity

20% of all WBC’s are lymphocytes

Not in the blood- in appendix, spleen, lymph nodes, tonsils etc

“wander” the body and don’t reside in one tissue

20 year lifespan

Classes of Lymphocytes

B (bone marrow derived) cells- 15%

Produce antibodies that bind to antigens

T (thymus derived) cells- 8-%

Cytotoxic t cells (Tc) attack foreign or infected cells

Helper t cells (Th) stimulate T and B cells

Suppressor T cells (Ts) inhibit T and B cells

NK (natural killer) cells- 5%

Attack infected or cancerous body cells

Lymphoid Organs and Tissues

Lymph Nodes

They clean lymph

Afferent vessels- multiple inputs

Efferent vessels- one or two outputs

Filled with B cells, T cells and macrophages

1-5mm, can be enlarged when actively fighting

Clustered in wet external areas (axillary, groin, intestine, throat etc)

Thymus

Behind the sternum- superior mediastinum

Continual atrophy throughout life- non functional after 50 y/o

Produces thymosins- which don’t enter general circulation due to blood-thymus barrier

Develops T lymphocytes

Spleen

Largest lymphatic organ

Left abdomen under diaphragm, within ribcage

Filters blood from pathogens

Stores iron, destroys old RBC and foreign substances in the blood

Difficult to suture if damaged, can be removed

Appendix

Located in lower right quadrant

Filled with lymphocytes

Controls growth of intestinal bacteria

Can get infected and inflamed, dangerous if ruptured (appendicitis)

MALT

Mucosa associated lymphoid tissue

Diffuse system scattered throughout mucosa of body

NALT- nasal associated lymphoid tissue (tonsils)

Palatine

Sublingual

Submandibular

Immunity

Immune response- employs multiple organ systems

Specific defenses- targeted toward a specific identified

threat

Non specific defenses- broadly aimed against all threats

Must be able to recognize self vs non-self

Autoimmune diseases- failure to distinguish self from

non self

Allergies- inappropriate immune response to harmless

substances (threat from non threat)

Non specific defense

Physical barriers- smoking, pollution etc

Phagocytes- cells and bacteria that don’t belong there

Interferons- go from infected cell to nearby cell to prevent replication

Complement system

Fever-

Inflammatory response- vasodilation

Specific Defenses

Naturally acquired immunity

1. Pathogen enters the body

2. The antigen (pathogen) is engulfed by phagocytes

3. Phagocytes activate T cells

4. Activated helper T cells stimulate B cells

5. Activated and stimulated B cells produce and

release antigen-specific antibodies

6. Antibodies bind to antigen (pathogen)

7. Activated cytotoxic T cells attack and destroy

antibody-tagged pathogens

Specificity- immune response triggered by/ responds to a specific pathogen

Versatility- system must be ready to respond to any threat at any time

Memory- system remembers encountered threats to more efficiently respond to future

encounters

Tolerance- ability to recognize self or non self

Activation of helper t cell

Helper t cell activated by CD4 complex interacts with MHC 2 complex on APC cell

Activated helper T cell proliferates and the daughter cells release cytokines

Cytokines activate cytotoxic t cells

Activation of sensitized B cells

Activation of Th cell by APC cell

Activation of sensitized B cell by activated Th cell

Proliferation of activated B cells

Conversion of B cells to plasma cells and release antibodies

Antibodies (immunoglobulins)

Y shaped proteins that bind to specific antigens

Antibody generator

Four polypeptides- 2 small, 2 big

Antibody has two identical antigen-binding sites

Constant region defines 5 classes of antibodies (IgA, IgD, IgE, IgG, and IgM)

IgG Antibody

Most abundant antibody

80%

Freely crosses placenta to provide immunity to fetus

Responsible for HDN (hemolytic disease of the newborn)

IgE antibody

Accelerates local inflammatory response

Bind to mast cells and basophils to stimulate release of histamine and heparin

IgD antibody

found only on the surface of B cells

employed during B cell sensitization and activation

IgM

Students also viewed