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Biol 1724 Lecture Notes (Ziser)Exam IV: endocrine system ���� nonspecific immunity

The Endocrine System

no clear distinction between nervous and endocrine systems

they are intimately interrelated � complement each other

Similarities

Both:coordinate and controlproduce biologically active chemicalsin some cases use same chemicalhormones affect nervous system/nervous sytem

affects hormone releasesone may override normal effects of the other:

eg Bld sugar: normal = 80-120 mg/100ml �regulated by hormones

stress � sympathetic stimulation� increases blood sugar levels

Differences:Nervous

localized effectstargets: other neurons, muscle cells, glands,transmits long range information by nerve

impulsesuses chemical signals (=neurotransmitters)

only cell to cellneurotransmitter only produced by neurons

immediate responseshort lived (ms – minutes)

Endocrinewidespread effectstargets: all tissuestransmits long range information as chemical

signals only = hormones, through circulatory systemgradual response (seconds – hours)longer – lived effects (minutes – days)

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Chemicals shared between Nervous and Endocrine SystemsFunctions

as Neurotransmitter as HormoneEndorphins binds to pain receptors in brain released from hypothalamus during

times of stressEnkephalins blocks pain perception adrenal medulla – blocks pain

sensationsDopamine “feel good” NT in limbic system &

midbraininhibits secretion of prolactin

Estrogen,Progesterone affects appetite center & body tempin hypothalamus and stimulatessexual arousal pathways

gonads and adrenal cortex - initiatesecondary sex characteristics, folliculardevelopment & menstrual cycle

Testosterone stimulates sexual arousal pathwaysand orgasm reflex

gonads and adrenal cortex - initiatesecondary sex characteristics &spermatogenesis

Norepinephrin,Epinephrin

“feel good” NT in limbic systemand sympathetic branch of ANS

adrenal medulla – maintainssympathetic response

Prolactin NT in brain anterior pituiitary – milk productionLeutinizing Hormone NT in brain Anterior Pituitary - maturation and

development of reproductive system

most if not all organs produce hormones

the endocrine system consists of several major glands and many minor glands

are ductless glands (endocrine vs exocrine glands)

all endocrine glands are richly supplied with blood capillaries

most are fenestrated capillary beds

their secretions affect virtually every aspect of physiology

at any one time there may be up to 40 major hormones and other minorhormones circulating in body

some general effects of hormones on body:a. enhance or moderate neural control of effectorsb. affects overall metabolic ratec. helps to maintain homeostasis of body’s

internal environment by regulating concentrations of salts,nutrients, hormones, and fluids

d. helps body cope with and respond toenvironmental changes that can cause infection, trauma, thirst,hunger

e. contributes to all aspects of the reproductiveprocess

f. provides smooth, sequential integration of all

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factors involved in growth and developmentg. affect moods and behavior

Physiology of Hormones

1. secreted from ductless glands directly into blood

2. secreted in response to specific stimuli

3. hormones can be secreted independently of oneanother

4. Many endocrine glands secrete more than onehormone

5. effective in minute quantities

6. major hormones are of two basic types:a. amino acid derived hormones

i. amines(acetylcholine, thyroid hormone, epinephrine, norepinephrine

ii. polypeptides and glycoproteins( ADH, Insulin, TSH)

b. steroid hormones(cortisol, testosterone, estrogen)

7. hormones are often derived from less active precursor in gland cells

eg. long chain “prohormone”� cut and spliced to form active hormone

8. hormones circulate in blood are often attached to carrier protein (inactive)

eg testosterone circulates in inactive form� must be activated by target cell

9. may be secreted for long periods of time

10. effects are highly specific to “target organ”

target cells respond only to specific hormones� requires specific binding site (receptor proteins)

even though every hormone comes in contact with every cell

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11. Most cells have receptors for more than one typeof hormone

hormones can interact with each other� synergistic effects = presence of 1 enhances effects

of other� antagonistic effects = 1 counteracts effects of other� permissive effects = one hormone “primes” target

organ for another hormone;

eg estrogen then progesterone on uterus

12. At the cellular level each hormone can affect a target cell in only a few ways:a. change in cell membrane permeabilityb. protein synthesis stimulated or inhibitedc. enzymes activated or inactivatedd. change in secretory activity of a cell

13. Each hormone can affect each target cell in>1 way

14. Maybe different effects in different target cells forsame hormone

15. Hormones don’t accumulate in blood

those that bind to target cells are destroyed� half-life ~ seconds – 30 minutes

excess are continually cleared by liver and kidney

typical duration of hormones effects:= 20 min to several hours

effects may disappear rapidly as blood levels dropor may persist even thought blood levels are low

therefore for prolonged effect� hormones must be continuously secreted

16. the extend of target cell activation can depend on:a. blood levels of hormonesb. relative # of receptor proteins on

target cellsc. affinity of binding

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Hormones effects are concentration dependentoverstimulation can cause desensitizationhyper and hypo secretion

� much of our knowledge of hormones effects comesfrom study of abnormal production

similar problems if too little or too many receptorproteins or target cells

Mechanism of Hormone Action on Target Cell

depends on hormone structure and location of receptors on target cell

A. Steroid Hormones

are nonpolar and fat soluble

and thyroid hormone which is also nonpolar)

receptors are located inside cytoplasm and nucleus� intracellular receptors

hormone enters cell and binds to receptor and activates it

hormone/receptor complex inters nucleus� binds to a protein on chromosome� triggers transcription

therefore: steroid hormones have a direct effect on DNA activity

B. Amino Acid Derived Hormones

are polar

cannot enter cell

use “second messenger” to produce effect on target cells

hormones attaches to specific receptor site on target cell

triggers enzyme “adenylate cyclase” (via G protein) to make “cyclic AMP” fromATP

cyclic AMP diffuses throughout cell and mediates target cell response tohormone

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mainly by activating one orm more different enzymes called “protein kinases”

each protein kinase hs a specific substrate that it acts on:� enzyme activation or inactivation� cellular secretion� membrane permeability� gene activation or inhibition

the time required for the onset of hormone effects varies greatly

� some hormones provoke immediate response

� others (eg steroid ) may require hours to days before their effects are seen

Control of Hormone Release

The synthesis and release of most hormones are regulated by some type ofnegative feedback system

three major mechanisms:1. Humoral2. Neural3. Hormonal

some endocrine glands respond to multiple stimuli

1. Humoral

hormones secreted in direct response to changing blood levels of certainchemicals in blood

affect endocrine gland directly

eg. parathyroid glandcells directly monitor conc of Ca++ionswhen Ca++ decline they respond by secreting PTH

eg. pancreasinsulin and glucagon secreted in response to blood sugar concentrations

eg. adrenal cortex aldosterone

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2. Neural

hormones secreted due to direct nervous stimulation

eg. adrenal glanddirectly stimulated by sympathetic fibers of ANSproduces same effects as Sympathetic NS but lasts 10 times longer:

∆ cardiac output∆ heart rate∆ alertness∆ respiratory rate

eg. Posterior Pituitarysecretes oxytocin and ADH in direct respnse to nerve

impulses from hypothalamus

3. Hormonal

Anterior Pituitary = master gland

secretes several hormones that control the secretion of other endocrineglands

���� Tropic Hormones

each tropic hormone has a target gland which it stimulates to produce itscharacteristic hormones

eg. TSH, ACTH, FSH LH

The release of trophic hormones is controlled by hypothalamus:

hypothalamus receives nerve impulses from all areas of brain

no direct neural connection between anterior pituitary and hypothalamus

they are connected by dense capillary bed

no blood brain barrier between them

hypothalamus contains neurosecretory cells

these cells serve as link between nervous and

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endocrine systems

neurosecretory cells are activated by nerveimpulses and reat by secreting neurohormones = releasing

hormones

produces specific Releasing Hormones foreach tropic hormone

eg. TSH-RH

releasing hormones travel in capillary bed to anterior pituitary

trigger release of appropriate tropic hormone

� translates nerve impulses into hormone secretions

sensory information in form of nerve impulses can be interpretedand acted on by the release of hormones =Neuroendocrine Reflex

eg. rapid response to stress

eg. thoughts and emotions affect body’s hormone levels

Hormones are switched off by negative feedback mechanismsrequire receptor – CNS – effector

eg. Negative Feedback for Hormonal Regulation

hypothalamus contains chemoreceptors for hormones switched on by tropic hormones

when levels get too high this inhibits the productionof releasing hormones

stops production of tropic hormones

stops production of specific hormone

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Minor/Temporary Endocrine Glands

Pineal Gland

located behind the midbrain and 3rd ventricle

not sure of all its functions

in lower animals it helps regulate cyclic activities:hibernationestrousmigration

is light sensitive � monitors photoperiod

in lower animals is called “3rd eye”some reptiles actually have 3rd eye in skull directly above pineal

gland

main hormone it secretes is melatoninlight suppresses productiondark stimulates production

light exposure suppresses melatonin secretion

In humans:� inhibits LH� inhibits ovarian function at night� may help regulate menstrual cycle� inhibits onset of puberty in males

seems to degenerate in adult??

Thymus

behind sternum, below thyroid

large in fetus and childmaximum size at puberty

degenerates in adult (replaced with fat)

functions as endocrine gland and as part of immune system

secretes thymosin� induces maturation and development of WBC’s

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Skin

produces cholecalciferolan inactive form of Vit D3

activated by UV

increases absorption of calcium by intestine

Kidneys

secrete erythropoietin� stimulates RBC production in bone marrow

Heart

atria contain some specialized muscle cells that secreteAtrial Natriuretic Peptide (ANP)

� reduces blood volume, pressure, Na+ conc

does this by:signaling kidney to increase productio of salty

urineand inhibiting aldosterone

Placenta

acts as temporary endocrine gland during pregnancy

releases 3 hormones:

a. chorionic gonadotropic hormone (CGH)

� maintains hormonal activity of ovary

pregnancy test

b. estrogens & progesterone

Stomach & Duodenum

mucosal lining secretes hormones to help control digestion:gastrin

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enterogastronesecretincholecystokinin

regulates secretion of:gastric juicespancreatic enzymesbile

Adipose Tissue

releases leptin

after uptake of glucose and lipids which is converted to fat

leptin binds to CNS neurons in hypothalamus

� produces sensation of satiety

Somatostatin

seems to be a local hormone

peptide of 14 amino acids

secreted by digestive epithelium and thyroid

has inhibitory effects on secretion of:GHinsulincalcitoninPTH

also inhibits secretion of immuniglobins

inhibits secretion of renin

inhibits secretion of bicarbonates and disgestive enzymes from pancreas

Somatomedin (IGF = Insulinlike Growth Factor)

affects many tissues

produced by liver

secondary hormone

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Anterior Pituitary monitors blood levels of IGF to control GH production

�in men GH causes liver to produce IGF whichstimulates cartilage development

� in women estrogen stim secretion of IGF causinguterine enlargement

� in women: in cartilage of long bones, estrogeninterferes with IGF causing bones to be shorter than in men

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Other Chemical Regulators

so far have studied two major types of regulatory molecules:neurotransmitters & neuromodulatorshormones

defined mainly by function, location, and action

a 3rd class of regulatory molecules are distinguished by the fact that�they are produced in many different organs�generally active in same organ that produces

them

= paracrine regulators

Paracrine Regulators

=eicosanoidsproduced in almost every organ and tissue of body

except RBC’snot officially part of endocrine systembiologically active lipids

(modified fatty acids, not steroids)

local regulators (= tissue hormones)made in small quantitiesshort lived

mainly prostaglandins and leukotrieneshave wide variety of effects in various systems:

immune response�regulate inflammatory process� role in pain, fever

cardiovascular system�role in blood pressure�vasomotor system = distribution of bloodflow

reproduction�ovulation� role in corpus luteum, endometriosis, PMS�induce labor

digestion� inhibit gastric secretions� intestinal peristalsis

respiration� constriction/dilation of blood vessels� role in asthma

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clottingeg thromboxane

�constricts blood vessels�promotes platelet aggregations

urinary functionfat metabolism

Hormone Interactions

while each hormone has a specific function

hormones rarely act alone to maintain homeostasis

homeostasis usually involves several hormones working together in complexways to regulate metabolic levels:

synergists � hormomes which tend to cause thesame effect

eg. ADH & aldosterone

antagonists � hormones which produce opposite effects

eg. insulin & glucagon

permissive � hormones which only affect“preprimed” tissues

eg. progesteroneeg. Growth

Hormones that generally stimulate growth:growth hormone

�stimulates growth of cartilage at epiphyseal plates� stimulates growth in all tissues

(except brain & reproductive organs)�maintains adult tissues

thyroid hormones�regulates the amount of energy available for protein

synthesis�esp skeleton and nervous sytem and brain

low TH: retards growth, childlike proportionshigh TH: excessive growth, short stature,

demineralization in adults

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mineralocorticoidstestosterone

�especially skeletal growth

Hormones that generally inhibit growth:glucocorticoidsestrogen

eg. Calcium Homeostasis:

main hormones that maintain blood calcium levels:

PTH� stimulates osteoclasts� increases blood Calcium levels

Calcitonin� stimulates osteoblasts� decreases blood calcium

Estrogen & Testosterone� maintain bone density by

slowing osteoclast activity andpromoting osteoblast activity

eg. Carbohydrate Metabolism

one of best studied systems of hormone interactions

glucose is most utilized carbohydrate in body

circulates in blood until it is needed for any of several functions:

energy

glycogenglucose

lipids

proteins

other carbohydrates (eg. ribose)

energy = with oxygen is converted to carbon dioxide and water

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only energy source that the brain can use

storage = converted to glycogensynthesis of other carbohydrates, proteins, lipids

several hormones from various glands play a direct role in glucosehomeostasis

1. Insulin (Pancreas-Islet Cells)

accelerate transport of glucose into body cellsincreases rate of utilization of glucose by body cells

� lowers blood glucose levels

2. Glucagon (Pancreas-Islet Cells)

stimulates breakdown of glycogen in liver and release of glucose into blood

also stimulates synthesis of glucose from lacticacid, glycerol, etc (=gluconeogenesis)

� raises blood glucose levels

3. ACTH (Anterior Pituitary)

tropic hormone that affects glucocorticoidproduction

4. glucocorticoids (Adrenal Cortex)

converts amino acids and fats to glucose in liver cells

excess glucose is released into blood

� raises blood glucose levels

5. growth hormone (Anterior Pituitary)

shifts from glucose catabolism to fat catabolismincreases oxidation of fats; spares glucose

unused glucose is converted to glycogen tomaintain normal glycogen stores

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excess glucose spills into blood

� raises blood glucose levels

6. TSH (Anterior Pituitary)

tropic hormone that stimulates release of thyroid hormone

7. Thyroid Hormones (Thyroid)

may accelerate catabolism of glucose to cause lowered blood glucose levels

or

or have other effects that raise blood glucose levels

8. Epinephrin (Adrenal Medulla)

stimulates breakdown of glycogen to glucose inmuscle and liver cells

and release of glucose into blood

� raises blood glucose levels

[but can also stimulate release of insulin by pancreas]

of all hormones listed only insulin is major “hypoglycemic hormone”

all others are mainly “hyperglycemic hormones”

Diabetes

diabetes is a general name for a group of diseases

two major varieties:diabetes insipidusdiabetes mellitis (Types I & II)

Diabetes insipidus

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a disease associated with Posterior Pituitary

deficiency in ADH causes low reabsorption of water

large volumes of dilute urine are produced:

(up to 10 gallons/day vs normal 1 qt/day)

leads to electrolyte imbalances etc

Diabetes mellitis

10 Million diabetics in US

40,000 die anually as result of disorder

effects:reduces life expectancy by ~1/3rd

25 x’s greater rate of blindness17 x’s greater rate of kidney disease17 x’s greater rate of gangrene2 x’s greater chance of heart attack

diabetes is a group of disorders

may be triggered by:genetic factorsenvironmental factorsautoimmune diseasepregnancyobesity

two kinds:10% = Juvenile Onset Diabetes (Type I)90% = Maturity Onset Diabetes (Type II)

Type I Diabetes

develops before the age of 20 years

is result of malfunction of Islet cells in pancreas

dramatic decrease in the number of beta cells

insulin is not produced in sufficient quantities

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in all body cells:decreased glucose utilization

� cells can take in only ~ 1/4th normal amount ofglucose

levels of glucose build up in blood� 3-10 times normal = hyperglycemia

since glucose can’t be used alternate fuels are mobilized:

increased fat mobilizationfats in blood rise to up to 5x’s normalas cells shift to fat catabolism

� produce ketone bodies� lower blood pH = acidosis

� acetone breath� increased risk of atherosclerosis

without insulin to stimulate proteinsynthesis they are instead broken down and converted

to glucose in cells� tissue wasting

high levels of glucose in blood lead to largequantities of glucose spilling into urine

� diagnostic test for disease(used to taste it, now have chemical indicators)

� this draws large amts of water into urine

Type II

adult onset diabetes

body produces insulin but target cells don’t respond

receptor problem

related to obesity

possibly overstimulation of receptors�they decline in numbers until cells don’t respond

treatment mainly by dietary changes

Blood & Hematology

The human body is made up mostly of water;

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~60 - 65% (40 L)

Where is this water located?

This water can be visualized as occurring in several “compartments”:intracellular 62% 40% (25 L)extracellular 38% 20% (15 L)

interstitial 30% 16% (12 L) [80% of ecf]intravascular 8% 4% (3 L) [20% of ecf]

Intracellular

most of the fluid in the body = 2/3rd’sinside all body cells

Extracellular

all fluid outside cells~1/3rd of body watersome is in tissue spaces between cells

= interstitial (= intercellular)30% of total fluids

some is circulating in vessels= intravascular (blood and lymphatic systems)

8% of total fluids

These compartments are interconnected:

outside intravascular interstitial intracellular

maintaining water and salt balance in eachcompartment means maintaining a balance in body as a whole

they interact with the environment by specialized organ systems:respiratory systemexcretory systemdigestive system

Fluid inputs:digestive tract 2000mlmetabolism 500ml

TOTAL: 2500ml

Fluid outputs:kidneys 1300ml

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lungs 450mlskin 650mlintestine 100mlTOTAL: 2500ml

Body’s transport system plays key role in balancing fluids in the body’scompartments

� “river of life” Marieb

Transport system includes:Circulatory system (=cardiovascular system)

� bloodLymphatic system

� lymph

General Functions of these Transport Systems:Transport functions:

1. Pick up food and oxygen from digestive andrespiratory systems and deliver them to cells

2. pick up wastes and carbon dioxide from cells anddeliver to kidneys and lungs

3. Transport hormones, enzymes etc throughout the body

Homeostasis functions:

4. maintain fluid and electrolyte balances in tissues andcells

5. maintain acid/base balances in tissues and cells

6. help regulate temperature homeostasistransfers excess heat from core to skin for removal

Protective Functions:

7. Protect body from infection= “immune system”

------------------------------------------------------------------------Average person (150lb) has 4.8 L of blood

= 8% body weight

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loss of 15-30% of blood � pallor and weaknessloss of >30% � severe shock, death

arterial blood: bright red = oxyhemoglobinvenous blood: darker red

viscosity = 4.5 - 5.5pH = 7.35 – 7.45temperature = 38º C (100.4º F) [thorax]

the amount of blood varies inversely with amount of excess body fat� less fat = more blood/unit wt

Composition:

plasma 55% of volumeformed elements45%

Plasma

the liquid part of blood

clear straw colored fluid

serum = plasma with clotting factors removed

90% water;

10% solutes>100 different solutessalts, ions, gasses, hormones, nutrients,wastesmost solutes are proteins

plasma proteins (8%):albumins 54-60%globulins 36-38%fibrinogen 4-7%

globulins= antibodies, part of immune system

albumins� (with other proteins) contribute to viscosity, osmotic

pressure & blood volume

fibrinogen

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� (with some albumins) clotting

most blood proteins synthesized by liver

globulins produced by immune cells

Formed Elements

about 45% of whole blooderythrocytes (RBC’s) –most, 45%, of formed elementsleukocytes (WBC’s)thrombocytes (Platelets)

all three are produced by stem cell= hemocytoblast

1. Erythrocytes

main job is to carry oxygen to cells

also deliver some carbon dioxide to lungs

most abundant of the three types of formed elements99% of formed elements5.5 mil/mm3

males 5.1 – 5.8 mil/mm3

females 4.3 – 5.2 mil/mm3

equivalent to 2.5 trillion blood cells in whole body

7.5 µm diameter

biconcave disc thin center, thick edges� high surface/volume ratio

30% more surface area than sphere with same diametergreater efficiency of gas exchangearea of all RBC’s in body = >football field for gas exchange

� flexibleeasily deforms to fit through narrow capillariesaffects speed of bloodflowregulated by prostaglandins

in each RBC are 200-300 Million hemoglobin molecules

men’s RBC’s typically contain more hemoglobin than womens RBC’s

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males: 13-20 g/100mlwomen: 12-16 g/100ml

each hemoglobin consists of:a protein = globincombined with 4 pigment molecules = heme

each heme contains 4 Iron atomseach iron atom can combine with

1 O2 molecule

each hemoglobin molecule can combine with4 oxygen molecules

= oxyhemoglobin

therefore, each RBC can carry ~1 Billion O2 molecules

hemoglobin can also combine with and transport carbon dioxide

RBC Formation

Erythropoiesis (hematopoiesis)

RBC’s are formed from stem cells in bone marrow

these stem cells divide and go through several stages of development

hemoglobin require iron (65% of body’s iron is in blood)[the rest is in liver, spleen][free iron is toxic to cells]

Iron is absorbed through digestive tract

if not used immediately can be quickly lost:average intake of iron:

1.0-1.5 mg/day(12-15 mg intake; 5-10% absorbed)

average daily loss of iron:less than 1mg lost/day

males = .9 mg/dayfemales = 1.7 mg/day

requires B vitamins for absorption

also B12 & Folic Acid for DNA synthesis and cell proliferation

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nucleus becomes smaller and is eventually lost

as cell leaves marrow and enters blood it is 20% larger than older RBC’s= reticulocyte (~1-2% of RBC’s)

can monitor number of reticulocytes to get estimate of rate of erythropoiesis

kidneys produce hormone = erythropoietin that regulates erythropoiesis:hypoxic � secretes more erythropoietinexcessive O2 inhibits hormone production

testosterone enhances kidney production of erythropoietinestrogen and progesterone have no effect

average RBC lives 100-120 days

they are destroyed by fragmentation as they squeeze through capillaries

cells lining blood vessels (esp in liver spleen and bone marrow) phagocytizethe fragments

hemoglobin components are recycled after death:� biliverdin (green) & bilirubin

(yellow/orange) � bile� iron stored in liver

both are transported to liver

each day > 100 million RBC’s are replaced

Erythrocyte Disorders

1. Anemiassymptoms: pale

lack energylow hematocrit:

males 5.1 – 5.8 mil/mm3

females 4.3 – 5.2 mil/mm3

low hemoglobinmales: 13-20 g/100mlwomen: 12-16 g/100ml

kinds: hemorrhagic (bleeding)hemolytic (disease, parasites, drug reactions, genetic)aplastic (cancer)Iron deficiency

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Pernicious (no B12)

2. Abnormal Hemoglobin

anemia like symptoms

kinds: thalassemiasthin and delicate blood cells

sickle cell

3. Polycythemia

too many RBC’s8-11 million/mm3

hematocrit = 80%

increased viscosity

causes:overstimulation of stem cellshigh altitudeprolonged physical activityfluid lossgenetic factors

2. Leucocytes

4000-11,000/mm3 or 1% of blood volume

numbers are misleading since they do most of their work outside the bloodvessels

mainly function in protection of bodyas part of immune system

WBC’s are motile by amoeboid motionthey squeeze out of capillaries into tissue spacesattack and destroy bacteria and pathogensremove dead cells and tissues

slightly larger than RBC’s = 8µm diameter

large, irregular, lobed nucleus

live for a few hours to a lifetime

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5 different kinds of WBC’s:

the numbers of each type per unit of blood areclinically important

= differential WBC count

ID depends on presence and stainingcharacteristics of granules and nucleus:

neutrophils40-70%granulocyteattracted to sites of inflammationlifespan: hours - daysespecially bacteria and some fungiindicate: acute infections and appendicitis

eosinophils1-4%granulocyteespecially abundant in pulmonary mucosa and

dermiscounteract inflammatory chemicalseat proteins, not “bugs”lifespan: daysindicate: worms and protozoan parasites

basophils<1%granulocyteleast abundant of WBC’stissue basophils = Mast Cellsbind to Ig E � release of heparin and histamine

� leaky vesselsenhance migration of WBC’s to sitelifespan: hours - days

lymphocytes20-45%agranulocytesonly few in “blood”T and B cellslifespan: hours to years

monocytes5-8%

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agranulocytesonly few in bloodin tissue become macrophageslifespan: monthsincreases: chronic infections, eg TB and viruses

mononucleosis

Formation

Leucopoiesis:

granular WBCs usually formed from stem cell s in bone marrow

agranular WBC’s are formed from stem cells in lymphatic tissue

sitmulated by hormone, CSF (colony stimulating factor) frommacrophages and T lymphocytes exposed to antigens and toxins

lifespan: hours to lifetime

Leukocyte Disorders

1. Leukocytosistotal WBC count >10,000/mm3

indicate:acute infections, eg appendicitisvigorous exerciseexcessive loss of body fluids

2. Leukopeniatotal WBC count <5,000/mm3

indicate:influenzameaslesmumpschickenpoxpoliomyelitisanemiaslead poisoning

3. Leukemiacancer characterized by uncontrolled production of

leucocytes

but large numbers are usually nonfunctional

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crowd out functioning WBC’s

may become anemic as normal marrow is crowdedout

myeloid leukemia> granulocytes

lymphoid leukemia> lymphocytes

3. Thrombocytes (Platelets)

small, irregular shape cell fragments

2-4 µm diameter

usually 250,000 – 500,000/mm3

no gender differences

short life span: ~10 days

formed in marrow, lungs and spleen by fragmentation of large cells(=megakaryocyte)

their production is controlled by thrombopoietin

play important role inhemostasis andblood clotting

Hemostasis

stoppage of blood flow

include:vascular spasm

reduces blood lossplatelet plug

1-5 seconds after injuryplatelets become sticky

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platelets swelldevelop spiky processesbecome sticky � adhere tenaceouslydegranulate � release serotonin &throboxane � enhance vascular spasmaggregating agens attract more platelets

prostaglandins may be involved

Blood Clotting

if injury is extensive clotting cascade is initiated

mechanism must be rapid to stop bleeding

involve over 30 different chemicals

each is activated in a rapid sequence= cascade (positive feedback)

1. trigger: rough spot in lining of blood vesselslow blood flow

(also, bedridden)

2. clumps of platelets adhere to site (1-2sec)3. platelets release serotonin and

thromboxane� constricts blood vessels at site of injury

4. platelets and damaged tissues release chemical(=thromboplastin, = prothrombin activator)

5. prothrombin (an inactive albumin)� becomes thrombin

6. thrombin converts fibrinogen to fibrin(fibrinogen – soluble protein)(fibrin – insoluble protein)

fibrin is a protein forming fine threads thattangle together forming a clot

clot retraction30-60 minutesdraws edges of clot together

fibrinolysis= clot dissolution

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occurs continuouslyplasmins & fibrolysin = clot busters

Thrombocyte Disorders

body has mechanism that prevent spontaneous clotting without vesseldamage:

- normal lining of vessels is smooth� platelets do not adhere

- blood also contains antithrombins� inactivate thrombin

eg. heparin (a natural blood constituent)

1. sometimes clots are triggered by internal factorstwo conditions favor clots:

rough spots on blood vesselsatherosclerosis may trigger clotting

abnormally slow flow of bloodbedridden or imobilized patients

these may be caused by:atherosclerosissevere burnsinflammationslow flow

thrombus – a fixed persistant clotembolism – a traveling clot

2. Bleeding Disorders (=Hemophilias)inability of blood to clot in normal amount of timemay be caused by

decreased # of plateletsliver diseaseinability to form various clotting factors

prothrombin and fibrinogen are produced in liverrequire vitamin K (absorbed from intestine)

vitamin K requires bile to be digested and absorbed

if bile ducts becfome obstructed results in vitaminK deficiency

� liver cant produce prothrombin at

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normal rate

eg. factor VIIcomprises 83% of cases

eg. factor Xa sex linked condition

Blood Types

blood type refers to the kinds of antigens found on the surface of blood cells(esp RBC’s)

related to immunity and how the body protects itself from pathogens:

our immune system recognizes and distinguishesbetween “self” and “nonself”:

self = all proteins and other chemicals thatare part of our bodies; that belong there

nonself = any proteins or chemicals that don’t belong

antigen = any foreign substance that enters ourbody

antibody = special proteins made by our immunesystem to remove foreign substances

many antigens are present on surface of blood cells

only a few are important in transfusions:ABO systemRh system

If these antigens are attacked by our antibodies it causes agglutination(clumping) of cells

[antibodies are agglutinins: cause clumping]

leads to:heart attackstrokekidney failureetc

most important consideration in transfusions:

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don’t want recipient’s antibodies to react with donor’s antigens

BloodType

Antigens antibodiesproduced

can donateblood to

can receiveblood from

AA anti B A, AB A, O

BB anti A B, AB B, O

AB A & B neither AB A, B, AB, O(universalrecipient)

O none both A, B, AB, O(universaldonor)

O

% Frequency in US PopulationBloodGroup

White Black Asian NativeAmerican

A 40 27 28 16B 11 20 27 4AB 4 4 5 <1O 45 49 40 79

even type O donors must be cross matchedsince many other antigens are present and some may cause reactions

Rh incompatability:

RhoGAM blocks the mothers immune systems response and prevents hersensitization to Rh+ blood of child.

RhoGAM is a serum containing anti-Rh agglutinins that agglutinate the Rhfactors that get into her blood

Circulatory System

large, multicellular organisms need good transport system to supply all cellswith nutrients and oxygen, to get rid of carbon dioxide and wastes, and todistribute hormones

major connection between external and internal environment:

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everything going in or out of body must go through the circulatorysystem to get to where its going

two major transport systems in body:circulatory (cardiovascular) systemlymphatic system

circulatory system works in conjunction with lymphatic system= an open system

circulatory system consists of “plumbing” and “pumps”:1. blood travels within a closed system of

vessels;never leaves vessels

circuit of blood first described by W. Harvey, 1628idea was vigorously opposed

2. has muscular pump that helps to move it

is one of first organ systems to appear in developing embryo� heart is beating by 4th week

The Heart

about size and shape of closed fist

beats >100,000 x’s/day

lies in mediastinum, behind sternum

lower border of heart (=apex) lies on diaphragm

heart is enclosed in its own sac, = pericardium(=pericardial sac)(parietal pericardium) composed of tough fibrousouter layer and inner serous membrane

outer surface of heart is also covered with serousmembrane (= visceral pericardium) (=epicardium) continuous with thepericardium

between the 2 membranes is pericardial fluid�lubrication

wall of heart:epicardium = visceral pericardium

thin & transparent serous tissuemyocardium = cardiac muscle cell

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most of heartbranching, interlacing contractile tissueacts as single unit (gap junctions)

endocardium = delicate layer of endothelial cellscontinuous with inner lining of blood vessels[endocarditis]

interior of heart is subdivided into 4 chambers:atria = two upper chambers

with auriclessmaller, thinner, weaker

ventricles = two lower chamberslarger, thicker, strongerleft ventricle much larger and thicker than

right ventricle

There are 4 major vessels attached to heart:2 arteries (take blood away from heart):

aorta- from left ventricle

pulmonary trunk- from right ventricle

2 veins (bring blood back to heart):vena cava (superior & inferior)

- to right atriumquickly splits into 2 pulmonary arteries

pulmonary veins (4 in humans)- to left atrium

There are also 4 one-way valves that direct flow of blood through the heart inone direction:

2 Atrioventricular (AV) valvesheld in place by chordae tendinaeattached to papillary muscles

� prevent backflow (eversion)keeps valves pointed in direction of

flowbicuspid (Mitral) valve

- separates left atrium and ventricle- consists of two flaps of tissues

tricuspid valve- separates right atrium and ventricle- consists of three flaps of tissues

2 Semilunar valves at beginning of arteries leaving the ventricles

aortic SL valve

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at beginning of aortapulmonary SL valve

at beginning of pulmonary trunk

Histology of Heartcardiac muscle fibers:

striated1 nucleusbranched cellsT tubules and SR less developed than skeletal mm

separated by intercalated discs� myocardium behaves as single unit

but atrial muscles separated fromventricular muscles by conducting tissue sheath

� atria contract separately from ventricles

mitochondria account for 25% of cardiac musclecells

(compared to 2% of skeletal muscle cells)� greater dependence on oxygen than skeletal

muscles� can’t build up much oxygen debt

more adaptable in nutrient use; can use:glucosefatty acids (preferred)lactic acid

refractory period lasts 250 msalmost as long as contraction phase

(vs 1-2 ms in skeletal muscle)� prevents tetanus

Conducting System

heart has some specialized fibers that are modified cardiac muscle cells

don’t contract; fire impulses that coordinate contraction of heart muscle

innervated by autonomic NS

consists of:SA Node

intrinsic rhythm70-75 beats/min

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initiates stimulus that causes atria to contract(but not ventricles directly due to separation)

AV Nodepicks up stimulus from SA Nodeif SA Node is not functioning it can act as a pacemaker

=ectopic pacekmaker (usually slower intrinsic rhythm)AV Bundle (Bundle of His)

connected to AV Nodetakes stimulus from AV Node to ventricles

Purkinje Fiberstakes impulse from AV Bundle out to cardiac mucscle fibers

of ventricles causing ventricles to contract

the heart conducting system generates a small electrical current that can bepicked up by an electrocardiograph

=electrocardiogram (ECG; EKG)

ECG is a record of the electrical activity of the conducting systembody is a good conductor of electricity (lots of salts)potential changes at body’s surface are picked up by 12 leads

ECG is NOT a record of heart contractions

R

P T

Q S

P wave = passage of current through atria from SA Nodeatrial depolarization

QRS wave = passage of current throughventricles from AV Node – AV Bundle – PurkinjeFibersventricular depolarization

T wave = repolarization of ventricles(atrial repolarization is masked by QRS)

by measuring intervals between these waves can get idea of how rapidly theimpulses are being conducted

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amplitude of waves also gives info on condition of conducting system andmyocardium

Abnormalities of ECG’s = arrhythmias

1. bradycardia (<60 bpm)decrease in body temperaturesome drugs (eg digitalis)overactive parasympathetic systemendurance athletes

2. tachycardia (>100 bpm)increased body temperature � feveremergencies, stress activation of sympathetic NSsome drugsmay promote fibrillation

3. fluttershort bursts of 200-300 bpmbut coordinated

4. fibrillationrapid, uncoordinated contractions of individual muscle cellsatrial fibrillation is OK

(since it only contributes 20% of blood to heart beat)ventricular fibrillation is lethalelectrical shock used to defibrillate and recoordinate contractions

5. AV Node Blocknormal P - Q interval = 0.12 – 0.20 secondschanges indicate damage to AV Node

� difficulty in signal getting past AV Node

1st º block:>0.20 seconds

2nd º block:AV Node damaged so only so wave passes

through ventricles only after every 2-4 P waves3rd º block: (complete block)

no atrial waves can pass throughventricle paced by different ectopic pacemakertherefore beat abnormally slow

Cardiac Cycle

1 complete heartbeat (takes ~ 0.8 seconds)

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consists of:systole � contraction of each chamber

diastole � relaxation of each chamber

two atria contract simultaneously

as they relax, ventricles contractventricular systole (atrial diastole) = 0.3 secventricular diastole = 0.5 sec

contraction and relaxation of ventricles produces characteristic heart soundslub-dub

lub = systolic soundcontraction of ventricles and closing of

AV valvesdub = diastolic sound

shorter, sharper soundventricles relax and SL valves close

abnormal sounds: “murmurs”� defective valves

congenitalrheumatic (strep antibodies)septal defects

relationship of cardiac cycle, ECG, heart sounds

Cardiac Output

CO = Heart RateX Stroke volume= 75b/m X 70ml/b= 5250 ml/min (=5.25 l/min)

~ normal blood volume

A. Heart Rate:innervated by autonomic branches to SA and AV

nodescontrol center in medullareceives sensory info from:

baroreceptors (stretch)in aorta and carotid sinusincreased stretch � slower

chemoreceptorsmonitor carbon dioxide and pH

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more CO2 or lower pH � faster

Other Factors that Affect Heartrate:1. hormones

epinephrin � fasterthyroxine � fasteracetylcholine ?

2. ionslow Calcium � slowerhigh Calcium � faster

spastic heart contracitionshigh Sodium � blocks Ca++ � slowshigh Potassium � faster

may cause cardiac arrest3. temperature

heat increases heart rate4. age

younger = faster, slows with age5. gender

women = faster (72-80 bpm)men = slower (64-72 bpm)

6. exerciseincreases during exercisealso heart beats slower in physically fit

7. emotionsfear, anxiety, anger � increase HRdepression, grief � reduce HR

any marked, persistent changes in rate may signal cardiovascular disease

B. Stroke Volume:healthy heart pumps ~60% of blood in itnormal SV = ~70 ml

SV = EDV (end diastolic vol) – ESV (end systolic vol)

affected by:mean arterial pressure

back pressureheart contractility

indicates amt of damageamount of stretch

Starling’s Law: within physiological limits the heart pumps allthe blood that returns to it without undue damming of bloodin veins.

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intrinsic regulatory mechanisms permit adaptation of theheart to varying rates of venous return.

>stretch = >strength of contraction

venous returnviscosity

(>RBC’s, dehydration, blood proteins)

Blood Pressure

measured as mmHg

blood flow in arteries depends on:1. pressure gradient created by heart beat2. resistance - counteracts pressure

Blood Flow = Difference in pressure Peripheral resistance

blood circulates by going down a pressure gradient:

Pulse Pressure:Pulse Pressure = Systolic Pr – Diastolic Pr

eg. 120/80; then PP = 40 mmHg

Mean Arterial Pressure:represents the average of Sys & Diast BP’sMAP = Diastolic Pr + 1/3rd x Pulse Pressure

arteriesvariable

systolic = 130-5 mmHgdiastolic = 85-90 mmHg

capillaries35 – 15 mmHg

veins6 – 1 mmHglarger veins near 0 mmHg

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Pulmonary Blood Pressure

heart pumps ~5l of blood per minute� 5 liters in systemic circuit� 5 liters in pulmonary circuit

change in pressure:systemic circuit:

averages 100 0 �difference = 100 mmHg

high resistance

pulmonary circuit:averages 15 5

� difference = 10 mmHg

low resistance� no pulmonary edema

Measuring Blood Pressureuse sphygmomanometerusually use brachial arteryprocedure:

a. increase pressure above systolic to completely cut off blood flow in artery

b. gradually release pressure until 1st spurt(pulse) passes through cuff

= systolic pressurec. continue to release until there is no

obstruction of flowsounds disappear

= diastolic pressure

normal BP = 110-140 / 75-80 [mm Hg]

top number = systolic pressureforce of ventricular contraction

bottom number = resistance of blood flowmay be more importantindicates strain to which vessels are

continuously subjectedalso reflects condition of peripheral vessels

Normal Blood Pressure varies with:

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agekids 90/60; adults 120/80; old 150/82

genderracesocioeconomic statusmoodphysical activitypostureetc

sclerosis � high diastolic pressure

Main factors affecting blood pressure:1. cardiac output2. peripheral resistance3. blood volume

� a change in any of these could cause a corresponding change in blood pressure

1. Cardiac Outputphysical condition of the heartalready discussed cardiac output

2. Peripheral Resistancefactors that affect peripheral resistance are

mediated by autonomic nervous sytemPeripheral resistance is also affected by the

condition of the vessels themselves and by blood-born chemicals

a. Vasomotor Control Center (medulla)works in conjunction with cardiac centers

both arteries and veins can dilate

mainly sympathetic control� activation can cause constriction

eg. in skin or dilation eg in muscles

b. Condition of vesselseg atherosclerosis inhibits flow

� raises blood pressure

eg. obesity leads to many additional vesselsthat blood must pass through

� raises blood pressure

c. Blood Borne chemicals

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numerous blood-borne chemicals influenceshort term control of blood pressure

act directly on vascular smooth muscle or onvasomotor system

eg. NOsecreted by endothelial cellslocalized vasodilation� lowers BPvery brief effect, quickly destroyedis the major antagonist to sympathetic

vasoconstriction

eg. viagra stim production of NO

eg. inflammatory chemicalshistamines, kinins, etcpotent vasodilators � lower BPincrease capillary permeability

eg. nicotineintense vasoconstriction � raise BPsimulates sympathetic release of NE

eg. alcoholdepresses VMCinhibits ADH releasevasodilation (esp of skin vessels)� raises BP

(also flushing of face)

3. Blood Volumeblood pressure is directly affected by the volume

of fluids retained or removed from body:

greater volume � increases BPeg. excessive salts promote water

retentionlower volume � decreases BP

eg. dehydrationeg. internal bleeding

factors that regulate blood volume are mainlyrenal factors and are slower to change

� long term controls

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these factors can act as a system wide control overwhole body blood pressure

mainly involve control by the kidneys

baroreceptors quickly adapt to long term (chronic)changes in blood pressure

renal mechanisms step in to restore homeostasisby regulating blood volume

kidneys act both directly and indirectly to regulatearterial pressure:

a. Direct Renal Control of Blood Volumeinvolves regulation of blood volume by kidneys

greater BP:more filtration from kidney

� greater urine outputlower BP:

more reabsorption of water by kidney� lower urine output

b. Indirect Renal Control of Blood Volume= Long Term Controlsrenin-angiotensis mechanism

lower BP:� kidneys release enzyme = renin� renin triggers production of

angiotensin II� angiotensin causes:

vasoconstriction � raises BPrelease of ADH � conserves water to raise BP

Hypotensionlow BP � systolic <100usually not a cause for concern

� often associated with long healthy lifebut.

in some may produce dizziness when standingup too quickly (esp in older patients)

may be due to severe bleeding and lead tocirculatory shock

may hint at poor nutritioneg. <blood proteins

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Hypertensionif transient is normal:

adaptation during fever, exercise, strongemotions

if persistent is a cause for concern30% of those >50 yrs old suffer from

hypertensionusually asymptomatic for first 10-20 yrs

= silent killerprolonged hypertension is a major cause of:

heart failurevascular diseasekidney failurestroke

Blood Vessels & Circulation

blood flows in closed system of vesselsover 60,000 miles of vessels (mainly capillaries)

arteries ���� capillaries ���� veins (25%) (5%) (70%)

arteries & arterioles– take blood away from heart to capillaries

capillaries-actual site of exchange

venules & veins– bring blood from capillaries back to heart

arranged in two circuits:pulmonary: heart � lungs � heart

rt ventricle� pulmonary arteries (trunk)�lungs�pulmonaryveins�left atrium

systemic: heart � rest of body � heartleft ventricle�aorta�body�vena cava�rt atrium

heart is a double pumpoxygen deficient blood in pulmonary vein and vena cava

� usually blue on models

walls of arteries and veins consist of three layers:tunica adventitia

outer fibrous connective tissuetunica media

middle smooth muscle

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tunica intima (=interna)inner endothelium

Characteristics of Blood Vessels

Arteriescontain ~ 15% of all bloodpressure is variable

MAP ~ 93 varies from 100 – 40 mmHgthree layers:

thick layer of connective tissue for strengthheavily muscular to withstand pressure

large lumenmost organs receive blood from >1 arterial branch

provides alternate pathways

vasa vasorum = blood vessels within walls of large arteriessympathetic innervation

Arterioles~ 10% of all bloodaverage pressure ~40 –25 mmHgpressure decreases drastically in arterioles

� most resistance is here~ 1/2 of whole system

muscle tissue makes up major bulk of wallsinnervated by vasomotor nerve fibers of

autonomic NSmajor role in controlling the distribution of blood in

bodysympathetic stimulation � vasoconstriction

Capillariesmost of 62,000 miles of vesselsusually no cell >.1 mm away from a capillaryeach capillary <1mm longbut only contains ~5% of blood in bodyvariable pressure 35 – 15 mm Hg;

ave=25-12 mmHgthin walled - single cell layer thickextremely abundant in almost every tissue of

body1 inch3 of muscle = 1.5 million capillaries

A. density of capillaries varies with metabolic rate

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eg. cartilage and cornea have no capillarieseg. tendons and ligaments are poorly

vascularizedeg. cartilage and epithelial cells lack

capillarieseg. muscle, liver, lungs, kidneys have rich

blood supply

B. types of capillary structure:1. continuous

lining is uninterruptedadjacent cells joined by tight junctionsbut with intracellular clefts to allow

passage of fluids and small solutemost common typeeg. skin, muscles, lungs, adiposespecial: CNS

blood brain barrierno clefts

2. fenestratedsimilar to above but some cells are riddled

with poresmuch greater permeabilityeg. kidneys, endocrine glands, intestinal

mucosa3. sinusoidal (discontinuous)

highly modified “leaky” capillarieslarge clefts and fenestraeallows large molecuels and cells to passeg. bone marrow, liver, spleen

C. capillary beds:functional groupings of capillaries= functional units of circulatory system

arterioles and venules are joined directly bymetarterioles (=thoroughfare channels)

capillaries branch from metarterioles1-100/bed

cuff of smooth muscle surrounds origin ofcapillary branches

= precapillary sphincter

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amount of blood entering a bed is regulated by:a. vasomotor nerve fibersb. local chemical conditions

D. Velocity of blood flowblood flows slowest in capillaries

due to greater cross-sectional area of all capillariescombined:

�600 – 1000 x’s cs of aorta

provides greatest opportunity for exchange to occur

most materials pass to tissues by diffusion:fat soluble, CO2, O2 go through cell

membraneions and small molecules go through pores

(passive ion channels)large molecules pass by exocytosis

Veins & Venules60% of all blood is in veins~10% in venuleslow pressure:

12 – 8 mmHg venules6 – 1 mmHg veinslarger veins near 0

generally have a greater diameter than arteriesbut thinner walls

� more compliant

three layer are all thinner than in arteriestunica adventitia is thickest of three

but not as elastic as arterieslittle smooth muscle

large veins also contain vasa vasorum� blood vessels in walls

with sympathetic nerve innervation

Movement of Blood in Veins movement of blood in veins is not pressure

driven by the heart

venous blood flows due to:

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1. constriction of walls by ANSminor effect

muscle layer is very thin, veins arevery compliant

2. 1 - way valvesprevent backflowmost abundant in veins of limbs

quiet standing can cause blood to pool in veinsand may cause fainting

varicose veins: “incompetent” valvesesp. superficial veinsmay be due to

heredityprolonged standingobesitypregnancyincreased venous pressure

hemorrhoids:varicosities of anal veinsdue to excessive pressure from birthing or

bowel movements

3. venous pumpsmuscular pump

(=skeletal muscle pump)during contraction veins running thru

muscle are compressed and force blood in onedirection (toward heart)

respiratory pumpinspiration:

intrapleural pressure falls from –2.5 mm Hgto –6 mmHg while abdominal pressureincreases� creates pressure gradient in Inferior VenaCava to move blood toward heart

expirationincreasing pressure in chest cavity forces

thoracic blood toward heart

veins function to collect blood and act as bloodreservoirs

�with large lumens and thin walls they canaccommodate relatively large volumes of blood

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60-70% of all blood is in veins at any time

largest veins = sinuseseg. coronary sinus, dural sinus

most organs are drained by >1 venous brancheven more common than alternate arterial

pathways

� occlusion of veins rarely blocks blood flow

removal of veins during bypass surgeryusually not traumatic

Vasomotor Control System

circulation involves differential distribution of blood to various body regions

active body parts receive more blood than inactive parts

blood volume must be shifted to parts as they become more active

blood circulates because of pressure gradients

pressure gradients are created throughcardiac outputperipheral resistance

the greatest peripheral resistance is found in the arterioles85 at beginning35 at end 50 mmHg difference

individual arterioles can increase or decrease their resistance to bloodflow byconstricting or dilating

mediated by autonomic nervous sytem

vasomotor control center in medulla

works in conjunction with cardiac centers

mainly sympathetic control

both arteries and veins can dilate

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vasomotor control system can also shift blood to or from blood reservoirs inveins as needed:

large veinssinuses

skinliverspleen

sensory input from:

baroreceptors incarotid sinusaortic arch

� stretch inhibits VMC � vasodilation

chemoreceptorsmonitor oxygen and pH

in aortic arch and carotid sinusthese receptors also help to control

respiration

lower pH or O2 � vasoconstriction

cerebral cortex and hypothalamus can affect VMCeg. hypothalamus

fight or flight � vasoconstriction eg. cerebral cortex

emotions

Local Regulation of Blood Distribution

in addition to vasomotor reflex,local regulation of specific arterioles can alsodirect blood to organs needing it most

individual tissues can control the amount of blood they receive through someautoregulation (=intrinsic controls)

largely independent of systemic factors (VMC) noted above

Autoregulation involves:1. Metabolic controls2. Myogenic controls

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1. Metabolic controlschanges in the concentrations of specific nutrients

or waste products can cause vasodilation and relaxation ofprecapillary sphincters in affected tissues

eg. reduction in esp O2eg. increases in potassiumeg. increase in Hydrogen ions (lower pH),

lactic acid

2. Myogenic controlsinadequate blood flow to an organ can cause cell

damage or deathtoo much blood flow may rupture fragile vesselsthe physical effects of blood flowing to an organ causes direct localstimulation of its vascular tissue:

passive stretch � triggers constriction� higher local BP� slows blood flow to tissue

reduced stretch � triggers dilation� reduces local BP� increases blood flow to tissue

Angiogenesis

if short term changes cannot supply adequate oxygenor nutrients the body can respond by increasing the number of bloodvessels supplying the area

the number of blood vessels to a high demand area will increase

eg. heart with occluded vessels grows new ones

eg. people at high altitudes have greater number of vessels intissues throughout their bodies

Body Defenses & Immunity

immunity = resistance to disease

the immune system provides defense against all the microorganisms and toxiccells to which we are exposed

� without it we would not survive till adulthood

our body has many ways to prevent or to slow infections

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Many factors affect an individual’s overall ability to resist infections:Genetics: human diseases, zoonoses, etcAge: mainly an immune responseHealth: eg. protein deficiency � less phagocytic

activity eg. stress � lower resistance to disease

Hormones: eg. cortisone (a glucocorticoid)reduces inflammatory response

the immune system is a functional system rather than a system withdiscrete organs

� parts of many organs contribute to body defensealmost all organs in body play some role in immunity

� dispersed chemicals, cells and tissues� dispersal and transport via circulatory and

lymphatic systems

two major mechanisms that protect the body:1. Innate, nonspecific system of

a. physical and chemical barriersb. internal cells and chemicals

2. Adaptive system that fights specificpathogens

or, can view the immune system as a three tiered system of defensea. physical and chemical barriersb. chemical and cellular barriersc. specific defense mechanisms

Innate, Nonspecific Resistance

Physical Barriers

1st major level of protection from invasion and infection

nonspecific – treats all potential pathogens the same way

attempt to prevent entry of pathogens into body

1. Intact Skin

tightly packed cells filled with waxy keratin

thick, multiple layers of dead keratinized cells

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shed regularly

rarely, if ever, penetrated while intactonly a few parasitic worms (cercariae) can do this

if skin is broken:staphs and streps are most likely to get in

sebaceous glandsprovides protective film over skin

acidity of skin secretions ('acid mantle') inhibit bacterial &fungal growth; also contains

bacteriocidal chemicals

butif skin is moist, not cleaned frequently enough�may permit yeasts and fungi already present

to become a problem

2. Mucous Membranes

line all systems that open to outside of bodynasal hairs

trap pathogensmucous

thick, sticky, traps pathogenscilia

in resp sys move mucous out of system(‘ciliary escalator’ � 1-3 cm/hr)coughing and sneezing speed up process

gastric juicessecreted by lining of stomachcontains HCl and enzymes; highly acidic (pH~1.2-3.0)kill and dissolve most bacteria and toxins

except S. aureus and C. botulinum

but: Helicobacter pylori neutralizes acids to grow instomach

may cause gastritis or ulcersLacrimal Apparatus

continual blinking flushes and wipes awaypathogens

lysozyme kills and dissolves some bacteria

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(most G+ and some G- bacteria)(lysozyme also found in sweat, saliva, and nasalsecretions)

Salivacontinual flushing of bacteria to stomachlysozyme kills and dissolves some bacteria

Urinecontinual flushing of bacteria entering urethra

� low flow � bladder infectionacidity also inhibits bacterial growth

Vaginal Secretionsflushing and trapping pathogens in mucousacidity inhibits bacterial growth

but: some pathogens thrive in moisture and if theyoccur in large enough numbers they are able topenetrate eg. Treponema

Internal Cellular and Chemical Defenses

1. blood has nonspecific, antimicrobial chemicals thathelp to fight invaders:

eg. transferrins – bind to Fe to inhibit bacterialgrowth

2. Simple Phagocytosismany WBC’s travel through blood and tissues and

gobble up bacteria and foreign materialmostly neutrophils and macrophages (formed from

monocytes)migrate to area of infectionmonocytes enlarge on way to become

macrophagesengulf and destroy circulating pathogens

especially bacteriasome macrophages are “fixed macrophages” that

screen blood as it passes by� esp in liver, bronchial tubes of lungs, nervous

system, , spleen, lymph nodes, bone marrow peritonealcavity

[referred to as the reticuloendothelial system]eosinophils � can produce toxins and are most

active against parasitc worms

mechanism of phagocytosis:

57

1. Chemotaxischemical attraction to invaders, microbial products,

components of WBC’s or damaged cells2. Adherence

attachment to surface of foreign materialmay be hampered by capsules (eg. S. pneumonia, H.Influenza) or M proteins (eg. S. pyogenes)

� must trap them against rough surface(eg. blood vessel wall, clot, etc)

also can be more readily phagocytized if 1st coated withcertain plasma proteins that promote attachment(=opsonization)

3. Ingestionplasma membrane of phagocyte extends around

microorganism or cell4. Digestion

forms food vacuole inside WBCfuses with lysozomestakes 10-30 minutes to kill most bacteria

enzymes:lysozyme � hydrolyzes peptidoglycan of cell

walllipases, proteases, ribonucleases �

hydrolyzes other cellular componentssome enzymes also produce toxic oxygen

products: eg. O2-, H2O2, OH-

residual body discharges wastesnot all microorganisms are killed once phagocytized

eg. Staph and Actinobacillus actually producetoxins that kill phagocytes

eg. Chlamydia, Shigella, Mycobacterium,Leishmania (protozoan), and Plasmodiumcan survive inside phagocyte� they can prevent fusion of lysozome

eg. other microbes can remain dormant formonths

phagocytosis also plays a role in specific immunity

3. Natural Killer Cellsthe “pit bulls” of the defense systemanother kind of WBCpolice the body in blood and lymphpromote cell lysis of virus infected cells or cancer cellsnot phagocytic

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4. Inflammatory Responselarger response that prevents spread of infection

from localized areadamage to body’s tissues causes:

redness, pain, heat and swellingsometimes loss of function

overall, has beneficial effect:a. destroys injuring agentb. removes it and its byproducts or limits its

effectsc. repairs or replaces damaged tissues

occurs in three major stages:a. vasodilationb. phagocyte migration and phagocytosisc. tissue repair

a. Vasodilation and Increased Permeabilitydamaged tissues release histamines and

kininsblood vessels dilate in area of damage

�increased blood flow to areacauses swelling (edema), redness and heatthis allows defensive chemicals and clotting

factors and cells to move to the areaclot forms around area to prevent spread of

infectionb. Phagocyte Migration and Phagocytosis

within an hour phagocytes begin to accumulate at the site

as the flow of blood decreases, phagocytesstick to lining of blood vessels then squeeze out into tissuespaces

chemical attractants, eg. kinins, draw WBC’s to siteneutrophils arrive first, monocytes

predominate during later stagesas WBC’s die � pus accumulates

c. Tissue Repaircant be completed until all harmful substances

have been removed or neutralized

5. Feversystemic rather than local responsehypothalamic thermostat is reset to eg. 102.2 ºFproduced by pyrogens secreted by macrophages

when exposed to certain pathogens

59

fever symptoms:blood vessels constrictmetabolism increasesshivering helps maintain high tempskin remains cold – chills

slight increase in temperature:a. inhibits growth of some pathogensb. speed metabolism

for repair of body cellsand to enhance phagocytosis

c. cause liver and spleen to store zinc and ironboth are nutrients needed by bacteria

d. intensifies effects of other chemicalseg interferon

6. Complement Reactions:foreign substance may trigger cascade which activatescomplement proteins

=complement fixation~5% of all blood proteins (20 different ones) are

complement proteinsthey can operate nonspecifically or specificallycomplement proteins formed from liver cells, lymphocytes,

monocytestrigger a cascade reaction (inactive� active)

� initiation� amplification� effects

complement fixation can cause any of the following effects:a. cell lysis (cytolysis)

membrane attack complex forms“transmembrane channels”

�ddigests a hole in bacterial cell, killing itb. opsonization

makes pathogens stickier and easier forthe leukocytes to phagocytize

c. enhances infllammatory responsehelps trigger release of histamine and

chemical attractants for WBC’s

the effects of complement activation are shortlived

� they are quickly destroyedmalfunctions of system may result in some

60

hypersensitivity disorders

7. Interferonantiviral chemical secreted by infected cellsthey are host cell specific, not virus specific

� different tissues in same host producedifferent interferons

all interferons are small proteinsstable at low pHheat resistant

produced by infected cells and spread to uninfectedcells� stimulate synthesis of antiviral proteins that

disrupt various stages of viral multiplicationeffective for only short periods

� good for acute, short term infectionseg. colds, influenza

interferon is now produced in quantity by recombinant DNAtechnology

has only very limited effects on cancer cellshigh doses have side effects:

fatigue, fever, chills, joint pain, seizuresexperimentally used to treat HIV, Hepatitis, genital herpes,

influenza, common coldmight work better with other agents in combination