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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:
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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
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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
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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