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 control
produce biologically active chemicals
in some cases use same chemical
hormones affect nervous system/nervous sytem
affects hormone releases
one 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 effects
targets: other neurons, muscle cells, glands,
transmits long range information by nerve
impulses
uses chemical signals (=neurotransmitters)
only cell to cell
neurotransmitter only produced by neurons
immediate response
short lived (ms – minutes)
Endocrine
widespread effects
targets: all tissues
transmits long range information as chemical
signals only
= hormones, through circulatory system
gradual response (seconds – hours)
longer – lived effects (minutes – days)
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Chemicals shared between Nervous and Endocrine Systems
Functions
as Neurotransmitter
as Hormone
Endorphins
binds to pain receptors in brain
released from hypothalamus during
times of stress
Enkephalins
blocks pain perception
adrenal medulla – blocks pain
sensations
Dopamine
“feel good” NT in limbic system & inhibits secretion of prolactin
midbrain
Estrogen,Progesterone affects appetite center & body temp
gonads and adrenal cortex - initiate
in hypothalamus and stimulates
secondary sex characteristics, follicular
sexual arousal pathways
development & menstrual cycle
Testosterone
stimulates sexual arousal pathways
gonads and adrenal cortex - initiate
and orgasm reflex
secondary sex characteristics &
spermatogenesis
Norepinephrin,
“feel good” NT in limbic system
adrenal medulla – maintains
Epinephrin
and sympathetic branch of ANS
sympathetic response
Prolactin
NT in brain
anterior pituiitary – milk production
Leutinizing 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 minor
hormones circulating in body
some general effects of hormones on body:
a. enhance or moderate neural control of effectors
b. affects overall metabolic rate
c. 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 to
environmental changes that can cause infection, trauma, thirst,
hunger
e. contributes to all aspects of the reproductive
process
f. provides smooth, sequential integration of all
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factors involved in growth and development
g. 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 one
another
4. Many endocrine glands secrete more than one
hormone
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 type
of 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 permeability
b. protein synthesis stimulated or inhibited
c. enzymes activated or inactivated
d. 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 for
same 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 drop
or 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 hormones
b. relative # of receptor proteins on
target cells
c. affinity of binding
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Hormones effects are concentration dependent
overstimulation can cause desensitization
hyper and hypo secretion
much of our knowledge of hormones effects comes
from study of abnormal production
similar problems if too little or too many receptor
proteins 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” from
ATP
cyclic AMP diffuses throughout cell and mediates target cell response to
hormone
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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 of
negative feedback system
three major mechanisms:
1. Humoral
2. Neural
3. Hormonal
some endocrine glands respond to multiple stimuli
1. Humoral
hormones secreted in direct response to changing blood levels of certain
chemicals in blood
affect endocrine gland directly
eg. parathyroid gland
cells directly monitor conc of Ca++ions
when Ca++ decline they respond by secreting PTH
eg. pancreas
insulin 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 gland
directly stimulated by sympathetic fibers of ANS
produces same effects as Sympathetic NS but lasts
10 times longer:
∆ cardiac output
∆ heart rate
∆ alertness
∆ respiratory rate
eg. Posterior Pituitary
secretes 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 endocrine
glands
Tropic Hormones
each tropic hormone has a target gland which it stimulates to produce its
characteristic 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 nerve
impulses and reat by secreting neurohormones = releasing
hormones
produces specific Releasing Hormones for
each 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 interpreted
and 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 mechanisms
require 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 production
of 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:
hibernation
estrous
migration
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 melatonin
light suppresses production
dark 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 child
maximum 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 cholecalciferol
an 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 secrete
Atrial Natriuretic Peptide (ANP)
reduces blood volume, pressure, Na+ conc
does this by:
signaling kidney to increase productio of salty
urine
and 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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enterogastrone
secretin
cholecystokinin
regulates secretion of:
gastric juices
pancreatic enzymes
bile
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:
GH
insulin
calcitonin
PTH
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 which
stimulates cartilage development
in women estrogen stim secretion of IGF causing
uterine enlargement
in women: in cartilage of long bones, estrogen
interferes 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 & neuromodulators
hormones
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
=eicosanoids
produced in almost every organ and tissue of body
except RBC’s
not officially part of endocrine system
biologically active lipids
(modified fatty acids, not steroids)
local regulators (= tissue hormones)
made in small quantities
short lived
mainly prostaglandins and leukotrienes
have 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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clotting
eg thromboxane
constricts blood vessels
promotes platelet aggregations
urinary function
fat 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 complex
ways to regulate metabolic levels:
synergists hormomes which tend to cause the
same effect
eg. ADH & aldosterone
antagonists hormones which produce opposite
effects
eg. insulin & glucagon
permissive hormones which only affect
“preprimed” tissues
eg. progesterone
eg. 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 proportions
high TH: excessive growth, short stature,
demineralization in adults
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mineralocorticoids
testosterone
especially skeletal growth
Hormones that generally inhibit growth:
glucocorticoids
estrogen
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 and
promoting 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
glycogen
glucose
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 glycogen
synthesis of other carbohydrates, proteins, lipids
several hormones from various glands play a direct role in glucose
homeostasis
1. Insulin (Pancreas-Islet Cells)
accelerate transport of glucose into body cells
increases 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 lactic
acid, glycerol, etc (=gluconeogenesis)
raises blood glucose levels
3. ACTH (Anterior Pituitary)
tropic hormone that affects glucocorticoid
production
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 catabolism
increases oxidation of fats; spares glucose
unused glucose is converted to glycogen to
maintain 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 in
muscle 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 insipidus
diabetes 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 blindness
17 x’s greater rate of kidney disease
17 x’s greater rate of gangrene
2 x’s greater chance of heart attack
diabetes is a group of disorders
may be triggered by:
genetic factors
environmental factors
autoimmune disease
pregnancy
obesity
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 of
glucose
levels of glucose build up in blood
3-10 times normal = hyperglycemia
since glucose can’t be used alternate fuels are
mobilized:
increased fat mobilization
fats in blood rise to up to 5x’s normal
as cells shift to fat catabolism
produce ketone bodies
lower blood pH = acidosis
acetone breath
increased risk of atherosclerosis
without insulin to stimulate protein
synthesis they are instead broken down and converted
to glucose in cells
tissue wasting
high levels of glucose in blood lead to large
quantities 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’s
inside all body cells
Extracellular
all fluid outside cells
~1/3rd of body water
some 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 each
compartment means maintaining a balance in body as a whole
they interact with the environment by specialized organ systems:
respiratory system
excretory system
digestive system
Fluid inputs:
digestive tract
metabolism
TOTAL:
2000ml
500ml
2500ml
Fluid outputs:
kidneys
1300ml
20
lungs
skin
intestine
TOTAL:
450ml
650ml
100ml
2500ml
Body’s transport system plays key role in balancing fluids in the body’s
compartments
“river of life” Marieb
Transport system includes:
Circulatory system (=cardiovascular system)
blood
Lymphatic system
lymph
General Functions of these Transport Systems:
Transport functions:
1. Pick up food and oxygen from digestive and
respiratory systems and deliver them to cells
2. pick up wastes and carbon dioxide from cells and
deliver to kidneys and lungs
3. Transport hormones, enzymes etc throughout the
body
Homeostasis functions:
4. maintain fluid and electrolyte balances in tissues and
cells
5. maintain acid/base balances in tissues and cells
6. help regulate temperature homeostasis
transfers 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 weakness
loss of >30% severe shock, death
arterial blood: bright red = oxyhemoglobin
venous blood: darker red
viscosity
pH
temperature
=
=
=
4.5 - 5.5
7.35 – 7.45
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
formed elements 45%
55% of volume
Plasma
the liquid part of blood
clear straw colored fluid
serum = plasma with clotting factors removed
90% water;
10% solutes
>100 different solutes
salts, ions, gasses, hormones, nutrients,wastes
most 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 blood
erythrocytes (RBC’s) –most, 45%, of formed elements
leukocytes (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 elements
99% of formed elements
5.5 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 diameter
greater efficiency of gas exchange
area of all RBC’s in body = >football field for gas exchange
flexible
easily deforms to fit through narrow capillaries
affects speed of bloodflow
regulated 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:
women:
13-20 g/100ml
12-16 g/100ml
each hemoglobin consists of:
a protein = globin
combined with 4 pigment molecules = heme
each heme contains 4 Iron atoms
each iron atom can combine with
1 O2 molecule
each hemoglobin molecule can combine with
4 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/day
females
=
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 erythropoietin
excessive O2 inhibits hormone production
testosterone enhances kidney production of erythropoietin
estrogen 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) phagocytize
the 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. Anemias
symptoms:
pale
lack energy
low hematocrit:
males
females
low hemoglobin
males:
women:
kinds:
5.1 – 5.8 mil/mm3
4.3 – 5.2 mil/mm3
13-20 g/100ml
12-16 g/100ml
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: thalassemias
thin and delicate blood cells
sickle cell
3. Polycythemia
too many RBC’s
8-11 million/mm3
hematocrit = 80%
increased viscosity
causes:
overstimulation of stem cells
high altitude
prolonged physical activity
fluid loss
genetic factors
2. Leucocytes
4000-11,000/mm3 or 1% of blood volume
numbers are misleading since they do most of their work outside the blood
vessels
mainly function in protection of body
as part of immune system
WBC’s are motile by amoeboid motion
they squeeze out of capillaries into tissue spaces
attack and destroy bacteria and pathogens
remove 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 are
clinically important
= differential WBC count
ID depends on presence and staining
characteristics of granules and nucleus:
neutrophils
40-70%
granulocyte
attracted to sites of inflammation
lifespan: hours - days
especially bacteria and some fungi
indicate: acute infections and appendicitis
eosinophils
1-4%
granulocyte
especially abundant in pulmonary mucosa and
dermis
counteract inflammatory chemicals
eat proteins, not “bugs”
lifespan: days
indicate: worms and protozoan parasites
basophils
<1%
granulocyte
least abundant of WBC’s
tissue basophils = Mast Cells
bind to Ig E release of heparin and histamine
leaky vessels
enhance migration of WBC’s to site
lifespan: hours - days
lymphocytes
20-45%
agranulocytes
only few in “blood”
T and B cells
lifespan: hours to years
monocytes
5-8%
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agranulocytes
only few in blood
in tissue become macrophages
lifespan: months
increases: 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) from
macrophages and T lymphocytes exposed to antigens and toxins
lifespan: hours to lifetime
Leukocyte Disorders
1. Leukocytosis
total WBC count >10,000/mm3
indicate:
acute infections, eg appendicitis
vigorous exercise
excessive loss of body fluids
2. Leukopenia
total WBC count <5,000/mm3
indicate:
influenza
measles
mumps
chickenpox
poliomyelitis
anemias
lead poisoning
3. Leukemia
cancer 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 crowded
out
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 in
hemostasis and
blood clotting
Hemostasis
stoppage of blood flow
include:
vascular spasm
reduces blood loss
platelet plug
1-5 seconds after injury
platelets become sticky
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platelets swell
develop spiky processes
become sticky adhere tenaceously
degranulate release serotonin &
throboxane
enhance vascular spasm
aggregating 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 vessel
slow 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 that
tangle together forming a clot
clot retraction
30-60 minutes
draws edges of clot together
fibrinolysis
= clot dissolution
30
occurs continuously
plasmins & fibrolysin = clot busters
Thrombocyte Disorders
body has mechanism that prevent spontaneous clotting without vessel
damage:
- 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 factors
two conditions favor clots:
rough spots on blood vessels
atherosclerosis may trigger clotting
abnormally slow flow of blood
bedridden or imobilized patients
these may be caused by:
atherosclerosis
severe burns
inflammation
slow flow
thrombus – a fixed persistant clot
embolism – a traveling clot
2. Bleeding Disorders (=Hemophilias)
inability of blood to clot in normal amount of time
may be caused by
decreased # of platelets
liver disease
inability to form various clotting factors
prothrombin and fibrinogen are produced in liver
require vitamin K (absorbed from intestine)
vitamin K requires bile to be digested and
absorbed
if bile ducts becfome obstructed results in vitamin
K deficiency
liver cant produce prothrombin at
31
normal rate
eg. factor VII
comprises 83% of cases
eg. factor X
a 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 distinguishes
between “self” and “nonself”:
self = all proteins and other chemicals that
are part of our bodies; that belong there
nonself = any proteins or chemicals that don’t
belong
antigen = any foreign substance that enters our
body
antibody = special proteins made by our immune
system to remove foreign substances
many antigens are present on surface of blood cells
only a few are important in transfusions:
ABO system
Rh system
If these antigens are attacked by our antibodies it causes agglutination
(clumping) of cells
[antibodies are agglutinins: cause clumping]
leads to:
heart attack
stroke
kidney failure
etc
most important consideration in transfusions:
32
don’t want recipient’s antibodies to react with donor’s antigens
Blood
Type
Antigens
A
antibodies
produced
anti B
can donate
blood to
A, AB
can receive
blood from
A, O
A
B
anti A
B, AB
B, O
B
AB
A&B
neither
AB
O
none
both
A, B, AB, O
(universal
donor)
A, B, AB, O
(universal
recipient)
O
Blood
Group
A
B
AB
O
% Frequency in US Population
White
Black
Asian
Native
American
40
27
28
16
11
20
27
4
4
4
5
<1
45
49
40
79
even type O donors must be cross matched
since many other antigens are present and some may cause reactions
Rh incompatability:
RhoGAM blocks the mothers immune systems response and prevents her
sensitization to Rh+ blood of child.
RhoGAM is a serum containing anti-Rh agglutinins that agglutinate the Rh
factors that get into her blood
Circulatory System
large, multicellular organisms need good transport system to supply all cells
with nutrients and oxygen, to get rid of carbon dioxide and wastes, and to
distribute hormones
major connection between external and internal environment:
33
everything going in or out of body must go through the circulatory
system to get to where its going
two major transport systems in body:
circulatory (cardiovascular) system
lymphatic 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, 1628
idea 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 fibrous
outer layer and inner serous membrane
outer surface of heart is also covered with serous
membrane (= visceral pericardium) (=epicardium) continuous with the
pericardium
between the 2 membranes is pericardial fluid
lubrication
wall of heart:
epicardium
= visceral pericardium
thin & transparent serous tissue
myocardium
= cardiac muscle cell
34
most of heart
branching, interlacing contractile tissue
acts as single unit (gap junctions)
endocardium
= delicate layer of endothelial cells
continuous with inner lining of blood vessels
[endocarditis]
interior of heart is subdivided into 4 chambers:
atria = two upper chambers
with auricles
smaller, thinner, weaker
ventricles = two lower chambers
larger, thicker, stronger
left 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 atrium
quickly 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 in
one direction:
2 Atrioventricular (AV) valves
held in place by chordae tendinae
attached to papillary muscles
prevent backflow (eversion)
keeps valves pointed in direction of
flow
bicuspid (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
35
at beginning of aorta
pulmonary SL valve
at beginning of pulmonary trunk
Histology of Heart
cardiac muscle fibers:
striated
1 nucleus
branched cells
T tubules and SR less developed than skeletal mm
separated by intercalated discs
myocardium behaves as single unit
but atrial muscles separated from
ventricular muscles by conducting tissue sheath
atria contract separately from ventricles
mitochondria account for 25% of cardiac muscle
cells
(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:
glucose
fatty acids (preferred)
lactic acid
refractory period lasts 250 ms
almost 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 rhythm
70-75 beats/min
36
initiates stimulus that causes atria to contract
(but not ventricles directly due to separation)
AV Node
picks up stimulus from SA Node
if 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 Node
takes stimulus from AV Node to ventricles
Purkinje Fibers
takes 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 be
picked up by an electrocardiograph
=electrocardiogram (ECG; EKG)
ECG is a record of the electrical activity of the conducting system
body 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 Node
atrial depolarization
QRS wave
=
passage of current through
ventricles from AV Node – AV Bundle – Purkinje
Fibers
ventricular depolarization
T wave
=
repolarization of ventricles
(atrial repolarization is masked by QRS)
by measuring intervals between these waves can get idea of how rapidly the
impulses are being conducted
37
amplitude of waves also gives info on condition of conducting system and
myocardium
Abnormalities of ECG’s = arrhythmias
1. bradycardia (<60 bpm)
decrease in body temperature
some drugs (eg digitalis)
overactive parasympathetic system
endurance athletes
2. tachycardia (>100 bpm)
increased body temperature fever
emergencies, stress activation of sympathetic NS
some drugs
may promote fibrillation
3. flutter
short bursts of 200-300 bpm
but coordinated
4. fibrillation
rapid, uncoordinated contractions of individual muscle cells
atrial fibrillation is OK
(since it only contributes 20% of blood to heart beat)
ventricular fibrillation is lethal
electrical shock used to defibrillate and recoordinate contractions
5. AV Node Block
normal P - Q interval = 0.12 – 0.20 seconds
changes indicate damage to AV Node
difficulty in signal getting past AV Node
1st º block:
>0.20 seconds
2
nd
3rd
º block:
AV Node damaged so only so wave passes
through ventricles only after every 2-4 P waves
º block: (complete block)
no atrial waves can pass through
ventricle paced by different ectopic pacemaker
therefore beat abnormally slow
Cardiac Cycle
1 complete heartbeat (takes ~ 0.8 seconds)
38
consists of:
systole contraction of each chamber
diastole relaxation of each chamber
two atria contract simultaneously
as they relax, ventricles contract
ventricular systole (atrial diastole) = 0.3 sec
ventricular diastole
= 0.5 sec
contraction and relaxation of ventricles produces characteristic heart sounds
lub-dub
lub = systolic sound
contraction of ventricles and closing of
AV valves
dub =
diastolic sound
shorter, sharper sound
ventricles relax and SL valves close
abnormal sounds: “murmurs”
defective valves
congenital
rheumatic (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
nodes
control center in medulla
receives sensory info from:
baroreceptors (stretch)
in aorta and carotid sinus
increased stretch slower
chemoreceptors
monitor carbon dioxide and pH
39
more CO2 or lower pH faster
Other Factors that Affect Heartrate:
1. hormones
epinephrin faster
thyroxine faster
acetylcholine ?
2. ions
low Calcium slower
high Calcium faster
spastic heart contracitions
high Sodium blocks Ca++ slows
high Potassium faster
may cause cardiac arrest
3. temperature
heat increases heart rate
4. age
younger = faster, slows with age
5. gender
women = faster (72-80 bpm)
men = slower (64-72 bpm)
6. exercise
increases during exercise
also heart beats slower in physically fit
7. emotions
fear, anxiety, anger increase HR
depression, grief reduce HR
any marked, persistent changes in rate may signal cardiovascular disease
B. Stroke Volume:
healthy heart pumps ~60% of blood in it
normal SV = ~70 ml
SV
=
EDV (end diastolic vol) – ESV (end systolic vol)
affected by:
mean arterial pressure
back pressure
heart contractility
indicates amt of damage
amount of stretch
Starling’s Law: within physiological limits the heart pumps all
the blood that returns to it without undue damming of blood
in veins.
40
intrinsic regulatory mechanisms permit adaptation of the
heart to varying rates of venous return.
>stretch = >strength of contraction
venous return
viscosity
(>RBC’s, dehydration, blood proteins)
Blood Pressure
measured as mmHg
blood flow in arteries depends on:
1. pressure gradient created by heart beat
2. 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’s
MAP = Diastolic Pr + 1/3rd x Pulse Pressure
arteries
variable
systolic = 130-5 mmHg
diastolic = 85-90 mmHg
capillaries
35 – 15 mmHg
veins
6 – 1 mmHg
larger veins near 0 mmHg
41
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 Pressure
use sphygmomanometer
usually use brachial artery
procedure:
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 pressure
c. continue to release until there is no
obstruction of flow
sounds disappear
= diastolic pressure
normal BP = 110-140 / 75-80 [mm Hg]
top number = systolic pressure
force of ventricular contraction
bottom number = resistance of blood flow
may be more important
indicates strain to which vessels are
continuously subjected
also reflects condition of peripheral vessels
Normal Blood Pressure varies with:
42
age
kids 90/60; adults 120/80; old 150/82
gender
race
socioeconomic status
mood
physical activity
posture
etc
sclerosis high diastolic pressure
Main factors affecting blood pressure:
1. cardiac output
2. peripheral resistance
3. blood volume
a change in any of these could cause a
corresponding change in blood pressure
1. Cardiac Output
physical condition of the heart
already discussed cardiac output
2. Peripheral Resistance
factors that affect peripheral resistance are
mediated by autonomic nervous sytem
Peripheral 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 vessels
eg atherosclerosis inhibits flow
raises blood pressure
eg. obesity leads to many additional vessels
that blood must pass through
raises blood pressure
c. Blood Borne chemicals
43
numerous blood-borne chemicals influence
short term control of blood pressure
act directly on vascular smooth muscle or on
vasomotor system
eg. NO
secreted by endothelial cells
localized vasodilation lowers BP
very brief effect, quickly destroyed
is the major antagonist to sympathetic
vasoconstriction
eg.
viagra stim production of NO
eg. inflammatory chemicals
histamines, kinins, etc
potent vasodilators lower BP
increase capillary permeability
eg. nicotine
intense vasoconstriction raise BP
simulates sympathetic release of NE
eg. alcohol
depresses VMC
inhibits ADH release
vasodilation (esp of skin vessels) raises BP
(also flushing of face)
3. Blood Volume
blood pressure is directly affected by the volume
of fluids retained or removed from body:
greater volume increases BP
eg. excessive salts promote water
retention
lower volume decreases BP
eg. dehydration
eg. internal bleeding
factors that regulate blood volume are mainly
renal factors and are slower to change
long term controls
44
these factors can act as a system wide control over
whole 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 homeostasis
by regulating blood volume
kidneys act both directly and indirectly to regulate
arterial pressure:
a. Direct Renal Control of Blood Volume
involves regulation of blood volume by kidneys
greater BP:
more filtration from kidney
greater urine output
lower BP:
more reabsorption of water by kidney
lower urine output
b. Indirect Renal Control of Blood Volume
= Long Term Controls
renin-angiotensis mechanism
lower BP:
kidneys release enzyme = renin
renin triggers production of
angiotensin II
angiotensin causes:
vasoconstriction raises BP
release of ADH conserves water to
raise BP
Hypotension
low BP systolic <100
usually not a cause for concern
often associated with long healthy life
but.
in some may produce dizziness when standing
up too quickly (esp in older patients)
may be due to severe bleeding and lead to
circulatory shock
may hint at poor nutrition
eg. <blood proteins
45
Hypertension
if transient is normal:
adaptation during fever, exercise, strong
emotions
if persistent is a cause for concern
30% of those >50 yrs old suffer from
hypertension
usually asymptomatic for first 10-20 yrs
= silent killer
prolonged hypertension is a major cause of:
heart failure
vascular disease
kidney failure
stroke
Blood Vessels & Circulation
blood flows in closed system of vessels
over 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)lungspulmonary
veinsleft atrium
systemic: heart rest of body heart
left ventricleaortabodyvena cavart atrium
heart is a double pump
oxygen 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 tissue
tunica media
middle smooth muscle
46
tunica intima (=interna)
inner endothelium
Characteristics of Blood Vessels
Arteries
contain ~ 15% of all blood
pressure is variable
MAP ~ 93 varies from 100 – 40 mmHg
three layers:
thick layer of connective tissue for strength
heavily muscular to withstand pressure
large lumen
most organs receive blood from >1 arterial branch
provides alternate pathways
vasa vasorum = blood vessels within walls of large arteries
sympathetic innervation
Arterioles
~ 10% of all blood
average pressure ~40 –25 mmHg
pressure decreases drastically in arterioles
most resistance is here
~ 1/2 of whole system
muscle tissue makes up major bulk of walls
innervated by vasomotor nerve fibers of
autonomic NS
major role in controlling the distribution of blood in
body
sympathetic stimulation vasoconstriction
Capillaries
most of 62,000 miles of vessels
usually no cell >.1 mm away from a capillary
each capillary <1mm long
but only contains ~5% of blood in body
variable pressure 35 – 15 mm Hg;
ave=25-12 mmHg
thin walled - single cell layer thick
extremely abundant in almost every tissue of
body
1 inch3 of muscle = 1.5 million capillaries
A. density of capillaries varies with metabolic
rate
47
eg. cartilage and cornea have no capillaries
eg. tendons and ligaments are poorly
vascularized
eg. cartilage and epithelial cells lack
capillaries
eg. muscle, liver, lungs, kidneys have rich
blood supply
B. types of capillary structure:
1. continuous
lining is uninterrupted
adjacent cells joined by tight junctions
but with intracellular clefts to allow
passage of fluids and small solute
most common type
eg. skin, muscles, lungs, adipose
special: CNS
blood brain barrier
no clefts
2. fenestrated
similar to above but some cells are riddled
with pores
much greater permeability
eg. kidneys, endocrine glands, intestinal
mucosa
3. sinusoidal (discontinuous)
highly modified “leaky” capillaries
large clefts and fenestrae
allows large molecuels and cells to pass
eg. bone marrow, liver, spleen
C. capillary beds:
functional groupings of capillaries
= functional units of circulatory system
arterioles and venules are joined directly by
metarterioles (=thoroughfare channels)
capillaries branch from metarterioles
1-100/bed
cuff of smooth muscle surrounds origin of
capillary branches
= precapillary sphincter
48
amount of blood entering a bed is regulated by:
a. vasomotor nerve fibers
b. local chemical conditions
D. Velocity of blood flow
blood flows slowest in capillaries
due to greater cross-sectional area of all capillaries
combined:
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
membrane
ions and small molecules go through pores
(passive ion channels)
large molecules pass by exocytosis
Veins & Venules
60% of all blood is in veins
~10% in venules
low pressure:
12 – 8 mmHg venules
6 – 1 mmHg veins
larger veins near 0
generally have a greater diameter than arteries
but thinner walls
more compliant
three layer are all thinner than in arteries
tunica adventitia is thickest of three
but not as elastic as arteries
little 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:
49
1. constriction of walls by ANS
minor effect
muscle layer is very thin, veins are
very compliant
2. 1 - way valves
prevent backflow
most abundant in veins of limbs
quiet standing can cause blood to pool in veins
and may cause fainting
varicose veins: “incompetent” valves
esp. superficial veins
may be due to
heredity
prolonged standing
obesity
pregnancy
increased venous pressure
hemorrhoids:
varicosities of anal veins
due to excessive pressure from birthing or
bowel movements
3. venous pumps
muscular pump
(=skeletal muscle pump)
during contraction veins running thru
muscle are compressed and force blood in one
direction (toward heart)
respiratory pump
inspiration:
intrapleural pressure falls from –2.5 mm Hg
to –6 mmHg while abdominal pressure
increases
creates pressure gradient in Inferior Vena
Cava to move blood toward heart
expiration
increasing pressure in chest cavity forces
thoracic blood toward heart
veins function to collect blood and act as blood
reservoirs
with large lumens and thin walls they can
accommodate relatively large volumes of blood
50
60-70% of all blood is in veins at any
time
largest veins = sinuses
eg. coronary sinus, dural sinus
most organs are drained by >1 venous branch
even more common than alternate arterial
pathways
occlusion of veins rarely blocks blood
flow
removal of veins during bypass surgery
usually 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 through
cardiac output
peripheral resistance
the greatest peripheral resistance is found in the arterioles
85 at beginning
35 at end
50 mmHg difference
individual arterioles can increase or decrease their resistance to bloodflow by
constricting 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
51
vasomotor control system can also shift blood to or from blood reservoirs in
veins as needed:
large veins
sinuses
skin
liver
spleen
sensory input from:
baroreceptors in
carotid sinus
aortic arch
stretch inhibits VMC vasodilation
chemoreceptors
monitor oxygen and pH
in aortic arch and carotid sinus
these receptors also help to control
respiration
lower pH or O2 vasoconstriction
cerebral cortex and hypothalamus can affect VMC
eg. 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 also
direct blood to organs needing it most
individual tissues can control the amount of blood they receive through some
autoregulation (=intrinsic controls)
largely independent of systemic factors (VMC) noted above
Autoregulation involves:
1. Metabolic controls
2. Myogenic controls
52
1. Metabolic controls
changes in the concentrations of specific nutrients
or waste products can cause vasodilation and relaxation of
precapillary sphincters in affected tissues
eg. reduction in esp O2
eg. increases in potassium
eg. increase in Hydrogen ions (lower pH),
lactic acid
2. Myogenic controls
inadequate blood flow to an organ can cause cell
damage or death
too much blood flow may rupture fragile vessels
the physical effects of blood flowing to an organ causes direct local
stimulation 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 oxygen
or nutrients the body can respond by increasing the number of blood
vessels 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 in
tissues throughout their bodies
Body Defenses & Immunity
immunity = resistance to disease
the immune system provides defense against all the microorganisms and toxic
cells to which we are exposed
without it we would not survive till adulthood
our body has many ways to prevent or to slow infections
53
Many factors affect an individual’s overall ability to resist infections:
Genetics: human diseases, zoonoses, etc
Age: mainly an immune response
Health: 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 with
discrete organs
parts of many organs contribute to body defense
almost 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 barriers
b. internal cells and chemicals
2. Adaptive system that fights specific
pathogens
or, can view the immune system as a three tiered system of defense
a. physical and chemical barriers
b. chemical and cellular barriers
c. 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
54
shed regularly
rarely, if ever, penetrated while intact
only a few parasitic worms (cercariae) can do this
if skin is broken:
staphs and streps are most likely to get in
sebaceous glands
provides protective film over skin
acidity of skin secretions ('acid mantle') inhibit
fungal growth; also contains
bacteriocidal chemicals
bacterial &
but
if 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 body
nasal hairs
trap pathogens
mucous
thick, sticky, traps pathogens
cilia
in resp sys move mucous out of system
(‘ciliary escalator’ 1-3 cm/hr)
coughing and sneezing speed up process
gastric juices
secreted by lining of stomach
contains 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 in
stomach
may cause gastritis or ulcers
Lacrimal Apparatus
continual blinking flushes and wipes away
pathogens
lysozyme kills and dissolves some bacteria
55
(most G+ and some G- bacteria)
(lysozyme also found in sweat, saliva, and nasal
secretions)
Saliva
continual flushing of bacteria to stomach
lysozyme kills and dissolves some bacteria
Urine
continual flushing of bacteria entering urethra
low flow bladder infection
acidity also inhibits bacterial growth
Vaginal Secretions
flushing and trapping pathogens in mucous
acidity inhibits bacterial growth
but: some pathogens thrive in moisture and if they
occur in large enough numbers they are able to
penetrate eg. Treponema
Internal Cellular and Chemical Defenses
1. blood has nonspecific, antimicrobial chemicals that
help to fight invaders:
eg. transferrins – bind to Fe to inhibit bacterial
growth
2. Simple Phagocytosis
many WBC’s travel through blood and tissues and
gobble up bacteria and foreign material
mostly neutrophils and macrophages (formed from
monocytes)
migrate to area of infection
monocytes enlarge on way to become
macrophages
engulf and destroy circulating pathogens
especially bacteria
some 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 peritoneal
cavity
[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. Chemotaxis
chemical attraction to invaders, microbial products,
components of WBC’s or damaged cells
2. Adherence
attachment to surface of foreign material
may 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 with
certain plasma proteins that promote attachment
(=opsonization)
3. Ingestion
plasma membrane of phagocyte extends around
microorganism or cell
4. Digestion
forms food vacuole inside WBC
fuses with lysozomes
takes 10-30 minutes to kill most bacteria
enzymes:
lysozyme hydrolyzes peptidoglycan of cell
wall
lipases, proteases, ribonucleases hydrolyzes other cellular components
some enzymes also produce toxic oxygen
products: eg. O2-, H2O2, OHresidual body discharges wastes
not all microorganisms are killed once phagocytized
eg. Staph and Actinobacillus actually produce
toxins that kill phagocytes
eg. Chlamydia, Shigella, Mycobacterium,
Leishmania (protozoan), and Plasmodium
can survive inside phagocyte
they can prevent fusion of lysozome
eg. other microbes can remain dormant for
months
phagocytosis also plays a role in specific immunity
3. Natural Killer Cells
the “pit bulls” of the defense system
another kind of WBC
police the body in blood and lymph
promote cell lysis of virus infected cells or
not phagocytic
cancer cells
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4. Inflammatory Response
larger response that prevents spread of infection
from localized area
damage to body’s tissues causes:
redness, pain, heat and swelling
sometimes loss of function
overall, has beneficial effect:
a. destroys injuring agent
b. removes it and its byproducts or limits its
effects
c. repairs or replaces damaged tissues
occurs in three major stages:
a. vasodilation
b. phagocyte migration and phagocytosis
c. tissue repair
a. Vasodilation and Increased Permeability
damaged tissues release histamines and
kinins
blood vessels dilate in area of damage
increased blood flow to area
causes swelling (edema), redness and heat
this allows defensive chemicals and clotting
factors and cells to move to the area
clot forms around area to prevent spread of
infection
b. Phagocyte Migration and Phagocytosis
within an hour phagocytes begin to accumulate
at the site
as the flow of blood decreases, phagocytes
stick to lining of blood vessels then squeeze out into tissue
spaces
chemical attractants, eg. kinins, draw WBC’s to site
neutrophils arrive first, monocytes
predominate during later stages
as WBC’s die pus accumulates
c. Tissue Repair
cant be completed until all harmful substances
have been removed or neutralized
5. Fever
systemic rather than local response
hypothalamic thermostat is reset to eg. 102.2 ºF
produced by pyrogens secreted by macrophages
when exposed to certain pathogens
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fever symptoms:
blood vessels constrict
metabolism increases
shivering helps maintain high temp
skin remains cold – chills
slight increase in temperature:
a. inhibits growth of some pathogens
b. speed metabolism
for repair of body cells
and to enhance phagocytosis
c. cause liver and spleen to store zinc and iron
both are nutrients needed by bacteria
d. intensifies effects of other chemicals
eg interferon
6. Complement Reactions:
foreign substance may trigger cascade
which activates
complement proteins
=complement fixation
~5% of all blood proteins (20 different ones) are
complement proteins
they can operate nonspecifically or specifically
complement proteins formed from liver cells, lymphocytes,
monocytes
trigger 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 it
b. opsonization
makes pathogens stickier and easier for
the leukocytes to phagocytize
c. enhances infllammatory response
helps trigger release of histamine and
chemical attractants for WBC’s
the effects of complement activation are short
lived
they are quickly destroyed
malfunctions of system may result in some
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hypersensitivity disorders
7. Interferon
antiviral chemical secreted by infected cells
they are host cell specific, not virus specific
different tissues in same host produce
different interferons
all interferons are small proteins
stable at low pH
heat resistant
produced by infected cells and spread to uninfected
cells
stimulate synthesis of antiviral proteins that
disrupt various stages of viral multiplication
effective for only short periods
good for acute, short term infections
eg. colds, influenza
interferon is now produced in quantity by recombinant DNA
technology
has only very limited effects on cancer cells
high doses have side effects:
fatigue, fever, chills, joint pain, seizures
experimentally used to treat HIV, Hepatitis, genital herpes,
influenza, common cold
might work better with other agents in combination
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