Transcript P2b lecture by sub Teri


Transport


Protection



O2, CO2, nutrients, wastes, hormones, and heat
Platelets & clotting
WBCs:
 Immunity &
 Inflammation
Regulation


“Chemistry”
 pH & buffering of ECF & blood
“Amount”
 Fluid and electrolyte balance
You have about 4-6 liters of
blood (think 5!)
≈ 8% of total body weight
100.4 degrees F
Plasma =clear extracellular
fluid (& mostly water)
“Cells” float in the plasma
Erythrocytes
Leukocytes
Platelets

Viscosity = resistance to flow


whole blood ≈ 5 times as viscous as H2O
Osmolarity = has to do with # of
dissolved particles (see p. 104-105 for
review)

total number of dissolved particles in the
blood is important!
 sodium ions, protein (albumins) & RBCs =
most important affectors of blood osmolarity

Molarity = # of moles (of substance) per liter of solution
Osmolarity = # of osmoles per liter of solution

WHAT?!




e.g.


1 osmole = 1 mole of dissolved PARTICLES (not necessarily = to
the number of moles of the SUBSTANCE you put in!)
Depends on whether the substance is IONICALLY bonded or
COVALENTLY bonded
1 Mole glucose  1 osm glucose solution
BUT:

1 Mole NaCl  2 osm Na+ + Cl- solution
(NaCl disassociates in solution to twice the number of particles)

TAKE HOME MESSAGE: The total number of particles in blood vs. ECF is
important! Water will move into compartment with more particles (think, “to try
to disperse them” and balance osmolarity).
Therefore:
Balance between
Blood and ECF
depends on:
Ignore details of picture for now - just get main idea,
that osmolarity is really IMPORTANT and helps govern
which way fluid will move!
1) Filtration OUT of
capillary
-Pressure,
viscosity &
osmolarity
2) Reabsorption by
OSMOSIS
High
blood osmolarity:
causes fluid absorption into blood (from gut & ECF) = raises BP
Low
blood osmolarity:
causes fluid to remain in tissues = lowers BP, may result in
edema

Plasma – liquid “matrix” (of vascular connective tissue)


Serum remains after plasma clots
3 major categories of plasma proteins

albumins - most abundant
 contributes to viscosity and osmolarity

globulins (antibodies)
 provide immune system functions
 alpha, beta and gamma globulins

fibrinogen
 precursor of fibrin threads that help form blood clots

Plasma proteins formed by liver

except globulins (produced by plasma cells=transformed B lymphocytes in
connective tissues)
Colloid Osmotic
Pressure: is the
contribution of
proteins to the
osmolarity of blood
Plasma Protein Deficiency:
-liver disease or
-starvation
Changes Body Osmolarity
Balance!
Kwashiorkor Example:
Canabalize tissues  muscle wasting
Low Protein Diet  low protein levels in body  low blood osmolarity 
Fluid buildup in tissues  & ascites

Nitrogenous compounds



Nutrients



amino acids
 from dietary protein or tissue
breakdown
nitrogenous wastes (urea)
 toxic end products of catabolism
 normally removed by the kidneys
glucose, vitamins, fats, minerals, etc
O2 and CO2
Electrolytes

Na+ makes up 90% of plasma cations
BUN
Creatinine

Iron
(animation is the next “slide” – just know terms below!)

Ferric (Fe3+) vs Ferrous (Fe2+)
 stomach acid converts Fe3+ to absorbable Fe2+

Binds to THREE different proteins:





Vitamin B12 and Folic Acid


Gastroferritin – in stomach
Transferrin – in bloodstream
Apoferritin + Fe2+ = Ferritin (stored in liver)
Iron used in: bone marrow for hemoglobin, muscle for
myoglobin and all cells use for cytochromes in mitochondria
rapid cell division
Vitamin C and Copper

cofactors for enzymes synthesizing RBCs

Hemopoietic tissues produce blood cells
yolk sac produces stem cells
 liver stops producing blood cells at birth
 spleen remains involved with WBC
production
 red bone marrow

 pluripotent stem cells
 hemopoiesis produces RBCs, WBCs and platelets

Biconcave cells
7.5 M diameter
 Blood type determined by surface glycoprotein and
glycolipids
 Cytoskeletal proteins (spectrin & actin) give membrane
durability, but wear out ≈ 4 months
 No mitochondria
= anerobic respiration
 Eject nucleus so must make
all proteins in advance
 Spleen = RBC “graveyard”
 ≈ 2.5 million released into
circulation every second!

18-27

Gas transport - major function

increased surface area/volume ratio
 due to loss of organelles during maturation
 increases diffusion rate of substances

33% of cytoplasm is hemoglobin (Hb)
 O2 delivery to tissue and CO2 transport to lungs

Carbonic anhydrase (CAH)
produces carbonic acid from CO2 and water
 important role in gas transport and pH balance



Carry oxygen from the
lungs to your tissues (&
some CO2 from tissues
to lungs)
Contain hemoglobin, a
protein molecule that
actually carries the O2

Heme groups



conjugate with each
protein chain
 hemoglobin molecule
can carry four O2
oxygen binds to central
ferrous ion (Fe2+)
Globins - 4 protein
chains


2 alpha and 2 beta
chains
Except in fetus (HbF) gamma chains replace
beta chains; whole thing
binds O2 better
= due to switching over from Fetal Hemoglobin
(HbF) to Adult Hemoglobin (HbA) after birth
= increased hemolysis of fetal RBCs causes
increase in blood levels of bilirubin!
(We’ll talk about the advantages and
disadvantages of Fetal Hemoglobin in the next
unit - just know the above for now!)

“RBC count” and “hemoglobin concentration”
indicate amount of O2 blood can carry

hematocrit (packed cell volume) = % of blood
composed of cells (think ≈ 45%)
 men 42- 52% cells; women 37- 48% cells

hemoglobin concentration of whole blood (think ≈ 15%)
 men 13-18g/dL; women 12-16g/dL

RBC count (think ≈ 5 million per cm3 - that’s cubic centimeter)
 men 4.6-6.2 million/L; women 4-2-5.4 million/L
Higher
Lower
This is what a hematocrit capillary tube looks like the person is measuring the hematocrit percentage.

Negative feedback control:
drop in RBC count causes
hypoxia in tissues
 EPO production stimulates
bone marrow
 RBC count  in 3 - 4 days
(count too high = polycythemia)


Causes of Hypoxemia?



low levels O2 (altitude)
increase in exercise
loss of lung tissue in
emphysema


2.5 million RBCs/sec
Development takes 3-5 days


First committed cell - erythrocyte colony forming unit



reduction in cell size, increase in cell number, synthesis of
hemoglobin and loss of nucleus
has receptors for erythropoietin (EPO) from kidneys!
Erythroblasts multiply and synthesize hemoglobin
Discard nucleus to form a reticulocyte


named for fine network of endoplasmic reticulum
0.5 to 1.5% of circulating RBCs
Iron removed from heme
and converted (stepwise)
into bilirubin
Bilirubin
 is released into blood
plasma (kidneys  yellow
urine = urochrome)


liver secretes into bile
concentrated in gall
bladder: released into
small intestine; bacteria
create urobilinogen
(brown feces)
18-36

Polycythemia - an excess of RBCs (excessive
erythropoiesis)
 Always triggered by hypoxemia, no matter what the
cause
 Primary Polycythemia
 Cancer of erythropoietic cell line in red bone marrow
 hematocrit as high as 80%!!


Secondary Polycythemia (from hypoxemia)
 From dehydration, emphysema, high altitude, or
physical conditioning
Dangers of polycythemia

increased blood volume, pressure, viscosity
 can lead to embolism, stroke or heart failure


Anemia is a deficiency in O2 carrying-capacity of the
blood!
Due to:
 Low hemoglobin in the cells
 OR Too few RBCs
Symptoms:
 Pallor
 Weakness
 Tiredness
 Unable to
exercise without
getting out of
breath

Inadequate erythropoiesis or hemoglobin
synthesis






inadequate vitamin B12 from poor nutrition or lack of
intrinsic factor (pernicious anemia)
Don’t
iron-deficiency anemia
make
kidney failure and insufficient erythropoietin enough
aplastic anemia - complete cessation of
Hemorrhagic anemias
Hemolytic anemias
Lose cells
faster than
you can
make
them




Tissue hypoxia and necrosis
Low blood osmolarity (tissue edema)
Low blood viscosity (heart races and pressure
drops)
Short of breath and lethargic



Hereditary Hb ‘defect’
common in peoples of
African descent
 Recessive allele
modifies hemoglobin
structure under low O2
conditions
(hypoxemia)
 Due to a single amino
acid substitution only!
1 in 500 African
Americans have the
disease
1 in 1000 to 1400
Hispanic-Americans

Antigens

unique molecules on cell surface
 used to distinguish self from foreign
 foreign antigens generate immune response

Antibodies

secreted by plasma cells
 as part of immune response to foreign matter

Agglutination
antibody molecule binding to antigens
 causes clumping


RBC antigens
=Branched
sugars

Or called
agglutinogens
(because they’re
not antigenic to
YOU, who made
them)
 A and B

on RBC surface

Your ABO blood type is determined by
presence or absence of antigens
(agglutinogens) on RBCs

type A person has A antigens
 (although they’re not antigenic to YOURself)
type B person has B antigens
 type AB has both antigens
 type O has neither antigen

 most common - type O
 rarest - type AB


Antibodies (agglutinins); anti-A and -B
Appear 2-8 months after birth; at maximum
concentration at 10 yr.

Anti -A and/or -B (both or none) are in plasma
 you do not form antibodies against your antigens

Agglutination


each antibody can attach to several foreign antigens at
the same time
Responsible for mismatched transfusion reaction

Agglutinated RBCs block blood vessels and hemolyze

free Hb blocks kidney tubules, causes death

Universal donor



Type O
lacks antigenic branched sugar on RBC surface
donor’s plasma may have antibodies against
recipient’s RBCs, however …

(but transfused volume is smaller than amount of blood in recipient’s body - hopefully)
 may give packed cells (minimal plasma)

Universal recipient


Type AB
lacks plasma antibodies; no anti- A or B

Rh (D) agglutinogens discovered in rhesus
monkey in 1940
Rh+ blood type has D agglutinogens on RBCs
 Rh frequencies vary among ethnic groups


Anti-D agglutinins not normally present

form in Rh- individuals exposed to Rh+ blood
 Rh- woman with an Rh+ fetus or transfusion of
Rh+ blood
 no problems with first transfusion or pregnancy

Occurs if mother has formed antibodies
and is pregnant with 2nd Rh+ child


Anti-D antibodies can cross placenta
Prevention

RhoGAM given to pregnant Rh- women
 binds fetal agglutinogens in her blood so she
will not form Anti-D antibodies
Fig. 18.16

Rh antibodies attack fetal blood

causing severe anemia and toxic brain syndrome




5,000 to 10,000 WBCs/L
Conspicuous nucleus
Travel in blood before migrating to connective
tissue
Protect against pathogens
(We’ll talk more about WBCs in Lymphatic
System & Immunity lecture)

Neutrophils ( in bacterial infections)
 phagocytosis of bacteria
 release antimicrobial chemicals

Eosinophils ( in parasitic infections or allergies)
 phagocytosis of antigen-antibody complexes,
allergens and inflammatory chemicals
 release enzymes to destroy parasites

Basophils ( in chicken pox, sinusitis, diabetes)
 secrete histamine (vasodilator)
 secrete heparin (anticoagulant)


Lymphocytes ( in diverse infections and immune
responses)
 destroy cells (cancer, foreign, and virally infected
cells)
 “present” antigens to activate other immune cells
 coordinate actions of other immune cells
 secrete antibodies and provide immune memory
Monocytes ( in viral infections and inflammation)
 differentiate into macrophages
 phagocytize pathogens and debris
 “present” antigens to activate other immune cells

These things are usually included:





Hematocrit
Hemoglobin concentration
Total count for RBCs, reticulocytes, WBCs, and
platelets
Differential WBC count
RBC size and hemoglobin concentration per RBC

Leukopoiesis




Colony-forming units in each cell line (in bone
marrow)
T lymphocytes complete development in thymus
Red bone marrow stores and releases
granulocytes and monocytes
Circulating WBCs do not stay in bloodstream
granulocytes leave in 8 hours and live 5 days longer
 monocytes leave in 20 hours, transform into
macrophages and live for several years
 WBCs provide long-term immunity (decades)

Fig. 18.18



Leukopenia = low WBC count (<5000/L)
 causes: radiation, poisons, infectious disease
 effects: elevated risk of infection
Leukocytosis = high WBC count (>10,000/L)
 causes: infection, allergy and disease
 differential count - distinguishes % of each cell type
Leukemia = cancer of hemopoietic tissue

Actually causes a HIGH WBC count, but cells are immature and not
able to perform proper functions

So it is AS IF you had far too few WBCs!
acute and chronic - death in months or  3 years
effects - normal cell % disrupted; impaired clotting




Platelets
Fibrinogen
Compare:
small Lymphocyte
Erythrocyte
Platelet

Small fragments of megakaryocytes



2-4 m diameter; contain “granules”
amoeboid movement and phagocytosis
Functions
secrete vasoconstrictors
 stick together to form temporary platelet plugs
 secrete clotting factors
 initiate formation of clot-dissolving enzyme
 chemically attract neutrophils and monocytes to sites of
inflammation
 phagocytize bacteria


All 3 steps involve
platelets
Pain receptors 
through reflex arc,
cause constriction
of vessel
 Smooth muscle
injury
 Platelets release
serotonin
(=vasoconstrictor)

Normally endothelium =
smooth
 Broken vessel exposes
rough collagen
 Platelet pseudopods
STICK to rough collagen
and other platelets
 Pseudopods contract
and draw walls of vessel
together forming a
platelet plug

18-64

GOAL = to convert
Fibrinogen to Fibrin
Threads

Fibrinogen (a plasma
protein) is converted into
fibrin threads which form
the clot

TWO DIFFERENT ways
this can be initiated:
 Clotting factors coming
from within the blood
itself OR
 Clotting factors from
vessel wall
18-65



GOAL of BOTH pathways to
make Fibrin Threads by
activating Fibrinogen
Two DIFFERENT ways to
get to Factor X (‘weird’, but
handy)
Extrinsic pathway
Clotting factors come from
OUTSIDE the blood itself
 Initiated by damaged tissues
 Fewer steps to Factor X, so
takes about 15 seconds


Intrinsic pathway
Clotting factors all found IN
the blood
 Initiated by platelets
 More steps, so takes 3-6
minutes!


Some books have ERROR 
Calcium required for either
pathway!



Factor X gets activated
by either pathway
(intrinsic or extrinsic)
Factor X activates
something….
… that activates the
‘FINAL ACTIVATOR’
Thrombin

Thrombin causes Fibrin
threads to form by
activating Fibrinogen

Then they form 3-D mesh
throughout platelet plug,
entrapping RBCs, WBCs
etc.
ERROR 


Most of the clotting
factors are made
in the liver
Liver diseases
compromise
clotting!

Platelet-derived growth factor secreted by
platelets and endothelial cells


repair damaged vessel
Fibrinolysis (dissolution of a clot)

plasmin, a fibrin-dissolving enzyme (clot buster)



Genetic lack of any clotting factor affects
coagulation
Sex-linked recessive (on X chromosome)
Physical exertion causes bleeding and
excruciating pain


18-70
transfusion of plasma or purified clotting factors
factor VIII produced by transgenic bacteria


Embolism - clot traveling in a vessel
Thrombosis - abnormal clotting in unbroken
vessel



most likely to occur in leg veins of inactive people
pulmonary embolism - clot may break free, travel from
veins to lungs
Infarction may occur if clot blocks blood supply
to an organ (MI or stroke)

18-71
650,000 Americans die annually of thromboembolism
Next – A Bit About
Blood Vessels



Arteries carry blood away from heart
Veins carry blood back toward heart
Capillaries connect smallest arteries to veins
Tunica interna (intima)
= smooth inner layer of
simple squamous
endothelium; with Internal
elastic lamina (frequently
seen)
Tunica media
= middle layer, usually
thickest;
smooth muscle,
collagen, some elastic
fibers woven among
cells sometimes
Tunica externa (or tunica
adventitia)
= outermost layer of
loose connective tissue
with vasa vasorum in
larger arteries

Arterioles (= resistance vessels)




control amount of blood to various organs, by dilating
or constricting
Innervated by Sympathetic neurons
Systemic body arterioles partially constricted at all
times normally to maintain blood pressure!
Metarterioles


short vessels connect arterioles to venules through
capillary beds
Have smooth muscle cells that form precapillary
sphincters around entrance to each capillary
1. Continuous - occur in most tissues

endothelial cells have tight junctions with
intercellular clefts (allow passage of solutes)
2. Fenestrated - kidneys, small intestine


organs that require rapid absorption or filtration
filtration pores – spanned by very thin glycoprotein layer allows passage of only small molecules
3. Sinusoids – liver,
spleen, bone marrow

irregular blood-filled
spaces; some have extra
large fenestrations, allow
proteins and blood cells
to enter


Sinus rhythm – 70-80 BPM (beats per minute)
w/Vagal innervation, called Vagal Tone
SA node intrinsic rate = 100 BPM


Ectopic focus – any region of spontaneous firing that
is not SA



So Vagus innervation SLOWS intrinsic heart rate!
nodal rhythm - set by AV node, 40 to 50 bpm
intrinsic ventricular rhythm - 20 to 40 bpm
Arrhythmia - abnormal cardiac rhythm

heart block: failure of conduction system
 bundle branch block
 total heart block (damage to AV node)

Angina pectoris



partial obstruction of coronary blood flow can cause
chest pain
pain caused by ischemia, often activity dependent
Myocardial infarction


complete obstruction causes death of cardiac cells in
affected area
pain or pressure in chest that often radiates down left
arm


Short, branched cells, one central nucleus
Intercalated discs join myocytes end to end



interdigitating folds -  surface area
mechanical junctions tightly join myocytes:
 fascia adherens: actin anchored to plasma membrane;
transmembrane proteins link cells
 desmosomes
electrical junctions - gap junctions allow ions to flow