Blood
Chapter 19
OVERVIEW
Basics about blood
• Functions
• Properties
• Components
– Plasma
– Formed elements
Erythrocytes (RBC's)
•
•
•
•
Structure
Hematocrit
The kidney & EPO
Disorders: Anemia
Leukocytes (WBC's)
• 5 types
• Disorders
• Clinical tests
Platelets
• Hemostasis (clotting)
• Bleeding disorders
Basics about blood
Three main functions of blood:
1. DISTRIBUTION
"Blood gases" (O2, CO2)
Nutrients
Waste products – pick up & remove
Hormones
2. REGULATION
Regulate body temperature
Regulate pH (with buffers)
3. PROTECTION
Prevent blood loss (by clotting)
Prevent infection (w WBCs)
Blood Properties & Composition
Tissue type: Connective
Normal volume: 4-5L (depending on sex/size)
• increases by about a liter w/cardio!
Normal blood pH: between 7.35-7.45
Two components:
1. Plasma – the liquid part – a liquid ECM!
2. "Formed elements" – cells & cell parts
suspended in the plasma
• Erythrocytes (=red blood cells, or RBC's)
– CARRY OXYGEN
• Leukocytes (white blood cells, or WBC's)
– IMMUNE DEFENSE
• Platelets (specialized cell fragments)
– CLOTTING
Can separate plasma from
formed elements by centrifuging:
Plasma
"Buffy coat"
(buffy = cream-colored)
Erythrocytes
Plasma, "buffy coat" and erythrocytes
Plasma: Water with dissolved proteins, nutrients, etc.
("serum" = plasma minus the clotting proteins)
"Buffy coat": WBCs and platelets
Red blood cells:
Contain hemoglobin (Hb)
Formed elements
Plasma
Liquid containing dissolved substances
55-60% of blood volume
• 90% water
• 7% dissolved "plasma proteins"
• ~3% other solutes:
• Dissolved Gases – O2, CO2
• Nutrients – ex: glucose, carbohydrates, amino
acids, lipid components, vitamins
• Electrolytes – ex: Na+, K+, Ca2+, HCO3• Wastes – ex: lactic acid, urea, creatinine
• Hormones – ex: Insulin, cortisol, etc.
Examples of plasma proteins
Plasma protein:
Function:
look
it's not an e
Albumin
Main function is just to be a big inert protein
Keeps blood osmotic pressure high so won't lose water
Immune proteins
DEFENSE
Lots of types
Most important: GAMMA-GLOBULINS (= "antibodies") "g-globulins"
Transport proteins
Carry specific things through blood
Example: TRANSFERRIN
Carries iron back to bone marrow to make RBCs
(Iron is recycled when an RBC dies)
Clotting proteins
Stop bleeding if a blood vessel has been cut
Example: FIBRINOGEN - Inert form of clotting protein FIBRIN
Ready to form clot if necessary
Formed elements: 3 types
Erythrocytes
function: carry oxygen
(= red blood cells = RBC's)
Platelets
function: form
blood clots
when needed
Leukocytes (of various types)
(= white blood cells = WBC's)
function: defense
(immunity)
ALL formed elements are made by BONE MARROW
"HEMATOPOIESIS" =
production of RBCs, WBCs and platelets
Subcategories of hematopoiesis:
Erythropoiesis = production of RBCs
Leukopoiesis = production of WBCs
Neutrophil
Thrombopoiesis = production of platelets
Review
Blood is composed of:
A.
B.
C.
D.
Plasma and proteins
Water and cells
Plasma and formed elements
Plasma and cells
OVERVIEW
Basics about blood
• Functions
• Properties
• Components
– Plasma
– Formed elements
Erythrocytes (RBC's)
•
•
•
•
Structure
Hematocrit
The kidney & EPO
Disorders: Anemia
Leukocytes (WBC's)
• 5 types
• Disorders
• Clinical tests
Platelets
• Hemostasis (clotting)
• Bleeding disorders
Erythrocytes
("Red Blood Cells")
•
5 million RBC/mL
•
"Biconcave" shape
•
No nucleus, few organelles
– Life span of 100-120 days
– have to constantly make more
Contains hemoglobin (Hb) – large
protein, many copies inside each RBC
(~1 billion copies per RBC)
•
(mL = milliliter = cc = cubic centimeter)
•
Function: gas transport
•
Major contributor to blood viscosity
Side view (cut)
Top view
Hematocrit
(aka "packed cell volume", PCV)
100%
Plasma
Buffy coat
45%
Erythrocytes
0%
Hematocrit = percent of blood volume that is RBCs
Normal hematocrit:
Men ~47% (± 5%)
Women ~42% (± 5%)
Red blood cells are full of a protein called
HEMOGLOBIN (Hb) look
Hb (not Hg)
Hb binds to O2 in lungs,
releases it in tissues
Hemoglobin has four peptide chains
("globin" chains)
Each chain has one
"heme" group in middle
•
•
How many O2 molecules
can one hemoglobin transport?
Heme group has one
iron atom (Fe)
Iron atom can hold one
O2 molecule
FOUR
Hemoglobin has slightly different colors
when bound to different things
• Oxyhemoglobin
– Hemoglobin that is carrying O2
– Bright red
• Deoxyhemoglobin
–
–
–
–
Hemoglobin not carrying O2
Dark red
DEOXYGENATED BLOOD IS NOT BLUE!
IT IS DARK RED
• Carboxyhemoglobin
– Hemoglobin bound to CO (carbon monoxide)
– 200X higher affinity (than O2) for Hb
• Binds tightly; blocks O2 from binding
– Die from lack of O2 even though O2 is present
– Brighter/pinker red than usual ("cherry red")
ANEMIA
Low oxygen-carrying capacity of the blood
Many causes. Three examples to know:
1. Not enough hemoglobin being made
Most common form: Iron-deficiency anemia
Most common cause: not enough iron in diet
20% of US women!
2. Not enough RBC's
Various causes
example: Vitamin B12 deficiency anemia
(Vit. B12 only available from animal foods)
(other causes: Blood loss; bone marrow not working)
3. RBC's dying young
(should live ~120 days)
example: sickle-cell anemia – due to a single mutation
Hb crystallizes into spikes, distorts/kills the RBC's
How can the body detect and correct anemia?
With a negative feedback loop!
• Detector cells & control center: specialized cells in kidney
• If low O2: kidney cells secrete hormone ERYTHROPOIETIN (Epo)
• Effector: bone marrow (target cells of Epo)
Bone marrow responds to Epo by making more RBC's
Review
Oxygen binds to the __________ portion of hemoglobin.
A.
B.
C.
D.
globin
oxyhemoglobin
heme
amino acid
Review
Each hemoglobin can transport
__________ oxygen atoms.
A.
B.
C.
D.
4
8
400
8000
OVERVIEW
Basics about blood
• Functions
• Properties
• Components
– Plasma
– Formed elements
Erythrocytes (RBC's)
•
•
•
•
Structure
Hematocrit
The kidney & EPO
Disorders: Anemia
Leukocytes (WBC's)
• 5 types
• Disorders
• Clinical tests
Platelets
• Hemostasis (clotting)
• Bleeding disorders
Leukocytes
( = White Blood Cells = WBCs)
•
<1% of blood volume - but important!
•
Fully functional cell, has nucleus
(unlike RBCs)
•
Special movement abilities:
– Diapedesis – movement through capillary
walls to get to other tissues
– Chemotaxis – movement toward certain
cell-communication molecules
•
Function: defense against disease
Leukocytes in blood plasma can be categorized
by whether they have "granules" or not
3 types of
granulocytes
2 types of
agranulocytes
(Plus some other types that stay in tissues and
do not usually circulate in blood)
5 types of leukocytes
that are common in blood plasma
1. Neutrophils
2. Eosinophils
3. Basophils
Granulocytes:
(Names refer to which
stains they pick up)
All have LOBED NUCLEI
All have GRANULES full of
things they can release
4. Lymphocytes
5. Monocytes
Agranulocytes:
Named for often being found in lymph
nodes & other lymphoid tissues
Named for having single nucleus w/o lobes
(which is also true of lymphocytes btw)
Granulocytes:
1. Neutrophils
The most common WBC
in circulation
“1st responder”
EATS BACTERIA
• Most abundant of all WBC's (>50%)
• Bacteria slayers
• "Professional phagocytes" – engulf &
swallow invaders
• Go to injured tissues to kill invaders
Granulocytes:
2. Eosinophils
Involved in ALLERGIES
& AUTOIMMUNE DISORDERS
• ~2-4% of WBCs
• Probably evolved to fight parasitic worms
– Many eosinophils can gang up together & kill 1
much bigger worm
– Smaller prey: eosinophils can be PHAGOCYTIC
– If no parasitic worms: seems to "look for an
enemy" and start attacking harmless things...
causing allergies
• Stimulates inflammation
Granulocytes:
3. Basophils
Responsible for most
INFLAMMATION
(example: injury, mosquito bite, asthma)
•
<1% of WBCs – rare, but always some
• NOT phagocytic!
• Functions by releasing numerous granules
that contain:
– Histamine - enhances inflammation
– Heparin – anticoagulant
• Also involved in allergies
Next: Agranulocytes
1. Neutrophils
2. Eosinophils
3. Basophils
Granulocytes:
4. Lymphocytes
Agranulocytes:
5. Monocytes
Agranulocytes:
4. Lymphocytes
2nd most common WBC
in circulation.
Can specifically recognize
"NON-SELF" molecules
• ~30% of circulating WBCs
• Move back & forth from blood to the
lymphoid tissues (lymph nodes, etc.)
• Can recognize & attack "NON-SELF"
antigens
– Subtypes: T cells, B cells
(probably also "natural killer cells")
– T cells check other body cells (activate
immune cells; kill infected body cells)
– B cells produce ANTIBODIES
Agranulocytes:
5. Monocytes
PHAGOCYTIC
Often elevated in viral diseases
• 3–8% of WBCs
• Leave blood, enter tissues, becomes
either a macrophage or a dendritic cell
• Phagocytic
• Especially important for attacking viruses
• Tend to put pieces of things they ate on
their cell surfaces, show it to lymphocytes
("antigen-presenting" behavior) – helps
activate lymphocytes
Fun fact: Mononucleosis, which is caused by a
virus, got its name because it tends to cause
high # of monocytes
Review
1. Neutrophils
2. Eosinophils
3. Basophils
Granulocytes:
4. Lymphocytes
Agranulocytes:
5. Monocytes
Which WBC is this?
Granulocyte or agranulocyte?
• Probably evolved to fight parasitic worms
• Stimulate inflammation
• Involved in allergies
EOSINOPHIL
(a type of
granulocyte)
Which WBC is this?
Granulocyte or agranulocyte?
•
•
Can recognize & attack NON-SELF antigens
– Subtypes: T cells, B cells, natural killer cells
– T cells check other body cells
– B cells produce ANTIBODIES
2nd most common WBC
LYMPHOCYTE
(a type of agranulocyte)
Clinical tests to
evaluate WBC's:
1. Count them
too many = leukocytosis = usually some type of infection
too few = leukopenia = immune system may be shutting
down, or leukocytes are dying (Suffix "-penia" = deficiency)
(Suffix "-emia" = "in the blood")
abnormal WBCs = leukemia
LEUKEMIA
Large number of abnormal WBC's
Almost always due to CANCER IN THE BONE MARROW
Lots of WBCs made, but most are nonfunctional
Immune system collapse
(Also: Not enough platelets & RBCs produced by bone marrow)
A second, more detailed method to see
what's going on with your WBC's:
2. How many of the different types? "WBC Differential"
Why this is useful:
Different types of WBCs tend to multiply in response
to different kinds of diseases/infections
Example: high eosinophils = allergies
WBC Differential – Typical results
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
60%
30%
6%
3%
1%
"Never
Let
Monkeys
Eat
Bananas"
"CBC" (Complete Blood Count)
= count every possible thing about BLOOD CELLS
Hematocrit
# RBCs per ml
amount hemoglobin (Hg) per red blood cell
# WBCs per ml
# platelets per ml
... plus some other tests
Review
An elevated neutrophil count would be
indicative of __________.
A.
B.
C.
D.
an allergic reaction
a cancer
a bacterial infection
a parasitic infection
Review
Leukemia is a general descriptor for which
of the following disorders?
A.
B.
C.
D.
An abnormally low white blood cell count
Overproduction of abnormal leukocytes
Elevated counts of normal neutrophils
Overproduction of abnormal erythrocytes
OVERVIEW
Basics about blood
• Functions
• Properties
• Components
– Plasma
– Formed elements
Erythrocytes (RBC's)
•
•
•
•
Structure
Hematocrit
The kidney & EPO
Disorders: Anemia
Leukocytes (WBC's)
• 5 types
• Disorders
• Clinical tests
Platelets
• Hemostasis (clotting)
• Bleeding disorders
Spot the Platelets, aka THROMBOCYTES
(tiny pieces of cells)
What are platelets?
• Cytoplasmic fragments
– Produced by thrombopoiesis in bone marrow
– bud off megakaryocytes
• Function: Help stop bleeding - HEMOSTASIS
("Blood-stopping")
How platelets bud off
of their parent cell:
(Hematopoietic
stem cell)
(Myeloid cell line)
(Megakaryoblast)
Repeated mitosis
without cytokinesis
Megakaryocyte
Platelets have a very short
lifespan (~7-10 days) so each
megakaryocyte keeps making
thousands of new platelets
Newly formed
platelets
Hemostasis – Stopping Bleeding
Vasoconstriction
Platelet
plug
Blood
clot
Platelet
Vessel
injury
Endothelial
cells
1. Vascular spasm
Collagen
fibers
2. Platelet plug formation
3. Coagulation
All three steps involve platelets
(PS - your book lists two more steps)
The platelets' main job:
Know when to get sticky
"Platelet plug"
Clot too slowly =
Clot too easily =
increased risk of bleeding to death
increased risk of embolism
(clot blocking a blood vessel)
In the last step – COAGULATION –
fibers form!
Mat of FIBRIN precipitates out of blood to form
fibers, traps RBCs
Creates a THROMBUS (a clot):
But where did the fibrin come from?
From FIBRINOGEN, an inactive form:
FIBRINOGEN
(soluble)
FIBRIN
(insoluble)
But what catalyzes that reaction?
THROMBIN, an enzyme!
This is its only job: Turn fibrinogen into fibrin
THROMBIN
catalyzes
FIBRINOGEN
(soluble)
FIBRIN
(insoluble)
But how come thrombin doesn't create
clots all the time?
Prothrombin
THROMBIN
catalyzes
FIBRINOGEN
(soluble)
FIBRIN
(insoluble)
There is a theme here:
All clotting proteins are kept deactivated till needed
Coagulation –
The Full Story
"Cascade" of clotting proteins
start activating each other
All are kept inactive until needed
Activation triggered by TISSUE
DAMAGE or DAMAGED BLOOD
VESSEL
(...or sometimes by blood sitting very still
for an unusually long period)
Why so many steps?
Factor
XII
Factor
IX
Factor
VIII
Factor
X
Prothrombin
activator
Thrombin
Fibrin
Each activated factor activates many more
molecules in next step of sequence
Allows RAPID CLOTTING
Reaction cascade (time)
Factor
XI
What happens if coagulation doesn't work?
Hemophilia
Inability to form normal blood clots
•
•
Usually platelet plug can form, but fibrin won't form (missing one of the
clotting factors). Blood keeps oozing out of the blood vessel for days
Usually GENETIC – problem with one of the clotting proteins
THROMBOSIS – the opposite problem
Clot too much or in wrong place
Clot terminology:
Thrombus – a stationary clot in an intact blood vessel
(not necessarily blocking blood flow yet)
Thrombosis – the state of having a thrombus
example: "Deep Vein Thrombosis"
Embolus – a piece of a thrombus that breaks loose and
goes floating through the circulatory system
(dangerous!)
EMBOLISM – an embolus that has gotten stuck in another blood
vessel and is blocking blood flow.
An embolism can kill the "downstream" tissues.
examples: pulmonary embolism, cerebral embolism
Terminology:
"Thromb-" = anything to do with clotting
"Embol-" = anything to do with stopping flow
Thrombosis is sometimes genetic, but
often can be triggered by hormones, obesity, inactivity
Liz Logelin
died 24 hr after giving birth
Brittany Oswell
died after plane flight
Some risk factors:
Anything that increases estrogen
Obesity
Inactivity for multiple hours
Anticoagulants
Medications that stop coagulation (stop clotting)
•
Heparin – inhibits thrombin formation
– May be used when collecting blood, for tests that
require the blood to stay liquid ("heparinized tube")
(usually a "green-top tube")
•
Aspirin – keeps platelets from “sticking”
together + prevents their release of clotting
substances
– Often recommended for patients that have a
history of thrombosis/embolisms
– Helpful for heart attack survivors / people with
atherosclerosis – helps prevent small clots from
blocking coronary arteries
Covid-19 seems to stimulate blood clotting
Review
Name the three steps of clotting
1. Vascular spasm
2. Platelet plug formation
3. Coagulation (fibrin mesh forms)
Review
A blood clot has broken loose and has gotten stuck
in a blood vessel of the lungs. It is completely
blocking blood flow. This clinical emergency is
known as:
A. Thrombopoiesis
B. Leukemia
C. Anemia
D. Embolism