Microscopic Anatomy
Unit 2 Anatomy and Physiology
Cells, Cells, Cells
http://www.youtube.com/watch?v=u
54bRpbSOgs
What do we know about cells?
• Make up all livings things
• Cells range from 1/3-1/13 in comparison to
the size of a dot in an exclamation point in
your book. Some can be up to 2 feet
• Cells are flat, round, threadlike, or irregular
• Work together to allow proper functioning of
life.
Draw what you know
• In your notes, take 5 minutes to draw what a
standard cell looks like
Cell structure
• All human cells possess:
– Nucleus (except mature RBC)
– Organelles
– Cytoplasm
– Cell membrane
Cell membrane
•
•
•
•
Also known as plasma membrane
Acts as a protective covering
Helps to hold cell contents together
Responsible for allowing material in and out of
the cell
• It is “selectively permeable”
Transport Methods
• Transport methods are used for the
movement of materials across the cell
membrane
• Passive transport- requires no extra energy to
complete the movement.
• Active transport- requires additional energy to
complete the movement
Passive Transport
• Osmosis- water travels through selectively permeable
membrane until concentrations are equalized.
• Diffusion- most common transport- substance of
higher concentration moves to an area of lesser
concentration
• Filtration- pressure is applied to move water across the
membrane (like people getting pushed through
turnstiles during rush hour)
• Facilitated diffusion- variation of diffusion- substance is
helped across the membrane (like an usher helping you
to your seat)
Pathology connection
• Read pages 64 and 65 in your book
• In your own words explain how these diseases
work.
Active Transport
• Active transport pumps require energy (ATP)
to move.
• Like facilitated diffusion pumps use a protein
carrier to move material
• Endocytosis- used for the INTAKE of liquid and
food.
• Exocytosis is used to get substances OUT of
the cell.
Pathology connection
• Read page 67 and 68
• Put into your own words how this disease
works.
Other Structures
• Ribosomes- found in the ER or floating in
cytoplasm.
– Made of RNA– site production for enzymes and proteins that are
needed for cell repair and reproduction.
• Centrosomes- specialized that contain
centrioles that help with cell division
Other Structures
• Mitochondria- tiny bean shaped organelles that
provide up to 95% of the body’s energy needed
for cellular repair, reproduction, and movement.
• Endoplasmic Reticulum- series of channels in the
cytoplasm formed from folded membranes
– Rough ER- (has ribosomes on the surface) synthesizes
protein
– Smooth ER- (no ribosomes) synthesizes lipids and
steroids
Other Structures
• Golgi Apparatus- receives protein from ER and
prepares it to be shipped to the cell
membrane and then eventually out.
(exocytosis)
• Lysosomes- contain powerful enzymes that
clean up waste.
• Cytoskeleton- provides shape of cell
• Flagella- tail like whip used for movement
Pathology Connection
• Read page 73-75 in book
Mitosis
• Cellular reproduction
– Process of making a new cell, also know as cell
division
– Sorts chromosomes and is the only way to reproduce
human cells asexually.
• Eukaryotic- human cells
• DNA- chromosomes must be completely copied
for a new cell to divide
• Bacterial cells (prokaryotic) divide in two through
binary fission- simple division
Cell cycle
• 2 major phases:
– Interphase- not dividing but preparing for cell division
by stockpiling materials
– Mitotic phase- 2 major portions consist of dividing
and sorting genetic material, and cytokinesis divides
the cytoplasm
• Phases of MITOSIS
–
–
–
–
Prophase
Metaphase
Anaphase
telephase
Phases
• Prophase- nucleus disappears, chromosomes appear,
centrioles move towards side of cell.
• Metaphase- chromosomes line up in the middle of the
cell.
• Anaphase- chromosomes splits and because spindles
pull them apart
• Telophase- chromosomes go to opposite ends of cell,
spindle disappears, and nuclei reappear.
*Mitosis is used any time cells need to be replaced:
repairs cuts to normal and heals broken noses.
http://www.youtube.com/watch?v=NR0mdDJMHIQ
Quiz!
Microorganisms
•
•
•
•
Bacteria
Viruses
Fungi
protozoa
Bacteria and Viruses
• Bacteria:
– make up largest group of pathogens.
– Harmless bacteria (normal flora) live in our body
• Virus:
– More basic pathogen than bacteria
– Infectious particle with protective covering- capsid
– Can not grow, or reproduce themselves
– Need a host cell
Fungi and Protozoa's
• Fungi:
– Can be one celled or multi-celled
– Mycelia travels out cells to absorb nutrients
– Can be good
– Can be carried through spores (seed like /wind)
• Protozoa:
– One celled animal found in ponds and soil
– Disease is caused by swallowing them or bitten by
an infected insect.
TISSUES
Tissues
• What is a tissue?
– A collection of similar cells that act together to
preform a function.
– There are many different types:
•
•
•
•
Epithelial
Connective
Muscle
Nervous
Epithelial Tissue
• Covers and lines the body and organs on the body
• shapes– Squamous- flat
– Cuboidal-cube shaped
– Columnar-column shaped
• Layers
– Simple- one layer
– Stratified- several layers
– Pseudostratified (irregularly layered- skinny at the top
and fat at the bottom)
Classes of Epithelia
Connective tissue
• Most common tissue
• Found in organs, bones, muscles, nerves,
membranes and skin
• Job is to hold things together and support
• Types– Areolar
– Adipose or Fat
– Dense
– Synovial membrane
Areolar
• Fine delicate webs of tissue that help hold
other tissues together
Adipose (fat)
• We need these tissues in our bodies for it to
properly function
Tendons, Ligaments and Bone
• Dense tissue that act as cable wires and
bridges for the body
Muscle Tissue
• Provides means for movement in the body
• Three types
– Skeletal: attached to bones and causes movement
by contracting and relaxing. Voluntary muscles
– Smooth: form the walls of hollow organs. Example
would be our digestive system organs. Involuntary
muscles.
– Cardiac- found in the walls of the heart. Work
together to create the heart beat
Nervous Tissue
• Acts as a rapid messenger service for the
body.
• Two types of nerve cells
– Neurons- conductors of information
– Neuroglia (glia)- help hold neurons in place
• Dendrites are branchlike formation that make up part
of the neuron.
Tour De Life
•
•
•
•
Book issue
Book Overview
Book Procedures
Assignment Expectations
Tissues Review
• Cells of same type joined together
• 60%-99% water
• Groups of tissues
– Epithelial
• Shapes
• Layers
– Connective
• types
– Nerve
• cells
– Muscle
• Smooth
• Skeletal
• cardiac
Organs and Systems
• Organs: two or more tissues joined together
for a specific purpose
• Systems: organs and other body parts joined
together for a particular function
Tissues Lab
• Need paper and pencil
• View each slide
• View each slide on each objective
Tissue ID
• Tissue ID quiz
• Do not move:
– Stage
– Objective
– Microscope covering
Diagnostic Testing
Overview of Diagnostic testing
• There are many types of diagnostic testing
(too many to cover at one time)
• A diagnostic tests helps determine the specific
cause of various signs or symptoms
• Important: test results are not the sole
diagnosis of a patient.
• Important: one abnormal test result does not
make a diagnosis
How does diagnostic testing impact
medical costs?
• https://www.youtube.com/watch?v=sBUtENln
Fic
Blood Basics
• Plasma- liquid portion that makes up the
blood.
• Erythrocytes- Red, medium sized, 500 RBC:30
platelets. Used to carry oxygen and other
materials throughout the body
• Leukocytes-White, largest, 1 WBC:30 platelets.
Used to fight infection.
• Thrombocytes- Platelets, smallest 1:WBC 30:
500 RBC
Blood Testing
• Blood samples- usually obtained from veins
• Other ways to obtain blood
– Pin prick (to test blood sugar levels)
– Arteries (to test oxygen levels)
General blood disorders
• Anemia- is red blood a cell disorder. (fewer
RBC than normal)
• Leukocytosis/Leukopenia- higher (cytosis) and
lower (penia) amount of WBC than normal
• Thrombocytopenia- fewer than normal
platelets
• What would patients present with for signs
and symptoms?
Centrifuge
• When blood is drawn it must be separated.
• Spun at a very high speed
• Heavy cells sink to bottom , and lighter cells
stay on top
Types of blood tests
• Complete blood count- count of all cells in the
blood.
• Pro Time- tests bloods ability to clot
• PTT- also a test for clotting ability
– Blood chemistry- is noted because disease will
cause an alteration of their values.
Urine Testing
• Although it is 95% water is contains thousands of
dissolved substances.
• Most substances found in the urine are found in
the blood.
• You CAN drink it. (up to a certain amount of hours
after production)
• Dipsticks- can be read at home by the patient and
tests for properties of : bilirubin, glucose,
hemoglobin, ketones, leukocyte, nitrite, pH
protein.
https://www.youtube.com/watch?v=4U_x
mfSwYSw
https://www.youtube.com/watch?v=T
uWiy4_VDWY
Specific Urine test
• When assessing urine note: color, specific gravity,
concentration, odor, and pH
• Turbidity- determines if bacteria is present if cloudy
• Sugar- can detect diabetes
• Protein- continuous excretion can mean renal disease
• Ketone- relates to metabolism. Should not have high
amounts in the urine.
• Bacteria- may indicate UTI
• Sediment Examination- accounts for the accurate
number of cells. Is less invasive than a biopsy or blood
test
Fecal Testing
• Aids in detection of GI issues, parasites, ulcerative
colitis, and gall stones.
• When assessing stool note:
– Amount, consistency, form and shape
– pH
– Color
•
•
•
•
Yellow- diarrhea
Tan- duct bile blockage
Black- upper GI bleeding
Red- lower GI bleeding
– Blood in the stool may indicate cancer, colitis, diverticulitis, etc.
– Mucous in the stool may indicate inflammation of the rectal canal
Cerebral Spinal Fluid Testing
• CSF is found in the brain and in the central canal
of the spinal cord.
• CSF- acts a shock absorber, regulates intracranial
pressure, and influences brain functions like
homeostasis.
• When assessing CSF note:
– Color- should be colorless like water
– Cell counts- should not contain WBC, and neutrophils,
and mononuclear cells should be regulated.
Culture and Sensitivity Testing
• Patient sample is taken from an infected area
and placed in a growth medium to grow and
then later be identified.
• Different pathogens will grow in different
shapes, sizes, and colors. (normal flora may
also grow in the medium)
Cardiac Diagnostics
• ECG/EKG- electrocardiogram- monitors how
electrical impulses travel through the heart.
• Holter Monitor- records all cardiac activity in a
24 hour period.
• Stress Testing- walking at various speeds to
induce physical exertion to determine
symptoms that may indicate heart disease.
Scopes
• Correct term is Endoscope- scope enters the
body to obtain a better view of a region.
• Different types of endoscopy– Otoscope- external ear exam (most common)
– Bronchoscope- “head scope” examines regions of
the head.
– Gastroscope- examines the stomach
– Laparoscope- examines abdominal region
– Cytoscope- examines bladder anatomy
Pulmonary Function Testing
• Assesses flow and volume of air into and out
of the lungs.
• Determines the level of lung function in
diseases like asthma, emphysema, chronic
bronchitis, and cystic fibrosis.
• Results often depend on the participation of
the patient.
Sleep Testing
• Polysomnography- sleep studies
• Looks at:
– Air flow in and out of nose and mouth
– Eye movement to determine sleep stage
– Movement of breathing muscles
– Monitor brain waves
– Heart rate
– Oxygen levels
Pharmacogenetics
How Genetic Information Is Used to Treat Disease
Maureen Knabb
West Chester University
West Chester, PA
At Children’s Hospital, Two 14-yr-old Girls
Meet in the Children’s Ward
• Laura loves sports, is an excellent student, and
plays soccer. The last few months she has been
very tired and bruises easily.
• Beth enjoys animals and the theater. She seems
to pick up colds easily and recently suffered
from a high fever and swollen lymph nodes.
• After a visit to the doctor, they have blood tests
performed.
63
Blood Test Results
Here are their results:
RBC count
Hemoglobin
Hematocrit
WBC count
Platelet count
Laura
2.6
8.2
23
6.5
50
Beth
3.5
11.1
32
2.0
120
Units
million/mm3
g/dl
%
thousand/mm3
thousand/mm3
Turn to your neighbor and discuss these results.
What differences do you see in the results between
the two girls? Do you think that they have the same
disease or a different disease?
64
Blood Cell Review
Why are the girls having these symptoms?
• Red Blood Cells = Erythrocytes
• White Blood Cells = Leukocytes
• Platelets = Thrombocytes
Turn to your neighbor and
discuss the structural similarities
and differences that you see in
the cells labeled 1-5.
65
Red Blood Cells (RBCs)
A. Structure
• Biconcave disc
• Lack nucleus and organelles
B. Function
• Transport O2 via hemoglobin
C. Normal values
• RBC count = 4.0-5.2 million/ mm3
• Hemoglobin = 11.8-15.5 g/dl
• Hematocrit = 36-46 %
66
Red Blood Cells (RBCs)
D. Abnormal values
• Low = anemia
• Weakness
• Fatigue
• Shortness of breath
• High = polycythemia
• Can lead to blood flow
difficulty
67
White Blood Cells (WBCs)
A. Types
• Neutrophil
• Eosinophil
• Basophil
• Monocyte
• Lymphocyte (shown here)
B. Function
• Combat infection
C. Normal values
• WBC count = 4.5-13.2 thousand/ mm3
68
White Blood Cells (WBCs)
D. Abnormal values
• Low
• Immunodeficiency
• Failure to make
WBCs in the bone
marrow
• Leads to increased
susceptibility to
infection
• High
• Infection
• Leukemia
69
Platelets
A. Structure
• Small cell fragments
• Lack nucleus
• Contain granules
B. Function
• Blood clotting
C. Normal values
• Platelet count = 140-450 thousand/mm3
70
Platelets
D. Abnormal values
• Low
• Excessive bleeding
• Bruising
• High
• Blood clots
71
CQ1: The blood test result(s) that explain Laura’s
fatigue is (are) __________.
A) Low RBC count
B) Low hemoglobin concentration
C) Low hematocrit
D) All of the above
Laura
Beth
RBC count
2.6
3.5
Normal range (14 yr
old F)
4.0-5.2 million/ mm3
Hemoglobin
8.2
11.1
11.8-15.5 g/dl
Hematocrit
23
32
36-46 %
WBC count
6.5
2.0
Platelet count
50
120
4.5-13.2 thousand/
mm3
140-450
thousand/mm3
72
CQ2: Laura bruises easily because she has a ____ .
A) Low RBC count
B) Low hemoglobin concentration
C) Low hematocrit
D) Low WBC count
E) Low platelet count
Laura
Beth
RBC count
2.6
3.5
Normal range (14 yr
old F)
4.0-5.2 million/ mm3
Hemoglobin
8.2
11.1
11.8-15.5 g/dl
Hematocrit
23
32
36-46 %
WBC count
6.5
2.0
Platelet count
50
120
4.5-13.2 thousand/
mm3
140-450
thousand/mm3
73
CQ3: The blood test result for Beth related to swollen
lymph nodes and frequent infections is _____ .
A) Low RBC count
B) Low hemoglobin concentration
C) Low hematocrit
D) Low WBC count
E) Low platelet count
Laura
Beth
RBC count
2.6
3.5
Normal range (14 yr
old F)
4.0-5.2 million/ mm3
Hemoglobin
8.2
11.1
11.8-15.5 g/dl
Hematocrit
23
32
36-46 %
WBC count
6.5
2.0
Platelet count
50
120
4.5-13.2 thousand/
mm3
140-450
thousand/mm3
74
A Bone Marrow Biopsy Is Performed
Both girls are diagnosed with acute lymphoblastic leukemia, an abnormal
production of immature lymphocytes.
75
What is Acute Lymphoblastic Leukemia
(ALL)?
• Cancer of the white blood
cells characterized by excess
lymphoblasts.
• Most common in childhood
age 2-5.
• Symptoms of the disease
include anemia, sensitivity
to infection and bleeding
due to the overcrowding of
the bone marrow with the
cancer cells.
Bone marrow biopsy of patient with ALL
76
How Is ALL Treated?
• Thiopurine drugs
– 6-mercaptopurine (shown here)
• Prodrugs
– Must be converted to the active form
in the body
• Guanine analogs
– Act like guanine but disrupts DNA and
RNA synthesis
– Acts on rapidly dividing (cancer) cells
but also GI, skin, hair follicles, bone
marrow
• Narrow therapeutic index
– Dose to affect cancer cells is not
much higher than toxic dose
– Toxic dose = decrease ability of bone
marrow to make blood cells
• myelosuppression
77
CQ4: After 3 days, Beth’s condition is deteriorating
while Laura is feeling better. What could cause this
difference in response to the treatment?
A) Beth is more sensitive to the toxic effects of the drug.
B) More drug is converted to the active form in Beth, leading to
toxic levels.
C) The drug is not excreted in Beth, leading to toxic levels.
D) The drug is not inactivated in Beth, leading to toxic levels.
E) All of the above.
78
Drug Metabolism Basics
Prodrug
Drug
enzyme A
Inactive drug
enzyme I
• Prodrug needs to be metabolized by enzyme A to be active
– Poor metabolizers (low A activity) will need higher dose
– High metabolizers (high A activity) will need lower dose
• Drug needs to be metabolized to be inactivated
– Poor metabolizers (low I activity) will need lower dose
– High metabolizers (high I activity) will need higher dose
79
CQ5: Which of the following mechanisms will
lead to higher active drug dose?
Prodrug
Drug
enzyme A
Inactive drug
enzyme I
A) Increase activity of activating enzyme, decrease activity
of inactivating enzyme
B) Decrease activity of activating enzyme, decrease activity
of inactivating enzyme
C) Increase activity of activating enzyme, increase activity
of inactivating enzyme
D) Decrease activity of activating enzyme, increase activity
of inactivating enzyme
80
How Are Thiopurines Metabolized?
81
Thiopurine Metabolism
Active metabolite
Important
enzyme
CH3
CH3
Inactive metabolites
82
What Does the TPMT Enzyme Do?
• TPMT adds a methyl group
(CH3) to the sulfhydryl group
(SH) on the drug or its
metabolites
• Decreases the concentration of
the active drug metabolites,
thioguanine nucleotides
– Thio-GTP
– Thio-dGTP
• Acts indirectly to decrease the
effective dose of the drug
83
What Is the Relationship between
Drug Dose and TPMT Activity?
84
CQ6: Individuals with ___ TPMT activity would
show _____ TGN levels, leading to toxicity.
A) low, low
B) high, high
C) low, high
D) high, no change
85
TPMT Gene Has Different Forms (Alleles)
• High enzyme activity
– Homozygous dominant (wild type)
• Medium enzyme activity
– Heterozygous
• Low enzyme activity
– Homozygous recessive
86
Distribution of TPMT Activity in 298
Caucasian Adults
87
CQ7: Based on the graph, how many Caucasian
patients out of 300 would possess the low activity
form (less than 5 U/ml) of the TPMT enzyme?
A) Approximately 1 out of 300
B) Approximately 10 out of 300
C) Approximately 290 out of 300
88
Common Mutations of the TPMT Gene
89
How Does the TPMT Mutation
Decrease Enzyme Activity?
TPMT parameter
Wild
type
*3A
allele
*3B
allele
*3C allele
Formation (fmol/ mg/ hr)
335
268
349
220
Degradation t1/2 (hr)
18
0.25** 6.1**
18
** significantly different than wild type protein
Turn to your neighbor and try to determine which mutation is more
important for the change in degradation, exon 7 or exon 10?
90
CQ8: Beth has been diagnosed with the TPMT* 3a
gene. Her deterioration following treatment is due to:
A) Decreased TPMT activity due to increased enzyme
degradation.
B) Decreased TPMT activity due to decreased enzyme formation.
C) Decreased TPMT activity due to decreased enzyme
degradation.
D) Increased TPMT activity due to increased enzyme formation.
91
CQ9: Effective treatment of individuals like Beth
require:
A) Increased dose of drug
B) Decreased dose of drug
C) No change in drug dose
92
What Is “Pharmacogenomics”?
• The study of how genome-wide variation
affects the body's response to drugs.
• Benefits for patients include better drug
selection for initial treatment and more
accurate dosing.
• Benefits for drug companies include genetic
targeting of clinical trials for specific groups.
• The terms “pharmacogenetics” and
“pharmacogenomics” are often used
interchangeably
93
Another Example: Clopidogrel (Plavix)
Prodrug
Drug
enzyme A
Inactive drug
enzyme I
• Taken by about 40 million people in the world to
prevent blood clotting.
• CYP2C19 is responsible for its metabolic activation
(see enzyme A in the diagram above).
• At least one loss-of-function allele is carried by 24%
of the white non-Hispanic population, 18% of
Mexicans, 33% of African Americans, and 50% of
Asians.
• Homozygous carriers, who are poor CYP2C19
metabolizers, make up 3% to 4% of the population.
94
CQ10: Poor metabolizers of clopidogrel require _____
doses of drug to achieve an effective dose because the
CYP2C19 enzyme does not_____ the drug.
A) Higher, activate
B) Lower, activate
C) Higher, inactivate
D) Lower, inactivate
95
The Future of Pharmacogenomics
• Pharmacogenomics is slowly being integrated
into medical practice.
• Understanding the consequences of metabolizer
status and the frequency of variants in a given
population will be helpful when advising patients
about treatment options.
• See the FDA Pharmacogenomic Biomarkers in
Drug labels for a list of drugs and their associated
genetic biomarkers.
96
Potential Barriers to Genetic Testing
• Complexity of finding gene variations that
affect drug response
• Limited drug alternatives
• Disincentives for drug companies to make
multiple pharmacogenomic products
• Educating healthcare providers
• Fear of discrimination based on genetic test
results
97
CQ11: Which of the following do you think would be
the greatest potential barrier for genetic testing?
A) Complexity of finding gene variations that affect drug
response
B) Limited drug alternatives
C) Disincentives for drug companies to make multiple
pharmacogenomic products
D) Educating healthcare providers
E) Fear of discrimination based on genetic test results
98