Chapter 1
Cellular Function
General Concepts
• Must understand cellular processes to
understand disease.
• Pathophysiology: the study of the disorder or
breakdown of the human body’s function.
• Disease occurs when there is a disruption in
homeostasis or deviation from normal.
Homeostasis
• Dynamic process
• The relative consistency
of the body’s internal
processes
• Give and take system
• Equilibrium is necessary
for all cells
• Self-regulating
• Compensatory
• Negative feedback—
most common (e.g.,
temp regulation)
• Positive feedback (e.g.,
blood clot)
• May use many means to
correct one imbalance
Factors That
Determine Normality
• Age
• Gender
• Genetic and ethnic background
• Geographic area
• Time of day
• Environment: altitude, temp, etc.
• Remember, findings are only relevant to the
individual’s “normal.”
What is disease?
• A structural or functional change in the body
that is harmful to the organism.
• Pathology is the study of what disease does to
the body.
• Immunology is study of all aspects of the
immune system
Pathophysiology
(1 of 2)
• Etiology: cause or reason for the event
– May include agents, age, gender, health, nutritional
status, genetics, etc.
– Idiopathic: unknown
– Iatrogenic: unintended effect of a medical
treatment
– May be intrinsic or extrinsic
Pathophysiology
(2 of 2)
• Pathogenesis: development and evolution of a
disease
– Affected by time, quantity, location, and
morphologic changes
• Clinical manifestations
– Includes S/S of the disease, stages of the disease,
acute vs. chronic
Disease
• Epidemiology: patterns of diseases in a group
of people
• Levels of prevention
– Primary: do not have the disease and you are
trying to prevent it (e.g., vaccines)
– Secondary: disease detection (e.g., Pap smears and
yearly physicals)
– Tertiary: trying to prevent problems from the
disease or problem (e.g., rehabilitation)
Manifestations of Disease
• All the information gathered about the patient that relates
to the disease process:
– Symptoms—What the patient perceives to be wrong
(chest pain)
– Signs—Objective findings made by the examiner
(abnormal heart sounds)
– Laboratory Findings—Made by performing special
procedures (EKG)
• All these findings can lead to a diagnosis
Structural vs. Functional
Diseases
• Structural:
– Caused by lesions that occur within the body
– Can be genetic or developmental
– Caused by external or internal mechanisms
– Major categories:
• Genetic and developmental
• Acquired injuries and inflammatory disease
• Hyperplasia's and neoplasms
Structural vs. Functional
Diseases
• Functional:
– No visible lesions present initially
– Though over time, structural changes will appear
– Caused by a physiologic or functional change
• Structural and Functional Diseases can overlap
Causes of Disease
• There are many different causes of disease
– Exogenous/Endogenous
(exo= originating from outside the body, endo= originating
from inside the body, tissue, or cell)
– Direct physical injury
– Chemical injury
– Infection
• Some diseases are termed idiopathic, meaning no known cause
– MS, Guillian-Barre, Autoimmune Diseases)
Obstacles to Patient Care
• Obstacles to patient care are many:
– Availability of resources—this can include
financial, facility, societal, education…
– New information does not necessarily mean new
practice will be implemented (time lag)
– Though medical standards are based scientifically,
physicians do not always follow the guidelines
Evidence-Based Medicine
• Practice Guidelines issued by expert panels
• Guideline is the key word!
– These tell the physician what the standard
should be, not what they must do.
Treatment Focus
• The environment where the patient is being treated will
dictate the goal of care.
• Clinics focus on prevention and chronic disease
management
• Acute care focuses on treatment of the active illness or
disease process
Symptomatic Disease
Assessment
• The method used to diagnosis
symptomatic disease includes the
following:
– History
– Physical exam
– Visual exam of body recesses
– Palpation
– Percussion
Asymptomatic Disease
• Since chronic illness can cause damage to
the body before the patient knows they are
sick, there is an emphasis on diagnosing
illness as soon as possible.
• This often occurs at regular check-ups.
Asymptomatic Disease
• Since the patient is not yet experiencing
symptoms, screening exams are performed to
discover the disease in its early stage.
• The goal of screening is to either cure the
disease, or begin treatment to delay the
progression of the disease.
Screening
• There are many different screening tests
available.
• It is impractical to screen every patient for
every disease. Therefore, clinicians screen
patients for the diseases for which they
have risk factors.
• While screening is a very important tool, it
Preventative Medicine
• Immunizations and sanitation are
examples of how preventative medicine
has improved the health of society.
• Certain behaviors and lifestyles have
been shown to have a negative
association with various diseases.
• Example: Alcohol is linked with liver
disease
Preventative Medicine
• One of the major problems with preventative
medicine, is not every person visits a physician
regularly.
• Individuals at the greatest risk for chronic
illnesses often do not have access to health
care to be screened or receive treatment.
Preventative Medicine
• The screening for chronic illness must also be systematic,
though slightly different criteria are considered.
– History—this focuses on identifying risk factors
– Family history—this focuses on possible genetic linked
diseases
– Laboratory or radiographic tests
Diagnostic Tests and
Procedures
• Clinical procedures are simple tests performed by the
primary physician to screen for illness.
– Example: throat cultures
• Manipulative procedures are performed by specialists.
– Example: sigmoidoscopy
Radiologic Procedures
• There are a variety of radiologic procedures that can screen
or diagnosis disease.
– X-ray—This is the simplest form of radiography
– Computed tomography (CT)—A sophisticated x-ray
technique that generates sharply defined images
– Magnetic resonance imaging (MRI)—These create images
without using x-rays.
– Ultrasound—uses sound waves to view soft tissue
structures.
– Nuclear Medicine—Radioactive material is injected into
the patient, and then the patient is scanned to determine
where the material has settled.
Anatomic Pathology Tests and
Procedures
• After taking a biopsy of a lesion, the sample is
inspected by a pathologist and subjected to
various tests.
• Cytology examinations are commonly
performed on urine, sputum, and PAP smears.
Clinical Pathology
Tests and Procedures
• Clinical pathology is the part of laboratory that
is used most frequently in the hospital or clinic
setting.
• It is divided into chemistry, hematology,
microbiology, immunopathology, and
transfusion medicine.
Molecular Diagnosis and
Proteomics
• Each microorganism has its own unique
signature of genes that can be identified using
DNA or RNA sequencing.
• Proteomics is the mapping of the patterns of
proteins that support cancerous growths.
• These are both examples of using molecular
methods of diagnosis.
Cell Pathology
Cell worksheet
Cellular Attributes
• Ability to exchange material with their
environment
• Ability to obtain energy from organic nutrients
• Ability to manufacture complex molecules
• Ability to replicate themselves
Functional Cell Components
(1 of 10)
• Three major components of eukaryotic cells
– Nucleus
– Cytoplasm
– Cell membrane
Structure and Function of a
Normal Cell
Nucleus
• Every human cell except RBC’s and platelets
• Proteins, RNA, DNA, nucleic acids.
• Contains the cells genetic material
Cytoplasm
• All cells have cytoplasm
• More specialized cells have more cytoplasm
• Cytoplasmic organelles:
– Mitochondria: generate energy (ATP)
– Ribosomes: protein synthesis
– Endoplasmic reticulum:
– Golgi apparatus:
– Lysosomes:
Mitochondria
• Involved mostly in the generation of energy
• ATP generated is essential for all other cellular
functions
• ATP: adenosine triphosphate
• More specialized cells have more mitochondria
because they require more energy
• Aerobic metabolism—ATP
• Contains own DNA and ribosomes
Ribosomes
• Small granules of RNA
• Float freely in cytoplasm
• Synthesize the proteins and enzymes used
for that specific cells function
Endoplasmic Reticulum
• Meshwork of membranes in continuity
with the outer plasma membranes and
nuclear membranes on the other
• Rough: contains ribosomes for protein
export/secretion, highly developed in
specialized cells
• Smooth: catabolism of drugs, hormones,
nutrients
Golgi Apparatus
• Forms secretory granules and lysomes
• Synthesized proteins enter, are biochemically
altered, and packaged for removal from the cell.
• packages ER waste into lysomes and secretory
granules
Lysomes
• Membrane bound
• Originate from the Golgi apparatus
• Rich in lytic enzymes
• Contain acid hydrolases (digestive
enzymes)
Plasma Membrane
• Proteins, lipids, and carbohydrates
• Internal surface binds with the cytoplasm
• External surface is contact between cell
and the environment
– Receptors, adhesion molecules, signal
transducers, and metabolic channels.
– Rupture or damage that is not repaired leads
to cell death
– Requires a constant supply of energy (ATP)
Normal Cellular Function
• Cells  Tissues Organs
• Autocrine stimulation: eg T lymphocytes
have receptors for their own secretions (self
stimulating)
• Paracrine: eg release of hydrochloric acid
from gastric cells under the influence of
gastrin
• Endocrine: hormones released into the blood
(insulin)
• Neural: CNS coordinates body functions
Functional Cell Components:
Cytoskeleton
(8 of 10)
• Microtubules
– Cilia and flagella
• Hairlike processes
• Aid in movement
– Centrioles
• Barrel-shaped bodies
• Aid in chromosomal division
• Microfilament
– Threadlike structure
Functional Cell Components
(9 of 10)
• Cell membrane
– Semipermeable
– Contains receptors
– Involved in electrical conduction
– Regulates cell growth and proliferation
– Lipid bilayer
– Proteins
Functional Cell Components
(10 of 10)
• Membrane receptors
– Open and close ion channels
– Activate G protein-linked signals
– Activate enzyme-linked cell function
Cellular Transportation
• Passive
– Diffusion
– Osmosis
– Facilitated diffusion
• Active transport
• Endocytosis
– Pinocytosis
– Phagocytosis
• Exocytosis
Cell Cycle
(1 of 2)
• Cell proliferation
– Cells divide and reproduce
– Mitosis
• Prophase
• Metaphase
• Anaphase
• Telophase
– Meiosis
Cell Cycle
(2 of 2)
• Cell differentiation
– Proliferated cells become different and specialized
– Begins after fertilization
– Generalized to specific
Cell Injury
• Most diseases start with cell injury.
• Can be reversible to a point.
• In normal states, it is balanced with cell
renewal.
Reversible Cell Injury
• External influence that evokes a cellular response but does
not disrupt homeostasis
• Mild and short lived
• Hydropic change: cellular swelling in the cytoplasm,
gathers in the mitochondria
– Cell recovers by pumping up water
• Reduced energy production: swollen mitochondria results
in production of lactic acid instead of ATP
• Decreased protein synthesis: pH becomes acidic
• Increased autophagy:
Irreversible Injury
• Cells exposed to heavy doses of toxins, that
experience severe or prolonged hypoxia, or that
experience other injuries and cannot recover
– Damage to the nucleus (nuclear damage)
– Pyknosis: condensation of the chromatin
– Karyorrhexis: nuclear dust (fragmenting into smaller
pieces)
• Cells release contents into extracellular fluid with
death
– Cytoplasmic enzymes: Asparate Aminotransferase(AST)
Alanine Aminotransferase (ALT), Lactate Dehydrogenase
(LDH) can be detected in the blood
- Blood tests with these enzymes can indicate MI or
hepatitis
Causes of Major Cell Injury
• Hypoxia
• Anoxia
• Toxins
• Microbes
• Inflammation and Immune Reactions
• Genetic Disorders
• Metabolic Disorders
Hypoxia and Anoxia
•
•
•
•
•
•
Hypoxia: reduced oxygen in the cell
Anoxia: complete lack of oxygen in the cell
Lack of oxygen = cessation of energy production
Short term anoxia = reversible cellular damage
Prolonged hypoxia or anoxia lead to cell death
Some cells are more sensitive:
– Brain cells cannot survive for more than a few minutes
– Cardiac for 1-2 hrs
– Connective tissue is most resistant to anoxia
Toxins
• May be direct or indirect
• Direct: heavy metals like Mercury
(inactivate cytoplasmic enzymes)
• Many drugs or their metabolites cause
cell injury
Microbial Pathogens
• Bacteria produces toxins and exotoxins
• Viruses invade cells and destroy them from
within or integrate into the cellular genome
and force the cell to produce its own proteins
Inflammation and Immune
Reactions
• Cytokines, interferons, and complement proteins mediate
inflammation and immune responses
– Sometimes destroy normal cells with infected ones
• Genetic Disturbances: genetic inborn errors of metabolism
result in toxic metabolites accumulating in the cells
– Tay-Sachs (gangliosides accumulate in the lysosomes of
nerve and eye cells)
– Diabetes Mellitus
Causes of Cell Injury
• Physical agents
– Mechanical forces
– Extreme temperature
– Electrical
• Radiation
– Ionizing
– Ultraviolet
– Non-ionizing
• Chemical
– Poisonings
– Drugs
• Biological agents
• Nutritional imbalances
Mechanisms of Injury
• Ischemia
• Necrosis
• Free radicals
Death
• Anoxia, toxins leading to nuclear changes,
rupture of a cell membrane, cessation of cellular
respiration
• Necrosis: exogenously induced cell death
• Apoptosis: endogenously programmed cell death
• Autolysis: death of cells and tissues in a dead
organism that occurs as a result of cessation of
respiration/heartbeat
Necrosis
Apoptosis
• Suicide genes:
Gangrene
Caused by severe hypoxic injury
Dry
Coagulative
Wet
Liquefactive
Gas
Releases
Tissues
Clostridium
not
gas just
into cells!
tissue
Alterations in Cell Growth
and Replication
• Neoplasia = “new growth”
• Lacks normal controls and regulation
• Can originate in one organ
– Prostate most common in men
– Breast most common in women
– Lung leading cause of death in men and women
• Can also spread from another site
Carcinogenesis
• Cancer development
• Steps in carcinogenesis
1. Initiation: introduction of the agent
2. Promotion: initiation of uncontrolled growth
3. Progression: permanent malignant changes
• Heredity
• Oncogenes
• Carcinogens
Benign vs. Malignant Cancer
• Benign
– Slow, progressive, localized, well defined,
resembles host (more differentiated), grows by
expansion, does not usually cause death
• Malignant
– Rapid growing, spreads (metastasis) quickly, fatal,
highly undifferentiated
Clinical Manifestations
Change in bowel or bladder habits
A sore that doesn’t heal
Unusual bleeding or discharge
Thickening or lump in the breast or
elsewhere
Indigestion or difficulty swallowing
Obvious change in a wart or mole
Nagging cough or hoarseness
Complications
• Anemia
• Cachexia
• Fatigue
• Infection
• Leukopenia
• Thrombocytopenia
• Pain
Diagnosis
• Biopsy
– Can be done through
needle aspiration,
endoscopy, laparoscopy,
or excision
• Tumor markers
– Antigens on the surface
of tumor cells
– Used for screening,
diagnosing, monitoring,
treatment, and
establishing remission
• Miscellaneous
procedures
– X-rays, radioactive
isotope scanning,
computed tomography
scans, endoscopies,
ultrasonography,
magnetic resonance
imaging, positron
emission tomography
scanning
Classification
• Staging: TNM (tumor node metastasis); based
on spread of the disease
• Grading: according to histology
– I, II, III, and I: as it increases, the tumor is less
differentiated.
Treatment
• Three goals
– Curative
– Palliative
– Prophylactic
• Surgery
• Radiation
• Chemotherapy
• Hormone and
antihormone therapy
• Biotherapy
Chromosomes
• Contains genetic
information
• 23 pairs
• Sex chromosome
• Karyotype
• Phenotype
• Patterns of inheritance
– Homozygous
– Heterozygous
– Dominant
– Recessive
Genetic and
Congenital
Disorders
•
•
•
Caused by a mutation
800 disorders
Characterized by the patterns of transmission
Autosomal Dominant Disorders
(1 of 4)
• Transmitted from an affected parent to
offspring regardless of gender
• 50% chance of transmission
• Unaffected do not pass on the disorder
• Delayed onset
• Examples: Marfan syndrome and
neurofibromatosis
Autosomal Dominant Disorders
(2 of 4)
• Marfan syndrome
– Disorder of connective tissue
– Mutation on chromosome 15 (FBN1)
– FBN1 combines with other fibrillins and gives rise
to microfibrils
– Roles of microfibrils: strength, growth factor
release, tissue repair
– FBN1 mutation leads to reduced elasticity and
excess growth factor release
– Affects eyes, skeleton, and cardiovascular system
Autosomal Dominant Disorders
(3 of 4)
• Marfan syndrome
– Diagnosis
• History, physical examination, skin biopsy (presence of
fibrillin), genetic testing
– Treatment
• None, palliative
Autosomal Dominant Disorders
(4 of 4)
• Neurofibromatosis
– Neurogenic tumors
– Two forms
• Type 1: defect on chromosome 17 (NF1); subcutaneous
lesions, café-au-lait spots (at least 6 at birth), freckles,
scoliosis, erosive bone defects, and nervous system
tumors
• Type 2: defect on chromosome 22 (NF2); tumors of the
acoustic nerve
– Treatment
• Palliative removal of tumors
Autosomal Recessive Disorders
• Rare
• Both members of gene pair are affected
• Affects both genders
• One out of four will be affected
• Two out of four will be carriers
• Onset early
• Usually caused by a deficient enzyme
• Examples: PKU and Tay-Sachs
Autosomal Recessive
Disorders: PKU
(1 of 2)
• Mutation on chromosome 12 (PAH gene) leads
to an error in converting phenylalanine to
tyrosine
• Appears normal at birth then fails to meet
milestones
• Progressive neurological decline
• If untreated, can lead to severe intellectual
disability
Autosomal Recessive
Disorders: PKU
(2 of 2)
• Diagnosis
– Serum phenylalanine at 3 days old
– Prenatal screening: amniocentesis, chorionic villus
sampling
• Treatment
– Avoid high protein foods
– Limited amounts of starches
– Phenylalanine-lowering agents
– Gene and enzyme therapy
Autosomal Recessive
Disorders: Tay-Sachs
(1 of 2)
• Progressive disorder due to mutation of
hexosaminidase A
– Necessary to metabolize certain lipids
– Lipids accumulate, destroying and demyelinating
nerve cells
– Nerve cell destruction leads to a progressive
mental and motor deterioration
• Most are of Jewish decent
• Three forms: infantile, juvenile, adult (rare)
Autosomal Recessive
Disorders: Tay-Sachs
(2 of 2)
• Appears normal at birth,
then the infant begins to
miss milestones
• Progresses to seizures,
muscular rigidity, and
blindness
• Usually fatal by 5 years
of age
• Diagnosis: history,
physical examination,
and low serum and
amniotic
hexosaminidase A levels
• No cure
• Genetic counseling
suggested
X-Linked Disorders
(1 of 3)
• Sex-linked disorders are almost always X
linked.
• Males have a 50% chance of getting the
disorder from their mother.
• Females have a 50% chance of being carriers.
• All daughters of affected males will be
carriers, but none of their sons.
• Example: Fragile X syndrome
X-Linked Disorders
(2 of 3)
• Fragile X syndrome
– Associated with a single trinucleotide gene
(FMR1) sequence on the X chromosome, which is
repeated > 200 times
– Plays a role in synapse development
– Manifestations: long face with large mandible,
large ears, large testicles, mental retardation,
learning disabilities, speech delays, connective
tissue disorders, behavioral issues, and autism
spectrum disorder
X-Linked Disorders
(3 of 3)
• Fragile X syndrome
– Diagnosis: history, physical examination, genetic
testing
– Treatment: supportive
Multifactorial Inheritance
Disorders
(1 of 2)
• Result from an interaction between environmental
and genetic factors
• Less predictable
• Extremely common
• May be expressed at birth or later
• Examples: cleft lip/palate, clubfoot, congenital
dislocation of hips, congenital heart defects, pyloric
stenosis, urinary tract malformations, diabetes
mellitus, hypertension, cancer, and psychiatric
disorders
Multifactorial Inheritance
Disorders
(2 of 2)
• Cleft lip and palate
– Improper formation of soft tissues of mouth and
lips
• Unilateral or bilateral deformities lead to feeding and
nutritional issues
• Maternal smoking, diabetes, and seizure medication use
(first trimester) are important risk factors
– Diagnosis: prenatal ultrasound
– Treatment: surgery, speech therapy
Chromosomal Disorders
• May be related to abnormality in chromosomal
number and/or structure that occurs in meiosis
• Account for most early abortions
• More than 60 syndromes
Trisomy 21 (Down’s Syndrome)
(1 of 2)
• Risk increases with maternal age
• Caused from nondisjunction during meiosis
• Manifestations: small square head, upward
slant of eyes, small low-set ears, fat pad on
back of the neck, open mouth with protruding
tongue, simian crease, varying degrees of
mental retardation, and behavioral issues
Trisomy 21 (Down’s Syndrome)
(2 of 2)
• Also associated with congenital heart defects, ocular
issues, leukemia, respiratory complications,
gastrointestinal complications, hypothyroidism.
• 50% of patients with Down’s syndrome develop
Alzheimer's disease by age 50.
• Diagnosis: parental screening including
amniocentesis, hormone levels, 4D ultrasound.
• Treatment: symptomatic and supportive.
Monosomy X
(Turner’s Syndrome)
(1 of 2)
• Deletion of all or part of an X—occurs
spontaneously
• Specific gene(s) associated: not known
• No Y chromosome, so female
• Manifestations: gonadal streaks instead of
ovaries, short stature, increased weight, neck
webbing, small lower jaw, drooping eyelids,
small fingernails, and widely spaced nipples
Monosomy X
(Turner’s Syndrome)
(2 of 2)
• Also associated with coarctation of the aorta,
vision issues, hearing loss, renal and skeletal
abnormalities, infertility, and increased risk for
infections
• No mental retardation present
• Diagnosis: history, physical examination,
chromosomal testing, and serum hormone
levels
• Treatment: estrogen and growth hormones
Trisomy X
(Klinefelter’s Syndrome)
• One or more extra X
• Also associated with
chromosomes with the
learning disabilities,
presence of the Y
behavioral problems,
sexual dysfunction,
• Male appearance
pulmonary
disease,
• Often undetected
varicose veins,
• Manifestations:
osteoporosis, and breast
gynecomastia, small
cancer
testes and penis, tall
stature, increased weight, • Treatment: testosterone
and sparse body hair