Transcript Cells

Pathophysiology
Cellular Function
Presenter:
V. Alexander, DNP., ARNP
General Concepts
• Must understand cellular
processes to understand
disease
• Pathophysiology ?
• 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 feedbackmost common; eg. temp regulation
• Positive feedback- eg:
blood clot
• May use many means
to correct one
imbalance
Factors that Determine
Normality
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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”
Pathophysiology
• Etiology
 May include agents, age, gender, health,
nutritional status, genetics, etc
 Idiopathic
 Iatrogenic
 May be intrinsic or extrinsic
Pathophysiology
• Pathogenesis
 Affected by time, quantity, location,
and morphologic changes
• Clinical manifestations
 Includes S/S of the disease, stages of
the disease, acute v/s chronic
Disease
• Epidemiology
• Levels of prevention
 Primary
 Secondary
 Tertiary
Question
• Which of the following are sigs of infection in
a patient?
1. Bradycardia
2. Hypothermia
3. Increased body temperature
5. Increased neutrophils
6. Increased RBC
7. Increased WBC
8. Localized edema
9. Localized pain
Answer
• 3; 4; 6; 7; 8.
• 3. Increased body temp – inflammatory process to fight
infection
• 4. increased neutrophils – through phagocytosis these
specialized WBC ingest and destroy microorganisms
• 6. Increased WBC – WBC leaves blood vessels
• 7. localized edema – occurs when injury causes necrosis
• 8. localized pain – swelling or inflamed tissues increases
pressure on nerve endings
Cellular Attributes
• Ability to:
 exchange material with their
environment
 obtain energy from organic nutrients
 manufacture complex molecules
 replicate themselves
Functional Cell Components
• Three major components of eukaryotic
cells:
 Nucleus
 Cytoplasm
 Cell Membrane
Functional Cell Components
• Nucleus
 Contains chromatin and nucleolus
 At least one per cell
 Control Center
 Genetic Code
 Nucleoli
Functional Cell Components
• Cytoplasm
 Place for cell work
 Contains water, electrolytes,
suspended protein, neutral fats, and
glycogen
 Contains the organelles
Organelles
Functional Cell Components
• Ribosomes
 Site for protein synthesis
 Small particles of nucleoproteins
 May be attached to Endoplasmic
Reticulum (ER) or free
• Endoplasmic Reticulum (ER)
 Matrix of paired membranes and vesicles
 Tubular communication system
 Place where metabolic activity occurs
Organelles
Functional Cell Components
• Two Forms of Endoplasmic
Reticulum (ER):
 Rough-Produce proteins for
membranes and lysosomal enzymes
 Smooth-lipid, lipoprotein, and steroid
synthesis:
 Regulation of intracellular Ca+,
metabolism, and detoxification of
hormones and drugs
Functional Cell Components
• Golgi Apparatus
Organelles
 Site for carb production
• Lysosomes
 Breakdown cell products and
foreign bodies to be used
again
 Requires acidic environment
Functional Cell Components
Organelles
• Peroxisomes
 Controls free radicals
• Mitochondria
 Power plants
 Aerobic metabolism-ATP
 Number in a given cell varies depending
on the cell’s energy needs
 Contains own DNA and ribosomes
Functional Cell Components
Cytoskeleton
• Microtubules
 Cilia and Flagella
• Hair like processes
• Aid in movement
 Centrioles
• Barrel-shaped bodies
• Aid in chromosomal division
• Microfilament
 Threadlike structure
Functional Cell Components
• Cell Membrane
 Semi-permeable
 Contains receptors
 Involved in electrical conduction
 Regulates cell growth and
proliferation
 Lipid bilayer
 Proteins
Functional Cell Components
• Membrane receptors
 Open and close ion channels
 Activates G protein-linked signals
 Activates enzyme-linked cell function
Cellular Transportation
•
Passive
1. Diffusion
2. Osmosis
3. Facilitated diffusion
• Active transport
• Endocytosis
 Pinocytosis
 Phagocytosis
• Exocytosis
Na+ K+ ATP pump
Na+
K+
ADP
ATP
Cell Cycle
• Cell proliferation
 Cells divide and reproduce
 Mitosis
• Prophase
• Metaphase
• Anaphase
• Telophase
 Meiosis
Cell Cycle
• Cell differentiation
 Proliferated cells become different and
specialized
 Begins after fertilization
 Generalized to specific
Atrophy
 Workload
(or disease state)
 Functionality
Efficiency
in disease
-OR- state
Size
Size
organelles
of oforganelles
 Energy Usage
Hypertrophy
 Workload
(or disease state)
 ability to
 Functionality
meet demands!
in disease state
-OR-
 Size
Size
# oforganelles
organelles
 # of
 contractility
Hyperplasia
 Workload
Physiological state
types:to
 2ability
Compensatory
meet demands!&
Hormonal
 tissue
 rate ofsize
cell #
division
by 
of cells
 functionality
Metaplasia
Ex: Cigarette
Smoking
Pathological
Normal Cells
Abnormal
Cells
Replacement
Dysplasia
Epithelial
Tissue
Pathological
Mutation
Normal Cells
Abnormal
Shape & Size
Cell Injury
• Most disease start with cell
injury
• Can be reversible to a point
• Normal states - balanced with
cell renewal
Physiological Cell Death
Apoptosis
‘Programmed Suicide’
Normal process of cell
replacement & development
Ex:Ex:
endometrial
induced apoptosis
sloughing
during
during
Balance between death and regeneration
Immune
menstruation
response
Causes of Cell Injury
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Physical agents
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Mechanical forces
Extreme temp.
Electrical
Radiation
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Ionizing
Ultraviolet
Non-ionizing
• Chemical
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Pollution
Lead
Poisonings
Drugs
• Biological Agents
• Bacteria
• Viruses
• Parasites
• Nutritional Imbalances
Mechanism of Injury
• Ischemia
• Necrosis
• Free Radical
Necrotic Cell Death
Necrotic Cell Death
Coagulative
Gelatinous,
Firm
transparent
& opaque
protein
Liquefactive
Walled-Off
Brain & neurons
Liquid Goo
Caseous
Mycobacterium
‘Cased’-Off
Cheese
tuberculosis
Globules
Fatty
Opaque, Chalky
Breast, pancreas
Soapy
Gangrene
Caused by severe hypoxic injury
Dry
Coagulative
Wet
Liquefactive
Gas
Release
Tissues
Clostridium
gas
not into
just 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
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Cancer development
Steps in Carcinogenesis:
 Initiation
 Promotion
 Progression
• Heredity
• Oncogenes
• Carcinogens
Benign v/s Malignant
• Benign
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Slow, progressive, localized, well
defined, resembles host (more
differentiated), grow by expansion,
does not usually cause death
• Malignant
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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
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Anemia
Cachexia
Fatigue
Infection
Leukopenia
Thrombocytopenia
Pain
Diagnosis
• Biopsy
 Can be done through needle aspiration,
endoscopy, laproscopy, 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, CT
scans, endoscopies, US, MRI, positron
emission tomography scanning (PET scan)
Classification
• Staging -TNM (Tumor; Node;
Metastasis): based on spread of the
disease
• Grading-according to histology
 I, II, III, and IV-as it increases, the
tumor is less differentiated
Treatment
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3 goals:
 Curative
 Palliative
 Prophylactic
Surgery
Radiation
Chemotherapy
Hormone and antihormone therapy
Biotherapy
Chromosomes
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Contains genetic information
23 pairs
Sex chromosome
Karyotype
Phenotype
Patterns of inheritance
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Homozygous
Heterozygous
Dominant
Recessive
Genetic and Congenital
Disorders
• Caused by a mutation
• >800 disorders
• Characterized by the patterns of
transmission
Autosomal Dominant Disorders
• 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
• Marfan Syndrome
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Disorder of connective tissue
Mutation on chromosome 15
Results in elastin and collagen defects
Affects the eyes, skeleton, and cardiovascular
system
 Diagnosis
 History, physical examination, skin biopsy
(presence of fibrillin), genetic testing
 Treatment
• None, palliative
Autosomal Dominant Disorders
• Neurofibromatosis
 Neurogenic tumors
 A defect on chromosome 17 or 22
 Two forms:
• Type 1 - subcutaneous lesions, café-aulait spots (at least 6 at birth), freckles,
scoliosis, erosive bone defects, and
nervous system tumors
• Type 2 - Tumors of the acoustic nerve
 Treatment
• Palliative removal of tumors
Autosomal Recessive Disorders
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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 be a deficient enzyme
Examples: PKU and Tay-Sachs
Autosomal Recessive Disorders• PKU (phenylketonuria)
 Mutation on chromosome 12 leads to an error
in converting phenylalanine to tyrosine
 Appear normal at birth then fails to meet
developmental milestones
 Progressive neurological decline
 If untreated, can lead to mental retardation
 Diagnosis- serum phenylalanine at 3 days old
 Treatment:
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Avoid high protein foods
Limited amounts of starches
Phenylalanine lowering agents
Gene therapy
Autosomal Recessive Disorders
• Tay-sachs
 A deficiency or absence of
hexosaminidase A
• Necessary to metabolize certain lipids
• Lipids accumulate, destroying and
demyelinating nerve cells
• Leads to a progressive mental and
motor deterioration
 Most are of Jewish decent
Autosomal Recessive Disorders
• Tay-sachs
 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
• Sex-linked disorders are almost always X
linked
• Males have 50% chance of getting
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
• Fragile X syndrome
 Associated with a single tri-nucleotide gene
sequence on the X chromosome
 Lack of a protein necessary for neural tube
development
 Manifestations: long face with large
mandible, large ears, large testicles,
mental retardation, learning disabilities,
speech delays, connective tissue
disorders, and behavioral issues
 Diagnosis: history, physical examination,
genetic testing
 Treatment: supportative
Multifactorial Inheritance Disorders
• Results from an interaction between
environmental and genetic factors
• Less predictable
• Extremely common
• May be expressed at birth or later
• Examples: cleft lip or palate, clubfoot,
congenital dislocation of the hips, congenital
heart defects, pyloric stenosis, urinary tract
malformations, diabetes mellitus,
hypertension, cancer, and psychiatric
disorders
Chromosomal Disorders
• May be related to abnormality in
chromosomal number and/or
structure that occurs in meiosis
• Accounts for most of early abortions
• More than 60 syndromes
Trisomy 21 (Down’s syndrome)
• Risk increases with maternal age
• Caused from nondisjunction during
meiosis
• Manifestations: small square head,
upward slant of the eyes, small low set
ears, fat pad on the back of the neck,
open mouth with protruding tongue,
Simian crease, and varying degrees of
mental retardation
Trisomy 21 (Down’s syndrome)
• Also associated with congenital
heart defects, ocular issues,
leukemia, respiratory complications
• Diagnosis: parental screening
including amniocentesis, hormone
levels, four-dimensional ultrasound
• Treatment: symptomatic and
supportative
Monosomy X (Turner’s Syndrome)• Deletion of all or part of an X chromosome
• No Y chromosome - no female
• Manifestations: gonadal streaks instead of
ovaries, short stature, increased weight,
webbing of the neck, small lower jaw,
drooping eyelids, small fingernails, and
widely spaced nipples
• Also associated with coarctation of the
aorta, vision issues, hearing loss, renal
abnormalities, infertility, and increased risk
for infections
• No mental retardation present
Monosomy X (Turner’s Syndrome)• Diagnosis: history, physical
examination, and chromosomal
testing
• Treatment: estrogen and growth
hormones
Trisomy X (Klinefelter’s Syndrome)
• One or more extra X chromosomes with
the presence of the Y
• Male appearance
• Often undetected
• Manifestations: gynecomastia, small
testes and penis, tall stature, increased
weight, and sparse body hair
• Also associated with learning disabilities,
behavioral problems, sexual dysfunction,
pulmonary disease, varicose veins,
osteoporosis, and breast cancer
• Treatment: testosterone
The End
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THE END
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