Pathophysiology Cellular Function

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PathophysiologyCellular Function

• Presenter
• V. Alexander, DNP., ARNP

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General Concepts

• Must understand cellular processes to understand
  disease
• Pathophysiology ?
• Disease occurs when there is a disruption in
  homeostasis or deviation from normal

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Homeostasis

• Dynamic process
• The relative consistency of the bodys internal
  processes
• Give and take system
• Equilibrium is necessary for all cells

• Self-regulating
• Compensatory
• Negative feedback-most common eg. -temp
  regulation
• Positive feedback- eg blood clot
• May use many means to correct one imbalance

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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
  individuals normal

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Pathophysiology

• Etiology
• May include agents, age, gender, health,
  nutritional status, genetics, etc
• Idiopathic
• Iatrogenic
• May be intrinsic or extrinsic

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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

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Disease

• Epidemiology
• Levels of prevention
• Primary
• Secondary
• Tertiary

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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

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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

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Cellular Attributes

• Ability to
• exchange material with their environment
• obtain energy from organic nutrients
• manufacture complex molecules
• replicate themselves

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Functional Cell Components

• Three major components of eukaryotic cells
• Nucleus
• Cytoplasm
• Cell Membrane

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Functional Cell Components

• Nucleus
• Contains chromatin and nucleolus
• At least one per cell
• Control Center
• Genetic Code
• Nucleoli

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Functional Cell Components

• Cytoplasm
• Place for cell work
• Contains water, electrolytes, suspended protein,
  neutral fats, and glycogen
• Contains the organelles

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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
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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

Organelles
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Functional Cell Components

• Golgi Apparatus
• Site for carb production
• Lysosomes
• Breakdown cell products and foreign bodies to be
  used again
• Requires acidic environment

Organelles
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Functional Cell Components

• Peroxisomes
• Controls free radicals
• Mitochondria
• Power plants
• Aerobic metabolism-ATP
• Number in a given cell varies depending on the
  cells energy needs
• Contains own DNA and ribosomes

Organelles
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Functional Cell Components

• Microtubules
• Cilia and Flagella
• Hair like processes
• Aid in movement
• Centrioles
• Barrel-shaped bodies
• Aid in chromosomal division
• Microfilament
• Threadlike structure

Cytoskeleton
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Functional Cell Components

• Cell Membrane
• Semi-permeable
• Contains receptors
• Involved in electrical conduction
• Regulates cell growth and proliferation
• Lipid bilayer
• Proteins

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Functional Cell Components

• Membrane receptors
• Open and close ion channels
• Activates G protein-linked signals
• Activates enzyme-linked cell function

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Cellular Transportation

• Passive
• 1. Diffusion
• 2. Osmosis
• 3. Facilitated diffusion
• Active transport
• Endocytosis
• Pinocytosis
• Phagocytosis
• Exocytosis

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Na K ATP pump
Na
K
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Cell Cycle

• Cell proliferation
• Cells divide and reproduce
• Mitosis
• Prophase
• Metaphase
• Anaphase
• Telophase
• Meiosis

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Cell Cycle

• Cell differentiation
• Proliferated cells become different and
  specialized
• Begins after fertilization
• Generalized to specific

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Atrophy
? Workload (or disease state)
? Efficiency -OR-
? Functionality in disease state
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Hypertrophy
? Size ? of organelles
? Workload (or disease state)
? ability to meet demands! -OR-
? Functionality in disease state
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Hyperplasia
? Workload Physiological state
? tissue size by ? of cells
? ability to meet demands!
2 types Compensatory Hormonal
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Metaplasia
Ex Cigarette Smoking
Pathological
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Dysplasia
Epithelial Tissue
Pathological
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Cell Injury

• Most disease start with cell injury
• Can be reversible to a point
• Normal states - balanced with cell renewal

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Physiological Cell Death
Apoptosis
Normal process of cell replacement development
Ex endometrial sloughing during menstruation
Ex induced apoptosis during Immune response
Balance between death and regeneration
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Causes of Cell Injury

• Physical agents
• Mechanical forces
• Extreme temp.
• Electrical
• Radiation
• Ionizing
• Ultraviolet
• Non-ionizing

• Chemical
• Pollution
• Lead
• Poisonings
• Drugs
• Biological Agents
• Bacteria
• Viruses
• Parasites
• Nutritional Imbalances

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Mechanism of Injury

• Ischemia
• Necrosis
• Free Radical

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Necrotic Cell Death
Necrotic Cell Death
Firm opaque
Walled-Off Liquid Goo
Cased-Off Cheese Globules
Opaque, Chalky Soapy
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Gangrene
Caused by severe hypoxic injury
Tissues not just cells!
Release gas into tissue
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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

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Carcinogenesis

• Cancer development
• Steps in Carcinogenesis
• Initiation
• Promotion
• Progression
• Heredity
• Oncogenes
• Carcinogens

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Benign v/s Malignant

• Benign
• Slow, progressive, localized, well defined,
  resembles host (more differentiated), grow by
  expansion, does not usually cause death
• Malignant
• Rapid growing, spreads (metastasis) quickly,
  fatal, highly undifferentiated

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Clinical Manifestations

• Change in bowel or bladder habits
• A sore that doesnt 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

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Complications

• Anemia
• Cachexia
• Fatigue
• Infection
• Leukopenia
• Thrombocytopenia
• Pain

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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)

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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

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Treatment

• 3 goals
• Curative
• Palliative
• Prophylactic
• Surgery
• Radiation
• Chemotherapy
• Hormone and antihormone therapy
• Biotherapy

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Chromosomes

• Contains genetic information
• 23 pairs
• Sex chromosome
• Karyotype
• Phenotype
• Patterns of inheritance
• Homozygous
• Heterozygous
• Dominant
• Recessive

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Genetic and Congenital Disorders

• Caused by a mutation
• gt800 disorders
• Characterized by the patterns of transmission

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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

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Autosomal Dominant Disorders

• Marfan Syndrome
• 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

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Autosomal Dominant Disorders

• Neurofibromatosis
• Neurogenic tumors
• A defect on chromosome 17 or 22
• Two forms
• Type 1 - subcutaneous lesions, café-au-lait 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

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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 be a deficient enzyme
• Examples PKU and Tay-Sachs

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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
• Avoid high protein foods
• Limited amounts of starches
• Phenylalanine lowering agents
• Gene therapy

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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

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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

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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

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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

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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

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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

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Trisomy 21 (Downs 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

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Trisomy 21 (Downs 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

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Monosomy X (Turners 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

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Monosomy X (Turners Syndrome)-

• Diagnosis history, physical examination, and
  chromosomal testing
• Treatment estrogen and growth hormones

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Trisomy X (Klinefelters 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

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The End

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• THE END
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