Pathophysiology Cellular Function Presenter: V. Alexander, DNP., ARNP

PathophysiologyCellular 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 feedback-

most common; eg. -temp regulation

• Positive feedback- eg: 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”

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. Bradycardia2. Hypothermia3. Increased body temperature5. Increased neutrophils6. Increased RBC7. Increased WBC8. Localized edema9. 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


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


• Cytoplasm Place for cell work Contains water, electrolytes,

suspended protein, neutral fats, and glycogen

Contains the organelles


• 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

Org

anel

les


• 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

Org

anel

les


• Golgi Apparatus Site for carb production

• Lysosomes Breakdown cell products and

foreign bodies to be used again

Requires acidic environmentOrg

anel

les


• 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

Org

anel

les

Functional Cell Components• Microtubules

Cilia and Flagella• Hair like processes• Aid in movement

Centrioles• Barrel-shaped bodies• Aid in chromosomal division

• Microfilament Threadlike structure

Cyt

oske

leto

n


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

proliferation Lipid bilayer Proteins


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

Cellular Transportation

• Passive 1. Diffusion2. Osmosis3. Facilitated diffusion

• Active transport• Endocytosis

Pinocytosis Phagocytosis

• Exocytosis

NaNa++ K K++ ATP pump ATP pumpNaNa++ K K++ ATP pump ATP pump

K+K+

Na+Na+

ATPATPATPATPADPADPADPADPATPATPATPATP

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

Sizeof organelles

Sizeof organelles

AtrophyAtrophyAtrophyAtrophy

Workload(or disease state)

Workload(or disease state) Size

of organelles

Sizeof organelles

Energy Usage Energy Usage Efficiency

-OR-

Efficiency-OR-

Functionalityin disease state


Size # of organelles




HypertrophyHypertrophyHypertrophyHypertrophy



contractility contractility

ability to meet demands!

-OR-


-OR-



rate of cell division

rate of cell division

HyperplasiaHyperplasiaHyperplasiaHyperplasia

WorkloadPhysiological state

WorkloadPhysiological state

functionality functionality



2 types:Compensatory &

Hormonal

2 types:Compensatory &

Hormonal

tissue sizeby # of cells

MetaplasiaMetaplasiaMetaplasiaMetaplasia

PathologicalPathologicalPathologicalPathological

Normal CellsNormal Cells

Ex: CigaretteSmoking

AbnormalAbnormalCellsCells

Replacement

DysplasiaDysplasiaDysplasiaDysplasia

PathologicalPathologicalPathologicalPathological

Normal CellsNormal Cells

Epithelial Tissue

AbnormalAbnormalShape & SizeShape & Size

Mutation

Cell Injury

• Most disease start with cell injury

• Can be reversible to a point

• Normal states - balanced with cell renewal

Physiological Cell DeathPhysiological Cell DeathPhysiological Cell DeathPhysiological Cell Death

ApoptosisApoptosis ‘Programmed Suicide’‘Programmed Suicide’

Normal process of cell replacement & development

Normal process of cell replacement & development

Ex: endometrial sloughing duringEx: endometrial sloughing duringmenstruationmenstruation

Ex: endometrial sloughing duringEx: endometrial sloughing duringmenstruationmenstruation

Ex: induced apoptosis duringEx: induced apoptosis duringImmune responseImmune response

Ex: induced apoptosis duringEx: induced apoptosis duringImmune responseImmune responseBalance between death and regenerationBalance between death and regeneration

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

Mechanism of Injury

• Ischemia

• Necrosis

• Free Radical

Necrotic Cell Death

CoagulativeCoagulativeCoagulativeCoagulative Gelatinous,Gelatinous, transparent proteintransparent protein

Gelatinous,Gelatinous, transparent proteintransparent protein

Necrotic Cell DeathNecrotic Cell DeathNecrotic Cell DeathNecrotic Cell Death

LiquefactiveLiquefactiveLiquefactiveLiquefactive Brain & neuronsBrain & neuronsBrain & neuronsBrain & neurons

CaseousCaseousCaseousCaseous MycobacteriumMycobacteriumtuberculosistuberculosis

MycobacteriumMycobacteriumtuberculosistuberculosis

FattyFattyFattyFatty Breast, pancreasBreast, pancreasBreast, pancreasBreast, pancreas

FirmFirm& opaque& opaque

FirmFirm& opaque& opaque

Walled-Off Walled-Off Liquid GooLiquid Goo

Walled-Off Walled-Off Liquid GooLiquid Goo

‘‘Cased’-Off Cased’-Off Cheese GlobulesCheese Globules

‘‘Cased’-Off Cased’-Off Cheese GlobulesCheese Globules

Opaque, ChalkyOpaque, ChalkySoapy Soapy

Opaque, ChalkyOpaque, ChalkySoapy Soapy

GangreneGangreneGangreneGangrene

DryDryDryDry CoagulativeCoagulativeCoagulativeCoagulative

WetWetWetWet LiquefactiveLiquefactiveLiquefactiveLiquefactive

Caused by severe hypoxic injuryCaused by severe hypoxic injuryCaused by severe hypoxic injuryCaused by severe hypoxic injury

GasGasGasGas ClostridiumClostridiumClostridiumClostridiumTissues not just cells!Tissues not just cells!Release gas into tissueRelease gas into 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: Initiation Promotion Progression

• Heredity

• Oncogenes

• Carcinogens

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

Clinical ManifestationsCChange in bowel or bladder habitsAA sore that doesn’t healUUnusual bleeding or dischargeTThickening or lump in the breast or

elsewhere IIndigestion or difficulty swallowingOObvious change in a wart or moleNNagging cough or hoarseness

Complications

• 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

• 3 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

• 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

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-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

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

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

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

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Pathophysiology Cellular Function Presenter: V. Alexander, DNP., ARNP