PH 370 Exam 1

Lectures 1-12

1. cells

2. tissues

3. organs

4. system

definitions

1. cells = basic building blocks of life,

2. tissues = groups of similar cell types that combine to form a specialized function

3. organs = 2+ types of tissue that perform similar functions

4. system = organization of organs that perform related functions necessary for survival

define cellular respiration

cellular respiration is a series of metabolic processes that transforms fuel molecules into energy (ATP) and waste products (CO2, H2O, heat)

• aerobic = citric acid/krebs cycle

  • requires oxygen, in mitochondria, produced additional 34 ATP molecs

• anaerobic = glycolysis

  • breakdown of glucose into 2 ATP molecs, absence of oyxgen, insufficient to support energy needs of body, in cytosol

describe cellular communication

binding affinity is how tightly bound receptors and ligands are → signal transduction

• ligands = signaling molecules, bind to receptors

• receptors = membrane bound or intracellular

describe the types of cellular ingestion

1. endocytosis = transport large substances into cells

2. phagocytosis = ingest large particles and release oxygen free radicals

describe the different types of cellular reproduction (do not need to know phases)

Etiology

Etiology is the study of the cause or origin of a disease or condition. It involves understanding the factors that contribute to the development of a disease, including biological, environmental, and lifestyle influences.

Pathogenesis

pathogenesis = how disease leads to structural/physio changes that result in disease (biologic understanding)

Pathophysiology

study of the pathogenesis of disease

Health vs. Disease

• health = when the body can perform vital functions normally/maintain homeostasis

• disease = significant disturbance in homeostasis

Risk vs. Etiologic Factor

• risk factors = increases probability of an indiv developing a disease or health condition

  • not all risk factors are etiologic factors

• etiologic factors = the cause of disease/condition

  • all etiologic factors are risk factors

Modifiable

Signs vs. Symptoms

• signs = evidence of disease observed on physical examination

• symptoms = indications of disease reported by patient

Prognosis (acute, terminal, chronic)

prognosis = the predicted course and outcome of disease

• acute = sudden onset, short duration

• terminal = diseases that will end in death

• chronic = slower, less severe onset and long duration

Edits to prognosis (remission, recurrence, relapse, exacerbation, complication)

• remission = reduction/disappearance of signs and symptoms, not a cure

• recurrence = return of sign/symptom after remission

• relapse = return of disease after its apparent cure

• exacerbation = increase in severity of a disease

• complication = related disease of other abnormal state in person already with disease

Disease vs. Disorder vs. Syndrome

• disease = signif disturbance in homeo of body that modifies vital functions

• disorder = abnormality in function, not a disease itself, may or may not have specific signs of symptoms

  • ex. OCD

• syndrome = a group of signs/symptoms related to a single underlying alteration in structure of function

  • ex. HELLP syndrome: breakdown of RBCs, abnormal liver function, low platelet count

Normal phase vs. preclinical phase vs. clinical phase of disease

• Normal phase = no disease, encounter exposures which initiaite pathologic changes, before biologic onset of disease

  • 1st degree prevention: remove causes of disease/immunization

• preclinical phase = after etiologic exposure, results from biologic onset of disease, symptoms not present

  • 2nd degree prevention = screen for, detect and treat disease early

• clinical phase = symptoms are present, disease is diagnosed, disease is treated

  • 3rd degree prevention = treat clinical disease to prevent death / complications

When do biologic changes start in relation to disease?

Biologic changes in relation to disease typically begin at the cellular or molecular level before clinical symptoms appear. This can occur during the early stages of disease development, often referred to as the preclinical phase, which may last for years. The exact timing varies depending on the disease and individual factors.

When are there symptoms of disease?

symptoms appear at the beginning of the clinical phase

• not present in preclinical phase

For disease, when do we screen? when do we treat?

• Screening (preclinical, 2nd degree): Typically recommended for asymptomatic individuals at risk for certain diseases (e.g., cancer, diabetes) based on age, family history, and risk factors.

• Treatment (clinical, 3rd degree): Initiated when a disease is diagnosed, symptoms are present, or screening results indicate a need for intervention

Primary vs. Secondary vs. Tertiary Prevention of disease

1. remove causes of disease / immunization

2. screening for, detect/treat disease early

3. treat clinical disease to prevent death/complications

Active vs. Passive Transport

Active vs. Passive Transport

• Active Transport: Movement of molecules against their concentration/electrochem gradient, requiring energy (ATP).

• Passive Transport: Movement of molecules down their concentration gradient without energy input.

Diffusion vs. Facilitated Diffusion

Both are forms of passive transport

• Diffusion: Movement of molecules from high to low concentration without energy.

• Facilitated Diffusion: Movement of molecules across a membrane via protein channels, also without energy, but requires specific transport proteins.

Phagocytosis vs endocytosis

both are cellular ingestion

• phagocytosis = ingest large particles and release oxygen free radicals

• endocytosis = transport large substances into cells

Proliferate vs. Differentiate

both are methods of cellular reproduction

• proliferate = increase the cell #

• differentiate = changes in physical and functional properties of cells; directs cell to develop into specific cell types

Apoptosis vs. necrosis

• apoptosis = programmed cell death, replace old cells w/ new, genetic signal

• necrosis = cell death related to cell injury / inflammation

both are cell death

Describe the plasma membrane

Describe the nucelus

Describe the cytoplasm

cytoplasm:

Describe the rough ER

Describe the smooth ER

Describe the mitochondria

Describe the golgi complex

Describe the lysosome

Describe the peroxisome

What is the cellular function of Transportation? What are its key features?

Cellular Function of Transportation: Transportation in cells refers to the movement of substances across cell membranes to maintain homeostasis and facilitate cellular processes.

Key Features:

• Passive Transport: Movement without energy (e.g., diffusion, osmosis).

• Active Transport: Movement requiring energy (e.g., pumps, endocytosis).

• Selectivity: Membranes regulate what enters/exits.

• Transport Proteins: Assist in moving substances.

What is the cellular function of ingestion? What are its key features?

Cellular Function of Ingestion

Ingestion is the process by which cells take in nutrients and other substances from their environment.

Key Features

• Nutrient Uptake: Cells absorb essential nutrients for energy and growth.

• Endocytosis: Involves mechanisms like phagocytosis (cell eating) and pinocytosis (cell drinking).

• Membrane Dynamics: Involves the alteration of the cell membrane to engulf materials.

• Metabolic Processing: Ingested materials are processed for cellular metabolism and function.

What is the cellular function of secretion? What are its key features?

Secretion = extracellular release of prods

Secretion is the process by which cells produce and release substances to the external environment or into bodily fluids.

Key Features:

• Types of Substances: Includes hormones, enzymes, neurotransmitters, and waste products.

• Mechanisms: Can occur via exocytosis, where vesicles fuse with the plasma membrane.

• Regulation: Controlled by various signals, including hormonal and neural stimuli.

• Role in Homeostasis: Maintains balance in bodily functions and communication between cells.

What is the cellular function of respiration? What are its key features?

cellular respiration is a series of metabolic processes that transforms fuel molecs into energy (ATP) and waste products (CO2, H2O, heat)

• glycolysis

  • breakdown of glucose to 2 ATP molecs

  • absence of oxygen (anaerobic)

  • insufficient to support energy needs of body

  • in cytosol

• aerobic

  • citric acid / krebs cycle

  • in mitpo

  • produces additional 34 ATP molecs

What is the cellular function of communication? What are its key features?

Cellular communication is essential for coordinating activities within and between cells.

• ligands and receptors work together to transduct signals

What is the cellular function of reproduction? What are its key features?

The cellular function of reproduction is to produce new cells, ensuring growth, repair, and maintenance of tissues.

• proliferation and differentiation

What are the specialized functions in some cells? What are their key features?

Describe Hypertrophy: what it is, why, how is it different from normal?

hypertrophy is a cellular response to stress. it is when a cell increases in size due to hormone signaling or increase in workload.

Describe Metaplasia: what it is, why, how is it different from normal?

Metaplasia is the changing of one cell type to another in response to a persistent stressor

• change to a cell better suited to environ

• stressor removed → cells return to original type

• may lead to pathogenic changes

Describe Atrophy: what it is, why, how is it different from normal?

Atrophy is a cellular response to stress which causes a decrease in size of a cell. this can be due to lack of movement, decrease O2 supply, nutritional deprivation, removal of hormone signals

Describe Hyperplasia: what it is, why, how is it different from normal?

hyperplasia is an increase in the # of cells in response to stress

Describe Dysplasia: what it is, why, how is it different from normal?

dysplasia is a change in cell size, shape, uniformity, arrangement, and structure in response to a stressor.

• look abnormal under microscope

• may return to normal or progress to cancer

Screening vs. Diagnosis

screening is the use of testing to sort out apparently well persons (asymptomatic) who probably have disease from those who probably do not. a goal of screening is to increase lead time.

• Screening: done in preclinical phase, 2nd degree

  • Purpose: To identify individuals at risk for a condition.

  • Method: Often involves tests or questionnaires that are not definitive.

  • Example: Mammograms for breast cancer screening.

• Diagnosis: clinical phase, 3rd degree

  • Purpose: To confirm the presence of a specific condition.

  • Method: Involves detailed tests and evaluations.

  • Example: Biopsy to diagnose cancer.

Lead time definition

Lead time is the interval by which the time of diagnosis is advanced by screening and early detection compared to usual time of diagnosis

Prevalence (point vs period)

prevalence = % of pop affected w disease for specified period

• point prev = prev at specific point in time

• period prev = prev over given period of time

Prev = (# of self reported cases in the study)/(# of persons in the study pop)

Incidence

% of specific pop thats newly affected w a disease in a given period of time

= (# ppl newly ill) / (# ppl at risk)

Define all-cause morality, group-specific mortality, and cause-specific morality

• all cause = % of the pop that died during time period

• group specific = % of pop of interest that died over period

• cause specific = % of the pop that died due to a specific cause in period

Case fatality rate

the probability of dying from a disease, given that you have the disease

Proportionate mortality

% of total deaths that are due to a specific cause

What is the key criteria for screening programs?

1. importance / seriousness of outcome

2. alter natural history of disease

3. technically feasible

4. consider costs and benefits

5. acceptable to indiv and healthcare professional

6. recognized treatment

Describe USPSTF:

1. who are they?

2. what do they do and how do they do it?

3. What do their recommendations mean? (A, B, C, D, I)

US preventative services task force

• the decision making body in the US that sets the guidelines for screening programs: who, when, where, how

• indep panel of experts in primary care and prevention

• systematically review the evidence

• develops evidence based recommendations for clinical preventative services

• pushed online and in peer reviewed medical journals

• they review the evidence: benefits and harms of a preventative service in a primary care pop without symptoms

  • certainty and magnitude of net benefit

  • assignment of a letter grade

A - recommend service (high certainty of substancial net benefit)

B - recommend service (high certainty of moderate net benefit)

C - recommend selectively (moderate certainty small net benefit)

D - recommends against service / certainty of no net benefit

I - insufficient to assess → ?

Genetics vs. Genomics

• genetics = study of single genes and their effects on health

  • 9/10 top CODs have a genetic component

• genomics = study of all the genes in the genome including their interactions (includes diseases with genetic and environmental contributions)

DNA

• directs all cell activites

• 4 chem bases (AT/CG), double stranded phosphate backbone, bases connected via H bonds

intron vs exon

• intron = noncoding portion of DNA, spliced out

• exon = sections that code for proteins

Genes, chromosome, nucleosome

• genes = discrete functional units, contain genetic code for protein synth, long stretches of DNA seq

• chromosome = packaging unit for DNA, each chromo contains 1000s of genes, most cells in body are somatic

  • diploid = 46 chromos

    • 22 pair + 2 sex chromos

• nucelosome = a repeating unit of DNA that is wrapped around a core of proteins and is the fundamental building block of chromatin

Locus

locus = gene’s location on a chromosome

Autosome vs. Sex chromosome

Autosome vs. Sex Chromosome

• Autosome:

  • Non-sex chromosomes.

  • Humans have 22 pairs of autosomes.

  • Involved in determining most traits.

• Sex Chromosome:

  • Determine an individual's sex.

  • Humans have 1 pair (XX for females, XY for males).

  • Carry genes related to sexual development.

Diploid vs. Haploid

Diploid vs. Haploid

• Diploid (2n):

  • 46 chromos: 22 pair + 2 sex chromos

  • Contains two complete sets of chromosomes (one from each parent).

  • Found in somatic (body) cells.

  • Example: Human cells (46 chromosomes).

• Haploid (n):

  • 1 chromo of original pair, 22 autosomes, 1 sex chromo

  • Contains one complete set of chromosomes.

  • Found in gametes (sperm and egg cells).

  • Example: Human gametes (23 chromosomes).

Gametes

• each have 23 chromos

• hapoid

• ova/sperm = products of meiosis by specialized cells in ovary or testes

• meiosis = division that reduces the # of chromos in a parent cell by ½ and produces 4 gamete cells

Alleles

alleles are alternate forms of a gene, one allele on each paired chromo get one allele from each parent

• homozygous = same allele from each parent

• heterozygous = diff allele from each parent

Meiosis vs. Mitosis

Meiosis vs. Mitosis

Mitosis:

• Purpose: Cell division for growth and repair.

• Result: Two identical daughter cells (diploid).

• Phases: One division (prophase, metaphase, anaphase, telophase).

Meiosis:

• Purpose: Production of gametes (sperm and eggs).

• Result: Four genetically diverse daughter cells (haploid).

• Phases: Two divisions (Meiosis I and Meiosis II).

Key Differences:

• Mitosis: Identical cells; Meiosis: Diverse cells.

• Mitosis: One division; Meiosis: Two divisions.

Dominant vs. recessive vs. co-dominant

single gene traits

• dominant = alleles that always produce their trait if present on either chromo

• recessive = alleles that only produce trait if present on both chromos

• co dom = alleles that both produce trait

Abnormal chromosome diseases

• not inherited from a carrier parent

• due to loss of chromo or extra chromo

• loss of autosomal chromo = incompatible with life

• karyotype = visual appearence of chromos

1. Congenital Diseases = present at birth or shortly after, not caused by genetic abnormalities, due to failure in development, cannot be transmitted to offspring

Describe gene disorders (???)

hereditary disorders: tracked via circle/square diagram

• caused by inheriting defective genes that produce a defective protein or no proteins

• clear understanding of inheritance patterns

Autosomal dominant pattern of inheritance

a. what are some gene applicable gene disorders?

• single gene disorder

• males and females affected equally

• only need one parent

• huntingtons, osteogenesis imperfect, marfan syndrome

Autosomal Recessive pattern of inheritance

a. what are some gene applicable gene disorders?

• males and females equally affected

• need 2 carriers

• cystic fibrosis, PKU, sickle cell anemia

Sex Linked inheritance pattern

a. what are some gene applicable gene disorders?

• x linked diseases more common bc X chromo is bigger

• more common in males bc only one X chromo

• color blindness, hemophilia, duchenne’s muscular dystrophy

Familial pattern of inheritance

a. what are some gene applicable gene disorders?

• several diseases cluster in families, patterns not understood

• can be multifactoral: several genes, shared environ

• can use epidemiologic methods to estimate heritability

• diabetes, allergies, epilepsy

Cancer

cancer = malignant tumor of potentially unlimited growth that expands locally by invasion and systematically by metastasis

• cancer includes 100+ diff diseases

Malignant vs. benign

• malignant = life threatening, rapid growth, invade surrounding tissue, may metastasize, irregular surfaces, cells dont resemble cells of origin, no uniform appearance, not encapsulated

  • prefix + carcinoma = of epithelial origin

  • prefix + sarcoma = of supportive tissue

• benign = not life threatening, slow growth, remain local, wont metastasize smooth and symmetrical surface, look like cells of origin, uniform experience, encapsulated

  • tissue or origin + “oma”

Metastatic

• metastasis = the development of secondary malignant growths

• metastasize = spread to other sites in body via metastasis

Polyp

polyp = projects from an epithelial surface

• cell or tissue or origin + “oma”

• benign tumor

Carinogens

initiator (1) and promoter (2) of carcinogenesis

Carcinogenesis

carcinogenesis = the process of how cancer goes from normal to cancerous; uncontrolled cell division due to DNA mutations

1. Initiation = result of permanent genetic change due to a carcinogen (initiator)

2. Promotion = expansion of initiated cell by hyperproliferation in response to carcinogen

   i. Altered apoptosis, tissue remodeling, and/or increaased inflammaion

3. Progression = stepwise transformation to malignancy, increased growth rate, invasiveness, metastasis and alteration in morphology

What are the stages of carcinogenesis? Describe them.

1. Initiation - needs a carcinogen to initiate

2. Promotion - needs a carcinogen to hyper proliferate

3. Progression - stepwise transformation to malignancy

What are the patterns of cancer trends? (geography, incidence, survival)

• #2 COD in US

• wide geo var in cancer incidence / mortality

What are the genes responsible for cell division? How do these lead to cancer?

The 4 types of genes that are responsible for cell division are Oncogenes, tumor suppressor genes, suicide genes, DNA repair genes

1. Oncogenes = tell cells when to divide

2. tumor suppressor genes = tell cells when not to divide

3. suicide genes = control apoptosis

4. dna repair genes = can cause cancer when they are mutated, which can lead to errors in DNA that cause cells to grow out of control

   • mutations can be inherited or acquired

Describe Oncogenes

mutated genes that can cause cancer by causing cells to grow and divide uncontrollably

Tumor Suppressor genes

genes that regulate cell growth and division to prevent cancer

• represent the opposite side of cell growth control, normally acting to inhibit cell proliferation and tumor development

suicide genes

a gene that will cause a cell to kill itself through the process of apoptosis

DNA repair genes

genes that code for proteins which actively identify and fix damage to DNA within a cell

Describe the role of the immune system in cancer (???)

a. failure - (???)

b. immunosuppression - immunosuppressive meds are risk factor for cancer

c. infections - many infectious pathogens are risk factors for cancer

Describe the cancer prevention strategies

1. anti-initiation

   • alteration of carcinogen metabolism

   • removal of DNA reactive molecs: decrease phase 1 enzymes which damage dna thru oxidation and increase phase 2 enzymes which excrete carcinogens by reacting w free radicals (eat more antioxidants)

   • enhancement of DNA repair

2. anti-promotion/progression

   • scavenging electrophiles and free radicals, decreasing inflammation, suppressing proliferation (growth factors, estrogen), enhancing apoptosis, decreasing angiogenesis

3. behavioral factors

4. treatment

   1. local = surgery, radiation therapy

   2. systemic = chemo, hormone therapy, immunotherapy

can reduce cancer burden via prevention, screening, and treatment

stress vs stressor

• stress = threat or percieved threat to homeostasis

• stressor = agents or conditions that can produce stress and endanger homeostasis

negative feedback

negative feedback causes the variable to change in a way that is opposite the initial change

• most homeostatic mechs

• initiating corrective mechs

• involves input from nervous and endocrine systems (HPA axis)

• goal to prevent sudden drastic change

general adaptation syndrome - alarm, resistance, exhaustion stage

GAS = physiologic stages after response to stress

1. alarm stage: initial stages after stress exposure, fight/flight response

   • catecholamines and cortisol are released and other hormones are suppressed (growth, thyroid, reproductive)

2. resistance stage: body begins to repair itself after initial shock: chronic hypercortisolism and longterm hormone suppression is detrimental and ineffective

   • irritability, frustration, poor concentration

3. exhaustion stage: chronic stress results, energy depletion and weakened immune system, signif loss of homeostasis, fatigue, burnout, depression and anxiety

allostatic load

Allostatic load is the consequences of sustained or repeated activation of mediators of allostasis

• leads to wear and tear and decreased efficiency of the system

• our bodies are flexible; can slightly change set point in stress response

Adaptive functions - which are increased? decreased?

stress impacts adaptive functions

• increases: vigilance, oxygenation, focused attention, nutrition to body

• decreases: eating, growth, reproduction

Describe the homeostatic control mechanisms

1. stimuli = factor that changed in the persons environ

2. receptor = structure/organ that monitors changes in environ and sends info to the control center

3. control center = determines the set point for variable, analyzes info and coords response

4. effector = structure/organ that carries out response directed by control center

How do multiple effectors work?

multiple effectors allow stress system to achieve balance in multiple ways because the brain can utilize multiple effectors in response → more efficient and safeguard against failure of one effector

What is the role of the brain is responding to stress?

• amygdala indentifies stressor

• → hypothalamus releases hormones to act on autonomic nervous system

• → secretes catecholamies / fight or flight response and activates HPA axis

HPA response / fight or flight

1. what signals

2. how the system can be shut down with negative feedback

stress → hypothalamus → CRH → pituitary gland → ACTH → adrenal gland → cortisol → neg feedback

• Cortisol increases metabolism, vasoconstriction, anti inflammation, regulate blood glucose

• catecholamines = also secreted from adrenal glands but as a neurologic response to receptive organs (can also have neg feedback on system)

• CRH = corticotrophin releasing hormone

• ACTH = adrenocorticotropic hormone

Acute vs. chronic inflammation

• chronic inflammation = persistent or recurrent state of inflammation lasting several weeks or longer

  • results from unrelenting injury, persistent infectious process, prolonged exposure to toxic agent, autoimmune condition, obesity, aging, chronic illness consequences

• acute inflamm response = expected body response to tissue injury, can be measured in hours/days

endogeneous vs. exogeneous

stimuli for acute inflammation

• endogeneous = factors within the body that result in cellular/tissue injury

  • tissue necrosis, immune rxns

• exogeneous = factors that invade/injure the body from the outside

inflammatory diseases (“-itis)

diseases characterized by inflammation of tissue or organ = arthritis (joints), colitis (colon), cystitis (bladder), otitis media (middle ear)

• inflamm at core of many chronic conds

• we should try to shut down the inflamm response

5 cardinal signs of inflammation

1. calor = heat

2. rubor = redness

3. dolor = pain

4. tumor = swelling

5. functio laesa = loss of function