Pathophysiology (Ch1-3)

Pathology

investigation of structural alterations in cells, tissues, and organs which help identify the cause of a particular disease.

Pathophysiology

the study of underlying changes in body physiology (molecular, cellular and organ systems) the result from disease or injury.

Diagnosis

identification of the disease

Prognosis

expected outcome of disease

Epidemiology

Study of how disease is distributed in populations and identification of the factors influencing the distribution

Etiology

the study of the cause of disease or condition.

Predisposing factors

components that increase the likelihood of a disease occurring, but do not directly cause the disease.

Precipitating factors

factors that trigger or activate a disease or condition.

Sign vs Symptom

• Objective indication of disease that can be analyzed and observed by others

• Subjective indication of disease that is experienced by the patient

Clinical manifestations

Signs and symptoms/evidence of disease

Syndrome

Combination of signs and/or symptoms characteristic of a particular disease.

Complications

a condition that arises during the course of a disease or because of medical treatment. It typically develops during or after the initial phase of the primary disease.

Sequelae

Condition that is a long term or permanent consequence of a disease. Sequelae occur after an illness, injury, or medical condition has been treated or resolved.

Remission

symptoms disappear

Relapse/Recurrence

symptoms return

Exacerbations

symptoms more severe

Acute vs Chronic disease

Acute: sudden onset, short duration

Chronic: slow onset, longer duration

Incidence vs Prevalence

Incidence: # of new cases of a disease or condition within a defined period and for a defined population

Prevalence: # of individuals of a defined population who already have a disease or condition

Mortality vs Morbidity

Mortality: # of deaths in a given population

Morbidity: departure from physiologic or psychological well-being and encompasses disease, injury, and disability

Leading causes of death in the United States (2024)

• Heart disease, cancer, accidents, stroke, chronic lower respiratory disease, alzheimer, diabetes, nephrotic (kidney) disease, chronic liver disease, suicide

Cell Organelle Functions

• Nucleus (store DNA)

• Smooth ER (lipids); Rough ER (protein)

• Lysosomes/Peroxisomes (break down waste)

• Mitochondria (produce ATP)

• Golgi apparatus (protein + lipid modification for transport)

• Ribosomes (synthesize proteins)

• Cell membrane (separation, barrier)

• Cilia (move substances across the cell, act as a sensory antenna)

Extracellular matrix

complex network of proteins, sugars, and other molecules that surrounds and supports cells in tissues

• glycoproteins, collagens, elastin,

Cell junctions (cell-to-cell adhesion)

tight junctions: barriers

desmosomes and belt desmosomes: unite cells

gap junctions: communication (will perform gating, which enables uninjured cells to protect themselves from neighbors)

hemidesmosomes: anchors cell to basement membrane

cellular communication

• paracrine: secreting cell targets local cells

• autocrine: secreting cell targets itself

• hormonal: secretes into the bloodstream to reach target

• neurohormonal: secreting cell is a hormone and releases into blood

• contact signaling via gap junctions

The Cell Cycle

G0-G2 Interphase

• G1 phase: period between M phase and start of DNA synthesis, prep

• S phase: DNA is synthesized

• G2 phase: RNA and protein synthesized

• M phase: nuclear and cytoplasmic division

Cyclins

proteins control progression through cell cycle

CDK

Cyclin-dependent kinases, phosphorylate targets that regulate cell cycle

Organ and body size depend on:

• Cell growth: how big

• Cell division: how rapidly

• Cell survival: how long it lives

Regulated by extracellular signal molecules

Growth factors - Stimulate an increase in cell mass/size (cell growth)

Mitogens - Induce or stimulate mitosis (cell division)

Survival factors - Inhibit apoptosis (cell survival)

Somatic Cells

Contain 46 chromosomes (23 pairs)

• Diploid cells

• formed through mitosis

Gametes (sperm/egg)

contain 23 chromosomes

• haploid cells: one member of each chromosome pair (formed through meiosis)

Autosomes/Sex chromosomes

Autosome

• 1-22 of the 23 pairs of chromosomes in males and females

• The two members are virtually identical and thus said to be homologous

Sex chromosome: Remaining pair of chromosomes

• In females, it is a homologous pair (XX)

• In males, it is a hemizygous pair (XY)

Aneuploidy

• A human somatic cell that does not contain a multiple of 23 chromosomes

• A cell containing three copies of one chromosome is trisomic (trisomy)

• Monosomy is the presence of only one copy of any chromosome

• Monosomy is lethal for autosomes, but infants can survive with trisomy of certain chromosomes

Partial trisomy

Only an extra portion of a chromosome is present in each cell

Chromosomal mosaicism

Trisomy occurring only in some cells of the body

Autosomal Dominant Inheritance

Affected offspring are usually produced by the union of a normal parent with an affected heterozygous parent

• Recurrence risk in these instances is 50%

Penetrance and Expressivity

Related to autosomal dominant inheritance

Penetrance: percentage of individuals with a specific genotype who also express the expected phenotype

Expressivity: Extent of variation in phenotype associated with a particular genotype

Autosomal Recessive Inheritance

Recurrence risk for offspring is 25%

• Males and females are equally affected

• Example: Cystic fibrosis

• consanguinity increases risk of recessive disorders

Sex-linked inheritance

• Genetic conditions caused by mutations on sex chromosomes

• Most sex-linked traits are located on the X chromosome and are said to be X-linked

• X-linked recessive traits are the most common

X-linked disorders

• are usually expressed by males because females have another X chromosome to counteract the abnormal gene

• Affected males cannot transmit the genes to sons, but they can to all daughters

• Females become carriers for the disease

• Sons of female carriers have a 50% risk of being affected

Barr body

One X chromosome in females is permanently inactivated early in embryonic

development

Sex-limited traits

only occur in one sex, often because of anatomical differences

Sex-influenced traits

occur much more often in one sex than the other

• ex. male-pattern baldness, autosomal dominant breast cancer

Down Syndrome

trisomy of chromosome 21

• IQ ranges from 20-70 (intellectual disability)

• Male/female findings: virtually all males sterile, some females can reproduce

• musculoskeletal system

• systemic disorders: congenital heart disease

• mortality: abt 75% of fetuses with Down Syndrome abort spontaneously/stillborn

Triple X Syndrome

above average height, mild intellectual disabilities, delayed speech development, premature ovarian failure, menstrual irregularities

Turner Syndrome

(45, X), monosomy of X

Klinefelter Syndrome

(47, XXY)

male appearance, 50% develop female-like breasts

Fragile X Syndrome

Fragile site on the long arm of the X chromosome

• Associated with intellectual disability; second in occurrence to Down syndrome

• Higher incidence in males because they have only one X chromosome

DNA Methylation

• Results from attachment of methyl group to cytosine

• Renders genes inactive - roles in human development and disease

• Abnormal changes to DNA methylation are involved in several cancers

Histone modifications

• histones are proteins that facilitate compaction of DNA into the nucleus of a cell

• Histone modifications can up-regulate or down-regulate nearby gene expression

• They are critical for normal development

Epigenetics and Maternal Care

• Alteration to methylation states could help explain why exposure to stress early in life can modulate behavior in adulthood

ex. Fetal Alcohol Syndrome

Basement membrane

a thin, strong sheet of specialized extracellular matrix that supports and anchors epithelial and endothelial cell layers to underlying connective tissues

Collagen vs Elastin vs Fibronectin

Collagen: provides high tensile strength

Elastin: allows tissue to stretch

Fibronectin: mediates cell adhesion

Mitosis vs Meiosis

Mitosis is asexual reproduction, creates diploid cells (forms somatic cells). Meiosis is sexual reproduction, creates haploid cells (gametes)

Homologous versus Hemizygous

Homologous: two sets of matching chromosomes (ex. Females are XX)

Hemizygous: having only one copy of a gene instead of two (ex. Males are XY)

Karyotyping

A complete set of chromosomes in an organism’s cell

• Visual examination of chromosome

• Useful for identification of gross abnormalities

• Cannot detect single-gene mutations

Diseases caused by abnormalities in chromosome structure

Duplication: Huntington’s disease

Deletion: Cri du chat

X inactivation

One X chromosome in females is permanently inactivated early in embryonic development (barr body)

Genomic imprinting

Imprinting example: deletion of 4 million base pairs of long arm of chromosome 15

• Prader-willi

• Angelman