Midterm 2 Flashcards
What are some common causes of cell injury?
-inadequate oxygenation
-physical, thermal, or chemical agents
-ionizing radiation
-toxins
-microbes
-inflammation and immune reactions
-nutritional imbalance
-genetic and metabolic defects
-aging
What is meant by an acute mild injury to a cell?
-hydropic change (too much water is cell)
-steatosis (fatty spots in the liver)
-fast and reversible
-reverts to normal when the cause of injury disappears
-brief, visible cell change
-ex. brief hypoxia or anoxia
What is meant by a chronic mild injury to a cell?
-intracellular accumulations
-altered growth and differentiation
-can still be reversible (because it is mild)
Give examples of intracellular accumulations
-cholesterol
-protein
-pigment
-environmental particles
Describe atrophy
-decrease in cell number, cell size, and work output
-adaptation to diminished resources
-often reversible (not always)
What are the causes of atrophy?
-disuse
-denervation (neurogenic)
-hormones
-malnutrition
-ischemia (restricted blood flow)
-aging
Describe hypertrophy
-increase in cell size and work output
-adaptation to increased workload and/or increased endocrine stimulation
-often reversible
-most often seen in muscle tissue as muscle has few stem cells and cannot meet increased demand through growing new cells; it must adapt by cell enlargement
-hypertrophy of the heart muscle cells in the long-term can result in heart failure and death
Describe hyperplasia
-increase in cell number in an organ or tissue
-adaptation to increased workload and/or endocrine stimulation
-often reversible
-when the organ or tissue gets bigger because of an increase in cells
-pregnancy
-most pathologic hyperplasias are due to excessive hormonal and growth factor stimulation
What is the difference between hyperplasia and hypertrophy?
Hypertrophy is an increase in tissue or organ size because the cells adapted to become bigger
Hyperplasia is an increase in tissue or organ size because of an increase in the number of cells
They are stimulated by the same signals and can occur at the same time
What is the difference between hyperplasia and cancer?
Hyperplasia is a strictly regulated adaptation to a particular stressor and is reversible
Cancer is uncontrolled cell proliferation that will not be reversed by the removal of the stressor
Describe metaplasia
-change from one cell type to another
-only occurs in epithelium and mesenchyme (connective tissue)
-often reversible
-caused by chronic injury
-adaptation to an injurious stressor
-may be a precursor to dysplasia and cancer
Describe dysplasia
-abnormal cell growth
-cells vary in size, shape, and organization
-still considered “adaptive” because it is reversible
-means disorder growth
-haphazardly arranged, large, dark nuclei that reflect the chromosomal chaos within
-can become malignant but is reversible
-ex. why we get Pap smears
Remember: dysplasia is an adaptive process and does not necessarily mean cancer, it can revert back to normal structure and function
What are the two types of cell death?
- Necrosis– pathological cell death (disease)
- Apoptosis– programmed cell death (natural suicide)
Describe necrosis
-usually due to ischemia/hypoxia/anoxia
-often occurs in a contiguous block of cells
What are the 4 principle types of necrosis?
- coagulative necrosis
- liquefactive necrosis
- caseous necrosis
- fat necrosis
Although there are technically 6 types we will only look at the 4 most common
Describe coagulative necrosis
-characterized by a gel-like change in blocks of freshly dead cells
-most common type of necrosis
-solid organs like the kidney, liver, and heart are most often effected
-can block arteries which cause ischemia and either a heart attack or stroke
-cell detail is intact
Describe liquefactive necrosis
-happens in organs that don’t have connective tissue (like the brain)
-cell death in which the dead tissue dissolves into fluid
-most often caused by bacterial infection
Describe caseous necrosis
-a variant form of coagulative necrosis with limited liquefication and obliterated cellular detail
-the most common cause is tuberculosis infection
-the dead tissue looks like soft, off-white cheese
Describe fat necrosis
-specialized form of liquefactive necrosis that occurs only in fat
-especially common around the pancreas
-pancreatic disease (ex. trauma) liberates pancreatic digestive enzymes that convert pancreatic fat into glycerol and fatty acids and then the fatty acids combine with calcium to create soap– which makes them look like cancer on x-rays
-look like white, chalky deposits
Describe apoptosis
-programmed natural cell death
-activated by internal forces (like embryological development) and external forces (like disease)
-the cell wants to die so they are activated to die rather than killed
What two heritable properties define cancer cells?
- autonomy
- anaplasia
Describe cell proliferation
the programmed generation of new daughter cells divided from progenitor (parent) cells
-under the control of genes
-types: mitosis and meiosis
Describe autonomy of cancer cells
-altered cellular proliferation (the loss of regulated balance of cell division may result in overproliferation)!!
-cancerous cells exhibit excessive cellular proliferation (they grow and reproduce uncontrollably)– which means they are autonomous
Describe cell differentiation
-the orderly process of cellular maturation to achieve a specific function
-under the control of genes, growth factors, nutrients, and stimulation from the external environment
-a regulated balance of undifferentiated and differentiated cells is needed to maintain homeostasis
Describe anaplasia
-altered cellular differentiation!!
-the loss of regulated differentiation renders the cell incapable of carrying out its designed function
-cancerous cells exhibit a loss of cellular differentiation (lose ability to carry out specific functions and do not die when supposed to– anaplastic)
What is the difference between a tumour and cancer?
tumour refers to new growth (neoplasm) which can be either benign or malignant
cancer is malignant neoplasm
all cancers are tumours but not all tumours are cancers
What is the root cause of cancer? (this question will be on test)
DNA damage (mutation)
What is a carcinogen?
-any substance, radionuclide, or radiation that is an agent directly involved in causing cancer
-ex. sunlight, cigarette smoke, industrial chemicals, human papillomavirus, and contact carcinogens
What is cancer pathogenesis?
the process by which a mutated cell proliferates into an undifferentiated population of cells capable of metastasis
Describe the monoclonal origin theory
-that cancer originates from a single mutated cell
-cancer begins with mutations developing in several genes in a single cell and that cell eventually becoming autonomous and anaplastic
Which genes can cause cancer when altered?
- mutator genes– code for proteins that repair mutated DNA
- oncogenes– code for proteins involved in cell growth
- tumour suppressor genes– code for proteins that prohibit proliferation of cells and regulate apoptosis
Describe initiation-promotion-progression
- initiation– the irreversible alteration of a cancer-related gene
- promotion– the proliferation of the initiated (mutated) cell due to promoter exposure
- progression– the autonomous proliferation of the mutated cells
What size is the smallest detectable mass?
about 1 gram or the size of a grape, which can take 10-20 years
Describe the morphology of a tumour cell
-nuclei often considerably larger than normal
-nuclei often have bizarre shapes
-chromatin is coarse and clumped
-nuclei often contain abnormal numbers of chromosomes (aneuploidy)
-more cells in mitosis than normal
-pleomorphic (variable in size and shape)
Define aneuploid
-abnormal number of chromosomes
What are the differences between benign and malignant tumours?
Benign: slow growing, low mitotic index, well-differentiated, well-defined capsule, not invasive and do not metastasize
Malignant: rapid growth, high mitotic index, poorly differentiated, unencapsulated, invasive, spread through bloodstream and lymphatic system
What are the 7 hallmarks of neoplasia? (this question will be on the exam)
- self-sufficiency of growth signals
- evasion of growth suppression signals
- unlimited proliferation
- avoidance of apoptosis
- recruitment of nutrients via angiogenesis
- tissue invasion and spread (mal. neoplasms only)
- evasion of immune surveillance
Define angiogenesis
-the formation of new blood vessels and a critical step in the progression of a tumour
Describe direct extension
-infiltration of malignant neoplasm into adjacent tissues
-aided by secretion of enzymes that breakdown adjacent tissues
Define metastasis
-the discontinuous spread of tumour from one sit to another and is the most reliable sign of malignancy
-results in cancer spread beyond adjacent tissues
What are the types of metastasis?
- lymphatic spread– spread via lymphatic channels (carcinomas)
- hematogenous spread– spread via blood vessels (sarcomas and some carcinomas)
- seeding (aka transcoelomic spread)– spread via body cavities
Describe the seeding the soil theory of cancer
-states that it is difficult for cancer cells to survive outside their region of origin, so in order to metastasize they must find a location with similar characteristics
-provides decent guidelines for where to examine a patient for the most frequent areas of neoplasm spread
What is staging/grading?
evaluating the degree of invasiveness and metastasis– important for treatment decisions
What are some clinical manifestations of cancer?
-lymphadenopathy
-fever
-anemia
-anorexia and cachexia
-fatigue
-venous thrombosis
-paraneoplastic syndromes
Describe lymphadenopathy
-abnormality in the size or character affecting one or more lymph nodes
-in many cases, especially with carcinomas, the first tissue invaded is the local lymph nodes
-most commonly caused by infection, but can also be a sign of cancer (hard and painless have increased chance of malignancy)
Define cachexia
-wasting away
-can be a side effect of cancer treatment
What are paraneoplastic syndromes?
-syndromes caused by the hormones secreted by cancer cells
-ex. cushing syndrome and hypercalcemia
Define autosome
any chromosome that is not a sex chromosome
Define heterozygous
a different gene variant found on both alleles
Define homozygous
the same gene variant found on both alleles
Define congenital
present at birth (not always genetically determined, ex. zika)
Define hereditary
derived from parents (not all hereditary are congenital, ex. Huntington disease only manifests in the 3rd or 4th decade of life)
What are the causes congenital and hereditary diseases?
- Chromosomal abnormalities
- Gene abnormalities
- Multifactorial diseases
Define Multifactorial diseases
Diseases which encompass both gene abnormalities and environmental effects in combination.
Define Nondisjunction
Failure of homologous chromosomes in germ cells to separate from one another during first or second meiotic division.
- During anaphase I or anaphase II
- Will leave one daughter cell with one extra chromosome and one with a chromosome too few
- Missing autosome - cell will not survive
What is Turner Syndrome?
A common sex-linked disorder in females caused by the absence of one X chromosome (XO)
- Hypogonadism
- Growth retardation
- Short stature
- Webbing of the neck
- Low posterior hairline
- Broad chest
- Cubitus valgus (arm mobility)
- Streak ovaries: decreased reproductive ability
What is Triple X Syndrome?
A common sex-linked disorder in females caused by an extra X chromosome (XXX)
- Taller than average
- Increased distance between eyes
- Poor muscle tone
- Curve in pinky finger
- 20 point lower average IQ
- Developmental delays
- Increased risk of Lupis
- Normal fertility: extra X is not passed on
What is Klinefelter Syndrome?
A common sex-linked disorder in males caused by an extra X chromosome (XXY)
- Caused by either increased maternal age or irradiation of either parent
- Wide range of clinical manifestations
- Reduced body and facial hair
- Gynecomastia (man bobs)
- Testicular atrophy
What is XYY Syndrome?
A common sex-linked disorder in males caused by an extra Y chromosome (XYY)
- Caused by nondisjunction of Y chromosome in meiosis II
- May experience learning delays
- IQ normal
- Testosterone normal
- Behavioral problems may occur however aggression levels are generally considered normal
- Usually not heritable
What are the causes of Down Syndrome?
- Nondisjunction during gametogenesis (95%)
- Translocation (few)
- Nondisjunction in zygote (rare)
Describe Trisomy 13 (Patau Syndrome)
Multiple organ defects (nervous system, musculoskeletal, urogenital, etc.)
Describe Trisomy 18 (Edwards Syndrome)
Cleft lip and palate; abnormal development of skull, brain and eyes; congenital heart defect; polydactyly
What is Sickle Cell Disease?
- point mutation of chromosome 11
- causes hemoglobin S protein structure (sickle shaped red blood cells)
- not flexible, can stick to vessel walls, slows or stops the flow of blood and cannot carry enough oxygen
- autosomal recessive gene mutation
What are the delayed effects of sickle cell disease?
-Chromic anemia and hemolysis
- Jaundice
- Pain
- Stroke
- Chronic organ damage
- In high-income countries life expectancy is 40-60
- Heterozygous condition protects people from malaria
What is Cystic Fibrosis?
- Point mutation occurs in CFTR gene (defect in the transport of chloride ions and increased absorption of Na+ and water to the blood)
- abnormally thick mucous secretions
- recessive, autosomal, hereditary gene mutation
What are the delayed effects of Cystic Fibrosis?
- Pancreatic abnormalities
- Pulmonary lesions
- GI tract
- Male genital tract: sterility
these are caused by the blockage of various ducts throughout the body
Define Bronchiectasis
Permanent enlargement of parts of the airways of the lung
Define Emphysema
The destruction of the alveoli
Define Atelactasis
The collapse of part of or all of a lung
Define Cor pulmonale
An enlargement and eventual failure of the right ventricle of the heart, usually caused by pulmonary hypertension
Define Meconium ileus
Newborn babies can’t pass their first stool
Define Phenylketonuria
- Autosomal mutation in PAH gene on chromosome 12 results in loss of enzyme PAH preventing Phe conversion to Tyr
- Increase of plasmatic Phe from birth onwards impairs brain development
- After 6 months, severe intellectual disability
What is Huntington disease? (Chorea)
- rare, fatal, autosomal-dominant, hereditary, non-congenital degenerative disorder
- caused by a misfolded essential neuron protein that builds up
- caused by a series of repeated DNA bases, CAG
- typically develops from age 20 - 55 (average 40 - 50)
Define Epigenetics
- Above or in addition to genetics to explain differentiation
- Chemical modifications of DNA sequences that alter the expression of genes, resulting in disease and phenotypic variations
What are the 3 types of epigenetic modifications?
- DNA methylation
- Histone modification
- Microribonucleic acids (miRNAs)
Define DNA methylation
The addition or removal of a methyl group to specific cytosine bases
- occurs at specific sequences in the promoter region of a gene
- When a DNA sequence in the promoter region of a gene becomes heavily methylated, DNA is less likely to be transcribed into messenger RNA (mRNA)
- This causes a gene to become transcriptionally inactive or silent
- On CG locations
Define Histone post-translational modification
The acetylation and deacetylation of histone tails
- conversion of heterochromatin to euchromatin is due to acetylation of the histone ‘tails’
- The gene becomes transcriptionally active
- DNA wraps around histones to form chromatin
- plays a major role in determining what genes get turned on or off
- If these lysines are deacylated, then the euchromatin shrinks back into its condensed heterochromatin form and the RNA polymerase can’t reach and transcribe that DNA
Define RNA based mechanisms
The generation of specific tiny RNA fragments to inhibit RNA translation
MicroRNA gene silencing
- Perform critical functions during development and cell differentiation
- microRNAs meet up with proteins to form the RISC complex, which can bind to targeted mRNA and form double stranded mRNA. Double stranded mRNA is foreign and destroyed along with targeted mRNA (a way of silencing a gene even after mRNA is made)
Define Fragile X Syndrome
- X-linked dominant mutation (kinda) Remember however that females with FMR1 mutations will have a mosaic pattern
- Caused by the expansion of the CG repeat in the FMR1 gene on the X chromosome
- The FMR1 provides instructions for making a protein called FMRP, which is present in many tissues, including the brain, testes, and ovaries. These mutations prevent transcription of the gene.
- Second to Down Syndrome as a major cause of intellectual disability
- Average IQ of 40 in males, variable in females
- long, thin face with a prominent jam with large protruding ears is also common
- Hypotonia (muscle weakness)
- Macroorchidism in males (big balls)
What happens when MLH1 becomes inactive? (methylation of the promoter region of MLH1)
- damaged DNA accumulates
- colon tumors
- plays a significant role in other cancers
- mutations can accumulate, that would otherwise be repaired (CANCER)
Define Methylation
Addition of one or more methyl group to CG bases in a gene promoter. Turns a gene off
Define Demethylation
Removal of one or more methyl groups from CG bases in a gene promoter. Turns a gene on
Define Hypermethylation
Excess methylation above what is normal in that cell type
Define Hypomethylation
Removal of more methylation then what is normal for that cell type
Define Acetylation
Addition of one or more acetyl groups to the lysine residues of histone tails. Converts heterochromatin to euchromatin. Turns multiple genes on.
Define Deacetylation
Removal of one or more acetyl groups from the lysine residues of histone tails. Converts euchromatin to heterochromatin. Turns multiple genes off.
