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HistoPathology > [P] Week 1: The Cell As a Unit of Health and Disease - Part 1 > Flashcards

[P] Week 1: The Cell As a Unit of Health and Disease - Part 1 Flashcards

1
Q

If pathology is defined as the study of suffering or the study of disease then what does “pathos” and “logos” stand for?

A
  • Pathos: suffering
  • Logos: study
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2
Q
  • This is defined as the study of the structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease
  • It serves as the bridge between the basic sciences and clinical medicine
  • It is the scientific foundation for all of medicine
A

Pathology

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3
Q

General vs. Systemic Pathology

  1. Alterations in specialized organs and tissues responsible for disorders that involve these organs
  2. Reactions of cells and tissues to abnormal stimuli and to inherited defects, the main causes of disease
A
  1. Systemic
  2. General
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4
Q
  1. The human genome contains around ____ DNA base pairs
  2. Within the genome, there are only about ____ protein-encoding genes, constituting just ____ of the genome
A
  1. 3.2 billion
  2. 20,000
  3. 1.5%
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5
Q

These genes are the blueprints that instruct the assembly of enzymes, structural elements, and signaling molecules within the 50 trillion cells that make up the human body

A

Protein-encoding genes

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6
Q

5 Major Classes of Functional Non-protein-coding Sequences

  1. These provide binding sites for transcription factors
  2. These are for factors that organize and maintain higher order chromatin structures
  3. These are described as jumping genes (e.g. transposons)
  4. Refers to telomeres (chromosome ends) and centromeres (chromosome tethers)

A. Mobile Genetic Elements
B. Promoter and Enhancer Sequences
C. Binding Sites
D. Special Structural Regions of DNA
E. Non-coding Regulatory RNAs

A
  1. (B) Promoter and Enhancer Sequences
  2. (C) Binding Sites
  3. (A) Mobile Genetic Elements
  4. (D) Special Structural Regions of DNA
  5. (E) Non-coding Regulatory RNAs

Note: (E) has no description in the transes but it constitutes the 5

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7
Q

Most of the genetic variations (polymorphisms) associated with diseases are located in what regions of the genome?

A

Non-protein-coding regions

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8
Q

Person-to-person variation susceptibility to diseases and response to environmental agents and drugs, is encoded in less than ____ of our DNA which is about ____ base pairs

A
  1. 0.5%
  2. 1.5 million
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9
Q

Refers to heritable changes in gene expression not caused by alterations in DNA sequences (phenotype diversity cannot be explained by DNA changes)

A

Epigenetics

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10
Q

What are the 2 most common forms of DNA variation in the human genome ?

A
  1. Single Nucleotide Polymorphisms (SNPs)
  2. Copy Number Variations (CNVs)
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11
Q

Single Nucleotide Polymorphisms (SNPs) or Copy Number Variations (CNVs)

  • Are almost always biallelic (only two choices exist at a given site; e.g. A or T)
  • There are more than 6 million of these
  • Occurs across the genome (about 1% in the coding regions)
  • A useful marker if co-inherited with a disease-associated pleomorphism as a result of physical proximity (linkage equilibrium)
  • Displays a weak effect on disease susceptibility
A

Single Nucleotide Polymorphisms (SNPs)

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12
Q

Single Nucleotide Polymorphisms (SNPs)

  1. This element alters gene expression and disease susceptibility
  2. This variant has no effect on gene function or individual phenotype
A
  1. Genomic Regulatory Element
  2. “Neutral” Variant
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13
Q

Single Nucleotide Polymorphisms (SNPs) or Copy Number Variations (CNVs)

  • Is biallelic and simply duplicated or deleted in some individuals
  • Deals with complex rearrangements of genomic material, with multiple variants in the human population
  • Is responsible for between 5 million and 24 million base pairs of sequence difference between any two individuals
  • 50% of these involve gene-coding sequences
A

Copy Number Variations (CNVs)

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14
Q
  1. All cells of the body have (the same/different) genetic compositions
  2. Differentiated cells have distinct structures and functions that arise as a result of (lineage-specific/inheritance-specific) gene expression programs, depending on epigenetic factors
A
  1. The same
  2. Lineage-specific
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15
Q

TOF: Genomic sequences are translated but NOT transcribed

A

False (reverse; genomes cannot be translated as they are not proteins)

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16
Q

MicroRNAs (miRNAs) vs. Long noncoding RNAs (lncRNAs)

  • Refers to small RNA molecules
  • They do not encode proteins but rather modulate the translation of target messenger RNAs (mRNAs)
  • Are critical regulators of developmental pathways as well as pathologic conditions (e.g. cancer)
A

MicroRNAs (miRNAs)

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17
Q

MicroRNAs (miRNAs)

This is a mechanism of gene regulation in all eukaryotes

A

Post-transcriptional silencing of gene expression

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18
Q

MicroRNAs (miRNAs) vs. Long noncoding RNAs (lncRNAs)

  • Contains more than 200 nucleotides in length
  • They modulate gene expression
  • They bind to chromatin regions to restrict gene coding
  • There is increased transcription from gene promoters (e.g. cancer and atherosclerosis)
A

Long noncoding RNAs (lncRNAs)

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19
Q

The following are the roles of Long non-coding RNAs (lncRNAs) EXCEPT:
A. Gene Activation
B. Gene Suppression
C. Promotion of Ribosomal Modification
D. Assembly of Protein Complexes

A

C. Promotion of Ribosomal Modification (should be chromatin modification)

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20
Q

Gene editing advancements are associated with CRISPRs which stand for?

A

Clustered Regularly Interspaced Short Palindromic Repeats

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21
Q

Cas9 nuclease is an example of what kind of gene?

A

CRISPR-associated genes (Cas)

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22
Q

Cellular Constituents

  • Are “disposal” complexes that degrade denatured or otherwise “tagged” cytosolic proteins
  • The degradation of regulatory proteins or transcription factors can trigger the initiation or suppression of signaling pathways
A

Proteasomes

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23
Q

In antigen-presenting cells, the resulting short peptides are presented in the context of Class I or Class II MHCs to help drive the adaptive immune response. What component is responsible for cleaving the peptides into short ones?

A

Proteasomes

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24
Q

Cellular Constituents

  • These are intracellular organelles containing degradative enzymes that permit the digestion of macromolecules
  • Serves as the site of senescent intracellular organelle breakdown (autophagy) and where phagocytosed microbes are killed and catabolized
A

Lysosomes

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25
Q

Cellular Constituents

  • These contain catalase, peroxidase, and other oxidative enzymes
  • They play a specialized role in the breakdown of very long-chain fatty acids, generating hydrogen peroxide in the process
A

Peroxisomes

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26
Q

The Fluid Bilayers of Amphipathic Phospholipids

____ head groups face the aqueous environment while ____ lipid tails interact with each other to form a barrier for the ____ diffusion of large or charged molecules

A
  1. Hydrophilic
  2. Hydrophobic
  3. Passive
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27
Q

The Plasma Membrane

  • This can be phosphorylated, serving as an electrostatic scaffold for intracellular proteins
  • This can also be hydrolyzed by Phospholipase C to generate intracellular second signals (e.g. diacylglycerol and inositol triphosphate)
A

Phosphatidylinositol

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28
Q

The Plasma Membrane

  • These are located on the extracellular face
  • These support charge-based interactions that contribute to inflammatory cell recruitment and sperm-egg fusion
A

Glycolipids and Sphingomyelin

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29
Q

Glycolipids

Glycolipids, including ____ with complex sugar linkages and terminal ____ that confer negative charges, support charge-based interactions

A
  1. Gangliosides
  2. Sialic acids
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30
Q

Membrane Transport (Passive or Active?)

  • Oxygen (O2), carbon dioxide (CO2), and hydrophobic molecules diffuse easily through this
  • Is impermeable to charged ions and is dependent on the degree of hydration
  • It drives solutes via a concentration and/or electrical gradient between the inside and outside of the cell
A

Passive Diffusion

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31
Q

Membrane Transport (Passive or Active?)

  • Plasma membrane transport proteins are required for the uptake and secretion of ions and larger molecules required for cellular function (e.g. nutrient uptake and waste disposal)
  • It requires ATP as the solute moves against the concentration gradient
A

Active Diffusion

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32
Q

Membrane Transport (Proteins)

These create hydrophilic pores, which, when open, permit rapid movement of solutes (usually restricted by size and charge)

A

Channel Proteins

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33
Q

Membrane Transport (Proteins)

These bind to their specific solutes and undergo a series of conformational changes to transfer the ligand across the membrane

A

Carrier Proteins

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34
Q

Membrane Transport (Water Movement)

  1. H2O moves OUT of the cell
  2. H2O moves INTO the cell
A
  1. Hypertonic
  2. Hypotonic

Note: The point of reference is the PLASMA

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35
Q

Receptor-Mediated and Fluid-Phase Uptake Mechanisms

  1. Refers to the uptake of fluids or macromolecules by the cell
  2. The movement of endocytosed vesicles/intact proteins between the apical and basolateral compartments of cells (epithelial barriers)
  3. Refers to when macromolecules are exported out of the cell (vesicle is recycled to the plasma membrane)
A
  1. Endocytosis
  2. Transcytosis
  3. Exocytosis
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36
Q

Types of Endocytosis

  1. This makes use of caveolae, caveolin, and pinocytosis
  2. Contains major mechanisms for macromolecules bound to membrane receptors
A
  1. Caveolae-mediated Endocytosis
  2. Receptor-mediated Endocytosis
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37
Q

Types of Endocytosis

These are non-coated plasma membrane invaginations associated with GPI-linked molecules, cAMP binding proteins, src-family kinases, and the folate receptor

A

Caveolae (“little caves”)

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38
Q

Types of Endocytosis

This is a major structural protein of caveolae along with bound molecules and associated extracellular fluid

A

Caveolin

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39
Q

This is the intracellular scaffold (support) of proteins which has the ff. functions:
- Forms the shape of cells
- Maintains cellular polarity
- Provides a means for cell movement
- Maintains the positions of intracellular organelles

A

Cytoskeleton

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40
Q

Classes of Cytoskeletal Proteins

  • The most abundant cytosolic proteins in cells
  • Includes G and F actin (e.g. muscles)
A

Actin Microfilaments

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41
Q

Classes of Cytoskeletal Proteins

  • Provides characteristic tissue-specific patterns of expression
  • Includes vimentin, desmin, neurofilaments, glial fibrillary acidic protein, cytokeratins, and laminins
A

Intermediate Filaments

42
Q

Classes of Cytoskeletal Proteins

  • Involves thick fibrils
  • Has dimers of α and β tubulin associated with paired centrioles
  • Can elongate or shorten, move vesicles and organelles, and for mitotic separation and cilia and flagellar motion
A

Microtubules

43
Q

Intermediate Filaments

  1. Mesenchymal cells (fibroblasts, endothelium)
  2. Muscle cells that form the scaffold on which actin and myosin contracts
  3. Critical for neuronal axon structure and confers strength and rigidity
  4. Glial cells
  5. Epithelial cells (at least 30 of these are distinct)
  6. Intermediate filament proteins that form the nuclear lamina, define nuclear shape, and can regulate transcription

A. Laminins
B. Desmin
C. Vimentin
D. Cytokeratins
E. Neurofilaments
F. Glial Fibrillary Acidic Protein

A
  1. (C) Vimentin
  2. (B) Desmin
  3. (E) Neurofilaments
  4. (F) Glial Fibrillary Acidic Protein
  5. (D) Cytokeratins
  6. (A) Laminins
44
Q

Cells connect and communicate with each other via ____ complexes that form mechanical links and facilitate receptor-ligand interactions

A

Junctional

45
Q

3 Basic Types of Cell-Cell Interactions

  • Aka tight junctions
  • They seal adjacent epithelial cells together to create a continuous barrier that restricts the paracellular movement of ions and other molecules
  • They form a tight mesh-like network of macromolecular contacts between neighboring cells
  • A boundary that separates apical and basolateral membrane domains and helps to maintain cellular polarity
  • It facilitates epithelial healing and inflammatory cell migration across epithelial-lined mucosal surfaces
A

Occluding Junctions

46
Q

3 Basic Types of Cell-Cell Interactions

  • Aka adherens junctions and desmosomes
  • Mechanically attaches cells and their cytoskeletons to other cells or the ECM
  • e.g. Cadherin and Glycoprotein
A

Anchoring Junctions

47
Q

Type of Interaction

  1. Cadherin-Glycoprotein
  2. E-Cadherin-Belt Desmosome
  3. Integrin-Hemidesmosome

A. To the ECM
B. Cell to Cell
C. Utilizes Actin

A
  1. (B) Cell to Cell
  2. (C) Utilizes Actin
  3. (A) To the ECM
48
Q

3 Basic Types of Cell-Cell Interactions

  • Aka gap junctions; for communication
  • Chemical/electrical signals pass on from cell-to-cell, through pores, and with protein connections (small molecules)
  • There is a reduction of permeability by increased intracellular calcium and low pH
A

Communication Junctions

49
Q

What 2 organelles are part of the biosynthetic machinery of the cell?

A

The ER (smooth & rough) and Golgi Apparatus

50
Q

Biosynthetic Machinery of the Cell

  • For synthesis purposes
  • Prominent in the liver and gonads
  • Has no ribosomes as all molecules are for export
A

Smoother ER

51
Q

Biosynthetic Machinery of the Cell

The SER of the muscles are responsible for the release/sequestration of ____ ions which regulates contraction and relaxation

52
Q

Biosynthetic Machinery of the Cell

  • Comes with ribosomes
  • It translates mRNA to ER proteins
  • Has folds that form peptide complexes
  • If proteins are not folded, it leads to stress of this organelle
53
Q

Biosynthetic Machinery of the Cell

  • Contains stacked cisterns
  • Found in secretory cells (e.g. goblet cells in bronchi and plasma cells)
  • Glycosylates (removes oligosaccharides to the lysosomes) or recycles protein back to the ER
A

Golgi Apparatus

54
Q

What 2 organelles are for waste disposal?

A

Lysosomes and Proteasomes

55
Q

Waste Disposal

  • Functions best at a pH of ≤ 5 (contains 40 acid hydrolases)
  • A catabolic pathway by macromolecules
56
Q

Lysosomal Associations

  • Aka fluid phase pinocytosis
  • Material is internalized by the fluid-phase from the plasma membrane to the early and then late endosomes and ultimately arrives at the lysosome
  • These compartments are progressively acidified such that proteolytic enzymes become active in late endosomes and lysosomes
A

Receptor-Mediated Endocytosis

57
Q

Lysosomal Associations

  • It preserves cell viability during nutrient depletion
  • Waste products can be ferried into lysosomes by a process called autophagy
  • Through a mechanism involving the products of autophagy-related (Atg) genes, obsolete organelles are corralled by a double membrane derived from the ER
  • The membrane progressively expands to encircle a collection of organelles and cytosolic constituents, forming the definitive autophagosome
A

Senescent Organelles and Denatured Protein Complexes

58
Q

This process:
- Facilitates the turnover of aged and/or defunct structures
- Preserves viability during nutrient depletion
- Is involved in protective responses to intracellular infections
- Participates in intracellular repair
- Triggers programmed cell death (apoptosis)

59
Q

Lysosomal Associations

  • This is carried out by macrophages and polymorphonuclear neutrophils
  • The material is engulfed to form a phagosome that subsequently fuses with lysosomes
A

Phagocytosis

60
Q

Waste Disposal

  • Disposes of denatured or misfolded proteins using ubiquitin
  • These digest proteins into small (6 to 12 amino acids) fragments that can subsequently be degraded to their constituent amino acids and recycled
A

Proteasomes

61
Q

Waste Disposal

  • Many proteins destined for destruction are identified by covalently binding to this small protein
62
Q

Waste Disposal

These are unfolded and funneled into the polymeric proteasome complex—a cylinder containing multiple protease activities, each with its active site pointed at the hollow core

A

Polyubiquitinated molecules

63
Q

Cellular Metabolism and Mitochondrial Function

This membrane contains cristae (with respiratory enzymes)

A

Inner Membrane

64
Q

Cellular Metabolism and Mitochondrial Function

This membrane has porin proteins (aqueous canals permeable to small molecules)

A

Outer Membrane

65
Q

Cellular Metabolism and Mitochondrial Function

Components of the Inner Membrane:
1. Has enzymes for the citric acid cycle
2. Functions for the production of heat
3. The site for ATP synthesis

A. Inner membrane proteins
B. Core Matrix
C. Outside the membrane

A
  1. (B) Core matrix
  2. (A) Inner membrane proteins
  3. (C) Outside the membrane
66
Q

Mitochondria: Energy Generation

  1. Energy is producted through ____
  2. The major energy source is the synthesis of ____
  3. The energy used to generate heat is called as ____
  4. A source of ____ (increased in hypoxia, toxicity, injuries, mitochondrial aging)
A
  1. Oxidative phosphorylation
  2. ATP
  3. Thermogen
  4. Free radicals/H2O
67
Q

Mitochondria: Energy Generation

What is the half-life of the mitochondria?

A

1 to 10 days (degraded through mitophagy)

68
Q

Mitochondria: Energy Generation

TOF: The mitochondria are constantly undergoing fission and fusion with other newly synthesized ribosomes to support their renewal and defend themselves against degenerative changes

A

False (other newly synthesized mitochondria)

69
Q

Mitochondria: Energy Generation

This mitochondrial function is described with decreased ATP but increased lipid and nucleic acid proteins

A

Intermediate Metabolism

70
Q

Mitochondria: Energy Generation

This phenomenon burns substrates to their core CO2 and H2O, leaving no carbon moieties to use for building lipids and proteins. Rapidly dividing cells (both benign and malignant) increase their uptake of glucose and glutamine and switch to aerobic glycolysis.

A

Warburg Effect

71
Q

Mitochondria: Energy Generation

The Warburg Effect is able to generate how much net ATP?

72
Q

Mitochondria: Energy Generation

Oxidative phosphorylation efficiently generates how many ATP molecules per glucose molecule?

73
Q

Mitochondria: Energy Generation

What are the 2 pathways of the mitochondria for cell death?

A

Necrosis and Apoptosis

74
Q

Cell Death

External cellular injury (toxins, ischemia, and trauma) can damage the mitochondria, inducing the formation of “Mitochondrial Permeability Transition Pores” in the outer membrane which causes the ATP to drop therefore killing the cell

75
Q

Cell Death

  • Uses extrinsic/intrinsic signals
  • In damaged mitochondria, cytochrome C leaks out of the pore
  • Activated caspases lead to this type of cell death
76
Q

Cell Death

This process releases cytochrome C (and other proteins) into the cytoplasm which activate intracellular programmed cell death pathways

A

Mitochondrial Outer Membrane Permeabilization (MOMP)

77
Q

Cellular Activation and Signalling

Give the signal:
Many cells have an innate capacity to sense and respond to damaged cells (danger signals), as well as foreign invaders such as microbes

A

Danger & Pathogens

78
Q

Cellular Activation and Signalling

Give the signal:
Mediated through adhesion molecules and/or gap junctions, wherein gap junction signaling is accomplished between adjacent cells via hydrophilic connexon channels that permit the movement of small ions (e.g., calcium), metabolites, and second messenger molecules (e.g., cAMP)

A

Cell-Cell Contacts

79
Q

Cellular Activation and Signalling

Give the signal:
Mediated through integrins (may be considered in the context of leukocyte attachment to other cells during inflammation)

A

Cell-ECM Contacts

80
Q

Cellular Activation and Signalling

Give the signal:
The most important components include (1) growth factors; (2) cytokines, mediators of inflammation and immune responses; and (3) hormones

A

Secreted Molecules

81
Q

Cellular Activation and Signalling

Give the pathway:
Only cells in the immediate vicinity are affected. To accomplish this, there can be only minimal diffusion, after which the secreted signal is rapidly degraded, taken up by other cells, or trapped in the ECM

A

Paracrine Signaling

82
Q

Cellular Activation and Signalling

Give the pathway:
Occurs when molecules secreted by a cell affect that same cell. This can be a means to entrain groups of cells undergoing synchronous differentiation during development, or it can be used to amplify (positive feedback) or dampen (negative feedback) a particular response

A

Autocrine Signaling

83
Q

Cellular Activation and Signalling

Give the pathway:
Activated neurons secrete neurotransmitters at specialized cell junctions (i.e., synapses) onto target cells

A

Synaptic Signaling

84
Q

Cellular Activation and Signalling

Give the pathway:
A mediator is released into the bloodstream and acts on target cells at a distance

A

Endocrine Signaling

85
Q

Cellular Activation and Signalling

Give the receptor:
- Includes transcription factors that are activated by lipid-soluble ligands that can easily transit plasma membranes
- In other cases, a small and/or nonpolar signaling ligand produced by one cell type can influence the activity of adjacent cells

A

Intracellular Receptors

86
Q

Cellular Activation and Signalling

Give the receptor:
- Are generally transmembrane proteins with extracellular domains that bind activating ligands.
- Ligand binding can: (1) open ion channels; (2) activate an associated GTP-binding regulatory protein (G protein); (3) activate an endogenous or associated enzyme (often a tyrosine kinase); and (4) trigger a proteolytic event or change protein binding stability to activate a latent transcription factor

A

Cell-Surface Receptors

87
Q

The Nucleus

____% of the genome regulates gene expression or binds proteins

88
Q

Intrinsic Proliferative Capacity of Cells

Give the capacity:
Is continuously being lost and replaced by maturation from tissue stem cells and by proliferation of mature cells (e.g. hematopoietic cells and surface epithelia)

A

Labile (Continuously-Dividing) Tissues

89
Q

Intrinsic Proliferative Capacity of Cells

Give the capacity:
Quiescent in the G0 stage of the cell cycle; with minimal proliferative activity in their normal state; capable of dividing in response to injury or loss of tissue mass (e.g. liver, kidney, and pancreas)

A

Stable Tissues

90
Q

Intrinsic Proliferative Capacity of Cells

Give the capacity:
Terminally differentiated and nonproliferative in postnatal life (e.g. neurons and cardiac myocytes)

A

Permanent Tissues

91
Q

The maintenance of a cell population is by what?

A

Cell Proliferation (Growth)

92
Q

Cell Cycle

  1. Pre-synthesis growth
  2. The second stage
  3. Pre-mitotis growth
  4. Mitosis

A. M
B. DNA Synthesis
C. G1
D. G2

A
  1. (C) G1
  2. (B) DNA Synthesis
  3. (D) G2
  4. (A) M
93
Q

If the cell cycle sequence is not followed, what happens to cellular growth?

A

It arrests

94
Q

Cell Cycle Regulators

These are proteins needed for cell cycle progression

95
Q

Cell Cycle Regulators

This enzyme phosphorylates protein by forming complexes and acts as surveillance to sense DNA or chromosome damage

A

CDK (Cyclin-Dependent Kinase)

96
Q

These types of cells:
- Give rise to all types of differentiated tissues
- Are capable of self-renewal and asymmetric division
- Replace damaged cells and maintain tissue population

A

Stem Cells

97
Q

Stem Cells

These can renew any cell type (totipotential) and can induce special cells to grow in cultures

A

Embryonal Stem Cells

98
Q

Stem Cells

These cells renew only normal tissues (e.g. hematopoietic stem cells will only replenish blood components)

A

Adult Stem Cells

99
Q

Stem Cells

Stem cells express this antigen which provokes rejection in transplantation

  • Cells from the same patient: no rejection
  • Cells from another person: rejection
A

HLA (human leukocyte antigen)

100
Q

Stem Cells

Stem cells are located in the ____, between normal cells, and they are latent until stimulated

A

Basal Layer

HistoPathology (14 decks)

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