General pathology intro (G) Flashcards
What are pathogenic factors which cause diseases?
Exogenous stimuli and endogenous defects capable of altering the homeostatic condition
What is ethology?
Discipline that studies the causes of diseases
What is pathigenesis?
Mechanism of action by which the causes act
What is a disease?
Detectable deviation of the homeostatic condition
2 kinds of etiological factors
Intrinsic (genetic)
Acquired (extrinsic)
4 kind of causes for extrinsic etiological factors
Physical
Chemical
Food
Biological
2 diseases related only to genetic factors
Muscular dystrophy
Haemophilia
What are most diseases classified as?
Multifactoral
Example of multifactorial diseases (3)
Cancer
Diabetes
Cardiovascular diseases
Example of cancer which is genetic and what gene is effected
Breast cancer (BRACA1 gene)
Example of cancer which is due to exogenous factors
Lung cancer
What is epidemiology?
Diseases studied at the level of population
What is clinical medicine?
Diseases studied at the level of individual
What is pathophysiology?
Diseases studied at the level of organ or system
What is histopathology?
Dieseases studied at the level of tissue
What is cytopathology?
Diseases studied at the level of cells
What is biochemistry?
Diseases studied at the level of organelles
What is molecular biology?
Diseases studied at the level of genes
What is biophysics?
Diseases studied at the level of molecules
What is a proteasome?
Multiprotein complex involved in the degradation of the polypeptides within a cell
What is the molecule of life?
DNA
Length of DNA present in a cell
2 m
How many billions base pairs in DNA present in a cell?
3.2 bill
Name of the 2 arms of DNA
P arm
Q arm
Name of the transcriptionally inactive chromatin
Heterochormotin (dark)
Name of the transcriptionally active chromatin
Euchromatin (light)
5 levels of DNA condensation
Double helix DNA
Chromatin: DNA strand with histones
Chromatin condensed during interphase
Chromatin condensation during prophase
Chrimosomes during metaphase
How many genes are present in a cell?
About 30,000
How many types of polymerase are found in a cell?
3
2 types of class II genes
Constitutive genes
Inducible genes
What is a basal promotor
The shortest sequence by which RNA polymerase II can initiate transcription
What are inducible promote ?
Response elements
What are heat shock protein caused by?
Internal stress
What is HSF?
Heat shock factor
What is HSP
Heat shock protein
Synthesis of which proteins is increased when induced to stress?
Heat shock factor
What are the 2 steps in transcription regulation?
Changes in the local structure of the gene
The basal transcription apparatus bind to the promotor
3 domains in transcription factor domains
Dimerization domain (some dimer factor)
DNA-binding domain
Activation domain
What do enhancers do?
Influence the activity of the promote
Where can regulatory sequences be located?
Variable distances from the gene, upstream or downstream and in both orientation
What is methylation?
Addition of a methyl group
What does methylation typically suppress?
Gene expression
How does methylation typically suppress gene expression?
By increasing the interaction between DNA and histones
What do acetylation and deacetylation do?
Regulate gene expression
How does methylation of DNA and histones eggiest nucleosomes?
Cause them to pack tightly
How many genes encode for miRNA?
About 1000
What is the enzyme called that can cut the RNA?
Dicer
3 types of cells on the basis of replicators potential
Labile
Stable
Permanent
What are labile cells?
Continuously dividing/proliferating
Example of labile cells
Epithelial cells
Haemopoietic stem cell
What are stable cells?
Can divide but not constantly
Example of stable cells
Epithelial cells
Smooth muscle cells
Fibroblast
Endothelial cells
What are permanent cells?
Non-dividing/proliferating cells
Example of permanent cells
Cardiac and skeletal myocytes
CNS neurons
!How long does it take for a cell to divide?!
Varies from cell to cell but the mean value is 24 hours
!How many red blood cells present in the human body?!
5-6 million per mm^3
How long does DNA replication take?
8 hours
How long does mitosis take?
1 hour
Fundamental mechanisms regulating the cell cycle consists of the activity of which 2 protein complexes?
Cyclin
Cycline-dependant kinases (CDK)
Why are cyclins called cyclins?
Because they are synthesised and degraded in the process
Which amino acids can be phosphorylated?
Tyrosine (most important)
Serine
Threonine
2 examples for inhibit kinases (INK)
P16
P21
pH of blood
7.4
What kind of RNA is polymerase I (nucleol)?
Ribosomal RNA
What kind of RNA is polymerase II (nucleplasm)?
Messenger RNA
What kind of RNA is polymerase III (nucleoplasm)?
RNA transfer
What is a promoter?
DNA seq that regulate transcription
What is an enhancer?
Reinforcement element
What kind of structure does an enhancer have?
Modular
What kind of structure does a promoter have?
Modular
What kind of sequence does promoter have?
Common and specific
What kind of localisation does enhancer have?
Variable
What does an inducible promoter contain?
Basal sequences and specific response elements
What is a basal promoter?
Shortest seq which RNA polymerase ii can initiate transcription
What does basal promoter contain?
Common or constructive regulatory seq.
What is the function of basal promoter?
Allow correct localisation of starting complex to regulate efficiency of transcription
What does the basal transcription apparatus RNA polymerase ii require to initiate transcription?
Ancillary factors
What type of transcriptional factors one binds to specific sequences?
Inducible
Which transcriptional factors are not specific to particular genes?
Constitutive
Which transcriptional factors constitute basal apparatus for transcription?
Constitutive
Which transcriptional factors are only able to bind to target seq in activated form?
Inducible
Which 2 properties must transcription factors have?
Recognise specific localised target seq. in promoters, enhancer or other reg elements
Interact w/ RNA polymerase or other transcriptional factors
What is gene expression associated with?
DNA demethylation
What happens if there is methylation close to a promoter?
Absence of transcription
What is histone methylation?
Methyl group is transferred to AA of histone proteins
What decides if there is an increase or decrease in transcription of genes after histone methylation?
Which AA is methylated and how many groups are attached
Where does methylation usually take place?
R residues of Arg and Lys at N-terminal end of histones
What effect does it have that methylation usually suppresses gene expression?
Increases the interaction between DNA and histones
In what areas is acetylation increased?
Areas containing active genes
What is deacetylation a prerequsite for?
Condensed and inactive structure
What cuts RNAds into smaller fragments (19-21 bp)?
The enzyme DICER
What does the fundamental mechanism regulating cellcycle consist of?
Activity of protein complex formed by cyclin and cyclin-dependant kinases (CDK)
2 chromatin remodelling factors
Histone deacetylases
Histone Methyltransferase
What happens to chromatin when RB is hypophosphorylated?
Compact and inhibiting possibility of transcription
What happens to chromatin when RB is phosphorylated?
Chromatin is accessible to transcriptional factors including E2F for transcription of S-phase genes