Phase 1 - Non Anatomy Flashcards
What is histology ?
The study of microscopic structures of biological tissues
What is cell theory ?
All living things are composed of one or more cells
The cell is the basic unit of life
New cells arise from pre-existing cells
What are the 4 types of tissue ?
CT
Epithelial
Muscle
Nervous
What are the 7 steals of epithelial cancer ?
Dedifferentiation
Growth in situ
Invasion of CT
Local invasion
Approaching vessels
Entering vessels
Dissemination (metastasis)
Outline fixation ?
Freezing (about -80 degrees) by dry ice or liquid nitrogen
Chemical fixation = aldehyde based
TISSUE PRESERVATION
Outline embedding?
Frozen samples
Paraffin wax used to embed
PROVIDES SUPPORT FOR SECTIONING
Outline sectioning ?
Thinner = higher resolution
MICROTOME USED TO CUT THIN SECTIONS
Outline staining ?
Non-specific or specific
COLOURS THE TISSUE
What does H&E staining do ?
H (BASIC) = stains acidic structures blue (nucleus)
E (ACIDIC) = stains basic structures pink (cytoplasm)
What is PAS staining used for ?
Complex carbs and glycogen
Tissue stained with PAS = PAS+
Stains mucus, BM, brush borders
Where is simple squamous epithelium found ?
Lining of blood vessels
Lining of heart
Alveoli
Lining of serous membranes
Some kidney tubules (bowman’s capsule + glomerulus)
Where is simple cuboidal epithelium found ?
Kidney tubules
Glands and their ducts
Lining of terminal bronchioles
Surface of the ovaries
Where is simple columnar epithelium found ?
Glands and some ducts
Bronchioles of the lungs
Auditory tubes
Uterus
Uterine tubes
Stomach
Intestines
Gallbladder
Bile ducts
Ventricles of the brain
Where is stratified squamous epithelium found ?
Keratinised = skin
Non-keratinised = mouth, throat , larynx, oesophagus, anus, vagina , INFERIOR URETHRA, cornea
Which part of a cell is replaced by keratin ?
The cytoplasm
These cells are dead
Where are Pseudostratified epithelial cells found ?
Lining of nasal cavity
Nasal sinuses
Auditory tubes
Pharynx
Trachea
Bronchi
ALMOST ALWAYS CILIATED WITH GOBLET CELLS
Where are transitional epithelial cells found ?
Lining of urinary bladder
Ureters
Superior urethra
Pelvis of the kidney
Give 5 examples of SDGs
End poverty
End hunger
Well-being
Quality education
Gender equality
What are SDHs ?
The chances someone has of living a healthy life, due to conditions they live in
How do SDGs relate to SDHs ?
Healthcare wise, focus on equity rather than equality. Ensuring those in challenging conditions have an extra box to stand on the help them reach the same height as those in more favourable conditions.
What structure gives a prickle cell appearance ?
Desmosomes
What is the mucus secreted by goblet cells composed of ?
Proteoglycans (modified carbs)
What staining is best for goblet cells ?
PAS
Which layer of skin contains fibroblasts ?
Dermis
What do fibroblasts produce ?
Collagen 1
What shape is neutrophil nuclei ?
Multi-lobed
What shape is monocyte nucleus ?
Horseshoe - shaped
What are characteristics of eosinophils ?
Bi-lobed nucleus
Large granules
What cell initiated vitamin D production in the skin ?
Keratinocyte
What cell junction is interrupted in epidermolysis bullosa ?
Hemi-desmosomes
What cells/ tissue type is characterised by clear voids when staining ?
Lipids , adipose tissue
Why do lipids appear empty ?
They are dissolved during processing
What initiates apoptosis within cells ?
Release of cytochrome C from the mitochondria to cytosol
What is the function of the RER ?
Protein synthesis
What is the function of the SER ?
Lipid synthesis
Calcium storage
What is the function of lysosomes ?
Degrade unwanted molecules
What do perioxisomes do ?
Perform biochemical reactions
Breakdown fatty acids
What are lamins and where are they found ?
Intermediate filaments
Found in nuclei of all eukaryotic cells
What is the nuclear lamina ?
Composed of lamins
Organisation, membrane support, chromatin organisation
What are microtubules composed of ?
Alpha and beta tubulin
What do kinesins do ?
Move cargo away from centrosome
What do dyneins do ?
Move cargo towards centrosome
What is the cytoskeleton of cilia called ?
Axonemes, allow bending and are composed of microtubules and dynein
What are Microfilaments polymers of ?
Actin
What are the 2 cell-cell junctions and what are the comprised of ?
Adherens : actin (+E-Cadherin)
Desmosomes : IF
What are the 2 cell-ECM junctions and what are the composed of ?
Focal adhesions = actin
Hemi-desmosomes = IF
What are tight junctions ?
Regulation of paracellular permeability
From apical(upper) and basolateral (lower) domains to create a diffusion barrier
What are GAP junctions ?
Cell-cell junctions
Allow passage if small molecules
Involved in electrical signalling
Composed of = hexamers + connexins
What is Kartangers syndrome ?
Lack of dynein arms (cilia)
What is Tay-Sachs disease ?
Failure of gene that encodes lysosomal enzymes
What does ubiquitination do ?
Targets protein for degradation
What are the degradation methods ?
Lysosomal = long-half life, membrane proteins
Proteosomal = short-halfllife , metabolic enzymes + defective proteins
What is the order of skin layers from superficial to deep ?
Stratum corneum
Stratum lucidum (only in thick skin)
Stratum granulosum
Stratum spinosum
Stratum basale
BM
What is the dermis composed of ?
CT = collagen 1, elastin, ground substance
Fibroblasts
What are the two layers of the dermis ?
Papillary - superficial
Reticular - deep (vasculature)
What are Meissners corpuscles and where are they found ?
Rapidly acting mechanoreceptors responsible for touch
Found in the papillary dermis
What are Pacinian corpuscles and where are they found ?
Detect deep pressure and vibration
Subcutis (adipose tissue)
Where are stem cells found in the epidermis ?
Stratum basale
What are merkel cells and where are they found ?
Responsible for sensation
Found in epidermis ( mainly basal layer)
What are langerhans cells and where are they found ?
Dendritic, antigen presenting cells
Epidermis (stratum spinosum + papillary dermis)
Are melanocytes and where are they found ?
Protect from radiation + skin pigmentation via melanin
Basal layer
What are mast cells and where are they found ?
Inflammatory mediator producers
Produce chemotactic factors for eosinophils and neutrophils
Found in DERMIS
What is a partial thickness wound ?
Epidermis + some dermis
What is a full thickness wound ?
Epidermis + all of dermis + deeper structures
What are the 3 phases of wound healing ?
Inflammatory (24-48 hours)
Proliferative (1-2 days)
Remodelling
Outline the inflammatory stage
Platelets initiate blood clot
Neutrophils + macrophages attracted to site
Dead disuse phagocytosed
Outline the proliferation stage
Epithelial cells loosen adhesions
Migrate and cover the granulation tissue
Once covered, keratinocytes prolif
Type 3 collagen formed
Blood vessel forms (angiogenesis)
Outline the remodelling phase
Collagen switched from type 3 to type 1
Final strength only returns to 70-80% at 1 year
What are the 5 conditions for valid consent ?
With capacity
Informed
Voluntary
Not coerced
Not manipulated
What is an example of a live attenuated virus ?
Polio
Rabies
What is an example of a conjugate vaccine ?
Streptococcus pneumoniae
Where do T lymphocytes mature ?
The thymus
What are the secondary lymphoid organs ?
Tonsils
Lymph nodes
Spleen
Peyers patches
Appendix
What colour does GRAM+ turn ?
Purple
What could does GRAM- turn ?
Pink
What makes GRAM- stain ?
Thinner cell wall
Give 2 examples of GRAM+ Cocci
Staphylococcus aureus
Staphylococcus pneumoniae
Give 2 examples of GRAM+ Rods
Listeria monocytes
Corynebacterium diphtheriae
Give an example of GRAM- Cocci
Neisseria meningiditis
Give 2 examples of GRAM- Rods
E.coli
Salmonella
What are sterile body sites ?
Blood
CNS
Lower respiratory tract
Sinuses
Renal system (down to posterior urethra)
Female reproductive tract (down to cervix)
Eye
What is the SIRS classification for sepsis ?
2 or more : Temp outwith 36-38, HR>90, RR >20 or PaCO2 <4.3 kPa
What are the 3 categories of sepsis ?
Sepsis = SIRS with infection
Severe sepsis = Sepsis with hypoxia, acidosis or cerebral dysfunction
Septic shock = Severe sepsis with hypotension despite fluid resus or ionotropic support
What are the 4 main signs of inflammation?
Rubour
Calor
Tumour
Dolor
What causes inflammation ?
ILs + TNF
Leukotrines
Platelet activating factor
Histamine
Clotting system (Bradykinin)
Complement
What is complement ?
A cascade of proteins in serum
Activated by antibody
Amplifies immune response
Directly kills pathogens or attract immune cells
What are the 4 stages of immune cell migration ?
Rolling adhesion
Tight binding
Diapedesis
Migration
What is humoral immunity ?
Antibody from B cells (immunoglobulins)
What is cell-mediated immunity ?
Due to T cells
Intracellular
Where do B cells mature ?
The bone marrow
What are CD4 T cells ?
Helper cells
Recognise antigen presented MHC II on the surface of antigen presenting cells and help them
What are CD8 T cells ?
Cytotoxic
Recognise antigen presented on MHC I and can be induced to kill
What happens to T cells in the thymus ?
Removal of auto-reactive cells to prevent autoimmunity
What cell expresses MHC II ?
Macrophage
What antibody type is the first produced in response to infection ?
IgM
What is an example of how a single base mutation effects a protein ?
Sickle cell anaemia
GAG —> GTG at 6th codon
Outline the hierarchy of stem cell potency
Totipotent
Pluripotent
Multipotent
Unipotent
What are induced pluripotent stem cells ?
iPSCs are a way to make pluripotent stem cells without embryos
Treated with TFs (Oct-3/4, SOX2, c-Myc) to switch in genes and induce pluripotency
What are the 4 types of shock ? (DOCH pneumonic)
Distributive
Obstructive
Cardiogenic
Hypovolemic
What is distributive shock ?
Failure of vasoregulation , severe peripheral vasodilation
Due to sepsis, anaphylaxis or neurogenic causes
What is obstructive shock ?
Barriers to cardiac flow or filling
Pulmonary embolism, cardiac tamponade, tension pneumothorax
What is cardiogenic shock ?
Pump failure
MI , arrhythmias, mechanical
What is hypovolaemic shock ?
Loss of blood
Haemorrhage (trauma, GI bleeding) , burns
What is the trauma triad of death ?
Blood clotting problem —> increased lactic acid
Acidic blood —> decreased heart performance
Low body temperature —> decreased coagulation
What is Class 1 shock ?
HR <100
BP = normal
RR 14-20
Urine output 30 ml/hr
Mental status normal
What is class 2 shock ?
HR >100
BP = normal
RR 20-30
Urine output 20-30 ml/hr
Mental status mild anxiety
What is class 3 shock ?
HR >120
BP = decreased
RR 30-40
Urine output 5-15 ml/hr
Mental status anxious
What is class 4 shock ?
HR >140
BP = decreased
RR >40
Urine output negligible
Mental status confused
What are the 5 steps in the cycle of enquiry?
Acquire
Ask
Assess
Apply
Appraise
What protein mutation causes sickle cell ?
Globin
What is added to blood to stop it clotting ?
Sodium citrate
What happens to coagulation if your replace calcium with chelated calcium ?
Coagulation doesn’t occur
What effect does benzamidine (protease inhibitor) have on coagulation ?
Coagulation takes longer
What molecule is a zymogen ?
Prothrombin
What is the mechanism of action of alteplase ?
It converts plasminogen to plasmin
what is NOT a high risk fluid ?
Urine / faecal matter
Saliva
Sweat
Vomit
(Unless blood stained)
What are general investigations?
Bloods
Imaging
Cultures
What’s are pathology specific investigations?
Cytology sampling - fluids, fine needle
Tissue sampling - biopsy, reaction
Immunohistochemistry
Genetic profiling
What are the 4 cellular responses to stress ?
Hyperplasia = multiplying
Hypertrophy = growth
Atrophy = shrinkage
Metaplasia = changing cell type
What happens if cellular stress is long term ?
Apoptosis
Necrosis
Inflammation
(Possibly neoplasm)
What is dysplasia ?
Abnormal/atypical cells due to a failure of differentiation
What are two key features of dysplasia ?
Pleomorphic nuclei
Mitotic figures
How does HER2 work ?
RTK pathway
What does HER2 over expression suggest in breast cancer ?
More aggressive cancer
What is the treatment for HER2 specific breast cancers ?
Herceptin
What occurs in colon cancer ?
MSI, caused by damage to the MMR system leading to damaged DNA being passed down to new cells making them more prone to cancer causing mutations
Occurs in 15% of colon cancers, better prognosis
Immunotherapies can benefit MSI colon cancers
What is the staging tool for neoplasm spread ?
TNM classification
Tumour - local invasion
Node - lymph nodes
Metastasis - distant tissues
What is the narrowest part of the uterine tube ?
Isthmus
What prevents premature implantation ?
Zona pellucida
What day is the morula formed ?
4
What are the 2 layers of blastocyst ?
ICM - forms embryo and extra embryonic tissues
Trophoblasts - contribute to placenta
What are the 3 important structures during gastrulation ?
Primitive streak
Notochord
Neural tube
At which end does the primitive streak form ?
Caudal end
What are the 2 layers of the bilaminar disc ?
Epiblast
Hypoblast
What happens during gastrulation ?
Invagination creates 3 germ layers
What is derived from the ectoderm ?
Epithelial linings of skin, moth and anus
Cornea and eye lens
Nervous system
Adrenal medulla
What is derived from mesoderm ?
Skeletal system
Muscles (except some smooth muscle)
Excretory system
Circulatory and lymphatic systems
Reproductive systems
Dermis
What is derived from the endoderm ?
Internal linings
Liver
Pancreas
Thymus
Thyroid and parathyroid
What are 3 proto-oncogenes ?
EGFR
HER2
BRAF
Give an example of a deletion/point mutation to form an oncogene
Ras : G protein that transducers signals from cell surface receptors
Mutation causes constantly ‘on’
30% of all tumours screened have Ras mutations
Give an example of a gene amplification mutation to give an oncogene ?
HER2 : transmembrane receptor that receives signals from other cells
Amplified in 20% of breast cancers
Give and example of chromosome rearrangement mutation giving an oncogene
Chromosome 22 bcr gene + chromosome 9 abl gene
Philadelphia translocation
Hybrid gene in chronic myeloid leukaemia (CML)
What growth factor induces angiogenesis ?
VEGF
What happens during prophase ?
Chromatin condensation
Nucleolus disappears
What happens during pro-metaphase ?
Nuclear membranes dissolve
Chromosomes attach to microtubules
What happens during metaphase ?
Spindle fibres align chromosomes along the metaphase plate
What happens during anaphase ?
Paired chromosomes separate and move to opposite sides of the cell
What happens during telophase ?
Chromatids arrive at opposite poles
New membranes form
Chromosomes decondense
Spindle fibres dispense