Foundation Flashcards
What are the determinants of pulse pressure?
Stroke volume
Compliance of aorta
What may cause low pulse pressure?
Distended arteries
Low stroke volume
What does a low pulse pressure lead to?
Small waveform
What may cause a small amplitude and upstroke of the carotid arterial waveform?
Slow blood ejection
Low stroke volume
What causes a fourth heart sound audible at the apex?
Atrial kick caused by decreased ventricular compliance
Why do you produce an atrial kick?
Ventricles have higher pressure so atria have to contract harder to shut atrioventricular valve
What murmur does an aortic stenosis cause?
Systolic murmur
Why is an aortic stenosis louder on expiration?
During expiration, blood being pushed into systemic circulation and out of pulmonary circulation due to greater intrathoracic pressure
More blood flow through left side of heart > louder heart sounds
Why do right-sided heart sounds increase in volume on inspiration?
During inspiration bloodflow increases to venous and pulmonary circulations, because of less intrathoracic pressure > greater preload,
More blood flow through right side of heart
What are the changes to the cardiovascular system when a person stands up?
Force of gravity causes blood to pool in lower extremities > blood pressure initially decreases
Baroreceptor reflex acts to increase heart rate and contractility
What is the role of a finometer?
Measures real-time
- Blood pressure
- Heart rate
- Stroke volume
- Cardiac output
- Total peripheral resistance
How does nicotine act on the body?
Cholinergic receptor agonist
Acts on autonomic ganglia, skeletal muscle, and CNS
What are the side effects of nicotine use?
Tachycardia Mild increase in contractility Anxiety Tremors Nausea Sore throat Mouth irritation
How does caffeine act on the body?
Adenosine receptor agonist Phosphodiesterase inhibitor Acts on - Heart - Vasculature - Airways - Skeletal muscle - CNS
What are the side effects of caffeine use?
Tachycardia Mild increase in contractility Anxiety Tremors Sleeplessness
What is the definition of maximum resolving power?
Smallest distance between 2 points at which 2 points distinguishable
What is the difference between a transmitting electron microscope (TEM), and a scanning electron microscope (SEM)?
TEM = cross-sections SEM = scans surfaces
Why is fixation following removal of tissue from the body important?
Prevents autolysis and bacterial colonisation
How does formalin act as a fixative?
Chemically cross-links molecules to lock them in place
Describe the process of embedding
Fixed tissues gradually dehydrated in solutions of alcohol
Alcohol replaced with xylene
Why is paraffin embedding necessary?
To stiffen tissues > can be sectioned thinly
What occurs after the tissue is sectioned?
Sections rehydrated by passing through series of xylene and alcohol
Put on glass slides
Stained
Covered with coverslip
What does haematoxylin bind to?
Acidic/anionic compounds
What colour does the nucleus stain?
Blue/purple
What are tissues that stain with haematoxylin called?
Basophilic
What does eosin bind to?
Basic/cationic compounds
What colour does the cytoplasm and extracellular matrix generally stain?
Pink
What are tissues that stain with eosin called?
Eosinophilic
Define amphophilic
Stains with both eosin and haematoxylin
What cell components stain amphophilic?
Cytoplasm of cells producing lots of protein with abundant rough endoplasmic reticulum (RER)
What is the life span of platelets?
8-10 days
Where is red bone marrow contained in adults?
Axial skeleton and proximal femur
Where does foetal haematopoiesis mainly occur?
Foetal liver
How is cell production controlled in haematopoiesis?
Growth factors
Microenvironment
Able to respond to sudden demand for extra cells of particular type
What is the structure of collagen fibres?
3 polypeptide alpha chains which form triple helix
What are the three types of connective tissue fibres?
Embryonic connective tissue
Connective tissue proper
Specialised connective tissue
Where is type I collagen found?
Within connective tissue proper
Where is type II collagen found?
Cartilage
Intravertebral discs
Where is type III collagen found?
Reticular fibres
Where is type IV collagen found?
Basement membranes
Where is type VII collagen found?
In anchoring fibres that link basement membranes
Depending on how the section is cut, how may fibroblasts appear?
Round nuclei/long, thin nuclei
What is the role of reticulin fibres?
Provide delicate supporting framework in certain tissues; eg:
- Bone marrow
- Liver
Describe the structure of elastin
Central core of elastin
Surrounding network of fibrillin microfibrils
Why is ground substance frequently not seen on H&E sections?
Lost on preparation
What are the components of ground substance?
Glycosaminoglycans (GAGs) - Hyaluronic acid - Proteoglycans Glycoproteins - Fibronectin - Fibrillin - Laminin
What is extracellular matrix composed of?
Fibres and ground substance
What are the roles of extracellular matrix?
Mechanical support
Control of cell growth and differentiation
Scaffolding for cell proliferation
Synthesis and storage of various growth factors
What are the resident cells of the extracellular matrix?
Fibroblasts Myofibroblasts Macrophages Mast cells Mesenchymal stem cells Adipocytes
What are the types of wandering cells that may be found in the extracellular matrix?
Lymphocytes
Eosinophils
Plasma cells
Basophils
Which cells are responsible for the synthesis of extracellular matrix?
Fibroblasts
What are some examples of dense regular connective tissue proper?
Tendons
Ligaments
Aponeuroses
Where are the nuclei located in adipocytes?
Sometimes visible on edge of cells
Why does bone stain both pink and purple with a H&E stain?
Ground substance stains purple
Matrix largely collagen, so stains pink
What are the components of the extracellular matrix in the basement membrane?
Predominantly type IV collagen
Heparan sulphate
Structural glycoproteins
- Involved in linking integrins of epithelial cells to extracellular matrix
What are the differences between bacterial and higher-order cells?
Have no ER Nucleus not membrane bound No membrane-bound organelles 70S ribosomes, compared to eukaryotes (80S) Replicate by binary fission
What are the key components of bacteria?
Cytoplasmic membrane Cytoplasmic matrix Ribosomes Genome Cell wall
What is the difference between prokaryotic and eukaryotic ribosomes?
Prokaryotic: 50S + 30S = 70S
Eukaryotic: 60S + 40S = 80S
How can bacteria acquire new genes horizontally?
Plasmids Transposons Integrons Bacteriophages Pathogenicity islands
Describe a Gram positive cell wall
Plasma membane > thick peptidoglycan layer
Describe a Gram negative cell wall
Plasma membrane = inner membrane > thin peptidoglycan layer > periplasmic space > outer membrane
What is the structure of lipopolysaccharide (LPS)?
Lipid A attached to core polysaccharide, with repeating units of O-Ag attached
What is the main function of flagella?
Movement
What is the main function of fimbriae or pilli?
Attachment
What is the main function of capsules?
Short-term survival
What is the main function of endospores?
Long-term survival
What are flagella composed of?
Basal body
Hook filament made of flagellin protein
What are fimbriae composed of?
Pilin
What are endospores?
Specialised, resistant, dormant structures
What is the difference between sporulation and germination?
Sporulation = bacteria to spore Germination = spore to bacteria
What are the phases of bacterial growth?
Lag
Log
Stationary
Death
Define facultative anaerobes
Can grow with/without air
Define aerotolerant anaerobes
Can survive in oxygen but won’t grow
Define microaerophiles
Grow best in low oxygen concentrations
What is the set point?
Level at which variable varies upon
What is the comparator?
Acts to integrate sensory information > sends signal to effector
What is the effector?
Receives signal from comparator > makes change to variable
What is the diurnal variation in temperature?
0.6 degrees higher in late afternoon
What is the menstrual variation in temperature?
1 degree higher post-ovulation
Why is thermal energy balance crucial?
Metabolic enzymes have narrow operational temperature range
What controls body temperature?
Hypothalamus
What happens when ambient temperature is high, in terms of body temperature control?
Sweating occurs sooner
Sweat volume decreases
Sweat Na concentration decreases > retains fluid volume and electrolytes
What initiates the increase in set-point temperature during fever?
Pyrogens = endotoxins/cytokines
Induce synthesis of prostaglandin > raises set point temperature
What produces severe combined immunodeficiency (SCID)?
Defective common gamma chain
What is the hygiene hypothesis?
Increase in autoimmunity and allergies because of too clean environment
Immune system has to attack something, so attacks self and innocuous substances
What are the two arms of the immune system?
Innate
Adaptive
Does innate immunity form immunological memory?
No
Can innate immunity distinguish self from non-self?
Yes
What are the barrier tissues of innate immunity?
Skin
Mucosa
What are the soluble factors of innate immunity?
Complement
Cytokines and mediators
Antimicrobial peptides
What are the cell-associated factors of innate immunity?
Pattern recognition receptors (PRRs)
- Toll-like receptors (TLRs)
Cytokines and mediators
Antimicrobial peptides
What are the cells of innate immunity?
Granulocytes - Neutrophils - Eosinophils - Basophils Monocytes/macrophages Dendritic cells (DCs) Natural killer (NK) cells
What is the speed of adaptive immunity?
Slow
What is the specificity of adaptive immunity?
Highly specific
Does adaptive immunity for immunological memory?
Yes
What are the cells of adaptive immunity?
T cells
B cells
What are various types of T cells?
Th1 Th2 Th17 Tfh Cytotoxic T cells Semi-invariant T cells - NKT cells - MAIT cells Gamma-delta T cells
What are the fundamental principles of immune recognition?
Immunological recognition
Immune effector mechanisms
Immune regulation
Immunological memory
What do are some innate effector mechanisms?
Phagocytosis
Microbicidal agents
Complement
What bridges innate and adaptive effector mechanisms?
DC collects Ag
Transports Ag to local draining lymph node
Presents Ag to naive T cells
What are the three main functions of B cell immunity?
Neutralisation
Opsonisation
Complement activation
What is the soluble form of the B cell receptor (BCR)?
Ab
What curtails the immune response after it is no longer required?
Inhibitory cytokines - IL-10 - TGF-beta Treg cells - Contact inhibition - Produce cytokines
What is the point of immunological memory?
More rapid and more effective response on 2nd exposure to Ag
What is meant by polarity of epithelial cells?
Contain different domains
- Apical
- Lateral
- Basal
Are epithelial tissues vascular?
No
Describe how the structure of cilia enables it to function
Organised core of microtubules allowing movement in coordinated waves
What are the different types of intercellular junctions?
Tight
Adherens
Desmosomes
Gap
What are the four main groups of cell adhesion molecules (CAMs)?
Cadherins
Integrins
Selectins
Immunoglobulin superfamily
What are cadherins a component of?
Adherens junctions
How do cadherins function in intercellular adhesion?
Link to anchoring proteins, which bind to cytokeratin intermediate filaments in cell
What is a mucosa/mucous membrane?
Lines body passages that communicate with exterior
Comprises of surface epithelium and underlying supportive connective tissue = lamina propria
Sometimes has underlying layer of smooth muscle = musclarin mucosae
What is a serosa/serous membrane?
Lines pericardial, pleural and peritoneal cavities, and tunica vaginalis
Comprises of surface mesothelium and underlying supportive connective tissue
What is erosion?
Local defect in surface epithelium due to necrosis
What is an ulcer?
Local defect in mucosa/endothelium/skin due to necrosis
What type of epithelium are simple tubular glands made of?
Simple columnar
What type of epithelium are sweat glands made of?
Stratified cuboidal
What do exocrine glands secrete?
Proteins/lipids/glycoproteins
What is a serous secretion?
Protein in aqueous medium
What exocrine glands secrete a serous secretion?
Pancreatic acini
Salivary glands
Lacrimal glands
What is a mucous secretion?
Glycoprotein in aqueous medium
What secretes a mucous secretion?
Respiratory tract
Gastrointestinal tract
Cervix
Why do goblet cells stain white in H&E?
Don’t pick up stain
What are serous acini?
Secretory unit formed by serous cells, usually found at terminal branches of ducts
Describe the duct system, starting from secretory cells
Secretory cells secrete into acinus > secretes into lumen of duct
What is the role of desmosomes in the epidermis?
Helps epidermis withstand tearing forces
What is a virion?
Virus particle
What is a capsid?
Protective protein shell surrounding genome
What is a capsomere?
Clusters of capsid protein subunits
What is a nucleocapsid?
Capsid most closely associated with viral nucleic acid
What is a naked virus?
Virus without envelope
What is a viral envelope?
Lipid membrane derived from host cell membrane surrounding nucleocapsid
Contains virally encoded glycoproteins
What is a viral matrix?
Some viruses have protein layer connecting capsid and envelope glycoproteins
What is the purpose of capsid symmetry?
To protect genome from breakdown by nucleases
What is the purpose of multiple-shelled capsids?
Virus very hardy and can survive passage through gut; eg: rotavirus
How can we gain information about viruses?
X-ray crystallography
Electron microscopy
What are the types of viral genomes
ssDNA dsDNA ssRNA - Positive sense - Negative sense dsRNA
Describe how latex agglutination can be used for diagnosing infection
If Ag present, will cross-link latex particles and cause clumping
What is a solid phase assay?
Ag of interest attaches to solid phase > known Ab with label attached added > binds to Ag > signal
Describe the principles of immunohistochemistry
Uses enzyme labels instead of fluorescent labels
If known Ab binds Ag, an anti-Ab Ab with enzymatic label binds > converts substrate to coloured product
Describe how a capture assay is performed
Capture Ab attached to solid phase > Ag of interest added > binds to capture Ab > add specific Ab (with label) to Ag of interest > binds to Ag > signal
What is DNA hybridisation?
Uses complementary DNA sequences with radioactive labels > bind to DNA of Ag of interest
Diagnosis with detection of bound probe
Why are PCR primers based on 16S rRNA?
Each 16S rRNA strand unique for each bacterial species
What are the two types of culture media?
Liquid (broth)
Solid (agar)
What is the Widdal test and why is it used?
Test to determine Ab titre
How is a solid phase assay used to detect the presence of antibodies in a patient’s serum?
Known Ag attached to solid phase > patient’s sample added > Ab binds to Ag > add anti-human Ig with label > binds to patient’s bound Ab
What does a normal cell look like molecularly?
pH correct for function of cellular enzymes
ATP-dependent NA/K pump keeps Na out and K in
Ribosomes attached to RER continue normal protein synthesis
Cytosolic Ca concentration low
Membranes of cell, mitochondria, and lysosomes intact
What is ischaemia?
Loss/reduction of blood supply
What is hypoxia?
Reduced oxygen in blood supply
What happens when a cell first becomes hypoxic?
Transition to anaerobic glycolysis
What happens as the cell continues to be in a hypoxic state?
Lactic acid build up > pH lowered > Na/K pump fails > Na accumulates > iso-osmotic gain of water > protein synthesis reduced > ribosomes detach from RER > Ca released into cell from mitochondria and SER
What does lowered pH in a cell look like?
Clumping of nuclear chromatin
What does failure of the Na/K pump in a cell look like?
Cell swelling
What does reduced protein synthesis look like in a cell?
Reduced cell function
What will released Ca damage within the cell?
Mitochondria
What does mitochondrial damage within a cell look like?
Mitochondrial swelling
What can increased intracellular Ca do in muscle cells?
Impair contractile function
Can be symptomatic in heart
Which hypoxic changes are reversible if oxygen supply is restored?
ATP depletion
Anaerobic glycolysis
Mitochondrial impairment
Increased cytosolic Ca
What is the point of irreversible injury related to?
Sensitivity of cell/tissue to injury
Type, severity, and/or duration of injury
What is irreversible cellular damage characterised by?
Severe, irreversible mitochondrial dysfunction
Membrane damage
What is severe mitochondrial dysfunction?
Irreversible inability to generate ATP
Abnormal oxidative phosphorylation
Release of pro-apoptotic proteins
What can oxidative stress damage within a cell?
Lipid - cell membrane
Proteins
DNA - mutations
What happens in membrane damage of a cell?
Increased cytosolic Ca activates enzymes to break down cell parts
- Phospholipase
- Protease
- Endonuclease
- ATPase
Membrane of cell, mitochondria, and lysosomes disrupted
Is cell membrane rupture clinically detectable?
Yes, in blood; eg:
- Cardiac enzymes
- Liver enzymes
- Muscle enzymes
What are the cytoplasmic changes in necrosis?
Loss of normal definition
Hypereosinophilic/Pale due to oedema or intracellular accumulations
What is karyolysis?
Faded/pale/absent nuclei
What is pyknosis?
Round, shrunken, condensed, basophilic nucleus
What is karyorrhexis?
Speckled basophilic dots, nuclear dust/debris
Where does coagulative necrosis occur?
Solid organs
What is coagulative necrosis due to?
Ischaemia primarily
What does coagulative necrosis look like macroscopically?
Pale, solid lesion
What does coagulative necrosis look like microscopically?
Eosinophilic
Anucleate
Ghost cells
Persist for days-weeks
Where does caseous necrosis occur?
Anywhere
What is caseous necrosis due to?
Mycobacterium tuberculosis (Mtb) infection
What does caseous necrosis look like macroscopically?
Soft
Creamy white
Cottage cheese
What does caseous necrosis look like microscopically?
Amorphous eosinophilic cell debris
Where does liquefactive necrosis occur?
Brain if ischaemia
Anywhere if bacterial/fungal infection
What causes liquefactive necrosis?
Ischaemia in brain
Bacterial fungal infection
What does liquefactive necrosis look like macroscopically in the brain?
Liquid, viscous mass
What does liquefactive necrosis look like microscopically in the brain?
Eosinophilic neurons
Primarily macrophages
What does liquefactive necrosis look like macroscopically when it is not in the brain?
Collection of yellow liquid = pus
What does liquefactive necrosis look like microscopically when it is not in the brain?
Purulent exudate
Where does fibrinoid necrosis occur?
Vessels
What causes fibrinoid necrosis?
Immune complex deposition
What does fibrinoid necrosis look like microscopically?
Amorphous eosinophilic ring of deposited proteins within wall of vessel
What does the apoptosis pathway need?
Functioning caspases and ATP
What is the relationship between apoptosis and necrosis?
Apoptosis can occur independently, sequentially, or simultaneously with necrosis
Is there an inflammatory response with apoptosis?
No
Is there a loss of cell membrane integrity with apoptosis?
No
What can trigger apoptosis?
Release of pro-apoptotic proteins
Death receptor-ligand interaction
Cytotoxic T cell attack
What is autolysis?
Post-mortem/post-removal of tissue from body - enzymatic digestion of tissue
What types of intracellular accumulations can sub-lethal injury cause?
Fat/lipid/cholesterol
Proteins
Pigment
Distinguish histologically between the three types of muscle in cross-section
Skeletal = peripheral nuclei Cardiac = central nuclei, thick Smooth = central nuclei, thin
Distinguish histologically betwen the three types of muscle in longitudinal section?
Skeletal muscle = peripheral nuclei, very fine striations, long
Cardiac = central nuclei, striations, branching
Smooth = central elongated nuclei, no striations, no branching
What is the role of Z-discs in muscles?
Anchor thin filaments and form boundary with next sarcomere
What is the sliding filament mechanism?
Neither thick nor thin filaments shorten
Cross-bridge between 2 overlaps more > sarcomere shortens > muscle contraction
What is the role of dense bodies in smooth muscle?
Anchors actin filaments
Contraction draws dense bodies together > shortens cell
What is the extent of regeneration of the three types of muscle?
Skeletal = limited Cardiac = none Smooth = reasonable
What is the role of myoepithelial cells?
Surrounds some exocrine glands
Contract via actin and myosin to squeeze out contents
What is the role of myofibroblasts?
Derived from activated fibroblasts and function to pull wound closed
What is the role of pericytes?
Regulate capillary blood flow by contracting around capillaries
What are the three layers of connective tissue wrapping nerves?
Epineurium = wraps whole nerve Perineurium = wraps fascicles Endoneurium = wraps individual axons
In which phase of the cell cycle does DNA replication occur in?
S phase
What do autosomal dominant pedigrees look like?
Vertical transmission of phenotype
Lack of skipped generations
Equal numbers of affected males and females
What do autosomal recessive pedigrees look like?
Horizontal appearance of phenotype, especially among siblings
Equal numbers of affected males and females
Heterozygotes = carriers, generally healthy
Parents of affected child = obligate carriers
What do X-linked recessive pedigrees look like?
Absence of father-son transmission
Apparently skipped generations when genes passed through female carriers
Affected males much more common
What do X-linked dominant pedigrees look like?
Twice as common in females as males
Skipped generations uncommon
Males hemizygous
What does mitochondrial inheritance look like?
Female transmission
Males don’t transmit
What is the difference in response between acute and chronic inflammation?
Acute = earliest Chronic = later
What is the difference in duration between acute and chronic inflammation?
Acute = short, mins-days Chronic = weeks-months-years
What are the features of acute inflammation?
Neutrophils
Fluid and protein exudate
Vasodilation
Macrophages
What are the features of chronic inflammation?
Macrophages
Lymphocytes
Plasma cells
Associated fibrosis/scarring
Describe the process of leukocyte migration
Leukocyte rolling > integrin activation by chemokines > stable adhesion of leukocytes due to high-affinity integrins > migration through endothelium
What are the three main types of inflammatory exudate?
Purulent/suppurative
Fibrnous
Serous
What is a pathogen associated molecular pattern (PAMP)?
Highly conserved molecules/molecular patterns in microbes
Enable discrimination between self and foreign
Where are TLRs located?
Always associated with membrane
- Plasma
- Endosome
Where are RIG-I-like receptors (RLRs) located?
Associated with mitochondria
What do RLRs detect?
Cytosolic DNA
What do NOD-like receptors (NLRs) detect?
DNA
What do neutrophils do?
Phagocytosis
Activation of bactericidal mechanisms
What do eosinophils do?
Killing of Ab-coated parasites
What do basophils do?
Promotion of allergic responses and anti-parasitic immunity
What organ produces complement?
Liver
What are the three pathways of the complement pathway?
Classical
Lectin
Alternative
Where do all three complement pathways converge?
C3b covalently bound to surface components of pathogen > - Recruitment of inflammatory cells - Opsonisation of pathogens - Perforation of pathogen cell membrane Death of pathogen
What are macrophages?
Tissue-resident forms of circulatory monocytes
What do macrophages do?
Phagocytose
Recruit other cells
Scavenge
- Clear dead cells and cell debris
Where are mast cells found?
Connective tissues
What do mast cells release?
Histamine
Cytokines
- IL-4
- IL-13
What are the cardinal signs of inflammation?
Heat Redness Swelling Pain Loss of function
Which bacteria associate with cells?
Commensals
Which bacteria adhere to cells?
Pathogens
How do pathogenic bacteria adhere to cells?
Fimbriae
Non-fimbriae adhesins
How do pathogenic bacteria enter host cells?
Through cells via pathogen-mediated endocytosis initiated by bacterial surface proteins
Between cells
What are the outcomes of invasion that result in survival of bacteria?
Can remain within epithelium
Can translocate deeper
How can extracellular pathogens evade phagocytosis?
Production of leukocidins
Production of anti-inflammatory toxins and enzymes
Interfere with host enzymmes
How do capsules contribute to virulence?
Electrostatic repulsion
Resemble host components
Mask underlying structures
Prevent opsonisation
How do antibodies work against encapsulated bacteria?
Abs bind to capsules and activate classical pathway of complement
IgG-coated bacteria therefore doubly opsonised
How is adaptive immunity overcome?
Direct immunosuppression
Expression of weak Ags
Ag diversity
Ag modification
How do superantigens work?
Cause non-specific activation of T cells and massive cytokine release > mass inflammation
What is pharmacokinetics?
What body does to drug
What is pharmacodynamics?
What drug does to body
What does potency relate to?
Affinity
How does dosage differ depending on potency?
More potent drug will need lower dose for same effect as less potent drug
What is a full agonist?
Drug elicits largest possible response
What is a partial agonist?
Drug elicits lesser effect than largest possible response
What are the possible outcomes of acute inflammation?
Resolution
Healing by repair
Chronic inflammation
How long will chronic inflammation persist for?
Until damaging stimulus eradicated
What are the characteristics of granulomatous inflammation?
Epithelioid macrophages
Multinucleate giant cells
+/- necrosis
What causes a granulomatous inflammation?
Certain persistent/non-degradable Ags
What infections can cause granulomatous inflammation?
TB Leprosy Syphilis Fungal infections Parasitic infections
What unknown causes can cause granulomatous inflammation?
Sarcoidosis
Crohn’s disease
What are the two subtypes of granulomatous inflammation?
Immune granulomas
Foreign body granulomas