Pathology Flashcards
What are the key diagnostic tests for SLE, Sjögren’s syndrome and scleroderma respectively?
SLE - Anti-dsDNA antibody
Sjögren’s - anti-ribonucleoprotein antibodies (anti-SS-A and anti-SS-B)
Scleroderma -DNA topoisomerase I (Scl-70) antibody
All are characterised by ANA
Sjögren’s syndrome is associated with increased risk for which cancer?
B-cell lymphoma
What is CREST syndrome?
Calcinosis (plus anti-Centromere antibody)
Raynaud phenomenon
Esophageal dysmotility
Sclerodatyly
Telangiectasia
Describe the 3 tissue types relevant for tissue regeneration with examples
- Labile tissues: continuously cycle to regenerate tissue e.g bowel (stem cells in mucosal crypts); skin (stem cells in basal layer); bone marrow (haematopoietic stem cells)
- Stable tissues: quiescent but can reenter cell cycle e.g. hepatocytes (liver), proximal renal tubule (kidney)
- Permanent tissue: lack regenerative potential e.g. myocardium, skeletal muscle, neurons (damage to these tissues will be repaired via fibrous scar)
What is the marker of haematopoietic stem cells
CD34+
What are the 3 main components of granulation tissue?
Fibroblasts (deposit type III collagen), capillaries (provide nutrients), myofibroblasts (contract wound)
When granulation tissue is converted to scar, type X collagen is replaced by type Y collagen
X = III (3); Y = I (1)
Occurs via collagenase , which requires zinc as a cofactor . Type I collagen will give the tissue more strength
Where are each type of collagen typically located?
Type 1 = bONE; type 2 = cartilage (car-‘two’-lage); type III = blood vessels, granulation tissue, embryonic tissue; type 4 = basement membrane
Revise key growth factors involved in wound repair
TGF-alpha: epithelial & fibroblast growth factor
TGF-beta: important fibroblast growth factor; inhibits inflammation
PDGF: endothelium, smooth muscle, fibroblast growth factor
FGF: angiogenesis; skeletal development
VEGF: angiogenesis
What are the 2 ways cutaneous healing can occur?
Primary intention - wound edges approximated -> minimal scar formation
Secondary intention - wound edges NOT approximated -> granulation tissue fills the defect, contraction of myofibroblasts will contract the wound
Contrast hypertrophic scar vs keloid?
Hypertrophic scar - excess of type I collagen
Keloid - excess of type III collagen
What is Dubin-Johnson syndrome?
Deficiency of bilirubin canalicular transport protein causing elevated conjugated bilirubin. Autosomal recessive disorder. Characterised by very dark liver, but otherwise rarely clinically significant.
What is Crigler-Najjar syndrome?
Genetic disorder of bilirubin metabolism. Absent UGT (uridine glucuronosyltransferase) -> unable to breakdown bilirubin
It presents in baby, causes kernicterus and is usually fatal
Pruritus in obstructive jaundice is due to elevated plasma ___
Bile acids
List 4 groups of chemicals that mediate acute inflammation and list examples for each
1) Vasoactive amines: histamine, serotonin
2) Lipid products (metabolites of arachidonic acid, present in phospholipid membranes): prostaglandin, leukotrienes, TxA2
3) Cytokines: IL-1, IL-6, TNF
4) complement pathway
Histamine causes vaso(constriction/dilatation) and (increases/ decreases) vascular permeability
Vasodilatation, increases
Serotonin is produced in which cells?
Platelets, certain neuroendocrine cells (e.g. GIT)
Which enzymes produce prostaglandins and leukotrienes respectively?
Cyclooxygenase and lipooxygenases
Montelukast is a ____ used in _____
Leukotriene receptor antagonist; asthma
DiGeorge syndrome is the failure to form the 3rd and 4th ____ and is due to a ___ microdeletion. It causes __ cell deficiency
Pharyngeal pouches; 22q11; T cell deficiency (due to lack of thymus) - also hypocalcaemia (lack of parathyroids) and abnormalities of heart, great vessels and lower face
Low immunoglobulin levels (e.g. due to CVID) increases the risk for what types of infection? (Broad categories)
Bacterial, enterovirus, Giardia
C5-9 deficiency increases the risk for ____ infection
Neisseria
What are the 2 hallmarks of acute inflammation?
Oedema and neutrophils
Innate immunity is a broad, non-specific system that includes epithelium, mucous, complement and which types of cells?
Neutrophils, eosinophils, basophils, macrophages, mast cells
Toll-like receptors (TLRs) are found on which cells?
Macrophages & dendritic cells.
TLRs recognise PAMPs (pathogen associated molecular pattern) and binding results in R activation & gene upregulation e.g. including NF-kappa B -> immune mediation
Which molecules mediate vasodilation and increased vascular permeability
PGI2/ PGD2/ PGE2. Note that vasodilation occurs at arteriole, vascular permeability usually occurs at post-capillary venule
Leukotrione B4 (LTB4) is produced via the ____ pathway. It attracts and activates ____
5-lipooxygenase; neutrophils. LTs mediate vasoconstriction (increasing vascular permeability) and cause bronchospasm
Which complement proteins activate mast cell degranulation?
What are the other 2 mechanisms by which mast cells are activated?
C3a, C5a
Tissue trauma
Cross-linking of surface IgE with Ag
Describe the 3 pathways of complement activation:
Classical: C1 binds to IgG/ IgM bound to antigen (“GM makes classic cars”)
Alternative: microbial products directly activate complement
Mannose-binding lectin (MBL): MBL binds mannose on microorganisms and activates complement
Hageman factor (factor _____) is an inactive pro inflammatory protein produced in the liver. It is activated in the ___ clotting pathway upon exposure to sub endothelial or tissue collagen and plays an important role in ___
XII
Extrinsic pathway
DIC, especially in severe gram negative sepsis. Subsequently activates coagulation + fibrinolytic system, complement and Kinin system (bradykinin).
Pain in acute inflammation is mediated by ___ and ___
PGE2 and bradykinin (these sensitise sensory nerve endings)
What is the primary metastatic site for colorectal cancer?
Liver (due to venous drainage pathway via portal system)
Anal tissue above the pectinate line drains to ____ nodes , whereas that below the pectinate line drains to ____ nodes (include multiple stations)
ABOVE: internal iliac nodes;
BELOW: superficial inguinal nodes -> deep inguinal nodes + external iliac nodes
Metastatic calcification occurs due to ____ and typically affects interstitial tissues of gastric mucosa, kidneys, lungs, systemic arteries and pulmonary veins - these tissues all have an internal (ACIDIC/ ALKALINE) compartment in common
Hypercalcaemia; alkaline (they excrete acid)
What are the main chemotactic agents?
Leukotrienes (LTB4), activated complement C5a, cytokines (IL-8 family) and bacterial products
What are the two main opsonins and their respective receptors?
IgG (Fc fragment) - binds FcgR
C3b - binds CR 1-3 (also bound by fibronectin/ laminin)
Opsonisation is most effective when simultaneous C3 and Fc binding occurs
Another opsonin is collectins
The relevant gene for familial hypercholesterolaemia is located on which chromosome? What is the inheritance pattern?
Chromosome 19
Autosomal dominant
What are the most common types (3) of nonrandom structural chromosomal abnormalities in tumour cells?
Balanced translocation;
Deletions;
Gene amplification
True or false: streptococcus pneumoniae release toxins that cause necrosis of lung tissue in pneumonia
False
They induce chemotaxis but elicit no major toxins (therefore cause inflammation WITHOUT necrosis)
True or false: most antibiotics are lipid soluble
False! Most antibiotics are NOT lipid soluble. Therefore they have difficulty passively diffusing through gram NEGATIVE membrane (lipid bilayer)
Clostridium spp. are gram ____ bacterium
Positive
Gram ___ bacteria contain/ release endotoxins whereas gram ___ bacteria contain/ release exotoxins
Positive
Negative
Which gram negative bacterium is one of the few to excrete a clinically significant exotoxin?
Pseudomonas aeruginosa
What is the definitive treatment for synergistic bacterial gangrene?
Surgery - wide excision + drainage
(Antibiotics and hyperbaric O2 can be supplemental therapies)
What is the main virulence factor of streptococcus pneumoniae?
Its capsule
Allows it to escape phagocytosis & spread in lung/ bloodstream
What are the main sites of systemic miliary tuberculosis?
Liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes and epididymis
List 4 situations that delay/ inhibit wound contraction?
Steroids, burns, skin grafting, XRT
What does the autoclave process involve for sterilisation?
Pressured steam at 121 degrees for 15mins
What is SIRS criteria?
Any 2 of the following:
Tachycardia >90bpm
Temp <36 or >38
RR >20
WCC <4 or >12 or >10% immature band forms
What is qSOFA criteria?
RR ≥22
SBP ≤100
Altered mental status
What are the 4 types of healing?
1) Resolution
2) Regeneration
3) Fibrous repair
4) Remodelling
In graft rejection, CD4+ (TH) cells are stimulated by ____ on graft cells and CD8+ (Tc) cells by ____
CD4+ (TH) - class II HLA
CD8+ (Tc) - class I HLA
Ig classes are named according to their ____ chain
Heavy
IgM, IgG, IgE, IgA, IgD
Class switching is induced by binding of ____ to ______ and secretion of which cytokines?
TH2 TCR binding to Ag-MHC class II complex on B cell surface
(Also co-binding of CD40L/ with CD40)
IL-4,5,6,13, TGFß, TNFa, IFN
- IL-4,13: IgE, some IgG
- IL-5, TGFß: IgA , some IgG
- IFN: IgG
True or false: the Ab-Ag combination is determined by covalent linkage
False
It is shape-determined, and the combination is divalent
What does HLA stand for? Which chromosome are the genes located?
Human leukocyte antigen
Chromosome 6
MHC class I are found on _____ cells and recognise ____
MHC class II are found on _____ cells and recognise ____
Class I - all nucleated cells; recognise viral/ self Ag
Class II - antigen presenting cells; recognise foreign Ag (bacterial)
Which Ig can cross the placenta?
It does this by binding to placental Fc-Rs
IgG