Pathology Flashcards
what cells are predominantly found in pus and what substance is responsible for their recruitment
neutrophils recruited by interleukin 8
what substance is responsible for recruitment of lymphocytes
IL-2
what is interleukin 1 responsible for
inducing fever and acute inflammation
produced mainly by dentritic cells, macrophages, epithelial and endothelial cells
difference between puertz-jegers and juvenille polyposis syndrome
both cause hamartous polyps throughout GI tract
puertz-jegers also causes hyperpigmentation of lips, mouth, hands and genitalia. Can cause GI or breast cancer
Juvenille polyposis can cause colorectal cancer
what acid/base abnormality may be found in cystic fibrosis
metabolic alkalosis and hypokalaemia
due to H20/Na losses in sweat and renal H/K wasting
mode of action of ivacaftor
used in CF
Holds gate of CFTR channel open –> Cl flows through cell membrane
mode of action of lumacaftor / tezacaftor
used in CF
helps CFTR protein to form the right 3D shape
what are the anti-platelet antibodies directed against in ITP
GIIa/IIIb
features of ITP
occurs in children after viral illness
normal PT/APTT but prolonged bleeding time
low platelets
brown atrophy
atrophy and diffuse lipofuscin
lipofuscin is composed of peroxidised and polymerized membrane lipids
benign finding in older patients
how to differentiate iron deficiency anaemia and thalassaemia on blood count
both cause microcytic anaemia
RBC distrubution width - elevated in iron deficiency but normal in thalassaemia
presentation of tuberous sclerosis
intellectual disability
autism
seizures
mitral regurgitation
skin lesions (Ash-leaf spots, shagreen patches)
multiple benign tumours (hamartomas)
renal angiomyolipomas
cardiac rhabdomyoma
skin finding in tuberous sclerosis
ash spots
shagreen patches
mode of inheritance of tuberous sclerosis
autosomal dominant
genetic defect in tuberous sclerosis
mutations in tumour suppressor gene TSC1 on chromosome 9 and TSC2 on chromosome 16
dysplasia vs metaplasia
dysplasia is change in cell structure
metaplasia in change in cell type
intrinsic vs extrinsic pathway of apoptosis
intrinsic = mitochondrial pathway involved in remodelling
extrinsic = death receptor pathway
what proteins regulate intrinsic pathway of apoptosis
Bax and Bak (Bad for survival) promote cell death by forming pores in mitochondrial membrane releasing cytochrome C
BCL-xl and BCL-2 (Be Clever Live) promote cell survival by keeping the mitochondria impermeable inhibiting cytochrome C release
disease caused by over expressed BCL-2
follicular lymphoma
BCL-2 is antiapoptoic = decreased casoase activation = tumorgenesis
what is autoimmune lymphoproliferative syndrome and its pathophysiology
disorder caused by defective Fas-FasL interaction = failure of clonal deletion = increased numbers of self reacting lymphocytes
presents with lymphadenoathy, hepatosplenomegaly and autoimmune cytopenias
what regulates extrinsic pathway of apoptosis
ligand receptor interactions
Fas L binding to Fas (CD95) or TNF alpha binding to its receptor
describe the role of cytotoxic T cells and NK cells in apoptosis
release granules containg perforin and granzyme B. perforin forms a pore for granzyme to enter target cell
what type of necrosis occurs with CNS infarcts
liquefactive
necrosis type - neutrophils release lysosomal enzymes that digest the tissue
liquefactive
necrosis histology - preserved cellular architecture but nuclei disappear; increase cytoplasmic binding of eosin stain
coagulative necrosis (ischaemia/infarcts in most tissues)
necrosis histology - early cellular debris and macrophages, late cystic spaces and cavitation
liquifactive (CNS infarct, bacterial abscess)
necrosis histology - fragmented cells and debris surrounded by lymphocytes and macrophages. Cheese like gross appearance
caseous (TB, systemic fungi)
necrosis histology - outlines of dead fat cells without peripheral nuclei; saponification of fat
fat necrosis (injury to breast, pancreatitis)
necrosis histology - vessel wall contain eosinophillic layer of proteinaceous material
fibrinoid (immune vascular reactions ie. polyarteritis nodosa, non immune vascular reactions i.e. preeclampsia, hypertensive emergency)
fibrinoid necrosis is due to what type of hypersensitivity reaction
type 3 hypersensitivity reaction
necrosis with chalky white appearance
chalky white appearance = saponification –> fatty acids bind Ca. Found in fat necrosis esp enzymatic from pancreatitis.
what part of the heart is most susceptible to infarct
subendocardium of LV
what part of the kidney is most susceptible to infarct
straight segment of proximal tubule (medulla) and thick ascending limb (medulla)
red vs white infarcts
red infarcts occur in venous occlusions and in organs that have multiple blood supplies i.e. lung, liver
white infarct occurs in organs with single end arterial blood supply i.e. heart, kidney
why does radiotherapy kill cancer cells more than healthy cells
because cancer cells have dysfunctional DNA repair mechanisms in addition to high replicative states
features of acute radiation syndrome
occurs when the body is exposed to high levels of ionizing radiation
N&V, diarrhoea, hair loss, erythema, cytopenias, headache, altered mental status
how does radiation cause damage
formation of free radicals
concentrically laminated calcified spherules
psammoma bodies
what conditions are psomamma bodies found in
Please MOM dont forget the Milk
Papillary thyroid cancer
Meningioma
Ovarian carcinoma (serous)
Mesothelioma
Milk (prolactinoma)
how does amyloidosis appear on congo red stain and H&E stain
Congo red stain: red/orange on nonpolarized light, apple green perfringence on polarized light
H&E stain: amorphous pink
pathophysiology of amyloidosis
extracellular deposition of protein in an abnormal fibrillar form (beta pleated sheet configuration) resulting in cell injury and apoptosis
features of amyloidosis
heart - restrictive cardiomyopathy
kidneys - nephrotic syndrome
GI - hepatosplenomegaly
Neuro - peripheral neuropathy
Skin - waxy thickening, easy bruising
type of amyloidosis found in multiple myeloma and fibril protein affected
primary amyloidosis
AL fibril protein (from Ig Light chains)
type of amyloidosis found in inflammatory conditions like RA, psoriasis and the fibril protein affected
secondary amyloidosis
AA (serum Amyloid A)
what fibril protein is affected in dialysis related amyloidosis
beta 2 microglobulin
what type of amyloidosis is associated with ageing and the fibril protein affected
transthyretin amyloidosis
transthyrin protein
what type of necrosis is a cheese like appearance found on histology
caseous necrosis i.e. TB, systemic fungi
what type of necrosis can hypertensive emergencies cause
fibrinoid necrosis
describe the pathophysiology of fever
pyrogens (e.g. LDS) induce macrophages to release IL-1 and TNF which increases COX activity in perivascular cells of anterior hypothalamus which increases PGE2 = increase temperature set point
acute phase reactants such as CRP are induced by what substance
predominantly IL-6
acute phase reactant that fixed complement and fascilitates phagocytosis
CRP (opsonin)
what acute phase reactant decreases iron absorption and iron release
hepcidin (elevated in anaemia of chronic disease)
what is responsible for persistant acute inflammation
IL-8
what substances are responsible for resolution and healing after acute inflammation
IL-10 and TGF-beta
what are the dominant cell type in chronic inflammation
macrophages
Th1 cells secrete IFN-gamma (proinflammatory)
Th2 cells secrete IL-4 and IL-13 (repair and antiinflammatory)
vitamin C causes impaired wound healing at what stage
stage 2 wound healing
zinc deficiency impairs wound healing at what stage
stage 3 because collagenases require zinc to function, they break down type III collagen to replace it with type I which increases strength of tissue
caseous vs non caseous granulomas and what conditions they are found in
caseous granulomas have a central necrosis. Found in infections i.e. TB, fungi
non-caseous found in non-infectious causes i.e. sarcoidosis, cohns disease
predominant cell in granulomatous inflammation
macrophages (with abundant pink cytoplasm) surrounded by lymphocytes and multinucleated giant cells (formed from multiple fused macrophages)
describe how anti-TNF therapy can cause hypercalcaemia
causes breakdown of granulomas = activating macrophages. Activated macrophages increase 1alpha-hydroxylase whicch increases viamin D activity
excessive production of what substance is associated with keloid scars
TGF-beta
pathophysiology of scar formation
occurs when repair cannot be exceeded with cell regeneration alone. Nonregenerated cells are replaced by connective tissue.
what type of collagen synthesis and organisation occurs in the development of hypertrophic and keloid scars
hypertrophic - type III, parallel
keloid - type I and type III, disorganised
what is a risk factor in the development of keloid scar
darker skin
hypertrophic scar vs keloid scar –> what extends further than origional scar border
keloid
what interleukin is involved in the granulomatous inflammation
IL-12
describe the process of granulomatous inflammation
APC present antigens to CD4 T helper cell and expresses IL-12. T helper cell then differentiates into TH1 cell which secretes INF-Y which activates macrophages. Activated macrophages release cytokines such as TNF alpha which form epithelioid macrophages and giant cells = GRANULOMA
what defines carcinoma insitu vs invasive carcinoma
whether it invades the basement membrane or not
in situ doesnt, innvasive carinoma penetrate through the basement membrane sing metaloprotinases + cell-cell contacts lost by E-cadherin
carcinoma vs sarcoma
carcinoma = epithelial origin
sarcoma = mesencymal origin
what are hamartomas
disorganized overgrowth of tissue in their native location (non neoplastic)
mechanisms by which tumour cells can succesfully invade the immune system
immune evasion in cancer is a hallmark which prevents the immune system from attacking tumour cells
tumour cells decrease expression of MHC class I so cytotoxic t cells unable to recognise cells
they secrete immunosuppressive factors and recruit regulatory T cells to down regulate immune system
they up regulate immune check point molecules which inhibit immune response
what is the most common cancer
skin (basal > squamous > melanoma)
what is the 1st and 2nd leading cause of death in the US
1st - heart disease
2nd - cancer
top 3 common cancers in male, females and children
male: prostate, lung, colon
female: breast, lung, colon
children: leukaemia, CNS, neuroblastoma
top 3 cancers with the highest mortality in males, females and children
male: lung, prostate, colon
female: lung, breast, colon
children: leukaemia, CNS, neuroblastoma
sarcoma vs carcinoma route of metastasis spread
carcinoma - lymphatics
sarcoma - haematogenously
4 carcinomas that spread haematogenously
follicular thyroid cancer
choriocarcinoma
renal cell carcinoma
hepatocellular carcinoma
most common primary tumour to spread to;
1) bone
2) liver
3) lung
4) brain
1 - bone = prostate
2 - liver = colon
3 - lung = colon
4 - brain = lung
what is field cancerisation and examples
replacement of a large area of normal cells by premalignant cells due to widespread carcinogen exposure. affected area is at increased risk of developing mulitple primary malignancies
i.e. head and neck cancers with tobacco smoke, urothelial cancer with urinary carcinogens, skin cancer with exposure to UV rays
oncogenes associated with lung adenocarcinoma
ALK and EGFR
cancers associated with HER2
breast and gastric carcinoma
oncogenes associated with papilarry thyroid cancer
RET and BRAF
cancer associated with NMYCC
burkitts lymphoma
cancer associated with NMYC-N
neurblastoma
cancers associated with BCL -2
follicular and diffuse large B cell
cancers associated with c-KIT oncogene
GI stromal tumour
mastocytosis
cancers associated with BRAF oncogene
melanoma, non-hodgkins, colorectal, papillary thyroid, hairy cell leukaemia
what toxin is found in exposure to stored grains and nuts ? type of cancer associated ?
aflatoxins (aspergillus)
hepatocellular carcinoma
what toxin is found in exposure to chaemotherapy ? cancer associated ?
ankylating agents
leukaemias/lymphomas
what toxin is found in exposure to the textile industry (e.g. dyes)?
cancer associated?
(2-naphthylamine found in tobacco smoke)
aromatic amines
transitional cell carcinoma
what toxin are people exposed to with herbicides (vineyard workers), metal smelting, wood preservation ? cancer associated ?
arsenic
hepatic angiosarcoma, lung cancer, squamous cell carcinoma
what cancer are people at risk of with exposure to nickel, chromium, beryllium and silica
lung cancer
what toxin are people exposed to who work making PVC pipes and cancer associated ?
vinyl chloride
hepatic angiosarcoma
what toxin is found in smoked foods and what cancer is this asociated with
nitrosamines
gastric cancer
what cancer does liver fluke (clonorchis sinensis) cause
cholangiocarcinoma
what cancer does HTLV-1 cause
adult T cell leukaemia/lymphoma
associations with elevated hcg
hydatiform mole, choriocarcinoma, testicular cancer, mixed germ cell tumour
cancer associated with raised calcitonin
medullary thyroid cancer
cancer associated with raised chromogranin
neuroendocrine tumours
what is the role of immunohistochemical staining of tumour cells
used to determine the primary site of metastases and characterize tumours that are difficult to classify
what tumour may be identified on chromogranin and synaptophysin stain
neuroendocrine - small cell carcinoma, carcinoid tumour, neuroblastoma
what tumour may be identified on cytokeratin stain
epithelial tumours (squamous cell carcinoma)
what tumour may be identified on desmin stain
desMin = muscle
rhabdomyosarcoma
what tumour may be identified on GFAP stain
Gfap = neuroGlia (astrocytes, schwann cells, oligodendrocytes)
astrocytoma, glioblastoma
what tumour may be identified on neurofilament stain
neuronal tumours e.g. neuroblastoma
what tumour may be identified on PECAM-1/CD-31 stain
vascular tumours e.g. angiosarcoma
what tumour may be identified on vimentin stain
viMEntin = MEsenchymal tissue
mesenchymal tumours e.g. sarcoma, endometrial, renal cell, meningioma
