Pathology Flashcards
what pathways does apoptosis have
intrinsic and extrinsic pathways
general occurrences during apoptosis (4)
- eosniphilic cytoplasm
- cell shrinkage
- karyorrhexis (nuclear fragmentation)
- apoptotic bodies
what happens in karyorrhexis?
endonucleases cleave at internucleosomal regions into 180bp fragments
what does radiation therapy do to cells
free radicals and dsDNA breakage –> apoptosis of tumors and surrounding tissue
when does intrinsic pathway apoptosis occur? (3)
- regulating factor taken away from proliferating cells
- after injurious stimuli
- anti/pro apoptotic factor ratio
examples of intrinsic pathway apoptosis (4)
- removal of IL-2 after completed immuno reaction
- radiation, toxins, hypoxia
- BAX and BAK (pro-apoptotic)
- Apaf-1 (pro-apoptotic)
pro-apoptotic factors (3)
BAX
BAK
Apaf-1
anti-apoptotic facotrs (1)
- Bcl-2
What does Bcl-2 do
binds to Apaf-1 and inhibits it so that it cannot release cytochrome C
too much bcl-2?
too little apaf-1 and you get tumorgenesis (ex follicular lymphoma)
what mechanism is extrinsic pathway apoptosis?
- ligand receptor
FasL to Fas (CD95)
CD95?
Fas
thymus negative selection is what pathway of apoptosis
extrinsic pathway
necrosis definitino
enzymation degradation and protein denaturation 2/2 exogenous injury
where does coagulative necrosis occur (3)
tissue supplied by end-arteries
- heart
- liver
- kidney
order of what happens in coagulative necrosis
- proteins degrade first
2. enzymatic degradation
where does liquefactive necrosis occur and when
occurs in CNS 2/2 high fat content
brain bacterial abscess
order of what happens in liquefactive necrosis
- enzymatic degradation from lysosomal release
2. Then protein degradation
when does caseous necrosis occur (3)
- TB
- systemic fungi
- nocardia
acid fast?
where does fatty necrosis occur (2)
- pancreas
2. breast
pancreatitis leads to what?
saponification
fatty necrosis
what does fatty necrosis look like on staining
calcium deposits appear dark blue
what does fibrinoid necrosis look like on stain
amorphous and pink on H&E
where can you see fibrinoid necrosis? (2)
vessels
- vasculitidies (HSP, churg-strauss)
- malignant HTN
types of gangrenous necrosis
- dry
2. wet
when is there dry gangrenous necrosis
ischemic coagulative
when is there wet gangrenous necrosis
infection
common locations for gangrenous necrosis (2)
- limbs
2. GI tract
Examples of causes of atrophy (7)
- low endogenous hormones (post-menopause ovaries)
- high exogenous hormones (thyroid, steroids)
- low innervation (MN damage)
- low blood flow/nutrients
- low metabolic demand (paralysis)
- high pressure (nephrolithiasis)
- occlussion of secretory ducts (CF)
Examples of reversible cell injury (7)
- ATP depletion
- cellular/mito swelling 2/2 ATPase dysfunction
- ribosome detachment 2/2 swelling
- MB blebbibg 2/2 swelling
- nuclear chromatin clumping
- low glycogen
- fatty change
Examples of irreversible cell injury (4)
- nuclear pyknosis, karyorrhexis, karyolysis
- plasma MB damage
- lysosomal rupture
- mitochondrial permeability/vacuolization
Examples of damage from ROS (6)
- retinopathy of prematurity
- bronchopulmonary dysplasia
- CCl4 –> liver necrosis and fatty change
- Acetaminophen o/d
- Fe overload
- Reperfusion injury esp after thrombolytic therapy
ischemia susceptible region of heart
subendocardium (LV)
ischemia susceptible region of kidney (2)
- straight segment of proximal tubule (medulla)
2. thick ascending limb (medulla)
ischemia susceptible region of liver
area around central vein (zone III)
ischemia susceptible region of colon (2)
- splenic flexure
2. rectum
chromatolysis … what is it?
attempt at increasing protein synthesis following axonal damage
what do you see in chromatolysis? (3)
- round cellular swelling
- displacement of nucleus to periphery
- dispersion of RER throughout cytoplasm
what does nissl substance stain?
RER
red infarct from what
hemorrhagic
where does red infarct occur? (3)
loose tissue with multiple blood supplies
- liver
- lungs
- intestines
Red = Reperfusion
pale infarct where (3)
solid tissue with single blood supply
- heart
- kidney
- spleen
distributive shock
- TPR
- CO/venous return
- PCWP
low TPR
high CO/venous return
low PCWP
what does distributive look like?
warm dry skin 2/2 vasodilation
need to use pressors b/c unresponsive to fluids 2/2 vasodilation
Cardiogenic shock
- TPR
- CO/venous return
- PCWP
high TPR
low CO/venous return
elevated PCWP
Hypovolemic shock
- TPR
- CO/venous return
- PCWP
high TPR
low CO/venous return
decreased PCWP
treating cardiogenic/hypovolemic shock
responds to fluids
Acute cellular inflammatory response
- onset time
- duration time
- seconds-minutes
- lasts minutes to days
Acute cellular inflammatory response
- involved cells
- what happens
- neutrophils, eosinophil, Ab-mediated
- resolution, abscess formation, progression to chronic inflammation
Chronic cellular inflammatory response
- cells involved
- what happens
- mononuclear cells and fibroblasts for persistent destruction and repair
- granuloma (nodular collection of epithelioid macrophage and giant cells)
- scarring and amyloidosis
what is it that leads to increased ESR in inflammation
fibrinogen coats RBCs and causes them to aggregate
high ESR states (5)
- most anemias
- infection
- cancer (MM)
- pregnancy
- autoimmune d/o
low ESR states (3)
- sickle cell (shape lowers ESR)
- polycythemia (dilute)
- CHF (unknown reason)
4 steps of leukocyte extravasation
- margination and rolling
- tight-binding
- diapedesis
- migration through interstitium
factors involved in leukocyte margination and rolling
- cellular to endothelial interaction
cellular to endothelial reaction:
- Sialyl-Lewis …P-selectin
- Sialyl-Lewis …E-selectin
- L-selectin … GlyCAM-1 and CD34
factors involved in leukocyte tight-bonding
- cellular to endothelial interaction
- CD11/18 integrins (LFA-1, Mac-1) … ICAM-1 (CD54)
- VLA-4 integrin … VCAM-1 (CD106)
factors involved in leukocyte diapedesis
- cellular to endothelial interaection
- PECAM-1 (CD31) … PECAM -1 (CD31)
factors involved in leukocyte migration
-cellular to endothelial interaction
- various things … chemotaxis mediated through C5a, IL-8, kalligkrein, Plt-activating factor
examples of exudate causing stuff (4)
- lymphatic obstruction
- inflammation
- infection
- maligancy
examples of transudate causing stuff (3)
- CHF (hydrostatic pressure)
- cirrhosis (decresaed oncotic pressure)
- Na retention
what’s the specific gravity number differentiating exudate and transudate
1.012
phases of wound healing (3)
when do they occur
- inflammatory (immediate)
- proliferative (2-3 days)
- remodeling (1 week later)
what does EGF do in wound healing
stimulates cell growth via TyrKin Rec
TGF-beta does what in wound healing (3)
angiogenesis
fibrosis
cell cylce arrest
PDGF does what in wound healign (3)
- vascular remodeling
- SMC migration
- stimulate fibroblast growth for collagen synthesis
cells involved in inflammatory wound healing (3)
- platelets
- neutrophils
- macrophages (a little later just to clean up)
clotters and eaters
cells involved in proliferative wound healing (5)
- fibroblasts
- myofibroblasts
- endothelial cells
- keratinocytes
- macrophages
the rebuilders, supporters, and clean up
cells in remodeling wound healing
fibroblasts
what collagen stuff happening in wound healing
collagen III replaced by collagen I –> increases tensile strength of tissue
pathogenesis of granulomatous disease
TH1 cells secrete IFN-g –> activates macrophages –> they release TNF-alpha –> induces and maintains granuloma formation
examples of granulomatous diseases (13)
- TB
- Sarcoidosis
- Crohn
- Fungal
- myco leprae
- Syphilis
- Wegener granulomatosis
- Churg-Strauss
- Bartonella (cat scratch)
- Berrylliosis
- Listeria monocytogenes
- Francisella tularensis
- schistosomiasis
types of calcification (2)
- dsytrophic
2. mestastatic
dystrophic calcification caused by what
local deposits 2/2 necrosis
calcium state in dystrophic calcification
usually normocalcemic
not a/w hyper-Ca
metastatic calcification caused by what
diffuse deposits 2/2 hypercalcemia OR
high calcium-phosphate product
states of hypercalcemia (3)
- primary hyperparathyroidism
- sarcoidosis
- hypervitamoniosis D
states of high calcium-phosphate product (4)
- CRF
- secodnary hyperparathyoriodism
- long-term dialysis
- warfarin
where is calcium usually in metastatic calcification?
- what environments
- examples
alklaloid environments
interstitial tissue of: 1. kidneys 2. lungs 3. gastric mucosa b/c they lose acid quickly
how does Fe poisoning kill?
peroxidation of cell MB lipids –> cell death
what stains show amyloidosis
congo red stain
what does congo red stain look like in polarized light
apple green birefringence
what is primary amyloidosis ?
AL
deposits of light chains
causes of primary amyloidosis (AL)?
- plasma cell d/o
2. MM
what does primary amyloidosis cause? (6)
- nephrotic syndrome
- restrictive cardiomyopathy
- arrhyhtmia
- easy bruising
- hepatomegaly
- neuropathy
what is secondary amyloidosis?
AA
chronic conditions with fibrils made of serum Amyloid A
where can you see secondary amyloidosis (4)
- RA
- IBD
- Spondyloarthropathy
- protracted infection
what is P-glycoprotein
MDR-1
the channel that pumps out toxins from the cell to keep it alive
reversible plasias (3)
hyperplasia
metaplasia
dysplasia
irreversible plasias (3)
anaplasia
neoplasia
desmoplasia
what is desmoplasia
fibrous tissue formation in response to neoplasm
tumor grading has to do with
- what are the numbers
differentiation and mitotic activity
1-4 from well differentiated to poorly anaplastic
tumor staging based on what
localization and spread
TNM staging involves?
tumor size
node involvement
mets
Carcinomas spread how
lymphatic spread
which carcinomas can spread hematogenously as well as lymphatically (4)
- RCC via renal vein
- HCC via hepatic vein
- Follicular carcinoma of thyroid
- Choriocarcinoma
sarcomas spread how
hematogenously
benign sarcomas 6)
- hemangioma (vessels)
- leiomyoma (SMC)
- rhabdomyoma (striated muscle)
- fibroma (connective tissue)
- osteoma (bone)
- lipoma (fat)
Cachexia is mediated by what (3)
- TNF-alpha
- IFN-gamma
- IL-6
what is called cachectin?
TNF-alpha
what condition a/w visceral malignancy
acanthosis nigricans
what condition a/w squamous cell carcinoma of skin
actinic keratosis
what condition a/w malignant melanoma
dysplastic nevus (skin lesions)
xeroderma pigmentosum / albinism a/w what neoplasms (3)
- melanoma
- basal cell carcinoma
- squamous cell carcinoma of skin
what condition a/w aggressive malignant non-Hodgkin lymphoma
AIDS
what condition a/w Kaposi sarcoma
AIDS
what condition a/w lymphomas
autoimmune (hashimoto, SLE)
what condition a/w malignant lymphomas?
immunodef
what condition a/w ALL and AML
Down syndrome
what condition a/w thymoma (2)
- myasthenia gravis
2. pure RBC aplasia
what condition a/w esophageal adenocarcinoma
barrett esophagus
what condition a/w squamous cell carcinoma of esophagus
Plummer-Vinson syndrome (low Fe)
what condition a/w gastric adenocarcinoma
- chronic atrophic gastritis
- permicious anemia
- postsurgical gastric remnants
what condition a/w colonic adenocarcinoma
UC
what condition a/w HCC
cirrhosis
what neoplasm a/w polycythemia (2)
- RCC
2. HCC
what condition a/w small cell lung cancer (3)
- Cushing
- Lambert Eaton
- SIADH
what condition a/w lung cancer
dermatomyositis
what condition a/w squamous cell lung cancer
hypercalcemia
what neoplasms a/w TS (3)
- giant cell astrocytoma
- renal angiomyolipoma
- cardiac rhabdomyoma
what neoplasms a/w radiation exposure (4)
- leukemia
- sarcoma
- papillary thyroid cancer
- breast cancer
what neoplasms a/w Paget disease of bone (2)
- secondary osteosarcoma
2. fibrosarcoma
examples of oncogenes (10)
- Bcr-abl
- bcl-2
- BRAF
- c-kit
- c-myc
- HER2/neu
- L-myc
- N-myc
- Ras
10 Ret
what does Bcr-abl code for and what condition a/w (2)
tyrosine kinase
- CML
- ALL
what does bcl-2 code for and what condition a/w (2)
anti-apoptotic mitochondrial factor
- follicular lymphoma
- undifferentiated lymphoma
what does BRAF code for
and what condition a/w
serine/threonine kinase
melanoma
what does c-kit code for and what condition a/w
cytokine receptor for stem cell factor
GI stromal tumor (GIST)
what does c-myc code for and what condition a/w
TF
Burkitt lymphoma
what does HER2/neu code for and what condition a/w
tyrosine kinase
- breast
- ovarian
- gastric carcinoma
what does L-myc code for and what condition a/w
TF
lung
what does N-myc code for and what condition a/w
TF
Neuroblastoma
what does Ras code for and what condition a/w (3)
GTPase
- colon
- lung
- pancreatic
what does Ret code for and what condition a/w (2)
tyrosine kinase
- MEN 2A
- MEN 2B
what does BRCA1 and 2 code for and a/w (2)
DNA repair enzymes
- breast cancer
- ovarian cancer
what does CPD4/SMAD4 code for and a/w?
DPC (deleted in pancreatic cancer)
pancreatic cancer
what does DCC code for
deleted in colon
colon cancer
what does NF1 code for and a/w ?
Neurofibormin, a RAS GTPase activating protein
NF1
what does NF2 code for and a/w?
Merlin (schwannomin) protein
NF2
what does p16 code for and a./w?
cyclin-dep kinase inhibitor 2A
melanoma
what does p53 code for and a/w
TF for p21 … blocks G1 to S
most cancers
Fraumeni (AR cancer syndrome): breast, leukemia, adrenal gland
what is PTEN and a/w?
TSG
breast, prostate, endometrial
what does Rb do and a/w? (2)
inhibits E2F … blocks G1 to S
- retinoblastoma
- osteosarcoma
what genes mutated in TS
TSC1
VHL codes what and a/w?
inhibits hypoxia inducible factor 1a (HIF-1a)
VHL
AlkPhos used to monitor what (4)
- mets to bone
- liver disease
- Paget disease of bone
- seminoma (placental aklphos)
AFP used to monitor what (5)
- HCC
- hepatoblastoma
- yolk sac (endodermal sinus) tumor
- testicular cancer
- mixed germ cell tumor
beta-hCG used to monitor what (3)
- hydatiform moles
- choriocarcinomas
- testicular cancer
what do you use to monitor breast cancer?
CA-15/3
CA-26/29
what do you use to monitor pancreatic adenocarcinoma
CA-19/9
what do you use to monitor ovarian cancer
CA-125
what do you use to monitor medullary thyroid carcinoma
calcitonin
what are some neural crest origin cancer (4)
- melanoma
- neural tumo
- schwannoma
- Langerhans cell Histiocytosis
what do you use to monitor neural crest origin cancers
S-100
what do you use to monitor hairy cell leukemia
TRAP
EBV can cause what cancer
- Burkitt lymphoma
- Hodgkin lymphoma
- nasopharyngeal carcinoma
- CNS lymphoma inimmunom
What viruses can cause HCC? (2)
- HBV
2. HCV
what virus can cause kaposi sarcoma
HHV-8
what causes cervical, penile, headneckthroat cancer
HPV 16,18
H pylori can cause what cancers (2)
- gastric adenocarcinoma
2. MALT lymphoma
adult T-cell leukemias and lymphomas can be caused by what microbe
HTLV-1
what microbe can cause cholangiocarcinoma
liver fluke (clonorchis sinensis)
what microbe can cause squamous cell bladder cancer
schisotoma haematobium
Aflatoxin
- produced by what
- causes what cancer
- aspergillus
- HCC
Arsenic can cause what cancers (3)
- angiosarcoma
- lung cancer
- squamous cell carcinoma
asbestos causes what cancer 2)
- bronchogenic carcinoma
- meothelioma
bronchogenic > meso
cigarette smoking causes what cancer (6)
- transitional cell carcinoma
- SCC and adenocarcinoma of esphageus
- RCC
- squamous cell CA or laynx
- squamous and small cell CA of lung
- adenocarcinoma of pancreas
nitrosamines
- where found
- causes what cancer
- smoked foods
- gastric cancer
2nd leading cause of lung cancer after smoking
Radon
Vinyl chloride causes what
hepatic angiosarcoma
what paraneoplastic syndrome a/w Hodgkin lymphoma?
- leads to
1,25-VitD –> hypercalcemia
what paraneoplastic syndrome a/w small cell lung carcinoma (3)
ACTH –> cushing
anti-presyn CaCh –> LES
Autoimmune subacute cerebellar degeneration –> dizzy, ataxia
what paraneoplastic syndrome a/w small cell lung CA and some intracranial neoplasms
ADH –> SIADH
what malignancies have EPO production as neoplastic syndrome? (6)
- RCC
- thymoma
- hemangioblastoma
- HCC
- leiomyoma
- pheochromocytoma
what malignances have PTHrP production as neoplastic syndrome (3)
- squamous cell lung CA
- RCC
- breast cancer
psammoma bodies found where (4)
- Papillary CA thyroid
- Serous papillary cystadenoCA of ovary
- Meningioma
- Malignant mesothelioma
which mets go to brain (6)
- lung
- brain
- GU
- osteosarcoma
- melanoma
- GI
which mets go to liver
- colon
- stomach
- pancreas