Pathology Flashcards
Pyknosis
irreversible condensation of chromatin in the nucleus of a cell undergoing apoptosis
Karyorrhexis
destructive fragmentation of a dying cell (cell undergoing apoptosis); irreversible
Karyloysis
Dissolution of the chromatin/Fading of the nucleus of a dying cell; part of apoptosis; irreversible
Apoptosis vs Necrosis
Apoptosis–>no inflammation; form apoptotic bodies, which are phagocytosed
Necrosis –> swelling and inflammation; intracellular components extravasate
Cell injury that’s reversible with oxygen:
- decreased ATP synthesis
- Cellular swelling (ie no ATP –> impaired Na/K pump)
- Nuclear chromatin clumping
- decreased glycogen
- fatty change
- ribosomal detachment (decreased protein synthesis)
Cell injury that’s irreversible
- Nuclear pyknosis, karyolysis, karyhorrhexis (all processes involved in apoptosis)
- Calcium influx–> caspase activation
- plasma membrane damage
- lysosomal rupture
- mitochondiral permeability (ie with intrinsic pathway of apoptosis)
Areas that are susceptible to hypoxia:
- Watershed areas –> Splenic flexure and ACA/MCA
- Subendocardial tissue of heart
- Proximal Tubule in cortex of Kidney
- Thick Ascending limb in medulla of kidney
- Neurons
- Area around central vein of liver
Red vs Pale Infarcts
Red = hemorrhagic; happens in tissues with loose collaterals, like liver, lungs, intestine; or, after reperfusion of an area
Pale happen in solid tissues with old one blood supply (like heart, kidney, spleen)
What causes reperfusion injury?
Damage by free radicals
Hypovolemic/Cardiogenic Shock vs Septic Shock findings:
Hypovolemic/Cardiogenic:
- LOW-output failure
- increased TPR
- Low cardiac output
- Cold, Clammy pt
Septic Shock:
- HIGH-output failure
- decreased TPR
- dilated arterioles, high venous return
- Hot patient
Mediators of fluid exudation in inflammation:
- Histamine
- Serotonin
- Bradykinin
Acute phase cytokines associated with inflammation?
IL-1
IL-6
TNF-alpha
Metalloproteinases:
Enzymes involved in remodeling of ECM following injury
–> require ZINC! this is why Zinc deficiencies result in delayed wound healing!
Why is vitamin C important for wound healing?
–>fibrosis, need collagen for deposition of ECM; need vitamin C for collagen!
Two supplements given to pts who are healing:
- Vitamin C (for collagen)
- Zinc (for metalloproteinases)
5 steps of Leukocyte Extravasion:
1) Rolling (E- and P-Selectins and Sialyl Lewis leukocyte)
2) Tight binding (ICAM and Integrin)
3) Diapedesis (PECAM)
4) Migration (Bacterial products and chemotactic signals = C5a, IL-8, LTB4, Kallikrein)
5) Phagocytosis
signals for neutrophil chemotaxis?
C5a
IL-8
Leukotriene B4
Kallikrein
Delayed separation of umbilicus, and abnormal integrin:
Leukocyte Adhesion Deficiency
Which vitamins are anti-oxidants (can eliminate free radicals)?
A, C, E
3 phases of wound healing: When does each phase occur? which cells are the mediators? characteristics?
1) Inflammatory
2) Proliferative
3) Remodeling
1) Inflammatory:
- ->occurs immediately
- ->Mediators: platelets, neutrophils, macrophages
- ->form clot, neutrophils go into tissue, macrophages clean up
2) Proliferative:
- ->2-3 days after wound
- ->Mediators: fibroblasts, myofibroblasts, endothelial cells, keratinocytes
- ->granulation tissue, collagen, angiogenesis, epithelial cell proliferation, dissolve clot, wound contraction
3) Remodeling:
- ->1 week after wound
- -> Mediators: Fibroblasts
- -> Type I collagen replaces type III collagen (type I is for late wound repair; type III is for granulation/early wound repair)
Type of collagen involved in early wound healing? late wound healing?
-Early wound healing –> granulation tissue –> Collagen Type III
Late wound repair –> Scar tissue –> Type I collagen (stronger)
Pathogenesis of granuloma formation:
Th1 cells secrete IFN-gamma –> activate macrophages –> macrophages secrete TNF-alpha –> induces and maintains granuloma formation
***If give pt with a granuloma an anti-TNF drug –> drug can break down granulomas, leading to disseminated disease
Transudate vs Exudate:
- Transudate:
- Hypocellular
- Protein poor
What is the ESR?
- -> Erythrocyte sedimentation rate
- -> inflammatory products, like fibrinogen, coat RBCs, causing them to aggregate. So, when put in test tube, aggregated RBCs fall at a faster rate….
3 conditions with DECREASED ESR?
- Sickle Cell (weird RBC shape!)
- Polycythemia (too many RBCs!)
- CHF (not sure why…)
5 states in which have increased ESR?
- inflammation
- infection
- cancer
- pregnancy
- SLE
Bence Jones
=amyloid seen in multiple myeloma; derived from Ig light chains
Beta-amyloid
amyloid protein in Alzheimer’s deases
Beta-2-microglobulin
protein seen in dialysis-associated amyloidosis
*note: have B2-microglobulin on MHC I; this amyloid is derived from MHC-I proteins
Transthyretin
protein seen in senile cardiac amyloidosis
A-CAL protein
protein seen in Medullary Carcinoma of the thyroid
–>derived from Calcitonin
Carcinoma in situ =
Pre-invasive
- ->cells have not yet invaded basement membrane, but neoplastic cells encompass entire thickness
- ->have high nuclear/cytoplasmic ratio and clumped chromatin
What enzymes do neoplastic cells use to invade the basement membrane?
Collagenases and Hydrolases (metalloproteinases)
Hamartoma =
mass of MATURE tissue ENDOGENOUS to site from where it originates (similar to hyperplasia…)
Hyperplasia = Metaplasia = Dysplasia = Anaplasia = Neoplasia = Desmoplasia =
Which of these processes are reversible? irreversible?
Hyperplasia–> increased # of cells
Metaplasia–> one adult type replaced by another
Dysplasia–> abnormal growth, loss of cellular orientation, shape, size; commonly pre-neoplastic
Anaplasia–>abnormal cells, lack differentiation; very primitive; little/no resemblance to tissue of origin
Neoplasia–> uncontrolled, excessive, clonal proliferation of cells
Desmoplasia–> fibrous tissue formation in response to neoplasm
Features of Anaplastic cells:
- high nucleus:cytoplasm ratio
- prominent nucleoli
- nuclear chromatin clumpin
- lots of mitotic figures
Are mature teratomas benign or malignant?
in women–> benign
in men–> malignant
Hemangioma
benign tumor of blood vessels; usually affect infants, then disappear spontaneously in the months following birth
Angiosarcoma
malignant tumor of blood vessels; chronic lymphedema is a predisposing factor (ie following a radical mastectomy with axillary lymph node dissection to treat breast cancer)
Rhabdomyoma and Rhabdoymyosarcoma
benign and malignant tumors of skeletal muscle
Fibroma
benign tumor of connective tissue
Cachexia
loss of weight, muscle atrophy, fatigue –> occurs in chronic disease
-mediated by: TNF-alpha, IFN-gamma, IL-6
Neoplasms associated with Down Syndrome?
- ALL
- AML
Neoplasms associated with Tuberus Sclerosis (facial angiofibroma, seziures, MR, ash leaf spots)?
- Cardiac rhabdomyoma (about 2/3rds of TS pts)
- Astrocytoma
- Angiomyolipoma
Neoplasm associated with Barrett’s esophagus?
-Esophageal adenocarcinoma
Neoplasm associated with Plummer-Vinson syndrome (atrophic glossitis, esophageal webs, anemia; all d/t iron deficiency)?
-Squamous cell carcinoma of esophagus
Neoplasm associated with Ulcerative Colitis?
Colonic adenocarcinoma
Neoplasm associated with autoimmune diseases (ie Hashimoto’s, Myasthenia gravis)?
Lymphoma
Neoplasmas associated with radiation exposure?
- Sarcoma
- Papillary thyroid cancer
Neoplasm associated with Sjogren’s?
B-cell lymphoma
Neoplasm associated with Cirrhosis (alcoholic, hepatitis B/C)
Hepatocellular carcinoma
Neoplasms associated with Paget’s disease of bone?
- secondary osteosarcoma
- fibrosarcoma
Homer-Wright Pseudorosettes:
Neuroblastoma
abl gene
CML
–>tyrosine kinase
c-myc
Burkitt’s lymphoma
–>transcription factor
bcl-2
follicular and undifferentiated lymphomas
–>anti-apoptotic molecule
erb-B2
Breast, ovarian, gastric carcinomas
–>tyrosine kinase
ras
Colon carcinoma
–>GTPase
L-myc
Lung tumor
–>transcription factor
N-myc
Neuroblastoma (childhood adrenal medulla tumor)
–>transcription factor
ret
MEN 2a and 2B
–>tyrosine kinase
c-kit
Gastrointestinal Stromal Tumor
–>cytokine receptor
Rb
- Retinoblastoma
- Osteosarcoma
p53
- Li-Fraumeni syndrome
- various cancers
BRCA1 and 2
- ->DNA repair protein
- ->Breast and ovarian (1), just breast (2)
p16
melanoma
APC
colorectal cancer (associated with FAP and Gardner’s syndrome)
WT1
Wilm’s tumor
NF1
Neurofirbomatosis I
NF-2
Neurofibromatosis 2
DPC
Pancreatic cancer
DCC
Colon Cancer
PSA
Prostate-specific antigen
–>used to screen for prostate carcinoma
CEA
nonspecific tumor marker for colorectal and pancreatic cancers; also gastric, breast, medullary thyroid carcinomas
alpha-fetoprotien = tumor marker for:
- Hepatocellular carcinomas
- also for yolk sac tumors
Beta-hCG = tumor marker for:
“HCG”
- Hydatidoform moles
- Choriocarcinomas
- Gestational trophoblastic tumors
CA-125 = tumor marker for:
-ovarian tumors
S-100 = tumor marker for:
- melanoma
- Scwannomas
(both are derived from neural crest)
Alkaline Phosphatase = tumor marker for?
- metastases to bone
- Paget’s disease of bone
- obstructive biliary disease
TRAP = tumor marker for?
= Tartrate-resistant acid phosphatase
–>marker for Hairy cell leukemia (B-cell neoplasm)
“TRAP the Hairy animal!”
CA-19 = tumor marker for?
Pancreatic adenocarcinoma
Calcitonin = tumor marker for?
Medullary thryoid carcinoma
Cancer associated with HIV (not with HIV-associated conditions; just with HIV)?
Primary CNS lymphoma
Cancer associated with H. pylori?
Gastric adenocarcinoma and lymphoma
Cancer associated with Aflatoxins (aspergillus)?
Hepatocellular carcinoma
cancer associated with vinyl chloride?
Angiosarcoma
Cancer associated with Nitrosamines (smoked food)?
Gastric cancer
4 cancers associated with smoking?
- Squamous cell carcinoma
- Squamous cell and small cell carcinoma
- Renal cell carcinoma
- Transitional cell carcinoma
2 cancers associated with asbestos
- Mesothelioma
- Bronchogenic carcinoma
2 cancers associated with Arsenic?
- Squamous cell carcinoma
- Angiosarcoma
Cancer associated with Naphthalene/Aniline dyes?
Transitional Cell Carcinoma of bladder
Cancer associated with alkylating agents?
Leukemia
Cancer associated with radon (coal mines, basements)?
Lung cancer
Psammoma bodies: found in?
“PSMM”
- Papillary cancer of thyroid
- Serous cancer of ovary
- Meningioma
- Malignant mesothelioma
