Pathology Flashcards by Ali K

Eosinophilic cytoplasm
Basophilic nucleus
Pyknosis (nuclear shrinkage)
Karyorrhexis (DNA fragmentation)
No inflammation

APOPTOSIS

DNA laddering (180 bp multiples) sensitive sign

occurs when regulating factors like interleukins are withdrawn from proliferating cells

endonucleases cleave DNA at internucleosomal linker regions which are at 180 base pair intervals

How well did you know this?

Not at all

Perfectly

Intrinsic (mitochondrial) pathway of apoptosis

Involved in embryogenesis and response to injuring stimuli (e.g. radiation, toxins, hypoxia)

p53 activation activates BAX/BAK
BAX/BAK induce cytochrome c release
APAF-1 binds cytochrome c
Induces caspase 9 activation and caspase cascade
Nuclear fragmentation and cytoskeletal dispersion
Formation of cytoplasmic blebs (apoptotic bodies)
Apoptotic bodies phagocytosed by macrophages

Inhibited by Bcl-2 binding of APAF-1

How well did you know this?

Not at all

Perfectly

Overexpression of bcl-2 leading to over-inhibition of APAF-1 and thus tumorigenesis.

Follicular lymphoma - t[14;18]

How well did you know this?

Not at all

Perfectly

Extrinsic (death receptor) pathway

FasL (cytotoxic T-cells) binding to Fas (TNF family)
Fas trimerized and binds FADD
Activates initiator caspases (8, 9)
Activates executioner caspases

How well did you know this?

Not at all

Perfectly

Defective Fas-FasL interactions.

AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME

Interaction necessary in thymic medullary negative selection - results in autoimmune disease

How well did you know this?

Not at all

Perfectly

Cell outlines preserved

Cytoplasmic hypereosinophilia

COAGULATIVE NECROSIS

Seen in ischemia and infarcts (except brain) - Proteins denature then undergo enzymatic degradation

How well did you know this?

Not at all

Perfectly

Early cellular debris and macrophages
Later cystic spaces and cavitation (e.g. brain)
Neutrophils and cell debris seen with bacterial infection

LIQUEFACTIVE NECROSIS

Seen in bacterial abscesses and brain infarcts (high fat content)

Neutrophils release lysosomal enzymes that digest tissue - Enzymatic degradation precedes protein denaturing

How well did you know this?

Not at all

Perfectly

Fragmented cell and debris surrounded by lymphocytes and macrophages.

CASEOUS NECROSIS

Seen in TB, systemic fungi, and Nocardia - Macrophages wall off the infecting organism creating granular debris

How well did you know this?

Not at all

Perfectly

Outlines of dead fat cells without peripheral nuclei
Saponification of fat (combined with Ca)
Appears dark blue on H/E stain

FAT NECROSIS

Seen in acute pancreatitis or traumatic breast injury - Damaged cells release lipase which breaks down triglycerides in fat cells

How well did you know this?

Not at all

Perfectly

Vessel walls are thick and pink on H/E stain

FIBRINOID NECROSIS

Seen in vasculitis and malignant HTN - Immune complexes combine with fibrin to cause vessel wall damage

How well did you know this?

Not at all

Perfectly

Histology of wet and dry gangrene after chronic ischemia.

Dry (ischemia) appears like coagulative necrosis

Wet (superinfection) appears like liquefactive superimposed on coagulative

How well did you know this?

Not at all

Perfectly

Cellular/mitochondrial swelling
Nuclear chromatin clumping
Membrane blebbing
Decreased glycogen
Fatty change
Ribosomal/polysomal detachment

REVERSIBLE CELLULAR INJURY

Reversible with O2 - e.g. stable angina

How well did you know this?

Not at all

Perfectly

Plasma membrane damage
Nuclear pyknosis (condensation), karyorrhexis (fragmentation), or karyolysis (fading)
Mitochondrial permeability and vacuolization
Mitochondrial phospholipid-containing amorphous densities
Lysosomal rupture

Irreversible cellular injury

How well did you know this?

Not at all

Perfectly

Regions of the brain most susceptible to hypoxia/ischemia.

ACA/MCA/PCA boundaries

Specifically Purkinje cells of cerebellum and pyramidal cells of hippocampus/neocortex

How well did you know this?

Not at all

Perfectly

Region of the heart most susceptible to ischemia.

Subendocardium

How well did you know this?

Not at all

Perfectly

Region of the kidney most susceptible to ischemia.

Straight segment of proximal tubule (medulla)

Thick ascending limb (medulla)

How well did you know this?

Not at all

Perfectly

Region of the liver most susceptible to ischemia.

Zone III - around central vein

How well did you know this?

Not at all

Perfectly

Region of the colon most susceptible to ischemia.

Splenic flexure

Rectum

How well did you know this?

Not at all

Perfectly

Occurs in…
Venous occlusion
Reperfusion
Tissues with multiple blood supplies (liver, lung, intestine, testes)

Red (hemorrhagic) infarct

How well did you know this?

Not at all

Perfectly

Occurs in solid organs with single end-arterial supply (heart, kidney, spleen)

Pale (anemic) infarct

How well did you know this?

Not at all

Perfectly

Mediators of acute inflammation - outcome includes complete resolution, abscess formation, or chronic inflammation.

Neutrophils
Eosinophils
Antibodies

How well did you know this?

Not at all

Perfectly

Mediators of chronic inflammation or persistent destruction and repair associated with blood vessel proliferation and fibrosis - outcome includes scarring and amyloidosis.

Monocytes/macrophages (granulomas)
Lymphocytes
Plasma cells
Fibroblasts

How well did you know this?

Not at all

Perfectly

Round cellular swelling
Displacement of nucleus to periphery
Dispersion of Nissl (RER) substance throughout cytoplasm

CHROMATOLYSIS

Reaction of neuronal cell body to axonal damage - reflects increased protein synthesis

How well did you know this?

Not at all

Perfectly

Degeneration of axon distal to site of injury - Macrophages remove debris and myelin.

Wallerian degeneration

Cell body undergoes cellular edema - Axonal reaction

How well did you know this?

Not at all

Perfectly

Large areas of basophilic staining on H/E Small bony tissue Thick fibrotic walls Patient is normocalcemic

DYSTROPHIC CALCIFICATION Localized Ca deposition in abnormal tissues secondary to injury or necrosis

Ca deposition in interstitial tissues of kidney, lung, and gastric mucosa as these tissues are more basic ``` Seen in... Primary hyperparathyroidism Sarcoidosis Hypervitaminosis D CKD with secondary hyperparathyroidism Long-term dialysis Calciphylaxis Warfarin ```

METASTATIC CALCIFICATION Widespread Ca deposition in normal tissue secondary to hypercalcemia or high calcium-phosphate product levels

Step 1 of leukocyte extravasation

MARGINATION AND ROLLING Margination - Hemoconcentration increases contact with endothelial lining at postcapillary venules Rolling - Endothelial E/P selectins binds leukocyte Sialyl-Lewis Note - In lymph nodes GlyCAM-1/CD34 binds leukocyte L-selectins

Leukocyte Adhesion Deficiency type 2 Note - More mild (no delayed umbilical cord separation)

Defect in leukocyte adhesion due to decreased Sialyl-Lewis on leukocytes

Step 2 of leukocyte extravasation.

TIGHT-BINDING Endothelial ICAM-1 binds leukocyte CD18 b-2 Integrins (LFA-1, MAC-1)

Leukocyte Adhesion Deficiency type 1

Defect in leukocyte tight binding due to defective CD18 integrin subunit

Step 3 of leukocyte extravasation.

DIAPEDESIS/TRANSMIGRATION Leukocyte interaction with PECAM-1 at intercellular junctions

Retinopathy of prematurity | Bronchopulmonary dysplasia

Oxygen toxicity

``` Very elevated collagen synthesis Disorganized collagen organization Possible progressive growth Frequent recurrence Increased incidence in darker skin Extends beyond borders of original wound (claw-like projections) ```

KELOID Normal variant is hypertrophic scar formation

Secreted by activated platelets and macrophages Vascular remodeling and smooth muscle cell migration Fibroblast growth for collagen synthesis

PDGF

Mediators (2) stimulating angiogenesis.

FGF | VEGF

Requires tyrosine kinases (EGFR/ErbB1) | Cell growth

EGF

Mediator for tissue remodeling.

Metalloproteinases

Angiogenesis Fibrosis Cell cycle arrest

TGF-b

Mechanism and effector cells of inflammatory wound healing (< 3 d).

Clot formation Increased vascular permeability Debris clearing Platelets Neutrophils Macrophages

Mechanism and effector cells of proliferative wound healing (3 d - weeks).

``` Deposition of granulation tissue and TIII collagen Angiogenesis Epithelial proliferation Clot dissolution Wound contraction ``` ``` Fibroblasts Myofibroblasts Endothelial cells Keratinocytes Macrophages ```

Mechanism and effector cells of remodeling wound healing (1 week - 6 months)

TIII collagen replaced by TI collagen Increased tensile strength of tissue (70-80% original) Fibroblasts

Mechanism of granulomatous disease.

Th1 cells secrete IFN-y Macrophages activated Macrophages release TNF-a Induces and maintains granuloma Caseating if infectious Noncaseating if autoinflammatory

Reason to test for latent TB before starting anti-TNF therapy.

Blocking TNF-a causes breakdown of sequestering granulomas, and promotes disseminated disease.

Mechanism of increased ESR in inflammation.

Fibrinogen coats RBCs and causes increased aggregation.

``` ESR in... Anemia Cancer ESRD Nephrotic syndrome Pregnancy ```

Elevated

``` ESR in... SCD Polycythemia Microcytosis HF Hypofibrinogenemia ```

Decreased

Increased congo-red staining Increased apple-green birefringence on polarized light Increased eosinophilic staining within glomerular mesangium and tubular basement membranes on H/E

AMYLOIDOSIS Abnormal aggregation of proteins/fragments form b-pleated sheets - result in damage and apoptosis

``` Amyloidosis resulting in... Nephrotic syndrome Restrictive cardiomyopathy Easy bruising Hepatosplenomegaly Neuropathy ```

AL (PRIMARY) AMYLOIDOSIS Deposition of Ig Light chains secondary to plasma cell disorder or MM

``` Multisystem amyloidosis seen in... Rheumatoid arthritis IBD Spondyloarthropathy Familial mediterranean fever Protracted infection ```

AA (SECONDARY) AMYLOIDOSIS Deposition of serum Amyloid A fibrils

Amyloidosis seen in ESRD or long-term dialysis - may present as carpal tunnel.

DIALYSIS RELATED AMYLOIDOSIS Deposition of B2-microglobulin fibrils

Inherited polyneuropathy or cardiomyopathy due to transthyretin gene mutation.

Heritable/familial amyloidosis

Slow progression of cardiac dysfunction in older patients due to deposition of wild-type transthyretin in ventricles.

Age-related (senile) amyloidosis

Deposition of atrial natriuretic peptide - common in normal aging.

Isolated atrial amyloidosis

Deposition of amylin in pancreatic islets of a patient with DMT2.

Islet amyloid polypeptide (IAPP)

Deposition of B-amyloid cleaved from amyloid precursor protein (APP)

Alzheimer disease

Yellow-brown pigment formed by oxidation and polymerization of autophagocytosed organelle membranes - seen in autopsies of older patients.

Lipofuscin

Abnormal (non-neoplastic) proliferation of cells with loss of size, shape, and orientation - may progress to CIS.

Dysplasia

``` Progression from dysplasia to neoplastic growth Increased N/C ratio Clumped chromatin Encompass entire thickness Intact basement membrane ```

Carcinoma in situ/preinvasive

Loss of cell-cell contacts (inactivation of E-cadherin), and invasion of basement membrane (metalloproteinases including collagenase/hydrolase).

Invasive carcinoma

Disorganized overgrowth of tissue in their native location (e.g. Peutz-Jeghers).

Hamartoma

Incidence of skin cancers (greatest to least).

Basal Squamous Melanoma

Top 3 most common cancers (greatest to least).

Prostate/Breast Lung Colorectal

Top 3 cancers with the highest mortality (greatest to least).

Lung Prostate/Breast Colorectal

Cause of paraneoplastic Acanthosis Nigricans.

Gastric adenocarcinoma

Cause of paraneoplastic sign of Leser-Trelat - sudden onset multiple seborrheic keratoses.

GI adenocarcinomas

Causes of paraneoplastic hypercalcemia - elevated PTHrP

``` Squamous cell carcinoma Renal cell carcinoma Bladder Breast Ovarian Lymphoma (calcitriol) ```

Cause of paraneoplastic... Cushing's (ACTH) SIADH (ADH) Cerebellar degeneration (Hu, Yo, Tr antigens in Purkinje) Encephalitis (Hu antigens in neurons) Lambert-Eaton (presynaptic P/Q-type NMJ Ca channels)

SCLC

Causes (5) of paraneoplastic polycythemia - elevated EPO.

``` Renal cell carcinoma HCC Pheochromocytoma Hemangioblastoma Leiomyoma ```

Cause of paraneoplastic... Pure red cell aplasia/anemia with low retics Good syndrome (hypogammaglobulinemia) Myasthenia gravis

Thymoma

``` Cause of paraneoplastic... Trousseau syndrome (migratory superficial thrombophlebitis) Nonbacterial thrombotic (marantic) endocarditis (deposition of sterile platelet thrombi) ```

Pancreatic adenocarcinoma

``` Cause of paraneoplastic anti-NMDA receptor encephalitis presenting as... Psychiatric disturbance Memory deficits Seizures Dyskinesias Autonomic instability Language dysfunction ```

Ovarian teratoma

Cause of paraneoplastic Opsoclonus-myoclonus ataxia (dancing eyes, dancing feet).

Neuroblastoma (children) | SCLC (adults)

Cause of paraneoplastic cerebellar degeneration (anti Hu, Yo, Tr antigens in Purkinje cells)

SCLC Hodgkin's lymphoma Gynecologic cancers Breast cancers

ALK = receptor tyrosine kinase oncogene

Lung adenocarcinoma

BCR-ABL = tyrosine kinase oncogene

CML | ALL

BCL-2 = antiapoptotic oncogene

Follicular/diffuse large B cell lymphoma

BRAF = serine/threonine kinase oncogene

Melanoma | Non-Hodgkin's lymphoma

c-KIT = cytokine receptor oncogene

GIST

c-MYC = transcription factor oncogene

Burkitt lymphoma | Diffuse large B cell lymphoma

HER2/neu (c-cerbB2) = tyrosine kinase oncogene

Breast carcinoma | Gastric carcinoma

JAK2 = tyrosine kinase oncogene

Chronic myeloproliferative disorders

KRAS = GTPase (RAS/MAP) oncogene

Colon cancer Lung cancer Pancreatic cancer

MYCL1 = transcription factor oncogene

Lung tumor

MYCN = transcription factor oncogene

Neuroblastoma

RET = tyrosine kinase oncogene

MEN2A/B | Medullary thyroid cancer

APC = tumor suppressor gene

FAP

BRCA1/2 = DNA repair tumor suppressor genes

Breast cancer | Ovarian cancer

CDKN2A = p16 (blocks G1 to S) tumor suppressor gene

Melanoma | Pancreatic cancer

DCC = tumor suppressor gene

Colon cancer ("Deleted in Colon Cancer")

DPC4/SMAD4 = tumor suppressor gene

Pancreatic cancer ("Deleted in Pancreatic Cancer")

MEN1 = Menin tumor suppressor gene

MEN1

NF1 = Ras inhibiting protein tumor suppressor gene (Neurofibromin)

NF1 - Chromosome 17 ("17 letters in Neurofibromatosis")

NF2 = Merlin (schwannomin) protein tumor suppressor gene

NF2

PTEN = tumor suppressor gene

Breast cancer Prostate cancer Endometrial cancer

Rb = tumor suppressor gene When hypophosphorylated (active) binds E2F to block G1 to S - Phosphorylated by CDK

Retinoblastoma | Osteosarcoma

TP53 = tumor suppressor gene activating p21 Note - p21 blocks G1 to S

Most human cancers Li-Fraumeni syndrome (Sarcoma, Breast, Blood, Adrenal) Aflatoxins

TSC1/2 = Hamartin/Tuberin tumor suppressor gene

Tuberous sclerosis

VHL = tumor suppressor gene inhibiting hypoxia inducible factor 1a

Von Hippel-Lindau

WT1/2 = tumor suppressor genes

Wilms Tumor (nephroblastoma)

``` Virus associated with... Burkitt's lymphoma Hodgkin's lymphoma Nasopharyngeal carcinoma Primary CNS lymphoma ```

EBV

HPV subtypes associated with cervical, penile, anal, and head/neck cancer.

HPV-16/18

Bacteria associated with... Gastric adenocarcinoma MALT lymphoma

H. pylori

Retrovirus associated with adult T-cell leukemia/lymphoma.

HTLV-1

Trematode associated with cholangiocarcinoma.

Clonorchis sinensis (liver fluke) Treat with Praziquantel

Trematode associated with squamous cell bladder cancer.

Schistosoma haematobium (blood fluke) Treat with Praziquantel

Cancer associated with Aflatoxins from Aspergillus.

HCC

Cancer associated with alkylating agents (e.g. Cyclophosphamide).

Leukemia/Lymphoma

Cancer associated with aromatic amines (e.g. Benzidine, Naphthylamine).

Transitional cell carcinoma of the bladder

Carcinogen associated with.. Angiosarcoma of the liver Lung cancer Squamous cell carcinoma

Arsenic

Cancers associated with asbestos exposure.

Bronchogenic carcinoma > Mesothelioma

Histological change associated with carbon tetrachloride.

Centrilobular necrosis and fatty change of the liver.

``` Carcinogen associated with... SCC/adenocarcinoma of the esophagus SCC of pharynx Squamous cell lung cancer/SCLC Pancreatic adenocarcinoma Renal cell carcinoma Transitional cell carcinoma of the bladder Cervical carcinoma ```

Cigarette smoke

Carcinogen associated with... SCC of esophagus HCC

Ethanol

Carcinogen associated with ionizing radiation.

Papillary thyroid cancer

Cancer associated with Nitrosamines (smoked foods).

Gastric cancer

Cancer associated with Radon exposure.

Lung cancer (2nd leading cause)

Cancer associated with Vinyl chloride.

Angiosarcoma of the liver

Cancers associated with Psammoma bodies - laminated, concentric spherules of dystrophic calcification. ("PSaMMoma")

Papillary carcinoma of thyroid Serous papillary cystadenocarcinoma of ovary Meningioma Mesothelioma

``` Serum tumor marker for... Metastases to bone Metastases to liver Paget's disease of bone Seminoma ```

Alkaline Phosphatase

``` Serum tumor marker for... HCC Hepatoblastoma Yolk sac (endodermal sinus) tumor Mixed germ cell tumor Neural tube defects Abdominal wall defects ```

a-Fetoprotein

``` Serum tumor marker for... Hydatidiform moles Choriocarcinoma (gestational trophoblastic disease) Testicular cancer Mixed germ cell tumor ```

b-hCG Produced by syncytiotrophoblasts of the placenta

CA 15-3/CA 27-29 are serum tumor markers for...

Breast cancer

CA 19-9 is serum tumor marker for...

Pancreatic adenocarcinoma

CA 125 is serum tumor marker for...

Ovarian cancer

Calcitonin is serum tumor marker for...

Medullary thyroid carcinoma

``` Serum tumor marker for... Colorectal cancer Pancreatic cancer Gastric cancer Breast cancer Medullary thyroid carcinoma ```

CEA (carcinoembryonic antigen)

May elevate PSA in absence of prostate cancer.

BPH | Prostatitis

Classically seen in adrenal cell carcinoma and used to pump out toxins (e.g. chemotherapy) from cancer cells.

P-glycoprotein

Mediators of cachexia.

TNF IFN-y IL-1 IL-6

Carcinomas (4) which spread hematogenously like sarcomas, rather than via lymphatics.

HCC Choriocarcinoma Renal cell carcinoma Follicular thyroid cancer

Tumors most commonly metastasizing to the brain (greatest to least). ("Lots of Bad Stuff Kills Glia")

``` Lung Breast Skin (Melanoma) Kidney (RCC) GI ```

Tumors most commonly metastasizing to the liver (greatest to least).

Colon Stomach Pancreas

Tumors most commonly metastasizing to the bone (greatest to least). ("Pretty Boys Like To Kiss")

Prostate (blastic) / Breast (mixed) | Lung (mixed) / Thyroid (lytic) / Kidney (lytic)

Tumors most commonly metastasizing to the lungs (greatest to least). ("Bats Can Phly Blind")

Breast Colon Prostate Bladder

Multiple nuclei located peripherally in the shape of a horse-shoe

LANGERHANS GIANT CELLS Form in granulomas in response to CD4+ Th1 activation of macrophages

Mechanism of T-cell evasion by tumor cells

PD-L1 binds PD-1 on T-cells B7 binds CTLA-4 as co-receptor Inhibition of CD8 T cells

enzyme responsible for activation of inactive procarcinogens

cytochrome p450 oxidase system

anaplastic tumors have what type of cell

giant cells