Pathology Flashcards
Apoptosis What is it? What is required? Phys Inflammation Histo Clean up?
Programmed cell death
ATP required
Cytosolic caspases mediate cellular breakdown
No inflammation
Shrinkage, Pyknosis (nuc shrinkage), Basophilia, Blebbing, Nuclear Fragmentation (karyorrhexis), Apoptotic bodies
Phagocytosis
Intrinsic Apoptosis Pathway
What process is it involved with?
Mechanism
Mito involvement
Tissue remodeling in embryogenesis and after exposure to injurious stimuli
Growth factor withdrawn from proliferating cells
Changes in proportions of anti and pro apoptotic factors lead to ↑ mito permeability and ctyochrome c release
Extrinsic Apoptosis Pathways
Fas ligand binding to Fas Receptor (CD95)
Tc cells release Perforin and Granzyme B
Necrosis
What causes it?
Process?
Inflammation?
Exogenous injury
Enzymatic degradation and protein denaturation –> Intracellular components extravasate
Inflammation
Coagulative Necrosis
Heart, Liver, Kidney
Liquefactive Necrosis
Brain, Bacterial Abscess, Pleural Effusion
Caseous Necrosis
TB, Systemic Fungi
Fatty Necrosis
Peripancreatic fat (saponification via lipase)
Fibrinoid Necrosis
Blood vessels
Gangrenous Necrosis
Dry
Wet
Where?
Dry: Ischemic Coagulative
Wet: Bacteria
Limbs and GI tract
Reversible Cell Injury
What is required?
PathoPhys
Histo
Oxygen
↓ ATP synthesis, ↓ Glycogen
Swelling (impaired Na/K pump), Chromatic clumping, Fatty Change, Ribosomal detachment
Pro-apoptotic Mito protein
Bax
Anti-apoptotic Mito Protein
Bcl-2
Irreversible Cell Injury
Pathway
What happens to the cell?
Histo
Ca influx –> caspase activation
Plasma membrane damage, Lysosomal Rupture, Mito Permeability
Pyknosis, Karyolysis, Karyorrhexis
Location of Brain susceptible to ischemic injury
ACA/MCA/PCA boundary area
Location of Heart susceptible to ischemic injury
Subendocardium of LV
Location of Kidney susceptible to ischemic injury
Straight segment of PT in medulla
Thick Ascending Limb in medulla
Location of Liver susceptible to ischemic injury
Central Vein (zone III)
Location of Colon susceptible to ischemic injury
Splenic Flexure and Rectum
Red Infarcts What kind of infarct? What kind of tissue? Organs? When?
"Red = Reperfusion" Hemorrhagic Tissue with collaterals Liver, Lungs, Intestines Following reperfusion
Hypoxic Ischemic Encephalopathy affects what kind of cells?
Pyramidal Cells of Hippocampus and Purkinje cells
Pale Infarcts
What kind of tissue?
Organs?
Solid tissues with a single blood supply
Heart, Kidney, Spleen
Reperfusion injury is due to…
Free Radicals
Hypovolemic Shock
Output
TPR
Presentation
Low output
↑ TPR
Cold and Clammy
Cardiogenic Shock
Output
TPR
Presentation
Low output
↑ TPR
Cold and Clammy
Septic Shock Output TPR Vasculature Presentation
High output
↓ TPR
Dilated arterioles, High venous return
Hot
Atrophy
What is it?
Possible causes?
Reduction in size or # of cells
↓ hormones, innervation, blood flow nutrients
↑ pressure
Occlusion of secretory ducts
Characteristics of Inflammation
Redness, Heat, Swelling, Loss of Function
Vascular component of inflammation
↑ vascular permeability, vasodilation, endothelial injury
Cellular component of inflammation
Neutrophil mediated
Acute component of inflammation Mediators Onset Duration Possible outcomes
Neutrophils, Eosinophils, Abs
Seconds to minutes
Minute to days
Resolution, Abscess, Chronic inflammation
Chronic component of inflammation Mediators Characteristic Associated with... Outcomes
Mononuclear cells
Persistent destruction and repair
Blood vessel proliferation. Fibrosis
Scarring, Amyloidosis
Granuloma
Histo
Pathway
Nodular collection of Epithelioid Macrophages and Giant Cells
Th1 secretes IFNγ which activates Macs which secrete TNFα
Leukocyte Extravasation
Steps w/ mediators
1.Rolling:
Vasculature: E and P selectins. Leukocyte: Sialyl-Lewis
2. Tight Binding
V: ICAM. L: LFA1 (integrin)
3. Diapedesis (between endothelial cells)
V: PECAM. L: PECAM
4. Migration
Leukocyte (neutrophil) chemotactic factors
“CLIK”
C5a, LTB4, IL8, Kallikrein
How do free radicals damage cells?
Membrane lipid peroxidation
Protein modifications
DNA breakage
Free Radicals
What causes them?
How are they eliminated?
Radiation, Metabolism of drugs, Redox rxns, Nitric Oxide (NO), Transition metals, Leukocyte oxidative burst
Enzymes (Catalase, SOD, Glutathione Peroxidase), Decay, Antioxidants (A, C, E)
Free Radical Diseases
ROP, Bronchopulmonary Dysplasia, CCl4 –> liver necrosis (fatty change), Acetominophen OD, Hemochromatosis, Reperfusion
Would Healing Phases
Inflammatory, Proliferative, Remodeling
Would Healing Inflammatory Phase
When?
Mediators
What happens?
Immediate
Platelets, Neutrophils, Macrophages
Clot formation and ↑ permeability
Would Healing Proliferative Phase
When?
Mediators
What happens?
2-3 days after injury
Fibroblasts, Myofibroblasts, Endothelial cells, Keratinocytes, Macrophages
Deposition of granulation tissue and collagen. Angiogenesis, Epithelial cell proliferation, Dissolution of clot, Wound contraction (via myofibroblasts)
Would Healing Remodeling Phase
When?
Mediators
What happens?
1 week
Fibroblasts
Collagen III replaces Collagen I –> ↑ tensile strength of tissue
Granulomatous Diseases
TB
Fungal Infections (Histoplasmosis, Coccidioidomycosis)
Treponema Pallidum (Syphilis)
M Leprae (Leprosy)
Bartonella Henselae (cat scratch disease)
Sarcoidosis, Crohn’s Disease, Wegener’s, Churg Strauss
Berylliosis, Silicosis
Transudate Cellularity? Protein? Specific gravity Causes
Hypocellular
Low protein
Less than 1.012
↑ hydrostatic pressure, ↓ oncotic pressure, Na retention
Exudate Cellularity? Protein? Specific gravity Causes
Cellular
Protein rich
Greater than 1.02
Lymphatic obstruction or Inflammation
Iron Poisoning
MoA
Acute
Chronic
Peroxidation of membrane lipids
Acute gastric bleeding
Chronic: Metabolic acidosis, Scarring –> GI obstruction
Amyloidosis
What is it?
What does it cause?
Appearance of tissue?
Abnormal aggregation of proteins into β-pleated sheets
Cell damage and apoptosis
Waxy appearance
AL Amyloidosis
What kind of protein?
What disorders present with it?
Organ systems affected
Ig Light chains
Plasma cell disorder or Multiple Myeloma
Renal (nephrotic), Cardiac (failure, arrhythmia), Hematologic (easy bruising), Hepatomegaly, Neuropathy
AA Amyloidosis
What kind of protein?
What diseases?
Systems involved?
Amyloid A fibrils
RA, IBD, Spondyloarthropathy, Chronic Infections
Multiple systems like in AL
Dialysis Related Amyloidosis
What kind of protein?
What kind of pt?
Presentation
β2 microglobulin
ESRD on long term dialysis
Carpal tunnel syndrome and other joint issues
Heritable Amyloidosis
Genetics
Disease
Transthyretin (TTR or prealbumin) gene mutation
ATTR neurologic/cardiac amyloidosis
Age-Related (Senile) Amyloidosis
What kind of protein?
Organs affected
Progression
wt TTR
Systemic: deposited in myocardium and other sites
Slower progression of cardiac dysfunction vs AL
Organ Specific Amyloidosis
What is affected?
Example with protein
A single organ
Alzheimer’s Disease due to deposition of amyloid-β protein from APP
Anaplasia
Abnormal cells lacking differentiation
Desmoplasia
Fibrous tissue formation in response to neoplasm
Tumor Grade
Degree of cellular differentiation
Tumor Stage
TNM
Degree of localization/spread based on site and size
Tumor Size
Node Involvement
Metastases
Tumor stage vs grade re prognostic value
Stage has more prognostic value
Epithelium tumor names
Benign
Malignant
Adenoma, Papilloma
Adenocarcinoma, Papillary carcinoma
Tumor of Blood Vessels
Benign
Malignant
Hemangioma
Angiosarcoma
Tumor of Smooth Muscle
Benign
Malignant
Leiomyoma
Leiomyosarcoma
Tumor of Striated Muscle
Benign
Malignant
Rhabdomyoma
Rhabdomyosarcoma
Tumor of Connective Tissue
Benign
Malignant
Fibroma
Fibrosarcoma
Tumor of Bone
Benign
Malignant
Osteoma
Osteosarcoma
Tumor of Fat
Benign
Malignant
Lipoma
Liposarcoma
Cachexia
Presentation
Disease with it?
Mediated by
Wt loss, Muscle atrophy, Fatigue
Cancer, AIDS, Heart Failure, TB
TNFα, IFNγ, IL6
Neoplasm of Down Syndrome
ALL, AML
Neoplasm of Xeroderma Pigmentosum or Albinism
Melanoma, Basal Cell Carcinoma, Squamous Cell Carcinoma of the Skin
Neoplasm of Chronic Gastritis, Pernicious Anemia, Postsurgical Gastric Remnant
Gastric Adenocarcinoma
Neoplasm of Tuberous Sclerosis
Giant Cell Astrocytoma, Renal Angiomyolipoma, Cardiac Rhabdomyoma
Neoplasm of Actinic Keratosis
Squamous cell carcinoma of the skin
Neoplasm of Barrett’s Esophagus
Esophageal adenocarcinoma
Neoplasm of PVS
Squamous cell carcinoma of the esophagus
Neoplasm of Paget’s Disease of Bone
Osteosarcoma, Fibrosarcoma
Neoplasm of Immunodeficiency States
Malignant Lymphomas
Neoplasm of AIDS
Malignant Lymphomas and Kaposi Sarcoma
Neoplasm of autoimmune disease
Lymphoma
Neoplasm of Acanthosis Nigricans
Visceral Malignancy (Stomach, Lung, Uterus)
Neoplasm of Dysplastic Nevus
Malignant Melanoma
Neoplasm of Radiation Exposure
Leukemia, Sarcoma, Papillary Thyroid Cancer, Breast Cancer
abl
What kind of protein?
Tumor
Product
Oncogene
CML
Tyrosine Kinase
c-myc
What kind of protein?
Tumor
Product
Oncogene
Burkitt’s Lymphoma
Transcription factor
bcl2
What kind of protein?
Tumor
Product
Oncogene
Follicular and undifferentiated lymphoma
Anti-apoptotic molecule
HER2/neu (c-erbB2)
What kind of protein?
Tumor
Product
Oncogene
Breast, Ovarian, Gastric Carcinoma
Tyrosine Kinase
ras
What kind of protein?
Tumor
Product
Oncogene
Colon Carcinoma
GTPase
L-myc
What kind of protein?
Tumor
Product
Oncogene
Lung Tumor
Transcription Factor
N-myc
What kind of protein?
Tumor
Product
Oncogene
Neuroblastoma
Transcription Factor
ret
What kind of protein?
Tumor
Product
Oncogene
MEN 2A and 2B
Tyrosine Kinase
c-kit
What kind of protein?
Tumor
Product
Oncogene
GI stromal tumor
Cytokine Receptor
Rb
What kind of protein?
Tumor
Product
Tummor Suppressor
Retinoblastoma, Osteosarcoma
Normally inhibits E2F thus blocking G1 –> S transition
p53
What kind of protein?
Tumor
Product
Tummor Suppressor
Most human cancers, Li-Fraumeni Syndrome
Transcription factor for p21. Normally blocks G1 –> S transition
BRCA1 and BRCA2
What kind of protein?
Tumor
Product
Tummor Suppressor
Breast and Ovarian Cancer
DNA repair protein
p16
What kind of protein?
Cancer
Tummor Suppressor
Melanoma
BRAF
What kind of protein?
Tumor
Product
Tummor Suppressor
Melanoma
B-raf
APC
What kind of protein?
Cancer?
Tummor Suppressor
Colorectal cancer
WT1
What kind of protein?
Tumor
Tummor Suppressor
Wilm’s Tumor (Neuroblastoma)
NF1
What kind of protein?
Tumor
Product
Tummor Suppressor
Neurofibromatosis type 1
RAS GTPase activating protein (RAS GAP)
NF2
What kind of protein?
Tumor
Product
Tummor Suppressor
Neurofibromatosis type 2
Merlin (Schwannomin) protein
DPC4
What kind of protein?
Tumor
Product
Tummor Suppressor
Pancreatic Cancer
“Deleted in Pancreatic Cancer”
DCC
What kind of protein?
Tumor
Product
Tummor Suppressor
Colon Cancer
“Deleted in Colon Cancer”
PSA
Function
When is it elevated?
Screen utility?
Follow prostate carcinoma
Prostate carcinoma, BPH, Prostatitis
Questionable
Prostatic Acid Phosphatase maker for…
Prostate carcinoma
CEA marker
Name
Cancers associated with it?
CarcinoEmbryonic Antigen
Colorectal and Pancreatic Cancer
Gastric, Breast, and Medullary Thyroid Carcinoma
α-FetoProtein
Normally made by
Marker for what kind of cancers?
Normally made by fetus
Hepatocellular carcinoma, NonSeminomatuous germ cell tumor (ovary, testis)
βhCG: Marker for what kind of tumors?
Hydatidiform moles and Choriocarcinomas (Gestational trophoblastic disease)
CA-125 marker for
Ovarian Cancer
S-100 marker for
Melanoma, Neural tumors, Schwannomas
ALP marker for
Metastases to bone, Liver, Paget’s Disease of bone
Bombesin marker for…
Neuroblastoma, Lung, and Gastric Cancers
TRAP
Name
Marker for…
“Trap the Hair Animal”
Tartrate Resistant Acid Phosphatase
Hairy Cell Leukemia (B cell neoplasm)
CA-19-9 marker for
Pancreatic Adenocarcinoma
Calcitonin marker for
Medullary Thyroid Carcinoma
HTLV-1 leads to what cancer?
Adult T cell leukemia/lymphoma
HBV and HCV lead to what cancer?
Hepatocellular Carcinoma
EBV leads to what cancer?
Burkitt’s Lymphoma, Hodgkin’s Lymphoma, Nasopharyngeal Carcinoma, CNS lymphoma (in immunosuppressed pts)
HPV leads to what cancer?
Cervical carcinoma (16, 18)
Penile/anal carcinoma
Upper Respiratory SCC
HHV8 leads to what cancer?
Kaposi sarcoma, Body Cavity Fluid B cell lymphoma
H. pylori leads to what cancer?
Gastric Adenocarcinoma and Lymphoma
Liver Fluke (Clonorchis sinensis) leads to what cancer?
Cholangiocarcinoma
Aflatoxin
Made by what organism?
Organ affected?
Impact?
Aspergillus
Liver
Hepatocellular carcinoma
Vinyl Chloride
Organ affected?
Impact?
Liver
Angiosarcoma
CCl4
Organ affected?
Impact?
Liver
Centriolobular Necrosis and Fatty Change
Nitrosamines
Where are they from?
Organ affected?
Impact?
Smoked foods
Stomach
Gastric Cancer
Cigarette smoke
Organ affected?
Impact?
Larynx: Squamous Cell Carcinoma Lung: Squamous and Small cell carcinoma Kidney: Renal cell carcinoma Bladder: Transitional cell carcinoma Pancreas: Pancreatic adenocarcinoma
Asbestos
Organ affected?
Impact?
Lung
Bronchogenic carcinoma > Mesothelioma
Arsenic
Organ affected?
Impact?
Skin: Squamous Cell Carcinoma
Liver: Angiosarcoma
Naphthalene (aniline)
Organ affected?
Impact?
Bladder
Transitional Cell Carcinoma
Alkylating Agents
Organ affected?
Impact?
Blood
Leukemia
Paraneoplastic ACTH
Made from…
Effect
Small cell carcinoma of the lung
Cushing’s syndrome
Paraneoplastic ADH
Made from…
Effect
Small cell carcinoma of the lung and intracranial neoplasms
SIADH
Paraneoplastic PTHrP
Made from…
Effect
Small cell carcinoma of the lung, Renal cell carcinoma, Breast cancer
HyperCa
Paraneoplastic VitD
Made from…
Effect
Hodgkin’s Lymphoma and some Non-Hodgkin’s Lymphoma
HyperCa
Paraneoplastic EPO
Made from…
Effect
Renal Cell Carcinoma, Hemangioblastoma, Hepatocellular carcinoma, Pheochromocytoma
Polycythemia
Paraneoplastic Abs against presynaptic Ca channels
Made from…
Effect
Small Cell Carcinoma of the Lung
Lambert Eaton Syndrome
Psammoma Bodies
Appearance
Seen in what?
Laminated, Concentric, Calcific Spherules
“PSaMMoma”
Papillary Adenocarcinoma of the Thyroid
Serous Papillary cystadenocarcinoma of the ovary
Meningioma
Malignant Mesothelioma
Cancer epidemiology in Men
Incidence
Mortality
Prostate (32%), Lung (16%), Colon/Rectum (12%)
Lung (33%), Prostate (13%)
Cancer epidemiology in Women
Incidence
Mortality
Breast (32%), Lung (13%), Colon/Rectum (13%)
Lung (23%), Breast (18%)
Cancers that metastasize to Brain
Lung, Breast, GU, Osteosarcoma, Melanoma, GI
Cancers that metastasize to Liver
Colon, Stomach, Pancreas
Cancers that metastasize to Bone
What bones are more common?
Prostate (blastic), Breast (lytic and blastic), Lung (lytic), Thyroid, Testes
Axial skeleton
Metastatic Brain tumors
Frequency
Location
Appearance
50% of brain tumors are metastatic
Gray/White Junction
Multiple well circumscribed tumors