Pathology Flashcards
1
Q
The cause of a disease and some examples.
A
Etiology; toxins, pathogens, infections, immunologic abnormalities, genetic abnormalities, nutritional imbalances, trauma
2
Q
The biochemical and molecular mechanisms of disease development.
A
Pathogenesis
3
Q
The structural alterations induced in the cells and organs of the body caused by the disease
A
Morphological, functional, and molecular changes
4
Q
The functional consequences of the etiology, pathogenesis, and morphological changes
A
Clinical manifestations
5
Q
A departure in normal function, appearance, or sensation experienced and reported by the patient that is indicative of a disease.
A
Symptom
6
Q
Any abnormality indicative of disease that is discovered by a clinician via physical exam or tests?
A
Sign
7
Q
What do stains usually behave as?
A
Acids and bases
8
Q
What type of molecule would be basophilic?
A
Anions, or molecules with a net negative charge
9
Q
What molecules are acidophilic?
A
Cations; with a net positive charge
10
Q
What is hypoxia? Ischemia?
A
Low oxygen; blockage of blood flow
11
Q
what do immune responses generate that can damage healthy cells and lead to cell death?
A
Inflammation
12
Q
What constitutes a reversible injury?
A
Where the function of a cell is bad, but can ultimately be reversed to normal function
13
Q
What two morphologic changes correlate to reversible injury?
A
Fatty changes (appearance of lipid/triglycerides bound in cytoplasm in vacuoles) and cell swelling (incr permeability of cell mem)
14
Q
What are the most common “points of no return” causing irreversible cell injury?
A
No restoration of mitochondrial function; loss of structure and function of plasma membrane and intercellular membranes; loss of DNA/chromatin structure integrity
15
Q
What is unregulated cell death (or “accidental”) which is the result of severe cell damage beyond salvage? What may cause this?
A
Necrosis; trauma, ischemia, hypoxia, etc
16
Q
What is a more organized cell death that is mediated via receptors and regulatory proteins?
A
Apoptosis
17
Q
What response is a good differentiation between apoptosis and necrosis?
A
Inflammatory response, its more present in necrosis
18
Q
How can leakage of cellular materials via necrosis be useful clinically?
A
Can be signs of disease or dysfunction (troponin and CK detection = MI; transaminases=hepatitis; alkaline phosphotase= hepatic bile duct epithelium)
19
Q
What is pyknosis? What event could this be observed during? (What histological markers are evident?)
A
Nuclear shrinkage and basophilia of a cell after necrosis (Condensing DNA into a shrunken, dark mass)
20
Q
What causes the basophilia of a necrotic nucleus to fade during pyknosis?
A
DNase activity degrading DNA during karyolysis
21
Q
What is coagulative necrosis? Where can this occur? What are characteristics?
A
Necrosis where underlying tissue is preserved and lasts several days; solid organs as a result of ischemia (NOT CNS); firm texture, lack of access from enzymes to underlying tissue via denaturing them
22
Q
What immune cells persist and are anucleated in coagulative necrotic tissues? What cells clean up?
A
Eosinophils; macrophages and neutrophils phagocytose cell debris
23
Q
What necrosis type is a result of rapid accumulation of inflammatory cells from bacteria or fungal infections that digest local tissues and give it a viscous form?
A
Liquefactive necrosis
24
Q
What is not necessarily a distinctive pattern of cell death that is more prevalent in a clinical setting where a limb loses nutrition/o2 supply via coagulative necrosis and involves multiple tissue layers?
A
Gangrenous necrosis
25
What necrosis morphology forms lesions called granulomas due to collections of WBC, and is characteristic of tuberculosis?
Caseous necrosis
26
What necrosis usually found in the pancreas (acute pancreatitis) results from active pancreatic lipases that have leaked out of acinar cells to the adipose of the peritoneum? What appearance does this have?
Fat necrosis; chalky-white (fat saponification) due to Ca2+ combination
27
What necrotic morphology can occur due to severe hypertension where antigens and antibodies are deposited in the walls of blood vessels and leak out?
Fibrinoid necrosis
28
What is the main activator of apoptosis?
Caspases
29
What is the most common pathway of apoptosis? What leaks out of this membrane to trigger apoptosis-activating enzyme and subsequent death?
Mitochondrial (intrinsic) pathway: cytochrome c when mito cell mem becomes permeable
30
What protein controls the mitochondrial cell membrane permeability? What proteins, responsible for apoptosis triggering, does this hold back?
BCL-2; Bax and Bak
31
What causes/triggers the intrinsic apoptosis pathway? What sensors pick these events up?
Misfolded proteins, growth factor deprivation, damaged DNA; BH3 sensors shift to Bax and Bak
32
What does Bax and Bak do when triggered?
Bore holes into the mitochon membrane and allow for release of cytochrome c
33
What are the prototypical cell death receptors on the exterior cell membrane?
FAS and type 1 TNF
34
Where is the FAS ligand (FasL) expressed mainly?
Cytotoxic T-cells
35
What cell death mechanisms do the following induce:
hypoxia, oxidative stress, accumulation of misfolded proteins, DNA damage, and inflammation
```
Necrosis
Necrosis
Apoptosis
Apoptosis
Either (depending)
```
36
What is hypertrophe? What is hyperplasia? Are they independent?
Increase in cell size resulting in increased organ size (cells w/ limited dividing capacity like muscles); increase in # of cells;
They can happen simultaneously
37
What is the shrinkage of cell size caused by the loss of cell substance? What can cause this?
Atrophe;
Caused by decreased workload, loss of innervation, loss of blood supply, loss of endocrine stim, aging
38
What is the adaptation where cell types (epithelial or mesenchymal) is replaced by another cell type? Why?
Metaplasia; old cell types are exposed to a stress it isnt equipped to handle, so it changes to a cell type that can (cig smoke is a good example)
39
What is autophagy and when does it occur?
Lysosomal digestion of the cell’s own components;
During nutrient deprivation
40
What are the four main pathways of intracellular accumulations?
Inadequate removal of normal substances due to defects in packaging and transport
Accumulation of abnormal endogenous substances resulting from genetic defects in folding
Failure to degrade a metabolite due to enzyme deficiency
Accumulation of exogenous substances where cell does not have enzymes to degrade it or ability to exocytose it
41
Where are fatty changes most common?
Liver (also heart, kidney, skeletal muscle, etc)
42
Accumulation of partially folded proteins, which aggregate in the _____________, is an example of defective intracellular transport
ER of the liver
43
What can ER stress caused by partially folded proteins induce?
Apoptosis
44
What deficiency is a common source of slow-folding proteins that get locked in partially folded intermediates?
Alpha1-antitrypsin deficiency
45
Deficiency in enzymes that synthesize or break down glycogen result in what?
Accumulation and apoptosis
46
Anthracosis is derived from what?
Carbons that are inhaled into the respiratory tract and are phagocytosed by alveolar macrophages. (Black pigment in draining lymph, histologically)
47
Deposits of calcium under dead or necrotic tissue from normal Ca metabolism
Dystrophic calcificationq
48
Occurs in normal tissues as a side effect of hypercalcemia
Metastatic calcification
49
What is an important cause of aortic stenosis in the elderly?
Dystrophic calcification (under aging/damaged aortic valves)
50
What are main causes of metastatic calcification?
Parathyroid hormone increased secretion (usually by malignant tumors)
Accelerated tumor destroying bone (by tumors)
Vitamin-D intoxication and sarcoidosis
Renal failure (phosphate retention-> hyperparathyroidism)
51
What are the external manifestations of inflammation?
Heat, redness, swelling, pain, loss of function
52
What are the causes of inflammation?
Infections, tissue necrosis, foreign bodies, and hypersensitivity of immune responses
53
What are the characteristics of purulent inflammation?
Production of pus, usually secondary to bacterial infection that causes liquefactive tissue necrosis
54
What is the defect, or excavation, of surface organ tissue produced by the shedding of inflamed necrotic tissue?
Ulcer: ID as a big hole between epithelia and a pit in the CT (histology)
55
What are the results of chronic inflammation?
Infiltration of mononucleated cells, cell damage, connective tissue replacement of damaged tissue (scarring)
56
Chronic inflammation characterized by collections of active macrophages associated with central necrosis. What large, macrophage-fused structure is associated?
Granulomatous inflammation; Giant cell
57
What tissue necrosis is associated with granulomatous inflammation?
Caseous necrosis
58
What decides wether tissue is regenerated or scarred?
Level of surface trauma
59
What cells are best at regenerating? What cells are bad at it and almost always scar?
Rapidly dividing cells (epithelium, WBC, liver and GI epithelium)
Cardiac cells, neural cells, CNS
60
What type of tissue (general) is constantly being lost and must regenerate constantly?
Labile tissues (GI epi, skin, uterus and fallopian tubes, transitional epithelium, oral cavity, etc)
61
What cells are usually not replicating (in G0 of mitosis), but can replicate in response to injury?
Stable cells (parenchymal liver and solid organ, endothelial, fibroblasts, smooth muscle)
62
What tissue type (general) are terminally differentiated and cannot proliferate?
Neurons and cardiomyocytes (and cells that undergo hypertrophy)
63
What are the four general steps in scar formation?
Inflammation, angiogenesis, granulation tissues, remodeling of CT
64
What macrophage types induce inflammation and cell death via ROS, NO, lysosomal enzymes? What are they stimulated by?
M1 macrophages; INF-gamma, TLR-ligands
65
What type of macrophages have anti-inflam effects, wound repair and fibrosis? What is presentation of this stimulated by?
M2 macrophages; IL-3,4
66
What cytokine is the most important for synthesis and deposition of connective tissue proteins in the formation of granulation tissue?
TGF-beta
67
What factors impair tissue repair?
Infection, diabetes, glucocorticoids, mechanical factors, poor perfusion, foreign bodies, and location/type/extent of injury
68
What is a keloid?
A scar that goes beyond its prior borders and does not regress
69
What contributes to conditions such as liver cirrhosis, idiopathic pulmonary fibrosis, and end-stage kidney disease?
Parenchymal fibrosis that replaces functional cells/tissue with CT
70
What are the two terms for increased blood volume in a tissue?
Hyperemia, congestion
71
What differentiates types of incr blood volume in tissues?
Hyperemia: active process from arteriolar dilation and increased bloodflow at inflamm sites or exercised skeletal muscle (redness)
Congestion: passive process from impaired outflow of venous blood (blue-ish color)
72
What is a result of longstanding congestion?
Tissue cell death (hypoxia) and tissue fibrosis; focal hemorrhages due to intravascular back pressure in capillaries
73
What is the accumulation of interstitial fluid in tissues?
Edema
74
What is the term for collections of fluid in body cavities? What is the term for severe, generalized edema in subq and body cavities?
Effusions; anasarca
75
What is colloid osmotic pressure produced by? What other force mediates fluid movement between vascular and interstitial space?
Plasma proteins; hydrostatic pressure (nearly balanced in homeostasis, but a net outflow into ISF and drained by lymphatics)
76
Where is fluid from lymph returned to the bloodstream?
Thoracic duct
77
What are causes of plasma protein loss? What can this lead to?
Liver disease and kidney disease; edema
78
What are non-inflammatory causes of edema?
Incr hydrostatic pressure; lower plasma osmotic pressure; lymphatic obstruction; sodium retention
79
Where does a DVT cause edema? What factor of water movement is increased/decreased?
Causes it in lower extremity distally to the DVT; increases hydrostatic pressure (local incr hstatic pressure)
80
How does congestive heart failure cause edema?
By increasing the generalized hydrostatic pressure in the venous system
81
What is the most important cause of low serum albumin levels? What else can cause this?
Nephrosis; cirrhosis and protein malnutrition also
82
What does increased sodium retention cause? How?
Incr hydrostatic pressure; it draws water into the vessels @ the kidneys (low renal function/ renal failure)
83
What are the main causes of hemorrhage?
Trauma, atherosclerosis, inflammatory or neoplastic erosion of vessel wall
84
How are large bleeds in the body cavity named?
Location (hemothorax, hemopericardium, hemoarthrosis, etc)q
85
What are minute (1-2mm) hemorrhages into the skin? What causes this?
Petechiae; low platelet count, loss of vascular wall support, VitC deficiency;
86
What are small (3-5mm) hemorrhages in the skin?
Parpura
87
What is the technical term for a 1-2cm subcutaneous hemorrhage? What cause the various colors?
Ecchymoses (bruise); hemoglobin phagocytized, bilirubin, hemosiderin
88
What are the factors of hemorrhages that determine severity?
Location of hemo., volume lost, rate of blood loss
89
What is the pathological component of blood clotting?
Thrombus
90
What are the four components of healthy clotting?
Arteriolar vasoconst., 1* hemostasis (platelet plug), 2* hemostasis (deposition of fibrin, clot stabilization and resorption
91
What vasoconstrictor is released from endothelial cells when an artery is damaged?
Endothelin
92
What promotes platelet adherence and activation in a ruptured artery?
von Willebrand factor (vWF) and collagen
93
What sets a cascade forming thrombin? What does thrombin do?
Exposed tissue factor -> factor VII -> thrombin;
Brings fibrin into a meshwork and adds another layer of platelets onto the platelet plug
94
What cell is the progenitor of platelets?
Megakaryocytes
95
What are required to start a coagulation cascade?
Enzyme, cofactor, and substrate bound to a phospholipid surface provided by active platelets, and calcium
96
What is the cofactor for coagulation?
Vit K
97
What is a coagulation enzyme antagonist commonly used clinically?
Meds like coumadin
98
What assay assesses the function of the extrinsic and common coagulation pathways?
Prothrombin time (PT)
99
What assay screens the function of the intrinsic coagulation pathway?
Partial thromboplastin time (PTT)
100
What enzyme breaks down fibrin and its polymerization?
Plasmin
101
Fibrin-derived D-dimers can be used how?
Clinical indication of thrombotic states
102
What plasminogen activator is synthesized by the endothelium and most active when bound to fibrin?
t-PA
103
What are the three primary factors that lead to intravascular thrombosis?
Endothelial injury, stasis/turbulent blood flow, hyper-coagulability of blood
104
Where is hypercoagulability most likely to create thrombosis?
Veins
105
What can happen to a thrombus after a thrombotic event?
Propagation (enlargement), embolization, dissolution (dissolve by fibrinolytic factors), organization and recanalization
106
What typically causes the majority of infarctions?
Arterial thrombosis/embolism
107
Neoplasms enjoy a degree of ________ and tend to ________ in size regardless of their local environment
Autonomy; increase
108
What is the prognosis of benign tumors?
Survival (v good)
109
What does “malignant tumor” imply?
Invasion and destruction of adjacent structures and distant site spread
110
What is the parenchyma of a tumor? Stroma?
The transformed neoplastic cells; host cells that supply CT, blood vessels, and host-derived inflammatory cells
111
What portion of the tumor determines its biological behavior?
Parenchymalq
112
What part of a tumor is crucial to growth and nutrition of the tumor?
Stroma
113
How is a benign tumor named?
Celltype-oma
114
Benign epithelial tumor nomenclature? Adenoma, papilloma, polyp
Ade- produce glandlike structures AND derived from them
Papilloma- epithelial benign tumors that produce finger-like fronds
Polyp- mass projecting above mucosa to create a macroscopically visible structure
115
Malignant tumor nomenclature: sarcoma
Derived from solid tissues (mesenchymal); tissuetype-sarcoma (chondrosarcoma)
116
Blood malignant tumor nomenclature?
Leukemias or lymphomas
117
Epithelial malignant neoplasm nomenclature?
Carcinomas; (adenocarcinomas are epithelial but show glandular growth patterns)
118
What three factors distinguish benign and malignant neoplasms?
Differentiation and anaplasia, local invasion, and metastasis
119
What functional capabilities can a well-differentiated neoplasm have? Anaplastic?
Retention of host-parenchymal function; no special function
120
What level of invasion separates malignant neo and benign neo?
Malignant: invasive af
121
What kind of cancer invests itself in the surrounding tissue and does not have encapsulated boundaries?
Malignant
122
How to malignancies metastasize?
Blood vessels, lymph vessels, and penetration into body cavities
123
What kind of malignant neo prefers lymphatic spread? Hematogenous? Is it a one-method only rule?
Carcinomas; sarcomas; no, they can use both
124
What are the most frequent secondary sites of hematogenous dissemination of malignancies?
Lungs and liver due to pulmonary and portal circulation
125
What are paraneoplastic syndromes?
Symptoms not explained by local invasion, metastasis, or elaboration of hormones in the tumor’s native tissue
126
What five groups encompass paraneoplastic syndromes?
```
Endocrine
Hematologic
Osteoarticular
Cutaneous
Neurologic
```
127
What locations of malignant neo can produce parathyroid hormone related protein (PTHrP)? What does this do?
Breast cancer, non-small cell lung, squamous cell carcinomas of the head and neck, esophagus carcinomas
Induce hypercalcemia
128
Release of ACTH or ACTH-like polypeptides cause what? From what cancer cells?
Cushing syndrome; small-cell lung carcinoma
129
What are two important acquired conditions that contribute to cancer?
Chronic inflammation and immunodeficiency
130
What are disruptions in epithelial differentiation that are indicative of increased risk of cancer development?
Precursor lesions
131
What are the four main functional classes of cancer genes?
Oncogenes, tumor suppressor genes, apoptosis-regulating genes, tumor-host cell interaction regulatory genes
132
What are oncogenes? What are proto-oncogenes?
Over-expressed versions of normal cell genes; participatory in signaling pathways that drive proliferation
133
How does growth factor synthesis contribute to cancer?
By producing the same growth factor that they have a receptor for (autocrine loop)
134
What are some common growth factors associated with cancer?
Platelet derived growth factor (PDGF); transforming growth factor (TGF-alpha); ERBB1; HER2 (ERBB2)
135
What are two important signal-transducing proteins associated with signaling downstream growth factors in cancer?
RAS and ABL
136
What is the most commonly mutated oncogene in human tumors? What type of DNA mutation causes this? What does it cause?
RAS; point mutation; continuous proliferation
137
What is a tyrosine-kinase proto-oncoprotein that is translocated from Chromosome 9 -> 22? What does it fuse with @ chrom 22? What does this induce?
ABL; BCR; BCR-ABL hybrid that self associates and unleashes continuous tyrosine-kinase activity
138
Stimulation of RAS and ABL lead to continuous stim of ________, which promotes expression of GF genes.
Nuclear transcription factors
139
What are some common nuclear transcription factors that upregulate expression of growth-promoting genes?
FOS, MYC, and JUN
140
_______ activates transcription of cyclin-dependent kinases (CDKs) that drive cells into the cell cycle. What else does _______ upregulate?
MYC; control pathways that make cell-division building blocks (AA, lipids, nucleotides, etc)
141
What silences CDK and downregulates cell division as a result?
CDK inhibitors
142
Defects in what stages of the cell cycle are important in cancer?
S/G1
143
What two major categories are involved in CDK-associated cancers?
Gain of function mutations of CDK and Loss of Function mutations in CDKI
144
What genes apply brakes to cell proliferation and can halt oncogene expression?
Tumor suppressor genes
145
What is a negative regulator of the cell cycle that is either actively or indirectly inactivated in most human cancers? (1st TS gene found)
Retinoblastoma gene (RB)
146
What is the most commonly mutated gene in human cancer (>70%)? What does it do?
TP-53; prevents neoplasm by: temp cell cycle arrest (quiescence), permanent cell cycle arrest (senescence), or apoptosis triggering
147
What is Li-Fraumeni syndrome? What does this mean for likelihood of developing cancer?
TP53 allele mutation (inherited); 25x greater chance of cancer
