Unit 1 General Concept Review Flashcards
Nucleus
Contains DNA and RNA arranged into chromatids.
Present in all cells except RBCs and platelets
Main overseer of cytoplasmic events
Cytoplasm
Cellular contents between cellular membrane and nucleus
Contains organelles and cytosol
Mitochondria
Organelle involved primarily in the (aerobic) production of ATP
Ribosomes
Small granules of rRNA
Either free or attached to RER
Protein synthesis (free => for internal use; RER => for export. Ish)
Cytosol
Fluid portion of cytoplasm
AKA intracellular fluid (ICF)
H2O, dissolved solutes, suspended particles
Hyaloplasm + microtubules and microfilaments
Smooth Endoplasmic Reticulum
Extends from RER
In liver, catabolism of drugs, hormones, carcinogens
Synthesis of steroids and fatty acids
In liver, kidneys and intestines, releases glucose into bloodstream
In muscles release Ca+
Rough Endoplasmic Reticulum
Protein production
Golgi Apparatus
Create secretory granules and lysosomes
Modify and package cellular products
Lysosomes
Membrane-bound digestive cytoplasmic organelles
Rich in lytic enzymes
Created by golgi apparatus
Hyaloplasm
Ground substance of cytoplasm;
Fluid portion of cytosl
Cytoskeleton
Composed of microfilaments (actin and myosin), microtubles, and intermediate filaments
Maintains cell shape; enables cell to adapt to external mechanical pressure.
Plasma membrane
Outer surface of cell.
Selectively permeable
Phosolipid bilayer
Hydrophobic inside, hydrophilic outside
Reversible cellular damage
Within range of homeostasis Cellular swelling and temporary loss of function: - reduced energy production - decreased protein synthesis - increased autophagy Membrane intact.
Irreversible Cell Damage
Overwhelming insult, toxins, anoxia –> nuclear changes and loss of membrane integrity
Atrophy
Decrease in the size of cells –> reduced tissue mass
Possible causes include age, poor nutrition, immobility
Hypertrophy
Increase in the size of individual cells –> increased tissue mass
Dysplasia
Inconsistent cell size and shape within a tissue.
Large nuclei, increased mitotic rate.
May indicate precancerous state
Hyperplasia
Increased number of cells –> increased tissue mass
Metaplasia
One mature cell type replaced by a different mature cell type
Apoptosis
Regulated, programmed cell death
Result of a series of molecular signals within cell
Cancer often involves impaired apoptosis
Autolysis
Death of cells and tissues in a dead organism
Necrosis
Exogenously induced cell death
Forms of necrosis
- coagulative
- liquefactive
- caseous
- enzymatic fat
Coagulative necrosis
Most common form of necrosis, most often caused by anoxia, most often in solid internal organs
Rapid inactivation of cytoplasmic hydrolytic enzymes –> prevents lysis of tissues
Tissues retain form and consistency
Liquefactive necrosis
Characterized by tissue dissolution.
Leukocytes invade necrotic tissue, release lytic enzymes, which transform solid tissue into liquid pus
Occurs most often in the brain
Secondary liquefaction
Tissue that have undergone coagulative necrosis may attract leukocytes and undergo liquefaction later on.
Caseous necrosis
Typically found in TB, as well as with some fungal infections
Coagulative necrosis with limited liquefaction
Enzymatic fat necrosis
Special form of liquefactive necrosis caused by action of LIPOlytic enzymes
Limited to fat tissue, usually around the pancreas. Usually digestive enzymes from damaged pancreas invade surrounding fatty tissue
Appears like liquified fat with whitish specks of calcium soap
Pancreatic enzymes degrade fat into ________. _______ react with _____ to create _______.
Glycerol and free fatty acids
Free fatty acids
Ca+
calcium soaps
Wet Gangrene
Bacterial infection of coagulated tissue, leading to secondary liquifaction
Dry Gangrene
Necrotic tissue dries out and becomes black and mummified.
Most often extremities, related to peripheral vascular disease
TB is associated with what sort of necrosis
caseous
Brains tend to undergo what sort of necrosis
liquefactive
Solid organs tend to undergo what sort of necrosis
coagulative
Fat surrounding the pancreas is prone to what sort of necrosis
enzymatic fat
Inflammation
The body’s nonspecific response to tissue injury
Cardinal signs of inflammation
Redness Swelling Heat Pain Loss of function
Pathogenesis of inflammation involves what four steps?
- changes in circulation of blood
- changes in vessel wall permeability
- release of soluble mediators of inflammation
- cellular actions
Inflammation: changes in circulation
First response to injury
- Vasoconstriction followed by vasodilation –> hyperemia
- blood flow slows –>congestion –> erythrocytes form rouleaux –> further impeding circulation
- WBC’s attach to endothelium (pavementing)
Inflammation: changes in vascular permeability
Second step
- increased pressure inside blood vessels and soluble mediators of inflammation cause endothelial cells to contract –> leaky endothelium
Difference between cell derived and plasma derived soluble mediators of inflammation
Plasma-derived must be activated
Cell-derived either prefab and stored in platelets and leukocytes, or created de novo
Histamine
Preformed SMI
Released by platelets and mast cells
=> immediate transient reaction
Increases endothelial leakiness
Bradykinin
Cell derived SMI, created de novo so takes longer to take effect.
Formed in plasma by activation of Coagulation Factory XII
Increases endothelial leakiness and incites pain.
Complement System
Cascade of protein activation following three paths (classical, alternative, lectin), all leading to formation of the Membrane Attack Complex (MAC)
Also causes histamine release, vasodilation, and promotes chemotaxis
Arachidonic Acid Derivatives
Cell membrane derived amino acids metabolized through two pathways:
- lipoxygenase
- cyclo-oxygenase
Lipoxygenase pathway
One of the Arachidonic Acid pathways
Creates:
1. leukotrienes (promote chemotaxis, increase vascular permeability)
2. lipoxins (inhibit chemotaxis)
Cyclo-oxygenase pathway
One of the arachidonic acid pathways
Produces
1. prostaglandins (vasodilation, vascular permeability, mediation of pain and fever)
2. thromboxane (platelet aggregation, thrombosis, vasoconstriction)
Soluble Mediators of Inflammation (SMIs)
Histamine
Bradykinin
Complement System
Arachidonic Acid Derivatives (Lipoxygenase and Cyclo-oxygenase pathways)
Cellular events associated with inflammation
Emigration of leukocytes
Phagocytosis
Chemotaxis
Leukocytes involved in inflammation
Polymorphonuclear neutrophils
Eosinophils
Basophils
Macrophages
Chemotaxis
Active movement of WBCs in respond to the release of chemical mediators
WBCs move up concentration gradient
Edema
Excess fluid in tissue
Local or systemic
Transudate
Fluid that filters through a membrane.
Contains very few proteins, cells
Exudate
Fluid with high concentration of cells and proteins.
In inflammation, formed by emigration of cells across vascular walls
Pus is a purulent exudate.
Polymorphonuclear neutrophils
Most numerous circulating WBC
Multi segmented nucleus
First to arrive.
Bactericidal, phagocytitic, releases cytokines
Eosinophils
2-3% of circulating WBCs
Segmented nucleus
Prominent in allergic reactions and inflammatory responses to parasites
Basophils
Less than 1% of circulating WBCs
Most prominent in IgE reactions
Precursor of mast cells
Macrophages
Derived from blood monocytes
Late to party (3-4 days), but long lived. Involved in chronic inflammation.
Phagocytitic and bactericidal
Acute inflammation
Removal of stimuli stops acute response
Possible outcomes: resolution, abscess formation, chronic inflammation.
Chronic inflammation
Either prolonged acute or persistent causative agents.
May not demonstrate classic cardinal signs
Secretory products of inflammatory cells cause fibrosis and more inflammation.
Outcomes: tissue destruction, fibrosis
7 kinds of inflammation
- Serous
- Fibrinous
- Purulent
- Ulcerative
- Pseudomembranous
- Chronic
- Granulomatous
Serous inflammation
Mild, occurs in early stages
Self limiting
Characterized by clear fluid
Viral infections, burns, arthritis
Fibrinous inflammation
Fibrin-rich exudate
More severe than serous.
Doesn’t resolve easily
Bacterial infections (strep throat, bacterial pneumonia, pericarditis)
Leads to fibrosis in parenchyma –> loss of function
Purulent inflammation
Caused by pus-forming bacteria such as staph and strep.
Pus can accumulate in mucosa, skin, internal organs
Abscess
Localized collection of pus
Pyrogenic cytokines
Interleukin 1
Tumour necrosis factor
Leukocytosis
Increase in circulating WBC
Loss of continuously dividing cells
AKA mitotic or labor cells
Continuously replacing
Resolution- minimal tissue damage; rapid recovery
Loss of quiescent cells
AKA facultative mitotic or stable cells
Don’t divide regularly but can be stimulated to divide by damage (or hepatocytes)
Regeneration: damaged tissue replace by identical tissue from proliferation by nearby cells.
Loss of non-dividing cells
AKA post-mitotic or permanent cells
Repair – damaged parenchymal tissue replaced with connective tissue
Functional capacity lost
Healing by first intention
Wound is clean, free of foreign material, non-necrotic, and edges are close together.
Delayed primary healing
Wound is left open, allowing debridement and cleaning before closure attempted
Healing by second intention
Large break in tissue, more inflammation
Longer healing times
Scar tissue (granulation tissue allowed to build instead of closing wound immediately)
Keloid scar
Excessive collagen
Scar overgrowth beyond limits of wound
Contraction
Fixation and deformity of joint
Adhesion
Bands of scar tissue that join two normally separated surfaces.
Hypersensitivity reaction
Allergic or autoimmune disorders
Abnormal immune response to exogenous antigen or endogenous anti-antigen
Ab-Ag reaction
The complex formed when antibodies and antigens bond to each other
Agglutination
Antibodies to insoluble antigens (like to RBCs) clump and separate from serum
Complement cascade –> cell lysis
Occurs in all IgM and IgG complexes
Type I Hypersensitivity
Anaphylactic or atopic
IgE and mast cells or basophils.
First exposure –> plasma cells produce specific IgE
Reexposure –> AgAb complex –> histamine.
Hay fever
Type 1 hypersensivity
Atopic dermatitis
Type 1 hypersensivity
Bronchial asthma
Type 1 hypersensivity
Anaphylactic shock
Type 1 hypersensivity
Type 2 hypersensivity
Cytotoxic Antibody-Mediated Reaction
Mediated by IgG or IgM
Often autoimmune
Reexposure activates complement –> cell lysis
Can be triggered by extrinsic or intrinsic factors.
Goodpastures
Type 2 hypersensivity
Autoimmune response to collagen type IV on basement membranes –> severe renal and pulmonary damage
Graves’ disease
Type 2 hypersensivity
Ab to TSH –> overproduction of thyroid hormone
Myasthenia gravis
Type 2 hypersensivity
Ab to ACh receptors –> muscle weakness and paralysis
Type 3 hypersensivity
Immune-complex mediated reaction
Overproduction of IgG and IgM –>Deposition of AgAb complexes in tissues
- triggers complement -> damage to tissues
Acute or chronic; local or systemic
SLE
Lupus
Systemic Type 3 hypersensitivity
Poststreptococcal Glomerulonephritis
Type 3 hypersensitivity
Follows strep throat –> AgAb complex sticks in glomerular basement membrane.
Polyarteritis nodosa
Type 3 hypersensitivity
Localized in small to medium sized arteries
Acute focal fibrinoid necrosis –>chronic destruction of blood vessel wall
Type 4 hypersensitivity
Cell-mediated Delayed-type reaction
T lymphocyte and macrophages aggregate and form granulomas
M tuberculosis
Type 4 hypersensitivity
Mycobacterium leprae
Type 4 hypersensivity
Sarcoidosis
Type 4 hypersensitivity
Idiopathic granulomatous disease
Contact dermatitis
Most common Type 4 hypersensitivity
No granulomas
5 classes of antibodies
IgG IgM IgA IgE IgD
IgM
Largest immunoglobulin
Neutralizes microorganisms.
May mediate Type 2 Hypersensitivity
First on scene
ABO antibody
IgG
Smallest and most numerous
Can mediate Type II Hypersensitivity
Can cross placenta
Acts as opsonin (makes bacteria tasty for phagocytes)
IgA
Mucus, breast milk, nasal secretions, tears.
IgE
Found in trace amounts in serum.
Created by mast cells
Mediates type I hypersensitivity
IgD
Bound to cell membranes on B cells.
Participates in B cell activation
Neoplasia
Uncontrolled, unregulated cell growth
Autonomous
Excessive
Disorganized
Benign vs malignant tumours: macroscopic
Benign: demarcated, often encapsulated.
Malignant: Unencapsulated, infiltrative
Benign vs malignant tumours: microscopic
Benign: resemble original tissue. Differentiated.
Malignant: anaplasic, undifferentiated
Anaplasia
Cells (often malignant) showing features not present in original tissue
Benign vs malignant tumours: cellular
Benign: uniform, similar features. Regular shaped nuclei
Malignant: nuclear pleomorphism. Large nuclei; aneuploid
Pleomorphism
Variability in size, shape, staining properties of tumour cell nuclei.
Aneuploid
Chromosomal abnormalities seem in malignant cells.
Metastatic spread can occur along what three pathways
Lymphatics
Blood
Body cavities/surfaces
~oma
Usually denote benign tumours of mesenchymal cells
Malignant ~Oma exceptions
Lymphoma
Glioma
Seminoma
~sarcoma
Denotes malignant tumour of mesenchymal cells
~blastoma
Malignant tumour of embryonic cells
Benign tumours from germ cells
Teratoma
Malignant tumours of germ cells
Teratocarcinoma
Cancer staging
Extent of tumour spread
Has better predictive value than grading
Size (T) , lymph node involvement (N), distant metastasis (M) – each assigned number in TNM system
Also I-IV and A-D scales
Cancer grading
I. Well differentiated
II. Moderately well differentiated.
III. Undifferentiated
Steps of carcinogenesis
- Ingestion of (pro)carcinogen
- initiation (genetic changes)
- Promotion (proliferation of affected cells)
- Conversion (to new cell type)
- Progression (acquisition of new features)
- Clonal expansion.
Proto-Oncogenes converted to oncogenes by:
- Point mutation
- Gene amplification
- Chromosomal rearrangement
- Insertion of viral genome. (HBV inserted in liver cancer genome)
Clinical manifestation of cancer
CAUTION
Change in bowel/bladder habit A sore that won't heal Unusual bleeding or discharge Thickening or lump in breast or elsewhere Indigestion of difficulty swallowing Obvious change in wart or mole Nagging cough or hoarseness
Cachexia
Wasting despite normal food intake
Paraneoplastic syndrome
Symptoms caused by cancer secretions, but not by local presence of cancer cells.
Incidence
Number of new cases in a specific time period in a specific population
Prevalence
Number of all cases in a specific population at a given time
Cancer incidence: men
Men
- Prostate
- Lung/bronchial
- Colorectal
Cancer incidence: women
- Breast
- Lung/bronchial
- Colorectal
Cancer mortality
- Lung/bronchus
- Prostate/breast
- Colorectal.
