Exam 1 Flashcards
1
Q
Define Pathology
A
The study of disease. The study of suffering and illness. Study of structural and functional changes in cells, tissues, and organs of the body that are cause or are caused by disease.
2
Q
Define Disease
A
The pattern of response of living organism to injury. When cells fail to adapt to the injury or the adaptive mechanism itself becomes harmful, disease results.
3
Q
Define Signs
A
Objective evidence of disease (e.g. blood in stool). May also be called physical sign.
4
Q
Define Symptoms
A
Subjective evidence of disease (e.g. “I am having abdominal pain”). Described by the patient. Also called clinical symptoms (e.g. pain, dizziness, nausea).
5
Q
Define Etiology
A
The cause of a disease process (e.g. lung cancer can be caused by smoking - this is the etiology of lung cancer). Also include biologic agents, chemical agents, or physical forces.
6
Q
Define Pathogenesis
A
The development of a given disease. The sequence of cellular events that take place from time of initial contact until expression of the disease. The mechanism of how a disease evolves until it becomes manifest (e.g. smoking causes a coating in your lungs, which gets into the DNA of the lung cells and causes mutations which cause cancer).
7
Q
Define Manifestations
A
The changes in structure and function of tissues, organs and system characteristic of disease (both gross anatomic and microscopic changes).
8
Q
Define Sequelae and Complications
A
The secondary consequences of a disease.
9
Q
Define Prognosis
A
The anticipated course of disease and final outcome (cure, remission, morbidity or mortality)
10
Q
Define Epidemiology (incidence and prevalence).
A
The study of disease in population. Within populations we can look for patterns in disease or study risk factors that predispose to disease.
The incidence represents the number of new cases arising in a population over a given time period, and prevalence is the total number of cases (new and existing cases) of the disease in a given population.
11
Q
Define Morbidity
A
Illness that impairs the well-being and normal function of a patient (living with disease).
12
Q
Define Mortality
A
Illness causing the death of a patient (death from disease).
13
Q
What was the leading cause of death in Canada in 2018?
A
Cancer
14
Q
What are the two categories of disease causes, explain:
A
Genetic causes: inherited genetic defects.
Environmental causes: exposure to cause of disease
*Diseases result from a variable interaction between the host (i.e. genetic and environmental factors).
15
Q
Define Iatrogenic
A
Complications (adverse event) from treatment. Unintended injuries, or complications resulting in death, disability or prolonged hospital stay that arise from health care management.
16
Q
Define Idiopathic
A
Of unknown etiology (cause of disease).
17
Q
What are the different categories of environmental causes of disease? Give examples of each.
A
- Physical agents: mechanical trauma (e.g. cuts), temperature (e.g. burns, frostbite, heatstroke), electrical burns (e.g. lightning), radiation, atmospheric pressure (e.g. deep water diving).
- Chemical agents: environmental or industrial exposure (e.g. asbestos), poisons/ toxins, drugs, iatrogenic disease, infections, and allergens.
18
Q
List the current techniques of pathology
A
Gross pathology, light microscopic examination and electron microscopy, immunohistochemistry, and molecular testing.
19
Q
Describe gross pathology
A
Technique which looks at the big picture, e.g. a whole organ, tissue, etc. Visual observations and descriptions (naked eye examination)
20
Q
Describe light and electron microscopy
A
Look at sections under a microscope (standard stains: hematoxylin - blue : stains DNA / nucleus, eosin - pink : stains extracellular matrix and cytoplasm
21
Q
Describe immunohistochemistry
A
Investigations of disease at the cellular level (e.g. shows a specific protein) - primary antibody recognizes antigen, then secondary antibody recognizes primary antibody - HRB on secondary antibody turns brown (stain = dab).
22
Q
Describe molecular testing
A
Analysis of DNA, RNA and protein. Sequence genes. Investigation of disease at the molecular level. e.g. chromosomal analysis.
23
Q
What does alternative classification of disease mean?
What are the alternative classifications?
A
More detailed classification of disease based on the pathogenesis or disease process.
-Injury
-Inflammation
-Infection
-Immunological reaction
-Neoplasia
-Metabolic or endocrine
-Nutritional
-Vascular disease
-Psychological factors
24
Q
Describe injury alternative classification of disease
A
Due to physical or chemical agent(s). At the cellular level, injury injury may be reversible and the cell/ tissue survives or adapts (atrophy, hypertrophy, hyperplasia), or irreversible leading to the death and degeneration of the cell.
25
Describe inflammation alternative classification of disease
The inflammatory response is common to many diseases (injury, etc.) but some diseases are thought to be primarily inflammatory (e.g. tonsillitis or acute apendicitis). A chronic inflammation response may also occur in certain allergic-type reactions and with certain viral or parasitic infections.
26
Describe infection alternative classification of disease
One of the most common forms of disease, infection usually produces mild to moderate symptoms. Infectious organisms (viruses, bacteria, parasites) can produce more serious illness in those whose immune systems are compromised. Cellular pathology depends on factors of both the attacking organism and the host's response.
27
Describe immunological response alternative classification of disease
The immune response is normally protective, but in some circumstances the reaction may become excessive (e.g. hypersensitivity to allergens - anaphylactic shock) or may act against the body's own cells (e.g. autoimmune disease) or may be absent or depressed (immunodeficiency, immunosuppressive therapy).
28
Describe neoplasia alternative classification of disease
Autonomous (on its own- in control) proliferation of cells, usually causing tumours or masses. These can be benign (will not spread) or malignant (can spread- metastasize). Latter more likely to kill patient.
29
Describe metabolic or endocrine alternative classification of disease
Disorders of enzymes, hormones, or secretory products (e.g. type 2 diabetes). Some metabolic diseases are genetic (e.g. congenital adrenal hyperplasia).
30
Describe nutritional alternative classification of disease
Deficiencies in proteins or calories due to insufficient supply (e.g. anorexia nervosa, kwashiorkor, marasmus), decreased absorption, transport or utilization (e.g. celiac disease) or specific vitamin or mineral deficiencies (e.g. scurvy). The flipside, excess calories or obesity is also a nutritional disease and can increase morbidity due to the increased risk of a number of conditions (e.g. hypertension, diabetes, atherosclerosis, heart attacks, and some cancers).
31
Describe vascular disease alternative classification of disease
One of the most common causes of death in developed countries. Narrowing of important blood vessels (atherosclerosis) underlies very common causes of morbidity and mortality as heart attacks and strokes.
32
Describe psychological factors alternative classification of disease
Psychological factors may both cause and effect disease processes. Psychological stress may lead to mental illness or worsen the existing somatic disease. Psychological factors are also an important factor in disease caused by addiction (drugs, alcohol, cigarettes, etc.)
33
What are the different causes or agents of cell injury?
-Physical: trauma, radiation, temp, changes in pressure
-Chemical: air pollutants, CO, pesticides, poisons, toxins, drugs
-Biological: infectious organisms, biological toxins
-Nutritional or metabolic: nutrient deficiencies / excesses, ischemia, lack of adequate blood supply - hypoxia
-Immune reactions: allergens, autoimmune disease
-Genetic defects: single gene disorders (sickle cell disease, hemophilia), chromosomal abnormalities (trisomy 21)
-Cellular aging: loss of normal repair mechanisms
34
Define adaptation
Adaptation can include regulation of cells receptors (up and down regulation), or changes in protein synthesis or turnover. In all cases of adaptation, if the stimulus is removed, the cells will revert back to their resting state.
35
What are the different types of adaptation?
Atrophy
Hypertrophy
Hyperplasia
Metaplasia
36
Describe Atrophy, what are the causes?
Decrease in mass due to decrease in cell size (decreased function).
-Due to decreased blood supply (ischemia), or nutritional and trophic factors.
E.g. can result from decreased workload (immobilization of limb, disuse), loss of innervation, diminished blood or nutrient supply, loss of endocrine or hormonal stimulation (interruption of trophic signals), and aging.
37
What is a physiological and pathological example of Atrophy?
Physiological: occurs in normal aging (shrinkage and loss of brain cells with age)
Pathological: disuse of skeletal muscle in immobilized limbs or denervation atrophy following loss of nerve input to a muscle.
38
Describe Hypertrophy
Causes?
Increase in cell size (increase synthesis of cellular protein and structural components and organelles - increased contents).
Accompanied by an augmented functional capacity.
Causes:
-increased functional demand (myocardial hypertrophy in hypertension, muscle hypertrophy in athletes)
-Physiologic (hormonal) hypertrophy - sex organs at puberty
39
Describe Hyperplasia
Causes?
Increase in number of cells in an organ or tissue caused by cell division.
Causes:
-Increased functional demand (increased RBCs in high altitude)
-Hormonal stimulation (endometrium in early phase of menstrual cycle)
-Persistent cell injury (skin in calluses)
40
What is a physiological and pathological example of Hypertrophy and Hyperplasia?
Often hypertrophy and hyperplasia occur together (can be separate as well tho). They are considered the opposite of atrophy.
Physiological: Uterus in pregnancy undergoes hypertrophy and hyperplasia to adapt and grow in order to contain a fetus.
Pathological: endometrial hyperplasia - unopposed estrogen, endometrial lining thickens and keeps going (menopause), keeps replicating out of control and can lead to endometrial carcinoma.
41
Describe Metaplasia
Change /conversion of one differentiated cell type into another. May result in decreased function or increased chance of malignancy. Often due to longterm exposure to unsuitable environments.
*protective mechanism but may have loss of function.
42
What is an example of metaplasia?
Respiratory epithelium in the bronchi exposed to debris on inhalation, cilia move it out of lungs but very small and can get overwhelmed - e.g. from smoking. Cells (ciliated columnar) are replaced by squamous cells (which lines your mouth - very tough). Now have no cilia to get rid of debris or smoke. Cells become dysplastic and then malignant (pathological).
Hyperplasia and metaplasia can both lead to dysplasia.
43
What is Dysplasia? What are the features of Dysplasia?
*What is the significance?
Alteration in size, shape, and organization of the cellular components of a tissue.
Broad term to describe the abnormal development of cells within tissue or organs.
Features:
-variation of shape and size of cells (cellular pleomorphism)
-variation in nuclear shape and size (nuclear pleomorphism)
-enlargement, irregularity and hyperchromatism of the nuclei
-disordered arrangement of the cell
*significance: dysplasia is a pre-malignant lesion
44
Contrast reversible vs irreversible cell injury
Cells lose functional activity relatively quickly as a result of biochemical derangements, while morphological changes of cell injury and death lag far behind.
-At early stages, mild forms of injury and functional/ morphological changes are completely reversible if stimulus is removed (has not progressed to severe membrane or nuclear damage yet).
-With continuing damage, cell injury becomes irreversible; the cell cannot recover and dies.
45
Describe reversible injury. What are the cellular changes that characterize reversible cell injury?
Injury caused by a variety of agents produces a characteristic cellular or hydropic swelling (increase in cell volume, characterized by a large, pale, and vacuolated cytoplasm and a normally located nucleus) when seen under a microscope. This swelling results from impairment of the process that controls ion concentrations in the cytoplasm. With removal of the stimulus, these changes are reversible and the cell reverts back to its normal state.
46
Describe irreversible injury.
If overwhelming injury occurs or occurs at a rate at which the cell cannot adapt, necrosis or cell death is the result. With continuing damage, cell injury becomes irreversible.
47
Describe the cellular changes of irreversible cell injury leading to necrosis
Irreversible changes include: membrane rupture, dispersal of organelles, breakdown of lysosomes, and activation of inflammatory response.
Types of irreversible responses include: interruption of membrane integrity; hydrolysis of phospholipids, proteins and nucleic acids; and necrosis, where organelles undergo a sequence of changes.
48
List the different types of necrosis
Coagulative necrosis - Gangrenous necrosis
Liquefactive necrosis
Fat necrosis
Caseous necrosis
Fibrinoid necrosis
49
Describe coagulative necrosis. Where is this typically found?
Most common form. Microscopically all the changes of necrosis are seen (eosinophilia, pyknosis, karyorrhexis, and karyolysis). Cells appear like "ghosts" of themselves in which the basic structural outline of the coagulated cell persists for a number of days, nucleus is gone though.
Typical of ischemic injury. See in heart and kidney because they have areas that are fed by one blood supply. If this supply is cutoff - get coagulative necrosis. Tends to be firm.
50
What is eosinophilia?
Pinkness
51
What is pyknosis?
Pyknosis, or karyopyknosis, is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis.
Shrinkage
52
What is karyorrhexis?
Karyorrhexis is the destructive fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm. It is usually preceded by pyknosis and can occur as a result of either programmed cell death, cellular senescence, or necrosis.
The pyknotic nucleus fragments
53
What is karyolysis?
Complete dissolution of nuclear components of a dying cell.
54
Describe gangrenous necrosis
"Wet gangrene" is used to refer to coagulative necrosis (most frequently of a limb) when there is superimposed infection with a liquefactive component.
If the necrotic tissue dries out (with no infectious component) it becomes dark black and mummified and is called "dry gangrene". Typically in limbs, compromised vascular supply.
55
Describe liquefactive necrosis. What are examples?
Rapid loss of tissue architecture and digestion of the dead cells. Most often seen in the CNS, lungs or in the presence of bacteria (typical of bacterial damage).
Due to action of hydrolytic enzymes, not firm, more mushy. Can get cavities.
E.g. stroke in the brain, or abscess in the lung.
56
Describe fat necrosis. What is an example?
Specific to fat (adipose) tissue. Released enzymes digest fat and combines with calcium to form chalky-white deposits.
E.g. pancreatitis (seen most commonly with injury to the pancreas), damage to breast tissue
57
Describe caseous necrosis. Example?
Soft, friable, 'cheesy-like (goat cheese - crumbly)' material.
Characteristic of tuberculosis - airborn pathogen, goes into your lung, body tries to break it down, see accumulation of macrophages - trying to eat it up.
58
Describe fibrinoid necrosis
Blood vessel wall gets so damaged that it is replaced by fibrid.
59
Define Apoptosis. Give physiological and pathological examples.
Energy-dependent process specifically designed to switch off unneeded of damaged cells and eliminate them. Morphologic manifestation of programmed cell death.
-Physiological: During embryogenesis in shaping fingers and toes; the physiological involution of thymus during development; endometrium during menstrual cycle.
-Pathological: Following radiation injury in some cancer
60
Define Necrosis
Uncontrolled process of cell death in response to overwhelming injury.
Characterized by certain structural changes including intense eosinophilia (pinkness) of the cytoplasm and pyknosis (shrinkage), karyorrhexis (the pyknotic nucleus fragments) and karyolysis (dissolution) of the nucleus.
61
Contrast Apoptosis vs Necrosis. How is it determined whether a cell undergoes necrosis or apoptosis?
The magnitude and type of injurious stimulus can determine whether a cell undergoes apoptosis or necrosis. Severe damaging stimuli tend to result in necrosis and lower-grade stimuli and immune-mediated damage tend to cause apoptosis.
*A critical factor seems to be how much cellular ATP is available after cell damage (apoptosis is energy-dependent). With severe depletion of ATP the necrotic pathway is followed.
62
List the different mechanisms of injury
-Generation of Reactive Oxygen Species (ROS)
-Ischemic and Hypoxic cell injury
-Ischemia/ Reperfusion injury
-Chemical or Drug-related cell injury
-Intracellular accumulations
63
Describe how the generation of reactive oxygen species can cause cell injury
Partially reduced or reactive oxygen species are identified as a likely cause of cell injury. They can initiate lipid per-oxidation leading to a loss of membrane integrity, cross-link essential proteins, damage DNA or form secondary damaging ROS (e.g. lipid peroxide radicals).
* The body has several mechanisms to detoxify these potentially damaging substances (because formed during normal metabolism also), but when these endogenous systems become overwhelmed damage can occur.
64
Describe Ischemia and how it causes cell injury
Ischemia is the reduction or interruption of blood flow (both oxygen and substrates for glycolysis disappear). Inadequate blood supply to an area of tissue.
Most common type of cell injury and an important cause of coagulative necrosis (infarction).
Acute cellular swelling (caused by net gain of sodium and iso-osmotic gain of water). Also causes a reduction in protein synthesis.
Disturbances are reversible if oxygen is restored
65
Describe Hypoxia
Reduced levels of oxygen. Similar effects as Ischemia, however, ischemia has the added layer of not delivering substrates as well.
66
Describe Ischemia/ Hyperfusion injury
The restoration of blood flow (after Ischemia) can result paradoxically in additional injury (not always).
67
Describe chemical or drug-related cell injury
Chemicals can cause cell injury and damage directly (e.g. heavy metals; chemotherapeutic agents), or indirectly following metabolism to active metabolites.
68
What is the apoptosis process?
Apoptotic cells initiate their own death by the activation of proteases known as caspases and endogenous endonucleases that breakdown the cell nucleus and cytoskeleton. The cell nucleus collapses, the cell shrinks and is cleaved into membrane-bound clumps enclosing organelles (apoptotic bodies). The membrane bound material is recognized and quickly engulfed by phagocytic cells.
69
Define inflammation
-reaction of living tissue to injury
-dynamic process that starts with the injury and culminates with healing or repair
-primarily a protective response, but it may be potentially harmful
-stereotyped process regardless of the nature of the injury
-intensity, duration and outcome is modified by a variety of host factors and factors related to the etiological agent
-in order for inflammation to occur, injury has to be non-lethal
70
Define acute inflammation
Short duration (minutes- days); PMNs; exudation.
Complex series of events which include vascular changes, cellular events and mediation by chemical substances (edema, and neutrophil-predominant).
71
Define chronic inflammation
Longer duration; lymphocytes & macrophages; tissue repair
72
What are the agents causing inflammation?
Trauma, immunologic reactions, anoxia, metabolic injury, physical agents (heat, cold), and biologic agents (infection).
73
What are the vascular events of acute inflammation?
1. Transient vasoconstriction of arterioles
2. Vasodilation: first of the arterioles and then the remaining microcirculation. Increased blood flow = redness (rubor), heat (calor).
3. Permeability changes: vascular bed becomes more permeable - allowing leukocytes to exit the bloodstream. Exudation of fluid = edema/ swelling (tumor). With loss of cells and proteins from the intravascular compartment, the viscosity of the intravascular compartment increases, RBC packing occurs, and blood begins to flow more slowly.
74
What're the 6 methods by which the endothelium becomes leaky during inflammation?
1. Endothelial cell contraction leading to wide intercellular gaps.
2. Junctional disruption
3. Direct endothelial injury
4. Leukocyte dependent endothelial injury
5. Increased transcytosis
6. New blood vessel formation
75
What is Starling's hypothesis?
Movement of fluid between vessels and tissue governed by balance between 4 forces. The normal fluid balance is maintained by two opposing sets of forces:
1. Fluid moves out by:
-osmotic pressure of interstitial fluid (very low)
-intravascular hydrostatic pressure (measures 32 mmHg at arterial end, 12 mmHg at venous end)
2. Fluid moves in by:
-osmotic pressure of plasma proteins (= oncotic pressure, = colloid osmotic pressure, COP, -measures 26 mmHg, reflects amount of serum protein - albumin)
-tissue hydrostatic pressure (tissue tension - 3-4 mmHg)
76
Describe transudate
Results from disturbances in starling forces.
Factors that increase intravascular hydrostatic pressure (vasodilation) or decrease intravascular osmotic pressure (decreased albumin) will give a net increase in interstitial fluid and edema.
77
Describe exudate
Results from damage to capillary wall.
In inflammation, leaky endothelium (due to permeability changes) cause loss of high protein fluid and nucleated cells with reduction of intravascular osmotic pressure and increased interstitial osmotic pressure causing further impairment of return of fluid to blood vessels (venules) producing marked inflammatory edema.
78
What are the cellular events of acute inflammation? When do they occur in reference to vascular events?
1. Margination: when blood is viscous WBCs are pushed to the periphery of vessels because of slugding of RBCs (rouleaux formation).
2. Rolling: WBCs tumble and trasiently adhere to the endothelium via selectin molecules.
3. Adhesion: WBCs firmly stick to endothelial surfaces.
4. Transmigration/ Diapedesis: Leukocytes must squeeze between endothelial cells at intercellular junctions and then penetrate the basement membrane.
5. Chemotaxis: chemotactic agents bind GPCR receptors on leukocytes and activate intracellular signalling. Cause movement in certain direction.
6. Activation: Leukocyte surface receptors recognize the offending agents (e.g. microbes) which signals functional response ("activation" - i.e. secretion of cytokines).
7. Phagocytosis: a. Recognition and attachment
b. Engulfment c. Killing and/ or degradation (oxygen-dependent and independent mechanisms).
79
Define Chemotaxis
Unidirectional migration of leukocytes towards an attractant or locomotion oriented along a chemical gradient.
Chemotactic factors can be exogenous or endogenous.
80
What are chemical mediators? What are the general principles of chemical mediators?
Chemical mediators direct the vascular and cellular events in acute inflammation.
-Are produced locally by cells at the site of injury or may be circulating within the plasma
-Most induce their effects by binding to receptors on target cells
-May stimulate cells to release secondary effector molecules
-May act on only a few targets, or may have widespread activity
-Function is generally tightly regulated
-Potential to have harmful effects - why tightly regulated
81
What are the morphological patterns of acute inflammation?
The general histomorphological features of acute inflammation are of dilated small blood vessels and accumulation of neutrophils and fluid in extravascular tissue.
*Occasionally special morphological patterns are superimposed, depending on the cause, severity and the particular tissue/ site involved:
-Serous inflammation
-Fibrinous inflammation
-Suppurative or Purulent inflammation/ abscess
-Ulcer
82
Describe the Serous morphological pattern of inflammation
Usually due to mild injuries
Outpouring of thin fluid derived from plasma or mesothelial cells
In tissues: identified with difficulty (abnormally dilated spaces, fine precipate of protein)
E.g. skin blister from a burn, pleural effusion from an early pneumonia
83
Describe the Fibrinous morphological pattern of inflammation
More severe inflammations (vessels sufficiently damaged to allow passage of large molecules such as fibrinogen, which results in fibrin getting deposited in the extracellular space)
Characteristic inflammation in the lining of body cavitie (eg. meninges, pericardium, pleura) - fibrinous pericarditis of rheumatic fever
Characteristic gross appearance
Microscopically easily identifiable because precipitated fibrin is deeply acidophilic, shows stranding/ banding/ partly fibrillary
If fibrin not removed, may lead to scar
84
Describe the Suppurative or Purulent morphological pattern of inflammation (abscess)
Characterized by the accumulation of pus/ purulent exudate (=neutrophils, liquefactive necrosis, edema fluid)
Certain bacteria characteristically produce pyogenic infections and are therefore referred to as pyogenic ("pus producing") bacteria
- Abscess vs Empyema
85
Define abscess
Localized collections of purulent exudate in tissue
86
Define Empyema
Localized collections of purulent exudate in pleural cavity
87
Describe Ulcer morphological pattern
An epithelial surface has become necrotic and eroded, with associated sub-epithelial acute and chronic inflammation
e.g. peptic ulcer disease exudate containing a large number of RBCs
88
What are the outcomes of acute inflammation?
1. Complete resolution
2. Healing by connective tissue replacement
3. Progression to chronic inflammation
89
Describe chronic inflammation
Lasts 2 weeks or longer.
Microscopic features include a mononuclear-predominant inflammatory infiltrate, tissue destruction, and tissue replacement by proliferative connective tissue (attempts at repair).
Sometimes preceded by unsuccessful acute inflammation but also occurs without any.
90
What are the two forms that chronic inflammation are subdivided into?
1. Non-specific: chronic inflammation as microscopic features are described
2. Granulomatous: special type of tissue reaction where body attempts to wall-off and isolate the affected site. Granuloma is composed of a central focus usually of necrotic tissue surrounded circularly by macrophages (usually modified to epithelioid cells, which are surrounded by a rim of lymphocytes.
Cytokines IL2 and IFN-gamma are important for immune granulomas.
91
What are the two types of clinical manifestations of inflammation?
Local and systemic
92
Describe the local manifestations of inflammation
Cardinal signs and symptoms of inflammation:
-rubor = redness
-calor = heat
-tumor = swelling
-dolor = pain
-functio laesa = impaired function
93
Describe the systemic manifestations of inflammation
SIRS - Systemic Inflammatory Response Syndrome consists of several clinical and pathological changes:
-Fever
-Acute phase reactants (plasma proteins - mostly synthesize in the liver - which increase in response to inflammation)
-Leukocytosis
-Other (increased heart rate, increased blood pressure, decreased sweating, rigors - shivers, anorexia, somnolence)
94
What is Pyrogen?
Any substance capable of producing fever
95
What are the two types of reactions of tissue repair?
1. Regeneration: The cells replacing those lost in inflammation are identical cells to those lost. This occurs by proliferation of uninjured residual cells and/ or maturation of tissue stem cells.
2. CT deposition / scar formation: The cells replacing those lost in inflammation consist of different cells to those lost. This occurs by the laying down of connective (fibrous) tissue i.e. scarring
*Both can contribute to, in varying degrees, to tissue repair
96
What decides whether regeneration alone can provide tissue repair?
Depends upon:
1. Proliferative potential of the cell type affected
2. Whether or not there has been damage to the extracellular matrix (ECM)
97
What are the 3 groups that the cells of the body are divided into based on their regenerative capacity?
Which cells result in healing by regeneration alone, and which result in healing by CT deposition/ scarring?
-Labile Cells: Continue to proliferate throughout life. (E.g. Epidermis, epithelia lining body cavity, blood cells)
-Stable cells: Low normal level of replication but able to divide in response to stimuli. Considered to be in G0 phase, but can be stimulated to re-enter the cell cycle. (Epithelia of most parenchymal organs)
-Permanent cells: Cannot divide in post-natal life. These cells have left the cell cycle (e.g. cardiac muscle).
*Damage to labile and stable cells may result in healing by regeneration, depending on whether there has also been damage to the ECM.
*Damage to permanent cells will result in healing by CT deposit/ scarring.
98
List the sequential steps of cutaneous wound healing (example of CT deposition/ scarring)
1. Hemostatic plug / crust formation (provides a quick provisional closure to the wound)
2. Inflammatory Phase
3. Proliferative Phase (granulation tissue + re-epitheliazation)
4. Remodelling/ Cicatrization (conversion of loose CT in the granulation tissue to a stable fibrous scar)
99
What is cutaneous healing by first intention (or primary repair/ union)?
Type of cutaneous wound repair that follows when the edges of the wound are in apposition
100
What is cutaneous healing by second intention (or secondary repair/ union)?
Type of cutaneous wound repair that follows considerable loss of tissue and the edges of the wound cannot be approximated
101
What are the complications of cutaneous wound healing?
-Deficient scar formation = dehiscence
-Excessive scar formation (hypertrophic scar or keloid)
-Contractures (permanent tightening of the muscles, tendons and skin, causing joints to shorten and become very stiff).
102
What are the local factors which negatively influence the rate of healing?
-Decreased blood supply
-Denervation
-Local infection
-Foreign bodies
-Necrotic tissue
-Mechanical stress
-Hematoma
-Increased size of the wound
103
What are the systemic factors which negatively influence the rate of healing?
-Decreased blood supply
-Age
-Anemia
-Malignancy
-Malnutrition
-Obesity
-Infection
-Organ failure
104
What is Neoplasia? Define Neoplasm
New growth = tumour
Neoplasm: an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists in the same excessive manner after the cessation of the stimulus which evoked the change.
105
Define the following:
Oncology?
Cancer?
Malignant tumour?
Benign tumour?
Oncology: (oncos = tumour) study of tumours
Cancer: malignant neoplasm
Malignant tumour: tumour that invades and spreads to distant sites
Benign tumour: tumour that does not invade or spread.
106
How are benign tumours named? What are some examples and some exceptions?
Have suffic "oma" following tissue type. Majority are named by tissue type, some are named by architectural patterns.
E.g. Adenoma: benign tumour that forms gland or originating from glands.
Papilloma: benign tumours with finger-like projections
Polyp: elevated mucosal lesions (descriptive term)
Nevus: benign tumour of melanocytes
exceptions: melanoma/ lymphoma
107
How are malignant tumours named? What are some examples?
A similar system as benign neoplasms is used. Malignant tumours composed of mesenchymal cells are called sarcoma (sar= fleshy). Malignant tumours composed of epithelial cells are called carcinoma.
E.g. Adenocarcinoma: malignant epithelial tumour with cells forming glandular growth pattern
Squamous cell carcinoma: malignant epithelial tumour composed of squamous cells
Fibrosarcoma: malignant tumour composed of fibrous tissue.
Leiomyosarcoma: malignant tumour of smooth muscle
108
What is a Teratoma?
Consists of 2 or more germ layers arising from mesenchymal cells. Ovary & testis. Could either be benign or malignant.
108
What is a Teratoma?
Consists of 2 or more germ layers arising from mesenchymal cells. Ovary & testis. Could either be benign or malignant. Can sometimes open them up and they are full of hair or teeth - differentiate around the diff germ layers. Often benign - cured by taking out.
109
What are Choristoma and Hamartoma?
Choristoma: Ectopic rest. Not more than one germ layer - disorganized tissue - tissue not usually there e.g. adrenal tissue where it is not supposed to be - hernia.
Hamartoma: disorganized normal tissue in normal location. Not more than one germ layer, made up of tissue normally there. E.g. lung hamartoma, cartilage, fat and epithelium - usually there in lungs.
110
Define edema. What is the normal control mechanism opposing edema?
Accumulation of abnormal fluids in the interstitial/ intercellular tissue - swelling of the subcutaneous tissues.
Normal control mechanism depends on starling's law.
111
Define homeostasis
Process of maintaining a constant internal environment despite changing external conditions. Several factors must be regulated including:
Temperature
Heart rate
Respiratory rate
Blood pressure
Water balance
Blood sugar levels
112
What conditions will edema occur under?
1. An increase in intravascular hydrostatic pressure: due to increased venous pressure (e.g. congestive heart failure - right side failure - peripheral edema, deep venous thrombosis of lower legs)
2. A fall in colloid osmotic pressure of plasma: due to hypoproteinemia (e.g. liver disease as cirrhosis - decrease synthesis of albumin, renal failure - loss of albumin in urine, malnutrition)
3. Lymphatic obstruction: accumulation of interstitial fluid because of insufficient reabsorption and deficient removal of proteins, the latter increasing the oncotic pressure of the fluid in the interstitial space (e.g. cancer, inflammation, postsurgical lymphedema)
4. Sodium retention: causes both increase in hydrostatic pressure and reduced vascular osmotic pressure. (e.g. kidney disease)
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What are the two types of edema classifications?
-Localized edema: occurs due to 1. increased hydrostatic pressure due to vascular obstruction 2. lymphatic obstruction: compression by tumour or inflammation.
-Generalized edema: occurs due to 1. increased hydrostatic pressure (heart failure) 2. decreased oncotic pressure (colloid osmotic pressure) due to - loss of albumin in renal failure - decreased synthesis of albumin (liver failure) 3. Sodium retention - kidney disease
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What is Hyperaemia?
The tissue appears red - because of engorgement with oxygenated blood.
E.g. Acute inflammation, skeletal muscle during exercise
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What is congestion?
Impaired venous drainage results in stasis and the accumulation of deoxygenated blood. Due to increase in venous hydrostatic pressure.
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Define Thrombosis. What is a thrombus?
Formation of mass (clotted blood) in the heart or blood vessels.
Mass is called "thrombus" and it consists of:
-Red blood cells
-White blood cells
-Platelets
-Fibrin
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What are the causes of thrombosis?
-Vessel wall damage/ alteration: injury / tear, inflammation
-Changes in blood flow: stasis (slow circulation), lack of activity, decreased cardiac output, increased blood viscosity
-Changes in blood composition
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What is the Prognosis (outcome) of thrombosis?
-Obstruct vessels
-Breakdown - emboli
-Dissolved
-Organized and may recanalize
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What are the complications thrombi?
-Fragments of thrombus break off and result in thromboembolization / emboli
-Reduced blood flow to a tissue / organ resulting in ischemic injury or infarction
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Define embolism
Occlusion (blockage) of a blood vessel by a mass (embolus) transported to the site through the blood stream.
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What are the different types of embolism? Prognosis? Complications?
-Thrombi (most common type, thromboemboli arise from thrombi and range in size, may occur in either arteries or veins.
-Gas (air) = divers
-Fat = often fracture of large bones
-Tumour
-Other = foreign body, drug addicts
*The prognosis and complications are very similar to that of Thrombosis / Thrombus (can undergo: lysis, propagation, organization and/ or recanalization, can result in ischemic injury and infarction)
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What are the causes of Ischemia? Effects?
-Decreased blood supply (inadequate blood supply)
-Obstruction of blood vessel by : thrombus, embolus, pressure (outside pressure), damage of the vessel wall (inflammation)
*Effects: depends on degree of ischemia. No effects if there is alternate blood supply. Tissue death (infarction) if severe and complete.
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What is infarction?
An area of necrosis which typically is produced by ischemia. Infarct area is wedge-shaped. Infarction is an irreversible process and healing occurs by fibrosis.
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What are the types of infarct?
-White infarct (arterial occlusion, solid organs as heart, spleen, kidney and brain, leg gangrene)
-Red infarct (venous or arterial occlusion, loose tissue as lung, dual blood supply, and brain and intestine).
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Define Hemorrhage
Hemorrhage (bleeding): a discharge or escape of blood from the blood vessels into the surrounding tissues or to the exterior of the body or into a body cavity.
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What are the causes of hemorrhage?
-Trauma to large blood vessels due to surgical procedures or fracture
-Weakened artery (from atheroslcerosis, e.g. abdominal aortic aneurysm; congenital weakness, e.g. berry aneurysm in Willis circulation)
-Infections (e.g. pulmonary tuberculosis)
-Invasive tumours (erosion of vessel wall)
-Hypertension (increase intraluminal blood pressure)
-Hemorrhagic diatheses (spontaneous hemorrhage): affecting capillaries including -thrombocytopenia, severe decrease in number of platelets, deficiency of coagulation/ clotting factors
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What is hematoma?
Bleeding into the soft tissues
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What is purpura?
Diffuse, superficial hemorrhages in the skin, as large as 1 cm
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What is ecchymosis?
A larger superficial hemorrhage (e.g. black eye); skin discolouration reflects products of heme degradation from hemoglobin in the RBCs.
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What is petechia?
A pinpoint hemorrhage (1-2 mm) usually in the skin; represent rupture of capillaries or arterioles and mainly involving skin, mucous membranes, and serosal surfaces.
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What is hemothorax/ hemopericardium?
Collection of blood in the pleural cavities due to trauma or rupture of aorta. Collection of blood in the pericardial cavity around heart due to rupture of heart or aorta.
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What is hemoperitoneum?
Collection of blood in the abdominal cavity due to rupture of an aortic aneurysm or trauma to liver, spleen aorta.
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What is hemoarthrosis?
Collection of blood in joint
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Define shock
Characterized by failure of the circulatory system to maintain an appropriate blood supply to the microcirculation with resultant inadequate perfusion of vital organs.
*Generalized inadequate perfusion of all cells and tissue of vital organs.
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What is shock due to?
-Decreased blood volume
-Decreased cardiac output
-Redistribution of blood
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What are the types of shock?
1. Hemorrhagic/ hypovolemic
2. Cardiogenic
3. Septic
4. Anaphylactic/ Neurogenic
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Describe Hypovolemic shock (hemorrhagic)
Due to loss of fluid from the vascular compartment (decreased blood volume)- as a result of:
-Loss of blood - hemorrhage (external) or massive internal hemorrhage
-Decrease plasma volume (burns)
-Fluid loss e.g. diarrhea, excessive urine formation, sweating or vomiting
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Describe Cardiogenic shock
Inability of the heart to pump blood (myocardial infarction, pericardial tamponade - fluid accumulates in the pericardium around the heart)
Extensive impairment of cardiac output (pulmonary embolism)
*Hypovolemic and cardiogenic shock result in decreased perfusion.
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Describe Septic shock
Bacteremia
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Describe Anaphylactic / Neurogenic shock
Anaphylaxis: allergic condition
Neurogenic: anaesthesia, injury of spinal cord
*Peripheral vasodilation associated with anaphylaxis, neurogenic, and septic shock (due to release of factors (cytokines, bacterial endotoxins, etc.) that cause dilation and increased permeability of the vessels).
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What is the effect of shock?
The result of decreased tissue perfusion is hypoxic or anoxic cell injury which may lead to further decline in cardiac output (for example as a result of renal failure, further endothelial cell damage).
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Features of anaplastic (undifferentiated) cells?
-Variable cell size & shape (cellular pleomorphism)
-Variable nuclear size & shape (nuclear pleomorphism)
-Hyperchromatic nuclei
-Increased mitosis and atypical mitosis
-Loss of polarity
-Tumour giant cell
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What are the phases of malignant tumour growth?
1. Transformation
2. Growth of transformed cell
3. Local invasion
4. Distant metastases.
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What is grading?
An estimate of aggressiveness of the neoplasm and based on the level of differentiation.
*commonly based on differentiation, mitosis, and necrosis
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What is staging?
Based on tumour size, lymph node spread, and metastasis to other organs. Staging is based on size of primary lesion, extent of spread to regional lymph nodes, and the presence or absence of blood-borne metastases.
Clinical staging: based on evidence acquired prior to the decision as to definitive treatment.
Pathological staging: includes information obtained at surgery and from examination of tissues by the pathologists.
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List 4 types of carcinogenic agents
Chemicals
Physical agents (such as radiation)
Oncogenic virus
Bacteria
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What are the two classes of oncogenic viruses?
1. DNA oncogenic viruses
2. RNA oncogenic viruses
