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Patho 2023 > Pathophysiology (Exam 4) > Flashcards

Pathophysiology (Exam 4) Flashcards

1
Q

what are the mechanisms that cells respond to injury

A
  1. homeostasis
  2. adaptation
  3. cell injury
  4. cell death
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2
Q

what is homeostasis?

A

Cells maintain their intracellular environment within a narrow range of physiological parameters

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3
Q

what is adaptation

A

As cells encounter physiological stresses or pathological stimuli, they can undergo adaptation, achieving new steady state and preserving viability and function by changing their size, number, and form
1. this involves the 5 forms

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4
Q

what is cell injury

A

Occurs when cells are stressed to the point that they are unable to adapt

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5
Q

what is cell death

A

Is one of the most crucial events in the evolution of disease in any tissue or organ
Can lead to necrosis or apoptosis

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6
Q

what are the 5 major cellular adaptations in response to injury or stimuli

A

Hypertrophy
Hyperplasia
Atrophy
Metaplasia
dysplasia

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7
Q

what is hypertrophy

A

An increase in the size of cells resulting in increase in the size of an organ

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8
Q

where does hypertrophy only occur (and example)

A
  • in cells capable of dividing
    –> Striated muscle cells in both skeletal muscle and heart
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9
Q

hypertrophy is commonly caused by increased workload which includes _____?

A
  1. Physiological stimuli
    - Estrogen-induced uterus enlargement during pregnancy
  2. Pathological conditions
    - Hypertension
    - Aortic valve
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10
Q

what is hypertrophy characterized by and examples

A
  1. increased protein synthesis
    –>Mechanical triggers such as stretching
    –> Hormonal triggers like adrenergic hormones
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11
Q

what is hyperplasia

A
  • Increase in the number of cells
    –> Not cell size
  • Can be pathological or physiological
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12
Q

what are examples of physiologic hormonal hyperplasia

A

Proliferation of the female mammary epithelium during puberty

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13
Q

what is an example of physiologic compensatory hyperplasia

A

Regeneration of partially resected liver by the remaining hepatocytes or liver cells

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14
Q

what are examples of pathologic hyperplasia

A
  • Typically the result of excessive hormonal or growth factor stimulation
  • Hyperplastic tissue may eventually become malignant
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15
Q

hyperplasia has a specific example of proliferation. what is it?

A

proliferation of connective tissue cells during wound healing

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16
Q

what is atrophy

A
  • Shrinkage in the cell size of the cell by the loss of cell substance
    –> No decrease in cell number
    –> Decrease in size of tissue or organ
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17
Q

what is atrophy frequently caused by:

A
  1. Decreased workload
  2. Loss of innervation
  3. Reduced blood supply
  4. Inadequate nutrition
  5. Aging
    –> Senile atrophy
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18
Q

what is the decreased in cell size in atrophy caused by:

A
  1. Increased protein degradation
  2. Reduced protein synthesis
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19
Q

what is metaplasia

A
  • Reversible change in which one adult cell is replaced by another adult cell
  • Often is a response to chronic inflammation and irritation that makes cells better able to withstand stress
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20
Q

what are examples of metaplasia

A
  1. Barretts esophagus
  2. Ciliated columnar epithelial cells of the trachea and bronchi help clear foreign materials and mucous
  3. In smokers, they may be replaced by squamous epithelial cells, which are more rugged but not ciliated
  4. This leads to coughing and increase in infections
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21
Q

why is metaplasia a precursor to malignancy

A

May be caused by reprogramming of stem cells rather than by transdifferentiation of mature cells

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22
Q

what is dysplasia

A

Characterized by deranged cellular growth of a specific tissue that results in cells that vary in size, shape, organization, and number
1. Adaptive in that it is potentially reversible after irritating cause has been removed

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23
Q

what is dysplasia associated with

A

chronic irritation and inflammation

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24
Q

when does dysplasia often occur

A

in metaplastic squamous epithelium in respiratory tract and uterine cervix

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25
Q

dysplasia is a strong precursor of malignancy; what is a cancer example?

A

Pap smears (cervical cancer)
– every 3 years from age 21
– 3-5 years hav test for ages 30-65

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26
Q

what two cellular adaptations can cause cancer

A
  1. metaplasia
  2. dysplasia
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27
Q

what are the 8 causes of cell injury

A
  1. oxygen deprivation
  2. chemical agents
  3. infectious agents
  4. immunological reactions
  5. genetic defects
  6. physical agents
  7. nutritional imbalances
  8. aging
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28
Q

what are examples for oxygen deprivation

A
  1. Hypoxia- oxygen deficiency
    –> Inadequate oxygenation of the blood- pneumonia
    –> Reduction in oxygen-carrying capacity of the blood- blood loss anemia or carbon monoxide poisoning in which forms a stable complex with hemoglobin that prevents oxygen binding
  2. Ischemia- loss of oxygenated blood supply to tissues
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29
Q

what are examples of chemical agents

A

Poisons, air pollutants, CO, asbestos

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30
Q

what are examples of infectious agents

A

Viruses, bacteria, fungi, parasites

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31
Q

what are examples of immunological reactions

A

Autoimmune diseases

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32
Q

what are examples of genetic diseases

A

Sickle cell anemia, familial hypercholesterolemia

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33
Q

what are examples for physical agents

A

Trauma, heat, cold, electric shock

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34
Q

what are examples for aging

A
  • Accumulation of damage by ROS
  • Loss of telomerase function
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35
Q

what are examples of nutritional imbalances

A
  • Typically indirect cause of injury
    1. Nutrition; deficiencies
    –> Caloric or vitamin
    2. Excess nutrition
    3. Diabetes
    –> Can be caused by obesity
    ——– Excess blood sugar can damage cells
    4. Atherosclerosis
    –> Can be caused by diet rich in fats
    ——– Can result of blockage of coronary arteries
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36
Q

what are the characteristics of reversible injury

A

cellular swelling and fatty change

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37
Q

explain cellular swelling

A

Result of failure of energy-dependent ion pumps in the plasma membrane, leading to an inability to maintain ionic and fluid homeostasis

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38
Q

examples fatty change

A

Occurs in hypoxic injury and various forms of toxic or metabolic injury, and is manifested by the appearance of small or large lipid vacuoles in the cytoplasm. Mainly occurs in cells involved in metabolism such as hepatocytes and myocardial cells

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39
Q

explain irreversible injury

A
  1. Inability to reverse mitochondrial dysfunction
    –> Lack of oxidative phosphorylation and ATP generation
  2. Profound disturbances in membrane function
    –> Membrane dysfunction
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40
Q

what is apoptosis

A

phagocytosis of apoptotic cells and fragments

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41
Q

what is necrosis

A

enzymatic digestion and leakage of cellular contents

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42
Q

what are the physiological causes of the apoptotic pathways

A
  1. Programmed destruction of cells during embryogenesis: many
  2. Involution of hormone-dependent tissues upon hormone deprivation: endometrial cell breakdown during menstrual cycle
  3. Cell loss in proliferating cell populations: intestinal crypt epithelia
  4. Elimination of potentially harmful self-reactive lymphocytes: before or after maturation
  5. Cell death induced by cytotoxic T lymphocytes
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43
Q

what are the pathological causes of the apoptotic pathways

A

DNA damage; accumulation of misfolded proteins; cell injury in certain infection (viral infections); pathological atrophy in parenchymal organs after duct obstruction (pancreas, kidney, and parotid gland)

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44
Q

what is the intrinsic pathway

A
  1. Mitochondrial (intrinsic) pathway
    - Cell injury
    GF withdrawal
    –> DNA damage (radiation, toxins, free radicals)
    –> Protein misfolding (ER stress)
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45
Q

what is the extrinsic pathway

A
  1. Death receptor (extrinsic) pathway
    - Receptor-ligand interactions
    –> Fas
    –> TNF receptor
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46
Q

what are the two apoptotic pathways

A

intrinsic and extrinsic

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47
Q

what is the role of BCL-2 in apoptosis

A
  • Bax, Bak, and Bad proteins can increase mitochondrial membrane permeability by forming a dimer and inserting into the mitochondrial membrane. So this is called pro-apoptotic proteins
  • Bcl-2 and Bcl-x can bind Bax family proteins and inhibit their function so this is called anti- apoptotic proteins
    1. central players
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48
Q

what is the role of Cytochrome C in apoptosis

A
  • Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases)
  • released from mitochondria can activate caspase-9 to initiate caspase cascade
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49
Q

what is the role of the 2 types of caspases in apoptosis

A

Initiators and executioner (caspase-3 and 7)

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50
Q

what is the role of activated caspases

A
  1. activate other proteases
    –> Degradation of cytoskeletal proteins
  2. can activate endonucleases
    –> Cleavage of DNA leading to DNA fragmentation (DNA ladder)
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51
Q

what is the role of blebs formation

A

Dying cells collapse into cytoplasmic buds and apoptotic bodies

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52
Q

what is the role of phagocytosis in apoptosis

A
  • bodies of macrophages
  • Dead cells are cleared before they can release their cytoplasmic contents
  • Prevents triggering an inflammatory response
  • Nothing remains of dead cell
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53
Q

what mechanisms of cell injury are there

A
  1. ATP depletion
  2. mitochondria damage
  3. membrane damage
  4. increased ROS
  5. calcium influx
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54
Q

what is the cell size of necrosis vs. apoptosis

A

necrosis: enlarged
Apoptosis: reduced

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55
Q

what is the nucleus of necrosis and apoptosis

A

necrosis: Pyknosis → karyolysis
Apoptosis: Fragmentation into nucleosome sized fragments

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56
Q

what is the plasma membrane for necrosis and apoptosis

A

necrosis: disrupted
apoptosis: Intact, but altered structure

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57
Q

what is the cellular contents of necrosis and apoptosis

A

necrosis: enzymatic digestion, leakage
apoptosis: Intact, in apoptotic bodies

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58
Q

what is the inflammation in necrosis and apoptosis

A

necrosis: frequent
apoptosis: none

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59
Q

does necrosis or apoptosis deal with physiologic or pathologic roles

A

necrosis: Invariably pathologic
apoptosis: Often physiologic; may be pathologic

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60
Q

what are the characteristics of acute inflammation

A
  1. Rapid in onset and short duration
    –> Minutes to days
  2. Accumulation of fluid and plasma proteins
    –> Exudation
  3. Accumulation of neutrophils
  4. Tumor necrosis factor (TNF), interleukin-1 (IL-1), chemokines
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61
Q

what are the characteristics of chronic inflammation

A
  1. Insidious and of longer duration (months to years)
  2. Tissue destruction by inflammatory cells
  3. Vascular proliferation and fibrosis
    –> Scarring
  4. Influx of lymphocytes and macrophages
  5. Interferon- y (IFN-y) by T cells and interleukin-I2 (IL-I2) by macrophages
    –> Synergistic stimulation
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62
Q

what are some characteristics of inflammation

A
  • Occurs upon infections or noxious stimuli
    –> Injuries, burns, foreign bodies, etc.
  • Eliminates harmful agents and necrotic cells
    –> Microbes and toxins
  • Initiates the healing process
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63
Q

inflammation can cause injury but what are the different types of responses

A
  1. Too strong response
    –> Severe infection
  2. Prolonged response
    –> Persistent or recurrent infection
  3. Inappropriate response
    –> Self-antigens in autoimmune diseases
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64
Q

what are some pharmacologic approaches of inflammation

A
  1. Glucocorticoids
  2. NSAIDs
  3. Antihistamines
  4. Leukotriene antagonists
  5. Biologics targeting cytokine signaling
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65
Q

what are the characteristics

A
  1. Heat
    – calor
  2. Redness
    – rubor
  3. Swelling
    – tumor
  4. Pain
    – dolor
  5. Loss of function
    – Functio laesa
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66
Q

what are the events occurring during the acute inflammation response

A
  1. Phagocytosis in tissues recognize offending agents and liberate chemical mediators of inflammation
  2. Chemical mediators widen blood vessels (vasodilation) and increase their permeability in the vicinity
  3. Plasma and circulating leukocytes diffuse to the location of the offending agents
    –> Leukocyte recruitment
  4. Activated leukocytes remove the offending agents
    –> Phagocytosis
  5. Leukocytes produce signaling molecules that suppress inflammation
    – Lipoxins
  6. The damaged tissue is repaired
    – Cell proliferation
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67
Q

what are some vascular stages responses

A
  1. vasodilation
  2. increased lipophilicty
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68
Q

whaat are some stages of cellular acute inflammation

A
  1. Leukocyte recruitment
  2. phagocytosis
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69
Q

what results in vasodilation

A
  1. Decrease in fluid velocity
  2. Increased viscosity
    –> Due to fluid loss to tissues
  3. Increased leukocytes settling along the inner surface of the blood vessels
    –> margination
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70
Q

what results in increased lipophilicty

A
  1. Gaps due to endothelial contraction
    –> Most common mechanism
    –> Histamines, leukotrienes, bradykinin
  2. Increase fluid life through endothelial cells
    –> transcytosis
  3. Direct endothelial traumatic injury
  4. Leukocyte dependent endothelial cell damage/death due to release of toxic mediators by leukocytes
  5. Leakage from new blood vessels that form at the site of injury
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71
Q

what changes can result from vascular changes

A
  1. Transudate
    –> Small holes
    –> Plasma with little proteins
    –> No cells
  2. Exudate
    –> Bigger holes
    –> Protein rich fluid with numerous cells
  3. Edema
    –> Accumulation of fluid and swelling at site of inflammation
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72
Q

what are the secret of events in leukocyte recruitment

A
  1. Margination
  2. Loose attachment and rolling
    –> Selectins
  3. Adhesion
    –> Integrins
  4. Transmigration
  5. Chemotaxis
    –> Bacterial products
    —–> LPS
    –> Chemokines
    –> Complement system
    —–> C5a
    –> Leukotriene B4 (LTB4)
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73
Q

what is involved in the recognition of phagocytosis

A

direct and indirect

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74
Q

what is the engulfment of phagocytosis

A
  • Receptor-mediated endocytosis
  • Pseudopods extend around foreign body and form a phagosome
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75
Q

what is the intracellular killing of phagocytosis

A
  1. Fusion of the phagosome with a lysosome (phagolysosome)
  2. Lysosomal degradation
    –> Digestive enzymes and defensins
  3. Release of toxic nitrogen and oxygen compounds (oxidative burst)
    –> H2O2, hydrochloric radical, NO
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76
Q

what is involved in direct recognition

A
  • microbes by pattern recognition receptors
    –> Toll-like receptors — LPS, flagellin, etc.
    –> Mannose receptors
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77
Q

what is involved in indirect recognition

A
  • Opsonins: IgG, C3b, and collectins (carb-binding lectins)
  • Coat of foreign body and dead cells
    –> Opsonization
  • Specific receptors recognize opsonins
    –> Fc receptor; C3b receptor
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78
Q

what are the functions of histamines

A
  • First mediator released upon acute inflammation but transient
  • Binds to type 1 receptor on endothelial cells and causes vasodilation and increases vascular permeability
  • H1 receptor antagonists are used as antihistamine drugs
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79
Q

what are the roles of PAF

A
  • Generated from phospholipids by phospholipase A2
  • Induces platelet aggregation
  • 100-1000 times more potent than histamine in inducing inflammation reactions
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80
Q

what are the roles of eicosanoids

A
  • Derived from polyunsaturated fatty acids such as arachidonic acid
  • has COX pathway
  • has lipoxygenase pathway
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81
Q

what is the cox pathway

A
  1. Prostaglandins
    - Complex inflammatory responses including fever and pain
  2. Thromboxane
    - Vasoconstriction, platelet aggregation
    - Inhibited by NSAIDs
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82
Q

what is the lipoxygenase pathway

A
  1. Leukotrienes
    - Similar to histamine but more potent and long acting
    - Significant contributors to allergic reactions
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83
Q

what are the 3 roles of plasma membranes

A
  1. thrombin and fibrinopeptides in clotting system
  2. bradykinin in the kinin system
  3. C3a, C5a, C3b in the complement system
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84
Q

describe the thrombin and fibrinopeptides in clotting system

A
  1. Thrombin activates leukocytes
  2. Fibrinopeptides, produced from digestion of fibrinogen by thrombin, increase vascular permeability; chemotactic
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85
Q

describe the C3a, C5a, C3b in the complement system pathway

A
  1. C3a and C5a increase vascular permeability and cause vasodilation (anaphylatoxins)
  2. C5a activates leukocytes; chemotactic
  3. C3b acts as opsonin
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86
Q

describe the bradykinin in the kinin system process

A
  1. Formed by cleavage of kinogens by a protease kallikreins
  2. Increases vascular permeability and causes vasodilation
  3. Causes pain
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87
Q

what is the function of cytokines

A
  1. Serotonin is transient and tightly regulated
  2. Have pleiotropic and redundant functions
  3. TNF-a and IL-1 and chemokines
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88
Q

describe TNF-a and IL-1

A
  1. The major cytokines that mediate inflammation
  2. Produced by many cells, but activated macrophages are the major source
  3. Generate cellular and systemic responses
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89
Q

describe chemokines

A
  1. Chemotactic cytokines
  2. Recruit and direct the migration of immune and inflammatory cells
  3. Generate a persistent chemotactic gradient
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90
Q

describe nitric oxide

A
  1. Short lived, local acting (seconds)
  2. Synthesized by inducible NO synthase (iNOS), which is induced by inflammatory cytokines and mediators
  3. Relaxation of vascular smooth muscle (vasodilation)
  4. Antimicrobial agent in activated macrophages
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91
Q

describe reactive oxygen species

A
  1. Short lived
  2. Synthesized by NADH oxidase pathway
  3. Superoxide radical, hydrogen peroxide, and hydroxyl radical
  4. Released extracellularly by neutrophils and macrophages after stimulation
  5. May cause tissue injury
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92
Q

describe tissue injury by lysosomal proteases

A
  1. Release of lysosomal constituents into the extracellular space
    –> Matrix degradation
    –> Destructive tissue injury
  2. Antiproteases inhibit lysosomal proteases
    –> A2-macroglobulin, al- antitrypsin, etc.
    –> Exist in the serum and extracellular matrix
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93
Q

what are the causes of lysosomal proteases

A
  1. Premature degranulation of lysosomes
  2. Phagocytosis attempts of large, flat surfaces (frustrated phagocytosis)
  3. Damage of leukocytes (ex. Urate crystals of gout)
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94
Q

what mediators are responsbile for plasma

A
  1. Factor 7
  2. Complement proteins
  3. acute-phase
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95
Q

what mediaotrs are responsible for cell derived

A
  1. performed
  2. newly synthesized
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96
Q

what mediators are responsible for vasodilation

A

Histamine, serotonin, PAF, kinins, complement

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97
Q

what mediators are responsible for increase vascular permeability

A

Histamine, serotonin, leukotrienes, PAF, kinins, prostaglandins

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98
Q

what mediators are responsible for chemotaxis

A

Leukotrienes, prostaglandins, chemokines, complement

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99
Q

what mediators are responsible for vascular smooth muscle relaxation

A

nitric oxide

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100
Q

what mediators are responsible for leukocyte activation

A

Leukotrienes, complement

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101
Q

what mediators are responsible for local endothelial activation

A

Cytokines (TNF, IL-1)

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102
Q

what mediators are responsible for killing of microbes

A

Nitric oxide, ROS

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103
Q

Describe the mechanism of the reciprocal relationship between macrophages and lymphocytes in chronic inflammation.

A
  1. Activated by macrophages presenting antigen fragments
  2. Activated lymphocytes release mediators including IFN-y
  3. IFN-y activates macrophages
  4. Activated macrophages release cytokines including IL-12
  5. IL-12 further activates lymphocytes
  6. Macrophages and lymphocytes persistently stimulate one another until the triggering antigen is removed
  7. Plasma cells, eosinophils, and mast cells are also present in chronic inflammation
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104
Q

explain the roles of macrophages

A
  1. Derived from circulating blood monocytes
  2. Activated by cytokines, bacterial products, mediators of inflammation, dead cells, etc → epithelioid macrophages
  3. Release various products, may cause tissue injury
  4. Macrophage accumulation persists in chronic inflammation
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105
Q

explain the role of lymphocytes

A
  1. B Cell, T cells, Natural Killer Cells
  2. A lymphocyte is a type of white blood cell in the immune system of most vertebrates
  3. Main type of cell found in lymph
  4. In chronic inflammation
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106
Q

what are the examples about macrophages in the release of products that may result in tissue injury

A
  1. Proteases
  2. Complement components, coagulation factors
  3. ROS and NO
  4. Eicosanoids
  5. Cytokines
  6. Growth factors → fibrosis
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107
Q

what is granulomatous inflammation

A
  1. Distinctive form of chronic inflammation
  2. Formation of granuloma
    –> Small (1-2 mm) lesion of epithelioid macrophages surrounded by lymphocytes
  3. Foreign body giant cells
    –> Multinucleated cells formed by coalesced macrophages
    –> Encapsulate and isolate the offending agents
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108
Q

what is granulomatous inflammation caused by ___

A
  1. offending agents not easily controlled by other inflammatory mechanisms
    –> Foreign bodies such as splinters, sutures, silica, and asbestos
    –> Microorganisms that cause tuberculosis, syphilis, sarcoidosis, deep fungal infections, and brucellosis
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109
Q

what is tissue regeneration?

A

Replacement of injured tissue with cells of the same type and function

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110
Q

what is tissue repair

A

Occurs when extent or nature of damage cannot be reversed by regeneration alone

111
Q

State the 4 stages of healing after tissue injury.

A
  1. hemostasis
  2. inflammation
  3. proliferation
  4. remodeling
112
Q

describe hemostasis

A
  1. Results in local vasoconstriction and activation of platelets and clotting factors to form a fibrin clot
  2. Creates a scaffold for migrating cells
  3. minutes
113
Q

describe inflammation

A
  1. hours
  2. Driven by platelet-derived mediators, bacteria, and secreted chemoattractants
114
Q

describe proliferation

A
  1. days
  2. Mediated by macrophage and fibroblast-derived growth factors
115
Q

describe remodeling

A
  1. weeks to months
  2. Transition from type 3 and type 1 collagen, restoring tensile strength of tissue
116
Q

State the common outcome of various signal transduction pathways of growth factors.

A

results in the change of gene expression

117
Q

what are the two forms of ECM and their key components

A

basement membrane and interstitial matrix

118
Q

describe the basement membrane

A
  1. Type 4 collagen
  2. Laminin
  3. proteoglycan
119
Q

describe the interstitial matrix

A
  1. Fibrillar collagens
  2. Elastin
  3. Proteoglycan and hyaluronan
120
Q

what are the determinants of regeneration vs. repair after tissue injury.

A
  1. nature of cells injured
  2. extent of injury
  3. underlying disease
  4. Presence or absence of ongoing inflammation
121
Q

describe the nature of cells injured

A

some cells (ex: adult cardiac myocytes) have marginal renewal capacity

122
Q

describe the extent of injury

A

The magnitude of injury may exceed regeneration capacity

123
Q

describe the underlying disease determinant

A

May impair proliferative response or remodeling (ex: diabetes)

124
Q

describe the Presence or absence of ongoing inflammation

A

Due to concurrent infection or other factors, continued release inflammatory mediators may disrupt balance toward repair

125
Q

what are the three key growth factors that regulate fibrosis.

A

PDGF, TFGb, & FGF-2de

126
Q

describe PDGF

A
  1. Platelet-derived growth factor
  2. Migration and proliferation of fibroblasts, smooth muscle cells, and macrophages
127
Q

describe TGFb

A
  1. Transforming growth factor
  2. Potent fibrogenic factor that stimulates collagen, fibronectin, and proteoglycan synthesis
  3. Inhibits collagen degradation
  4. Inhibits lymphocyte proliferation
  5. Has anti-inflammatory effect
128
Q

describe FGF-2

A
  1. Fibroblast growth factor
  2. Stimulates proliferation of endothelial cells
  3. Promotes migration of macrophages and fibroblasts to damaged areas
129
Q

List different classes of pathogens.

A

prions
Viruses
Bacteria
Fungi
parasites

130
Q

what are viruses

A
  1. Obligate intracellular pathogens
  2. Capsid (protein coats) and genome (RNA or DNA)
  3. Some are enclosed within an envelope derived from the cytoplasmic membrane of the host cells
  4. Cause lysis and death of the host cell during replication
  5. Some remain in a latent, nonreplicating state for long periods without causing disease
    –> Varicella zoster virus
  6. Some cause cancer
    –> Human papillomavirus
131
Q

what are bacteria

A
  1. Prokaryotic
  2. Microscopic shapes
    - Spherical
    –> Diplococci, staphylococci, streptococci
    - Elongated
    –> bacilli
    - Helical
    –> Spirilla (spirochete)
132
Q

what is spirochetes

A
  1. type of bacteria
  2. anaerobic
  3. Ex: borrelia burgdorferi (lyme disease), treponema pallidum (syphilis)
133
Q

what is mycoplasmas

A
  1. Much smaller than other bacteria
  2. No cell wall - resistant to cell-wall inhibiting antibiotics (ex. penicillins)
  3. Ex: mycoplasma pneumoniae (pneumonia)
134
Q

what is rickettsiaceae

A
  1. type of bacteria
  2. Obligate intracellular pathogens
  3. Transmitted via arthropod vectors (mites, fleas, ticks, lice)
  4. Ex: rickettsia rickettsia (Rocky Mountain spotted fever)
135
Q

what is chlamydiaceae

A
  1. type of bacteria
  2. Obligate intracellular pathogens
  3. Transmitted via person-to-person contact
  4. Ex: chlamydia trachomatis - sexually transmitted; cause conjunctivitis in newborns
136
Q

what are the two types of fungi

A

superficial mycoses and systemic mycoses

137
Q

what is superficial mycoses

A
  1. dermatophytosis
  2. Ringworm, athletes foot (tinea pedis), and jock itch (tinea cruris)
  3. caused by dermatophytes whose infection is limited to the cooler cutaneous surfaces
138
Q

what is systemic mycoses

A
  1. Serious fungal infections of deep tissue (rare)
  2. Candidiasis (yeast infection) - opportunistic infection of candida albican, which is commensal flora in skin, mucous membranes, and GI tract
  3. aspergillosis - a lethal form of pneumonia caused by aspergillus, a common mold in people with lung diseases or immunocompromised patients
139
Q

what is fungi

A
  • Intact immune mechanisms and competitions for nutrients provided by the bacterial flora normally keep colonizing fungi in check
  • A disease or an antibiotic therapy can upset the balance, permitting opportunistic infections
140
Q

what are the 3 types of parasites

A

protozoa, helminths, and parasitic arthropods

141
Q

what are protozoa

A
  1. Unicellular animals
  2. Ex: plasmodium (malaria) - vector-bone (mosquito)
  3. Ex: entamoeba histolytica (amebic dysentery, or amoebiasis), giardia duodenalis (giardiasis) - contaminated water and food
142
Q

what are helminths

A
  1. Wormlike parasites
  2. Ex: roundworms, tapeworms, flukes
  3. Transmission primarily through ingestion of fertilized eggs (ova) or the penetration of infectious larval stages through the skin
143
Q

what are parasitic arthropods

A
  1. Ectoparasites - mites ( scabies ), chiggers, lice (head,body,pubic) and fleas
  2. May serve as vectors of other infectious diseases, such as bubonic plague (fleas)
144
Q

what are the different modes of transmissions from pathogens

A

penetrations, direct contact, indigestion, inhalation

145
Q

describe penetrations

A
  1. Any disruption may allow the invasion of pathogens, which normally cannot penetrate intact skin or mucous membranes
  2. Ex: abrasions, burns, needles, insect, and animal bites
146
Q

what are the two routes of direct contact

A

sex and congenital infections

147
Q

describe sexually transmitted infections

A
  1. Transmitted by the exposure of the intact skin or membrane to pathogens
  2. Ex: gonorrhea, syphilis, chlamydia, and genital herpes
148
Q

describe congenital infections

A
  1. Infection of a child during gestation or birth from mother (vertical transmission)
  2. Ex: Toxoplasmosis, Others (syphilis, varicella zoster, parvovirus B19), Rubella, Cytomegalovirus infection, and Herpes simplex virus (TORCH infection) and HIV
149
Q

describe ingestion

A
  1. Cholera, typhoid fever, amoebic dysentery, food poisoning, etc.
  2. The low pH of the gastric acid acts as a barrier for many pathogens, but some are resistant to the low pH (ex: shigella and giardia) → differences in the infectious dose
  3. The normal bacterial flora of the bowel compete with pathogens
150
Q

describe inhalation

A
  1. Bacterial pneumonia, meningitis, and tuberculosis
  2. Viral infections such as measles, mumps, chickenpox, flu, common cold, and COVID
  3. The respiratory tract is equipped with multiple-tiered defense system (mucous membrane, coughing, antibodies, and enzymes, phagocytosis, etc)
  4. Smoking and diseases such as cystic fibrosis impair the defense system
151
Q

what are the types of sources for parasites to get in

A

endogenous, exogenous, person, fomites, animal, vector, place

152
Q

describe endogenous sources

A

Opportunistic infection acquired from the host’s own microbial flora

153
Q

describe what the sources do

A
  1. Location, host, object, or substance from which the infectious agent was acquired
    –> Who, what, where, and when
154
Q

describe exogenous sources

A

environment
– water, food, soil, air

155
Q

describe person sources

A

direct contact

156
Q

describe fomites as sources

A
  1. An inanimate object contaminated with infected body fluids
  2. Rhinovirus through shared toys
  3. HIV Hepatitis B virus by shared syringes
157
Q

describe animals as sources

A
  • Zoonoses - infectious diseases passed from other animal species to humans
  • Ex: HIV, rabies, plague, flu, SARS, MERS, etc.
  • 70% of emerging viral infections
158
Q

describe vectors as sources

A
  1. Biting arthropod
    - Ex; lyme disease, west nile virus
159
Q

describe place as a source

A
  1. Healthcare associated infection (nosocomial infection)
  2. Community acquired
160
Q

what are the stages of disease courses

A

incubation period, prodromal stage, acute stage, convalescent stage, and resolution stage

161
Q

describe the incubation period

A

Active replication of a pathogen without recognizable symptoms

162
Q

describe the prodromal stage

A
  1. Initial appearance of symptoms
  2. Mild fever, myalgia, headache, and fatigue (somewhat nonspecific)
163
Q

describe the acute stage

A
  1. Max impact of the infectious process
  2. Inflammation and tissue damage (more specific)
164
Q

describe the convalescent stage

A

Progressive elimination of the pathogen

165
Q

describe the resolution stage

A

Tool elimination of a pathogen

166
Q

describe virulence factors

A
  1. Substances or products generated by infectious agents that enhance their ability to cause disease
167
Q

what pathological functions of does virulence factors have?

A

exotoxins, endotoxins, adhesion factors, evasive factors, invasive factors

168
Q

describe exotoxins

A
  1. Proteins released by pathogenic bacteria
  2. Inactivate key cellular constituents (ex: diphtheria toxin inhibits protein synthesis)
  3. Many are superantigens inducing excessive and nonspecific inflammatory responses
    –> Bind to MHC of antigen-presenting cells and t-cell receptors
    –> T cells are activated regardless of the antigen presented on MHC
169
Q

describe endotoxins

A
  1. Lipids and polysaccharides, not released (ex: lipopolysaccharides)
  2. Can induce clotting, bleeding, inflammation, hypotension, and fever (endotoxic shock)
170
Q

describe adhesion factors (adhesion)

A
  1. Bind to macromolecules on surface of host cells
  2. Adhesion is critical for the colonization of the pathogens
  3. Some pathogens form a mucous layer (slime)
171
Q

describe evasive factors

A
  1. Inactivate host’s immune system
  2. Ex: leukocidins form pores in the cell membrane of neutrophils and macrophages
  3. Some pathogens survive and reproduce within phagocytes after phagocytosis by neutralizing lysosomal contents with evasive factors
172
Q

describe invasive factors

A
  1. Facilitate the penetration of anatomic barriers
  2. Ex; pseudomonas aeruginosa collagenase breaks skin
173
Q

what does commensalism mean

A
  1. colonizing bacteria acquire nutrition and host is neither benefit nor are harmed
    –> Commensal bacteria in a human body (normal flora) are 10x more than human cells
174
Q

what does mutualism mean

A
  1. both the microorganisms and the host derive benefits from the interaction
    -> Infectious disease
    -> Infectious agents
175
Q

what does incidence mean

A

The number of new cases of an infectious disease that occur within a defined population ( ex: per 100,000 people ) over an established period of time ( ex: monthly, quarterly, yearly)

176
Q

what does disease prevalance mean

A

The number of active cause at a given time in a population

177
Q

what does endemic mean

A

Describes relatively stable incidence and prevalence in a particular geographical region

178
Q

what does epidemic mean

A

Describes an abrupt and unexpected increase in the incidence of disease over endemic rates

179
Q

what does pandemic mean

A

Refers to the spread of disease beyond continental boundaries

180
Q

what do fomites mean

A

An animate object contaminated with infected body fluids

181
Q

what do zoonoses mean

A

Infectious diseases passed from other animal species to humans

182
Q

what do nosocomial infection mean

A

Healthcare associated infection

183
Q

what does congenital infection mean

A

Infection of child during gestation or birth from mom

184
Q

what does prodromal stage mean

A

Initial appearance of symptoms

185
Q

what does acute stage mean

A

Max impact of infectious process

186
Q

what does convalescent stage mean

A

Progressive elimination of the pathogen

187
Q

what is a exotoxin

A

Proteins released by pathogenic bacteria

188
Q

what is a endotoxin

A

Can induce a lot of things (endotoxic shock)

189
Q

what is a superantigen

A

Induces excessive and nonspecific inflammatory responses

190
Q

State the three key elements of shock.

A

Shock is a life threatening condition of circulatory failure that results in inadequate oxygenation of body tissues

191
Q

Identify the component of gram negative bacteria that mediates septic shock.

A

endotoxin

192
Q

Define edema.

A

Accumulation of fluid in interstitial space of body tissues

193
Q

Describe the role of adrenomedullin in modulating vascular function.

A

In intravascular space enhances the endothelial barrier, reducing movement of solutes out of vascular space. When it does this ADM enters the interstitial space and mediates the relaxation in vascular smooth muscle, resulting in lower BP (vasodilation)

194
Q

State the primary drivers of the movement of fluid into and out of vascular space.

A
  1. Hydrostatic pressure
    –> Drives fluid out of vascular space
  2. colloid osmotic pressure
    –> Draws fluid back into vascular space
195
Q

what are common clinical causes of edema.

A
  1. Increased capillary permeability
  2. Increased capillary hydrostatic pressure
  3. Decreased capillary oncotic pressure
  4. Lymphatic obstruction (lymphedema)
196
Q

what is transudate

A

protein poor

197
Q

what is exudate

A

protein rich

198
Q

describe the mechanism of Increased capillary permeability

A
  • Local causes: cellulitis
  • Systemic causes: sepsis, hypersensitivity reactions
199
Q

describe the mechanism of Increased capillary hydrostatic pressure

A
  • Local causes: compartment syndrome, chronic venous insufficiency
  • Systemic causes: heart failure, renal failure, pregnancy
200
Q

describe the mechanism of Decreased capillary oncotic pressure

A
  • Systemic causes: protein deficient states (nephrotic syndrome cirrhosis)
201
Q

describe the mechanism of Lymphatic obstruction (lymphedema)

A
  • Local causes: tumor, trauma, infection (filariasis)
202
Q

Name the 4 main types of shock and their most common causes.

A
  1. distributive
  2. hypovolemic
  3. cariogenic
  4. obstructive
203
Q

what are the causes of distributive shock

A
  • Sepsis
  • Anaphylaxis
  • Neurogenic
204
Q

what are the causes of hypovolemic shock

A
  • Hemorrhage
  • Severe burns
  • Severe vomiting, diarrhea
205
Q

what are the causes of cariogenic shock

A
  • Myocardial infarction
  • Ventricular arrhythmia
  • Cardiomyopathy
  • Valvular disease
206
Q

what are the causes of obstructive shock

A
  • Cardiac tamponade
  • Pulmonary embolism
  • Pneumothorax
207
Q

describe distributive shock

A
  • Normal/high output SvO2
    1. Symptoms:
  • hypovolemia and hypotension that leads to vasodilation in the release of inflammatory response
    2. Echocardiographic signs
  • Normal cardiac chambers and preserved contractility
208
Q

describe hypovolemic shock

A
  • Low SvO2 and low venous pressure
    1. Symptoms:
  • leads to loss of plasma or blood volume
    2. Echocardiographic signs
  • Small cardiac chambers and normal or high contractility
    –> Triad with hypothermia → coagulopathy → acidosis
209
Q

describe cariogenic shock

A
  • Low SvO2 and high venous pressure
    1. Symptoms:
  • deals with cardiogenic shock and everything related to your heart
    2. Echocardiographic signs
  • Large ventricles and poor contractility
210
Q

describe obstructive shock

A
  • Low SvO2 and high venous pressure
    1. Symptoms:
  • obstructive shock is characterized by a blockage in blood flow caused by massive (causes listed)
    2. Echocardiographic signs
  • Depends on the cause
211
Q

what are single gene disorders?

A

recessive, dominant, autosomal, sex-linked

212
Q

what is recessive

A

Observed in absence of normal allele (homozygous)

213
Q

what is dominant

A

Observed in presence of normal allele (heterozygous)

214
Q

what is autosomal

A

chromsomes 1-22

215
Q

what is sex-linked

A

x and y chromosomes

216
Q

what are Mendelian traits

A

autosomal dominant, autosomal recessive, and x linked recessive

217
Q

what is autosomal dominant

A
  1. 50% chance passing trait to child
    –> Same probability for M/F
  2. Unaffected relatives/siblings do not transmit disorder
  3. Age of onset is delayed for some
    –> Huntington’s disease
    –> Appear later in life for signs/symptoms
218
Q

what is autosomal recessive

A
  1. If both parents have mutant gene
    –> 25% = affected child
    –> 50% = carrier child
    –> 25% = noncarrier child
    –> Same probability for M/F
  2. Unaffected siblings may be carriers (67%)
  3. All children of affected parent are carriers
  4. Age is early in life for many conditions
  5. Symptoms tend to be more uniform than dominant disorders
219
Q

what is x-linked recessive

A
  1. Circle with blue dot inside = carrier female
  2. 50% chance of passing gene to sons and daughters
    –> Daughters unaffected
    –> Males who receive gene are affected
  3. Affected males
    –> Do not pass to sons
    –> Pass mutant gene to daughters
  4. Only males are affected
    –> Females can be affected if father has trait and has children with female (rare)
220
Q

what are examples of x linked diseases

A
  1. Hemophilia A & B
  2. Joint bleeding, muscle hematoma, soft tissue bleeding
    –> A = factor 8
    –> B = factor 9
  3. Incidence
    –> A - 1: 5000
    –> B - 1: 30,000
  4. Mutations
    –> A - inversion & small deletions
    –> B - missense
221
Q

what is penetrance

A
  1. Many people who have a mutation in a specific gene show any traits associated with defects in that gene
  2. Complete: 100%
  3. Incomplete: <100%
  4. Even if people do not have pentrance they still have the gene but just do not show it
222
Q

what is expressivity

A
  1. Mutations in a gene give rise to different outcomes in different people
    - Number
    - Identity (types)
    - Extent (severity)
  2. Ranges from complete to minimal
223
Q

what is expressivity affected by

A
  1. Other genes
  2. Environment
  3. Age
  4. Exposure to harmful chemicals/ conditions
224
Q

what are silent mutations

A

Replacement of a single nucleotide that results in the same amino acid still so you cannot see if there has beena mutation because the sequence does not change

225
Q

what are missense mutations

A

Replacement of single nucleotide
&
Incorrect amino acid, which may produce a malfunctioning protein

226
Q

what are nonsense mutations

A

Replacement of single nucleotide
&
Incorrect amino acid, shortening of protein

227
Q

what are insertions

A

Frameshift
&
Insertion of a single nucleotide
&
Incorrect sequence, will produce a malfunctioning protein

228
Q

what are deletions

A

Frameshift
&
Deletion of a single nucleotide
&
Incorrect sequence, will produce a malfunctioning protein

229
Q

complete loss of function =

A

amorphic

230
Q

partial loss of function =

A

hypomorphic

231
Q

gain of function =

A

hypermorphic

232
Q

dominant negative =

A

inhibits activity of unmutated protein

233
Q

Acquisition of a new property =

A

neomorphic

234
Q

what is a genetic variant

A

a change is sequence of genes

235
Q

what does pathogenic mean

A
  1. Responsible for causing disease
  2. Well supported by research
  3. Referred to as mutations
236
Q

what is likely pathogenic

A
  1. Probably responsible for disease causing
  2. Not enough research to be sure
237
Q

what is uncertain significance mean

A
  1. Not confirmed to cause disease
  2. Not enough research
238
Q

what is Likely benign

A
  1. Probably not responsible for disease
  2. Not enough research to be sure
239
Q

what is benign

A
  1. Not responsible for disease
  2. Strong research to rule out disease link
240
Q

what is an inherited variant

A
  • Passed from parent to child
  • Present throughout a person’s life in virtually every dell in the body
  • Germline variants- present in the parent’s egg or sperm cells (germ cells)
241
Q

what is a non-inherited variant

A
  1. Occur at some time during a person’s life
  2. Not found in every cell in the body
  3. Somatic variants- occur in somatic cell (cells other than sperm and egg cells)
  4. Not passed to the next generation
  5. Can be caused by environmental factors (e.g. UV radiation) or result from an error in DNA replication
242
Q

what is a new (de novo) variant

A
  1. Found in a child but not either parent (no family history of the disorder)
  2. May occur
    –> In a parent’s egg or sperm cell but is not present in any of their other cells
  3. Variants acquired during development can lead mosaicism
243
Q

what is meant by karyotype analysis and how it can be used to diagnose genetic diseases.

A

a. Tells if chromosomes are:
1. Missing
2. Duplicated
3. Broken
4. Have deletions, insertions, or inversions
b. Report:
1. Total # of chromosomes
2. Sex chromosome
3. Description of abnormality
4. Ex: 47, XY, +21 (male with trisomy 21)

244
Q

describe the most common genetic changes that cause down syndrome and turner syndrome.

A

a. Down syndrome
– Trisomy 21 type: 47, XX, +21
– Translocation type: 46, XX, der(14;21)(q10;q10), +21
– Mosaic type: 46, XX/47, XX, +21
b. Turner syndrome
– Monosomy X

245
Q

what are Cytogenetic disorders

A
  1. Chromosomal abnormalities are frequent
    –> Approx 1/200 newborn infants
  2. Changes in chromosome number or structure
    –> Autosomes or sex chromosomes affected
  3. Disorders characterized by a change in autosome number are more severe than single gene disorders
246
Q

what is translocation

A

Transfer part of one chromosome to another

247
Q

what is an isochromosome

A

Centromere divides horizontally rather than vertically, resulting in 2 short arms and 2 long arms

248
Q

what is a deletion

A

loss of portion of chromosome

249
Q

what is an inversion

A

When there are 2 interstitial breaks in a chromosome, segment reunites but is flipped

250
Q

what is a ring chromosome

A
  1. Variant of deletion.
  2. After loss of segments from each end of the chromosome, arms unite to form a ring
251
Q

what are examples of recessive disorders

A

cystic fibrosis, loss of function, effects of mutations on drug discovery

252
Q

describe cystic fibrosis

A
  1. Most common lethal genetic disease that affects caucasian population (1/3200)
  2. Caused by loss of function mutations in cystic fibrosis transmembrane conductance regulator (CFTR)
  3. Many differ mutations
253
Q

what is loss of function in terms of recessive

A
  1. Unmutated copy of gene is unable to make up for loss of expression or activity from mutant gene
    –> No dosage compensation
254
Q

what is mutations effects on terms of recessive and drug discovery

A

a. CFTR variants have differ effects of CFTR
1. People with variants that have partial activity fare better than those with complete loss of function
2. Variants establish a dose response relationship
3. People with CFTR alleles with 10-20% have mild CF
–> Ivacaftor
——- Increase function of CFTR protein
——- Works only with specific genotype
——- Improves clinical symptoms

255
Q

what is triple repeat disease

A
  1. Some genes contain repeats of 3 nucleotides
  2. Longer repeats are associated with disruption of gene function
  3. 40 diseases associated with triplet repeats
    –> All are associated with neurodegeneration
  4. CAH repeats encode poly-glutamine (polyQ disorders)
  5. Mostly dominant
    –> Friedreich ataxia - only triplet disorder that is recessive
256
Q

what are examples of triple repeat

A

familial retardation and fragile X

257
Q

what is fragile X syndrome

A

Elongated face
Protruding ears
Low muscle tone

258
Q

what is familial dysfunction

A

FRM1 gene on X chromosome repeat (>45x)

259
Q

what is mitochondrial mutations

A

Have separate genome
Are inherited only from mother
Present in multiple copies/cells

260
Q

what is mitochondrial mutations caused by ?

A
  1. mutations in mitochondrial genes are rare
  2. Mutations in mitochondrial genes are transmitted to progeny by daughters, but not sons
261
Q

what Is affected from mitochondrial mutations

A
  1. Affected organs that depend most on oxidative phosphorylation
    –> Skeletal muscle, heart, brain
262
Q

wha tare imprinting defects

A
  1. Parent of origin transmission
  2. Some regions of DNA are turned off in copy received from mother or father
  3. Imprinting occurs in ovum or sperm and stably transmitted to all somatic cells derived from zygote
  4. If region turned off in maternal copy it is mutated in paternal copy, genes in that region will not be expressed
263
Q

what are examples of imprinting defects

A

prader- will and angel man and complex inheritance patterns

264
Q

what are prader will and angel man similarities

A
  1. Phenotypes are partially overlapping, but distinct
  2. Similar region of chromosome 15 deleted in both
265
Q

what is prader willi

A
  1. Deletion inherited from father
  2. Mental retardation, short stature, hypotonia, obesity, small hands and feet, hypogonadism
266
Q

what is angel man syndrome

A

1.Deletion inherited from mother
2. Mental retardation, ataxic gait, seizures, inappropriate laughter

267
Q

what are examples of autosomal dominant

A

complete loss of function, partial loss of function, and gain of function

268
Q

what are some mutations of autosomal dominance

A
  1. Familial hypercholesterolemia (FH)
  2. Mutations in the LDL receptor (LDL-R)
269
Q

what is complete loss of function in terms of dominance?

A
  1. Some variants act as dominant negatives
  2. Mutated proteins interferes with the function of unmutated version
  3. More severe
  4. Not able to make up for loss of expression or activity from mutant gene
  5. Osteogenesis imperfecta
270
Q

describe osteogenesis imperfecta

A
  1. Caused by defects in production of collagen
    –> Structure, support, strength
  2. Collagen trimer
    –> 2 subunits of alpha 1
    –> 1 subunit of alpha 2
271
Q

describe gain of function in autosomal dominance

A

Some PCSK9 mutations have gain of function and LDL-R levels are regulated by PCSK9

272
Q

describe LDL-R levels are regulated by PCSK9

A
  1. Binds LDL-R on cell surface
  2. Internalized with LDL-R
    3.Directs LDL-R to lysosome
  3. LDL-R completely degraded
  4. Reduces the number of LDL receptors on cell surface
273
Q

describe how some PCSK9 mutations have gain of function

A
  1. Increase affinity for LDL-R
  2. Enhance sorting of LDL-R to lysosome

Patho 2023 (37 decks)

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