Intro to Clinical Sciences Flashcards

(74 cards)

1
Q

Pathology:

Acute inflammation vs. Chronic inflammation

Cells involved?
Onset?
Duration?
Resolves?

A

Acute: Neutrophil inflammation

  • Sudden onset
  • Short duration
  • Usually resolves

Chronic: Leukocyte inflammation

  • Slow onset/follows acute
  • Long duration
  • May never resolve
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2
Q

Pathology:

Inflammatory cells

Mobile inflammatory cells? (3)
Other cells involved in inflammation? (2)

A

Neutrophils - pus cells (suppuration)

  • short lived
  • first on scene
  • phagocytic, lysosomal granules, release cytokines/chemokines to attract inflammatory cells

Macrophages

  • long lived
  • phagocytic, antigen presenting cells

Lymphocytes

  • long lived
  • release cytokines/chemokines to attract inflammatory cells
  • IMMUNOLOGICAL MEMORY

Endothelial cells

  • become sticky (allow adhesion) in areas of inflammation
  • become porous (allow cell migration)
  • grow into areas of damage to form new vessels
  • capillaries open (normally shut) in inflammation = redness
  • oedema = oncotic pressure in tissues due to migration of plasma proteins

Fibroblasts

  • Long lived
  • Form collagen (scarring) in areas of chronic inflammation
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3
Q

Pathology:

Example of Acute and Chronic inflammation

A

Acute = Acute appendicitis

  • Generalised pain around epigastric region then progresses to…
  • Right lower quadrant/McBurney’s point sharp pain = inflammation reaches abdominal wall

Chronic = Tuberculosis

  • Granulomas - mycobacteria
  • No initial inflammation
  • Fibrosis occurs
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4
Q

Pathology:

Treatment for Inflammation

A

NSAIDs: Ibuprofen, Aspirin (COX inhibitors)
Corticosteroids: Immune modulators
MOABs - targeted immune therapies

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5
Q

Pathology:

Resolution vs. Repair

A

Resolution:

  • Initiating factor removed
  • Tissue undamaged
  • Regeneration

Repair:

  • Initiating factor still present
  • Tissue damage
  • No regeneration
  • Replacement by collagen (fibroblasts)
    e. g.
  • Heart after MI
  • Brain after cerebral infarction
  • Spinal cord after trauma
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6
Q

Pathology:

Cells that regenerate?
Cells that cannot regenerate?

A

Cells that regenerate:

  • Hepatocytes
  • Pneumocytes
  • All blood cells
  • Gut epithelium
  • Skin epithelium
  • Osteocytes

Cells that cannot regenerate?

  • Myocardial cells
  • Neurones (CNS)
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7
Q

Pathology:

Define:
Thrombus
Thrombosis

Embolus
Embolism

A

Thrombus = blood clot within a vessel
Thrombosis:
Formation of a solid mass from blood constituents in an intact vessel in a living person
Causes laminar flow to be turbulent if larger enough can occlude
(Verkov’s Triangle)

Embolus = anything that causes embolism
Embolism:
Process of a solid mass (e.g. thrombus/air/fat) in the blood being carried in the circulation to a place it becomes stuck and occludes the vessel

e.g. a deep venous thrombosis of the leg veins which breaks off and embolises through the large veins and right side of the heart to the lungs

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8
Q

Pathology:

Define:
Ischemia
Infarction
Reperfusion injury

A

Ischemia = reduction in blood flow

Infarction = death of cells due to reduction in blood flow

Reperfusion injury = injury by superoxide radicals due to cellular response to elevated O2

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9
Q

Pathology:

Myocardial infarction is an example of…?

Which organs have dual blood/collateral supply?

Areas more susceptible to infarction?

A

End artery ischemia

Liver, Lungs, Brain - so infarctions are less likely to be fatal due to redundancy

Watershed ares - area boundary of adjacent arterial territories

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10
Q

Pathology:

Define..
Metaplasia
Hyperplasia
Dysplasia
Neoplasia
Atrophy
Hypertrophy 

Example for each?

A

Metaplasia – Transition from one cell type to another
e.g. metaplasia in bronchi of a smoker

Hyperplasia – increase in the number of cells within a tissue
e.g. Prostate gland – benign prostate hyperplasia

Dysplasia – Abnormal cell population
Neoplasia – Malignant new cells

Atrophy - Decrease in size of a tissue due to loss of number of cells
Hypertrophy - Increase in the size of a tissue caused by increase in size of constituent cells
e.g. Muscle atrophy/hypertrophy

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11
Q
Gastritis 
Common cause? 
Cell population? 
Cell type shift? 
Cancer risk?
A

Inflammation of the stomach
Helicobacter infection (Urea breath test, stain cells to diagnose)
Chronic or acute infection
Giant cells = lots of macrophages
Chronic gastritis increases risk of lymphoma

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12
Q

Atherosclerosis

Define
Where?
What’s in plaque?
Endothelial damage theory?

A

Build up of sclerotic plaque within arteries
Never within low pressure Common in high pressure
Early stage (reversible) - fatty streaks
Plaque = fibrous tissue, lipids, lymphocytes
Endothelial damage theory
- Free radicals, nicotine, carbon monoxide all damage (smoking) (vaping = fewer ROS but same nicotine)
- Hypertension = shearing forces on endothelial cells
- Poorly controlled diabetes = superoxide anions damage
- Hyperlipidaemia = direct damage to endothelial cells
- Pathogenesis
Recurrant endothelial cell injury

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13
Q

Pathology:

Define Apoptosis
Apoptotic detector protein?

Define Necrosis
Types of necrosis?

A

Apoptosis – programmed cell (singular) death due to apoptotic switch
e.g. DNA damage

P53 - gatekeeper of genome

Necrosis - traumatic cell death (multiple cells)
e.g. Frostbite, avascular necrosis

Types
Coagulative necrosis – thick and gooey
Liquefactive necrosis – (cerebral infarction)
Caseous necrosis – (Tuberculosis)

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14
Q

Pathology:

Define and give an example for:
genetic disease
congenital disease
acquired disease

A

Genetic disease - occurs primarily from a genetic abnormality
e.g. Sickle cell anaemia is caused by a point mutation in the β-globin chain of haemoglobin

Congenital disease - disease present at birth; can be genetic disease but also acquired
e.g. Rhesus haemolytic disease of the newborn

Acquired disease– disease occurs after birth; genetic and nongenetic environmental factors
e.g.

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15
Q

Pathology:

Give examples of pathology of ageing - Diagram!

Progeria = increased aging disease

A
  • Cross-linking or mutations of DNA
  • Telomere shortening: Hayflick limit
  • Time-dependent activation of ageing/death genes
  • Free radical accumulation
  • Cross linking of proteins
  • Loss of DNA repair mechanism
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16
Q

Pathology:

Common sites of carcinoma metastasis

Define adjuvant therapy

A
  • Lymph nodes (drainage route)
  • Bone, brain, liver (through the blood)

Adjuvant therapy = extra treatment given following surgical excision
e.g. radiotherapy to breast after lumpectomy
minimise the risk of micro metastases

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17
Q

Patholgy:

Define:

  • Carcinogenesis
  • Oncogenesis
  • Benign/Malignant tumour
A

Carcinogenesis - The transformation of normal cells to neoplastic cells (cancer) through permanent genetic alterations or mutations - MULTISTEP

Oncogenesis – Formation of benign and malignant tumours (tumour = cancer in solid tissue)

Benign tumour – a growth that is not cancer and does not invade or destroy nearby tissue
Malignant tumour – a growth which is cancer and can invade and metastasise

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18
Q

Pathology:

Carcinogenesis is…?
Period exposure/cancer?
Classes of carcinogenesis

A
Multistep process
Typically a latent interval between exposure and cancer
Classes: 
- Chemical
- Radiation (non and ionising)
- Biologic (hormones, parasites, mycotoxins
- Viral
- Host
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19
Q

Pathology:

Define;
Carcinoma
Sarcoma
Neoplasm

A

Carcinoma – cancer of the epithelium
Sarcoma – malignancy of connective tissue
Neoplasm – lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persist after the initiating stimulus has been removed – new growth

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20
Q

Pathology:

Structure of a neoplasm?
Maximum size before it must recruit vasculature to grow?

A
  • Neoplastic cells
    o derived from nucleated cells – need DNA
    o Synthetic activity is related to the parent cell (Thyroid cell still produces thyroxine)
    o Growth pattern related to parent cell
    o Monoclonal

Within Stroma
o Connective tissue framework (fibrin, collagen)
o Vasculature
o Neoplasm drives the formation of its stroma to nurture itself

2mm

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21
Q

Pathology:

Neoplasm behavioural classification

Histogenesis classification
Papilloma?
Adenoma?
Carcinoma?
Adenocarcinoma?
A

1) Benign - localised/non-invasive, slow growth, close resemblence to normal tissue
2) Borderline - defy binary like ovarian lesions
3) Malignant - invasive, metastasise, rapid growth, irregular border

The cell specific cell origin of a tumour
Neoplasm = …oma
Prefix depend on cell type

Papilloma
Benign neoplasm of squamous epithelium

Adenoma
Benign tumour of glandular or secretory epithelium

Carcinoma = Malignant tumour of epithelial cells
Prefix it with name of epithelial cell e.g. transitional cell carcinoma

Adenocarcinoma = carcinoma of glandular epithelium

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22
Q

Pathology:

In-situ neoplasia

What is invasion dependent on?

Define metastasis

A

In-situ neoplasia = epithelial neoplasms - no invasive carcinoma = no spread
Invasion = metastatic capaility

Invasion dependent on:

  • decreased cellular adhesion
  • increased cellular motility
  • production of lytic enzymes degrade surrounding tissue

Metastasis is the process by which a malignant tumour spreads from its primary site to produce secondary tumours at distant sites

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23
Q

Pathology:

Routes of metastasis, via:
Blood vessels?
Lymphatics?
Due to surgery?

A

Blood vessels = Haematogenous

Lymphatics = Trans-coelomic

Surgery implantation = iatrogenic

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24
Q

Pathology:

Metastatic cascade (Diagram test)
Haematogenous
A

Haematogenous metastasis:

1) Intravasation
2) Evasion of host immunity
3) Extravasion
4) Growth at metastatic site
5) Angiogenesis

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25
Pathology: Routes of metastasis - Vein invasion - From colon Appearance of bone mets on X-ray?
Vein: Vena cava - right side of the heart - Lung mets Can reinvade (PV -> LA/LV -> Aorta) and spread all around the body Colon: Portal vein to liver = hepatic mets "moth eaten bone"
26
Immunology: Describe: Innate immunity Adaptive immunity
II – Instictive, non-specific, present from birth, barrier to antigen, Slow response, No memory AI – Specific, acquired immunity, lymphocyte/antibody dependent, quick response
27
Immunology: Describe separated blood: Plasma Buffy coat Red layer
Plasma = straw coloured (90% water, electrolytes, proteins, lipids and sugars) Buffy coat is Leukocytes (WBCs) Haemtocrit: Erythrocytes (RBC) volume Platelets
28
Immunology: 3 Polymorphonuclear leukocytes? 3 Mononuclear leukocytes?
Poly: Neutrophils, Eosinophils, Basophils Mono: Monocytes (mature to macrophage in tissue), B-cells (mature to plasma cell), T-cells (CD4+, CD8+, Th17, T-regs
29
Immunology: Humoral factors Actions of complement (3) ? Which complement carries out each function?
Direct lysis (MAC – membrane attack complex) Chemotaxis - Attract leukocytes (C3a + C5a) Opsonisation (C3b)
30
Immunology: Describe: Innate immunity Adaptive immunity
II – Instictive, non-specific, present from birth, barrier to antigen, Slow response, No memory AI – Specific, acquired immunity, lymphocyte/antibody dependent, quick response Both = cells + humoral (Soluble) factors
31
Immunology: Describe separated blood: Plasma Buffy coat Red layer
Plasma = straw coloured (90% water, electrolytes, proteins, lipids and sugars) Buffy coat is Leukocytes (WBCs) Haematocrit: Erythrocytes (RBC) volume Platelets
32
Immunology: 3 Polymorphonuclear leukocytes? 3 Mononuclear leukocytes?
Poly: Neutrophils, Eosinophils, Basophils Mono: Monocytes (mature to macrophage in tissue), B-cells (mature to plasma cell), T-cells (CD4+, CD8+, Th17, T-regs
33
Immunology: Humoral factors Actions of complement (3) ?
Direct lysis (MAC – membrane attack complex) Chemotaxis - Attract leukocytes (C3a + C5a) Opsonisation (C3b)
34
Immunology: ``` Immunoglobulin characteristics: IgA IgD IgE IgG IgM ```
IgA – Dimer, Secretory IgA dimer IgD – Surface of mature B cells IgE – Hypersensitivity, mast cell surface crosslinking = degranulation + histamine IgG – Most predominant 75% IgM – Pentamer, found in blood; also find monomeric IgM on B-cells
35
Immunology: Cytokine function - Interferon - Interleukins - Colony stimulating factors - Tumour necrosis factor
- Interferon Viral infections - Interleukins IL-1 = pro-inflammatory IL-10 = anti-inflammatory - Colony stimulating factors Division/differentiation e.g. EPO - Tumour necrosis factor Inflammation and cytotoxicity, TNF-alpha causes increased adhesion (macrophage release)
36
Immunology: Examples of chemokines - Chemotaxic Receptors for chemokines?
``` CXCL "Chemokine ligand-1 CXC motif" CCL "Chemokine ligand 1" CX3CL XCL Chemokine ligands have specific receptors ```
37
Immunology: Physical and chemical barriers (diagram)
Skin: commensals, fatty acids, barrier Bronchi: mucus, cilia (sterile*) Gut: Stomach acid low pH, commensals in intestines Nose: turbulent air flow (turbinates) traps particles Tears: lysosymes Vagina: Low pH Urinary tract = flushing
38
Immunology: Define inflammation What happens? 2 key things?
“a series of reactions that bring cells and molecules of the immune system to sites of infection or damage” - Increased blood supply - Increased vascular permeability = increased ‘extravasation’ – immune cell transendothelial migration
39
Immunology: Steps of phagocytosis (5)
- Binding - Engulfment - Phagosome formation - Phagolysosome - MHC class II dependent antigen presentation
40
Immunology: Mechanisms of microbial killing? (in terms of oxygen)
- O2 dependent: ROS; superoxides, Nitric oxide | - O2 independent: Enzymes, proteins, pH denaturing
41
Immunology: What is foetal thymus T-cell selection?
Any T-cells that recognise self-antigens are removed
42
Immunology: Primary lymphoid? Secondary lymphoid? diagram?
Primary = Thymus or Bone marrow Secondary = Spleen, Lymph nodes, MALT?
43
Immunology: Which antigen corresponds to which MHC class, which T-cell and TCR? Extrinsic or intrinsic antigen? * **IMPORTANT*** * **DIAGRAMS***
``` MHC class I = Tc (CD8+) = Intrinsic antigens CD “hate”/8 = cytotoxic ``` MHC class II = T helper (CD4+) = Extrinsic antigens CD “four the people” = helper Help B-cell maturation Ab production to that antigen
44
Immunology: What needs to happen for TCR recognition and activation? Activation causes?
Co-stimulation: 1. MHC + TCR 2. CD80/86 + CD28 Activation = T-cell division, effector functions, memory
45
Immunology: Tc (CD8+) activated functions (3)
1. Cell lysis: release of perforin + granulysin 2. IFN gamma- macrophage activation 3. Chemokines – inflammatory cell recruitment
46
Immunology: How many epitopes can a B-cell be specific to? What happens to B-cells that recognise self-antigens (usually)?
B-cells are specific to one epitope (antigen) Undergo apoptosis in the bone marrow = B-cell selection
47
Immunology: T-helper cell activation (diagram) steps
``` APC presents extrinsic antigen (MHC class II) to TCR (CD4+) on niave T-cell = Stimulation of IL-12 release from APC = activation to CD4 Th1 cell ```
48
Immunology: T-cytotoxic cell activation (diagram) steps
CD8+ TCR combines with intrinsic antigen presented on MHC Class I on ANY cell = activation of naive CD8 to cT-cell
49
Immunology: Which immunoglobulins are expressed on B-cells?
Monomeric IgD Monomeric IgM (mIgD or mIgM)
50
Immunology: What are the functions of Immunoglobulins (antibodies) (4)
- Neutralisation of toxins - Opsonisation for phagocytosis - Link adaptive and innate immunity - Activate complement via complement cascade
51
Immunology: Th1 vs Th2 cells
Th1 = Macrophage activation (APC = IL-12 maturation) Th2 = B-cell activation (APC = IL-4 maturation)
52
Immunology: T-B cell cooperation What happens? What are the two resultant effector cells?
``` Th2 cells (primed to antigen) bind B-cells and secrete cytokines IL-4,5,10,13 = CLONAL EXPANSION Plasma cells = antibodies + Memory B-cells ```
53
Immunology: What are the functions of Immunoglobulins (antibodies)
- Neutralisation of toxins - Opsonisation for phagocytosis - Link adaptive and innate immunity - Activate complement via complement cascade
54
Immunology: B-cell activation steps? Activation through to long term
Specific antigen binds = activation Activated B-cell travels to lymph nodes and proliferate and differentiate into plasma cells CLONAL EXPANSION Plasma cells secrete antibody as IgM which then turn into IgG CLASS SWITCHING Memory B-cells generated as well as plasma cells – these stick around for years Re-stimulation of Memory B-cells leads to rapid secondary response
55
Immunology: Example of a vaccination? What is a toxoid?
Tetanus vaccine – Clostridium tetani Toxoid is an inactivated form of exotoxin
56
Immunology: Principal of vaccination
Memory B-cells formed against inactivated version of virus/exotoxin etc to prime the immune system elicit primary antibody response Subsequent exposure to that specific virus/toxin will be met with a secondary antibody response = aquired immunity
57
Immunology: Innate immunity relies on what to recognise fungi/bacteria/viruses?
Pattern recognition receptors – recognise conserved elements of pathogens so that we are able to deal with infections
58
Immunology: What do PRRs respond to? (3) 2 classes of PRRs?
Gram +ve/-ve (Bacteria) dsRNA (Virus) CpG motifs (DNA) Secreted/circulating PRRs Cell associated PRRs
59
Immunology: Example of circulating/secreted PRRs? What do they do?
Defensins, lectins Antimicrobial peptides which have direct killing effects and immune modulation
60
Immunology: Cell associated PRRs?
Toll-like receptor family (TLRs)
61
Immunology: Which TLRs are associate with viral patterns? Where are they found?
TLR3,7,8,9 Often found within endosomes within cells – As viruses are intracellular pathogens
62
Immunology: Which TLRs are associated with bacterial patterns?
TLR1,2,4,5,6 TLR4 (also senses viral proteins)
63
Immunology: What do Nod-like receptors detect? What do Rig like helicases detect?
NLRs - Intracellular microbial pathogens e.g. peptidoglycan RLHs - Intracellular viral dsRNA and DNA
64
Immunology: Roles of PRRs? (3)
- Balance of commensal organisms - Regulation of neutrophils - Maturation of immune system
65
Immunology: Damage recognition – 3 Extracellular damage molecules? 3 Intracellular damage molecules?
``` Extracellular: - Fibrinogen - Hyaluronic acid - Tenascin C Intracellular: - Heat shock proteins - Uric acid - mRNA ```
66
Immunology: What is passive immunity? What can it protect against? Long term memory? Antisera?
Transfer of preformed antibodies e.g. maternal antibodies across the placenta or via breast milk ``` Tetanus Diptheria Mumps Rubella Poliovirus ``` No long term memory Can’t react to antisera
67
Immunology: Why do vaccines not work in children under 2yoa?
Do not have mature enough B-cells which illicit immunological memory
68
Immunology: Artificial vs Natural passive immunity????
``` Natural = breast milk Artificial = injection of antisera (serum of preformed antibodies) ```
69
Immunology: What is Inoculation?
Introduction of viable organism into the subject
70
Immunology: Primary goal of immunisation?
Generate a primary antibody response (formation of memory B-cells) from an initial exposure without the risks associated with the actual infection
71
Immunology: Characteristics of Initial/primary response Ig? predominant? Affinity? Innate or adaptive?
IgM Low affinity Innate immune system
72
Immunology: ``` Characteristics of secondary response? Speed? Ig? predominant? Affinity? Innate or adaptive? ```
High affinity IgG Rapid and large response T-cell help Doesn’t rely on innate immune system - adaptive
73
Immunology: Vaccine adjuvant? E.g.?
Something that potentiates the immune response | e.g. TLR4 agonist
74
Immunology: BCG vaccine for Tuberculosis is an example of what type of antigen? Diptheria/tetanus? Types of antigen for vaccine? (5)
BCG = Whole organism – live attenuated or inactive pathogen Diptheria/tetanus = Subunit (toxoid – inactivated exotoxin) ``` Types: Whole organism Subunit Peptide DNA vaccine Engineered virus ```