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Phase 3 > General Pathological Mechanisms > Flashcards

General Pathological Mechanisms Flashcards

1
Q

Describe the changes seen in cells experiencing reversible cell injury

A
  • Cloudy swelling: osmotic disturbance due to loss of ATP-dependent sodium pump, which leads to sodium influx & build-up of intracellular metabolites
  • Cytoplasmic blebs, disrupted microvilli, swollen mitochondria
  • Fatty change
    > Accumulation of lipid vacuoles in cytoplasm caused by disruption of fatty acid metabolism (esp in liver)
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2
Q

List the characteristics of necrosis and the histological changes associated with it

A

Necrosis is uncontrolled cell death caused by injury due to external stimuli.
> it is always pathological

Histological changes
- Cell swelling
- Vacuolation
- Disruption of membranes of cell & its organelles - mitochondria, lysosomes & ER
- Release of cell contents (lysis) including enzymes causing adjacent damage & eliciting acute inflammation

  • Nuclear changes leading to nuclear dissolution & an anuclear necrotic cell

> Karyolysis (nuclear fading) - chromatin dissolution due to action of DNAases & RNAases

> Pyknosis (nuclear shrinkage) - DNA condenses into shrunken basophilic mass

> Karyorrhexis (nuclear fragmentation): pyknotic nuclei membrane ruptures & nucleus undergoes fragmentation

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3
Q

Describe the morphological subtypes of necrosis

A
  • Coagulative: firm, tissue outline retained
    > Haemorrhagic - due to blockage of venous drainage
    > Gangrenous - larger area, esp lower leg
  • Colliquitive - tissue becomes liquid & structure is lost e.g. infective abscess, cerebral infarct
  • Caseous - combination of coagulative & colliquitive, appearing “cheese-like” - classical for granulomatous inflammation e.g. TB
  • Fat: due to action of lipases on fatty tissue
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4
Q

Describe the differences between physiological and pathological apoptosis

A
  • Physiological
    > Embryogenesis: deletion of cell populations
    > Hormone-dependent involution; uterus, breast, ovary
    > Cell deletion in proliferating cell populations to maintain constant numvers
    > Deletion of inflammatory cells after inflammatory response
    > Deletion of self-reactive lymphocytes in thymus
  • Pathological
    > Viral infection (cytotoxic T lymphocytes)
    > DNA damage
    > Hypoxia/ischaemia
    > Autoimmune disease
    > Graft v host disease
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5
Q

Describe the characteristics of apoptosis and the morphology of cells undergoing apoptosis

A

Apoptosis refers to active controlled or “programmed” cell death - requires energy & distinct pathways are involved

> Cell contents do not leak due to intact cell membrane
Does not elicit an inflammatory response

Involves cell shrinkage and chromatin condensation
> Cytoplasmic blebs form and break off to form apoptotic bodies which are phagocytosed by tingible body macrophages

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6
Q

List endogenous and exogenous intracellular deposition

A

Endogenous
- Melanin
- Haemosiderin
- Bile
- Lipid
- Storage diseaes e.g. in liver, alpha-1-antitrypsin

Exogenous
- Tattoo pigment
- Carbon (anthracosis)
- Asbestos

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7
Q

Give examples of extracellular endogenous depositions

A
  • Amyloid
  • Fibrosis
  • Calcium
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8
Q

Describe the causes, clinical effects and microscopic views of amyloidosis

A

Abnormal folding of soluble protein fibrils into specific abnormal insoluble aggregates - beta pleated sheets
> Localised or systemic accumulation of protein aggregates outside cells

2 types
- AL amyloid: immunoglobulin light chain
> produced in B cell neoplasms e.g. multiple myeloma

  • AA amyloid: serum amyloid associated protein (normal acute phase protein) produced in the liver
    > Produced in chronic inflammation e.g. RA

Microscopy
- Congo red stain gives it green apple / pink appearance

Clinical effects: depend on site of amyloid deposition
- Kidney: renal impairment/failure
- Heart: heart failure
- Brain: dementia

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9
Q

Describe how tissue samples are processed in a pathology laboratory

A
  • Tissue removed at surgery and placed into formalin at theatre
  • Transported to pathology laboratory for gross examination
    > description of large specimens and trimming smaller ones
  • Tissue processing and embedding: specimen moved from water-based formalin through graded alcohols to xylene, then embedded in wax
  • Tissue sectioning in a microtome
  • Tissue staining, usually in H&E
  • Coverslipping and microscopy
  • Reporting (check ID & quality)
  • Special stains: mucin (epithelial cells), depositions e.g. fibrous tissue (Van Gieson, masson), infections…
  • Immunohistochemistry (infectious disease, cancer)
  • Molecular testing (PCR, FISH, NGS) - esp for cancer
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10
Q

Describe the clinical features of inflammation

A
  • Redness (rubor) - dilatation of small blood vessels
  • Heat (calor) - increased blood flow due to vasodilatation and fever
  • Swelling (tumour) - accumulation of fluid in ECM
  • Pain (dolor) - stretching of tissue due to oedema, mediators such as bradykinin and serotonin stimulate pain receptors
  • Loss of function (functio laesa) - movement is inhibited by pain or severe swelling
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11
Q

Describe the vascular changes elicited by inflammation

A
  • Vasodilatation: transient vasoconstriction then vasodilatation
    > starts in arterioles & increases blood flow
    > due to histamine and nitric oxide in vascular smooth muscle
  • Increased vascular permeability
    > contraction of endothelial cells leads to increased interendothelial spaces & escape of protein rich fluid exudate into extravascular tissue (oedema)
    > mediated by histamine, bradykinin, substance P
  • Vascular congestion/stasis
    > Slower flow of blood, increased concentration of chemical mediators
  • Endothelial activation
    > By mediators produced during inflammation; increased levels of adhesion molecules
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12
Q

Describe how inflammatory cells migrate to the site of inflammation

A
  • Margination
    > Neutrophil polymorphs are the first cells to migrate to the site of inflammation
    > White cells are more peripheral within the blood vessel due to vascular stasis
  • Rolling
    > white cells stick & detach from wall; mediated by selectins
    > upregulated by IL-1 and TNF (from macrophages & PMNs)
    > binds L-selectin on leucocytes
  • Migration
    > Chemokines act on leucocytes to stimulate migration across endothelium via interendothelial spaces into ECM
  • Chemotaxis
    > Cells follow a chemical gradient: bacterial products, cytokine IL-8, complement, leukotriene B
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13
Q

Describe how phagocytic cells remove pathogens

A

Opsonisation - surrounding pathogen with antigen-antibody complexes or complement

Engulfment using pseudopodia (within macrophages or neutrophils)

Formation of phagosomes
> fusion with lysosomes containing enzymes to form phagolysosomes

Material destroyed & removed from cell by pinocytosis

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14
Q

List the different types of mediators of inflammation

A
  • Histamine: from mast cells, basophils, platelets
  • Serotonin: from platelets
  • Prostaglandins; from mast cells, leucocytes
  • Leukotrienes: mast cells, leucocytes
  • Platelet activating factor: leucocytes, mast cells
  • Nitric oxide: endothelium, macrophages
  • IL-1, TNF, IL-6: macrophages, endothelial cells, mast cells
  • Chemokines: leucocytes, activated macrophages
  • Complement: plasma (liver)
  • Kinins: plasma (liver)
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15
Q

Define exudate and define the different types of exudates

A

An exudate is extracellular fluid with a high protein and cellular content
> allows delivery of nutrients, dilution of toxins, entry of antibodies & stimulates the immune response

  • Types

> Fibrinous: fluid rich in fibrin, often on seroral surface, meninges e.g. fibrinous pericarditis

> Suppurative (abscess): pus-forming, exudate rich in neutrphil polymorphs

> Haemorrhagic: severe vascular injury or depletion of coagulation factors

> Membranous: epithelium becomes coated in membrane formed of fibrin, epithelial cells & inflammatory cells

> Pseudomembranous: ulceration; surface exudate on mucosal/epithelial sites e.g. C. diff colitis

> Necrotising: gangrenous; high tissue pressure leading to vascular occlusion & thrombosis; necrosis and bacterial putrefaction leads to gangrene

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16
Q

Describe the structure and function of neutrophil polymorphs

A

Neutrophil polymorphs are granulocytes with a multi-lobed nucleus as well as a granular pink cytoplasm

Neutrophils leave the vascular space in response to chemotactic signals generated by inflammation

Functions: opsonisation, phagocytosis, releasing lysosomal products & propagating the response

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17
Q

Describe the structure and function of mast cells

A

Mast cells are predominantly found within the skin and GI tract

They are granulocytes characterised by a basophilic granular cytoplasm (granules contain histamine and heparin)

They are stimulated to release their contents by injury, complement & IgE
> Play a role in allergy and anaphylaxis
> Make eicosanoids to propagate the immune response

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18
Q

Describe the structure and function of macrophages and monocytes

A

Monocytes are circulating, while macrophages are tissue resident

Macrophages are large cells with irregularly shaped nuclei containing numerous lysosomes
> Carry out phagocytosis & act as antigen-presenting cells
> Also have a role in chemotaxis as they synthesise TNF, IL-1 & IL-6

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19
Q

Describe how complement works and its function

A

Complement is a cascade which can be activated via

  • Classical pathway: antigen-antibody complexes
  • Alternative pathway: bacterial products & products of dying cells in tissue necrosis
  • Components of kinin, coagulation & fibrinolytic systems

Leads to the activation of C5a, which is chemotactic for neutrophils, increases vascular permeability and releases histamine from mast cells (C3a is similar to C5a)

When activating complement, opsonisation occurs (via C4b, C2a, C3b) and there is activation of the membrane attack complex (C5b, C6, C7, C8, C9) resulting in cell death

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20
Q

Describe the function of the following plasma factors:
- Kinin system
- Coagulation system
- Fibrinolytic system

A
  • Kinin system is activated by coagulation factor XII
  • Bradykinin alters vascular permeability & mediates pain
  • Coagulation system: conversion of fibrinogen to fibrin, which forms part of the inflammatory exudate
  • Fibrinolytic system: plasmin lyses fibrin into fibrin degradation products
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21
Q

Describe the histopathology seen in chronic inflammation

A
  • Infiltrates of
    > Lymphocytes (large nuclei, little cytoplasm)
    » T cells: produce cytokines to attract & activate macrophages, involved in cell-mediated immunity
    » B cells: antibody production

> Plasma cells: clock face eccentric nucleus, perineuclear hof (Golgi body), dark purple cytoplasm, produce antibodies

> Macrophages: large cells with irregular nuclei and abundant cytoplasm
> Activated macrophage products perform the following functions

  • Tissue destruction: oxygen metabolites, proteases, neutrophil chemotactic factors, coagulation factors, arachidonic acid metabolites, NO
  • Fibrosis: growth factors (PDGF, FGF, fibrogenic cytokines (TGF-beta), angiogenesis factors, remodelling collagenases
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22
Q

Describe the histological characteristics of granulomatous inflammation

A
  • Predominant cell types are
    > Epithelioid macrophages: modified macrophages arranged in small nodules or clusters; mainly secretory role instead of phagocytosis

> Giant cells (fused epithelioid macrophages)

> Lymphocytes: CD4+ & CD8+; formation of granulomas can be a manifestation of T cell-mediated immune reaction (delayed type hypersensitivity); the antigen is presented to CD4+ T cells which produce IFN gamma & other cytokines, this activates macrophages & results in granuloma formation

> These form granulomas: collection of macrophages surrounded by lymphocytes, other macrophages & plasma cells

  • Necrosis can result , often in infective cases
    » Caseous necrosis in tuberculosis
    » Granulomas are also present in sarcoidosis, histoplasmosis, Crohn’s disease (without necrosis)
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23
Q

Describe the causes of granulomatous inflammation

A

Types of granulomatous inflammation: necrotising, non-necrotising & foreign body type

Can be caused by

> Infectious agents: tuberculosis (necrotising); leprosy; toxoplasmosis

> Foreign materials e.g. talc pleurodesis in patients with chronic pleural effusion or at a site of a previous operation if retained sutures

> Sarcoidosis, Crohn’s disease (Non-necrotising)

> Response to tumour e.g. Hodgkin’s lymphoma

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24
Q

List the phases of tissue healing

A
  • Formation of blood clot
  • Formation of granulation tissue > cell proliferation (fibroblasts) & collagen III deposition
  • Scar formation (fibrosis)
  • Wound contraction
  • Connective tissue remodelling
  • Recovery of tensile strength
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25
Q

Describe the phases involved in fracture healing

A
  • Inflammatory
    > Haematoma forms at the site of fracture
    > Prostaglandins recruit neutrophil polymorphs, macrophages, lymphocytes and fibroblasts
    > Granulation tissue, ingrowth of
  • Repair
    > Fibroblassts lay down stroma to support ingrowing vessels
    > Collagen matrix is laid down
    > Osteoid is secreted & mineralised leading to soft callus formation
    > Callus ossifies after 4-6 weeks by forming a bridge of woven bone between fracture fragments
  • Remodelling
    > Occurs slowly over months and years
    > Returns bone to its original shape, structure & mechanical strength
    > Facilitated by mechanical stress
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26
Q

Describe conditions associated with excess eosinophils

A
  • Hypereosinophilia syndrome
    > FIPL-1-PDGFRA-fusion induced hypereosinophilia
    > Fusion drives excess production of clone eosinophils
    > These drive inflammatory processes within the myocardium which damage myocytes in subendocardial distribution; fibrosis ensues
    > Presents clinically as a restrictive cardiomyopathy
  • Allergic rhinitis
  • Nasal polyps
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27
Q

Describe the clinical features of rheumatoid arthritis

A
  • Chronic inflammatory disease affecting the skin, blood vessels, heart, lungs, muscles & joints
  • Clinical features
    > Non-suppurative, proliferative synovitis
    > Destruction of articular cartilage
    > Inflammatory infiltrate: lymphocytes, plasma cells, dendritic cells, macrophages
    > Increased vascularity: vasodilatation & angiogenesis
    > Aggregation of fibrin
    > Pannus formation leading to erosion of cartilage and bone
    > Neutrophils in synovial fluid
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28
Q

Describe the characteristics of atherosclerosis

A

Endothelial injury caused by shear stress, smoking…

Monocytes adhere to the lining of the artery wall and become intimal macrophages

Scavenger receptors pick up lipids leading to the formation of foam cells

Build up of atheromatous plaque leads to the occlusion of vessels (stenosis)

Lymphocytes release chemical mediators recruiting more inflammatory cells

> Reduced blood supply to tissues so oxygen demand is not met, leading to ischaemia and symptoms of angina

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29
Q

Describe the characteristics of Chronic Granulomatous Disease (CGD)

A
  • Defect in NADPH oxidase system within phagocytes, including macrophages

> Heterogeneous, but usually X-linked

> Inability to kill intracellular organisms by respiratory burst (defective phagocytosis)

> Patients have repeated & recurrent infections
> Patients develop granulomata of lymph nodes, skin, lungs, liver & GI tract

30
Q

Describe the characteristics of ventricular septal defects (VSD)

A
  • Most common congenital cardiac malformation, associated with syndromes such as Down’s
  • Usually asymptomatic at birth and manifest a few weeks after
  • Characterised as an acyanotic congenital heart defect: left-to-right shunt, no signs of cyanosis at an early stage

> Uncorrected VSD can increase pulmonary resistance leading to the reversal of the shunt and corresponding cyanosis

31
Q

Describe the characteristics of spina bifida (myelomeningocoele)

A

Defect of the neural tube i.e. embryonic structure that develops into the spinal cord & brain wherein the neural tube fails to develop or close properly
> If this is towards the lower limbs - spina bifida - towards the head would be an encephalocoele

Spina bifida can be open or closed (spina bifida occulta)
> High dose folic acid is used to reduce the risk

32
Q

Define ectopia and give examples

A

Ectopia describes the abnormal location/position of an organ or tissue; can occur congenitally or as the result of an injury

> Ectopia cordis: displacement of the heart outside the body
Ectopic thyroid tissue: nodules of mature thyroid tissue located elsewhere in the neck
Ectopic pregnancy: implantation occurring in the fallopian tube rather than endometrium

33
Q

Define what is meant by a hamartoma and give an example of a condition in which they arise

A

A hamartoma is a tumour-like malformation composed of mature normal cells in their usual location but as a disorganised mass
> Composed of a mixture of mature tissue elements which would normally be found at that site which develop and grow at the same rate as surrounding tissue but in a disorganised manner

> Peutz-Jeghers syndrome: mutation of STK11 gene on chromosome 19p13.3
> Characterised by mucocutaneous pigmentation and hamartomatous polyposis in the jejunum & ileum
» Disorganised villi, mass of muscularis mucosa extending into lamina propria

34
Q

Define diverticulum and give an inherited and an acquired example of conditions characterised by the presence of diverticula

A

A diverticulum is a circumscribed pouch/sac caused by herniation of the lining of the mucosa of an organ through a defect in the muscular coat

E.g. Meckel’s diverticulum: congenital diverticulum in the terminal ileum
> Blind-ending duct which is the remnant of the yolk sac which nourished the embryo that failed to involute
> Contains all layers of the intestine (true diverticulum) & has ectopic tissue within it (pancreatic/gastric)

> Complications include inflammation, bleeding from ulcerated gastric tissue, perforation, obstruction/intussusception

E.g. sigmoid colon diverticula/diverticular disease
> Reduced dietary fibre in older adults: low residue in distal colon, constipation induces muscular hypertrophy, increased intraluminal pressure & outpouching of mucosa

> Complications: diverticulus, inflammation & ulceration (abscess formation, fistulae, haemorrhage) or repeated attacks (fibromuscular thickening, stenosis)

35
Q

Define intussusception and describe associated complications

A

Intussusception refers to the invagination of a portion of the small intestine usually into the large intestine
> common between 5-9 months of age, mostly at ileocaecal valve

  • Progressive compression of blood supply causes haemorrhagic necrosis
    > In older children can be associated with neoplasia
36
Q

Define metaplasia and give examples of when this might occur

A

Metaplasia is the reversible change from one fully differentiated cell type into another
> Adaptation that cells sensitive to a particular stress are replaced by cells better able to withstand the environment.

e.g. cigarette smokers - normal ciliated columnar epithelial cells of trachea & bronchi are replaced by stratified squamous epithelial cells

e.g. chronic gastroesophageal reflux - normal stratified squamous epithelium of the lower oesophagus may undergo metaplasia to gastric columnar epithelium (Barrett’s oesophagus)

37
Q

Define dysplasia and give an example of when this might occur

A

Dysplasia refers to disordered growth in which cells fail to differentiate fully but are contained by the basement membrane (not invasive)

> E.g. cervical intraepithelial neoplasia, CIN

Carcinoma in situ is a form of severe dysplasia - full thickness epithelial dysplasia extending from BM to epithelium surface (applicable only to epithelial neoplasms, no risk of metastasis as BM has not been breached)

38
Q

Define anaplasia

A

Loss of differentiation in tumour cells so they bear no resemblance to any mature tissue

39
Q

Describe the different routes of tumour spread and the tumours which usually spread through them

A
  • Local invasion
  • Lymphatic spread: usual initial mode of spread of carcinomas e.g. breast, colon, lung
    » Tumour travels to draining lymph nodes, e.g. breast cancer goes to axillary nodes, thereby to thoracic duct & systemic circulation
  • Perineural spread
  • Blood vessels (venous, not arterial)
    > Usual mode of spread of sarcomas; also carcinomas, but later than lymphatic
    » common sites of metastasis relate to the primary tumour and its routes of venous drainage e.g. liver, colon carcinoma via hepatic portal venous supply
  • Transcoelomic (serosal): common mode of spread of gastric adenocarcinoma and ovarian carcinoma
40
Q

Describe the staging system used to stage tumours

A

TNM system

  • Tumour: size and extent of local invasion of primary tumour e.g. T1-T4
  • Nodes: N0, N1, N2 depending on number of LNs involved
  • Metastasis e.g. M0 (none) or M1 (present)
41
Q

Describe Virchow’s triad

A
  • Hypercoagulable state e.g. oestrogen therapy, pregnancy, malignancy…
  • Vascular wall injury e.g. trauma, atherosclerosis, heart valve disease…
  • Circulatory stasis e.g. immobility, venous insufficiency, atrial fibrillation…
42
Q

Differentiate between an arterial and a venous thrombus

A

Arterial: white thrombus - many platelets, small amounts of fibrin (reflects high flow)

Venous: red thrombus - a lot of fibrin with trapped red cells (reflects indolent flow)

43
Q

Describe how a DVT might be diagnosed

A
  • Clinical decision rule: determine likelihood of DVT with Well’s Clinical Scoring System in A&E
  • Blood tests: fibrin D-dimer (especially when very elevated as D-dimer can be raised in other conditions such as pregnancy)
  • Image venous system of leg via compression ultrasound or venography
44
Q

List the outcomes following a DVT

A
  • painful swollen leg
  • pulmonary embolism
  • recurrent VTE
  • venous insufficiency
  • Post-thrombotic syndrome
    > persistent chronic pain
    > swelling
    > ulceration
45
Q

Describe the outcomes following a PE

A
  • Dyspnoea, chest pain, haemoptysis
  • Collapse (massive PE)
  • Death (fatal PE)
  • Recurrent VTE
  • Chronic thromboembolic pulmonary hypertension
46
Q

Describe the pathophysiology of coronary artery disease

A
  • Development of atheroma/plaques
  • Progressive narrowing & stenosis of artery
  • Plaque rupture
  • Acute thrombus with vascular occlusion & downstream ischaemia & infection
47
Q

Describe how an MI or acute coronary syndrome is diagnosed

A

History
- Chest pain, nausea, sweating

Clinical evidence of cardiac dysfunction: hypotension, tachycardia

ECG findings
STEMI - ST elevation

NSTEMI - ST depression or T inversion

Biochemical evidence of myocardial damage: elevated troponin

Visualisation of coronary arteries via cardiac catheterisation

48
Q

Describe the treatment of acute coronary syndrome

A
  • Prevent thrombus extension: anti-platelet agent like aspirin & clopidogrel; anticoagulant like LMWH
  • Remove the thrombus
    > Thrombolysis: alteplase, tenecteplase
    > Remove clot via percutaneous coronary intervention (PCI)
  • Widen the stenotic plaque
    > Balloon angioplasty, insert coronary artery stent
  • Prevent further thrombus: anti-platelet agent, statin
49
Q

List the complications following an MI

A
  • Death
  • Arrhythmia
  • Pericarditis
  • Myocardial rupture
  • Mitral valve prolapse
  • Left ventricular aneurysm +/- thrombus
  • Heart failure
50
Q

Define atrial fibrillation giving its characteristics

A

Atrial fibrillation is an arrhythmia characterised by the rapid and irregular beating of the atria of the heart; it increases the risk for clot formation, possibly leading to stroke

2 types: valvular & non-valvular AF

ECG changes include loss of P wave before QRS complex

51
Q

Describe the treatment of stroke and AF

A
  • Remove thrombus (rarely) but if done, via thrombolysis or carotid endarterectomy
  • Remove/correct source of thrombus
    > Anticoagulation (warfarin or DOAC)
    > Revert to sinus rhythm (cardioversion)
    > Replace defective heart valve
  • Address other CVD risk factors e.g. hypertension or hyperlipidaemia
52
Q

Describe the steps that are followed in a routine autopsy

A
  • External examination
    > Identification
    > General appearances: height, weight, BMI, skin, hair, eye colour, evidence of trauma
    > External disease: jaundice, finger clubbing, oedema, lymphadenopathy
    > Medical treatment (iatrogenic): scars, drains, IV lines
  • Internal examination
    > Evisceration: removal of thoracic, abdominal & pelvis organs, as well as brain
    > Organ dissection: inspection and dissection of organs for macroscopic assessment; tissue retained for microscopic assessment & toxicology performed
  • End of PM examination:
    > Organs returned to body cavity & death certificate issue
    > National Records Scotland regards the last condition recorded in Part 1 as the cause of death and records it in death statistics
    > Detailed information on completing this document is available from the guidance document from the Chief Medical Officer
53
Q

What is a berry aneurysm?

A

Congenital weakness in cerebral artery due to a lack of elastic fibres leads to subarachnoid haemorrhage from their rupture

54
Q

Describe the differences between the 2 types of pneumonia

A
  • Lobar pneumonia
    > Spreads through blood rather than down airways
    > Largely confined to one lobe
    > Gives lung a grey colour (grey hepatisation)
    > Severe illness
  • Bronchopneumonia
    > Spreads through airways and tends to be more generalised
    > Often develops on top of chronic lung disease and is a terminal event in debilitated patients
55
Q

Give the DDX for dizziness

A
  • Postural hypotension
  • Hypoglycaemia
  • Iron deficiency anaemia
  • Anxiety
  • Drugs e.g. hypotensive drugs, opioids e.g. morphine, glyceryl trinitrate (GTN), antibiotics
56
Q

Describe the causes of vertigo

A
  • Central (urgent), presents with new onset headache, prolonged & severe vertigo, severe nausea
    > Stroke or TIA: headache in posterior circulation stroke, double vision
    > Migraine: headache, photophobia, nausea
    > Head injury
    > Brain tumour
    > Illness/infection
    > Multiple sclerosis
  • Peripheral
    > Acute labyrinthitis (viral cause)
    > Vestibular neuronitis (inflammation of vestibular nerve post-infection)
    > Meniere’s disease
    > Benign Paroxysmal Positional Vertigo (BPPV)
57
Q

Describe the cause, diagnosis and treatment of BPPV

A

Caused by little calcium carbonate crystals (otoconia) coming loose within the canals
> Episodes triggered by head movements and last less than 1 minute

  • Diagnosed via Dix-Hallpike positional test, which will elicit torsional/rotatory nystagmus and vertigo
  • Treated with antihistamines (cyclizine), antiemetics (prochlorperazine, a phenothiazine), and the Epley manoeuvre
58
Q

Describe the symptoms of Meniere’s disease

A
  • Tinnitus
  • Severe vertigo not elicited by head movement
  • Hearing loss
  • Feeling of fullness/congestion in ear
59
Q

Describe the symptoms of a posterior circulation stroke

A
  • Vertigo
  • Imbalance
  • Unilateral limb weakness
  • Slurred speech
  • Double vision
  • Headache
  • Nausea
  • Vomiting
60
Q

Describe the Coombes and Gell Classification of the adaptive immune response

A
  • Immediate Hypersensitivity (Type I); mast cells & IgE
    > Response to the challenge occurs immediately e.g. asthma, eczema, hayfever, anaphylaxis
  • Antibody-mediated hypersensitivity (Type II)
    > Antibody recognises surface antigens in human cells
    > Inflammatory cells & complement activated e.g. autoimmune haemolytic anaemia
  • Immune-complex mediated (type III)
    > Complexes of antigens & antibodies binding to soluble antigens cause a response in the vasculature of an organ e.g. systemic lupus erythematosus
  • T-cell mediated or delayed type (Type IV)
    > Helper T cells or cytotoxic T cells infiltrate the area several days after exposure e.g. type I diabetes
61
Q

Describe the pathophysiology of allergy

A

The immune system is sensitised to an antigen & produces IgE in response
> B Cells activated & CD4 cells produce IL-4

> Mast cells primed with IgE
Re-exposure to antigen: binds to IgE associated with mast cells

> Mast cell degranulates releasing mediators

  • Early phase (within minutes)
    » Airway swelling - increased vascular permeability
    » Smooth muscle contraction
    » Immediate loss of airflow
  • Late phase (hours-days after)
    » Mediated through recruitment of T cells & other immune cells
    » Results in sustained smooth muscle contraction/hypetrophy and remodelling
62
Q

Give 3 examples of organ-specific autoimmune disease and explain the pathophysiology of one

A
  • Type I diabetes mellitus
  • Graves’ disease: affects the thyroid gland
    > Normally the pituitary gland releases TSH, which binds to its receptor and stimulates synthesis of thyroid hormones
    > Regulated by a negative feedback loop, so once enough hormone is produced the pituitary switches off TSH production

In the disease, autoantibodies (long-acting thyroid stimulating hormones) are made against the TSH receptor
> Antibody binds to receptor, mimicking TSH binding
> Stimulates thyroid cells to overproduce hormones
> Negative feedback loop still happens, suppressing TSH (but antibody continues to stimulate receptor) - results in hyperthyroidism

  • Myasthenia gravis
63
Q

Give 3 examples of systemic autoimmune disease and explain the pathophysiology of one

A
  • Rheumatoid arthritis
    > Clinical presentation: pulmonary nodules & fibrosis, pericarditis & valvular inflammation, small vessel vasculitis, soft tissue nodules, skin inflammation, weight loss, anaemia

> Pathophysiology:
> Rheumatoid factor (IgM and IgA directed against IgG Fc region form large immune complexes which reach high concentrations within synovial fluid)
> Inflammation leads to release of PAD (arginine deaminase) which converts arginine to citrulline; anti-citrullinated peptides (anti-CCP) are common in RA
They are soluble peptides which form immune complexes as CCP antibodies bind
Citrullinated proteins displayed on cell surface resulting in antibody binding (type II hypersensitivity)
Infiltration of activated macrophages, neutrophils, osteoclasts

  • Systemic Lupus Erythematosus (SLE)
  • Scleroderma
64
Q

Describe the biological treatments used in RA

A

Monoclonal antibodies specifically target inflammatory molecules

  • Anti-TNF: infliximab, etanercept
    » Reduces joint damage, risk of osteoporosis & cardiovascular disease
  • Anti IL-6 receptor e.g. tocilizumab
  • AntiCD20 e.g. rituximab
65
Q

Describe the different types of T cells and where they may be found

A
  • T cells mature in thymus, T cell receptor complex on surface part of which (CD3) recognises antigens
  • Subdivided by expression of surface molecules
  • CD4 + T cell (helper) - secrete cytokines, activate B cells
    > Th1: IFN-gamma secretion; host defense against intracellular microbes; inflammation
    > Th2: IL-4,1L-5,1L-13 secretion; host defense against helminths; allergic reactions
    > Th17: IL-17 secretion; host defense against some bacteria, inflammatory disorders
    > T regulatory cells: regulate function of other immune cells
  • CD8+ Y cell (cytotoxic)
    > Kill virally infected cells and tumour cells via the induction of apoptosis (introducing perforin + granzymes into the cell)
  • Natural killer (NK) T cells
66
Q

Describe the different types of major histocompatibility complexes (MHC)

A
  • Class I MHC is on all nucleated cells and presents to cytotoxic T cells
  • Class II MHC is restricted to dendritic cells, macrophages, B cells (antigen-presenting cells); presents to helper CD4+ T cell
67
Q

Describe the structure and function of antibodies

A

Antibody structure
> 2 heavy chains
> 2 light chains
> Fab region - antigen recognition happens in the arms (antigen binding sites found here)
> Fc region - binds to Fc receptors on phagocytes, activates complement

Functions:
> Neutralisation of bacterial toxins
> Agglutination
> Opsonisation (enhance phagocytosis)

> Complement activation: antibody-antigen complex activates classical pathway

68
Q

Describe the 5 isotypes of antibodies (differ in Fc regions)

A
  • IgG: main antibody of secondary immune response; can cross placenta
  • IgA: found in inner mucosal surfaces and secretions (mucus, saliva, tears, breast milk)
  • IgM: main antibody of primary immune response
  • IgD: found on cell membrane of B cells to recognise antigen; activates basophils and mast cells
  • IgE: responsible for allergic reactions; high affinity binding to mast cells through Fc epsilon receptor
69
Q

Describe the primary and secondary lymphoid organs

A
  • Primary lymphoid organs:
    > Bone marrow: B lymphocytes produced & matured
    > Thymus: selection of autoreactive cells to prevent autoimmunity
  • Secondary lymphoid organs
    > Spleen: filtering of blood, collection of blood-borne antigens, reservoir of RBCs & WBCs
    > Tonsils: within oral cavity to protect against foreign substances (palatine, lingual, tubal, pharyngeal)
    > Appendix
    > Lymph nodes: site of activation of adaptive immune response
    > Mucosa associated lymphoid tissues (MALT) and bronchial tract (BALT): GI tract, respiratory tract, urinary tract, reproductive tract…
70
Q

Describe the humoral immune response

A

Used for extracellular microbes or bacteria

  • Naive B lymphocytes activated as antigen binds to membrane immunoglobulin; antigen presented on cell by MHC-II proteins
  • T helper cell binds to antigen & is activated, releasing cytokines (costimulatory signals)
  • Cytokines cause B cells to proliferate - clonal expansion
  • B cells differentiate into daughter cells
    > IgM expressing plasma cells secrete early antibodies
    > Affinity maturation takes place, immune response becomes more targeted
    > IgG expressing B cells (isotype switching)
    > Memory B cells
  • Antibodies agglutinate & opsonise bacteria, neutralise bacterial toxins
  • Macrophages or complement will kill bacteria
71
Q

Describe the cell-mediated immune response

A
  • For intracellular microbes e.g. virus, cancerous cell, intracellular bacteria

Host cells present antigenic fragments as a complex with their own self markers (MHC class I)
> Cytotoxic T cells binds to antigen on antigen-presenting cell
> Cytotoxic T cells inject perforin into the cell membrane & introduce granzymes to induce apoptosis

Phase 3 (14 decks)

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