Mechanisms of Disease Flashcards
1
Q
What is the meaning of the prefix ana-
A
Absence
2
Q
What is the meaning of the prefix dys-
A
Disordered
3
Q
What is the meaning of the prefix hyper-
A
Excess over normal
4
Q
What is the meaning of the prefix hypo-
A
Deficiency below normal
5
Q
What is the meaning of the prefix meta-
A
Change from one state to another
6
Q
What is the meaning of the suffix -itis
A
Inflammatory process
7
Q
What is the meaning of the suffix -oma
A
tumour
8
Q
What is the meaning of the suffix -osis
A
State or condition
9
Q
What is the meaning of the suffix -oid
A
Bearing a resemblance to
10
Q
What is the meaning of the suffix -penia
A
Lack of
11
Q
What is the meaning of the suffix -cytosis
A
Increased number of cells
12
Q
What is the meaning of the suffix -ectasis
A
Dilation
13
Q
What is the meaning of the suffix -plasia
A
Disorder of growth
14
Q
What is the meaning of the suffix -opathy
A
Abnormal state lacking specific characteristics
15
Q
What is hypertrophy
A
An enlargement of an organ or tissue from an increase in the size of its cells
16
Q
What is hyperplasia
A
The enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells
17
Q
What is an embolus
A
A blood clot, air bubble, piece of fatty deposit, or other object which has been carried in the bloodstream to lodge in a vessel and cause an embolism
18
Q
What is a thrombus
A
A blood clot formed in situ within the vascular system of the body and impeding blood flow.
19
Q
What is a fistula
A
An abnormal or surgically made passage between a hollow or tubular organ and the body surface, or between two hollow or tubular organs.
20
Q
What is dysplasia
A
The presence of cells of an abnormal type within a tissue
21
Q
What is neoplasia
A
The presence or formation of new, abnormal growth of tissue
22
Q
What is differentiation of cells
A
The process by which cells, tissue, and organs acquire specialized features, especially during embryonic development.
23
Q
What is metastasis
A
The development of secondary malignant growths at a distance from a primary site of cancer
24
Q
What are the general principles of immune response
A
Multilayer defence Network of pathogen recognition Effective inter-cellular communication Multiple mechanisms of pathogen clearance Adaptive responses to changing pathogen Self-regulation
25
What is autoimmunity
Theoretical concept
The system of immune responses of an organism against its own healthy cells and tissues
Genetically determined
26
What are autoimmune diseases
Distinct clinical entities
Breakdown of self-tolerance
Environmental factors acting on favourable genetic background
27
What are causative associations with autoimmune diseases
Sex: likely due to normal influence, more common in women than in men
Age : autoimmunity is more common in elderly
Environmental triggers: infection, trauma-tissue damage, smoking
28
What is the pathophysiology of autoimmunity
Autoreactive B cells and autoantibodies: directly cytotoxic, activation of complement, interfere with normal physiological function
Autoreactive T cells: directly cytotoxic, inflammatory cytokine production
General inflammation and end organ damage
29
What are the general clinical features of autoimmune diseases
```
More than 100 different diseases
Can affect any organ
Onset in middle/old age
More common in elderly and in women
Leads to loss of organ function
Lifelong-chronic condition
Characteristic exacerbation and remission
Traditionally divided into organ specific or systemic
Common for diseases to overlap
```
30
What are organ specific vs systemic autoimmune conditions
Organ specific:
affect a single organ, autoimmunity restricted to auto antigens of that organ, overlap with other organ specific diseases, autoimmune thyroid disease is typical
Systemic:
affect several organs simultaneously, autoimmunity associated with auto antigens found in most cells of body, overlap with other non-organ specific diseases, connective tissue diseases are typical
31
What are examples of connective tissue diseases
Systemic lupus erythematosus
Scleroderma
Polymyositis
Sjorgrens syndrome
32
What are types of diagnostic tests for autoimmune conditions
Non-specific: inflammatory markers
| Disease specific: autoantibody testing, HLA typing
33
What is HLA
proteins/marker on most cells in the body
Stands for human leukocyte antigens
Immune system uses HLA to recognize which cells belong in body and which do not
34
Why are autoantibodies measured
```
Diagnostic
Early diagnosis
Pathogenic
Subtyping of patients
Monitoring of exacerbation/remission
Exclusion of diagnosis
Cost of treatment
```
35
What is immunosuppression
A natural or artificial process which turns off the immune response, partially or fully, accidentally or on purpose
36
What is immunodeficiency
The lack of an efficient immune system-susceptibility to infections
Usually secondary to the effects of external factors
Some are primary immondeficiencies caused by genetic defects in individual components of the immune system
Type of infection is a guide to the underlying cause
Laboratory tests confirm
37
What are causes of secondary immunodeficiencies
```
Stress
Surgery
Burns
Malnutrition
Cancer
Immunosuppressive effect of drugs
Irradiation
AIDS
Infections such as measles or TB
```
38
Define allergy and hypersensitivity
```
A reaction produced by the normal immune system, directed against innocuous antigens, in a pre-sensitised immune host
Undesirable
Damaging
Uncomfortable
Sometimes fatal
```
39
What is type I hypersensitivity
Primary response:
IgE antibody mediated mast cell and basophil degranulation
Releases:
Histamine, proteases, chemotactic factors
Fast onset (15-30 mins)
Blanched weal appears surrounded by an area of redness (weal and flare)
Late phase response (lipid mediators):
Releases:
Eosinophils
Central role for Th2 T cell
Prostaglandin, leukotrienes
40
What is anaphylaxis
Medical emergency
An acute, potentially life threatening, IgE mediated systemic hypersensitivity reaction
Clinical symptoms:
Severe abdominal pain, vomitting, diarrhoea, hoarseness, cough, shortness of breath, wheezing and cyanosis, respiratory arrest, hypotension, dizziness, loss of consciousness
41
What is the atopic triad
Asthma, rhinitis and eczema
42
What are type II hypersensitivity reactions and their clinical relevance
Cytotoxic
Mechanism:
IgG/IgM Ab response against combined self/foreign antigen at the cell surface
Complement activation/ phagocytosis/ ADCC
Clinical features:
Onset minutes to hours
Cell lysis and necrosis
Common antigens:
Penicillin
Diseases resulting in this:
Good pasture's nephritis
Blood transfusion reaction
43
What are type III hypersensitivity reactions and their clinical relevance
Immune complex
Mechanism:
IgG/ IgM Ab against soluble antigen immune complex deposition
Clinical features:
Onset 3-8hours
Vasculitis
Traditional cause:
Serum sickness
Associated diseases:
SLE
44
What are type IV hypersensitivity reactions and their clinical relevance
Delayed
Mechanism:
Antigen specific T cell mediated cytotoxicity
Clinical features:
Delayed onset 48-72 hours
Erythema induration
Common antigen:
Metals
Tuberculin test
Posion ivy
Associated diseases:
Contact dermatitis
45
Why do people get allergies
Components of the immune system responding to parasitic infection are also involved in allergic responses
The system has developed to produce a rapid tissue based response to re infection
Lack of infectious drive is a contributory factor
Combination of genetic and environmental factors
46
How are we sensitised
Allergen seen by dendritic cell -> presented to naïve T cell -> T cell differentiates into a Th2 cell -> secretes cytokines IL-4 and IL-13 which act as signals to naïve B cells -> naïve B cells become memory B cells which have specific IgE which will recognise the allergen on further exposure
47
What does the duel allergen exposure hypothesis suggest
Early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitisation, but early oral exposure to food allergen induces tolerance
48
What are the two types of cell adaptations
Hypertrophy: increase in muscle mass
Atrophy: decrease in muscle mass
49
What is necrosis
Severe cell swelling and rupture
Death of tissue following bioenergy failure and loss of plasma membrane integrity
Includes inflammation and repair
50
What is apoptosis
Internally controlled cell death
Individual cell deletion in physiological growth control and in disease
Activated or prevented by many stimuli
Increased apoptosis results in excessive cell loss
51
What is oncosis
Pre lethal changes preceding cell death
52
What are causes of cell injury
```
Hypoxia
Physical agents: temperature, trauma, radiation
Chemical agents: drugs
Immunologic reactions
Infectious agents
Genetic derangements
Nutritional imbalances
```
53
What is inflammation
A protective response to injury
Essential to survival
Aims to rid the body of the initial cause of the injury and consequences of such injury
54
What is acute inflammation
The initial tissue reaction to injury
Lasts minute, hours or days
Characteristic cell is the neutrophil polymorph
Blood vessel dilatation and increased permeability
55
What are the physical characteristics of acute inflammation
```
Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Loss of function (function laesa)
```
56
What are causes of acute inflammation
```
Physical agents
Infections
Hypersensitivity reaction
Chemicals
Tissue necrosis
```
57
What are the major components of acute inflammation
Changes in vessel calibre
Increased vascular permeability and fluid exudate (rich in protein) formation
Cellular exudate formation
58
What is exudate
Extravasuclar fluid with high protein conc, containing cellular debris, implies inflammation
59
What is transudate
Low protein, little to no cellular components
60
What is oedema
Excess fluid in interstitial tissue/serous cavities
61
What is Pus
Inflammatory exudate rich in neutrophils, dead cell debris and microbes
62
How does the fluid exudate form
Increased permeability of microvasculature results in escape of protein rich fluid into tissue
Causes:
Chemical mediators (histamine, NO, leukotriene)
Direct vascular injury (trauma)
Endothelial injury (bacteria and toxins)
63
What are the effects of fluid exudate
```
Dilution of toxins
Entry of antibodies
Transport of drugs
Fibrin formation
Delivery of nutrients and oxygen
Stimulation of the immune response
High turnover
```
64
How does cellular exudate form
Loss of fluid into tissues and increased calibre of vessels-slower blood flow and increase viscosity of blood-stasis
Neutrophils line up along vascular endothelium, stick to endothelium and migrate through wall into tissues
65
What are neutrophils
```
Produced in bone marrow
Commonest white cell in blood
Increase in acute inflammation
Motile, amoeboid, can move into tissues
Directional chemotaxis
Short life span (hours in tissues)
```
66
What are chemical mediators of acute inflammation
Vasodilation
Migration of neutrophils
Chemotaxis
Increased vascular permeability
67
What are the cell derived mediators of acute inflammation
```
Histamine
Prostaglandins
Lysosomal components
Leukotrines
Cytokines
```
68
What are the plasma derived mediators of acute inflammation
Complement system
Kinin system
Coagulation system
Fibrinolytic system
69
What are the results of acute inflammation
Usual result: resolution
Excessive exudate: suppuration -> discharge of pus or repair and organisation -> fibrosis
Excessive necrosis: repair and organisation -> fibrosis
Persistant causal agent: chronic inflammation -> fibrosis
70
What are the types of cell injury
Reversible: cell swelling, pallor, hydronic change, vacuolar degeneration
Irreversible: mitochondrial swelling, lysosomes swell, damage to membrane, leakage of enzymes
Ischaemic/reperfusion: new damage on repercussion mediated by free oxygen radicals
71
What are the types of necrosis and an example of each
```
Coagulative: Myocardial infarction
Liquefactive: bacterial or fungal infection, CNS hypoxia
Gangrenous: limb ischaemia
Caseous: tuberculosis
Fat necrosis
Fibrinoid necrosis
```
72
What is coagulative necrosis
Commonest form
Occurs in most organs
Cells retain their outlines
Protein coagulate and metabolic activity ceases
73
What is liquefactive necrosis
Seen in brain
Due to lack of substantial supporting storm
Neural tissue may totally liquify
74
What is gangrenous necrosis
Putrefaction of the tissue
Cause is mostly infectious/ bacteria
Appear black
Types:
Wet- gangrene with superimposed infection
Dry- ischaemic coagulative necrosis only
Gas- Superimposed infection with gas producing organism
75
What is caseous necrosis
Tuberculosis is main cause
Structureless dead tissue
Amorphous pink material in centre with necrotic debris
76
What are the causes of fat necrosis
Enzymes
| Trauma
77
When is fibrinoid necrosis present
In two conditions:
Malignant hypertension
Autoimmune diseases
78
What are the most important factors in determining the outcome of injury
The ability of the cells to replicate
| The ability of the cells to rebuild complex architectural structures
79
What are the characteristics of Labile cell populations
High normal turnover
Active stem cell population
Excellent regenerative capacity
Eg Epithelia
80
What are the characteristics of Stable (quiescent) cell populations
Low physiological turnover
Turnover can massively increase if needed
Good regenerative capacity
Eg Liver, renal tubules
81
What are the characteristics of permanent cell populations
No physiological turnover
Long life cells
No regenerative capacity
Eg neurons, striated muscles
82
What are the characteristics of stem cell populations
```
Prolonged self renewal
Asymmetric replication
Reservoirs present in many adult tissues
Located in specific areas
Survival of stem cells is crucial to regeneration
```
83
What is the difference between healing by regeneration and by repair
Regeneration:
tissue returns to normal
Restitution of specialised function
Repair:
Fibrosis and scarring
Loss of specialised function
84
How do organisations 1 and 2 repair damaged cells
1:
The repair of specialised tissue by formation of a fibrous scar
Basic stereotyped pathological process
Production of granulation tissue and removal of dead tissue by phagocytosis
2:
Granulation tissue contracts and accumulates collagen, forming a scar
Organisation is a common consequence of pneumonia and infarction
Organised area - firm and puckered
85
What is granulation tissue made up of
New capillary loops
Phagocytic cells: neutrophils and macrophages
Myofibroblasts
86
What is healing by first intention from a surgical wound
Clean uninfected wound
Good haemostats
Edges opposed with sutures or staples
Edges joined by a thin layer of fibrin, eventually replaced by a collagen covered surface epidermis. Coagulated blood forms the scab. Fibrin join should not be disrupted. Epidermis grows over defect or if the wound is gaping then can grow down into defect but then usually stop growing and become reabsorbed but can remain and grow to form a keratin filed cyst
Only residual defect is the inability to reconstruct the elastic network within the dermis.
87
What is healing by second intention from a surgical wound
```
Wound edges not apposed
Extensive loss of tissue
Apposition not physically possible
Large haematoma
Infection
Foreign body
Not a fundamentally different process from first intention
More Florid granulation tissues reaction
More extensive scarring
```
Healing by secondary intention tissue defect is larger. Becomes replaced by granulation tissue which eventually contracts leaving a scar
88
What are the factors that inhibit healing
```
Local:
Infection
Haematoma
Blood supply
Foreign bodies
Mechanical stress
```
```
Systemic:
Age
Drugs
Anaemia
Diabetes
Malnutrition
Catabolic states
Vit C deficiency
Trace metal deficiency
```
89
What is fracture healing
Haemorrhage around and within the bone
Haematoma is organised
Removal of necrotic fragments
Osteoblasts lay down disorganised woven bone (callus)
Romodelling according to mechanical stress
Replacement by more orderly lamellar bone
90
How does the brain heal
Neurones are terminally differentiated and supporting tissue is glial cells rather than collagen and fibroblasts etc and so these can proliferate. Hence damaged tissue is removed, often leaving cyst
Results in gliosis rather than scarring
91
What are the characteristics of chronic inflammation
```
Innate and adaptive immunity
Lasts weeks, months, years
Angiogenesis, fibrosis
Macrophages, lymphocytes, plasma cells
Results in amyloidosis (protein misfold), cachexia, anaemia
```
92
What is chronic inflammation
Inflammation of prolonged duration
tissue destruction and repair happening at the same time
Mononuclear inflammatory cells
Fibrosis
93
What are the causes of chronic inflammation
Progression from acute inflammation
Recurrent episodes of acute inflammation
Persistent infection by certain microorganisms
Prolonged exposure to potentially toxic agents
Autoimmunity
Other unknown causes
94
What is a granuloma
Collection of activated epithelioid macrophages (pink cytoplasm, indistinct cell membranes, oval nucleus)
95
What is granulomatous inflammation
Granuloma
Surrounded by mononuclear leucocytes
Caseating or non-caseating
May also contain multinucleate giant cells
96
What is an atheroma
Intimal lesion that protrudes into a vessel wall.
Consists of a raised lesion with a soft core of lipid (mainly cholesterol and cholesterol esters) and is covered by a fibrous cap
97
What vessels are affected by atheroma
```
Bifurcations
Abdominal aorta
Coronary arteries
Popliteal arteries
Carotid vessels
Circle of willis
```
98
What are the risk factors of atheroma
```
Non-modifiable:
Increasing age
Male gender
Family history
Genetic abnormalities
```
```
Modifiable:
Hyperlipidemia (LDL:HDL)
Hypertension
Cigarette smoking
Diabetes
C-reactive proteins
```
99
What causes atherosclerosis
```
Starts with damage or injury to the inner layer of an artery
Damage is caused by:
High blood pressure
High cholesterol
An irritant, such as nicotine
Certain diseases, such as diabetes
```
100
What is a fatty streak
The earliest lesion in atherosclerosis
Composed of lipid filled foamy macrophages
Begins as multiple minute flat yellow spots that eventually coalesce into streaks >= 1cm
These lesions are not significantly raised and do not cause disturbance
Not all fatty streaks are destined to progress to atheromatous plaque
Coronary fatty streaks begin to form in adolescence at the same anatomical sites that later tend to develop plaques
101
What is an atherosclerotic plaque
Consists of intimal thickening and lipid accumulation
Appears white yellow and superimposed thrombus on the plaque appears red
Plaque impinges on the vessel lumen
102
What is the sequelae of atherosclerosis
Rupture, ulceration or erosion of the intimal surface exposes the blood to highly thrombogenic substances and induces thrombosis then lumen occlusion then ischemia
Haemorrage into plaque
Atheroembolism
Aneurysm formation
103
What is a thrombus
A solid mass of blood constituents formed within the vascular system in vivo
Arterial thrombosis most commonly superimposed on atheroma
Venous thrombosis is most commonly due to stasis
104
What are the differences between a clot and a thrombus
```
Clot:
Platelets not involved
Occurs outside vessel or inside
Red
Gelatinous
Not attached to the vessel wall
```
```
Thrombus:
Platelets involved
Occurs only inside vessel
Red (venous) or pale (arterial)
Firm
Attached to vessel wall
```
105
What is the sequelae of thrombosis
```
Occlusion of vessel
Dissolution
Incorporation into vessel wall
Recanalisation
Embolisation
```
106
What is an embolus
A mass of material in the vascular system able to become lodged in vessel and block its lumen
Most emboli are derived from thrombi
Most common - pulmonary embolus derived from deep vein thrombosis
107
What are the types of emboli
```
Thrombus derived
Atheromatous plaque material
Vegetation on heart valves (infection carditis)
Fragments of tumour (causing metastasis)
Amniotic fluid
Gas
Fat
```
108
What is a systemic emboli
Generally originate from the heart or atheromatous plaque
Sequelae od myocardial infarction
Atrial fibrillation
Infective endocarditis - heart valve vegetations
Can cause - CVA, TIA, gangrene, bowel necrosis
109
What is hypoxia
A state of reduced oxygen availability in tissue which causes cell injury by reducing aerobic oxidative respiration
The effects can be reversible or can result in adaptation
If prolonged then tissue hypoxia causes necrosis
Causes:
Inadequate blood oxygenation
Decreased blood oxygen-carrying capacity
Ischaemia
110
What is ischaemia
Localised tissue hypoxia resulting from a reduction in blood flow to an organ or tissues
Most commonly caused by obstruction to arterial supply by mechanisms such as severe atherosclerosis, thrombosis, embolism
111
What is the difference between generalised hypoxia and ischaemia
Generalised hypoxia:
Impaired oxygen supply
Other metabolites still supplied
Ischaemia:
Decreased supply of metabolites including glucose
Glycolytic anaerobic respiration fails due to lack of glucose
Build up of metabolites impairs anaerobic respiration further
Ischaemia injures tissues faster/ more severely than generalised hypoxia
112
What is infarction
Tissue necrosis as a consequence of ischaemia
113
What is ischaemia repercussion injury
Generation of reactive oxygen species by sudden repercussion of ischaemic dysfunctional tissues
114
What are the main causes of infarction
Thrombosis/ embolism
Rupture/ thrombosis of atherosclerotic plaque
Most commonly in arterial vessels
```
Other rare causes:
Vasospam
Atheroma expansion
Extrinsic compression (tumour)
Twisting of vessel roots (volvulus)
Rupture of vascular supply (AAA)
```
115
How are infarctions classified
```
Morphologically by colour
Red: haemorrhagic
Dual blood supply
Venous infarction
White: anaemic
Single blood supply hence totally cut off
```
116
What is a low-flow infarction
Infarction in areas of diminished blood flow in vulnerable anatomical regions
117
What is portal vasculature
Blood supplied via other parenchymal capillary beds
118
What are watershed regions
Point of anatomises between 2 vascular supplies
119
What is a pathophysiological state of shock
Reduced systemic tissue perfusion resulting in decreased oxygen delivery to the tissues
Causes a critical imbalance between oxygen delivery and oxygen requirements of the tissues
Impaired tissue perfusion and prolonged oxygen deprivation leads to cellular hypoxia and derangement of cellular biochemistry and eventually organ dysfunction
120
What is the result of shock
Cell death due to hypoxia
End organ damage
Multi organ damage
Death
121
What are the classifications of shock
Hypvolaemic:
Cardiogenic
```
Distributive:
Anaphylactic
Septic
Toxic shock syndrome
Neurogenic
```
122
What is hypovolaemic shock
Intra-vascular fluid loss
decrease venous return to heart
decrease stroke volume
decrease cardiac output
123
What are the causes of hypovolaemic shock
Haemorrhage
| Non-haemorrhagic fluid loss such as diarrhoea, vomiting and third spacing
124
What is third spacing
Acute loss of fluid into internal body cavities
| This space losses are common postoperatively and in intestinal obstruction, pancreatitis or cirrhosis
125
What is cariogenic shock
Cardiac pump failure resulting in decrease in carbonmonoxide
126
What are the four categories of cariogenic shock
Myopathic
Arrythmia-related
Mechanical
Extra-cardiac
127
What does the effect of vascular occlusion depend on
Nature of blood supply
The rate of occlusion
The tissue vulnerability to hypoxia
The blood oxygen content
128
What are the characteristics of bacteria
Simple single cell organisms
Lack a membrane bound nucleus
Prokaryotes
129
What are the types of flagella
```
They enable organisms to find sources of nutrition and penetrate host mucus
Monotrichous: one tail
Lophotrichous: many tails on one slide
Amphitrichous: One tail each side
Peritrichous: Tails all around
```
130
What are the fimbriae of a gram negative cell
Specialised structures that aid adhesion to host cells and colonisation
131
What is the function of the capsule or slime layer of bacteria
Polysaccharide material protecting bacteria from phagocytosis, desiccation, immune attack, antibiotics
Allows microorganism to pass through musus
Prevents complement-mediated killing
132
What are endospores
Metabolically inert form which are triggered by environmental factors and adapted for long term survival
133
How are bacteria classified
```
Gram stain (ability to retain a crystal violet-iodine dye complex when cells are treated with acetone or alcohol)
Cell shape
Endospore
Atmospheric preference
Fastidiousness
Key enzymes
DNA (16S sequence)
```
134
How do bacteria replicate
Binary fission: cells divide into two identical daughter cells. asexual, creates new bacteria, no exchange of genetic material
Conjugation: transfer of transposable elements. sharing of transposable elements, creates no new bacteria, some genetic diversity
Transformation: picking up plasmids from the environment. creates no new bacteria, introduces some genetic diversity to the population.
Transduction: transfer of genetic information via a viral vector. introduces some genetic diversity into a population.
135
What are the characteristics of fungi
Eukaryotic
Most possess a cell wall made of chitin
Disease-causing fungi can be yeast like or moulds
136
What do moulds cause
Common, superficial infections such as ringworm and athletes foot
Uncommon, severe infections such as aspergillosis and mucormycosis
137
What is the structure of aspergillus
Grow in mats of tiny filaments known as hyphae that form mats called mycelia
Hyphae may or may not be subdivided into separate compartments by cross walls known as septa
138
How do fungi replicate
Sexual or Asexual
| Via spores
139
What are the types of parasites
Protozoa: Unicellular eukaryotes-
- Intestinal: Entamoeba, Glardia, Cryptosporidium
- Non-intestinal: Plasmodium, Leishmania, trypanosoma
Helminths (worms):Multicellular eukaryotes-
- Intestinal: Enterobius (pinworm), Taenia (tapeworm), Asceris (Roundworms)
- Non intestinal: schistosoma
140
How are protozoa classified
```
Generally classified according to morphology and means of locomotion
Flagellates: giardia
Amoebae: entamoeba
Cilliates: balantidium
Apicomplexa or sporozoa: plasmodium
```
141
How do protozoa replicate
Reproduce asexually by fission
May require a second or third host to complete lifecycle
May form hardy cysts
142
What are the characteristics of viruses
Obligate intracellular parasites
Every class of organism suffers from virus infection
Comprise a nucleic acid core wrapped in a protein coat called a capsid
Some viruses have an envelope made of lipid but some are naked
Rely entirely on other cells for their replication
143
How do viruses replicate
1. Attachment/penetration: attachment proteins on virus bind receptors on cells, determines host-range, penetration by endocytosis or direct membrane fusion
2. Uncoating: Genome is released from capsid during or after penetration, genetic material targeted to nucleus
3-5. Early viral proteins produced: using cellular machinery for transcription, encode viral enzymes, crucial for carrying out next stages in life cycle
3b: Genome replication: viral genetic replication occurs in host nucleus, many hundreds of thousands of new viral genomes can be produced
3-5. Late viral proteins produced: structural proteins of virus, capsid/surface proteins
6. Viron assembly: genetic information assembles inside protein coat (nucleocapsid), for enveloped viruses, viral proteins concentrated at membrane with nucleocapsid and virus buds through membrane
Viron release: lytic- bursts cell releasing visions and buds through plasma membrane, lysogenic- integrate into host cell DNA and replicate along with host cells, passed onto daughter cells, can transform to lytic cycle
144
How are viruses classified
```
Essentially based on characteristics:
nature of nucleic acid (rna/ dna)
symmetry of the capsid
Presence or absence of an envelope
Dimensions of the virion and capsid
```
145
What are prions
Misfolded protein
Unlike viruses they have no genetic material
Can be inherited and spread via contaminated material or occur spontaneously
Aggregate and cause misfoldng of native proteins (chain reaction)
146
What is pathogenicity and what are the requirements
```
the capacity of a microorganism to cause an infection
Requirements:
transmissibility
establishment in or on a host
harmful effect
persistence
```
147
What is virulence
Used interchangeably to describe pathogenicity
The degree to which a microorganism is able to cause disease
Allows a relative description of pathogenic potential
148
What is infectivity
the ability of a microorganism to. become established on/in a host
Mediated by microbial ligand and host cell surface receptor
149
What are virulence factors
Components of microorganisms which aid its ability to cause infection
150
What are the virulence factors
Facilitation of adhesion
Toxic effects
Tissue damage
Interference with host defence mechanisms
Facilitation of invasion
Modulation of the host cytokine responses
151
What are the routes of transmission
Faecal-oral
Blood borne
Respiratory
Direct contact
152
What is the incubation period
Period between infection with the organism and manifestation of clinical features
153
What is the period of infectivity
Period during which a transmissible organism may be transmitted to another person
154
What is the impact of infection on the host
```
Inflammation
Abscess formation
Excessive host response to endotoxin
Toxic effects pf endotoxin
Granuloma formation
```
155
What is the meaning of colonisation
Establishment at a site in the body
156
What is microbiota
All the organisms in a given community
157
What is the microbiome
All the genes present within the microbiota
158
What does symbiosis mean
Two or more organisms co-exist in close physical association
159
What does normal flora/ microbiota mean
organisms found in a given location in a state of health
160
What are the types of symbiosis
Mutualism: Both organism benefit from symbiosis
Neutralism: Neither organism derives benefit or harm
Commensalism: One organism benefits, the other derives neither benefit nor harm
Parasitism: One organism (parasite) benefits at the expense of the other (host)
161
What are non-sterile and sterile sites
Non-sterile: have normal flora
| Sterile sites: No normal flora
162
What factors influence what organisms colonise what areas
```
Moisture
Temperature
pH
O2 availability
Nature of surface
```
163
What are the characteristics of skin
```
Variable temperature
Dry
Subject to abrasion
Aerobic environment
Nutrient-poor
Skin surface components
Skin flora:
Coagulase-negative staphylococci
Staphylococcus aureus
Propionibacterium species
```
164
What are the characteristics of the gingival crevice (between teeth and gums)
```
Constant temperature
Moist
Few physical challenges
Anaerobic environment
Bathed in nutrients
Mucosal surface components
```
165
What is the mouth flora
Viridans/oral streptococci
Anaerobes
Many others
166
What are the nasopharyngeal flora
```
Nostrils: skin flora, S. aureus
Pharynx: Respiratory and other pathogens:
Streptococcus pyogenes
Haemophilus influenzae
Streptococcus pneumoniae
Neisseria meningitides
S. aureus
```
167
What is the vagina flora
Pre-puberty:
Skin flora
Lower GI flora (E.coli)
Post-puberty:
Lactobacillus spp. Lactobacillus acidophilus
- Ferment glycogen
-Maintain pH=3, preventing overgrowth of other species
Skin flora
A few C. albicans
168
What is the GI tract flora
Stomach and small intestine: low gastric pH inhibits bacterial growth
Predominantly aerobic bacteria:
acid-tolerant lactobacilli
Helicobacter pylori
Large intestine:
95-99% anaerobes: bactericides spp. clostridium spp. bifidobacteria spp
Aerobic bacteria: enteric gram-negative bacilli: escherichia coli, klebsiella spp. enterobacter spp. proteus spp. citrobacter spp.
169
What are the benefits of normal flora
Metabolism: synthesis secondary metabolites/ vitamins
Colonisation resistance
Induction of cross-reactive antibodies
170
what are the characteristics of C diff
```
Hospital acquired infection
Main risk factor is antibiotic treatment
Perturbation of normal colonic microflora allows C diff overgrowth
Leads to toxin production
Diarrhoea. Pseudomembranous colitis
```
171
What are the pathologies of normal flora
Overgrowth
Translocation
Cross infection
172
What are the clinical effects of acute hyperammonaemia toxicity
```
Lethargy
Poor feeding
Vomiting
Tachypnoea
Convulsions
Coma
Death
It is a medical emergency and must be acted upon immediately
```
173
What are some signs of acute porphyria
```
Severe abdominal pain
Pain in chest, legs or back
Constipation or diarrhoea
Vomiting
Insomnia
Palpitations
High Blood pressure
Anxiety
Seizures
Mental changes
Breathing problems
Muscle pain/ tingling/ weakness/ paralysis
Red or brown urine
```
174
What are possible signs of photosensitive porphyria
```
Sensitivity to the sun/ artificial light
Sudden painful erythema and oedema
Blisters that take weeks to heal
Itching
Fragile skin
Increased hair growth
Red or brown urine
```
175
What are the mechanisms of disease of inborn errors of metabolism
Accumulation of toxin
Energy deficiency
Deficient production of essential metabolite/ structural component
176
What is the result of energy deficiency
Causes crisis presentations in defects of fatty acid oxidation
177
What is the result of defective receptors
Leads to androgen insensitivity syndrome
178
How are Inborn errors of metabolism diagnosed
Pre-symptomatic screening
| Investigation of symptomatic individuals
179
How are investigations of suspected inborn errors of metabolism in patients carried out
Metabolite testing
More complicated metabolite testing
Enzyme analysis/functional studies
Mutation/gene analysis
180
What is investigated in basic urine metabolic screening
```
Spot tests
Organic acids
Amino acids
Sugar Chromatography
Oligosaccharides/sialic acids
Mucopolysaccharides
```
181
What are the benefits of diagnosing inborn errors of metabolism
Treatment, improve prognosis
Identify cause of clinical problem
Genetic counselling
IEM act as models for other disorders
182
What is screened for Pre-natally
Neural tube defects:
Maternal serum and amniotic fluid
Ultrasound scan at 16 weeks
Down syndrome:
1st trimester: PAPA, HCG and nuchal translucency
2nd trimester: maternal serum AFP, HCG, inhibit and estriol
Test on the ascent
183
How is normal pH range maintained
Heavily dependent on buffers and excretion of CO2 and nitrogenous waste
184
How is H+ produced
Glucose incomplet metabolism (anaerobic) (glucose -> 2 lactate and 2 H+)
Triglycerides incomplete metabolism - ketogenesis (triglycerides -> free fatty acids + H+, free fatty acids -> ketones + H+)
Amino acid metabolism ureagenesis (metabolism of neutral amino acids results in the generation of H+)
185
What is a buffer
A solution which resists change in pH when an acid or base is added
Buffering ensures H+ ions are transported and excreted without causing damage to physiological processes
186
What are the functions of acids and bases
Acids are H+ donors (HCL-> H+ + CL-
| Bases are H+ acceptors (OH- + H+ -> H2O)
187
What is pH
Negative logarithm of the hydrogen ion conc (mol/L)
| pH= -log10[H+]
188
What is acidaemia
Low blood pH
189
What is acidosis
Abnormal process or condition that lowers arterial pH
190
What is Ka
Acid dissociation constant
| Ka = ([A-][H+]) / [HA]
191
What is pKa
Negative logarithm of Ka
pKa = -log10Ka
The lower the pKa, the stronger the acid
192
What is the Henderson- Hasselbalch equation
Explains how acids and bases contribute to pH and therefore [H+]
pH = pKa + log10 ([base]/[acid])
Therefore pH is proportional to [HCO3-]/ pCO2
193
What is the equation that is central to acid-base balance
H+ + HCO2- H2CO3 CO2 + H2O
194
What are the details of bicarbonate
Acts as a buffer, mopping up H+ ions
However it cannot buffer CO2
Equilibrium of CO2 requires non-bicarbonate buffers
195
What are the details of phosphate
Monohydrogen phosphate and dihydrogen phosphate form a buffer pair
196
What are the details of ammonia
Ammonia and ammonium ions form a buffer pair
197
How can proteins act as buffers
They contain weakly acidic and basic groups due to their amino acids composition and so can accept and donate H+ ions to some extent
198
What are the sites of acid base metabolism and how
Liver: Dominant site of lactate metabolism (Cori cycle), only site of urea synthesis (waste product of ammonia metabolism
Lungs: secretion of CO2, rate of elimination is equal to the rate of production so that blood pCO2 remains
GI tract: H+ secreted into stomach as HCL, Bicarbonate secreted by pancreas into duodenum -> needed to neutralise acid from stomach
Kidneys: Excretion of H+ in distal tubule, Reabsorption of bicarbonate in proximal tubule, Regeneration of bicarbonate in distal tubule
199
What is the oxyhemoglobin dissociation curve
The amount of o2 bound to Hb is determined by the pO2
Relationship is described but the curve
Curve shifts to the right where Hb has reduced affinity for O2 when:
Body temp increases
Patient is hypoxic or anaemic (increase 2,3 DPG)
[H+] increases
200
What is lactic acidosis
Can result from increase production (e.g. anaerobic gylcolysis) or decreased consumption (e.g. liver disease)
A form of metabolic acidosis
201
What is hyperammonaemia In liver failure
Liver is unable to perform urea cycle which normally converts toxic ammonia to urea for excretion in urine
Ammonia stimulates the respiratory centre causing the patient to hyperventilate and blow off CO2 -> leads increase in blood pH -> known as respiratory alkalosis
202
What is androgenesis
development of an embryo containing only paternal chromosomes due to failure of the egg to participate in fertilization.
Develops in an abnormal way to form hydatidiform moles.
Proliferation of abnormal trophoblast tissue and can develop into malignant trophoblastic tumour and results in no remaining embryo
203
What is parthenogenesis
Reproduction from an ovum without fertillization, especially as a normal process in some invertebrates and lower plants
Results in ovarian teratoma
204
What are pharmacokinetics
What the body does to the drug
205
What are Pharmacodynamics
What the drug does to the body
206
What is stratified medicine
Selecting therapies for groups of patients with shared biological characteristics
207
What is personalised medicine
Therapies tailored to the individual
208
What are pharmacogenetics
The study of inherited genetic differences in drug metabolic pathways which can affect an individuals response to drugs
209
How do genetic variations effect drugs
```
Absorption
Activation
Altered target
Catabolism
Excretion
```
210
What are the consequences of getting the pharmacogenetics wrong
Inactive drug - poor/ no response
Overactive drug - Excess toxicities (adverse reaction)
Financial costs to health services
211
How can genetics help in prescribing the correct medications
Identify genetic variations that lead to altered outcomes
Change dose of drug where appropriate
Use a different drug that works better
Guide new targeted drug development
Reintroduce effective drugs which have ADR in few patients
Stratified/ personalised medicine
Reduce financial costs of inappropriate treatment
212
How is the acid-base status of a patient determined
Blood gas machine measures:
Gases; pCO2, pO2
Metabolites: Glucose, lactate
Electrolytes: Sodium, Potassium, Chloride, Calcium
Co-oximetry: Total Hb, O2 saturation, OxyHb, COHb, MetHb
pH
Derived parameters: base excess, standard bicarbonate, total CO2, anion gap
213
What are the HCO3- levels and pCO2 levels for primary metabolic and respiratory acidosis and alkalosis
Metabolic acidosis: decreased HCO3-
Metabolic alkalosis: increased HCO3-
Respiratory Acidosis: Increased pCO2
Respiratory Alkalosis: decreased pCO2
214
What are the levels of pH for academia and alkalaemia
pH < 7.35 = academia
| pH > 7.45 = alkalaemia
215
What are respiratory and metabolic compensation
Respiratory compensation are changes in CO2 for metabolic disturbances
Metabolic compensation are changes in HCO3- for respiratory disturbances
Compensatory mechanisms aim to restore a neutral pH
216
What are the causes of metabolic acidosis
Increased acid formation: ketoacidosis, lactic acidosis, poisoning, inherited organic acidosis
Decreased acid excretion: Uraemia, RTA type 1
Loss of bicarbonate: GI (Diarrhoea, fistula), Renal (RTA type 2, carbonic anhydrase inhibitors)
Acid ingestion
217
What is the physiological response to metabolic acidosis
Buffering:
Acute increased [H+] resisted by bicarbonate buffering, causing decreased HCO3-
Compensation:
Respiratory: Respiratory centre stimulated -> hyperventilation to blow off CO2, self-limiting as generates additional CO2
Renal: Urine H+ excretion maximised, increased rate of regeneration of bicarbonate
218
How is metabolic acidosis managed
Identify and treat cause
Sodium bicarbonate by IV if pH < 7.00 or orally in CKD, RTA types 1 and 2
Rapid correction impairs O2 delivery, rebound alkalosis is possible
219
What are the causes of metabolic alkalosis
Administration of bicarbonate
Potassium depletion
Loss of H+ through vomiting
220
What is the physiological response to metabolic alkalosis
Buffering:
release of H+ from buffers
Compensation:
Respiratory: Reduced rest rate in order to retain CO2, Self-limiting as an increase in pCO2 stimulates the resp centre
Renal: Difficult, decreased GFR leads to high bicarbonate reabsorption, potassium deficiency contributes to persistence of alkalosis
221
How is metabolic alkalosis managed
Treat underlying cause
| Treat factors that sustain alkalosis such as replace the potassium
222
What are the causes of respiratory acidosis
Defective control of respiration:
CNS depression
CNS disease
Neurological disease
Defective respiratory function:
Mechanical
Pulmonary disease
223
What is the physiological response to respiratory acidosis
Buffering: limited buffering by haemoglobin
Compensation:
Respiratory: increased pCO2 stimulates respiratory centre but disease prevents adequate response
Renal: maximal bicarbonate reabsorption, almost all phosphate excreted as H2PO4-, Marked increase in urinary NH4+
224
How is respiratory acidosis managed
Treat underlying cause
Maintain adequate arterial pO2 but avoid loss of hypoxic stimulus to respiration
Avoid rapid correction of pCO2 as risk of alkalosis due to persistence of compensation
225
What are the causes of respiratory alkalosis
Central: Head injury, stroke, hyperventilation, drugs, sepsis, chronic liver disease
Pulmonary: pulmonary embolism, pneumonia, asthma, pulmonary oedema
Iatrogenic: excessive mechanical ventilation
226
What is the physiological response to respiratory alkalosis
Buffering: release of H+ from non-bicarbonate buffers
Compensation:
Respiratory: Inhibitory effect of decreasing pCO2 overwhelmed by primary cause
Renal: Decreased renal regeneration of bicarbonate (CO2 is substrate, therefore CO2 is preserved)
227
How is respiratory alkalosis managed
Treat underlying cause
Rapid symptomatic relief by re-breathing
Sedation or prevention of hyperventilation by mechanical ventilation
228
What do U and Es measure and estimate
Measure: Sodium, potassium, chloride, bicarbonate, urea, creatinine
Estimate: Water
229
What does epidemiology examine
Who gets the disease
230
What does aetiology examine
What causes the disease and what can stop it
231
What is a dendritic cell
Circulating the body, sampling environment and showing it to immune system
232
What is an antibody
Circulate, specific to certain proteins
233
What is a macrophage
Phagocytic cell
234
What are the results of histamine
```
Blood clots
Gastric acid secretion
blood vessels dilate
Bronchoconstriction
Increases the permeability of the capillaries
Adrenaline is released
Swelling and inflammation
Frequent heartbeat
```
235
How are people sensitised to antigens
Dendritic cell presents antigen, naive T cell differentiates into a Th2 cell, secretes cytokines IL-4 and IL-13 which act as signals to Naive B cells which become memory B cells which have specific IgE that will recognise the allergen on further exposure
236
What is the atopic march
The typical progression of allergic diseases that begin in early life, includes eczema, food allergy, asthma, hay fever.
237
How are allergies tested
Skin prick test
Intra dermal test
Oral challenge test
History taking
238
How is a skin prick test conducted
Positive control of histamine
Negative control of saline
Samples pricks of various antigens
239
What is the blood transfusion reaction
If incorrectly matched blood
Dendritic cells detect foreign antigen
Presents to B cells which make antibodies
Activates complement and have cytotoxic action
MAC attack complex (classical pathway)
Takes hours to a day
240
What is an autopsy
An examination of a body after death to determine the cause of death
241
Why are postmortems important
To document accurate data about the health of the population
Notification of communicable diseases
For education
To help catch the bad guy
To explain what happened to their loved one and aid the grieving process
Genetic testing
Provides evidence for legal proceedings
242
What are the types of postmortems
Coroners postmortems (don't need consent)
Hospital/ consent postmortems (needs consent)
CT postmortems
243
How do you perform postmortems
External exam
Evisceration
Dissection of organs
Reconstruction
244
What can be found in external examination
```
Rigor mortis
Decomposition
Hypostasis (blood moves to areas due to gravity)
Ligature mark
Old surgical scars
Stab wounds
```
245
What happens in the evisceration stage
```
Removal of organs
Cut in most efficient ways
Clip off the anterior rib cage
Removal of the small and large intestines
Then remove all the organs
```
246
The presence of which lines in solidified blood is diagnostic of pre-mortem thrombus
Lines of Zahn
247
How is the body reconstructed after a post mortem
All the organs go in a biodegradable bag in the body cavity and brain cavity is stuffed with cotton wool
248
What is the difference between stage and grade of a tumour
Stage: how far it has spread
Grade: How differentiated the cells are
249
What are the types of pathology
```
Histopathology
Haematology
Immunology
Cytopathology
Microbiology
Chemical pathology
Genetics
Toxicology
Forensics
```
250
What are the general principles of immune response
```
Protects us from threats in the environment
Multilayer defines
Network of pathogen recognition
Effective inter-cellular communication
Multiple mechanisms of pathogen clearance
Adaptive responses to changing pathogen
Self-regulation
Limitation of host damage
```
251
What are the proteins of the innate system
Cytokines: chemical signals which modulate cell activity or attract cells
Acute phase proteins: opsonise or present pathogens to the immune system
Complement proteins
252
What causes autoimmune disease
Immune regulation
Genetic make up Environment (infection, trauma-tissue, smoking)
Sex (hormonal influence)
Age (autoimmunity more common in elderly)
253
How does the coroner assess death
Who
When
Where
How
254
Why should you report a death to the corner
```
Unnatural
cause of death is not known
Not seen by a Dr within 14 days (or after death)
trauma, violence or suspicions
accident
workplace incident or industrial disease
suicide or self harm
poisoning or drugs overdose (prescribed or illicit)
neglect involved (or self neglect)
Prison or police custody
Mental Health Act section
surgical procedure or anaesthetic implicated
medical mismanagement or medical device
anything odd
```
255
What is a malignant epithelial tumour
Carcinoma
256
What is the most common type of autopsy
Coroners
257
What is histopathology
It involves the investigation and diagnosis of disease from the examination of tissues
258
What is degranulation
The release of pre-formed mediators from mast cells
259
What is cytopenia
The reduction in the number of blood cells
260
What is the prognosis
The term used to describe the anticipated course of a disease in terms of cure, remission or fate of the patient
261
What is pathogenesis
The mechanisms through which the aetiology of a disease produces its clinicopathological effects
262
What is bronchiectasis
Widening of the bronchi or their branches
263
What is anaplasia
The lack of a normal differentiated state, usually in a tumour
264
What is a granuloma
An infectious or foreign material that can't be degraded or removed and becomes engulfed in inflammatory tissue
265
What is DiGeorge syndrome
Thymic aplasia leading to lack of T cells
266
What does SCID mean
The immundeficiency seen in infants in which there is a failure of both T and B lymphocyte function
267
What does regeneration depend on
Tissue cell kinetics
Architecture
Stem cell survival
268
How can fracture healing go wrong
```
Misalignment
Movement
Infection (more common in compound fractures)
Interposed soft tissue
Pre-existing bone bathology
```
269
What is an ulcer
A local defect or excavation of the surface of an organ or tissue that is produced by sloughing of inflammatory necrotic tissue
270
What is a skin ulcer
Loss of area of epidermis and dermis to produce a defect even down to fat, muscle, tendons and bone
271
What are the causes of leg ulcers
```
Vascular 90%
-Venous 70%
-Arterial 10%
-Mixed 10%
Others 10%
```
272
What are the rarer causes of leg ulcers
Inflammatory (pyoderma gangrenous, panniculitis)
Neuropathic (peripheral neuropathy)
Malignant (SCC, BCC, lymphoma)
Vascular (vasculitis and CTD
Iatrogenic (pressure sores, drugs)
Infection (bacterial, fungal)
Metabolic (diabetes mellitus, calcinosis cutis)
Traumatic (accidental/ self induced)
Burns (chemical, electrical, thermal, radiation)
273
What are the risk factors of venous leg ulcers
Valvular incompetence (primary or secondary)
Previous damage to venous system (DVT, hypertension, peripheral oedema)
Obesity, immobility (poor muscle contraction -> venous pooling and hypertension
274
What are we looking for in a history about venous leg ulcers
Varices veins
Leg swelling
Blood clots in deep veins
Sitting or standing for long periods of time
End of day throbbing and aching in the calf muscles
High blood pressure
Multiple pregnancies (increased circulating volume)
Previous surgery
Obesity
Increasing age and immobility
275
What are we looking for upon examination about venous leg ulcers
Medial gaiter area most common
Less painful than arterial ulcer
Superficial, sloughy with ill defines borders
Associated signs of chronic venous hypertension
276
What causes arterial ulcers
Associated with peripheral vascular disease
Plaque build up in arteries that carry blood to lower limbs which hardens and narrows the arteries
Limits flow of oxygen rick blood to legs and other parts of body
Plaques made up of fat, cholesterol, calcium, fibrous tissue, and other substances in the blood
277
What are risk factors for arterial ulcers
```
Diabetes
Smoking
High blood lipids
High blood pressure
History of ischaemic heart disease, cerebrovascular disease or peripheral vascular disease
Renal failure
Obesity
Rheumatoid arthritis
Clotting and circulation disorders
```
278
What are we looking for in a history about arterial leg ulcers
Intermittent claudication
Rest pain or paraesthesia
Pain at ulcer site
Other symptoms of vascular disease eg angina
279
What are we looking for upon examination of arterial leg ulcers
```
Punched out painful ulcer
Lower leg/foot
Loss of hair appendages
Dry skin
Cool peripheries
Pale or cyanotic or pre-gangrenous toes
Position dependent ischaemia
Reduction in proximal and or peripheral pulses
```
280
What are the features of neuropathic ulcers
Due to distal polyneuropathy (motor/ sensory/ autonomic)
Under metatarsal heads/ heel
Painless but warm with pulses
281
What are the causes of neuropathic ulcers
```
Diabetes
Other causes of polyneuropathy
-Alcohol
-B1/B12 deficiency
- Charcot Marie Tooth
```
282
Why would a biopsy of an ulcer be performed
Clinically atypical ulcer
| To exclude or diagnose malignancy
283
How are leg ulcers managed
Treat the underlying cause of the ulcer
Treat the ulcer
Treat any associated infection
Debride necrotic material (remove slough/dead tissue)
284
What are the outcomes of acute inflammation
Resolution:
- phagocytosis of insulting agent
- fibrinolysis
- phagocytosis of debris
Repair:
- organisation (replacement by granulation tissue)
- fibrous scar
Chronic inflammation:
- organisation
- macrophages/ lymphocytes/ plasma cells
285
What causes a granulomatous inflammation
Bacterial (TB, leprosy)
Parasitic (schistosomiasis)
Fungal (histoplasma, cryptococcus)
Inorganic metals or dust (silicosis, berylliosis)
Foreign body (suture, vascular graft)
Unknown (sarcoidosis, ulcerative colitis)
286
What are examples of granulomatous diseases
Tuberculosis
| Sarcoidosis
287
What is an abscess
A localised collection of pus surrounded and walled off by a collection of capillaries, neutrophils and fibroblasts
288
What is an example of a stable cell
Hepatocyte
289
What's the most common type of leg ulcers
Venous
290
What is an exudate
Term used to describe protein-rich fluid associated with vascular leakage during acute inflammation
291
What is fibrosis
Common feature of chronic inflammation involving thickening and scarring of connective tissue
292
What term is used to describe bacteria that are able to cause the formation of pus
Pyogenic
293
What condition involves a chronic abscess in the bone marrow cavity
Osteomyelitis
294
What cell type secretes antibodies
Plasma cell
295
What is the type of necrosis associated with TB granulomas
Caseous
296
What is the transudate
Fluid that is low in protein with little or no cellular component
297
What is cholecystitis
Chronic inflammation of the gallbladder
298
What is pavementing
Term used to describe the adhesion of neutrophils to the vascular endothelium at sites of acute inflammation
299
What is cirrhosis
Clinical end-point of chronic inflammation of the liver
300
What cells are macrophages derived from
Monocytes
301
What colour do gram positive bacteria cells show as
Purple
302
What colour do gram negative bacteria cells show as
Red
303
What is the cycle of infection
Encounter -> entry -> spread -> evade defences -> multiply and damage -> disperse
304
What are endogenous sources of infection
Microorganisms from the host getting into the wrong place
305
What are exogenous sources of infection
Organisms originating from the external environment/ infected individuals
306
What is bacterial pneumonia
```
Infection of lower respiratory tract
Causes fluid to collect in the alveoli of the lungs
Can be caused by:
Streptococcus pneumonias
Staphylococcus aureus
Haemophilus influenzae
```
307
What is Gonorrhoea
```
STI
Caused by neisseria gonorrhoea
Symptoms:
-Discharge of pus from urethra
-burning sensation
-sterility
Sex bias to symptoms
```
308
How is Bacterial pneumonia encountered
Inhalation of air-borne droplets containing pathogen
Contact with mouth of infected individual
Contaminated blood
309
How is gonorrhoea encountered
Sexual contact with infected individual
Contact with urethral exudate
Vertical transmission (mother to child during birth)
310
What is the role of secretory immunoglobulin A (IgA) and where is it found
Found in mucosal secretions of respiratory tract and urogenital tract
Bind to pathogens and prevent them from adhering to host tissues
311
What is IgA protease
AN endopeptidase
Produced by S. pneumonia and N. gonorrhoeae
Degrades IgA
Targets amino acid sequence Pro-Pro-Y-Pro (Y= threonine, serine or alanine)
Breakdown products of IgA to stick to the outside of the pathogen
312
What is the incubation period
Period of time between infection with the organism and manifestation of clinical features
313
What is the period of infectivity
Period during which a transmissible organism may be transmitted to another person
314
How do pathogens multiply and cause damage
Need to acquire nutrients from the host to multiply
| Can cause direct damage or indirect damage
315
What are hyaluronidase and neuraminidase
Enzymes capable of degrading hyaluronic acid and sialic/neuraminic acid
316
What are hyaluronic acid and neuraminic acid
Both are targets as are components of interstitial cement in connective tissues (Hyaluronic) or epithelial cells (neuraminic)
Breakdown of these can provide nutrients, more space for organism to grow and activates immune system
317
What is endotoxin
Component of the outer membrane in N. gonorrhoeae
Isn't actively secreted
Released on cell death/lysis
Can cause uncontrolled activation of immune response: inflammation, severe tissue damage, multiple organ failure (sepsis)
318
What is the host response to endotoxin
```
Severe sepsis and or septic shock
T-lymphocyte response:
-cytokine release
-fever, riggers, hypotension, tachycardia, collapse
-cardiac and/or renal failure
Activation of the clotting cascade:
-disseminated intravascular coagulation
-depletion of clotting factors
Activation of complement
```
319
What is inflammation due to infection
Response to invasion/ tissue damage
Activation of complement and clotting systems, fibrinolysis and kinin system
Leukocyte adhesion and production of inflammatory mediators:
-local vasodilation
-reduction in endothelial barrier function
-increased vascular permeability
Phagocytosis of foreign material
320
What is erythema due to inflammation
Vasodilation causes increased blood flow
321
What is swelling due to inflammation
Increased vascular permeability allows extravasation of serum proteins and leukocytes,
swelling arises from consequent physical and osmotic effects
322
What is the cause of pain in inflammation
A number of different physical and biochemical changes in inflamed tissues
323
What is the cause of heat in inflammation
Increased blood flow
324
Why is there loss of function in inflammation
Secondary effect of swelling and pain
325
What is an exotoxin
```
Protein produced (and usually secreted) by living bacteria
Typically have quite specific effects on host
```
326
What is tetanus
```
Clostridium tetani
Infection of dirty wounds
Toxin production:
tetanospasmin
-produced on germination of spores
binds to nerve synapses
-inhibits release of inhibitory neurotransmitters
Death caused by respiratory paralysis
```
327
What are the types of TB
Primary TB: Ranke/Ghon complex: solitary granuloma with hilarious granulomatous
Post primary/ reactivation: Widespread granulomatous inflammation +/- cavitation, often apical
Miliary TB: Multiple disseminated 1-3mm pulmonary granulomas
Extrapulmonary TB: Diverse manifestations in bone, liver, kidneys, CNS etc
328
How does the host induce dispersal in certain examples
Inflammation of lung tissue:
- Production of fluid containing pathogen
- Induction of coughing
- Dispersal of pathogen via respiratory droplets
Damage to tissues of the genital tract and induction of immune response:
- Production of urethral discharge
- Dispersal via sexual contact
329
What is biochemical genetics
The study/ investigation of genetic disorders that affect the metabolic pathways of cells
330
What are the clinical effects of acute hyperammonaemia
Ammonia accumulates in patients with urea cycle defects
```
Lethargy
Poor feeding
Vomiting
Tachypnoea
Convulsions
Coma
Death
```
Medical emergency
331
What happens in porphyrias
Porphyrins accumulate
332
What are the signs of photosensitive porphyria?
```
Accumulation of Uroporphrin, coproporphrin, protoporphrin
Sensitivity to the sun/artificial light
Sudden painful erythema and oedema
Blisters that take weeks to heal
Itching
Fragile skin
Increased hair growth
Red or brown urine
```
333
What are the signs of acute porphyria?
```
Accumulation of ALA and PBG
Severe abdominal pain
Pain in chest, legs or back
Constipation or diarrhoea
Vomiting
Insomnia
Palpatation
Hypotension
Anxiety
Seizures
Mental changes
Breathing problems
Muscle pain, tingling, weakness, paralysis
Red or brown urine
```
334
What is the pathway of fatty acid oxidation
Triglycerides -> fatty acids -> fatty acid oxidation -> Acetyl CoA -> ketones/ TCA cycle -> energy
335
How are inborn errors of metabolism diagnosed
Pre-symptomatic screening:
- whole population
- selected groups
Investigation of symptomatic individuals:
- test body fluids for abnormal metabolites
- measure enzyme activities
- histochemical/immunochemical staining
- DNA analysis
336
What is the route for investigating those with potential inborn errors of metabolism
Metabolite testing -> more complicated metabolite testing -> enzyme analysis/functional studies -> mutation/gene analysis
337
What is screening
The process of identifying apparently healthy people who may be at increased risk of a disease or condition.
338
What are the Wilson and Hunger criteria of screening programmes
```
Disease must be sufficiently common
Natural history must be known
Early therapeutic intervention beneficial
Acceptable and affordable screening test
Diagnostic confirmatory test
```
339
What happens in newborn screening in the UK
All babies tested at day 5-8
Most samples taken in community by midwives
Regional laboratories perform tests and report results
Standards set by the UK Newborn Screening Program Centre
Nature of the programme defines by the national screening committee
340
What is on a newborn screening card
NHS number, name, address, DOB, GP, mother's details, DOS, gestation, weight, transfusion status, hospital status, repeat status
341
Why are samples in newborn screening poor quality
```
Spots of blood not soaked through
Too small a spot
Spotted from both sides or compressed
Multiple spotting
Contaminated
Expired card
Missing details
Too young for screening
```
342
What are the newborn screening standards
Timely collection of samples
Timely processing of samples and reporting data
Timely collection of repeats
All positive cases to be on treatment with referral within 3 days and by a set time frame (condition dependent)
All babies to be tested, including those identified as missed or incomers, up to one year of age
343
What is phenylketonuria
Severe intellectual disability if untreated
Excellent prognosis if treated from birth
Screening test is a bloodspot phenylalanine
Confirm diagnosis with plasma phenylalanine measurements
344
What is the natural history of untreated PKU
```
Severe intellectual disability
Seizures, tremors
Spasticity
Behavioural problems, irritability
Eczema in childhood
```
345
What is the treatment of PKU
Low phenylalanine diet
Bioprotein Supplementation
Large neutral amino acids
346
What is congenital hypothyroidism
Severe developmental delay if untreated
Excellent prognosis if treated from birth
Screening test is a bloodspot TSH
Confirm diagnosis with plasma thyroid function tests
Treatment with thyroxine, carefully monitored
347
What are haemoglobinopathies
Early detection and treatment of sickle cell disease
| Also detect carriers and compound heterozygotes with HbC/Dpunjab, E/Oarab, B-thalassaemia major
348
What is Maple syrup urine disease
Defect in branched chain 2 ketoacid dehydrogenase complex
Clinical effects:
Majority have the classical disease, presenting during the neonatal period, encephalopathy and cerebral oedema blush's poor feeding, ketoacidosis and seizures
Screening target is leucine
349
What is Homocystinuria
Defect in B-cystathionine synthase
Clinical effects:
Usually healthy at birth, diagnosis not usually made until 2-3 years
Myopia followed by dislocation of the lens, osteoporosis, thinning and lengthening of the long bones, mental retardation and thromboembolism
Without treatment 25% will die before age of 30 due to thromboembolism
Screening target is methionine
Secondary target is total homocysteine
350
What is a tumour
A swelling or mass of any kind
351
What is neoplasia
New uncontrolled growth of cells that is not under physiological control
Can be benign or malignant
352
What is a cancer
A generic term for a large group of diseases characterised by the growth of abnormal cells beyond their usual boundaries that can then invade adjoining parts of the body and/or spread to other organs
353
What are the hallmarks of cancer
```
Sustaining proliferating signalling
Evading growth suppressors
Avoiding immune destruction
Enabling replicative immortality
Activating invasion and metastasis
Inducing angiogenesis
Resisting cell death
Deregulating cellular energetics
```
354
What is embryological histogenesis
The formation of differentiated tissues from undifferentiated endoderm, ectoderm and mesoderm
355
What is tumour histogenesis
Tumours are named according to the tissues from which they arise
356
What is tumour differentiation
The extent to which a neoplasm resembles its tissue of origin
357
What are the meanings of each level of tumour differentiation
Well-differentiated: neoplasm closely resembles tissue of origin
Moderately-differentiated: neoplasm shows some resemblance to tissue of origin
Poorly-differentiated: neoplasm does not resemble tissue of origin
358
What is anaplasia
A neoplasm that is poorly differentiated and highly pleomorphic
359
What are the most common cancers in females in the UK
Breast 31%
Lung 13%
Bowel 10%
360
What are the most common causes of cancer deaths in females in the UK
Lung 21%
Breast 15%
Bowel 10%
361
What are the most common cancers in males in the UK
Prostate 26%
Lung 14%
Bowel 13%
362
What are the most common causes of cancer deaths in males in the UK
Lung 21%
Prostate 14%
Bowel 10%
363
What are the differences between benign and malignant tumours
Benign:
- Neoplasm does not invade surrounding tissues
- Does not metastasise
- slow rate of growth
- usually well differentiated
- Rarely fatal
Malignant:
- neoplasm does invade surrounding tissues
- may metastasise
- fast rate of growth (division exceeds cell death)
- Well -> moderate -> Poorly -> anaplastic
- Often fatal
364
How can a tumour cause effects
Effects of primary tumour
Effects of distant metastases
Paraneoplastic syndromes
365
What are the effects of primary tumour
Invasion into and replacement of normal tissues/ organs -> failure of that organ to function
Pressure on normal tissue -> failure of that organ to function
Invasion into blood vessels -> bleeding
Pressure on blood vessels -> ischaemia
Pressure/invasion into nerves -> loss of nerve function/ pain
Growth into lumen -> obstruction
Ulceration
366
What are the effects of distant metastases
When a cancer spreads to different parts of the body forming new (secondary) tumours
Invasion into/ pressure on organs normal tissues
Invasion into/ pressure on vessels
Invasion into/ pressure on nerves
Growth into lumen
367
What are paraneoplastic syndromes
Signs and symptoms that are not related to local effects of the primary tumours
Develop as a result of either -proteins/ hormones secreted by tumour cells
-Immune cross reactivity between tumour cells normal tissues
368
What is cancer cachexia
Where the tumour uses the energy stored in fat and muscle causing tissues to waste away
369
What is the stroma
Cells that support the parenchyma
370
What is the parenchyma and some examples
Cells that perform actual function of an organ
Eg:
Cells that do gas exchange (pneumocytes) in the lungs
Cells that contract in the heart (myocytes) causing it to contract
371
What do stroma contain
Many cell types
- blood vessels
- fibroblasts
- immune cells
372
What makes up the breast
```
Chest wall
Pectoralis major
Lobile
Nipple
Areola
Lactiferous duct
Adipose tissue
Skin
```
373
How often is a breast lump cancerous
~20% of the time
374
What is the triple assessment of breast cancer
Clinical: examination
Imaging: Ultrasound or mammogram
Pathology: biopsy and/or cytology
375
What are the features of a lump
```
Mobile (benign) or fixed (malignant)
Well defined (benign) or not (malignant
Smooth (benign) or irregular (malignant)
Firmness (soft then benign and firm then malignant)
Location
```
376
What are worrying nipple symptoms of breast cancer
Inversion
Rash
Discharge
377
What are the skin changes of breast cancer
Tethering or retraction
Oedema
Peau d'orange
Ulceration/fungating lesion
378
What are the clinical P codes of breasts
```
P1 normal
P2 Benign lesion
P3 Atypical, probably benign lesion
P4 Atypical, probably malignant lesion
P5 Malignant
```
379
How do things appear in a mammogram
Fat: radiolucent so black
| Solid masses: radio-opaque so white
380
How do things appear in an ultrasound
Fat: hypoechoic so white
| Fibroglandular breast tissue echogenic so black
381
What are the imaging R codes
```
R1 Normal
R2 Benign lesion
R3 Atypical, probably benign lesion
R4 Atypical, probably malignant lesion
R5 Malignant
```
382
What are the pathology B codes
```
B1 Normal
B2 Benign lesion
B3 Atypical, probably benign lesion
B4 Atypical, probably malignant lesion
B5 Malignant
```
383
What are the pathology C codes
```
C1 Insufficient
C2 Normal or Benign lesion
C3 Atypical, probably benign lesion
C4 Atypical, probably malignant lesion
C5 Malignant
```
384
What are BRCA gene mutations
Genes that encode tumour suppressor proteins are critical for cells to repair damaged DNA
Gene mutation: proteins not made or don't work properly - DNA damage in cells not repaired properly
~70% change of developing Breast cancer by 80
Peak incidence at lower age
385
What is cell adaptation
Cellular changes in response to changes in environment or demand
386
How can a cell adapt
```
Size
Number
Phenotype
Metabolic Activity
Function
```
387
Why do cells adapt
Acquire new, steady state of metabolism and structure
Better equipped to survive
Failure may lead to sub-lethal or lethal cell injury
388
Can epithelial cells adapt and why
Labile cell population
Active stem cell compartment
Highly adaptive in number and function
389
Can fibroblast cells adapt and why
Survive severe metabolic stress without arm
| EG lack of oxygen
390
Which cells cannot adapt and why
Cerebral neurons
Terminally differentiated and permanent cell population
Highly specialised function and easily damaged
391
What are the two types of cellular adaptation
Physiological: responding to normal changes in physiology or demand
Pathological: responding to disease related changes
392
What is atrophy
Reduction in size of organ or tissue by decrease in cell size and number
393
What are examples of atrophy
Physiological: Embryogenesis, uterus after pregnancy or menopause
Pathological: localised or generalised
394
What are the causes of pathological atrophy
```
Decreased workload (disuse atrophy)
Loss of innervation (denervation atrophy)
Diminished blood supply
Inadequate nutrition (cachexia)
Loss of endocrine stimulation
Pressure
```
395
What is metaplasia
Transformation of one differentiated cell type into another
Transdifferentiation of stem cells
Better adaptation to new environment
Can affect epithelium and mesenchymal tissues
Physiological or pathological
396
What is dysplasia
Earliest morphological manifestation of multistage process of neoplasia
In-situ disease; non invasive
Shows cytological features of malignancy but no invasion
397
What is a carcinoma in situ
A group of abnormal cells
