Exam Flashcards
(187 cards)
1
Q
Describe Neutrophils
A
First line defenders
Move rapidly to site of infection in large numbers
Most abundant but die fighting
Become phagocytic on exposure to infectious material
2
Q
Describe Macrophages
A
Develop from monocytes, chief phagocytic cells, robust cells
Free and fixed
3
Q
Describe Eosinophils
A
Mildly phagocytic
Defence against parasites and regulation of vascular mediators
4
Q
Describe Natural Killer Cells
A
Function = recognise and eliminate cells infected with viruses and eliminating cancer cells
Non-phagocytic large granular lymphocytes
Attack cells that lack “self” cell-surface receptors
Induce apoptosis in cancer cells and virus-infected cells
Secrete potent chemicals that enhance inflammatory response
5
Q
Purpose of Interleukins
A
Produced by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation
6
Q
Purpose of Interferons
A
Protect against viral infections
Released by viral infected cells and protect neighbouring cells; activate NK cells and macrophages.
7
Q
What line of defence is innate immunity?
A
1 and 2
8
Q
What line of defence is adaptive immunity?
A
3
9
Q
Outline innate immunity
A
Natural resistance
Epithelial barriers Mucous membranes Phagocytes NKC Chemical mediators (cytokines) Inflammation
10
Q
Outline adaptive immunity
A
Gained after birth Involves memory Specific ID of pathogens Recognition of self and non self Lag between exposure and response
Antigens
Immune cells (lymphocytes, antigen presenting cells, effector cells)
Humoral response
Cell-mediated response
11
Q
Outline primary response
A
Initial exposure
Has latent period or lag phase when B cell differentiation occurs
After 5-7 days an IgM antibody for specific antigen is detected
An IgG response equal or slightly less follows IgM response
12
Q
Outline secondary response
A
More rapid
Larger amounts of antibodies are produced from memory cells
Mature T cells already present
IgM produced in similar quantities to primary response byt IgG is significantly higher
13
Q
What is an allergy?
A
Exaggerated hypersensitivity response to environmental antigens
14
Q
What is hypersensitivity?
A
Exaggerated or inappropriate immunologic response to an antigen that results in disease or damage to the host
15
Q
What is autoimmunity?
A
Body defences are misdirected against the body’s tissues
Autoimmune disease occurs when autoantibodies and cytotoxic T cells start to damage the persons own tissue
16
Q
What is immunodeficiency?
A
Body defences are insufficient to protect the host
17
Q
Categories of transplant rejection
A
Hyperacute
Acute
Chronic
18
Q
Outline Hyperacute transplant rejection
A
Immediate and rare
Pre-existing antibody to the antigens of the graft
19
Q
Outline Acute transplant rejection
A
Takes days to months
Cell-mediated immune response against unmatched HLA antigens
Biopsy demonstrates infiltration of lymphocytes and macrophages characteristic of type IV reactions.
20
Q
Outline Chronic transplant rejection
A
Months or years after period of normal function
Slow, progressive organ failure
Inflammatory damage as a result of a weak cell-mediated reaction against minor HLAs
21
Q
What is Systemic lupus erythematosus
A
Chronic multisystem inflammatory disease
Autoantibodies against: nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets, etc.
Deposition of circulating immune complexes containing antibody against host DNA
Excessive levels of autoantibodies react with circulating antigens and form immune complexes, causes reactions in kidneys, brain, heart, spleen, lungs, GI tract, peritoneum and skin.
More common in females (10:1), esp 20-40 yrs
22
Q
CM of Systemic lupus erythematosus
A
Arthralgias or arthritis (90% of individuals) Vasculitis and rash (70–80%) Renal disease (40–50%) Haematologic changes (50%) Cardiovascular disease (30–50%)
23
Q
Tx of Systemic lupus erythematosus
A
No cure (as for most autoimmune diseases)
Aim to treat symptoms and suppress the autoimmune response
NSAIDS
Corticosteroids for serious active disease
Immunosuppressive drugs, e.g. methotrexate
Avoid UV exposure to reduce “flares”
Potential Rx with stem cell treatments
24
Q
Why doesn’t the body clear the HIV virus totally?
A
It has a high replication rate - main reason for lack to total clearance
Provirus can be hidden where it is not detectable by the immune system
High mutation rate - antigens to antibodies and CD8s have mutated so cannot recognise and destroy.
Mutation is continual.
25
Define drug abuse
using a drug in a fashion inconsistent with medical or social norms
26
Define drug addiction
chronic, relapsing brain disease process characterized by compulsive seeking and use of a specific psychoactive substance despite harmful consequences
27
Define drug tolerance
regular drug doses elicit a smaller response than initially, requiring higher and higher doses to elicit desired effects
28
Define psychological dependence
an intense, subjective need for a particular drug
29
Define physical dependence
a state where an abstinence syndrome will occur if drug use is discontinued
30
Define withdrawal syndrome
S&S that occur in physically dependent people when they discontinue drug use
31
Define cross tolerance
tolerance to one drug confers tolerance to another drug, usually same group
32
Define cross dependence
same for dependence
33
Diagnostic criteria for substance use disorder
Maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by 2 or more of the following, occurring within a 12 month period:
- Recurrent use resulting in failure to fulfill role obligations - - Recurrent use in situations where physically hazardous
- Continued use despite problems
- Tolerance
- Withdrawal
- Taken in larger amounts and longer than intended
- Persistent desire and unsuccessful quitting/controlling
- Time spent on activities relating to substance abuse
- Giving up other activities
- Continued despite knowing harmful effects
- Craving
34
Substance abuse involves which drugs
Schedule 8 or 9
35
What are schedule 8 drugs
Controlled drugs
Available for use but require restriction to reduce misuse or dependence
36
What are schedule 9 drugs
Prohibited substances
Substances which may be abused or misused
37
Neurobiology of Addiction
Voluntary users can become compulsive users as a result of molecular changes in the brain
Reward circuit is activated
Major transmitter is dopamine: regardless of what initiates the reward pathway, the end is the same
38
Factors that Contribute to Drug Abuse
```
Reinforcing properties of the drug
Physical dependence
Psychological dependence
Social factors
Drug availability
Vulnerability of the individual
```
39
Therapeutic use of alcohol
Antidote for antifreeze and methanol poisoning
Antiseptic (alcowipes)
Nerve blocks
40
Benefits from moderate consumption of alcohol
Prolongs life
Reduces risk of dementia, diabetes and cardiovascular disorders
Contributes to the joy of living
41
Cognitive effects of alcohol
Acute effects
- General depression of CNS function
- Enhances GABA-mediated inhibition
- Dose-dependent
- Activation of the reward circuit
- Binds with 5-HT3 receptors
Chronic effects
- Encephalopathy
- Effect on sleep
42
Physical effects of alcohol
- Cardiovascular system
- ↓respiration
- Liver damage
- Stomach
- Kidney
- Pancreas
- ↓blood glucose levels by inhibiting hepatic glucose output → risk for hypoglycaemia, masks signs (diabetics!)
- Sexual function
- Cancer: breast and colorectal cancer
- Pregnancy and lactation
43
What is Fatty Liver
Large amounts of fat accumulate in hepatocytes (steatosis)
Liver enlarges and becomes yellow
Damage reversible once alcohol is discontinued
44
What is Alcoholic Hepatitis
Often due to binge drinking
Inflammation and necrosis
Stimulates irreversible fibrosis
45
What is cirrhosis
```
Irreversible fibrosis of the liver
Fat deposits, ↑connective tissue
Loss of liver function
- Loss of hepatocytes
- Obstruction of biliary duct system
```
Cessation of alcohol reverses the fatty deposits but not the fibrosis or hepatocyte damage
46
CM of ALD
```
Tenderness/pain in Rt upper quadrant
Portal hypertension
Coagulation disturbance
Hepatic encephalopathy
Jaundice, pruritus
Feminisation
Weight loss, anorexia
Weakness
Diarrhoea, nausea
```
47
DX of ALD
History (social, work)
Questionnaires (AUDIT) and DSM-5 criteria
S & S
Liver US or biopsy
Bloods
- liver enzymes (ALT, AST, γ-GT)s and bilirubin
- serum albumin
- prothrombin time
- U & Es, FBC
48
TX alcohol use disorder
Reduce or stop alcohol intake (CBT, drugs)
Reduce portal hypertension (beta blockers)
Varices (balloon tamponade, vasopressin)
Bleeding (administration of clotting factors)
Ascites (diuretics, abdominal paracentesis)
Dietary intake (low protein, high carbohydrate, vitamin supplements)
Correct electrolyte and fluid imbalance and hypoglycaemia
Transplant in severe cirrhosis?
49
Drugs which facilitate alcohol withdrawal
Benzodiazepines
- Diazepam (drug of choice, tapered dosage over 6 days)
- Oxazepam, lorazepam (in severe liver disease)
Adjuncts to benzodiazepines
- Antipsychotics (haloperidol)
- Antiepileptics (carbamazepine)
- Antiemetics (metoclopramide)
- Thiamine (IM/IV and oral) and multivitamins
- Beta blockers (atenolol, propanolol)
- Review/cease drugs that ↑seizure risk (SSRIs)
50
Drugs used to Maintain Abstinence
Acamprosate (Campral)
- Structure similar to GABA
- Administered orally
- Adverse effects (diarrhoea, rash, nausea)
Naltrexone
- Pure opioid antagonist
- Administered orally, implants are being tested
- Adverse effects (nausea, headache, anxiety, sedation)
- Hepatotoxic
Disulfiram (Antabuse)
- Causes irreversible inhibition of aldehyde dehydrogenase
- Acetaldehyde syndrome (nausea, flushing, vomiting, headache, palpitations, chest pain)
51
Effects of Nicotine
Cardiovascular effects
- SNS and adrenal gland
- Arrhythmias
- Tachycardia
- Vasoconstriction
GI effects
- PNS, vomiting
- ↑gastric acid and motility
CNS effects
- Pregnancy and lactation
- Low birth weight
- Pre-term labour
- SIDS?
Up-regulation of receptors
- Tolerance
- Dependence
Acute poisoning
- 40mg can be fatal
- No specific antidote – activated charcoal can be given
- Monitor for respiratory depression and supportive treatment
Chronic toxicity from smoking
- Cancers
- Cardiovascular diseases
- COPD
52
Symptoms of withdrawal from nicotine
```
Craving
Irritability, restlesness
Frustration, anger
Anxiety
Sleep disturbances
Difficulty concentrating
↓heart rate
↑appetite, weight gain
```
53
“5 As” Model for treatment of tobacco addiction
Ask (screen all patients for tobacco use)
Advise tobacco users to quit
Assess willingness to make a quit attempt
Assist with quitting (offer medication and provide or refer to counseling)
Arrange follow-up contacts, beginning within the first week after the quit date
54
TX of tobacco addiction
Nicotine replacement therapy
- Chewing gum
- Lozenges and sublingual tablets
- Transdermal patches
- Mouth spray
- Inhaler
Other non-nicotine drug treatments
- Bupropion (Zyban)
- Varenicline (Chantix)
55
What is nicotine replacement therapy
High dose and combination therapy safe for heavy smokers
Smoking rate or serum cotinine
Assess adequacy of nicotine replacement by patient response or percent replacement
More complete nicotine replacement improves withdrawal symptom relief
Adverse effects usually minor and transient
Withdrawal symptoms
Nicotine overdose (tachycardia, palpitations, arrythmias)
56
Adverse reactions to NRT
```
Indigestion
Irritation of mouth and throat
Sinusitis
Irritation of mouth and throat
Take care if patient has dentures
Local site reactions
Insomnia, dizziness, agitation, lack of concentration
Fever, rash, nausea, dry mouth
```
57
What is nociception
perception of pain
58
What are neuromodulators
substances that alter pain transmission
Located in pathways of nervous system
Triggered by tissue injury and or inflammation
59
What is the endorphin response
Endorphins interact with the opiate receptors in the brain to reduce our perception of pain and act similarly to drugs such as morphine and codeine
60
What are opioid receptors
3 main classes of opioid receptors have been identified:
Mu (μ)
Kappa (К)
Delta (δ)
Analgesic drugs stimulate μ receptors with some action on К
61
Classic triad of acute toxicity
Respiratory depression
Coma
Pinpoint pupils
62
Immediate effects of heroin
Lower abdominal sensation similar to sexual orgasm
| Euphoria
63
Long term effects of heroin
```
Intense sadness
Irregular periods and infertility
No sex drive
Constipation
Damaged heart, lungs, liver and brain
Vein damage
Skin, heart and lung infections from injecting
Tolerance and dependence on heroin
Financial, work or social problems
```
64
Effects of first time heroin use
nausea
vomiting
dysphoria
65
Routes of administration of heroin
High lipid solubility
IV route preferred, but also smoking, nasal inhalation
Overdose
66
Signs of heroin overdose
```
Cognitive (sleepy, LOC)
Urinary retention
Itchiness
Arrhythmias
↓resps
Death
```
Rx: Naloxone, ventilation
67
Heroin withdrawal symptoms
Cravings for heroin
Restlessness, irritability, depression, crying
Diarrhoea, vomiting
↑HR
68
Why is Pethidine the choice of health professionals
Highly effective in oral route
Minimal effect on smooth muscle: fewer problems with constipation and urinary retention
Don’t get tell-tale signs of repeated injections
69
Routes of administration of oxycodone
Abusers crush tablet, snort powder or dissolve in water for IV
Controlled-release drug
Entire dose absorbed immediately with high risk of death
70
Immediate effects of oxycodone
Euphoria
Dental problems
Mood swings
71
Signs of oxycodone overdose
respiratory depression
arrhythmias
LOC
72
Treatment of acute toxicity / overdose
Naloxone
- pure opioid antagonist used to counter the effects of opioid, especially in overdose
- extremely high affinity for μ-opioid receptors in CNS
- reverse depression of CNS, respiratory system, and hypotension
- Naloxone may be combined with other opioids so when taken orally the opioid has effect but if misused the naloxone blocks the effect of the opioid
Naltrexone - structurally similar but has increased affinity for κ-opioid receptors over naloxone, can be administered orally, and has a longer duration of action.
Nalmefene - opioid receptor antagonist used in management of alcohol dependence.
73
Methods of opioid detoxification
Methadone:
Substitute methadone for dependent opioid to prevent abstinence syndrome as has cross-dependence.
Gradually reduce doses
Abstinence syndrome is mild (moderate influenza)
10 days
Clonidine:
Used for physically dependent person on opioids
Suppresses symptoms of abstinence (nausea, vomiting, diarrhoea, muscle aches, restlessness, anxiety and insomnia)
Doesn’t diminish opioid craving
Rapid and ultra-rapid withdrawal:
Given opioid antagonist to precipitate immediate withdrawal and accelerate withdrawal process
Done under GA or heavily sedated
Social/family support
Counselling
Rehabilitation
74
Long-term opioid addiction management
Three groups of medications:
1) opioid agonists
2) opioid agonist-antagonists
3) opioid antagonists
Methadone (opioid agonist)
Maintenance and suppressive therapy
Aim = avoid withdrawal symptoms, prevent addiction
Buprenorphine (opioid agonist-antagonist)
Maintenance therapy and detox facilitation
Aim = alleviate cravings, reduce drug use
Naltrexone (opioid antagonist)
Discourages renewed opioid abuse by blocking euphoria and other effects
75
Effects of barbiturates
Depressant effects are dose-dependent
Mild sedation to sleep to coma and death
Subjective effects similar to those of alcohol
76
Signs of immunodeficiency
Unusual or recurrent infection
T cell deficiency
B cell and phagocyte deficiency
Compliment deficiency
77
Types of immunodeficiency
Primary (congenital)
- rare
- genetic defect
Secondary (acquired)
- more common
- caused by other conditions (malnutrition, trauma, infection, AIDs, etc)
78
What is type 1 hypersensitivity
IgE mediated release of histamine
FIRST EXPOSURE
- allergen delivered to naive ThC in lymph node via antigen presenting cell
- ThC binds to antigen becoming primed in response to interleukins
- ThC release IL-4 causing B cell to produce IgE specific to antigen
- IgE binds to surface of mast cell
SUBSEQUENT EXPOSURE
- mast cell binds to antigen signalling mast cell to degranulate and release mediators generating allergic reaction
79
CM of type 1 hypersensitivity
```
Bronchial constriction
Oedema
Vasodilation and increased permeability of blood vessels
Gastric acid production increases
Urticaria
Low blood pressure
```
80
TX of type 1 hypersensitivity
Antihistamines
Clinical desensitisation
Adrenaline
81
What is type 2 hypersensitivity
Antibody-mediated destruction of cells
Antibody binds to tissue specific antigen
Self-reactive B cell is activated and produces IgM and IgG
Antigen binds to cell producing antigen antibody complex
COMPLEMENT SYSTEM
- small proteins work via enzymatic cascade to fight infection
- protein attracts neutrophils causing degranulation
MEMBRANE ATTACK COMPLEX
- insets into cell membrane allowing passage of fluid and molecules
- causes cell lysis
IgE ANTIBODY BINDS TO CELL
- causes phagocytes to target cell
NKC
ANTIBODY-MEDIATED CELLULAR DYSFUNCTION
- block receptors on cell
82
What is type 3 hypersensitivity
Mediated by immune complexes
Similar process to type 2 hypersensitivity but occurs with soluble antigens
Immune complex able to travel further in body and moves to basement layer of blood vessel
COMPLEMENT SYSTEM
- small proteins work via enzymatic cascade to fight infection
- protein attracts neutrophils causing degranulation
Neutrophil degranulares causing vasculitis and oedema
83
What is type 4 hypersensitivity
T cell mediated
Delayed reactions
- antigen taken to lymph node by APC
- ThC recognised antigen and binds
- APC releases IL-12 causing ThC to mature into effector cell
- ThC release substances causing ThC to proliferate and attract macrophages which create more ThC
- macrophages release proinflammatory cytokines causing leaky endothelial barriers allowing more immune cells into area causing inflammation
- KTC directly destroy cell
- cell presents antigen from inside cell
- T cell recognises and binds to molecule
- release perforin (perforate cell) and granzymes (cause apoptosis)
84
Size of bacteria
0.5 to 5 um
85
Shape of bacteria
COCCI
spherical cells occuring singularly, in pairs, clusters or chains
BACILLI
rod shaped cell with flagella for movement
SPIRILLA
twisted cell
```
VIBRIO
curved rod (comma)
```
86
Structure of bacteria
Rigid cell wall
Single circular chromosome of DNA
Plasmids
87
Purpose of plasmids
Carry non-essential information (eg resistance)
88
Reproduction of bacteria
asexually through binary fission
89
Bacteria are what kind of organism
Prokaryotic
90
Size of virus
12 - 350 nm
91
Shape of virus
Icosahedral (20 sides)
Helical
Bullet
92
Structure of virus
Sphere of protein containing RNA/DNA
| Essential components = nucleic acid, capsid, envelope
93
Replication of virus
Replicate inside host cell
| Use metabolic machinery of cell
94
What are antibacterials
- damage construction, structure, synthesis or function of cell wall
- interfere with protein synthesis by inhibiting ribosomes
- interfere with bacterial DNA
- interfere with metabolic processes
95
What are antivirals
- work against viral life cycle
- inhibit entry
- inhibit synthesis
- inhibit release
96
What are antifungals
- inhibit synthesis
| - inhibit function of membrane
97
What is antibiotic resistance
Developed resistance of bacteria by gaining genes that protect them from antibiotics
Genes arise through mutation or are acquired from other bacteria
98
What is antiviral resistance
Developed resistance of viruses
Virus replication is prone to errors resulting in a large number of variants. As the virus replicates and mutations occur, the genome changes resulting in resistance.
99
Causes of obesity
LIFESTYLE
- poor diet
- physical inactivity
- stress
- smoking
- socioeconomic
GENETIC
- 300 genes affect obesity
- account for 30%
METABOLIC
- increased cortisol
- polycystic ovarian syndrome
- hypothyroidism
100
Opioid reward pathway
Mesolimbic dopamine neurons release dopamine in response to numerous stimuli
Drug abuse bypasses natural neurotransmitters and acts directly on mesolimbic pathways
Amygdala is involved with connections to both ends of mesocortical dopamine pathway. Connections from ventral segmental area to the cause it to develop changes to remember the rewards of drug abuse.
Amygdala connects to the nucleus accumbens (involved in memory) and is triggered by substance abuse stimuli.
Repeated exposure creates pathological learning, hijacks entire reward system and addiction develops.
101
Outline alcohol metabolism
Metabolized in liver and stomach.
Alcohol is converted to acetaldehyde by alcohol dehydrogenase (slow)
Acetaldehyde is rapidly converted to acetic acid (byproduct NADH)
NADH buildup causes acidosis from lactic acid build-up and hypoglycemia from lack of glucose synthesis. It can also lead to weight gain, fatty liver, and heart attack.
Summary:
Enzyme catalyzes conversion of alcohol to acetaldehyde and hydrogen
H goes to make NADH, acetaldehyde loses another H. metabolized to acetate, released into blood stream,
The excess of NADH is thought to contribute to the liver damage that comes with excess alcohol.
102
Effects of acute alcohol overdose
Vomiting
Coma
Pronounced hypotension
Respiratory depression
103
Stages of ALD
Alcohol consumption
Fatty liver - steatosis
Alcoholic hepatitis - steatohepatitis
Alcohol cirrhosis
104
Outline Fatty Liver/Steatosis
Large amounts of fat accumulate in hepatocytes (steatosis)
Liver enlarges and becomes yellow
Damage reversible once alcohol is discontinued
105
Outline Alcoholic Hepatitis/Fibrosis
Often due to binge drinking
Inflammation and necrosis
Stimulates irreversible fibrosis
106
Outline cirrhosis
```
Irreversible fibrosis of the liver
Fat deposits - increased connective tissue
Loss of liver function
- Loss of hepatocytes
- Obstruction of biliary duct system
```
Cessation of alcohol reverses the fatty deposits but not the fibrosis or hepatocyte damage
107
Symptoms of ALD
```
Tenderness/pain in Rt upper quadrant
Portal hypertension
Coagulation disturbance
Hepatic encephalopathy
Jaundice, pruritus
Feminisation
Weight loss, anorexia
Weakness
Diarrhoea, nausea
Neurological issues
```
108
DX of ALD
History
Questionnaires (AUDIT) and DSM-5 criteria
Symptoms
Liver ultrasound or biopsy
Bloods
- liver enzymes (ALT, AST, γ-GT)s and bilirubin
- serum albumin
- prothrombin time
- U & Es, FBC
109
Symptoms of mild alcohol withdrawal
```
Anxiety
Agitation
Tremor
Nausea
Tachycardia
Hypertension
Disturbed sleep
Fever
```
110
Symptoms of severe alcohol withdrawal
Vomiting
Hyperventilation
Extreme agitation
Disorientation
Confusion
Paranoia
Delirium tremens
111
Types of Nicotine replacement therapy
```
Chewing gum
Lozenges and sublingual tablets
Transdermal patches
Mouth spray
Inhaler
```
112
Complications of obesity
CARDIOVASCULAR
- dyslipidaemia
- coagulation issues
- increased thrombus formation
- atherosclerosis
RESPIRATORY
- impaired respiratory function
- increased sleep apnoea
CANCER
- increased risk of reproductive, digestive, kidney, gallbladder and colon cancer
GALLBLADDER AND LIVER
- 3-4x greater risk of gallstones
- steatohepatitis
- osteoarthritis
MORTALITY
- 12x increase in the 25-35 year age group
113
DX of obesity
BMI (kg/m^2)
Waist circumference
Body fat composition
114
Calculation for BMI
kg/m^2
115
Purpose of adipose cells
Produce cytokines that regulate:
- food intake
- lipid storage
- metabolism
- insulin sensitivity
- female reproduction
Influence on
- immune system
- homeostasis
- blood pressure
- angiogenesis
116
TX of obesity
```
Motivation and support
Behavioural modification
Dietary factors
Physical activity
Orlistat (inhibit pancreatic lipase)
Gastric Banding
Gastric bypass
Sleeve gastrectomy
```
117
Stages of stress
ALARM
arousal of body defences
fight or flight
RESISTANCE AND ADAPTION
hormones exhance fight or flight mentality until the body has adapted
EXHAUSTION
progressive breakdown of compensatory mechanisms
onset of disease
118
What happens in the alarm phase of a stress reaction
arousal of body defences
| fight or flight
119
What happens in the resistance and adaptation phase of a stress reaction
hormones exhance fight or flight mentality until the body has adapted
120
What happens in the exhaustion phase of a stress reaction
progressive breakdown of compensatory mechanisms
| onset of disease
121
Response to stress
```
SNS
Hypothalamic pituitary adrenal axis
Increase CO and RR
Increase BP
Increase BGL and lipid levels
Altered immune response
```
122
How does stress link to inflammation and chronic disease
Chronic stress causes increased proinflammatory cytokines
Common in:
- CVD
- metabolic syndrome
- type two diabetes
- cancer
- aging
- etc
123
What is metabolic syndrome
Abdominal obesity + two of:
- elevated triglycerides
- low HDL cholesterol
- hypertension
- elevated plasma glucose
124
TX of metabolic syndrome
Decreased risk of CHD
| Prevent progression of type two diabetes
125
What is cancer
the uncontrolled proliferation of cells
126
Types of cancer
```
Carcinomas
Sarcomas
Ademoma
Adenocarcinoma
Terato-
```
127
What is a Carcinomas
Cancer of the endothelial and epithelial tissue
128
What is a Sarcomas
Cancer of the connective tissue
129
What is a Ademoma
Cancer of the glandular or ductal epithelium
Benign
130
What is a Adenocarcinoma
Carcinoma from glandular or ductal epithelium
131
What is a Terato- cancer
Cancer of the germ cells
132
Characteristics of benign cancer
```
Grow slowly
Well defines capsule
Non-invasive
Well differentiated
Low mitotic index
Does not metastasise
```
133
Characteristics of malignant cancer
```
Grows rapidly
Not encapsulated
Invasive
Poorly differentiated
High mitotic index
Spreads (metastasises)
```
134
Factors increasing the risk of cancer
```
DIET
high fat, low fibre, meat, aflotaxin, etc
links to cancers of the:
- bowel
- stomach
- prostate
- breast
- pancreas
```
OBESITY
links with BMI
increased fatty acid leading to hyperinsulinaemia and insulin resistance
```
ALCOHOL AND CIGARETTE USE
increases risk of developing cancer of the:
- pharynx
- larynx
- oesophagus
- liver
- lungs
- mouth
```
UV RADIATION
increases risk of basal and squamous cell carcinoma and melanoma
promotes skin inflammation and cytokine
```
OCCUPATIONAL HAZARD
increased risk of cancer of the:
- respiratory tract
- lungs
- bladder
examples
- asbestos
- fumes
- ionising radiation
- air pollution
```
135
What is autonomy
Cancer cells independent from normal cellular controls
Does not act like normal cells
136
What is anaplasia
Loss of differentiation
Increased nucleus size due to rapid replication
Normal function of cell is lost
No defines shape, size or growth
137
What is angiogenesis
Development of new blood vessels
| Needed for cancer to enlarge
138
What is metastasis
Spread of cancer to distant tissues and organs
139
How do you stage tumours
Using TNM staging
Tumour, nodes, metastases
140
Outline the tumour section of TNM staging
(size and location)
```
0 = organ free of cancer
1 = lesion less than 2cm
2 = lesion between 2-5cm
3 = skin or chest wall involves by invasion
```
141
Outline the nodes section of TNM staging
(quantity involved)
```
0 = no axillary nodes involved
1 = mobile nodes involved
2 = fixed nodes involved
```
142
Outline the metastases section of TNM staging
(extent)
```
0 = no metastases
1 = demonstatable metastases
2 = suspected metasteses
```
143
What is a stage 1 cancer
Cancer confined to organ
144
What is a stage 2 cancer
Cancer locally invasive
145
What is a stage 3 cancer
Cancer spread to nearby structures
146
What is a stage 4 cancer
Cancer metastasised to distant parts
147
Risks associated with colorectal cancer
Older
Family history
Diet (increased fat, sugar, decreased vitamin A, C, K)
148
CM of colorectal cancer
```
Bleeding
Altered bowel habits
Diarrhoea
Constipation
Urgency
Incomplete emptying
Pain
```
149
DX of colorectal cancer
Digital rectal exam
Faecal blood test
Xray
Cononoscopy
150
Risks associated with melanoma
Fair skin
Family history
Freckles and moles
3+ blistering sunburns before age 30
151
CM of melanoma
```
Asymmetry
Irregular boarders
Different colours
Diameter change
Evolution
```
152
DX of melanoma
Self exam
Biopsy
TNM staging
153
TX of melanoma
Excision
154
Risks associated with cervical cancer
Cigarette smoking
| HPV
155
CM of cervical cancer
Often none
156
Risks associated with lung cancer
Smoking
Asbestos
Family history
157
CM of lung cancer
```
Chronic cough
SOB
Wheezing
Haemoptysis
Pain
Hoarseness
Difficulty swallowing
Dyspnoea
Pleural effusion
Atelectasis
```
158
DX of lung cancer
```
History
Examination
Xray
Bronchoscopy
Lung biopsy
Lymph node biopsy
CT
MRI
PET
```
159
TX of lung cancer
```
Radiotherapy
Chemotherapy
Surgery
- lobectomy
- pneumonectomy
```
160
CM of liver cancer
```
Weakness
Anorexia
Weight loss
Fatigue
Bloating
Abdomen pain
Ascites
Jaundice
Increase liver size
```
161
DX of liver cancer
Ultrasound
CT
Biopsy
Symptoms
162
TX of liver cancer
Hepatectomy
Chemotherapy
Radiotherapy
Transplant
163
Risks associated with testicular cancer
Aged 15-35
Cryptorchidism
Genetics
164
CM of testicular cancer
Enlargement of testes
No pain initially
Dull heaviness in groin
Abdominal, groin, or testicular pain
165
DX of testicular cancer
Physical exa,
Ultrasound
CT
Cancer markers
166
Staging of testicular cancer
1 - tumour confined to testes
2 - tumour spread to lymph nodes
3 - metastases to other organs
167
TX of testicular cancer
Orchidectomy
Radiotherapy
Chemotherapy
168
Risks associated with leukaemia
```
History
Genetics
Radiation
Smoking
Drugs that suppress bone marrow
Infections
```
169
CM of leukaemia
```
Accumulation of blast cells
Bone marrow crowding and suppression
Anaemia
Decreased platelets
Decreased neutrophils
Bone erosion
Pain
Headaches
Lymph, spleen and liver enlargement
```
170
DX of leukaemia
Blood and bone marrow exam
171
TX of leukaemia
Chemotherapy
| Bone marrow or stem cell transplant
172
Outline antibody mediated immunity
B CELLS
1) Unspecialised B cell is activated by an antigen which is presented by direct exposure or via APC
2) B cell differentiate and proliferate to form clone cells
3) Most form plasma cells which secrete specific antibodies (immunoglobulins) capable of attaching to antigens
4) Others form memory cells stores in lymph nodes. They spread to body tissues to allow a faster response next time.
173
Outline cell mediated immunity
T CELLS
1) Unspecialised T cell is sensitised by an antigen which is presented by on a macrophage or B cell
2) T cell differentiates and proliferates to form clone T cells
3) Most become killer or helper T cells and migrate to areas high in antigens
4) Some become memory T cells which initiate faster response next time
5) some become suppressor T cells which act when immune activity becomes excessive or infection is dealt with. Release substances inhibiting B and T cell activity
174
Transmission of HIV
```
Blood, semen, vaginal secretions
Sexual contact
IV drug use
Blood products
Mother to infant
```
175
Progression of HIV
- Patient is infected with HIV
- HIV binds to CD4 cell and injects RNA
- Infected cell migrates to the lymph nodes and spleen
- Initial spike in HIV replication as many immune cells
- Acute HIV syndrome (3 weeks) causing flu-like symptoms
- Immune response initiated (increase in antibodies) allowing for partial control of virus
- Viral replication increases causing decrease in ThC
200-500 ThC = swollen lymph nodes, yeast infection
Less than 500 ThC = AIDs, fatigue, fever, decreased weight, diarrhea
176
AIDs defining characteristics
Recurrent pneumonia
Pneumocystis pneumonia
Fungal infection
Tumours : kapasi sarcoma, primary lymphoma
177
DX of HIV
ANTIBODY TEST
detect antibodies against HIV
only effective 3-17 weeks post infection
ANTIGEN ANTIBODY TEST
detect HIV and antibody
RNA/DNA TEST
detect viral RNA or copies of DNA
178
Management of HIV
```
Baseline evaluation
ThC count
Prophylaxis and early treatment
Reverse transcriptase inhibitors
Protease inhibitors
```
Highly active anti-retrovirus treatment
- slow HIV replication
- help immune system recover
179
Prevention of HIV
Largely education based
- safe sex
- clean needles
- etc
PrEP = pre-exposure prophylaxis
180
Types of antiretrovirals
Nucleoside analogue reverse transcriptase
Non nucleoside inhibitor
Protease inhibitor
Integrase inhibitor
181
Effect of nucleoside analogue reverse transcriptase
Block transcription of viral RNA to DNA
| When NRTIs are ceased, viral replication resumes
182
Effect of non nucleoside inhibitor
Bind to reverse transcriptase, altering the enzyme and making it ineffective
183
Effect of protease inhibitor
Inhibits HIV protease
HIV protease 'trims' proteins into the required sections
PI disrupts this and therefore the ability of HIV to replicate
184
Effect of integrase inhibitor
Viral DNA is transported to nucleus and incorporates into host DNA by viral integrase
Integrase inhibitor blocks this process
185
What are carcinogens
Substances which transform normal cells into tumours
186
Causes of cancer
GENETICS
- allow perforation
- disable apoptosis
- damage tumour suppressor genes
TELOMERES
- protective cap on chromosome
- become smaller with each replication
- cancer repairs their telomeres (immortal)
ONCOGENES
- mutant genes
- non-mutant state = direct protein synthesis and cell growth
- mutant state = promote cell proliferation and cancer
BACTERIAL
- Helicobacter pylori
- alters gastric epithelial cell cycle
- mutates DNA
- alters growth factors
VIRAL
- alter cellular DNA
- HPV
- Hep B and C
187
How does cancer escape the immune system
Lack tumour-specific antigens (not recognised as foreign)
Weakly immunogenic (poor immune response)
Genetically unstable (ineffective immune response)
Replicate quickly (immune system overwhelmed)
Secrete immunosuppressive molecules or enzymes
Surround self with collagen or fibrin (become invisible)
Shed their antigens (block antibodies and T cells)
